Rook's Textbook of Dermatology

Acanthosis nigricans

Definition

Acanthosis nigricans (AN) is a dermatosis that manifests as asymptomatic and symmetrical darkening affecting the skin of intertriginous areas, in particular the axillae, groins, submammary folds and neck. The skin in those regions is thickened, has a velvety texture, and may be studded by skin tags. It is particularly associated with obesity and insulin resistance.

Introduction and general description

AN may present as an isolated skin condition but may be associated with a large range of conditions ranging from obesity to endocrinopathies to internal neoplasms.

Epidemiology

Incidence and prevalence

Benign AN is very common, and affects up to 20% of adults and 7% of children; this increases threefold if only overweight children are considered [1, 2, 3]. Malignant AN is rare.

Age

AN can occur at any age. The benign form is most common in adults but may be present at birth and is not uncommon in obese children. The malignant form, which is rare, usually arises in older age groups but has been observed in children with Wilms tumours and osteogenic sarcomas [3].

Sex

AN has an equal sex ratio.

Ethnicity

AN is more common in patients with darker skins. In one study AN was observed in 1% of white people, 5.5% in Latino populations and 13.3% in African American populations [4].

Associated diseases

Obesity is the most common association with AN (previously called pseudo-AN), and can regress with weight loss [5].

Many syndromes (Box 87.2) have been associated with AN; they usually involve the endocrine system or accompany autoimmune disorders.

Malignant AN (described in more detail in Chapter 147) has been associated with an extensive range of internal cancers, but over 90% have been seen in patients with gastrointestinal cancer, of which two-thirds are gastric [6, 7, 8]. Other tumours associated with AN are listed in Box 87.3. Malignant AN may be accompanied by other cutaneous paraneoplastic phenomena, particularly florid cutaneous papillomatosis in which there is a rapid development of numerous warty papules on the trunk and the extremities that are clinically indistinguishable from viral warts (see Chapter 147).

Pathophysiology

The most common associations with benign AN are obesity [2, 9] and insulin resistance [1, 10, 11, 12]. Insulin-derived growth factor (IGF-1) receptors are overexpressed in obese patients with hyperinsulinaemia and insulin resistance [13]. IGF-1 can stimulate the proliferation of keratinocytes and dermal fibroblasts. Epidermal growth factor receptors and fibroblast growth factor receptors (FGFR) are also implicated. In Beare–Stevenson syndrome, activating mutations of FGFR2 have been identified, and in Crouzon syndrome and thanatophoric dwarfism, mutations of FGFR3 have been found [14]. FGFR3 mutations have been identified in the familial form of AN [15].

Some drugs may contribute to AN development: FGFR activation can be produced by certain medications used in stem cell transplantation, such as palifermin [16], and insulin can provoke the development of AN at injection sites by activation of IGF receptors.

In malignant AN, tumour-derived stimulating factors are produced, especially TGF-α, which is recognized by epidermal growth factor receptors. The levels of TGF decrease with tumour debulking, which may be followed by regression of the paraneoplastic phenomena [17].

Predisposing factors

AN is associated with a number of benign and malignant conditions with a common pathway of keratinocyte and fibroblast proliferation by circulating factors. Perspiration and/or friction are mechanical contributing factors which may be important in determining the characteristic distribution of AN in flexural areas.

Pathology

Despite its name, AN shows no or minimal acanthosis or hyperpigmentation microscopically. Histology shows hyperkeratosis and papillomatosis with finger-like upward projections of dermal papillae. Pigmentation is due to the hyperkeratosis; there is no increase in melanocyte numbers or in melanin production. Pseudo-horn cysts may be present. In mucosal lesions, parakeratosis may be observed [3].

Genetics

The familial form of AN is inherited in an autosomal dominant fashion. In familial AN, FGFR3 mutations have been identified [15].

Clinical features

History

AN usually starts as asymptomatic darkening of the skin of the neck, axillae and groins. With time, the patches become thicker and may develop skin tags in the affected areas. Pruritus is not common.

Presentation

AN presents as symmetrical velvety dark patches which are most commonly seen in the axillae, groins and on the back and sides of the neck (Figure 87.2). The back of the neck is the most common site in children. Skin tags (acrochordons) may be present in affected areas. AN may become widespread with delicate velvety furrowing of mucosal surfaces and involvement of the eyelids and conjunctivae. Associated nail changes include leukonychia and subungual hyperkeratosis.

Image described by caption. — **Figure 87.2** (a–c) Typical acanthosis nigricans in an obese 41-year-old man of South Asian descent with type II diabetes. Note associated striae and skin tags in the axilla (a), and darkening and velvety thickening of the skin around the root and nape of the neck (b,c).

Clinical variants

HAIR-AN is a familial syndrome, that manifests as hyperandrogenaemia, insulin resistance and acanthosis nigricans. It typically affects young black girls, who develop polycystic ovaries, hirsutism, clitoral hypertrophy and frequently have high plasma testosterone levels. This condition, which is also known as type A insulin resistance syndrome, is described in more detail in Chapters 90 and 149.

Type B insulin resistance syndrome is characterized by the association of AN with diabetes and hyperandrogenism, or with an autoimmune disease (including systemic lupus erythematosus, systemic sclerosis, Hashimoto thyroiditis and Sjögren syndrome).

Familial AN is rare and transmitted as an autosomal dominant trait with variable penetrance. It manifests early in life and tends to stabilize in the teenage years. In some patients, it can improve with age.

Drug-induced AN has been associated with many different medications, particularly hormones, insulin, systemic corticosteroids, testosterone and exogenous oestrogens, including oral contraceptives [18, 19]. One of the most common associations is with nicotinic acid. The dermatosis tends to resolve after discontinuation of the offending agent.

Generalized AN is very rare, and seen only in children. There is generalized hyperpigmenation and velvety thickening of the skin, and extensive investigation fails to show any associated systemic abnormality [20, 21, 22].

Acral AN is more common in skin phototypes 5 and 6. It is not associated with systemic disease, and manifests as a velvety thickening and hyperpigmentation of the skin on the dorsa of the hands and feet, especially the knuckles [23].

Unilateral AN (or naevoid AN) is very rare, and is assumed to arise from a somatic mutation during embryogenesis. It can appear in infancy, but not always, and cases have been reported with onset in childhood or adulthood. Clinically, it appears as a pigmented plaque, solitary or along a line of Blaschko, and resembles an epidermal naevus. Histopathologically, the typical changes of AN are seen. It has been described on the face and scalp, chest and abdomen, back and thighs [24].

Malignant or paraneoplastic AN (Figure 87.3) can be associated with an extensive range of internal cancers (see above and Box 87.3).

Differential diagnosis

The major differential diagnoses are as follows:

Addison disease.
Pellagra.
Haemochromatosis.
Fairly simple investigations will exclude these diagnoses.

Disease course and prognosis

Benign AN is not associated with systemic disease but generally persists and may be a significant cosmetic problem.

AN associated with metabolic abnormalities and insulin resistance may improve with treatment of the underlying condition. AN associated with obesity may improve with dietary restriction and weight loss.

The prognosis of patients with malignant AN is poor, with an average survival of only 2 years from diagnosis.

Investigations

In adult-onset AN, patients should be screened for underlying endocrinopathy or malignancy. A sensitive test for insulin resistance is serum insulin, the levels of which may be elevated before the onset of diabetes or elevation of glycosylated haemoglobin levels.

Management

Management of AN is the management of the underlying condition. In familial AN or AN not associated with an underlying condition, treatment is aimed at improving the cosmetic appearance of the condition.

Confluent and reticulated papillomatosis

Definition and nomenclature

Confluent and reticulated papillomatosis (CARP) is an uncommon disorder of epidermal keratinization characterized by the development of hyperkeratotic papules which coalesce into confluent and, in places, reticulated plaques on truncal skin. An abnormal reaction to commensal microorganisms has been postulated to play an aetiological role.

Introduction and general description

Gougerot and Carteaud first described this entity in 1927 [1]. It is a controversial disease and many had considered it to be a specific form of AN [2]. Diagnostic criteria have been established and it is now considered a specific form of cutaneous papillomatosis [3, 4].

Epidemiology

Incidence and prevalence

CARP is a rare disease and there are no data on the prevalence of the disease.

Age

CARP is predominantly a disease of young adults. In one series of patients, the mean age at onset was 19 years [2].

Sex

It is likely that the sex incidence is equal but different reports have shown a predominance of women in white populations but a predominance of men in Japan. A study from the Mayo Clinic [4] and a recent study from Lebanon shows an equal sex incidence [5].

Ethnicity

CARP has been reported in all ethnic groups.

Pathophysiology

The pathogenesis of CARP is poorly understood. It is thought that an abnormal host reaction to Malassezia organisms may be relevant in some patients [6, 7] and it has also been suggested that actinomycete bacteria may play a role [8]. These hypotheses are discussed in more detail later.8 However, the anti-inflammatory properties of the antibiotics might be the true reason for the response.

Abnormal keratinocyte differentiation has been found on transmission electron microscopy and by immunohistochemical studies,which show an increased expression of involucrin, keratin 16 and Ki-67 [9]. These changes might explain the clustering of the condition in some families [10, 11]. The number of Odland bodies is increased and this is associated with a higher turnover of epidermal keratinocytes as seen in psoriasis [12]. The role of metabolic abnormalities in the development of CARP is gaining supporters [2]. CARP has been associated with obesity and insulin resistance [13], as well as thyroid dysfunction and Cushing disease [14].

Pathology

There is hyperkeratosis and papillomatosis, with decrease in the thickness or disappearance of the granular cell layer. There may be increased melanin in the basal cell layer and in the stratum corneum, and this is reflected in the colour of the plaques. The dermis shows at most a mild non-specific inflammatory infiltrate [15].

Fungal stains frequently show Malassezia yeasts on the surface of the epidermis.

Causative organisms

A number of reports have demonstrated the presence of Malassezia organisms in CARP. This has led to speculation that CARP is due to an abnormal host reaction to Malassezia. Several studies have shown, however, that only about half of patients with CARP have significant yeast populations on affected skin [2, 6, 7]. Although some patients with CARP respond to topical imidazoles or other antifungal agents, about half of cases fail to respond [5, 6, 7] and in those cases only a few spores can be retrieved from the skin surface.

Some patients with CARP appear to respond to tetracycline and macrolide antibiotics, which has led to the suggestion that skin bacteria may be responsible for this disease. In 2005, a previously unknown actinomycete bacterium of the genus Dietzia was isolated from the skin of a patient with CARP. Sensitivity studies showed sensitivity to tetracycline and erythromycin and the patient cleared with tetracycline. The organism, which has subsequently been named Dietzia papillomatosis, has been implicated in a case of septicaemia but, to date, there have been no further reports linking it with CARP [8]. It has been suggested, however, that the response to antibiotics may be due to their anti-inflammatory rather than their antibacterial properties.

Genetics

Although familial forms of CARP have been reported [10, 11] they are too rare to postulate a genetic inheritance.

Clinical features (Figure 87.4)

History

The patient is usually a young postpubertal individual. Plaques of CARP are located mainly on the trunk, especially on the presternal, interscapular and epigastric areas. They are generally asymptomatic.

Presentation

Patients first notice pigmented, 1–2 mm diameter hyperkeratotic papules on the trunk. These coalesce to form greyish-blue plaques which are confluent at the centre but become reticular towards the periphery of the plaques. Over weeks or months, the plaques spread to involve the lower abdomen and pubic areas [2]. The face and limbs may be affected. Localized forms affecting only the face or pubic area have been reported [16, 17]. Mucous membranes are not involved. A number of different patterns of skin involvement have been described [18].

Differential diagnosis

The most common differential diagnoses proposed in cases of CARP include the following:

Acanthosis nigricans.
Macular amyloid.
Darier disease.
Epidermal naevus.
Plane warts.
Pityriasis versicolor.
Seborrhoeic keratosis.
Retention hyperkeratosis (deficient personal hygiene).

Disease course and prognosis

CARP is a chronic disease with remissions and exacerbations. If CARP responds to treatment, it often relapses when treatment is withdrawn.

Management

CARP is a chronic disease and is purely cosmetic, so no treatment is an option if the condition does not bother the patient. In overweight patients, weight reduction may result in improvement. In some women, CARP may improve during pregnancy or with the use of the oral contraceptive.

First line

A wide range of oral antibiotics have been found to be effective in CARP [21]: the most effective appears to be minocycline [4, 19, 20]. Topical mupirocin ointment has been of benefit in some cases [21].

Second line

Topical and systemic antifungal agents, including selenium sulphide shampoo, have been used with success in some patients [2, 22] but the results have been very variable. Topical retinoids and vitamin D analogues have been used with mixed results [23, 24, 25].

Third line

Both high- and low-dose isotretinoin have been used in the treatment of CARP with varying results [26, 27].

Pityriasis rotunda

Definition and nomenclature

Pityriasis rotunda (PR) [1] is a dermatosis of unknown cause that presents as perfectly round, slightly erythematous or hyperpigmented plaques, with fine scaling, usually located on the trunk or buttocks, arms and legs.

Introduction and general description

PR is a rare condition with very few reports in the literature. The most common form of PR is type 1 PR which is typically seen in older Asian or African individuals and is usually associated with underlying systemic disease or malignancy [2]: it may resolve with treatment of the underlying condition [2, 3]. Type 2 PR is usually familial and presents in younger white patients: it is not associated with underlying disease.

Epidemiology

Incidence and prevalence

PR is rare with most reports coming from South Africa, Sardinia or Japan.

Age

Type 1 PR is usually seen in patients in their 60s. Type 2 PR is usually seen in patients in their forties.

Sex

PR has an equal sex incidence.

Ethnicity

Most case reports of PR have come from South Africa in black populations and the few reports from the UK have been in patients of African descent [4]. Type 1 disease is also seen in East Asian patients with most reports from Japan; it is rare in white populations [5]: type 2 PR has been reported principally from Sardinia.

Associated diseases

Type 1 PR has been associated with hepatocellular carcinoma. In a series of 10 black patients from South Africa with PR, 70% were associated with hepatocellular carcinoma [6]. In a further study from South Africa examining hepatocellular carcinoma, 15.9% of 63 patients had PR [7]. In the South African black population, PR has been associated with a number of systemic diseases listed in Box 87.4.

In Asian populations, PR is associated with underlying malignancy but not specifically with hepatocellular carcinoma [8].

Pathophysiology

The aetiopathogenesis of PR is unknown. Histologically, it shares some characteristics with ichthyosis vulgaris and some authors feel it is a variant of this disease [9]. In South African patients it has been associated with malnutrition, but this is not generally accepted as a cause of the disease.

Pathology

Histological changes are restricted to the epidermis with hyperkeratosis and loss of the granular cell layer.

Genetics

Type 2 PR is inherited as an autosomal dominant trait [10].

Clinical features

History

PR is an asymptomatic condition and is often diagnosed incidentally in patients being investigated for other disease.

Presentation

PR presents as asymptomatic thin finely scaling plaques ranging from 0.5 to more than 20 cm in diameter located on the trunk, buttocks, arms and legs. The plaques, ranging in number from a few to more than 100, are sharply demarcated and can coalesce, forming polycyclic plaques. They are pink in lightly pigmented skin to dark brown in skin of phototypes 5 and 6 (Figure 87.5).

Clinical variants

PR types 1 and 2 are sporadic and familial, respectively (see earlier).

Differential diagnosis

Differential diagnosis includes post-inflammatory hyperpigmentation following fixed drug eruption, erythrasma, tinea corporis, pityriasis versicolor and psoriasis.

Disease course and prognosis

Once type 2 PR develops it usually persists lifelong. In type 1 PR associated with an underlying disease, treatment of the disease may result in resolution of the PR.

Investigations

A skin biopsy might be helpful to exclude other conditions, as the diagnosis of PR is one of exclusion.

Skin scraping and mycological examination will exclude dermatophytosis and pityriasis versicolor.

Management

Lesions of PR are notoriously resistant to therapy, but some improvement has been achieved with topical treatment.

Keratosis pilaris

Definition and nomenclature

Keratosis pilaris (KP) is an inherited abnormality of keratinization affecting the follicular orifices with varying degrees of keratotic follicular plugging, perifollicular erythema and follicular atrophy.

Introduction and general description

KP [1, 2] is a common skin condition, characterized by follicular keratotic papules and perifollicular erythema. Because up to half of the population present with the condition to some degree, it can be considered a variant of normal rather than a disease.

Epidemiology

Incidence and prevalence

KP is a very common condition affecting 50–80% of adolescents and about 40% of adults.

Age

KP often presents in the first decade of life and may worsen around puberty. In some patients, the disorder improves with age but any age group can be affected from childhood to old age.

Sex

Females appear to be more frequently affected than males.

Ethnicity

KP is not more prevalent in any racial group.

Associated diseases

KP may be associated with ichthyosis vulgaris and atopic eczema [3]. These conditions are, however, all common and the association may be coincidental. Some other reported associations are listed in Box 87.5. More recently, patients with BRAF-positive tumours under treatment with vemurafenib and sorafenib have been noted to develop KP as a side effect [4].

Pathophysiology

A plug of excess keratin is formed, possibly due to a defect of corneocyte adhesion at the follicular orifice, and this impedes the hair from emerging. The hair can become ingrown and result in an inflammatory response [18].

Pathology

Histology of KP shows hyperkeratosis, hypergranulosis and plugging of hair follicles. In the dermis, there is a mild perivascular lymphocytic infiltrate in the upper dermis.

Genetics

KP is inherited as an autosomal dominant trait with variable penetrance [18]. Reports have identified a partial monosomy in the short arm of chromosome 18 in patients with severe forms of KP and ulerythema ophryogenes [19].

Environmental factors

KP may show seasonal variation, improving in the summer [20].

Clinical features

History

KP generally starts in children, most commonly on the extensor surfaces of the upper arms, and can worsen around puberty.

Presentation

There are small, keratotic papules on the extensor aspects of the limbs, particularly the arms (Figure 87.6) and thighs [20]. The buttocks and the lumbar areas are also frequently affected. These areas acquire a ‘goose-bump’ appearance and rough texture. Lesions can become pustular with superficial pustules developing in affected follicles, precipitated by rubbing on clothing. On the buttock, deeper inflammatory lesions and nodules may develop.

Clinical variants

Erythromelanosis follicularis faciei et colli [21–23] is a condition that has been described as a subtype of KP and seen in India and other countries in the Far and Middle East. It manifests as follicular hyperkeratosis accompanied by erythema and hyperpigmentation, and affects, as the name indicates, the face, particularly the cheeks and neck (Figure 87.7).

KP atrophicans is a more inflammatory form of KP which results in follicular fibrosis and atrophy progressing to scarring alopecia. Three variants have been recognized as follows:

KP atrophicans faciei, also called ulerythema ophryogenes [24] or keratosis rubra pilaris faciei atrophicans, affects the cheeks and lateral eyebrows (Figure 87.8). There is fixed erythema, follicular plugging, pitted scarring and hair loss. It may be associated with common KP and may be inherited as an autosomal dominant trait [25].
Keratosis follicularis spinulosa decalvans has its onset in infancy, and affects the cheeks and nose [26]: follicular plugging results in follicular atrophy. The scalp may also be involved, resulting in scarring alopecia. It can be associated with palmoplantar hyperkeratosis.
Atrophoderma vermiculatum manifests in late childhood, and affects the cheeks and preauricular skin. The follicular plugging evolves towards reticulated atrophy of the skin (Figure 87.9) [27].

Differential diagnosis

KP may be confused with a large number of dermatoses including the following:

Darier disease.
Pityriasis rubra pilaris.
Atopic eczema.
Lichen nitidus.
Eruptive vellous hair cysts.

If follicular lesions become inflamed KP may be confused with the following:
Acne.
Folliculitis.

KP atrophicans faciei may be confused with rosacea.

Disease course and prognosis

In the majority of patients KP is a mild cosmetic disorder which improves with age. Hypopigmentation, hyperpigmentation and scarring may occur.

Investigations

KP is a clinical diagnosis for which no tests are normally required.

Management

KP is principally a cosmetic problem and many people do not know they have it. If it does not bother the patient, treatment is unnecessary. Benefit from topical therapy is often limited and many patients will not persist with it.

First line

Keratolytics, particularly salicylic acid. Lactic and glycolic acid preparations also reduce roughness of the skin. Treatment may need to be continued for many years.

Second line

Topical retinoids may reduce hyperkeratosis and can be very successful when combined with 10% urea containing moisturisers. Topical retinoids are particularly useful for KP atrophicans faciei [28].

Third line

In severe KP, oral isotretinoin has been successfully used but relapse occurs on cessation [29].

Fourth line

Patients with severe fixed erythema from KP atrophicans faciei have been successfully treated with pulsed dye laser [30, 31].

Lichen spinulosus

Definition and nomenclature

Lichen spinulosus (LS) [1, 2, 3] is a rare idiopathic condition, characterized by the appearance of hyperkeratotic follicular papules arranged into large plaques.

Introduction and general description

LS was first described by Adamson in 1908 [4] as an acute eruption of grouped keratotic papules which form into plaques. They appear suddenly and are distributed symmetrically on the extensor surfaces of the limbs or on the trunk and neck [1, 2, 3]. They are coarse to the touch and typically measure 2–5 cm in diameter.

Epidemiology

Incidence and prevalence

LS is a rare disorder. From the first description [4], no further reports of the disease appeared in the literature until 1990, when Friedman described 35 patients in a survey of 7435 patients attending a dermatology clinic in the Philippines, accounting for 0.5% of patients surveyed [3].

Age

LS is a disease of children and young adults with an average age of onset of 16.2 + 10.1 years [3].

Sex

Case reports suggest an equal distribution of LS in males and females.

Ethnicity

There is no predilection of LS in any ethnic group.

Associated diseases

LS is not usually associated with any underlying systemic disease. There have been case reports of LS in HIV infection, Crohn disease and alcoholism, Hodgkin disease and syphilis [5, 6, 7]. Previously, LS has been associated with certain drugs including thallium, gold and diphtheria toxin.

Pathophysiology

The cause of LS is unknown. Some authors feel that LS is a variant of KP: the conditions share the same features on histology.

Pathology

Hair follicles are dilated by a thick keratinous plug, and surrounded by a mild to moderate chronic inflammatory infiltrate.

Clinical features

History

LS generally erupts acutely and is asymptomatic.

Presentation

Individual papules are follicular, measuring 2–3 mm in diameter and raised 1 mm above the surface of the skin with a pointed keratotic spine. Papules coalesce into plaques ranging from 2 to 5 cm in diameter. The patches are symmetrical and distributed on the trunk, buttocks (Figure 87.10), neck, knees and elbows. The face, hands and feet are usually spared. Plaques erupt in crops, grow rapidly and then remain stationary.

Clinical variants

Spinulosis of the face, presenting with tiny keratotic spicules on the cheeks, may be a variant of LS.

Differential diagnosis

All other causes of follicular papules should be considered in the differential diagnosis, including KP, lichen nitidus, phrynoderma, and pityriasis rubra pilaris.

Disease course and prognosis

LS is a chronic but purely cosmetic disease. LS can persist for many years, but in most patients, it resolves spontaneously within 1–2 years.

Investigations

Diagnosis of LS is made clinically and can be supported by histology.

Management

Management of LS is aimed at improving the cosmetic appearance. The mainstays of treatment are topical retinoids and keratolytics [8].

Keratosis circumscripta

Definition

Keratosis circumscripta (KC) is a rare condition characterized by circumscribed areas of follicular hyperkeratosis.

Introduction and general description

KC was first described by Shrank in 1966 in 10 members of the Yoruba tribe in Nigeria [1]. It is rare and there remains controversy over its status as an individual dermatosis. In one report and review of the literature, the authors suggested that KC was in fact a form of psoriasis modified by environmental factors [2]. It has also been suggested that it is the same as type IV circumscribed juvenile-onset pityriasis rubra pilaris (see Chapter 36). Shrank's findings were, however, supported by a report of 10 patients from Kenya [3] and other authors have supported its recognition as an individual entity [4, 5].

Epidemiology

Incidence and prevalence

KC is rare.

Age

KC first develops in childhood and is persistent thereafter.

Ethnicity

KC was first described in an African tribe and is more common in phototype 6 skin.

Pathophysiology

The aetiopathogenesis of KC is unknown.

Pathology

Histology shows follicular plugging and moderate hyperkeratosis. There is no involvement of the dermis.

Genetics

The condition appears to be sporadic but clustering of cases within a particular ethnic group would support a genetic predisposition.

Clinical features

History

KC normally starts at the age to 3–5 years with lesions developing quickly over a period of 2–3 weeks.

Presentation

The lesions of KC are well-defined areas of diffuse and follicular hyperkeratosis affecting the extensor surfaces of the arms and legs and the trunk (Figure 87.11). In his original report, Shrank described elbow and knee involvement in all his patients and 4–5 cm round discs of follicular hyperkeratosis on each hip. The dorsa of the hands and feet were occasionally involved but the palms and soles were rarely affected. Lesions may become thickened and hyperpigmented or violaceous in colour.

Differential diagnosis

A number of dermatoses can be confused with KC but can be clinically differentiated from this disease. These include the following:

Type IV circumscribed juvenile pityriasis rubra pilaris (see Chapter 36).
Lichen spinulosus.
Psoriasis (see Chapter 35).

Disease course and prognosis

Once established, the condition persists. Patients tend not to develop new lesions but existing lesions may slowly increase in size and become more keratotic.

Management

KC is poorly responsive to treatment and generally does not improve with topical corticosteroids, topical retinoids or conventional keratolytics. 40% urea in white soft paraffin has been used successfully to improve the appearance of KC in one patient [3].

Phrynoderma

Definition

Phrynoderma, which literally means toad skin, is one of the cutaneous manifestations of vitamin A deficiency but may also be associated with other nutritional deficiencies. It manifests as follicular hyperkeratosis. It is described in more detail in Chapter 63.

Introduction and general description

Phrynoderma was first described by Nicholls in 1933 in African labourers and was recognized as a manifestation of vitamin A deficiency [1]. It is usually seen in children living in economically deprived countries.

Epidemiology

Incidence and prevalence

Phrynoderma is more common in countries where malnutrition is prevalent, but can also be seen in Europe in individuals with liver cirrhosis, malabsorption syndromes or anorexia nervosa and in those who abuse alcohol or are homeless [2]. In economically deprived countries, it is seen in <5% of children and adolescents [3]. Recently, it has been recognized as a complication after bariatric surgery [4, 5].

Age

Phrynoderma is commonest in children between the ages of 5 and 15 in economically deprived countries.

Sex

Sexes are equally affected.

Ethnicity

No data available.

Associated diseases

Liver cirrhosis.
Malabsorption syndromes.
Anorexia nervosa.
Alcohol abuse.
Nutritional deficiency following bariatric surgery.

Pathophysiology

Phrynoderma was initially thought to be due purely to vitamin A deficiency. Vitamin A is essential for normal cellular growth and division, and maintenance of the immune response. Lack of this vitamin results in abnormal epidermal keratinization as well as immunosuppression [6, 7, 8]. Phrynoderma has now been described in patients with normal vitamin A levels and has been associated with other nutritional deficiencies including including B complex, riboflavin, vitamin C, vitamin E, essential fatty acids and malnutrition [1].

Pathology

Follicles are dilated with compact keratin and patchy parakeratosis with no dermal reaction.

Clinical features (Figure 87.12)

History

Phrynoderma starts gradually with mostly non-pruritic lesions on the elbows.

Presentation

Phrynoderma manifests as groups of papules, each one around 3–4 mm in diameter, with a central keratotic plug [9, 10, 11]. The papules have a follicular distribution and give the skin a rough texture. The elbows and knees are the most commonly affected areas but the buttocks and extensor surfaces of the limbs may be affected. In generalized disease, the trunk and face may be affected. Papules are skin coloured or hyperpigmented. The condition is usually associated with ocular signs, such as night blindness, conjunctival xerosis and ulcerations [12].

Differential diagnosis

The differential diagnosis of phrynoderma includes the following:

Keratosis pilaris.
Lichen nitidus.
Lichen spinulosus.
Perforating disorders.
Pityriasis rubra pilaris.

Complications and co-morbidities

Ocular involvement including the development of Bitot spots, conjunctival xerosis and blindness may be associated with phrynoderma.

Investigations

All patients with phrynoderma should have their vitamin A levels measured. Serum vitamin A levels lower than 35 μmol/dL indicate hypovitaminosis.

In some patients with nutritional deficiency, there will be concomitant hypoproteinaemia. In this circumstance, values of vitamin A can appear reduced despite adequate vitamin A stores.

Management

Treatment involves the correction of poor diet and administration of a multivitamin preparation containing vitamin A, since poor diet often results in other concurrent deficiencies. Oral administration is preferred over parenteral therapy. The dosage, in children aged 8 years or above and adults is 100 000 units daily for 3 days, followed by 50 000 units daily for 2 weeks, and then 10 000 units daily for 2 months, until liver storage is adequate [13].

Trichodysplasia spinulosa

Definition and nomenclature

Trichodysplasia spinulosa is a rare and disfiguring condition caused by infection of the hair inner root sheath by a polyoma virus in immunocompromised patients.

Introduction and general description

This is a rare condition first described in 1999 in immunocompromised patients [1]. It is due to a novel polyoma virus that appears to infect keratinocytes of the inner root sheath of the hair follicle.

Epidemiology

Incidence and prevalence

Trichodysplasia spinulosa is rare with only a small number of reported cases in the world literature.

Age

Trichodysplasia spinulosa has been reported in immunosuppressed patients of all age groups [2].

Ethnicity

All ethnic groups can be affected.

Associated diseases

Most patients with trichodysplasia spinulosa are immunosuppressed following organ transplantation [3]. The disease has been reported in a patient with lymphocytic leukaemia [4]. There have been rare reports of trichodysplasia spinulosa associated with systemic lupus erythematosus [5].

Pathophysiology

Predisposing factors

The trichodysplasia spinulosa polyoma virus (TSPyV) is an opportunistic virus: immunosuppression, whether caused by disease or medication, is a prerequisite for the development of trichodysplasia spinulosa.

Pathology

In affected areas, the hair follicles show abnormal maturation with dilation of the follicular infundibulum, which is plugged by cornified eosinophilic keratinocytes containing large trichohyalin granules (see Chapter 89). Electromicroscopy shows 28 nm intracellular viral particles consistent with polyoma virus. Immunofluorescence studies using antibodies to trichohyalin and TSPyV VP1 protein have shown that the virus is restricted to the nuclei of inner root sheath cells [6]. However, virus has been identified using molecular techniques in the renal allograft of one affected patient [7].

Causative organisms

Trichodysplasia spinulosa is caused by TSPyV. TSPyV is a group I double-stranded DNA virus of the family Polyomaviridae and genus Orthopolyomavirus and is related to the Merkel cell polyoma virus. A study in the Netherlands [8] has shown that the virus is common in the general population with a seroprevalence of 70%; it only becomes symptomatic if a carrier is immunocompromised. In contrast to Merkel cell polyoma virus, TSPyV causes dysplasia rather than neoplasia.

Clinical features (Figure 87.13)

History

The original patient described by Haycox et al. [1] was a heart transplant recipient who developed alopecia of the eyebrows followed by the appearance of multiple painful follicular papules with spiny excrescences which then rapidly coalesced to form a leonine facies.

Presentation

Shiny follicular papules with central spiny keratotic spikes form on the facial skin. The condition progresses rapidly with multiple disfiguring lesions. Alopecia of the eyebrows and scalp may occur. The condition is usually asymptomatic but may be mildly pruritic.

Differential diagnosis

Trichodysplasia spinulosa is a very distinctive disease but in the early stages may be confused with other follicular keratotic dermatoses including the following:

Keratosis pilaris.
Lichen nitidus.
Follicular mucinosis.

Complications and co-morbidities

All patients are immunocompromised.

Disease course and prognosis

Trichodysplasia spinulosa progesses unless specifically treated or unless immunosuppression is withdrawn. There have been no long-term reports of this disease so long-term prognosis is speculative.

Investigations

Skin biopsy shows characteristic changes in the hair follicle. The virus can be identified using molecular or immunofluorescence techniques.

Management

Trichodysplasia spinulosa is a persistent disease. In organ transplant recipients, reduction of immunosuppression has resulted in some improvement. Antiviral treatment has been successful in some patients [9, 10] and one patient responded to surgery followed by topical tazarotene [11]. Firm guidance on management cannot be given due to the paucity of reports but oral antiviral therapy would appear to be the treatment of choice.

Flegel disease

Definition and nomenclature

Flegel disease (FD) is a rare dermatosis, first described by Flegel in 1958 [1]. It is characterized by the presence of flat keratotic papules on the lower legs and dorsa of the feet. It is a disease of the older adult, but it can be seen occasionally in younger persons.

Introduction and general description

FD is a rare dermatosis characterized by flat keratotic papules on the lower legs and dorsa of the feet. It is a disease of the older adult, but can appear occasionally in younger persons. Each papule measures 1–5 mm in diameter and is topped by a horny keratotic scale, the removal of which causes bleeding. Lesions are commonest on the dorsa of the feet and the lower legs, typically in older patients.

Epidemiology

Incidence and prevalence

FD is a rare disease and there are no prevalence data in the literature.

Age

FD is most commonly seen in mid to late adult life but cases in children have been reported [2].

Ethnicity

FD is seen in all racial groups but appears to be more common in white populations.

Associated diseases

A number of reports have suggested an association between endocrinopathies and FD [3], particularly diabetes.

Pathophysiology

The cause of FD is unknown. A number of hypotheses have been put forward. Some authors have suggested that UV light may play a role [4]. Electron microscopic studies have demonstrated a lack or paucity of Odland bodies in the stratum granulosum, suggesting a possible mechanism for localized hyperkeratosis [5, 6]. Immunological studies have shown that the dermal infiltrate in FD is predominantly T cell and that these cells are activated, suggesting that the disease could be the result of a cell-mediated immune response to keratinocytes [7].

Pathology

Microscopic examination of a well-developed papule shows characteristic histological features. The stratum corneum is markedly thickened, eosinophilic and compact, and the underlying stratum spinosum is compressed. Patchy parakeratosis may be present. The intervening granular layer is thinned or absent. The surrounding epidermis can show papillomatosis. There is a lymphocytic dermal infiltrate in a band-like distribution beneath the affected epidermis [5].

Genetics

Both a familial and a non-familial variant have been recognized. At least in some cases, the disease is inherited as an autosomal dominant trait [8].

Environmental factors

Some authors suggest that exposure to the sun may be involved in the pathogenesis of FD.

Clinical features (Figure 87.14)

History

Small keratotic papules develop on the lower legs in middle-aged to elderly patients and slowly spread up the legs. The lesions are asymptomatic.

Presentation

The lesions of FD are red/brown non-follicular keratotic papules measuring 1–5 mm in diameter. Rarely, the disease may affect the outer ear lobes, arms, palms, soles and oral mucosa [9]. If the scale is removed, the site is red and may have bleeding points. Involvement of the trunk is unusual but a generalized form of FD has been described [10].

Differential diagnosis

Diseases with localized areas of hyperkeratosis are considered in the differential diagnosis, as listed in Box 87.6.

Investigations

Skin biopsy will show the characteristic changes and will confirm a clinical diagnosis.

Management

FD is difficult to treat and medical treatment needs to continue for prolonged periods.

First line

The most consistent treatment results have been achieved with 5% fluorouracil, which needs to be continued for several months [11, 12, 13], dermabrasion and local excision [14].

Second line

Various systemic retinoids have been used with variable responses. Lesions tend to reform on cessation of treatment [15].

Third line

Treatment with topical vitamin D analogues have been reported with variable and inconsistent results [16, 17]. Topical retinoids and keratolytics have been used with disappointing results [12].

Multiple minute digitate keratoses

Definition and nomenclature

The term multiple minute digitate keratoses (MMDK) describes a rare clinically distinctive but aetiologically heterogeneous disorder of epidermal keratinization occurring in adults.

Introduction and general description

Multiple minute digitate hyperkeratoses is a term introduced by Goldstein in 1967 [1] and more fully characterized by Ramselaar and Toonstra in 1999 [2] for a rare disorder of keratinization in which multiple tiny spiky cutaneous keratoses appear in adult life. The more appropriate label MMDK is preferred to define this disorder [3].

Epidemiology

Incidence and prevalence

MMDK is a rare disorder.

Age

The genetic form generally presents between the ages of 20 and 30 years. MMDK associated with malignancy or other systemic disease presents later in life, typically in the sixth decade of life [4].

Sex

MMDK shows a slight male preponderance [1].

Ethnicity

No racial predilection has been identified.

Associated diseases

Post-inflammatory/reactive cases of MMDK may be associated with solar damage, radiotherapy or may be related to drugs including acitretin, simvastatin and ciclosporin [5].

Sporadic cases of MMDK may be associated with systemic disease or may be paraneoplastic [1, 6–8].

Pathophysiology

Three forms of MMDK have been proposed, although these divisions may not be real.

The genetic form appears to be inherited as an autosomal dominant trait and the disease becomes clinically apparent in the second and third decades of life.

MMDK has been associated with various drugs as well as following radiotherapy or chronic sun exposure.

Sporadic MMDK may be a paraneoplastic phenomenon but due to its rarity it is difficult to determine whether the associations with underlying neoplasms which have been noted are simply coincidental [6].

Pathology

Histologically, MMDK shows discrete columns of compact hyperkeratosis arising from acanthotic interfollicular epidermis. The granular cell layer is intact. The dermis is uninvolved. Under the electron microscope keratohyalin bodies are smaller than normal but Odland bodies are present. The pattern of keratin is otherwise normal [9].

Genetics

The early-onset familial form is inherited in an autosomal dominant fashion.

Clinical features

History

Patients report the sudden appearance of asymptomatic tiny spiny keratoses on the skin.

Presentation

MMDK are typically located on the trunk and proximal limbs and may number in the hundreds (Figure 87.15). They are tiny flesh-coloured spikes that measure up to 2 mm in length and are non-follicular. Case reports have described patients with lesions restricted to the palms and soles [7, 8].

Differential diagnosis

Other digitate keratoses including LS, phrynoderma, multiple filiform viral warts, trichodysplasia spinulosa and arsenical keratoses [10].

Investigations

In sporadic cases of MMDK, investigations for age-related underlying malignancy should be performed.

Management

There is no evidence for the treatment of MMDK. Reports have shown response to a number of treatments.

Porokeratoses

Definition and nomenclature

A porokeratosis is a clonal expansion of keratinocytes which differentiate abnormally but are not truly neoplastic. All forms of porokeratosis show a thin column of parakeratosis, the cornoid lamella, representing the active border. Squamous cell carcinomas may develop within lesions.

Introduction and general description

A porokeratosis is a clonal expansion of keratinocytes which differentiate abnormally but are not hyperproliferative. Porokeratoses may present as single or multiple lesions and may be localized or disseminated. All forms show a thin column of parakeratosis, the cornoid lamella, representing the active border [1, 2].

Mibelli described the classical form which bears his name in 1893. This was followed by descriptions of superficial and disseminated forms of porokeratosis by Respighi in 1893, linear porokeratosis in 1918, DSAP by Chernosky in 1966, disseminated palmoplantar porokeratosis by Guss in 1971 and punctate porokeratosis by Rahbari in 1977.

A working clinical classification of porokeratoses is shown in Box 87.7 [1, 2]. Lesions start as papules or plaques which develop into annular lesions with a thin, often thread-like elevated rim. Diagnosis is confirmed by finding the pathognomonic cornoid lamella on histological examination (Figure 87.16). It is likely that the different variants are related, as more than one type of porokeratosis has been reported in the same patient [3] and different types have been reported in different members of the same family [4]. Malignant change with development of squamous cell carcinoma may occur.

Epidemiology

Incidence and prevalence

Porokeratosis is listed as a rare disease and classified as such by Orphanet and the Office of Rare Diseases (ORD) of the National Institutes of Health. DSAP is the most common form [5].

Age

Classical porokeratosis of Mibelli and linear porokeratosis typically appear during infancy or childhood. Punctate palmoplantar porokeratosis and disseminated palmoplantar porokeratosis usually appear in adolescence while DSAP generally first manifest in adult life.

Sex

Porokeratosis of Mibelli, genital porokeratosis and punctate porokeratosis are more common in males whereas DSAP is more common in women. Linear porokeratosis has an equal sex ratio.

Ethnicity

All forms of porokeratosis are seen predominantly in pale fair-skinned ethnic groups.

Associated diseases

HIV infection [6].
Crohn disease [7].
Diabetes [8].
Liver disease [9].
Chronic renal failure [10].
Haematological and solid tumours [11].

Pathophysiology

Porokeratosis represents a clonal expansion of keratinocytes [12] which show abnormal differentiation but are not hyperproliferative [13]. The cornoid lamella, which is the hallmark of porokeratosis, is composed of parakeratotic keratinocytes which result from either faulty maturation or an acceleration of epidermopoiesis. It has been shown that there is reduced keratinocyte loricrin and filaggrin expression and abnormal premature keratinocyte apoptosis underlying the cornoid lamella, indicating dysregulation of terminal differentiation [1]. Furthermore, abnormal DNA ploidy in keratinocytes has been demonstrated [14]. In DSAP mutations in the SART3 and MeValonate Kinase (MVK) genes have been found [5]: MVK has a role in keratinocyte differentiation and may protect keratinocytes from apoptosis in response to damage from UV radiation [15].

Predisposing factors

Drug-induced immunosuppression in various diseases including organ transplantation may predispose to porokeratosis [16]. Natural or therapeutic exposure to UV radiation are recognized trigger factors for DSAP and porokeratosis of Mibelli.

Pathology

Identification of the cornoid lamella is essential for the diagnosis of porokeratosis. As this represents the peripheral thread-like border of the lesion it is essential that biopsy includes this border. Histologically, the cornoid lamella is a thin column of tightly packed parakeratotic keratinocytes within a keratin-filled invagination of the epidermis through the stratum corneum (see Figure 87.16) [1]. The underlying stratum granulosum may be absent or attenuated but is normal is other parts of the lesion. There is a perivascular or lichenoid lymphocytic infiltrate. Amyloid deposits have been reported in DSAP and in the intertriginous portion of perianal porokeratosis (porokeratosis ptychotropica). The central portion of a porokeratosis may show epidermal atrophy and areas of liquefaction degeneration.

Genetics

All forms of porokeratosis have been reported to have familial clusters with autosomal dominant patterns of inheritance but with variable penetration. A number of very different chromosomal loci have been identified in DSAP, including 12q23.2-24.1, 1p31.3-p31, 16q24.1-24.3 and 18p11.3 [17]. Linear porokeratosis follows the lines of Blaschko and may be systematized, indicating genetic mosaicism.

Environmental factors

Exposure to UV radiation is a factor in the induction of superficial actinic porokeratosis and porokeratosis of Mibelli.

Clinical features

History

Porokeratoses present with single or multiple papules or plaques which develop into annular lesions with a thin raised border. They are usually asymptomatic but may be pruritic and, if verrucous, may cause discomfort from pressure.

Presentation

Localized forms

Porokeratosis of Mibelli starts as a single or small group of keratotic papules which may be pigmented. These gradually grow over years to form one or more irregular plaques with a thin, keratotic and well-demarcated border. The central area may be atrophic, either hyper- or hypopigmented, hairless and anhidrotic (Figure 87.17). Lesions are generally distributed on the extremities but can occur anywhere on the body. Occasionally, giant and verrucous forms of the disease may occur [18].

Linear porokeratosis generally occurs in infancy as unilateral streaks or plaques of reddish-brown papules along limbs or the side of the trunk, head or neck following Blaschko lines, indicating underlying somatic mosaicism (Figure 87.18). There is a higher risk of malignant change in linear porokeratosis than in other forms of porokeratosis [19].

Punctate palmoplantar porokeratosis is a rare type of porokeratosis in which seed-like punctate keratoses form on the palms and soles during adulthood [1].

Genital porokeratosis is a rare localized type which it is important to be aware of as it is frequently misdiagnosed clinically. It occurs almost exclusively in men, more often affecting the scrotum than the penis (Figure 87.19) [20]. Vulval porokeratosis is much rarer [21].

Perianal porokeratosis which has been termed porokeratosis ptychotropica [22], is another very rare type which may be very inflammatory and thus elude diagnosis until appropriate biopsies have been taken (Figure 87.20).

Disseminated forms

DSAP is the most common form of porokeratosis [1, 5], representing more than half of all cases. The condition is often overlooked as the lesions may be quite inconspicuous to the casual observer. Few or multiple flesh-coloured, pink or reddish-brown finely scaling macules with a thin but well-defined raised border start to appear in early adult life, predominantly on the lower legs and arms (Figure 87.21). Palms and soles are not affected. Lesions are generally small, <1 cm diameter and usually asymptomatic. Patients will often give a history of worsening of the condition following sun exposure.

Disseminated superficial porokeratosis is not necessarily related to sun exposure and will then present in both sun-exposed and sun-protected sites, including sometimes oral mucosa and genitalia. It may be associated with immunodeficiency (e.g. organ transplantation, malignancy, HIV infection) or may develop sporadically during childhood [1].

Systematized linear porokeratosis is a disseminated variant of linear porokeratosis which may be unilateral or generalized and follows the lines of Blaschko [1, 23].

Disseminated palmoplantar porokeratosis (porokeratosis palmaris et plantaris disseminata) is a rare generalized form of punctate palmoplantar porokeratosis in which palmoplantar lesions which first appear in the third decade of life are succeeded by multiple widely disseminated wart-like keratoses in both sun-exposed and sun-protected areas including oral mucosa and genitalia and often following Blaschko lines [1, 24].

Transient acantholytic dermatosis

Definition and nomenclature

Transient acantholytic dermatosis (TAD) is a relatively common transient or persistent monomorphous, papulovesicular eruption mainly affecting the trunk which may be pruritic or asymptomatic It was first described by Grover in 1970 [1].

Introduction and general description

The term TAD is possibly misleading [2], for although it is self-limiting in some patients it may be very persistent in others. The physician needs a high index of suspicion to diagnose this disease, as clinically it resembles a number of inflammatory dermatoses and histologically is similar to several other dermatoses.

Epidemiology

TAD is a relatively common inflammatory dermatosis but there are no incidence data available. In a Swiss study [2], only 24 cases of TAD were found amongst 30 000 biopsies taken. Hospital studies of incidence in hospital referrals in the USA and France have shown an incidence of about 0.1% [3].

Age

TAD is a disease of older patients with a mean age at diagnosis of 61 years but may manifest throughout adult life [3].

Sex

The disease has a male predominance with a male to female ratio of 2.4 : 1 [3].

Ethnicity

TAD is commonest in white populations.

Associated diseases

TAD may be seen in conjunction with a number of other inflammatory dermatoses including psoriasis, asteatotic eczema, contact allergic dermatitis and contact irritant dermatitis. In one study, 11% of patients with TAD were found to have a concurrent inflammatory dermatosis [4].

TAD may also be associated with malignant disease including skin cancer and haematological malignancies [4].

Pathophysiology

The cause of TAD is unknown. A recent study has demonstrated autoantibodies against a number of proteins involved in keratinocyte development, activation, growth, adhesion and motility using proteomic microarrays to analyse immunoglobulin A (IgA) and IgG autoantibodies [5]. It is still unclear whether these autoantibodies are causative or are a reaction to the damage to keratinocytes seen in this disease.

Predisposing factors

TAD has been associated with exposure to natural UV radiation, heat and sweating, which has led to the hypotheses that the eccrine sweat glands are aetiologically involved. The disease has not, however been associated with artificial UV exposure and in some reports is more common in the winter [6]. A number of case series have reported the association of TAD with hospitalized and bedridden patients [7].

Pathology

The primary histological feature of TAD is the presence of small foci of acantholysis with dyskeratosis, intraepidermal clefting and sometimes vesicle formation (Figure 87.22). Five patterns of acantholysis have been described, present either singly or in combination. The incidence of these patterns observed in the three largest studies on TAD are: pemphigus vulgaris-like (47%), Darier-like (18%), spongiotic (9%), pemphigus foliaceus-like (9%) and Hailey–Hailey-like (8%) [2] (see Table 87.1).

Table 87.1 Histological patterns in transient acantholytic dermatosis [2].

Darier like	Suprabasal acantholysis with scattered dyskeratosis and apoptotic cells (corps ronds and grains) throughout the epidermis
Hailey–Hailey like	Acantholyisis throughout the stratum spinosum with more hyperplastic epidermis and no significant dyskeratosis
Pemphigus vulgaris like	Suprabasal acantholyisis often with large numbers of eosinophils present
Spongiotic	Epidermal oedema causing separation of keratinocytes and prominent desmosomes
Pemphigus foliaceus like	Superficial clefting in the superficial epidermis

Within the dermis, there is usually a sparse lymphohistiocytic, perivascular infiltrate. Lichenoid change with basal vacuolization has been reported; eosinophils and neutrophils may be present [8].

Environmental factors

TAD is reported to be more common in the winter but may be exacerbated by UV exposure and sweating.

Clinical features

History

Patients usually give a history of the sudden onset of itchy papules on the trunk.

Presentation

The normal presentation is of a papulovesicular erythematous eruption on the trunk of a middle-aged or elderly white male. It starts with small papules and vesicles that quickly crust and develop keratotic erosions (Figure 87.23). The eruption is usually very itchy and the patient presents with multiple excoriations, although in some patients there is no pruritus. In others, the distribution extends to cover the proximal limbs. In many patients, it may live up to its name and be transient, lasting 2–4 weeks; in some it may, however, persist for months or years or follow a chronic relapsing course.

Clinical variants

Some authors use the term ‘persistent and recurrent acantholytic dermatosis’ to encompass those cases which do not rapidly resolve.

Differential diagnosis

TAD has very characteristic clinical features and usually presents little problem in diagnosis. It may be confused with folliculitis, papular urticaria, scabies and herpes zoster. Galli–Galli disease, a rare acantholytic variant of Dowling–Degos disease occurs in a similar age group and may clinically resemble TAD but is usually more widespread, affecting the hands and groins and the reticulate pattern seen in Dowling–Degos disease may be present [9].

Complications and co-morbidities

TAD has been shown to be associated with skin cancer and in one study 8% of patients had a haematological malignancy [3].

Disease course and prognosis

TAD may resolve spontaneously after weeks or months or persist for years. There are no clinical or histological prognostic signs in this disease.

Investigations

Skin biopsy will confirm the clinical diagnosis. In view of the raised incidence of haematological malignancies seen in this disease, haematological work-up is advised.

Management

Patients should be advised to avoid sunlight exposure, strenuous exercise and heat, all of which may exacerbate the disease.

First line

In many patients, the disease resolves spontaneously after a few weeks and all that is needed is a potent topical corticosteroid for symptomatic relief. Topical vitamin D analogues and calcineurin inhibitors have been used. Systemic antihistamines can be used to control pruritus.

Second line

In more severe cases, short courses of systemic corticosteroids have been shown to give sustained improvement but rebound may occur. Systemic retinoids [10], phototherapy [11] and methotrexate have been used in more severe and refractory cases.

Third line

Recent case reports have claimed benefit from etanercept [12] and, in one patient with recalcitrant TAD, from photodynamic therapy [13].

Keratolysis exfoliativa

Definition and nomenclature

Keratolysis exfoliativa is a common disease of young adults in which discrete areas of superficial skin peeling occur on the palms, starting as air-filled blisters leading to a circinate or irregular annular pattern of scaling. This may be associated with localized hyperhidrosis.

Introduction and general description

Keratolysis exfoliativa represents an acquired form of non-inflammatory skin peeling. The condition was first described by Wende in 1919 [1].

Epidemiology

Incidence and prevalence

Keratolysis exfoliativa is a common condition but there are no epidemiological data available on it.

Age

Keratolysis exfoliativa typically affects young adults.

Sex

No sex predilection described.

Ethnicity

No data.

Associated diseases

Keratolysis exfoliativa may be associated with local hyperhidrosis.

Pathophysiology

The cause is unknown but a recent study suggests that premature corneodesmolysis is the main pathological mechanism [2]. This study showed no association with atopy and filaggrin mutations were not found.

Pathology

Histology and electron microscopy show cleavage and partially degraded corneodesmosomes within the stratum corneum [2]. There is no inflammatory infiltrate.

Environmental factors

Keratolysis exfoliativa often presents in the summer with warmer weather. It can be aggravated by detergents, solvents and irritants.

Clinical features (Figure 87.24)

History

Keratolysis exfoliativa starts as a sudden onset of discrete scaling on the palms of the hands.

Presentation

Keratolysis exfoliativa presents initially as small superficial blister-like air-filled pockets on the palms and palmar aspects of the fingers or occasionally the feet. These are formed as the result of focal separation of superficial layers of corneocytes from the stratum corneum. The roofs of the pockets rupture centrally as they expand centrifugally, leaving a ragged rim of residual scale surrounding an irregular superficial dry erosion. There is no irritation and vesicles are not present. Peeled areas of skin lack normal barrier function and may become dry and fissured, particularly on the fingertips.

Differential diagnosis

Keratolysis exfoliativa is a very distinctive disorder but may be confused with pompholyx, psoriasis, tinea manuum, epidermolysis bullosa simplex or acral skin peeling syndrome (see Chapter 65).

Complications and co-morbidities

Keratolysis exfoliativa may be associated with local hyperhidrosis.

Disease course and prognosis

Keratolysis exfoliativa is generally self-limiting but may recur each summer.

Investigations

No investigations are needed.

Management

Keratolysis exfoliativa is usually a self-limiting condition and treatment may not be needed. Patients should be advised to avoid contact with detergents and other irritants.

First line

Emollients and moisturisers, particularly moisturisers containing agents such as urea or salicylic acid. Topical steroids may exacerbate the condition by further drying the skin.

Xerosis cutis and asteatosis

Definition and nomenclature

Xerosis cutis (dry skin) and asteatosis (lacking in fat) are alternative terms used to describe an acquired abnormality of the skin which has lost its normal soft smooth surface and feels dry and rough to the touch. This may be the result of a range of endogenous and exogenous factors, especially ageing and low ambient humidity, and is associated with impaired epidermal barrier function. Xerosis cutis may be accompanied by pruritus (winter itch) and predisposes to eczematous inflammation (eczéma craquelé or asteatotic eczema).

Introduction and general description

Xerosis cutis is very common and almost physiological in old age. Xerosis cutis (dry skin) and asteatosis (lacking in fat) are alternative terms used to describe an acquired abnormality of skin which has lost its normal soft smooth surface and feels dry and rough to the touch. The condition is associated with an impaired barrier function of the stratum corneum, as reflected by increased transepidermal water loss (TEWL) and reduced water content. Xerosis may however be more accurately assessed by clinical examination [1].

Xerosis is also a common component of eczematous skin diseases, e.g. atopic eczema (atopic xeroderma). This is discussed in detail in Chapter 41.

Epidemiology

Incidence and prevalence

Xerosis cutis is very common and almost universal in old age.

Age

It generally first manifests in the seventh decade of life and progresses with age.

Sex

It appears to be slightly more common in men.

Ethnicity

Xerosis cutis is universal in older age groups. In children, it is said to be more prevalent in sub-Saharan Africa, possibly due to frequent use of soap and high local temperatures: TEWL has been shown to be higher in phototype 6 skin compared to other skin types [2].

Associated diseases

It may be observed in association with marasmus, malnutrition, diabetes, renal failure and renal dialysis.

Pathophysiology

Xerosis cutis was initially thought to be due to reduced sebum production with age. The major factors in the development of dry skin, however, appear to be changes in stratum corneum function and lipids [3]. There is a deficiency of all stratum corneum lipids as well as premature expression of involucrin and persistence of corneodesmosomes [4, 5, 6, 7]. Loricrin expression does not appear to be changed [5]. Dry skin also shows decreases in keratin 1 and 10 and an increase of keratin 5 and 14. In women, oestrogen substitution ameliorates dry skin, indicating a role for sex hormones [8].

Predisposing factors

More common in winter where humidity is low; central heating tends to aggravate the condition. Damage to the stratum corneum by excessive contact with soap or detergents or from frequent and prolonged bathing have each been proposed as additional exacerbating factors, although one study found no difference in bathing habits between patients with widespread asteatotic eczema and controls, suggesting that other unknown factors may play a role [9]. Lack of oestrogen is thought to be a contributory factor in postmenopausal women [8].

Pathology

No histological abnormalities apart from slight irregularity in the stratum corneum.

Environmental factors

Low humidity in the winter and the drying effects of central heating exacerbate xerosis cutis. The generally dry atmosphere in hospital wards increases the risk in frail elderly patients confined to hospital for prolonged periods. Targeted anticancer therapies may induce xerosis [10].

Clinical features

History

Dryness and scaliness of the skin is generally the first manifestation of the condition, followed by itching.

Presentation

Xerosis cutis most often affects the shins and may not affect any other area of the skin. It may become widespread but spares the face, neck, palms and soles. In elderly immobile hospitalized patients, it will frequently affect the abdomen and, in women, the anterior surfaces of the breasts, but spares the back and the undersurfaces of the breasts.

Affected skin looks dull, dry and covered with fine scale which sheds readily. The surface may become crazed with criss-cross superficial cracks in the stratum corneum giving the skin a crazy-paving look (Figure 87.25).

Clinical variants

Asteatotic eczema (eczéma craquelé). Xerosis cutis may progress to an eczematous inflammation in which the fissures in the skin surface become red, inflamed and itchy (Figure 87.26). Eczéma craquelé may sometimes be seen after episodes of acute distension of the skin, usually due to acute oedema (see Figure 87.28).

Differential diagnosis

Dry scaly skin is a component of many inflammatory skin diseases. These include atopic eczema (see Chapter 41), hereditary (see Chapter 65) and acquired ichthyosis (see earlier). Apart from the latter, these generally manifest at an early age.

Disease course and prognosis

Xerosis cutis is often seasonal, being worse or occurring only in the winter; it tends to worsen and become more persistent with age.

Management

Removal of precipitating factors: patients should be instructed to avoid applying potential irritants to the skin. Simple measures to increase the humidity of centrally heated rooms (e.g. placing a bowl of water close to radiators) may help.

First line

Emollients and moisturisers are the treatment of choice and usually result in rapid improvement.

Second line

If asteatotic eczema develops, anti-inflammatory treatment with a mild corticosteroid ointment may be necessary but long-term topical corticosteroids should be avoided, as these may further damage the skin barrier. Topical tacrolimus and pimecrolimus have also been advocated for the treatment of asteatotic eczema [11, 12].

Acute epidermal distension and acute oedema blisters

Definition and nomenclature

There are certain situations where the epidermis is unable to withstand forces which would normally not affect its integrity. Acute distension of uninflamed skin in the absence of disordered epidermal integrity may at times result in epidermal separation or disruption. Most commonly, this is due to acute dependent oedema, as from acute congestive heart failure, and results in large bullae which may be mistaken for bullous pemphigoid. Alternatively, the distension may result in disruption of epidermal cohesion manifesting as eczéma craquelé.

Introduction and general description

Subepidermal blistering is a well-recognized component of many skin disorders in which there are hereditary or acquired abnormalities affecting the normal adhesion of the epidermis to the dermis. It is also a normal reaction to excessive thermal or frictional trauma.

Bullae may also occur in otherwise normal skin as a consequence of the rapid onset of oedema. The speed of development of such acute oedema appears to be a more important risk factor than the degree of oedema. The blisters respond rapidly to reduction of oedema [1]. It has been described after attacks of angio-oedema as well as in the elderly following the sudden onset or exacerbation of oedema, e.g. after acute congestive heart failure [1, 2, 3, 4].

Epidemiology

Incidence and prevalence

Reported only in case series, but no structured studies available.

Age

May appear in any person who develops oedema acutely, though the elderly appear to be more susceptible [2].

Pathophysiology

Little is known about the pathophysiology of this disease. Ultrasound studies of acute oedema suggests that fluids accumulate more superficially in the dermis than following lymphoedema or chronic stasis [5, 6] which may sometimes be a contributory factor.

Pathology

Biopsies have shown marked epidermal spongiosis, and a slight lymphohistiocytic inflammatory infiltrate. Direct immunofluorescence was negative [2].

Clinical features

History

Acute onset of oedema without itching.

Presentation

Tense unilocular non-pruritic bullae appearing in areas of acute oedema (Figure 87.27).

Clinical variants

Acute cutaneous distension may alternatively result in disruption of the epidermis as seen in asteatotic eczema with crazing and fissuring of the epidermis and leakage of oedema fluid to the surface (Figure 87.28) [1, 7, 8].

Differential diagnosis

In the elderly population, autoimmune bullous diseases, particularly bullous pemphigoid, are an important differential diagnosis. The close temporal association with acute oedema, the absence of itching and the lack of spread to other areas of the body form important clues to the diagnosis.

Diabetic bullae (see Chapter 64) may resemble acute oedema blisters but are generally not so tense and they are not associated with acute oedema (Figure 87.29).

Patel N, Spencer LA, English JC III, et al. Acquired ichthyosis. J Am Acad Dermatol 2006;55:647–56.
Brazzelli V, Larizza D, Muzio F, et al. Acquired ichthyosis in a child with autoimmune thyroiditis. Pediatr Dermatol 2010;27:413–14.
Akpinar TS, Ozkok A, Bakkaloglu OK, et al. Acquired ichthyosis as a presenting finding of Hodgkin's lymphoma. Int J Hematol 2012;96:401–2.
Berrady R, Baybay H, Khammar Z, et al. Acquired ichthyosis and haematological malignancies: five cases. Ann Dermatol Vénéréol 2012;139:9–14.
Riesco Martínez MC, Muñoz Martín AJ, Zamberk Majlis P, et al. Acquired ichthyosis as a paraneoplastic syndrome in Hodgkin's disease. Clin Transl Oncol 2009;11:552–3.
Levy O, Tishler M. Acquired ichthyosis as the primary manifestation of renal cell carcinoma. Isr Med Assoc J 2009;11:121–2.
Morizane S, Setsu N, Yamamoto T, et al. Ichthyosiform eruptions in association with primary cutaneous T-cell lymphomas. Br J Dermatol 2009;161:115–20.
Harati A, Brockmeyer NH, Altmeyer P, et al. Skin disorders in association with monoclonal gammopathies. Eur J Med Res 2005;29:93–104.
Sparsa A, Boulinguez S, Le Brun V, et al. Acquired ichthyosis with pravastatin. J Eur Acad Dermatol Venereol 2007;21:549–50.
Sanli H, Akay BN, Sen BB, et al. Acquired ichthyosis associated with type 1 diabetes mellitus. Dermatoendocrinology 2009;1:34–6.
London RD, Lebwohl M. Acquired ichthyosis and hyperparathyroidism. J Am Acad Dermatol 1989;21:801–2.
Dykes PJ, Marks R. Acquired ichthyosis: multiple causes for an acquired generalized disturbance in desquamation. Br J Dermatol 1977;97:327–34.
Singh A, Thappa DM, Hamide A. The spectrum of mucocutaneous manifestations during the evolutionary phases of HIV disease: an emerging Indian scenario. J Dermatol 1999;26:294–304.
Milagres SP, Sanches JA, Milagres ACP, et al. Histopathology and immunohistochemical assessment of acquired ichthyosis in patients with human T-cell lymphotropic virus type 1-associated myelopathy. Br J Dermatol 2003;149:776–81.
Daniel DR, Rubin AI, Rabinowitz AD, et al. Acquired ichthyosis with systemic lupus erythematosus: both dermatoses in a single skin biopsy specimen. Cutis 2008;81:159–62.
Lee HW, Ahn SJ, Choi JC, et al. Acquired ichthyosis associated with an overlap syndrome of systemic sclerosis and systemic lupus erythematosus. J Dermatol 2006;33:52–4.
Tlacuilo-Parra JA, Guevara-Gutiérrez E, Salazar-Páramo M. Acquired ichthyosis associated with systemic lupus erythematosus. Lupus 2004;13:270–3.
Kutting B, Traupe H. Acquired ichthyosis-like skin disease: a challenge for diagnostic evaluation. Hautarzt 1995;46:836–40.
Aram H. Acquired ichthyosis and related conditions. Int J Dermatol 1984;23:458–61.
Elias PM, Brown BE, Ziboh VA. The permeability barrier in essential fatty acid deficiency: evidence for a direct role for linoleic acid in barrier function. J Invest Dermatol 1980;74:230–3.
Aggett PJ, Cavanagh HP, Matthew DJ, et al. Shwachman's syndrome: a review of 21 cases. Arch Dis Child 1980;55:331–47.
London RD, Lebwohl M. Acquired ichthyosis and hyperparathyroidism. J Am Acad Dermatol 1989;21:801–2.
Kelley BP, George DE, LeLeux TM, Hsu S. Ichthyosiform sarcoidosis: a case report and review of the literature. Dermatol Online J 2010;16(8):5.
Yosipovitch G, Hodak E, Vardi P, et al. The prevalence of cutaneous manifestations in IDDM patients and their association with diabetes risk factors and microvascular complications. Diabetes Care 1998;21:506–9.
Monnier VM, Bautista O, Kenny D, et al. Skin collagen glycation, glycoxidation and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type I diabetes: relevance of glycated collagen products versus HbA1C as markers of diabetic complications. Diabetes 1999;48:870–80.
King LE, Gates RE, Stoscheck CM, Nanney LB. The EGF/TGF alpha receptor in skin. J Invest Dermatol 1990;94(Suppl.):164S–170S.
Takashi S, Norihiro F, Shiohama A, et al. Filaggrin loss-of-function mutations are not a predisposing factor for atopic dermatitis in an Ishigaki Island under subtropical climate. J Dermatol Sci 2014;76:10–15.
DiGiovanna JJ, Robinson-Bostom L. Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermatol 2003;4:81–95.

Acanthosis nigricans

Brickman WJ, Binns HJ, Jovanovic BD, Kolesky S, Mancini AJ, Metzger BE. Acanthosis nigricans: a common finding in overweight youth. Pediatr Dermatol 2007;24:601–6.
Otto DE, Wang X, Garza V, Fuentes LA, Rodriguez MC, Sullivan P. Increasing body mass index, blood pressure, and acanthosis nigricans abnormalities in school-age children. J Sch Nurs 2013;29:442–51.
Sinha S, Schwartz RA. Juvenile acanthosis nigricans. J Am Acad Dermatol 2007;57:502–8.
Pattamadilok B, Devpura S, Syed ZU, et al. Quantitative skin color measurements in acanthosis nigricans patients: colorimetry and diffuse reflectance spectroscopy. Photodermatol Photoimmunol Photomed 2012;28:213–15.
Hud JA Jr, Cohen JB, Wagner JM, Cruz PD Jr. Prevalence and significance of acanthosis nigricans in an adult obese population. Arch Dermatol 1992;128:941–4.
Krawczyk M, Mykala-Ciesla J, Kolodziej-Jaskula A. Acanthosis nigricans as a paraneoplastic syndrome. Case reports and review of literature. Pol Arch Med Wewn 2009;119:180–3.
Singh SK, Rai T. A rare case of malignant acanthosis nigricans in a lady with ovarian cancer. Indian Dermatol Online J 2013;4(2):125–7.
Zhang N, Qian Y, Feng AP. Acanthosis nigricans, tripe palms, and sign of Leser-Trélat in a patient with gastric adenocarcinoma: case report and literature review in China. Int J Dermatol 2015;54:338–42.
Voorhees J, Goto K, Wolff C. Overweight, elevated blood pressure, acanthosis nigricans and adherence to recommended dietary and physical activity guidelines among Hmong and white middle school students. J Immigr Minor Health 2014;16:273–9.
Sadeghian G, Ziaie H, Amini M, et al. Evaluation of insulin reistance in obese women with and without acanthosis nigricans. J Dermatol 2009;36:209–12.
Scott AT, Metzig AM, Hames RK, et al. Acanthosis nigricans and oral glucose tolerance in obese children. Clin Pediatr 2010;49:69–71.
Stoddart ML, Blevins KS, Lee ET, Wang W, Blackett PR. Association of acanthosis nigricans with hyperinsulinemia compared with other selected risk factors for type 2 diabetes in Cherokee Indians: the Cherokee Diabetes Study. Diabetes Care 2002;25:1009–14.
Cruz PDJ, Hud JA. Excess insulin binding to insulin like growth factor receptors: proposed mechanism for acanthosis nigricans. J Invest Dermatol 1992;98:82S–85S.
McIntosh I, Bellus GA, Jabs EW. The pleiotropic effects of fibroblast growth factor receptors in mammalian development. Cell Struct Funct 2000;25:85–96.
Berk DR, Spector EB, Bayliss SJ. Familial acanthosis nigricans due to K650T FGFR3 mutation. Arch Dermatol 2007;143:1153–6.
Lane SW, Manharan S, Mollee PN. Palifermin-induced acanthosis nigricans. Intern Med J 2007;37:417–18.
Koyama S, Ikeda K, Sato M, et al. Transforming growth factor alpha-producing gastric carcinoma with acanthosis nigricans: an endocrine effect of TGF alpha in the pathogenesis of cutaneous paraneoplastic syndrome and epithelial hyperplasia of the esophagus. J Gastroenterol 1997;32:71–7.
Sawatkar GU, Dogra S, Bhadada SK, et al. Acanthosis nigricans: an uncommon cutaneous adverse effect of a common medication. Report of two cases. Indian J Dermatol Venereol Leprol 2013;79:553.
Mailler-Savage EA, Adams BB. Exogenous insulin-derived acanthosis nigricans. Arch Dermatol 2008;144:126–7.
Piccolo V, Russo T, Picciocchi R, et al. Generalised idiopathic benign acanthosis nigricans in childhood. Ann Dermatol 2013;25:375–7.
Denadai R, Souto RM, Auada-Souto MP. Generalised acanthosis nigricans without systemic disease associated. Dermatol Online J 2013;19(9):19614.
Gönül M, Kiliç A, Cakmak SK, Gül U, Ekiz OD, Ergül G. Juvenile generalised acanthosis nigricans without any systemic disease. Pediatr Int 2009;51:595–7.
Schwartz RA. Acral acanthosis nigricans (acral acanthotic anaomaly). J Am Acad Dermatol 2007;65:349–50.
Jeong JS, Lee JY, Yoom TY. Unilateral nevoid acanthosis nigricans in the submammary location. Ann Dermatol 2011;23:95–7.
Katz RA. Treatment of acanthosis nigricans with isotretinoin. Arch Dermatol 1980;116:110–11.
Mir A, Wu T, Orlow SJ. Cutaneous features of Crouzon syndrome with acanthosis nigricans. JAMA Dermatol 2013;149:737–41.
Sharda S, Panigrahi I, Gupta K, Singhi S, Kumar R. Newborn with acanthosis nigricans: can it be Crouzon syndrome with acanthosis nigricans? Pediatr Dermatol 2010;27:43–7.

Confluent and reticulated papillomatosis

Gougerot H, Carteaud A. Papillomatose pigmentee inominee. Bull Soc Fr Dermatol Syphiligr 1927;34:719–21.
Scheinfeld N. Confluent and reticulated papillomatosis: a review of the literature. Am J Clin Dermatol 2006;7:305–13.
Hamilton D, Tavafoghi V, Shafer JC, et al. Confluent and reticulated papillomatosis of Gougerot and Carteaud. Its relation to other papillomatoses. J Am Acad Dermatol 1980;2:401–10.
Davis MD, Weenig RH, Camilleri MJ. Confluent and reticulate papillomatosis (Gougerot–Caryeaud syndrome): a minocycline-responsive dermatosis without evidence for yeast in pathogenesis. A study of 39 patients and a proposal of diagnostic criteria. Br J Dermatol 2006;154:287–93.
Tamraz H, Raffoul M, Kurban M, et al. Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon. J Eur Acad Dermatol Venereol 2013;27:e119–23.
Roberts SO, Lachapelle JM. Confluent and reticulate papillomatosis (Gougerot–Carteaud) and pityrosporum orbiculare. Br J Dermatol 1969;81:841–5.
Yesudian P, Kamalam S, Razack A. Confluent and reticulated papillomatosis (Gougerot–Carteaud). An abnormal host reaction to Malassezzia furfur. Acta Derm Venereol 1973;53:381–4.
Natarajan S, Milne D, Jones AL, et al. Dietzia strain X: a newly described Actinomycete isolated from confluent and reticulated papillomatosis. Br J Dermatol 2005;153:825–7.
Kanitakis J, Zambruno G, Viac J, Thivolet J. Involucrin expression in keratinization disorders of the skin: a preliminary study. Br J Dermatol 1987;117:479–86.
Inalöz HS, Patel G, Knight AG. Familial confluent and reticulated papillomatosis. Arch Dermatol 2002;138:276–7.
Henning JP, de Wit RF. Familial occurrence of confluent and reticulated papillomatosis. Arch Dermatol 1981;117:809–10.
Jimbow M, Talpash O, Jimbow K. Confluent and reticulated papillomatosis: clinical, light and electron microscopic studies. Int J Dermatol 1992;31:480–3.
Hirokawa M, Matsumoto M, Iizuka H. Confluent and reticulated papillomatosis: a case with concurrent acanthosis nigricans associated with obesity and insulin resistance. Dermatology 1994;188:148–51.
Zhang CH, Zhang C, Wu J, et al. Confluent and reticulated papillomatosis associated with hyperthyroidism. Eur J Dermatol 2010;20:833–5.
Lee SH, Choi EH, Lee WS, Kang WH, Bang DS. Confluent and reticulated papillomatosis: a clinical, histopathological, and electron microscopic study. J Dermatol 1991;18:725–30.
Kim BS, Lim HJ, Kim HY, et al. Case of minocycline-effective confluent and reticulated papillomatosis with unusual location on forehead. J Dermatol 2009;36:251–3.
Lee D, Cho KJ, Hong SK, Seo JK, Hwang SW, Sung HS. Two cases of confluent and reticulated papillomatosis with an unusual location. Acta Derm Venereol 2009;89:84–5.
Rodriguez-Carreon AA, Arenas-Guzman R, Fonte-Avalos V, et al. Confluent and reticulated Gougerot–Carteaud papillomatosis: a case report of an excellent response to minocycline. Gac Med Mex 2008;144:67–70.
Jang HS, Oh CK, Cha JH, Cho SH, Kwon KS. Six cases of confluent and reticulated papillomatosis alleviated by various antibiotics. J Am Acad Dermatol 2001;44:652–5.
Fung MA, Frieden IJ, LeBoit PE, et al. Confluent and reticulate papillomatosis: successful treatment with minocycline. Arch Dermatol 1996;132:1400–1.
Gönül M, Cakmak SK, Soylu S, Kiliç A, Gül U, Ergül G. Successful treatment of confluent and reticulated papillomatosis with topical mupirocin. J Eur Acad Dermatol Venereol 2008;22:1140–2.
Nordby CA, Mitchell AJ. Confluent and reticulated papillomatosis responsive to selenium sulfide. Int J Dermatol 1986;25:194–9.
Bowman PH, Davis LS. Confluent and reticulated papillomatosis: response to tazarotene. J Am Acad Dermatol 2003;48(Suppl. 5):S80–1.
Carrozzo AM, Gatti S, Ferranti G, et al. Calcipotriol treatment of confluent and reticulated papillomatosis (Gougerot–Carteaud syndrome). J Eur Acad Dermatol Venereol 2000;14:131–3.
Ginarte M, Fabeiro JM, Toribio J. Confluent and reticulated papillomatosis (Gougerot–Carteaud) successfully treated with tacalcitol. J Dermatol Treat 2002;13:27–30.
Lee MP, Stiller MJ, McClain SA, Shupack JL, Cohen DE. Confluent and reticulated papillomatosis: response to high-dose oral isotretinoin therapy and reassessment of epidemiologic data. J Am Acad Dermatol 1994;31:327–31.
Erkek E, Ayva S, Atasoy P, Emeksiz MC. Confluent and reticulated papillomatosis: favourable response to low-dose isotretinoin. J Eur Acad Dermatol Venereol 2009;23:1342–3.

Pityriasis rotunda

Zur RL, Shapero J, Shapero H. Pityriasis rotunda diagnosed in Canada: case presentation and review of literature. J Cutan Med Surg 2013;17:426–8.
Findlay GH. Pityriasis rotunda in South African Bantu. Br J Dermatol 1965;77:63–4.
Grimalt R, Gelmetti C, Brusasco A, et al. Pityriasis rotunda: report of a familial occurrence and review of the literature. J Am Acad Dermatol 1994;31:866–71.
Sarkany I, Hare PJ. Pityriasis rotunda (pityriasis circinata). Br J Dermatol 1964;76:223–8.
Kahana M, Levy A, Ronnen M, Schewach-Millet M, Stempler D. Pityriasis rotunda in a white patient. Report of the second case and review of the literature. J Am Acad Dermatol 1986;15:362–5.
DiBisceglie AM, Hodkinson HJ, Berkowitz I, et al. Pityriasis rotunda. A cutaneous marker of hepatocellular carcinoma in South African blacks. Arch Dermatol 1986;122:802–4.
Berkowitz I, Hodkinson HJ, Kew MC, DiBisceglie AM. Pityriasis rotunda as a cutaneous marker of hepatocellular carcinoma: a comparison with its prevalence in other diseases. Br J Dermatol 1989;120:545–9.
Etoh T, Nakagawa H, Ishibashi Y. Pityriasis rotunda associated with multiple myeloma. J Am Acad Dermatol 1991;24:303–4.
Combemale P, L'Henaff N, Guennoc B. Pityriasis rotunda. Ann Dermatol Vénéréol 1993;120:287–8.
Swift PJ, Saxe N. Pityriasis rotunda in South Africa: a skin disease caused by undernutrition. Clin Exp Dermatol 1985;10:407–12.

Keratosis pilaris

Thomas M, Khopkar US. Keratosis pilaris revisited: is it more than just a follicular keratosis? Int J Trichol 2012;4:255–8.
Hwang S, Schwartz RA. Keratosis pilaris: a common follicular hyperkeratosis. Cutis 2008;82:177–80.
Mevorah B, Marazzi A, Frenk E. The prevalence of accentuated palmoplantar markings and keratosis pilaris in atopic dermatitis, autosomal dominant ichthyosis and control dermatological patients. Br J Dermatol 1985;112:679–85.
Wang CM, Fleming KF, Hsu S. A case of vemurafinib-induced keratosis pilaris like eruption. Dermatol Online J 2012;18:7.
Yosipovitch G, De Vore A, Dawn A. Obesity and the skin: skin physiology and skin manifestations of obesity. J Am Acad Dermatol 2007;56:901–16.
Occella C, Gargani FF, Rampini E, et al. Sindrome di Noonan e keratosis pilaris atrophicans faciei. Minerva Pediatr 1985;37:181–6.
Armour CM, Allanson JE. Further delineation of cardio-facial-cutaneous syndrome: clinical features of 38 patients with proven mutations. J Med Genet 2008;45:249–54.
Larregue M, Charoentier C, Laidet B, et al. Deficit en prolidase et en manganese. Ann Dermatol Vénéréol 1982;109:667–8.
Finn OA, Grant PW, McCallum DI, et al. A singular dermatosis of Mongols. Arch Dermatol 1978;114:1493–4.
Marks R. Follicular hyperkeratosis and ocular abnormalities associated with Fairbanks syndrome. Br J Dermatol 1967;79:118–19.
Perry HO, Su WP. Olmsted syndrome. Semin Dermatol 1995;14:145–51.
Guiller G, Sanciaume C, Hehunester JP, et al. Keratose pilare generalisee et hypervitaminose A chez une enfant insuffisante renale. Ann Dermatol Vénéréol 1982;109:1061–6.
Carnabuci GJ, Rosenberg PE. Monilethrix and keratosis pilaris. Arch Dermatol 1967;96:594.
Leachman SA, Kaspar RL, Fleckman P, et al. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc 2005;10:3–17.
Halal F, Seeton N, Wang NS. A distinct type of hydrotic ectodermal dysplasia. Am J Med Genet 1991;38:552–6.
Whittaker SJ, Griffiths WAD. Erythromelanosis follicularis faciei et colli. Clin Exp Dermatol 1987;12:33–5.
Wakelin SH, Lipscombe T, Orton DI, et al. Lithium induced follicular hyperkeratosis. Clin Exp Dermatol 1996;21:296–8.
Baden HP, Byers HR. Clinical findings, cutaneous pathology and response to therapy in 21 patients with keratosis pilaris atrophicans. Arch Dematol 1994;130:469–75.
Nazarenko SA, Ostroverkhova NV, Vasileva EO, et al. Keratosis pilaris and ulerythema ophryogenes associated with an 18p deletion caused by a Y/18 translocation. Am J Med Genet 1999;85:179–82.
Poskitt L, Wilkinson JD. Natural history of keratosis pilaris. Br J Dermatol 1994;130:711–13.
Lalit G, Anubhav G, Kumar KA, et al. Familial erythromelanosis follicularis faciei et colli with extensive keratosis pilaris. Int J Dermatol 2011;50:1400–1.
Sardana K, Relhan V, Garg V, et al. An observational analysis of erythromelanosis follicularis faciei et colli. Clin Exp Dermatol 2008;33:333–6.
Augustine M, Jayaseelan E. Erythromelanosis follicularis faciei et colli: relationship with keratosis pilaris. Indian J Dermatol Venereol Leprol 2008;74:47–9.
Dianzani C, Pizzuti A, Gaspardini F, et al. Ulerythema ophryogenes, a rare and often misdiagnosed syndrome: analysis of an idiopathic case. Int J Immunopathol Pharmacol 2011;24:523–7.
Oranje AP, van Osch LDM, Oosterwijk JC. Keratosis pilaris atrophicans: one heterogeneous disease or a symptom in different clinical entities? Arch Dermatol 1994;130:500–2.
Sequeira FF, Jayaseelan E. Keratosis follicularis spinulosa decalvans in a female. Indian J Dermatol Venereol Leprol 2011;77:325–7.
Luria RB, Conologue T. Atrophoderma vermiculatum: a case report and review of the literature on keratosis pilaris atrophicans. Cutis 2009;83:83–6.
Golusin Z, Jovanovic M, Poliacki M. Atrophic pilar keratosis of the face: case report. Med Pregl 2001;54:486–9.
Novick NL. Practical management of widespread, atypical keratosis pilaris. J Am Acad Dermatol 1984;11:305–6.
Alcántara González J, Boixeda P, Truchuelo Díez MT, et al. Keratosis pilaris rubra and keratosis pilaris atrophicans faciei treated with pulsed dye laser: report of 10 cases. J Eur Acad Dermatol Venereol 2011;25:710–14.
Rodríguez-Lojo R, Pozo JD, Barja JM, et al. Keratosis pilaris atrophicans: treatment with intense pulsed light in four patients. J Cosmet Laser Ther 2010;12:188–90.
Apalla Z, Karakatsanis G, Papageorgiou M, Kastoridou C, Chaidemenos G. A case of atrophoderma vermiculatum responding to systemic isotretinoin. J Dermatol Case Rep 2009 Dec 30;3(4):62–3.

Lichen spinulosus

Boyd AS. Lichen spinulosus: case report and overview. Cutis 1989;43:557–60.
Venkatesh A, Dupuis E, Prajapati V, Rao J. Generalized lichen spinulosus in a 4-year old boy without systemic disease. Arch Dermatol 2012;148:865–6.
Friedman SJ. Lichen spinulosus. Clinicopathologic review of thirty-five cases. J Am Acad Dermatol 1990;22:261–4.
Adamson HG. On a form of chronic superficial dermatitis in circumscribed patches with symmetrical distribution occurring in children. Br J Dermatol 1908;20:109–22.
Cohen SJ, Dicken CH. Generalized lichen spinulosus in an HIV-positive man. J Am Acad Dermatol 1991;25:116–18.
Kano Y, Orihara M, Yagita A, Shiohara T. Lichen spinulosus in a patient with Crohn's disease. Int J Dermatol 1995;34:670–1.
Kabashima R, Sugita K, Kabashima K, et al. Lichen spinulosus in an alcoholic patient. Acta Derm Venereol 2009;89:311–12.
Maiocco KJ, Miller OF. Lichen spinulosus: response to therapy. Cutis 1976;17:294–9.
Forman SB, Hudgins EM, Blaylock WK. Lichen spinulosus: excellent response to tretinoin gel and hydroactive adhesive applications. Arch Dermatol 2007;143:122–3.
Kim SH, Kang JH, Seo JK, et al. Successful treatment of lichen spinulosus with topical tacalcitol cream. Pediatr Dermatol 2010;27:546–7.

Keratosis circumscripta

Shrank AB. Keratosis circumscripta. Arch Dermatol 1966;93:408–10.
Soyinka F, Laja AO. Keartosis circumscripta. A distinct dermatological entity or a variant of psoriasis? Dermatologica 1978;156:341–50.
Verhagen AR, Soyinka F, Laja AO. Keratosis circumscripta. Dermatologica 1979;153:182–3.
Brumwell EP, Murphy SJ. Keratosis circumscripta revisited: a case report and review of the literature. Cutis 2007;79:363–6.
Shams M, Blalock TW, Davis LS. Keratosis circumscripta: a unique case and review of the literature. Int J Dermatol 2011;50:1259–61.

Phrynoderma

Nicholls L. Phrynoderma: a condition due to vitamin deficiency. Indian Med Gaz 1933;68:681–7.
West KP Jr, Mehra S. Vitamin A intake and status in populations facing economic stress. J Nutr 2010;140:201S–207S.
Ayyangar MC. Phrynoderma and nutritional deficiency. Indian J Dermatol Venereol Leprol 1967;33:13–24.
Ocón J, Cabrejas C, Altemir J, Moros M. Phrynoderma: a rare dermatologic complication of bariatric surgery. J Parenter Enteral Nutr 2012;36:361–4.
Barr DJ, Riley RJ, Greco DJ. Bypass phrynoderma. Vitamin A deficiency associated with bowel-bypass surgery. Arch Dermatol 1984;120:919–21.
Bleasel NR, Stapleton KM, Lee M, Sullivan J. Vitamin A deficiency phrynoderma: due to malabsorption and inadequate diet. J Am Acad Dermatol 1999;41(2 Suppl.):322–4.
Beisel WR. Single nutrients and immunity. Am J Clin Nutr 1982;35(2 Suppl.):417–68.
Chandra RK. Nutrition and immunity. Trop Geogr Med 1988;40:S46–51.
Ragunatha S, Kumar VJ, Murugesh SB. A clinical study of 125 patients with phrynoderma. Indian J Dermatol 2011;56:389–92.
Armstrong AW, Setyadi HG, Liu V, Strasswimmer J. Follicular eruption on arms and legs. Phrynoderma. Arch Dermatol 2008;144:1509–14.
Nakjang Y, Yuttanavivat T. Phrynoderma: a review of 105 cases. J Dermatol 1988;15:531–4.
Smith J, Steinemann TL. Vitamin A deficiency and the eye. Int Ophthalmol Clin 2000;40:83–91.
Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press, 2001.
Murthy SR and Prabhakaran VC. Phrynoderma and night blindness. Indian J Ophthalmol 2010 Mar–Apr;58(2)175–6.

Trichodysplasia spinulosa

Haycox CL, Kim S, Fleckman P, et al. Trichodysplasia spinulosa: a newly described folliculocentric viral infection in an immunocompromised host. J Investig Dermatol Symp Proc 1999;4:268–71.
Schwieger-Briel A, Balma-Mena A, Ngan B, et al. Trichodyplasia spinulosa: a rare complication in immunocompromised patients. Pediatr Dermatol 2010;27:509–13.
Blake BP, Marathe KS, Mohr MB, et al. Viral-associated trichodysplasia of immunosuppression in a renal transplant patient. J Drugs Dermatol 2011;10:422–4.
Lee JS, Fredericksen P, Kossard S. Progressive trichodysplasia spinulosa in a patients with chronic lymphocytic leukaemia in remission. Austalas J Dermatol 2008;49:57–60.
Moktefi A, Laude H, Brudy Gulphe L, et al. Trichodysplasia spinulosa associated with lupus. Am J Dermatopathol 2014;36:e70–4.
Kazem S, van der Meijden E, Kooijman S, et al. Trichodysplasia spinulosa characterised by active polyomavirus infection. J Clin Virol 2012;53:225–30.
Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyoma virus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol 2012;148:726–33.
van der Meijden E, Kazem S, Burgers MM, et al. Seroprevalence of trichodysplasia spinulosa-associated polyomavirus. Emerg Infect Dis 2011;17:1355–63.
Holzer AM, Hughey LL. Trichodysplasia of immunosuppression successfully treated with volganciclovir. J Am Acad Ddermatol 2009;60:169–72.
Spiring LC, Tomaszewski MM, Thomas DA. Viral-associated tichodysplasia in patients who are immunocompromised. J Am Acad Dermatol 2004;50:318–22.
Campbell RM, Ney A, Gohh R, et al. Spiny hyperkeratotic projections on the face and extremities of a kidney transplant recipient. Arch Dermatol 2006;142:1643–8.
Blake BP, Marathe KS, Mohr MR, et al. Viral-associated trichodysplasia of immunosuppression in a renal transplant patient. J Drugs Dermatol 2011;10:422–4.

Flegel disease

Flegel H. Hyperkeratosis lenticularis perstans. Dermatologica 1958;9:362–4.
Bean SF. The genetics of hyperkeratosis lenticularis perstans. Arch Dermatol 1972;106:72.
Krishnan A, Kar S. Hyperkeratosis lenticularis perstans (Flegel's disease) with unusual clinical presentation. Response to isotretinoin therapy. J Dermatol 2012;6:93–5.
Rosdahl I, Rosen K. Hyperkeratosis lenticularis perstans: report on three cases. Acta Derm Venereol 1985;65:562-4.
Kanitakis J, Hermier C, Hokayem D, et al. Hyperkeratosis lenticularis perstans (Flegel's disease). A light and electron microscope study of involved and uninvolved epidermis. Dermatologica 1987;174:96–101.
Jang KA, Choi JH, Sung KJ, et al. Hyperkeratosis lenticularis perstans (Flegel's disease): histologic, immunohistochemical, and ultrastructural features in a case. Am J Dermatopathol 1999;21:395–8.
Buchner SA. Hyperkeratosis lenticularis perstans (Flegel's disease). In situ characterization of T cell subsets and Langerhans cells. Acta Derm Venereol 1988;68:341–5.
Bean S. Hyperkeratosis lenticularis perstans: a clinical, histopathologic, and genetic study. Arch Dermatol 1969;99:705–9.
Price ML, Wilson Jones E, MacDonald DM. A clinicopathological study of Flegel's disease (hyperkeratosis lenticularis perstans). Br J Dermatol 1987;116:681–91.
Miljkovic J. An unusual generalized form of hyperkeratosis lenticularis perstans. Wien Klin Wochenschr 2004;116(Suppl. 2):78–80.
Wilson PD, Ive FA. Treatment of hyperkeratosis lenticularis perstans (Flegel) with topical fluorouracil. Dermatologica 1980;160:337–40.
Langer K, Zonzits E, Konrad K. Hyperkeratosis lenticularis perstans (Flegel's disease). Ultrastructural study of lesional and perilesional skin and therapeutic trial of topical tretinoin versus 5-fluorouracil. J Am Acad Dermatol 1992;27:812–16.
Pearson LH, Smith JG Jr, Chalker DK. Hyperkeratosis lenticularis perstans (Flegel's disease). Case report and literature review. J Am Acad Dermatol 1987;16:190–5.
Cunha Filho RR, Almeida HL Jr. Hyperkeratosis lenticularis perstans. An Bras Dermatol 2011;86(4 Suppl. 1):S76–7.
Duschet P, Schwarz T, Gshnait F, et al. Hyperkeratosis lenticularis perstans (Flegel's disease). Hautarzt 1985;36:299–301.
Blaheta HJ, Metzler G, Rassner G, Garbe C. Hyperkeratosis lenticularis perstans (Flegel's disease): lack of response to treatment with tacalcitol and calcipotriol. Dermatology 2001;202:255–8.
Metze D, Lubke D, Luger T. [Hyperkeratosis lenticularis perstans (Flegel's disease): a complex disorder of epidermal differentiation with good response to a synthetic vitamin D3 derivate.] Hautarzt 2000;51:31–5.

Multiple minute digitate keratoses

Goldstein N. Multiple minute digitate hyperkeratoses. Arch Dermatol 1967;96:692–3.
Ramselaar C, Toonstra J. Multiple minute digitate hyperkeratoses: report of two cases with an updated review and proposal for a new classification. Eur J Dermatol 1999;9:460–5.
Wilkinson SM, Wilkinson N, Chalmers RJG. Multiple minute digitate keratoses: a transient, sporadic variant. J Am Acad Dermatol 1994;31:802–3.
Miller A, Aires D, Fraga G. Multiple minute digitate hyperkeratoses: a case report. Dermatol Online J 2011;17(5):1.
Benoldi D, Zucchi A, Allegra F. Multiple minute digitate hyperkeratoses. Clin Exp Dermatol 1993;18:261–2.
Ferandiz C, Savall R, Baumann E. Multiple minute digitate hyperkeratosis (a paraneoplastic system?). Med Cutan Ibero Lat Am 1978;6:279–83.
Bordel-Gomez M. Palmoplantar spiny keratoderma associated with chronic lymphoid leukaemia. J Eur Acad Dermatol Venereol 2008;22:1507–8.
Handa Y, Sakakibara A, Araki M, et al. Spiny keratoderma of the palms and soles: report of two cases. Eur J Dermatol 2000;10:542–5.
Balus L, Donati P, Amantea A, et al. Multiple minute digitate hyperkeratosis. J Am Acad Dermatol 1988;18:431–6.
Caccetta TP, Dessauvagie B, McCallum D, Kumarasinghe SP. Multiple minute digitate hyperkeratosis: a proposed algorithm for the digitate keratoses. J Am Acad Dermatol 2012;67:e49–55.

Porokeratoses

Sertznig P, von Felbert V, Megahed M. Porokeratosis: present concepts. J Eur Acad Dermatol Venereol 2012;26:404–12.
Ferreira FR, Nogueira Santos LD, Nogueira Mendes Tagliarini FA, Lanzoni de Alvarenga Lira M. Porokeratosis of Mibelli: literature review and a case report. An Bras Dermatol 2013;88(6 Suppl. 1):179–82.
Dover JS, Phillips TJ, Burns DA. Disseminated superficial actinic porokeratosis: coexistence with other porokeratotic variants. Arch Dermatol 1986;122:887–9.
Cho E, Lee YB, Park HJI, et al. Coexistence of congenital linear porokeratosis and disseminated superficial actinic porokeratosis. Australas J Dermatol 2012;53:e30–1.
Touitou I, Galeotti C, Rossi-Semerano L, Hentgen V, Piram M, Koné-Paut I. The expanding spectrum of rare monogenic autoinflammatory diseases. Orphanet J Rare Dis 2013;8:162.
Rodriguez EA, Jakubowicz S, Chinchilla DA, et al. Porokeratosis of Mibelli and HIV infection. Int J Dermatol 1996;35:402–4.
Morton CA, Shuttleworth D, Douglas WS. Porokeratosis and Crohn's disease. J Am Acad Dermatol 1995;32:894–7.
Nakamura M, Fukamachi S, Tokura Y. Acute onset disseminated superficial porokeratosis associated with exacerbation of diabetes mellitus due to development of anti-insulin antibodies. Dermatoendocrinology 2010;2:17–18.
Hunt SJ, Sharra WG, Abell E. Linear and punctate porokeratosis associated with end-stage liver disease. J Am Acad Dermatol 1991;25:937–9.
Hernandes MH, Lai CH, Mallory SB. Disseminated porokeratosis associated with chronic renal failure: a new type of disseminated porokeratosis? Arch Dermatol 2000;136:1568–9.
Cannavo SP, Borgia F, Adamo B, et al. Simultaneous development and parallel course of disseminated superficial porokeratosis and ovarian cancer: coincidental association or true paraneoplastic syndrome? J Am Acad Dermatol 2008;58:657–60.
Fernandez-Flores A. Small lesions of porokeratosis show a normal proliferation rate with MIB-1. Acta Dermatovenerol Alp Pannonica Adriat 2008;17:22–5.
Kamata Y, Maejima H, Watarai A, et al. Expression of bleomycin hydrolase in keratinization disorders. Arch Dermatol Res 2012;304:31–8.
Otsuka F, Chi HI, Shima A. Cytological demonstration of abnormal DNA ploidy in the epidermis of porokeratosis. Arch Dermatol Res 1988;230:61–3.
Zhang SQ, Jiang T, Li M, et al. Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis. Nat Genet 2012;44:1156–60.
Kanitakis J, Euvrard S, Faure M, et al. Porokeratosis and immunosuppression. Eur J Dermatol 1998;8:459–65.
Luan J, Niu Z, Zhang J, et al. A novel locus for disseminated superficial actinic porokeratosis maps to chromosome 16q24.1–24.3. Hum Genet 2011;129:329–34.
Koley S, Sarkar J, Choudhary S, et al. Different morphological variants of hypertrophic porokeratosis and disseminated lesions of porokeratosis of Mibelli: a rare co-existence. Indian J Dermatol Venereol Leprol 2011;77:199–202.
Happle R. Cancer proneness of linear porokeratosis may be explained by allelic loss. Dermatology 1997;195:20–5.
Chen TJ, Chou YC, Chen CH, Kuo TT, Hong HS. Genital porokeratosis: a series of 10 patients and review of the literature. Br J Dermatol 2006;155:325–9.
Robinson JB, Im DD, Jockle G, et al. Vulvar porokeratosis: case report and review of the literature. Int J Gynecol Pathol 1999;18:169–73.
McGuigan K, Shurman D, Campanelli C, et al. Porokeratosis ptychotropica: a clinically distinct variant of porokeratosis. J Am Acad Dermatol 2009;60:501–3.
Hong J-B, Hsiao C-H, Chu C-Y. Systematized linear porokeratosis: a rare variant of diffuse porokeratosis with good response to systemic acitretin. J Am Acad Dermatol 2009;60:713–15.
Patrizi A, Passarini B, Minghetti G, et al. Porokeratosis palmaris et plantaris disseminata: an unusual clinical presentation. J Am Acad Dermatol 1989;21:415–18.
Chouery E, Guissart C, Mégarbané H, et al. Craniosynostosis, anal anomalies and porokeratosis (CDAGS syndrome): case report and literature review. Eur J Med Genet 2013;56:674–7.
Sander CA, Pfeiffer C, Kligman AM, et al. Chemotherapy for disseminated actinic keratoses with 5-fluorouracil and isotretinoin. J Am Acad Dermatol 1997;36:236–8.
Harrison S, Sinclair R. Porokeratosis of Mibelli: successful treatment with topical 5% imiquimod cream. Australas J Dermatol 2003;44:281–3.
Kim HS, Baek JH, Park YM, et al. Photodynamic therapy combined with CO₂ laser vaporization on disseminated superficial actinic porokeratosis: a report of 2 cases on the face. Ann Dermatol 2011;23(Suppl. 2):S211–13.
Marks S, Varma R, Cantrell W, et al. Diclofenac sodium 3% gel as a potential treatment for disseminated superficial actinic porokeratosis. J Eur Acad Dermatol Venereol 2009;23:42–5.
Bakardzhiev I, Kavaklieva S, Pehlivanov G. Successful treatment of disseminated superficial actinic porokeratosis with calcipotriol. Int J Dermatol 2012;5:1139–42.
Garg T, Ramchander, Varghese B, et al. Generalized linear porokeratosis: a rare entity with excellent response to acitretin. Dermatol Online J 2011;17(5):3.

Transient acantholytic dermatosis

Grover RW. Transient acantholytic dermatosis. Arch Dermatol 1970;101:426–34.
Streit M, Paredes BE, Braathen LR, et al. [Transitory acantholytic dermatosis (Grover disease). An analysis of the clinical spectrum based on 21 histologically assessed cases.] Hautarzt 2000;51:244–9.
Eaver J, Bergfeld WF. Grovers disease (transient acantholytic dermatosis). Arch Pathol Lab Med 2009;133:1490–4.
Davis MD, Dinneen AM, Landa N, et al. Grover's disease: clinicopathologic review of 72 cases. Mayo Clin Proc 1999;74:229–34.
Phillips C, Kalantari-Dehaghi M, Marchenko S, et al. Is Grover's disease an autoimmune dermatosis? Exp Dermatol 2013;22:781–4.
Scheinfeld N, Mones J. Seasonal variation of transient acantholytic dyskeratosis (Grover's disease). J Am Acad Dermatol 2006;55:263–8.
French LE, Piletta PA, Etienne A, et al. Incidence of transient acantholytic dermatosis (Grover's disease) in a hospital setting. Dermatology 1999;198:410–11.
Fernandez-Figueras MT, Puig L, Cannata P, et al. Grover disease: a reappraisal of histopathological diagnostic criteria in 120 cases. Am J Dermatopathol 2010;32:541–9.
El Shabrawi-Caelen L, Rütten A, Kerl H. The expanding spectrum of Galli-Galli disease. J Am Acad Dermatol 2007;56(5 Suppl.):S86–91.
Helfman RJ, Gables C. Grover's disease treated with isotretinoin. J Am Acad Dermatol 1985;12:981–4.
Breuckmann F, Appelhans C, Altmeyer P, et al. Medium-dose ultraviolet A1 phototherapy in transient acantholytic dermatosis (Grover's disease). J Am Acad Dermatol 2005;52:169–70.
Norman R, Chau V. Use of etanercept in treating pruritus and preventing new lesions in Grover's disease. J Am Acad Dermatol 2011;64:796–8.
Liu S, Letada PR. Successful novel treatment of recalcitrant transient acantholytic dermatosis (Grover's disease) using red light 5-aminolevulinic acid photodynamic therapy. Dermatol Surg 2013;39:960–1.

Keratolysis exfoliativa

Wende GW. Keratolysis exfoliativa. J Cutan Dis 1919;37:174.
Chang YY, van der Velden J, van der Wier G, et al. Keratolysis exfoliativa (dyshidrosis lamellose sicca): a distinct peeling entity. Br J Dermatol 2012;167:1076–84.

Xerosis cutis and asteatosis

Berry N, Charmeil C, Goujon C, et al. A clinical, biometrological and ultrastructural study of xerotic skin. Int J Cosmet Sci 1999;21:241–52.
Wesley NO, Maibach HI. Racial (ethnic) differences in skin properties: the objective data. Am J Clin Dermatol 2003;4:843–60.
Jensen JM, Förl M, Winoto-Morbach S, et al. Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging. Exp Dermatol 2005;14:609–18.
Choi EH, Man MQ, Xu P, et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol 2007;127:2847–56.
Engelke M, Jensen JM, Ekanayake-Mudiyanselage S, Proksch E. Effects of xerosis and ageing on epidermal proliferation and differentiation. Br J Dermatol 1997;137:219–25.
Ghadially R, Brown BE, Sequeira-Martin SM, et al. The aged epidermal permeability barrier. Structural, functional and lipid biochemical abnormalities in humans and a senescent murine model. J Clin Invest 1995;95:2281–90.
Simon M, Bernard D, Minondo AM, et al. Persistence of both peripheral and non-peripheral corneodesmosomes in the upper stratum corneum of winter xerosis skin versus only peripheral in normal skin. J Invest Dermatol 2001;116:23–30.
Dunn LB, Damesyn M, Moore AA, Reuben DB, Greendale GA. Does estrogen prevent skin aging? Results from the First National Health and Nutrition Examination Survey (NHANES I). Arch Dermatol 1997;133:339–42.
Li LF, Lan YZ. Bathing and generalized asteatotic eczema: a case-control study. Br J Dermatol 2008;159:243–5.
Valentine J, Belum VR, Duran J, et al. Incidence and risk of xerosis with targeted anticancer therapies. J Am Acad Dermatol 2015;72:656–67.
Schulz P, Bunselmeyer B, Brautigam M, Luger TA. Pimecrolimus cream 1% is effective in asteatotic eczema: results of a randomized, double-blind, vehicle-controlled study in 40 patients J Eur Acad Dermatol Venereol 2007;21:90–4.
Wollina U. The role of topical calcineurin inhibitors for skin diseases other than atopic dermatitis. Am J Clin Dermatol 2007;8:157–73.

Acute epidermal distension and acute oedema blisters

Cox NH, Chalmers RJG, Bhushan M. The acute edema/cutaneous distension syndrome. Arch Dermatol 2003;139:224–5.
Bhushan M, Chalmers RJ, Cox NH. Acute oedema blisters: a report of 13 cases. Br J Dermatol 2001;144:580–2.
Wiesen J, Gonzalez-Estrada A, Auron M. Postangioedema attack skin blisters: an unusual presentation of hereditary angioedema. BMJ Case Rep 2014; doi: 10.1136/bcr-2013-201482.
Fernández Romero D, Di Marco P, Malbrán A. Acute edema blisters in a hereditary angioedema cutaneous attack. Allergol Immunopathol (Madr) 2008;36:182–3.
Gniadecka M. Localization of dermal edema in lipodermatosclerosis, lymphedema, and cardiac insufficiency. High-frequency ultrasound examination of intradermal echogenicity. J Am Acad Dermatol 1996;35:37–41.
Gniadecka M, Quistorff B. Assessment of dermal water by high-frequency ultrasound: comparative studies with nuclear magnetic resonance. Br J Dermatol 1996;135:218–24.
Bhushan M, Cox NH, Chalmers RJG. Eczéma craquelé resulting from acute oedema: a report of seven cases. Br J Dermatol 2001;145:355–7.
Ishiguro N, Kawashima M. Striae-like epidermal distension: a newly recognized cutaneous manifestation in acute leg edema. Arch Dermatol 2002;138:641–2.

Acquired ichthyosis

Patel N, Spencer LA, English JC III, et al. Acquired ichthyosis. J Am Acad Dermatol 2006;55:647–56.
Brazzelli V, Larizza D, Muzio F, et al. Acquired ichthyosis in a child with autoimmune thyroiditis. Pediatr Dermatol 2010;27:413–14.
Akpinar TS, Ozkok A, Bakkaloglu OK, et al. Acquired ichthyosis as a presenting finding of Hodgkin's lymphoma. Int J Hematol 2012;96:401–2.
Berrady R, Baybay H, Khammar Z, et al. Acquired ichthyosis and haematological malignancies: five cases. Ann Dermatol Vénéréol 2012;139:9–14.
Riesco Martínez MC, Muñoz Martín AJ, Zamberk Majlis P, et al. Acquired ichthyosis as a paraneoplastic syndrome in Hodgkin's disease. Clin Transl Oncol 2009;11:552–3.
Levy O, Tishler M. Acquired ichthyosis as the primary manifestation of renal cell carcinoma. Isr Med Assoc J 2009;11:121–2.
Morizane S, Setsu N, Yamamoto T, et al. Ichthyosiform eruptions in association with primary cutaneous T-cell lymphomas. Br J Dermatol 2009;161:115–20.
Harati A, Brockmeyer NH, Altmeyer P, et al. Skin disorders in association with monoclonal gammopathies. Eur J Med Res 2005;29:93–104.
Sparsa A, Boulinguez S, Le Brun V, et al. Acquired ichthyosis with pravastatin. J Eur Acad Dermatol Venereol 2007;21:549–50.
Sanli H, Akay BN, Sen BB, et al. Acquired ichthyosis associated with type 1 diabetes mellitus. Dermatoendocrinology 2009;1:34–6.
London RD, Lebwohl M. Acquired ichthyosis and hyperparathyroidism. J Am Acad Dermatol 1989;21:801–2.
Dykes PJ, Marks R. Acquired ichthyosis: multiple causes for an acquired generalized disturbance in desquamation. Br J Dermatol 1977;97:327–34.
Singh A, Thappa DM, Hamide A. The spectrum of mucocutaneous manifestations during the evolutionary phases of HIV disease: an emerging Indian scenario. J Dermatol 1999;26:294–304.
Milagres SP, Sanches JA, Milagres ACP, et al. Histopathology and immunohistochemical assessment of acquired ichthyosis in patients with human T-cell lymphotropic virus type 1-associated myelopathy. Br J Dermatol 2003;149:776–81.
Daniel DR, Rubin AI, Rabinowitz AD, et al. Acquired ichthyosis with systemic lupus erythematosus: both dermatoses in a single skin biopsy specimen. Cutis 2008;81:159–62.
Lee HW, Ahn SJ, Choi JC, et al. Acquired ichthyosis associated with an overlap syndrome of systemic sclerosis and systemic lupus erythematosus. J Dermatol 2006;33:52–4.
Tlacuilo-Parra JA, Guevara-Gutiérrez E, Salazar-Páramo M. Acquired ichthyosis associated with systemic lupus erythematosus. Lupus 2004;13:270–3.
Kutting B, Traupe H. Acquired ichthyosis-like skin disease: a challenge for diagnostic evaluation. Hautarzt 1995;46:836–40.
Aram H. Acquired ichthyosis and related conditions. Int J Dermatol 1984;23:458–61.
Elias PM, Brown BE, Ziboh VA. The permeability barrier in essential fatty acid deficiency: evidence for a direct role for linoleic acid in barrier function. J Invest Dermatol 1980;74:230–3.
Aggett PJ, Cavanagh HP, Matthew DJ, et al. Shwachman's syndrome: a review of 21 cases. Arch Dis Child 1980;55:331–47.
London RD, Lebwohl M. Acquired ichthyosis and hyperparathyroidism. J Am Acad Dermatol 1989;21:801–2.
Kelley BP, George DE, LeLeux TM, Hsu S. Ichthyosiform sarcoidosis: a case report and review of the literature. Dermatol Online J 2010;16(8):5.
Yosipovitch G, Hodak E, Vardi P, et al. The prevalence of cutaneous manifestations in IDDM patients and their association with diabetes risk factors and microvascular complications. Diabetes Care 1998;21:506–9.
Monnier VM, Bautista O, Kenny D, et al. Skin collagen glycation, glycoxidation and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type I diabetes: relevance of glycated collagen products versus HbA1C as markers of diabetic complications. Diabetes 1999;48:870–80.
King LE, Gates RE, Stoscheck CM, Nanney LB. The EGF/TGF alpha receptor in skin. J Invest Dermatol 1990;94(Suppl.):164S–170S.
Takashi S, Norihiro F, Shiohama A, et al. Filaggrin loss-of-function mutations are not a predisposing factor for atopic dermatitis in an Ishigaki Island under subtropical climate. J Dermatol Sci 2014;76:10–15.
DiGiovanna JJ, Robinson-Bostom L. Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermatol 2003;4:81–95.

Acanthosis nigricans

Brickman WJ, Binns HJ, Jovanovic BD, Kolesky S, Mancini AJ, Metzger BE. Acanthosis nigricans: a common finding in overweight youth. Pediatr Dermatol 2007;24:601–6.
Otto DE, Wang X, Garza V, Fuentes LA, Rodriguez MC, Sullivan P. Increasing body mass index, blood pressure, and acanthosis nigricans abnormalities in school-age children. J Sch Nurs 2013;29:442–51.
Sinha S, Schwartz RA. Juvenile acanthosis nigricans. J Am Acad Dermatol 2007;57:502–8.
Pattamadilok B, Devpura S, Syed ZU, et al. Quantitative skin color measurements in acanthosis nigricans patients: colorimetry and diffuse reflectance spectroscopy. Photodermatol Photoimmunol Photomed 2012;28:213–15.
Hud JA Jr, Cohen JB, Wagner JM, Cruz PD Jr. Prevalence and significance of acanthosis nigricans in an adult obese population. Arch Dermatol 1992;128:941–4.
Krawczyk M, Mykala-Ciesla J, Kolodziej-Jaskula A. Acanthosis nigricans as a paraneoplastic syndrome. Case reports and review of literature. Pol Arch Med Wewn 2009;119:180–3.
Singh SK, Rai T. A rare case of malignant acanthosis nigricans in a lady with ovarian cancer. Indian Dermatol Online J 2013;4(2):125–7.
Zhang N, Qian Y, Feng AP. Acanthosis nigricans, tripe palms, and sign of Leser-Trélat in a patient with gastric adenocarcinoma: case report and literature review in China. Int J Dermatol 2015;54:338–42.
Voorhees J, Goto K, Wolff C. Overweight, elevated blood pressure, acanthosis nigricans and adherence to recommended dietary and physical activity guidelines among Hmong and white middle school students. J Immigr Minor Health 2014;16:273–9.
Sadeghian G, Ziaie H, Amini M, et al. Evaluation of insulin reistance in obese women with and without acanthosis nigricans. J Dermatol 2009;36:209–12.
Scott AT, Metzig AM, Hames RK, et al. Acanthosis nigricans and oral glucose tolerance in obese children. Clin Pediatr 2010;49:69–71.
Stoddart ML, Blevins KS, Lee ET, Wang W, Blackett PR. Association of acanthosis nigricans with hyperinsulinemia compared with other selected risk factors for type 2 diabetes in Cherokee Indians: the Cherokee Diabetes Study. Diabetes Care 2002;25:1009–14.
Cruz PDJ, Hud JA. Excess insulin binding to insulin like growth factor receptors: proposed mechanism for acanthosis nigricans. J Invest Dermatol 1992;98:82S–85S.
McIntosh I, Bellus GA, Jabs EW. The pleiotropic effects of fibroblast growth factor receptors in mammalian development. Cell Struct Funct 2000;25:85–96.
Berk DR, Spector EB, Bayliss SJ. Familial acanthosis nigricans due to K650T FGFR3 mutation. Arch Dermatol 2007;143:1153–6.
Lane SW, Manharan S, Mollee PN. Palifermin-induced acanthosis nigricans. Intern Med J 2007;37:417–18.
Koyama S, Ikeda K, Sato M, et al. Transforming growth factor alpha-producing gastric carcinoma with acanthosis nigricans: an endocrine effect of TGF alpha in the pathogenesis of cutaneous paraneoplastic syndrome and epithelial hyperplasia of the esophagus. J Gastroenterol 1997;32:71–7.
Sawatkar GU, Dogra S, Bhadada SK, et al. Acanthosis nigricans: an uncommon cutaneous adverse effect of a common medication. Report of two cases. Indian J Dermatol Venereol Leprol 2013;79:553.
Mailler-Savage EA, Adams BB. Exogenous insulin-derived acanthosis nigricans. Arch Dermatol 2008;144:126–7.
Piccolo V, Russo T, Picciocchi R, et al. Generalised idiopathic benign acanthosis nigricans in childhood. Ann Dermatol 2013;25:375–7.
Denadai R, Souto RM, Auada-Souto MP. Generalised acanthosis nigricans without systemic disease associated. Dermatol Online J 2013;19(9):19614.
Gönül M, Kiliç A, Cakmak SK, Gül U, Ekiz OD, Ergül G. Juvenile generalised acanthosis nigricans without any systemic disease. Pediatr Int 2009;51:595–7.
Schwartz RA. Acral acanthosis nigricans (acral acanthotic anaomaly). J Am Acad Dermatol 2007;65:349–50.
Jeong JS, Lee JY, Yoom TY. Unilateral nevoid acanthosis nigricans in the submammary location. Ann Dermatol 2011;23:95–7.
Katz RA. Treatment of acanthosis nigricans with isotretinoin. Arch Dermatol 1980;116:110–11.
Mir A, Wu T, Orlow SJ. Cutaneous features of Crouzon syndrome with acanthosis nigricans. JAMA Dermatol 2013;149:737–41.
Sharda S, Panigrahi I, Gupta K, Singhi S, Kumar R. Newborn with acanthosis nigricans: can it be Crouzon syndrome with acanthosis nigricans? Pediatr Dermatol 2010;27:43–7.

Confluent and reticulated papillomatosis

Gougerot H, Carteaud A. Papillomatose pigmentee inominee. Bull Soc Fr Dermatol Syphiligr 1927;34:719–21.
Scheinfeld N. Confluent and reticulated papillomatosis: a review of the literature. Am J Clin Dermatol 2006;7:305–13.
Hamilton D, Tavafoghi V, Shafer JC, et al. Confluent and reticulated papillomatosis of Gougerot and Carteaud. Its relation to other papillomatoses. J Am Acad Dermatol 1980;2:401–10.
Davis MD, Weenig RH, Camilleri MJ. Confluent and reticulate papillomatosis (Gougerot–Caryeaud syndrome): a minocycline-responsive dermatosis without evidence for yeast in pathogenesis. A study of 39 patients and a proposal of diagnostic criteria. Br J Dermatol 2006;154:287–93.
Tamraz H, Raffoul M, Kurban M, et al. Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon. J Eur Acad Dermatol Venereol 2013;27:e119–23.
Roberts SO, Lachapelle JM. Confluent and reticulate papillomatosis (Gougerot–Carteaud) and pityrosporum orbiculare. Br J Dermatol 1969;81:841–5.
Yesudian P, Kamalam S, Razack A. Confluent and reticulated papillomatosis (Gougerot–Carteaud). An abnormal host reaction to Malassezzia furfur. Acta Derm Venereol 1973;53:381–4.
Natarajan S, Milne D, Jones AL, et al. Dietzia strain X: a newly described Actinomycete isolated from confluent and reticulated papillomatosis. Br J Dermatol 2005;153:825–7.
Kanitakis J, Zambruno G, Viac J, Thivolet J. Involucrin expression in keratinization disorders of the skin: a preliminary study. Br J Dermatol 1987;117:479–86.
Inalöz HS, Patel G, Knight AG. Familial confluent and reticulated papillomatosis. Arch Dermatol 2002;138:276–7.
Henning JP, de Wit RF. Familial occurrence of confluent and reticulated papillomatosis. Arch Dermatol 1981;117:809–10.
Jimbow M, Talpash O, Jimbow K. Confluent and reticulated papillomatosis: clinical, light and electron microscopic studies. Int J Dermatol 1992;31:480–3.
Hirokawa M, Matsumoto M, Iizuka H. Confluent and reticulated papillomatosis: a case with concurrent acanthosis nigricans associated with obesity and insulin resistance. Dermatology 1994;188:148–51.
Zhang CH, Zhang C, Wu J, et al. Confluent and reticulated papillomatosis associated with hyperthyroidism. Eur J Dermatol 2010;20:833–5.
Lee SH, Choi EH, Lee WS, Kang WH, Bang DS. Confluent and reticulated papillomatosis: a clinical, histopathological, and electron microscopic study. J Dermatol 1991;18:725–30.
Kim BS, Lim HJ, Kim HY, et al. Case of minocycline-effective confluent and reticulated papillomatosis with unusual location on forehead. J Dermatol 2009;36:251–3.
Lee D, Cho KJ, Hong SK, Seo JK, Hwang SW, Sung HS. Two cases of confluent and reticulated papillomatosis with an unusual location. Acta Derm Venereol 2009;89:84–5.
Rodriguez-Carreon AA, Arenas-Guzman R, Fonte-Avalos V, et al. Confluent and reticulated Gougerot–Carteaud papillomatosis: a case report of an excellent response to minocycline. Gac Med Mex 2008;144:67–70.
Jang HS, Oh CK, Cha JH, Cho SH, Kwon KS. Six cases of confluent and reticulated papillomatosis alleviated by various antibiotics. J Am Acad Dermatol 2001;44:652–5.
Fung MA, Frieden IJ, LeBoit PE, et al. Confluent and reticulate papillomatosis: successful treatment with minocycline. Arch Dermatol 1996;132:1400–1.
Gönül M, Cakmak SK, Soylu S, Kiliç A, Gül U, Ergül G. Successful treatment of confluent and reticulated papillomatosis with topical mupirocin. J Eur Acad Dermatol Venereol 2008;22:1140–2.
Nordby CA, Mitchell AJ. Confluent and reticulated papillomatosis responsive to selenium sulfide. Int J Dermatol 1986;25:194–9.
Bowman PH, Davis LS. Confluent and reticulated papillomatosis: response to tazarotene. J Am Acad Dermatol 2003;48(Suppl. 5):S80–1.
Carrozzo AM, Gatti S, Ferranti G, et al. Calcipotriol treatment of confluent and reticulated papillomatosis (Gougerot–Carteaud syndrome). J Eur Acad Dermatol Venereol 2000;14:131–3.
Ginarte M, Fabeiro JM, Toribio J. Confluent and reticulated papillomatosis (Gougerot–Carteaud) successfully treated with tacalcitol. J Dermatol Treat 2002;13:27–30.
Lee MP, Stiller MJ, McClain SA, Shupack JL, Cohen DE. Confluent and reticulated papillomatosis: response to high-dose oral isotretinoin therapy and reassessment of epidemiologic data. J Am Acad Dermatol 1994;31:327–31.
Erkek E, Ayva S, Atasoy P, Emeksiz MC. Confluent and reticulated papillomatosis: favourable response to low-dose isotretinoin. J Eur Acad Dermatol Venereol 2009;23:1342–3.

Pityriasis rotunda

Zur RL, Shapero J, Shapero H. Pityriasis rotunda diagnosed in Canada: case presentation and review of literature. J Cutan Med Surg 2013;17:426–8.
Findlay GH. Pityriasis rotunda in South African Bantu. Br J Dermatol 1965;77:63–4.
Grimalt R, Gelmetti C, Brusasco A, et al. Pityriasis rotunda: report of a familial occurrence and review of the literature. J Am Acad Dermatol 1994;31:866–71.
Sarkany I, Hare PJ. Pityriasis rotunda (pityriasis circinata). Br J Dermatol 1964;76:223–8.
Kahana M, Levy A, Ronnen M, Schewach-Millet M, Stempler D. Pityriasis rotunda in a white patient. Report of the second case and review of the literature. J Am Acad Dermatol 1986;15:362–5.
DiBisceglie AM, Hodkinson HJ, Berkowitz I, et al. Pityriasis rotunda. A cutaneous marker of hepatocellular carcinoma in South African blacks. Arch Dermatol 1986;122:802–4.
Berkowitz I, Hodkinson HJ, Kew MC, DiBisceglie AM. Pityriasis rotunda as a cutaneous marker of hepatocellular carcinoma: a comparison with its prevalence in other diseases. Br J Dermatol 1989;120:545–9.
Etoh T, Nakagawa H, Ishibashi Y. Pityriasis rotunda associated with multiple myeloma. J Am Acad Dermatol 1991;24:303–4.
Combemale P, L'Henaff N, Guennoc B. Pityriasis rotunda. Ann Dermatol Vénéréol 1993;120:287–8.
Swift PJ, Saxe N. Pityriasis rotunda in South Africa: a skin disease caused by undernutrition. Clin Exp Dermatol 1985;10:407–12.

Keratosis pilaris

Thomas M, Khopkar US. Keratosis pilaris revisited: is it more than just a follicular keratosis? Int J Trichol 2012;4:255–8.
Hwang S, Schwartz RA. Keratosis pilaris: a common follicular hyperkeratosis. Cutis 2008;82:177–80.
Mevorah B, Marazzi A, Frenk E. The prevalence of accentuated palmoplantar markings and keratosis pilaris in atopic dermatitis, autosomal dominant ichthyosis and control dermatological patients. Br J Dermatol 1985;112:679–85.
Wang CM, Fleming KF, Hsu S. A case of vemurafinib-induced keratosis pilaris like eruption. Dermatol Online J 2012;18:7.
Yosipovitch G, De Vore A, Dawn A. Obesity and the skin: skin physiology and skin manifestations of obesity. J Am Acad Dermatol 2007;56:901–16.
Occella C, Gargani FF, Rampini E, et al. Sindrome di Noonan e keratosis pilaris atrophicans faciei. Minerva Pediatr 1985;37:181–6.
Armour CM, Allanson JE. Further delineation of cardio-facial-cutaneous syndrome: clinical features of 38 patients with proven mutations. J Med Genet 2008;45:249–54.
Larregue M, Charoentier C, Laidet B, et al. Deficit en prolidase et en manganese. Ann Dermatol Vénéréol 1982;109:667–8.
Finn OA, Grant PW, McCallum DI, et al. A singular dermatosis of Mongols. Arch Dermatol 1978;114:1493–4.
Marks R. Follicular hyperkeratosis and ocular abnormalities associated with Fairbanks syndrome. Br J Dermatol 1967;79:118–19.
Perry HO, Su WP. Olmsted syndrome. Semin Dermatol 1995;14:145–51.
Guiller G, Sanciaume C, Hehunester JP, et al. Keratose pilare generalisee et hypervitaminose A chez une enfant insuffisante renale. Ann Dermatol Vénéréol 1982;109:1061–6.
Carnabuci GJ, Rosenberg PE. Monilethrix and keratosis pilaris. Arch Dermatol 1967;96:594.
Leachman SA, Kaspar RL, Fleckman P, et al. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc 2005;10:3–17.
Halal F, Seeton N, Wang NS. A distinct type of hydrotic ectodermal dysplasia. Am J Med Genet 1991;38:552–6.
Whittaker SJ, Griffiths WAD. Erythromelanosis follicularis faciei et colli. Clin Exp Dermatol 1987;12:33–5.
Wakelin SH, Lipscombe T, Orton DI, et al. Lithium induced follicular hyperkeratosis. Clin Exp Dermatol 1996;21:296–8.
Baden HP, Byers HR. Clinical findings, cutaneous pathology and response to therapy in 21 patients with keratosis pilaris atrophicans. Arch Dematol 1994;130:469–75.
Nazarenko SA, Ostroverkhova NV, Vasileva EO, et al. Keratosis pilaris and ulerythema ophryogenes associated with an 18p deletion caused by a Y/18 translocation. Am J Med Genet 1999;85:179–82.
Poskitt L, Wilkinson JD. Natural history of keratosis pilaris. Br J Dermatol 1994;130:711–13.
Lalit G, Anubhav G, Kumar KA, et al. Familial erythromelanosis follicularis faciei et colli with extensive keratosis pilaris. Int J Dermatol 2011;50:1400–1.
Sardana K, Relhan V, Garg V, et al. An observational analysis of erythromelanosis follicularis faciei et colli. Clin Exp Dermatol 2008;33:333–6.
Augustine M, Jayaseelan E. Erythromelanosis follicularis faciei et colli: relationship with keratosis pilaris. Indian J Dermatol Venereol Leprol 2008;74:47–9.
Dianzani C, Pizzuti A, Gaspardini F, et al. Ulerythema ophryogenes, a rare and often misdiagnosed syndrome: analysis of an idiopathic case. Int J Immunopathol Pharmacol 2011;24:523–7.
Oranje AP, van Osch LDM, Oosterwijk JC. Keratosis pilaris atrophicans: one heterogeneous disease or a symptom in different clinical entities? Arch Dermatol 1994;130:500–2.
Sequeira FF, Jayaseelan E. Keratosis follicularis spinulosa decalvans in a female. Indian J Dermatol Venereol Leprol 2011;77:325–7.
Luria RB, Conologue T. Atrophoderma vermiculatum: a case report and review of the literature on keratosis pilaris atrophicans. Cutis 2009;83:83–6.
Golusin Z, Jovanovic M, Poliacki M. Atrophic pilar keratosis of the face: case report. Med Pregl 2001;54:486–9.
Novick NL. Practical management of widespread, atypical keratosis pilaris. J Am Acad Dermatol 1984;11:305–6.
Alcántara González J, Boixeda P, Truchuelo Díez MT, et al. Keratosis pilaris rubra and keratosis pilaris atrophicans faciei treated with pulsed dye laser: report of 10 cases. J Eur Acad Dermatol Venereol 2011;25:710–14.
Rodríguez-Lojo R, Pozo JD, Barja JM, et al. Keratosis pilaris atrophicans: treatment with intense pulsed light in four patients. J Cosmet Laser Ther 2010;12:188–90.
Apalla Z, Karakatsanis G, Papageorgiou M, Kastoridou C, Chaidemenos G. A case of atrophoderma vermiculatum responding to systemic isotretinoin. J Dermatol Case Rep 2009 Dec 30;3(4):62–3.

Lichen spinulosus

Boyd AS. Lichen spinulosus: case report and overview. Cutis 1989;43:557–60.
Venkatesh A, Dupuis E, Prajapati V, Rao J. Generalized lichen spinulosus in a 4-year old boy without systemic disease. Arch Dermatol 2012;148:865–6.
Friedman SJ. Lichen spinulosus. Clinicopathologic review of thirty-five cases. J Am Acad Dermatol 1990;22:261–4.
Adamson HG. On a form of chronic superficial dermatitis in circumscribed patches with symmetrical distribution occurring in children. Br J Dermatol 1908;20:109–22.
Cohen SJ, Dicken CH. Generalized lichen spinulosus in an HIV-positive man. J Am Acad Dermatol 1991;25:116–18.
Kano Y, Orihara M, Yagita A, Shiohara T. Lichen spinulosus in a patient with Crohn's disease. Int J Dermatol 1995;34:670–1.
Kabashima R, Sugita K, Kabashima K, et al. Lichen spinulosus in an alcoholic patient. Acta Derm Venereol 2009;89:311–12.
Maiocco KJ, Miller OF. Lichen spinulosus: response to therapy. Cutis 1976;17:294–9.
Forman SB, Hudgins EM, Blaylock WK. Lichen spinulosus: excellent response to tretinoin gel and hydroactive adhesive applications. Arch Dermatol 2007;143:122–3.
Kim SH, Kang JH, Seo JK, et al. Successful treatment of lichen spinulosus with topical tacalcitol cream. Pediatr Dermatol 2010;27:546–7.

Keratosis circumscripta

Shrank AB. Keratosis circumscripta. Arch Dermatol 1966;93:408–10.
Soyinka F, Laja AO. Keartosis circumscripta. A distinct dermatological entity or a variant of psoriasis? Dermatologica 1978;156:341–50.
Verhagen AR, Soyinka F, Laja AO. Keratosis circumscripta. Dermatologica 1979;153:182–3.
Brumwell EP, Murphy SJ. Keratosis circumscripta revisited: a case report and review of the literature. Cutis 2007;79:363–6.
Shams M, Blalock TW, Davis LS. Keratosis circumscripta: a unique case and review of the literature. Int J Dermatol 2011;50:1259–61.

Phrynoderma

Nicholls L. Phrynoderma: a condition due to vitamin deficiency. Indian Med Gaz 1933;68:681–7.
West KP Jr, Mehra S. Vitamin A intake and status in populations facing economic stress. J Nutr 2010;140:201S–207S.
Ayyangar MC. Phrynoderma and nutritional deficiency. Indian J Dermatol Venereol Leprol 1967;33:13–24.
Ocón J, Cabrejas C, Altemir J, Moros M. Phrynoderma: a rare dermatologic complication of bariatric surgery. J Parenter Enteral Nutr 2012;36:361–4.
Barr DJ, Riley RJ, Greco DJ. Bypass phrynoderma. Vitamin A deficiency associated with bowel-bypass surgery. Arch Dermatol 1984;120:919–21.
Bleasel NR, Stapleton KM, Lee M, Sullivan J. Vitamin A deficiency phrynoderma: due to malabsorption and inadequate diet. J Am Acad Dermatol 1999;41(2 Suppl.):322–4.
Beisel WR. Single nutrients and immunity. Am J Clin Nutr 1982;35(2 Suppl.):417–68.
Chandra RK. Nutrition and immunity. Trop Geogr Med 1988;40:S46–51.
Ragunatha S, Kumar VJ, Murugesh SB. A clinical study of 125 patients with phrynoderma. Indian J Dermatol 2011;56:389–92.
Armstrong AW, Setyadi HG, Liu V, Strasswimmer J. Follicular eruption on arms and legs. Phrynoderma. Arch Dermatol 2008;144:1509–14.
Nakjang Y, Yuttanavivat T. Phrynoderma: a review of 105 cases. J Dermatol 1988;15:531–4.
Smith J, Steinemann TL. Vitamin A deficiency and the eye. Int Ophthalmol Clin 2000;40:83–91.
Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press, 2001.
Murthy SR and Prabhakaran VC. Phrynoderma and night blindness. Indian J Ophthalmol 2010 Mar–Apr;58(2)175–6.

Trichodysplasia spinulosa

Haycox CL, Kim S, Fleckman P, et al. Trichodysplasia spinulosa: a newly described folliculocentric viral infection in an immunocompromised host. J Investig Dermatol Symp Proc 1999;4:268–71.
Schwieger-Briel A, Balma-Mena A, Ngan B, et al. Trichodyplasia spinulosa: a rare complication in immunocompromised patients. Pediatr Dermatol 2010;27:509–13.
Blake BP, Marathe KS, Mohr MB, et al. Viral-associated trichodysplasia of immunosuppression in a renal transplant patient. J Drugs Dermatol 2011;10:422–4.
Lee JS, Fredericksen P, Kossard S. Progressive trichodysplasia spinulosa in a patients with chronic lymphocytic leukaemia in remission. Austalas J Dermatol 2008;49:57–60.
Moktefi A, Laude H, Brudy Gulphe L, et al. Trichodysplasia spinulosa associated with lupus. Am J Dermatopathol 2014;36:e70–4.
Kazem S, van der Meijden E, Kooijman S, et al. Trichodysplasia spinulosa characterised by active polyomavirus infection. J Clin Virol 2012;53:225–30.
Fischer MK, Kao GF, Nguyen HP, et al. Specific detection of trichodysplasia spinulosa-associated polyoma virus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Arch Dermatol 2012;148:726–33.
van der Meijden E, Kazem S, Burgers MM, et al. Seroprevalence of trichodysplasia spinulosa-associated polyomavirus. Emerg Infect Dis 2011;17:1355–63.
Holzer AM, Hughey LL. Trichodysplasia of immunosuppression successfully treated with volganciclovir. J Am Acad Ddermatol 2009;60:169–72.
Spiring LC, Tomaszewski MM, Thomas DA. Viral-associated tichodysplasia in patients who are immunocompromised. J Am Acad Dermatol 2004;50:318–22.
Campbell RM, Ney A, Gohh R, et al. Spiny hyperkeratotic projections on the face and extremities of a kidney transplant recipient. Arch Dermatol 2006;142:1643–8.
Blake BP, Marathe KS, Mohr MR, et al. Viral-associated trichodysplasia of immunosuppression in a renal transplant patient. J Drugs Dermatol 2011;10:422–4.

Flegel disease

Flegel H. Hyperkeratosis lenticularis perstans. Dermatologica 1958;9:362–4.
Bean SF. The genetics of hyperkeratosis lenticularis perstans. Arch Dermatol 1972;106:72.
Krishnan A, Kar S. Hyperkeratosis lenticularis perstans (Flegel's disease) with unusual clinical presentation. Response to isotretinoin therapy. J Dermatol 2012;6:93–5.
Rosdahl I, Rosen K. Hyperkeratosis lenticularis perstans: report on three cases. Acta Derm Venereol 1985;65:562-4.
Kanitakis J, Hermier C, Hokayem D, et al. Hyperkeratosis lenticularis perstans (Flegel's disease). A light and electron microscope study of involved and uninvolved epidermis. Dermatologica 1987;174:96–101.
Jang KA, Choi JH, Sung KJ, et al. Hyperkeratosis lenticularis perstans (Flegel's disease): histologic, immunohistochemical, and ultrastructural features in a case. Am J Dermatopathol 1999;21:395–8.
Buchner SA. Hyperkeratosis lenticularis perstans (Flegel's disease). In situ characterization of T cell subsets and Langerhans cells. Acta Derm Venereol 1988;68:341–5.
Bean S. Hyperkeratosis lenticularis perstans: a clinical, histopathologic, and genetic study. Arch Dermatol 1969;99:705–9.
Price ML, Wilson Jones E, MacDonald DM. A clinicopathological study of Flegel's disease (hyperkeratosis lenticularis perstans). Br J Dermatol 1987;116:681–91.
Miljkovic J. An unusual generalized form of hyperkeratosis lenticularis perstans. Wien Klin Wochenschr 2004;116(Suppl. 2):78–80.
Wilson PD, Ive FA. Treatment of hyperkeratosis lenticularis perstans (Flegel) with topical fluorouracil. Dermatologica 1980;160:337–40.
Langer K, Zonzits E, Konrad K. Hyperkeratosis lenticularis perstans (Flegel's disease). Ultrastructural study of lesional and perilesional skin and therapeutic trial of topical tretinoin versus 5-fluorouracil. J Am Acad Dermatol 1992;27:812–16.
Pearson LH, Smith JG Jr, Chalker DK. Hyperkeratosis lenticularis perstans (Flegel's disease). Case report and literature review. J Am Acad Dermatol 1987;16:190–5.
Cunha Filho RR, Almeida HL Jr. Hyperkeratosis lenticularis perstans. An Bras Dermatol 2011;86(4 Suppl. 1):S76–7.
Duschet P, Schwarz T, Gshnait F, et al. Hyperkeratosis lenticularis perstans (Flegel's disease). Hautarzt 1985;36:299–301.
Blaheta HJ, Metzler G, Rassner G, Garbe C. Hyperkeratosis lenticularis perstans (Flegel's disease): lack of response to treatment with tacalcitol and calcipotriol. Dermatology 2001;202:255–8.
Metze D, Lubke D, Luger T. [Hyperkeratosis lenticularis perstans (Flegel's disease): a complex disorder of epidermal differentiation with good response to a synthetic vitamin D3 derivate.] Hautarzt 2000;51:31–5.

Multiple minute digitate keratoses

Goldstein N. Multiple minute digitate hyperkeratoses. Arch Dermatol 1967;96:692–3.
Ramselaar C, Toonstra J. Multiple minute digitate hyperkeratoses: report of two cases with an updated review and proposal for a new classification. Eur J Dermatol 1999;9:460–5.
Wilkinson SM, Wilkinson N, Chalmers RJG. Multiple minute digitate keratoses: a transient, sporadic variant. J Am Acad Dermatol 1994;31:802–3.
Miller A, Aires D, Fraga G. Multiple minute digitate hyperkeratoses: a case report. Dermatol Online J 2011;17(5):1.
Benoldi D, Zucchi A, Allegra F. Multiple minute digitate hyperkeratoses. Clin Exp Dermatol 1993;18:261–2.
Ferandiz C, Savall R, Baumann E. Multiple minute digitate hyperkeratosis (a paraneoplastic system?). Med Cutan Ibero Lat Am 1978;6:279–83.
Bordel-Gomez M. Palmoplantar spiny keratoderma associated with chronic lymphoid leukaemia. J Eur Acad Dermatol Venereol 2008;22:1507–8.
Handa Y, Sakakibara A, Araki M, et al. Spiny keratoderma of the palms and soles: report of two cases. Eur J Dermatol 2000;10:542–5.
Balus L, Donati P, Amantea A, et al. Multiple minute digitate hyperkeratosis. J Am Acad Dermatol 1988;18:431–6.
Caccetta TP, Dessauvagie B, McCallum D, Kumarasinghe SP. Multiple minute digitate hyperkeratosis: a proposed algorithm for the digitate keratoses. J Am Acad Dermatol 2012;67:e49–55.

Porokeratoses

Sertznig P, von Felbert V, Megahed M. Porokeratosis: present concepts. J Eur Acad Dermatol Venereol 2012;26:404–12.
Ferreira FR, Nogueira Santos LD, Nogueira Mendes Tagliarini FA, Lanzoni de Alvarenga Lira M. Porokeratosis of Mibelli: literature review and a case report. An Bras Dermatol 2013;88(6 Suppl. 1):179–82.
Dover JS, Phillips TJ, Burns DA. Disseminated superficial actinic porokeratosis: coexistence with other porokeratotic variants. Arch Dermatol 1986;122:887–9.
Cho E, Lee YB, Park HJI, et al. Coexistence of congenital linear porokeratosis and disseminated superficial actinic porokeratosis. Australas J Dermatol 2012;53:e30–1.
Touitou I, Galeotti C, Rossi-Semerano L, Hentgen V, Piram M, Koné-Paut I. The expanding spectrum of rare monogenic autoinflammatory diseases. Orphanet J Rare Dis 2013;8:162.
Rodriguez EA, Jakubowicz S, Chinchilla DA, et al. Porokeratosis of Mibelli and HIV infection. Int J Dermatol 1996;35:402–4.
Morton CA, Shuttleworth D, Douglas WS. Porokeratosis and Crohn's disease. J Am Acad Dermatol 1995;32:894–7.
Nakamura M, Fukamachi S, Tokura Y. Acute onset disseminated superficial porokeratosis associated with exacerbation of diabetes mellitus due to development of anti-insulin antibodies. Dermatoendocrinology 2010;2:17–18.
Hunt SJ, Sharra WG, Abell E. Linear and punctate porokeratosis associated with end-stage liver disease. J Am Acad Dermatol 1991;25:937–9.
Hernandes MH, Lai CH, Mallory SB. Disseminated porokeratosis associated with chronic renal failure: a new type of disseminated porokeratosis? Arch Dermatol 2000;136:1568–9.
Cannavo SP, Borgia F, Adamo B, et al. Simultaneous development and parallel course of disseminated superficial porokeratosis and ovarian cancer: coincidental association or true paraneoplastic syndrome? J Am Acad Dermatol 2008;58:657–60.
Fernandez-Flores A. Small lesions of porokeratosis show a normal proliferation rate with MIB-1. Acta Dermatovenerol Alp Pannonica Adriat 2008;17:22–5.
Kamata Y, Maejima H, Watarai A, et al. Expression of bleomycin hydrolase in keratinization disorders. Arch Dermatol Res 2012;304:31–8.
Otsuka F, Chi HI, Shima A. Cytological demonstration of abnormal DNA ploidy in the epidermis of porokeratosis. Arch Dermatol Res 1988;230:61–3.
Zhang SQ, Jiang T, Li M, et al. Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis. Nat Genet 2012;44:1156–60.
Kanitakis J, Euvrard S, Faure M, et al. Porokeratosis and immunosuppression. Eur J Dermatol 1998;8:459–65.
Luan J, Niu Z, Zhang J, et al. A novel locus for disseminated superficial actinic porokeratosis maps to chromosome 16q24.1–24.3. Hum Genet 2011;129:329–34.
Koley S, Sarkar J, Choudhary S, et al. Different morphological variants of hypertrophic porokeratosis and disseminated lesions of porokeratosis of Mibelli: a rare co-existence. Indian J Dermatol Venereol Leprol 2011;77:199–202.
Happle R. Cancer proneness of linear porokeratosis may be explained by allelic loss. Dermatology 1997;195:20–5.
Chen TJ, Chou YC, Chen CH, Kuo TT, Hong HS. Genital porokeratosis: a series of 10 patients and review of the literature. Br J Dermatol 2006;155:325–9.
Robinson JB, Im DD, Jockle G, et al. Vulvar porokeratosis: case report and review of the literature. Int J Gynecol Pathol 1999;18:169–73.
McGuigan K, Shurman D, Campanelli C, et al. Porokeratosis ptychotropica: a clinically distinct variant of porokeratosis. J Am Acad Dermatol 2009;60:501–3.
Hong J-B, Hsiao C-H, Chu C-Y. Systematized linear porokeratosis: a rare variant of diffuse porokeratosis with good response to systemic acitretin. J Am Acad Dermatol 2009;60:713–15.
Patrizi A, Passarini B, Minghetti G, et al. Porokeratosis palmaris et plantaris disseminata: an unusual clinical presentation. J Am Acad Dermatol 1989;21:415–18.
Chouery E, Guissart C, Mégarbané H, et al. Craniosynostosis, anal anomalies and porokeratosis (CDAGS syndrome): case report and literature review. Eur J Med Genet 2013;56:674–7.
Sander CA, Pfeiffer C, Kligman AM, et al. Chemotherapy for disseminated actinic keratoses with 5-fluorouracil and isotretinoin. J Am Acad Dermatol 1997;36:236–8.
Harrison S, Sinclair R. Porokeratosis of Mibelli: successful treatment with topical 5% imiquimod cream. Australas J Dermatol 2003;44:281–3.
Kim HS, Baek JH, Park YM, et al. Photodynamic therapy combined with CO₂ laser vaporization on disseminated superficial actinic porokeratosis: a report of 2 cases on the face. Ann Dermatol 2011;23(Suppl. 2):S211–13.
Marks S, Varma R, Cantrell W, et al. Diclofenac sodium 3% gel as a potential treatment for disseminated superficial actinic porokeratosis. J Eur Acad Dermatol Venereol 2009;23:42–5.
Bakardzhiev I, Kavaklieva S, Pehlivanov G. Successful treatment of disseminated superficial actinic porokeratosis with calcipotriol. Int J Dermatol 2012;5:1139–42.
Garg T, Ramchander, Varghese B, et al. Generalized linear porokeratosis: a rare entity with excellent response to acitretin. Dermatol Online J 2011;17(5):3.

Transient acantholytic dermatosis

Grover RW. Transient acantholytic dermatosis. Arch Dermatol 1970;101:426–34.
Streit M, Paredes BE, Braathen LR, et al. [Transitory acantholytic dermatosis (Grover disease). An analysis of the clinical spectrum based on 21 histologically assessed cases.] Hautarzt 2000;51:244–9.
Eaver J, Bergfeld WF. Grovers disease (transient acantholytic dermatosis). Arch Pathol Lab Med 2009;133:1490–4.
Davis MD, Dinneen AM, Landa N, et al. Grover's disease: clinicopathologic review of 72 cases. Mayo Clin Proc 1999;74:229–34.
Phillips C, Kalantari-Dehaghi M, Marchenko S, et al. Is Grover's disease an autoimmune dermatosis? Exp Dermatol 2013;22:781–4.
Scheinfeld N, Mones J. Seasonal variation of transient acantholytic dyskeratosis (Grover's disease). J Am Acad Dermatol 2006;55:263–8.
French LE, Piletta PA, Etienne A, et al. Incidence of transient acantholytic dermatosis (Grover's disease) in a hospital setting. Dermatology 1999;198:410–11.
Fernandez-Figueras MT, Puig L, Cannata P, et al. Grover disease: a reappraisal of histopathological diagnostic criteria in 120 cases. Am J Dermatopathol 2010;32:541–9.
El Shabrawi-Caelen L, Rütten A, Kerl H. The expanding spectrum of Galli-Galli disease. J Am Acad Dermatol 2007;56(5 Suppl.):S86–91.
Helfman RJ, Gables C. Grover's disease treated with isotretinoin. J Am Acad Dermatol 1985;12:981–4.
Breuckmann F, Appelhans C, Altmeyer P, et al. Medium-dose ultraviolet A1 phototherapy in transient acantholytic dermatosis (Grover's disease). J Am Acad Dermatol 2005;52:169–70.
Norman R, Chau V. Use of etanercept in treating pruritus and preventing new lesions in Grover's disease. J Am Acad Dermatol 2011;64:796–8.
Liu S, Letada PR. Successful novel treatment of recalcitrant transient acantholytic dermatosis (Grover's disease) using red light 5-aminolevulinic acid photodynamic therapy. Dermatol Surg 2013;39:960–1.

Keratolysis exfoliativa

Wende GW. Keratolysis exfoliativa. J Cutan Dis 1919;37:174.
Chang YY, van der Velden J, van der Wier G, et al. Keratolysis exfoliativa (dyshidrosis lamellose sicca): a distinct peeling entity. Br J Dermatol 2012;167:1076–84.

Xerosis cutis and asteatosis

Berry N, Charmeil C, Goujon C, et al. A clinical, biometrological and ultrastructural study of xerotic skin. Int J Cosmet Sci 1999;21:241–52.
Wesley NO, Maibach HI. Racial (ethnic) differences in skin properties: the objective data. Am J Clin Dermatol 2003;4:843–60.
Jensen JM, Förl M, Winoto-Morbach S, et al. Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging. Exp Dermatol 2005;14:609–18.
Choi EH, Man MQ, Xu P, et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol 2007;127:2847–56.
Engelke M, Jensen JM, Ekanayake-Mudiyanselage S, Proksch E. Effects of xerosis and ageing on epidermal proliferation and differentiation. Br J Dermatol 1997;137:219–25.
Ghadially R, Brown BE, Sequeira-Martin SM, et al. The aged epidermal permeability barrier. Structural, functional and lipid biochemical abnormalities in humans and a senescent murine model. J Clin Invest 1995;95:2281–90.
Simon M, Bernard D, Minondo AM, et al. Persistence of both peripheral and non-peripheral corneodesmosomes in the upper stratum corneum of winter xerosis skin versus only peripheral in normal skin. J Invest Dermatol 2001;116:23–30.
Dunn LB, Damesyn M, Moore AA, Reuben DB, Greendale GA. Does estrogen prevent skin aging? Results from the First National Health and Nutrition Examination Survey (NHANES I). Arch Dermatol 1997;133:339–42.
Li LF, Lan YZ. Bathing and generalized asteatotic eczema: a case-control study. Br J Dermatol 2008;159:243–5.
Valentine J, Belum VR, Duran J, et al. Incidence and risk of xerosis with targeted anticancer therapies. J Am Acad Dermatol 2015;72:656–67.
Schulz P, Bunselmeyer B, Brautigam M, Luger TA. Pimecrolimus cream 1% is effective in asteatotic eczema: results of a randomized, double-blind, vehicle-controlled study in 40 patients J Eur Acad Dermatol Venereol 2007;21:90–4.
Wollina U. The role of topical calcineurin inhibitors for skin diseases other than atopic dermatitis. Am J Clin Dermatol 2007;8:157–73.

Acute epidermal distension and acute oedema blisters

Cox NH, Chalmers RJG, Bhushan M. The acute edema/cutaneous distension syndrome. Arch Dermatol 2003;139:224–5.
Bhushan M, Chalmers RJ, Cox NH. Acute oedema blisters: a report of 13 cases. Br J Dermatol 2001;144:580–2.
Wiesen J, Gonzalez-Estrada A, Auron M. Postangioedema attack skin blisters: an unusual presentation of hereditary angioedema. BMJ Case Rep 2014; doi: 10.1136/bcr-2013-201482.
Fernández Romero D, Di Marco P, Malbrán A. Acute edema blisters in a hereditary angioedema cutaneous attack. Allergol Immunopathol (Madr) 2008;36:182–3.
Gniadecka M. Localization of dermal edema in lipodermatosclerosis, lymphedema, and cardiac insufficiency. High-frequency ultrasound examination of intradermal echogenicity. J Am Acad Dermatol 1996;35:37–41.
Gniadecka M, Quistorff B. Assessment of dermal water by high-frequency ultrasound: comparative studies with nuclear magnetic resonance. Br J Dermatol 1996;135:218–24.
Bhushan M, Cox NH, Chalmers RJG. Eczéma craquelé resulting from acute oedema: a report of seven cases. Br J Dermatol 2001;145:355–7.
Ishiguro N, Kawashima M. Striae-like epidermal distension: a newly recognized cutaneous manifestation in acute leg edema. Arch Dermatol 2002;138:641–2.