CHAPTER 193

Blistering Diseases

A blister (bulla) is a bubble of fluid that forms beneath a thin layer of dead skin. The fluid is a mixture of water and proteins that oozes from injured tissue. Blisters most commonly form in response to a specific injury, such as a burn or irritation, and usually involve only the topmost layers of skin. These blisters heal quickly, usually without leaving a scar. Blisters that develop as part of a systemic (bodywide) disease may start in the deeper layers of the skin and cover widespread areas. These blisters heal more slowly and may leave scars.

Many diseases and injuries can cause blistering, but three autoimmune diseases—bullous pemphigoid, dermatitis herpetiformis, and pemphigus vulgaris—are among the most serious. In an autoimmune disease, the body’s immune system, which normally protects the body against foreign invaders, mistakenly attacks the body’s own cells (see page 1124)—in this case, the skin.

Bullous Pemphigoid

Bullous pemphigoid is an autoimmune disease that causes blistering of the skin.

Bullous pemphigoid occurs when the immune system attacks the skin and causes blistering.

People develop large, itchy blisters with areas of inflamed skin.

Doctors can diagnose bullous pemphigoid by examining skin samples under a microscope and checking for certain antibody deposits.

Treatment involves corticosteroids and drugs that suppress the immune system.

Bullous pemphigoid tends to occur mainly in older people. It is a less serious disease than pemphigus, is rarely fatal, and does not result in widespread peeling of skin. It can involve a large portion of the skin, however, and can be very uncomfortable, with itchiness often the first sign of the disease.

In bullous pemphigoid, the immune system forms antibodies directed against the skin, resulting in large, tense, very itchy blisters surrounded by areas of red, inflamed skin. Blisters in the mouth are uncommon and are not severe. The areas of skin that are not blistered appear normal.

Diagnosis and Treatment

Doctors usually recognize bullous pemphigoid by its characteristic blisters. However, it is not always easy to distinguish it from pemphigus vulgaris and other blistering conditions, such as severe poison ivy. Bullous pemphigoid is diagnosed with certainty by examining a sample of skin under a microscope (skin biopsy). Doctors differentiate bullous pemphigoid from pemphigus vulgaris by noting the layers of skin involved and the particular appearance of antibody deposits.

Mild bullous pemphigoid sometimes resolves without treatment, but resolution usually takes months or years. Therefore, most people receive drug therapy. Nearly everyone responds quickly to high-dose corticosteroids, which are gradually reduced (tapered) after several weeks. The combination of nicotinamide and minocycline or tetracycline is sometimes successful. Sometimes azathioprine or cyclophosphamide is given as well for more severe disease. Immunoglobulin given intravenously is a safe, promising new treatment, especially for people who do not respond to conventional drug therapy. Although some local skin care may be needed, most people do not require hospitalization or intensive skin care treatment.

Dermatitis Herpetiformis

Dermatitis herpetiformis is an autoimmune disease causing clusters of intensely itchy small blisters and hivelike swellings.

In dermatitis herpetiformis, glutens in wheat, rye, and barley products cause the immune system to attack the skin.

People have small, itchy blisters and hivelike eruptions on various areas of the body.

Doctors diagnose dermatitis herpetiformis by examining skin samples under a microscope.

People usually respond to treatment with dapsone and a gluten-free diet.

Despite its name, dermatitis herpetiformis has nothing to do with the herpesvirus. In people with dermatitis herpetiformis, glutens (proteins) in wheat, rye, and barley products somehow activate the immune system, which attacks parts of the skin and causes the rash and itching. People with dermatitis herpetiformis often have celiac sprue (see page 165), which is an intestinal disorder caused by sensitivity to gluten, although they may not have symptoms from the celiac sprue. People also have a higher incidence of other autoimmune diseases, such as thyroiditis, systemic lupus erythematosus, sarcoidosis, and diabetes. People with dermatitis herpetiformis occasionally develop lymphoma in the intestines.

Small blisters usually develop gradually, mostly on the elbows, knees, buttocks, lower back, and back of the head. Sometimes blisters break out on the face and neck. Itching and burning are likely to be severe. Anti-inflammatory drugs, such as ibuprofen, may worsen the rash.

Did You Know…

Dermatitis herpetiformis is not related to the herpesvirus.

Diagnosis and Treatment

The diagnosis is based on a skin biopsy, in which doctors find particular kinds and patterns of antibodies in the skin samples.

The blisters do not go away without treatment. People are usually placed on a gluten-free diet (a diet that is free of wheat, rye, and barley). The drug dapsone, taken by mouth, almost always provides relief in 1 to 2 days but requires that blood counts be checked regularly. Once the disease has been brought under control with drugs and the person has followed a strict gluten-free diet for 6 months or longer, drug treatment usually can be discontinued. However, some people can never stop taking the drug. In most people, any reexposure to gluten, however small, triggers another outbreak. A gluten-free diet may prevent the development of intestinal lymphoma.

Pemphigus Vulgaris

Pemphigus vulgaris is a rare, severe autoimmune disease in which blisters of varying sizes break out on the skin, the lining of the mouth, the genitals, and other mucous membranes.

Pemphigus vulgaris occurs when the immune system mistakenly attacks proteins in the upper layers of the skin.

People experience severe blistering in the mouth and on other areas of the body, and sometimes sheets of skin peel off.

Doctors can diagnose pemphigus vulgaris by examining skin samples under a microscope.

Treatment usually involves corticosteroids or drugs that suppress the immune system.

Pemphigus develops most often in middle-aged or older people. It rarely develops in children. In this disease, the immune system produces antibodies that attack specific proteins that connect the epidermal cells (the cells in the top layer of skin) to each other. When these connections are disrupted, the cells separate from each other and from the lower layers

of the skin, and blisters form. Similar-appearing blisters occur with a less dangerous skin disorder, bullous pemphigoid.

Symptoms

The major symptom of pemphigus vulgaris is the development of clear, soft, usually painless (but sometimes itchy and tender) blisters of various sizes. In addition, the top layer of skin may detach from the lower layers in response to slight pinching or rubbing, causing it to peel off in sheets and to leave painful erosions.

The blisters often first appear in the mouth and soon rupture, forming painful sores (ulcers). More blisters and ulcers may follow until the entire lining of the mouth is affected, causing difficulty swallowing. Blisters form on the skin as well. These blisters then rupture, leaving raw, painful, crusted wounds. The person feels generally ill. Blisters may be widespread, and once ruptured, they may become infected. When severe, pemphigus vulgaris is as harmful as a serious burn. Similar to a burn, the damaged skin oozes large amounts of fluid and is prone to infection by many types of bacteria.

Did You Know…

Pemphigus vulgaris is usually fatal without treatment, but 90% of people survive if they receive treatment.

Diagnosis and Treatment

Doctors usually recognize pemphigus vulgaris by its characteristic blisters, but the disorder is diagnosed with certainty by examining a sample of skin under a microscope (skin biopsy). Sometimes doctors use special chemical stains that allow antibody deposits to be seen under the microscope. Doctors differentiate pemphigus vulgaris from bullous pemphigoid by noting the layers of skin involved and the particular appearance of antibody deposits.

Without treatment, pemphigus vulgaris is usually fatal. With treatment, 90% of people survive. High doses of corticosteroids are the mainstay of treatment. If the disease is controlled, the dose of corticosteroids is gradually reduced (tapered). If the person does not respond to treatment or the disease flares up as the dose is tapered, an immunosuppressant, such as azathioprine, cyclophosphamide, or rituximab, is also given. People with severe pemphigus vulgaris may also undergo plasmapheresis, a process in which antibodies are filtered from the blood (see box on page 1030). Immune globulin given intravenously is a new, safe and effective treatment for severe pemphigus vulgaris. Some people respond well enough to discontinue drug therapy, whereas others must continue taking low doses of the drugs for long periods.

In a hospital, the raw skin surfaces require extraordinary care, similar to the care given to people with severe burns. Antibiotics may be needed to treat infections in ruptured blisters. Dressings, sometimes coated with petroleum jelly, can protect raw, oozing areas.