Selected Skin Diseases With Systemic Involvement

Marcelo Ruiz, MD; Pilar Valdés, MD; Kenneth Tomecki, MD


Skin Therapy Letter. 2013;18(4) 

In This Article

Dermatitis Herpetiformis and Celiac Disease

Dermatitis herpetiformis (DH) is a chronic, intensely pruritic blistering disease characterized by symmetric grouped vesicles, papules, and wheals on the elbows, knees, scalp, and buttocks. It has a clear relationship to celiac disease (CD) and is considered the cutaneous manifestation of gluten sensitivity.[13] Despite this, the majority of DH patients have silent or mild gastrointestinal CD. Pathophysiologies of both disorders are closely related, involving genes and the environment. Human leukocyte antigens (HLA) DQ2 and DQ8 have been identified as predisposing factors.[13,14] Tissue transglutaminase (tTG or TG2) and epidermal transglutaminase (eTG or TG3) are thought to be the main autoantigens in CD and DH, respectively. tTG, an ubiquitous enzyme, plays a role in gluten intolerance by modifying gliadin (fraction of gluten) into an efficient autoantigen and forming tTG-gliadin immunogenic complexes. eTG is homologous to tTG, localized in the epidermis to maintain the cornified envelope integrity.[13,14]

Clinically, the primary lesions of DH (papules and vesicles) are often absent, replaced by erosions and excoriations, sometimes leading to lichenification. Purpura on the fingers and toes is an interesting clinical finding but not always present. It rarely has mucosal involvement.[13,14] Evolution with symptom-free months during summer occurs in some patients due to a beneficial sun exposure effect.[14]

Biopsy reveals a subepidermal cleft with neutrophils and a few eosinophils at the tips of dermal papillae, and direct immunofluorescence is confirmatory, by demonstrating pathognomonic granular deposition of IgA at the dermalepidermal junction.[13] Serologic tests are useful to aid diagnosis and monitor disease activity, looking for IgA-TG or antiendomysial antibodies. In DH, IgA antibodies can be specific for eTG, making the detection of specific IgA-eTG antibodies a promising tool that needs further validation.[13,14] Genetic testing for HLA DQ2 and DQ8 can be useful in some cases to rule out DH. Differential diagnosis includes linear IgA dermatosis, bullous pemphigoid, scabies, contact dermatitis, and bullous lupus erythematosus.[13]

A wide range of autoimmune disorders are associated with DH, such as diabetes type I or hypothyroidism, the latter being the most common. Screening for common autoimmune disorders is generally indicated. Clinical examination of the skin may reveal a concurrent autoimmune disease, such as vitiligo, primary biliary cirrhosis (jaundice), pernicious anemia, alopecia areata or lupus erythematosus.[14] Clinical signs of malabsorption may also be present, such as anemia due to iron, folate, or B12 deficiency, and caries or diffuse alopecia due to zinc deficiency. DH patients may also have a higher risk of developing non-Hodgkin lymphoma, particularly enteropathy-associated T-cell lymphoma. This is an important comorbidity to rule out, especially in longstanding, untreated DH or CD.[14,15]

Therapy is always based on a gluten-free diet. Skin lesions and pruritus of DH are rapidly responsive to oral dapsone. Other treatments include sulfasalazine and sulfamethoxypyridazine.[15]