HX02 From arsenic to rituximab: a history of dermatitis herpetiformis

Abstract Dr Edward Tilbury Fox was the first to describe dermatitis herpetiformis (DH) in 1872, calling it ‘hydroa herpetiformis’. In 1884, Louis Duhring first used the term ‘dermatitis herpetiformis’, due to the grouped herpetiform vesicles. Early therapies were limited: for the wealthy, a visit to Harrogate spa, oral arsenic and sulfur ointment were preferred; a 3-week stay in hospital was the alternative for others. Additional treatments included quinine, belladonna, strychnine and ergot. Norman Walker declared that the prognosis was: ‘good…if the patient does not commit suicide on account of the mental disturbance brought about by the itching, but with regard to a speedy cure it is undeniably bad’ (Walker N, Percival GH. An Introduction to Dermatology, 10th edn. Edinburgh: W. Green, 1939). Various early 20th century doctors noted anecdotal benefits of dietary restriction. In 1912, a patient with intractable DH cleared entirely after a fortnight taking nothing but water. Dermatologists struggled to persuade subsequent patients ‘to undergo more than two or three days of starvation’. The first major breakthrough came in 1950, when it was recognized that dapsone immediately abolished the itch and rash, and it became the mainstay of treatment. In 1966, Janet Marks showed the association between DH and coeliac disease (CD), noting the high proportion of patients with DH with abnormalities of the small intestinal mucosa. This was corroborated in 1968, when Lionel Fry observed improvements in the skin, intestinal mucosa and nutrition of a small number of patients with DH following a gluten-free diet (GFD). From 1977, once Timo Reunala proved in a larger study that both the disease burden and reliance on dapsone reduced drastically in patients maintaining a GFD, it became standard therapy. Jejunal biopsy is no longer routine in patients with DH; all are assumed to have gluten sensitivity. The 1969 observation of IgA deposits at the dermal papillae of uninvolved skin suggested the role of antibodies in its aetiology. In 1972, demonstration of the association of the specific human leucocyte antigen (HLA) haplotypes such as HLA-A8 with both DH and CD implied a genetic predisposition. Serum antiepidermal transglutaminase antibodies have since been shown to be a specific diagnostic marker for DH and CD. A GFD and dapsone remain the cornerstones of treatment, with IgA deposits on skin immunofluorescence the gold-standard diagnostic test. Rituximab has been reported to cause complete remission. Ongoing research into the immunopathogenesis of DH may lead to more targeted treatments.