Dermatitis Herpetiformis Clinical Presentation

Updated: May 08, 2017
  • Author: Jami L Miller, MD; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

Patients typically present with a waxing and waning, pruritic eruption on the extensor surfaces of the arms, knees, and buttocks. It may become generalized. Small vesicles may have been noted but have often been excoriated by the time of presentation to the physician. They may have associated worsening of disease with dietary intake of gluten. Many do not report any GI symptoms, even when prompted.

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Physical Examination

The diagnosis is suspected based on the distribution of the eruption.

Flesh-colored–to–erythematous excoriated papules or plaques with herpetiform (ie, small, clustered) vesicles are symmetrically distributed over extensor surfaces, including the elbows, knees, buttocks, and shoulders.

Dermatitis herpetiformis rarely occurs on the posterior (nuchal) scalp and face. Lesions occur infrequently on the oral mucosa, but males are more likely than females to have involvement of the oral and genital membranes. [31] Palms and soles are spared. Digital purpura resembling vasculitis can occur. Erythematous papules and urticarialike plaques occur less frequently; bullae are rare.

The eruption is intensely pruritic; patients often present with erosions and crusts in the absence of vesicles, which have ruptured due to excoriation.

Typical symptoms include burning, stinging, and intense itching. Rarely, if ever, are patients totally asymptomatic, although the degree of itching varies.

Dermatitis herpetiformis is a lifelong disease, although periods of exacerbation and remission are common.

See the image below.

Polymorphic lesions on extensor surface of arm. Polymorphic lesions on extensor surface of arm.
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Causes

Dermatitis herpetiformis is generally accepted as a cutaneous manifestation of celiac disease. The genetic predisposition to the development of gluten sensitivity underlies the disease.

Gluten is a protein present in grasses of the species Triticeae, which includes barley, rye, and wheat. Gliadin protein in these grains are high-affinity substrates for tissue transglutaminase (TTG). Gliadins can also be found in rice, corn, and oats, but these proteins are poor substrates for TTG and thus these tend to be tolerated. Buckwheat is also tolerated. [22, 23] Strict compliance with a gluten-free diet results in normalization of the small bowel mucosal changes and control of the cutaneous manifestations of dermatitis herpetiformis in most patients. levels of circulating antibodies also tend to normalize.

Although cornstarch does not contain gluten, 2 case reports describe patients with well-controlled dermatitis herpetiformis who had disease flares after ingesting cornstarch. [24]

The gluten-sensitive enteropathy does not cause symptoms in most dermatitis herpetiformis patients. Less than 10% exhibit symptoms of bloating, diarrhea, or malabsorption. However, greater than 90% show abnormalities upon endoscopic examination. Two thirds have villous atrophy detected on intestinal biopsy specimens. The other third shows elevated intraepithelial lymphocyte counts, increased T-cell receptor gamma/delta intraepithelial lymphocyte counts, or both.

The critical role of associated gluten-sensitive enteropathy in the pathogenesis of dermatitis herpetiformis is confirmed by the fact that resumption of a gluten-containing diet in patients with dermatitis herpetiformis results in a return of the characteristic skin disease.

Mild steatorrhea or other signs of mild malabsorption (eg, altered D-xylose absorption, iron or folate deficiency) can be demonstrated in 20-30% of patients with dermatitis herpetiformis.

Patients with dermatitis herpetiformis and no apparent GI disease can be induced into developing dermatitis herpetiformis by increasing gluten intake, which is often termed latent gluten-sensitive enteropathy.

IgA circulating immune complexes are present in 25-35% of patients with dermatitis herpetiformis, although no association with disease severity has been noted. These immune complexes also have been noted in patients with isolated gluten-sensitive enteropathy and are believed to be related to the presence of the gut disease. [6]

IgA antibodies to gliadin (a portion of wheat protein), reticulum, and smooth muscle endomysium have also been noted in patients with dermatitis herpetiformis and in those with isolated gluten-sensitive enteropathy.

IgA endomysial antibodies are most specific for gluten sensitivity and are found in 80% of patients with dermatitis herpetiformis and greater than 95% of patients with celiac disease. The presence of IgA antiendomysial antibodies correlates with the extent of the gut disease; [6, 25] however, some dermatitis herpetiformis patients do not have detectable IgA antiendomysial antibodies, even during episodes of active skin disease.

The criterion standard for the diagnosis of dermatitis herpetiformis remains the presence of granular deposits of IgA in normal-appearing perilesional skin. It is positive in 92.4% of patients.

Patients with bullous pemphigoid, [26]  cicatricial pemphigoid, Henoch-Schönlein purpura, and alcoholic liver disease also may have IgA deposits in normal skin; however, the pattern of IgA deposits is different from that seen in patients with dermatitis herpetiformis.

In patients with dermatitis herpetiformis, 10-15% of their first-degree relatives have dermatitis herpetiformis or celiac disease. HLA studies have conclusively established the presence of a genetic predisposition for dermatitis herpetiformis. Patients with dermatitis herpetiformis have an increased expression of the HLA-A1, HLA-B8, HLA-DR3, and HLA-DQ2 haplotypes. This is identical to the HLA association found in patients with isolated gluten-sensitive enteropathy. Most persons with these HLA types do not have dermatitis herpetiformis or gluten-sensitive enteropathy. Associations of HLA and dermatitis herpetiformis are as follows:

  • For HLA-B8, the association with dermatitis herpetiformis is 58-87%, versus 20-30% for control patients.
  • For HLA-DR3, the association with dermatitis herpetiformis is 90-95%, versus 23% for control patients.
  • For HLA-DQ2, the association with dermatitis herpetiformis is 95-100%, versus 40% for control patients.

Other associations include the following:

  • Associated GI conditions include gluten enteropathy, gastric atrophy, gastric hypochlorhydria, and pernicious anemia.
  • Associated autoimmune diseases include dermatomyositis, type 1 diabetes mellitus, myasthenia gravis, rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, and thyroid abnormalities. Thyroid abnormalities are present in as many as 50% of dermatitis herpetiformis patients and include hypothyroidism, hyperthyroidism, thyroid nodules, and thyroid cancer. [27]
  • Neurologic manifestations such as ataxia have been rarely described. [28]
  • Associated neoplastic conditions include GI lymphomas and non-Hodgkin lymphoma; patients are at increased risk of developing these cancers. [29] A gluten-free diet may reduce the incidence of dermatitis herpetiformis–associated lymphomas.
  • Celiac disease usually involves more severe and widespread intestinal involvement. Celiac disease has been associated with genetic abnormalities, including Down syndrome, Turner syndrome, and William syndrome. Liver disease, neurologic disorders, and other skin diseases are also increased in celiac disease, possibly due to common HLA regions on chromosome 6 or immune molecule cross-reactivity.
  • Gastric manipulation (surgery) may induce dermatitis herpetiformis.
  • Several chemicals have been associated with induction of dermatitis herpetiformis, including potassium iodide and cleaning solutions.
  • Case reports have described dermatitis herpetiformis induced by medications. Leuprolide acetate, inhibitors of tumor necrosis factor-alpha, anti-influenza medications, and progesterone-containing contraceptives have been reported in association with development of dermatitis herpetiformis. [13, 30]
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Complications

Complications are related to the gluten-sensitive enteropathy, the risk of developing lymphomas, and the potential adverse effects of medications, particularly dapsone.

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