Recently I “accidentally” diagnosed a severely pruritic man with dermatitis herpetiformis (DH). He had seen leading authorities for his life-altering pruritic dermatosis, that clinically and histologically was an eczematous eruption. On the off chance that it might be bullous pemphigoid, I repeated a skin biopsy and direct immunofluorescence – I was surprised to see granular IgA and C3 at the epidermal-dermal junction, diagnostic of DH. His serum tissue transglutaminase IgA antibodies were positive. Just 50 mg of dapsone afforded immediate relief and he has thrived on a gluten-free diet. Not everyone is so fortunate.
Other therapeutic options for DH include sulfasalazine, sulfapyridine, cyclosporine, prednisone, azathioprine, colchicine, tetracyclines, nicotinamide, mycophenolate mofetil, and rituximab. Topical therapies such as steroids and dapsone gel may help reduce pruritus (1).
Albers et al presented the case of an octogenarian man with DH not controlled by gluten-free diet (with poor adherence), dapsone, and conventional immune-suppressing agents who responded to treatment with rituximab according to the lymphoma protocol (4 weekly infusions of 375 mg/m2). His prednisone was tapered off one month after completion of rituximab treatment, but he was also continuing azathioprine as maintenance therapy. Thirteen months after treatment, the patient had achieved complete resolution of pruritus and clinical manifestations of the disease, as well as normalization of antibodies against epidermal and tissue transglutaminases. He achieved complete clinical and serological remission and has remained symptom-free up to 18 months following treatment. The authors suggested that rituximab is a viable therapeutic option for recalcitrant DH, although they state: “Appropriateness of treatment with rituximab should be decided on the basis of the patient’s disease burden, immune status, and comorbidities because rituximab carries some risk for hypogammaglobulinemia and immunosuppression.” (2)
As in celiac disease, the risk of non-Hodgkin’s lymphoma is significantly increased in DH, although a strict gluten-free diet for > 5 years seems to protect against lymphoma in DH. Interestingly, in celiac disease the lymphoma risk is limited to enteropathy associated T-cell lymphoma in the small bowel, whereas B-cell lymphomas predominate in DH (3).
Although rituximab has improved the prognosis of all B-cell derived lymphoproliferative diseases, there are many unanswered questions about its use. Per Pavanello et al, “It is possible that the profound immunosuppression secondary to B-cell depletion may contribute to expansion of tumor cells.” (4). According to Avivi et al, anti-CD20 monoclonal antibodies used in treating CD20⁺ lymphomas and autoimmune diseases, appear to have broader functions than just eradicating malignant B-cells and decreasing autoantibody production. Rituximab-induced T-cell inactivation, reported both in-vitro and in-vivo, may contribute to the increased risk of T-cell-dependent infections (5). A concern always looming in the background is the risk of progressive multifocal leukoencephalopathy (PML). Fortunately, rituximab-associated PML is a rare event, occurring in < 1 in 20,000 patients with rheumatoid arthritis. Eighteen cases have occurred with other rheumatologic diseases, with an unknown denominator. Despite the rarity of rituximab-associated PML, ongoing vigilance is required (6).
When I signed a consent form to receive radiation therapy in 1989, I was warned about the risk of future lymphoma. I signed without hesitation saying “I’ll deal with it should it happen. I can’t worry about that now”. If was miserable with DH and rituximab was the answer to my misery, I’d take it without hesitation. Since DH is all about the intestine, however, my gut feeling is that we still need to do our utmost to get patients to comply with gluten-free diet and avoid the risk of immunosuppression, if possible.
- Antiga E, Caproni M. The diagnosis and treatment of dermatitis herpetiformis. Clin Cosmet Investig Dermatol 2015; 8: 257-65.
- Albers LN, et al. Rituximab treatment for recalcitrant dermatitis herpetiformis. JAMA Dermatol 2017; 153: 315-8.
- Collin P, et al. Dermatitis herpetiformis: A cutaneous manifestation of coeliac disease. Ann Med 2017; 49: 23-31.
- Pavanello F, et al. Rituximab: 13 open questions after 20 years of clinical use. Cancer Treat Rev 2017; 53: 38-46.
- Avivi I, et al. Anti-CD20 monoclonal antibodies: beyond B-cells. Blood Rev 2013; 27: 217-23.
- Molloy ES, et al. The risk of progressive mutifocal leukoencephalopathy in the biologic era. Rheum Dis Clin N Am 2017; 43: 95-109.
* The cartoon is from the website “Sim and Choppers” – I am not the Warren depicted (I hope!)