Dermatitis herpetiformis (DH), described over 100 years ago, is a life-long blistering skin disease that can appear at any age. As an inflammatory disease of the skin, DH has been considered as the specific cutaneous manifestation of celiac disease. A major landmark in the research of DH was the discovery of granular IgA deposits in the upper papillary dermis. Although the specific IgA autoantibody responsible for the pathogenesis of DH is unknown, the presence of IgA is considered essential in the pathogenesis of DH. However, one of the main goals in the research on DH is still to resolve the enigma of IgA deposition in the skin, what is the antigen, and how IgA plays a role in blister formation. As an advanced company in the field of therapeutic molecular development, Creative Biolabs established mature IgA research platforms and we are glad to share our experience about DH and IgA with our clients over the world.
Clinical Presentation of Dermatitis Herpetiformis
DH is characterized by pruritic papulovesicular and excoriations presenting symmetrically on extensor skin surfaces, while granular IgA deposits and a predominantly neutrophilic infiltrate at the dermal papillae are typical histopathology presentations in the diagnosis. Moreover, virtually all patients with DH have evidence of celiac disease on histologic examination of small-bowel biopsies, which explains the reason for a response to a lifelong gluten-free diet like celiac disease patients.
Fig.1 Immunofluorescence of fibrillar IgA deposition (left) and neutrophils clustered in the superficial dermis (right). (Ko, 2010)
IgA and Dermatitis Herpetiformis
DH represents a paradigmatic model of autoimmune disease which can be switched on or off by a known external trigger, as referred the gluten. Although the pathogenesis of DH relying on a complex inflammatory network along the gut-skin axis remains only partly understood at present, epidermal transglutaminase (eTG) has been identified as the main autoantigen of DH, which can bind to anti-eTG IgA. However, one theory suggests that eTG is shed to the dermal-epidermal junction where it binds to anti-eTG IgA, while an alternative hypothesis suggests that eTG/IgA complexes exist as circulating immune complexes, which can deposit at the dermal-epidermal junction. Anyway, a complex interplay stimulates neutrophil adherence to the activated endothelium, which probably binds to IgA/eTG aggregates through the Fc IgA receptor and releases proteases, finally inducing the cleavage of the dermal-epidermal junction.
Fig.2 Pathogenesis of dermatitis herpetiformis. (Antiga, 2019)
Treatment of Dermatitis Herpetiformis
Since DH is the specific cutaneous manifestation of celiac disease, all the patients require a gluten-free diet. Moreover, a gluten-free diet in DH is a way to prevent complications rather than just a symptomatic treatment for skin lesions, it should be maintained for all life. However, cutaneous manifestations may last months or even years after the introduction of a gluten-free diet. Therefore, the pharmacologic treatment of DH is required to control itching and skin rash. Dapsone has been considered the first-line treatment in patients with DH for over 70 years, while sulfonamides drugs, colchicine, and cyclosporin A have been proposed for DH recently. Moreover, biologics may become the next step in DH pharmacologic treatment.
Fig.3 Patient with small excoriated papules and vesicles on the upper arm (left) with rapid resolution after treatment with oral dapsone (right). (Ko, 2010)
Although the mechanism of DH is not totally clear, IgA is commonly regarded as an important factor in pathogenesis. If you are interested in the research of DH, or for more details in the research of the therapeutic molecular field, please feel free to contact us.
References
- Ko, C. J.; et al. Fibrillar IgA deposition in dermatitis herpetiformis-an underreported pattern with potential clinical significance. Journal of cutaneous pathology. 2010, 37(4), 475-477.
- Antiga, E.; et al. Dermatitis herpetiformis: novel perspectives. Frontiers in immunology. 2019, 10, 1290.
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