Daniel Creamer1 and Michael Gossop2
1Department of Dermatology, King's College Hospital, London, UK
2National Addiction Centre, King's College London, London, UK
Far from being an exceptional and ‘deviant’ behaviour, the use of illicit drugs is relatively common and is found among all sections of society. The misuse of drugs is often thought of as mainly a problem among adolescents and young adults but it also occurs among children and older adults, although patterns of use tend to differ in different age groups.
The terms used to describe illicit drug use are often vague and poorly defined, and this is especially true of the terms ‘misuse’ and ‘abuse’ which have no precise medical or scientific meaning. Drug-taking behaviours may occur as experimental use, occasional and recreational use, or as regular and dependent use of drugs. Drug taking may be conceptualized in terms of three dimensions. These are: consumption behaviours (e.g. frequency of use, dose levels, route of administration), substance-related problems (intoxication, accidents and injury, overdose, infections) and severity of dependence (withdrawal symptoms, impaired behavioural control). These three dimensions can be regarded as being conceptually distinct and separate. In reality, of course, they may be related (sometimes closely) in a number of ways. Drug dependence (addiction) differs fundamentally from the mere use of drugs: it is manifested, psychologically and behaviourally, in feelings of compulsion to use drugs and difficulty in resisting those urges, and these changes are underpinned by neurophysiological changes in the brain.
Many forms of drug use, but especially drug dependence, can cause a wide range of serious health and social problems, and the use of medical health services among persons with substance use disorders is far higher than for the general population. All doctors can expect to see substantial numbers of patients who use illegal drugs, though this will often not be made explicit at the time of seeking treatment. In a national study of treatment outcomes for individuals receiving treatment for drug addiction, about half of them were found to have attended an accident and emergency department in the 2 years prior to starting addiction treatment, and a quarter had at least one admission to a hospital for a medical problem; more than-two thirds had also visited a general practitioner [1]. Physicians should bear in mind that drug users’ concerns about problems with their physical health are often an important motivating factor that may lead them to seek substance use treatment.
The costs of drug abuse in the UK cannot be calculated precisely, but they are known to be massive. Every year the problems associated with drug abuse and its consequences cost the country many billions of pounds. A recent estimate in the USA suggested that in 2007 illicit drug use cost the US economy more than US$193 billion [2]. Health costs include the treatment of a wide range of medical problems as well as the treatment of psychiatric and addiction problems. Medical care costs associated with heroin addiction and its associated medical complications account for a large proportion of the treatment costs. Other costs are incurred by social services, and for policing, interdiction and processing offenders within the criminal justice system.
For the dermatologist, skin eruptions induced by illicit drugs may be encountered in a variety of clinical settings. Dermatoses in this group of patients may range from pharmacological side effects of the drug to cutaneous complications of drug administration [3].
Cannabis is the most widely used of the illicit drugs, and a conservative estimate suggests that about 78 million Europeans (about 20% of all 15–64-year-olds) have used cannabis on at least one occasion, and an estimated 22.5 million have used it in the previous year [4].
Cannabis, or marijuana, is prepared from the plant Cannabis sativa and can be eaten, drunk or, as is most common in Europe and America, smoked. Pharmacologically cannabis is a complex substance; the main active components are the cannabinoids, tetrahydrocannabinol being the most psychoactive constituent. The subjective effects of cannabis include a sense of relaxation, coupled to a heightened sensory awareness.
The short-term side effects of cannabis include a reddening of the eyes, dry mouth and a slight rise in blood pressure. If a large dose is taken then the user may develop intense anxiety, which can be misinterpreted as an acute psychiatric illness. Convincing evidence that true schizophrenia can be induced by long-term cannabis use is lacking [5].
Chronic cannabis use can cause cannabis arteritis, a subtype of thromboangiitis obliterans, which may lead to peripheral necrosis, most often of the lower limbs [6] (see Chapter 103). It is thought to be caused by the vasoconstrictive effects of Δ-9-tetrahydrocannabinol and other unidentified contaminants. Cannabis arteritis presents with Raynaud phenomenon and, if neglected, digital necrosis. Duplex ultrasound can differentiate between cannabis arteritis and atherosclerosis [6]. Revascularization and reperfusion of an affected extremity should occur with discontinuation of cannabis along with antiplatelet and vasodilator therapies [7].
The misuse of volatile substances (sometimes, though inaccurately, referred to as ‘glue sniffing’) may involve the inhalation of aerosols, glues, lighter fuel, thinners and other solvents, and is primarily a problem found among children and young adolescents. Reliable prevalence estimates are difficult to obtain. However, it is thought that between 3.5% and 10% of adolescents may have at least experimented with volatile substances [8]. Solvent fumes are normally inhaled through the nose (‘sniffing’) or via a plastic bag held tightly around the mouth (‘bagging’) or with a solvent-soaked rag placed in the mouth (‘huffing’). Aerosolized cleaning products for electronic equipment can be inhaled by placing the canister nozzle straw into a nostril (‘dusting’).
A characteristic perioral or perinasal papular eruption with pustules, known as ‘glue sniffer's rash’, is caused by a non-specific contact reaction and may be encountered in chronic users of inhalants [9]. The abuse of aerosolized cleaning fluid has been associated with cutaneous and mucosal blistering, and also with angio-oedema [10]. Chemical burns around the nose and mouth caused by solvent irritancy have been also reported [11].
Ecstasy is the name given to N-methyl-3,4-methylenedioxymetamphetamine (MDMA), a drug which is taken orally. It is mainly used as a ‘dance drug’ and has widespread usage in the ‘dance’, ‘rave’ and ‘techno’ scenes. Ecstasy has unique psychoactive properties, producing a controllable emotional state of relaxation and happiness. Doses are generally in the range of 75–150 mg, the effects starting within 30 min of taking the drug by mouth. The peak effects tend to occur during the next hour, and then diminish over the following 2 h.
Among the more common side effects of ecstasy are tension in the jaw and grinding of the teeth (bruxism). Anxiety, palpitations and an increase in blood pressure may also occur. Acute hepatotoxicity is recognized, while the exertion that follows fast dancing may compound the pharmacological effects of ecstasy resulting in collapse, convulsions and acute kidney injury [12]. Hyperthermia is another potentially life-threatening side effect that may be mediated by increased dopamine release acting on D1 receptors [13].
’Ecstasy pimples’ describe a facial dermatosis occurring in individuals shortly after the consumption of ecstasy [14]. The dermatosis consists of inflammatory papules and pustules, but no comedones, similar to perioral dermatitis [14].
Crystal methamphetamine (meth) is made by the reduction of ephedrine or pseudoephedrine through a toxic and flammable process, often in mobile ‘meth labs’, using batteries and fertilizers. It can be injected, smoked or snorted. Methamphetamine induces euphoria and gives the user a feeling of increased energy; the ‘high’ lasts for up to 10 h.
The side effects of crystal meth are predominantly psychological or psychiatric. Anxiety and irrational fear is a short-term problem. Prolonged, heavy use of meth may be accompanied by persecutory symptoms resembling those of paranoid schizophrenia [15].
The commoner cutaneous side effects of crystal meth abuse are xerosis and pruritus. Pruritus and formication (‘meth mites’) are well recognized and can lead to skin picking, especially on the face [16]. A florid form of tooth decay, ‘meth mouth’, is also well recognized and characterized by severe caries, excessive tooth wear and gum disease [17]. It is caused by poor oral hygiene, bruxism, xerostomia and, perhaps, a reduction in saliva pH. Resorption of gingival bone from tooth decay and gum disease contributes to a loss of volume of the lower face, which exaggerates the premature ageing characteristic of crystal meth abuse [18].
Cocaine is extracted from Erythroxylum coca plant in the form of a paste. It is then purified into a water-soluble powder that can be inhaled, ingested orally or mixed with water and injected. It can only be smoked as ‘crack cocaine’, a free base, hard, brittle substance produced after neutralization with sodium bicarbonate or ammonia mixed with water. Cocaine is a sympathomimetic that causes euphoria within minutes or seconds if smoked.
Inhalation of cocaine results in nasal inflammation, while the local vasoconstrictor effect may lead to mucosal necrosis. Cocaine-induced midline destructive lesions are exacerbated by microtraumas to the nasal mucosa complicated by Staphylococcus aureus infections [19]. The continuous consumption of high doses of cocaine is associated primarily with psychological side effects: the user may experience feelings of persecution or, in extreme cases, develop a toxic psychosis [20].
Formication may occur with cocaine usage and, as in other similar situations, may result in skin picking [21]. A few case reports have identified long-term cocaine abusers who have developed pyoderma gangrenosum (PG). In one report, PG occurred on the legs in conjunction with cavitating chest lesions; investigations revealed a positive level of perinuclear antineutrophil cytoplasmic antibodies (ANCA), indicating a Wegener granulomatosis-like syndrome [22]. In this patient, episodes of PG were associated with periods of cocaine use, while remission from PG coincided with cocaine abstinence [22].
Since 2010 there have been case reports of cocaine users developing cutaneous vasculitis [23] (see Chapter 102). The causative substance is an adulterant, levamisole, used as a cocaine-bulking agent [24]. Levamisole-induced vasculitis presents with purpuric retiform lesions, typically on the ears, cheeks, nose and extremities [24]. Lesional skin may become confluent to produce large areas of cutaneous necrosis or haemorrhagic bullae [24]. Histologically, lesions demonstrate a leukocytoclastic vasculitis and/or thrombotic vasculopathy involving small or medium-sized vessels [25]. Many patients are found to have a positive ANCA, as well as other autoantibodies [26].
Heroin (chemical name, diacetylmorphine) is synthesized from morphine, which is a naturally occurring substance extracted from the seed pod of the Asian opium poppy plant. The most common forms of heroin are a white powder or a black sticky substance (called ‘black tar’). Heroin base (common in Europe) must be mixed with an acid such as lemon juice to dissolve in water; the hydrochloride salt (common in the USA) only requires water to be dissolved. Heroin is usually injected, but can be smoked or snorted. Intravenous injection of heroin induces an instantaneous sensation of ecstasy (the ‘rush’) followed by a period of detached and dreamy relaxation (the ‘high’).
’Krokodil' is the jargon term for an opiate drug being used increasingly in Eastern Europe and elsewhere. It is manufactured by boiling codeine tablets with a number of other substances to yield a suspension containing desomorphine [27]. Krokodil has a swift onset and short half-life.
The major side effects of heroin use relate to the dangers of drug injection, most notably the risk of infection with HIV and hepatitis viruses. However the drug itself is recognized to impair sexual drive and to cause impotence.
Itching at the site of the injection, the central face and genital skin is common with heroin use. However, in a blinded cross-over study, itch and urticaria were more severe in 39 injecting drug users when given morphine compared with heroin [28]. Pemphigus vegetans, fixed drug eruptions, toxic epidermal necrolysis and necrolytic migratory erythema (not associated with glucagonoma) have all been described with long-term heroin consumption [29]. Krokodil contains numerous toxic contaminants that cause damage to the blood vessels and soft tissues. Thrombophlebitis, abscesses and skin and soft tissue necrosis are all common with krokodil and produce widespread cicatricial and scaly skin changes reminiscent of crocodile skin, hence the name [27].
The skin is the tissue most prominently affected by injecting drug use [30]. The commonest cutaneous stigma of drug use is a line of puncture scars distributed over a vein, or parallel to it. The typical progression of venous access sites used over time starts with the antecubital fossae followed by the upper arms and then the hands. As accessible veins become sclerosed, the drug user will utilize veins in the neck, feet, legs, groins, digits and even the penis [31]. Post-inflammatory hyperpigmentation occurs at sites of injections; more specifically ‘soot tattooing’ may occur from flamed needles [32]. When all veins have been destroyed, users may inject subcutaneously or intramuscularly, known as ‘skin popping’, which results in circular, pale, atrophic (or hypertrophic) scars measuring 1–2 cm in diameter [30]. Necrotizing ulcers may also develop as a consequence of skin popping, and are caused by infection or the irritant properties of the drug or adulterant [30]. Injection of the analgesic drug pentazocine may cause ulceration, panniculitis, sclerosis and hyperpigmentation [33]. Large areas of cutaneous fibrosis interspersed with ulceration can complicate methadone injection [34].
Injection by the intra-arterial route may occur once venous access is no longer obtainable and is accompanied by post-injection pain, cyanosis and oedema [35]. Cutaneous necrosis may be caused by arterial thrombosis or by particulate material within the injected drug, leading to embolic infarction. Irreversible, non-pitting oedema (lymphoedema) of the dorsum of the hands, the puffy hand syndrome, is caused by damage to cutaneous lymphatics from long-term IV drug use [36].
Cutaneous infections are a common complication of IV drug abuse. A retrospective study in a London teaching hospital over a 5-year period identified a cohort of 124 injecting drug users requiring 191 admissions. Skin and soft tissue infections were the commonest reason for admission (58%) [37]. Abscesses, cellulitis and necrotizing lesions occur frequently. One study of IV drug users found that 11% of subjects reported having at least one abscess in the past 6 months [38], and a fivefold higher risk associated with ‘skin popping’ in comparison with IV injection [39]. Most bacterial infections are caused by the subject's own skin flora, with Staphylococcus aureus and Streptococcus species being the most common pathogens [40]. A number of factors contribute to skin infection, including contamination of drugs, non-sterile equipment, lack of aseptic technique, HIV positivity, intradermal injection and ‘booting’, which is the jargon term for repeatedly flushing and pulling back during injection [41]. Injecting ‘speedballs’ (a mixture of cocaine and heroin) is a recognized risk factor for skin abscesses; it has been suggested that the vasoconstrictive effect of cocaine may enhance the risk of skin sepsis [42]. Other bacterial pathogens isolated in skin infections include Gram-negative and anaerobic organisms, which may originate from the mouth since drug addicts are known to use saliva as a skin cleanser and as a drug diluent.
Over the past 20 years cases of wound botulism have been reported occurring among injecting drug users in the USA and Europe [43, 44]. Injection sites become infected with the anaerobic, spore-forming bacterium Clostridium botulinum, which releases a neurotoxin causing cranial nerve palsies and descending flaccid paralysis (botulism). In many of these cases C. botulinum has been isolated from the drugs used, particularly black-tar heroin. Many of the patients had injected the drug subcutaneously, suggesting the role of skin popping. There has also been a cluster of tetanus cases in the UK among drug users, suggesting contamination of drugs with Clostridium tetani [45]. Necrotizing fasciitis due to clostridial infection is also seen. In a US study of necrotizing fasciitis in injection drug users, all 32 patients were injecting black-tar heroin; it was caused by clostridial infections in 24 of the cases, eight of which were Clostridium sordelli [46]. Skin infections caused by other virulent organisms have been reported, including Candida [47] and Panton–Valentine leucocidin-elaborating S. aureus [48].
In 2013, the cost to the UK National Health Service of treating soft tissue infections in drug users was estimated at £77 million per year [37].