Clinical Dermatology

Diagnostic Hallmarks

1. Distribution - elbows, knees, sacrum, and scapular areas
2. Herpetic-like clustering of vesicles
3. Immunofluorescent biopsy studies: granular deposits of immunoglobulin A (IgA) in the papillary dermis
4. Rapid response to dapsone therapy

Clinical Presentation

As its name “herpetiform” implies, the very uncommon condition, dermatitis herpetiformis, is characterized by the presence of clustered, small vesicles. The individual vesicles are usually 2-6 mm in diameter, but larger blisters are occasionally present. The clusters, each containing 5-20 vesicles, are most often found on the buttocks, sacrum, scapulae, and extensor surfaces of the arms and legs. They occur bilaterally and exhibit considerable symmetry. There is usually a brisk inflammatory response around the vesicles, such that they appear to be arising from an erythematous plaque.

Pruritus is generally intense and is accompanied by vigorous scratching. For this reason, most patients have few intact vesicles and, instead, demonstrate multiple, clustered, excoriated papules. When excoriations are more prominent than vesicles, the disease takes on an eczematous (dermatitis) appearance . New lesions appear in crops even while old lesions are healing. Excoriated lesions generally heal with a hypopigmented center and a surrounding collar of hyperpigmentation.

Asymptomatic small bowel disease regularly occurs in association with dermatitis herpetiformis. Bowel biopsy reveals changes similar to, but milder than, those found in gluten enteropathy. Several types of autoimmune disease, including glomerulonephritis and thyroid disease, have also been noted in patients with dermatitis herpetiformis.

A suspected clinical diagnosis must be confirmed by biopsy. The presence of a subepidermal vesicle with plentiful perivesicular neutrophils on routine histology is suggestive, the finding of granular IgA deposits (with or without C3) in the papillary dermis of perilesional skin on direct immunofluorescent microscopy is pathognomonic.

Course and Prognosis

Dermatitis herpetifonnis occurs most commonly in young adults and those of middle age. It is a chronic disease that lasts indefinitely. The pruritus, if left untreated, is extremely debilitating, but otherwise there is little morbidity. The gluten enteropathy remains asymptomatic in most patients. A very few patients have developed intestinal lymphomas late in the course of the disease.

Pathogenesis

Genetic factors are presumably important, since approximately 90% of patients have the HLA markers of B8, DR3 or DQw2. Familial cases are uncommon, however, suggesting that one or more precipitating factors are also necessary. The regular presence of IgA and the frequent presence of complement components in the papillary dermis suggest that immune factors playa role, but the antigen responsible for this deposition has not been positively identified. It is likely that the antigen is related to gluten perhaps with cross-reactivity between gluten and small connective tissue microfibrils. At the clinical level, gluten sensitivity certainly seems to play some important role, since in most cases a gluten-free diet, if it is strictly adhered to, leads to both bowel and skin improvement. Indirect immunofluorescent testing reveals no circulating IgA antibody directly corresponding to the deposited IgA present on direct immunofluorescent microscopy. Circulating immune complexes and various other antibodies (especially antiendomysial antibodies) are often found, but their meaning is presently unknown.

Therapy

Nearly all patients with dermatitis herpetiformis respond immediately and completely to treatment with sulfapyridine or dapsone. Dapsone, the drug of choice, is used in a dose of about 100 mg/ day. Some clinicians start with 25 mg/ day and build to the needed dose, whereas others simply start with the full 100 mg/day. Numerous side effects can occur with dapsone therapy; these, along with recommendations for periodic laboratory testing, are found in Chapter 3. Sulfapyridine is used when dapsone is not tolerated. The usual dose is about 2.0 g/ day. With either drug the dosage is tapered to maintenance levels once response has occurred. Remissions once obtained can usually be continued indefinitely, as resistance to medication does not seem to occur. Strict adherence to a gluten-free diet will in many cases allow the dose of dapsone to be lowered, and in some cases the dose can be discontinued altogether. Unfortunately, patient compliance with such diets is usually rather poor.

This entry was posted on Monday, August 27th, 2007 at 9:01 am and is filed under Vesiculobullous Diseases. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.