Dermatitis herpetiformis

Discussion

The cutaneous lesions in DH can be extensive, but in mild cases only a few scattered lesions can be seen on the skin,¹ making the diagnosis of DH difficult. The activity of the eruption might fluctuate in different patients but, without any treatment, the rash rarely disappears for longer than a few weeks.¹ Each of our patients fulfilled 4 out of 5 criteria for DH diagnosis.

Differential diagnosis of DH is made against other auto-immune blistering conditions (such as linear IgA disease and bullous pemphigoid), itchy dermatoses (such as atopic dermatitis, nummular [discoid] eczema, and scabies¹), and psychiatric conditions like neurotic excoriations and dermatitis artefacta. In mild cases, DH might not often be suspected, especially when the patient concomitantly has atopic dermatitis or some other itching skin disease.¹

Similarly, even minor itching lesions in patients with CD warrant dermatologic consultation to confirm or exclude DH, as there are some differences in the management and follow-up of these 2 phenotypically distinct gluten-sensitivity disorders.¹

Dermatitis herpetiformis, the skin’s expression of CD, is induced by the presence of IgA antibodies and epidermal transglutaminase (the main autoantigen) stored in the papillary dermis and vessel walls.¹⁵

Both diseases might appear in the same family and share a strong association with class II histocompatibility locus antigens DR3 and DQw2, and with alleles DQA1*0501 and B1*0201 of chromosome 6.¹⁵ The physiopathogenic mechanism of CD seems to be related to a T-cell response to gluten peptides and the ubiquitous enzyme tissue transglutaminase, which acts as an autoantigen and enhances the immunogenicity toward gluten peptides.¹⁵ This immune response leads to a Th2 cytokine release and to activation of metalloproteinases and of the humoral system, which induces production of IgA and IgM antibodies against gliadin and other modified peptides.¹⁵ The triggered immune system–induced gut mucosal changes range from complete disruption of the mucosal architecture with villous flattening and crypt hyperplasia, to a slight increase in the inflammatory infiltrate, both in the epithelium and the lamina propria.¹⁵

In DH the immune complexes are composed of IgA antibodies, and epidermal transglutaminase is considered the main autoantigen.¹⁵ A cascade of events follows the immune complex deposition, such as activation of neutrophil chemotaxis, cytokine synthesis in the skin with complement activation, and release of metalloproteinases that break down the connective tissue of the dermis and lead to cleavage of the dermal-epidermal junction, which then leads to vesicle formation.¹⁵ This pathophysiologic scenario was evident from the histology examinations of our 4 patients.

Other atypical clinical findings in DH are the presentation in childhood of nonpruritic, deep dermal papules and nodules on the buttocks, hands, and extensor surfaces,¹⁶ isolated erythematous palmar and plantar plaques,¹⁷ and isolated palmar purpura.³ In our cases, patients 1 and 4 displayed several 1- to 2-mm purpuric lesions on the hands and feet, similar to those described by McGovern and Bennion.³ Cutaneous biopsies of the purpuric lesions were conducted, which revealed focal epidermal necrosis, papillary edema with numerous neutrophils and extravasated erythrocytes, and superficial and mild perivascular lymphocytic infiltrate.³ In one area of the slide there was a subepidermal cleavage filled with neutrophils and fibrin, suggesting DH.³ Similar purpuric, pseudopurpuric, and hemorrhagic palmar lesions associated with DH have been reported by other authors.^3–13 This cutaneous sign (purpuric or petechial lesions) on the hands or feet should alert physicians to the possibility of a DH diagnosis when associated with cutaneous itching and excoriated lesions in a DH distribution pattern.

Because DH is considered the cutaneous form of CD, a proven diagnosis of DH in a patient should be used as a diagnostic marker for bowel damage recognition.³ Therefore, small-bowel biopsy might be unnecessary even in DH patients with gastrointestinal symptoms. Diet adherence can be monitored by serologic testing and skin lesion observation, as DH features usually reappear within a few days after gluten ingestion.³

The absence of gastrointestinal symptoms in our patients saved them having bowel biopsies. A gluten-free diet is the treatment of choice for patients with CD and DH because both enteropathy and cutaneous eruption are dependent on gluten ingestion.¹⁴ Dapsone is a valid therapeutic option for patients with DH during the first 2 years after diagnosis, until the gluten-free diet becomes effective.¹⁴ Patient 1 had glucose-6-phosphate dehydrogenase deficiency, and was therefore treated with a combination of tetracycline and nicotinamide, resulting in satisfactory symptomatic control. For patients who cannot tolerate or are unresponsive to dapsone or other sulfonamide drugs, some authors propose alternative therapies such as heparin,¹⁸ tetracycline and nicotinamide,¹⁹ or cyclosporine.²⁰