Dupilumab effective in refractory bullous pemphigoid1
Bullous pemphigoid (BP) is a subepidermal immunobullous disorder characterised by autoantibodies against skin basement membrane zone (BMZ). Antibodies in BP are predominantly against BP180 and BP230, found within the hemidesmosomes of basal keratinocytes. Recently evidences of increased IL-4 and IL-13 cells in the blood and blister fluid of BP patients has given insight into role of IL-4 and IL-13 in the pathogenesis of BP.2 Dupilumab is a fully humanised monoclonal antibody against the IL-4 receptor α (IL-4Rα) subunit recently approved for atopic dermatitis. Recently a case of refractory bullous pemphigoid being successfully treated with dupilumab was reported in the Australasian Journal of Dermatology.
A 61-year-old woman presented with a 5-year history of generalised erythema, papules associated with severe itching initially diagnosed as atopic dermatitis. Patient later developed blisters. Biopsy from blisters showed a subepidermal blister with a lymphocytic and eosinophilic inflammatory infiltrate in papillary dermis. Direct immunofluorescence revealed linear deposits of C3 in the dermo-epidermal junction. The diagnosis of BP was made and the patient was started on methylprednisolone (0.5 mg/kg/day).
After 2 flares during the tapering of methylprednisolone, azathioprine 100mg daily was added to the regimen. The condition still relapsed and progressed to involve the face. Patient developed cushingoid phenotype with osteoporosis due to steroids. Due to patient's severe disease status and treatment side effects dupilumab was added to the treatment with an initial loading dose of 600 mg administered subcutaneously followed by a weekly 300 mg subcutaneous injection. With this novel treatment pruritus disappeared within one month, while no new blister developed.
At 5-month follow-up visit, the patient was in clinical remission, and azathioprine and topical steroids were then stopped. No flare was observed during tapering of methylprednisolone. Therapy for BP can be challenging, especially in recalcitrant cases. Systemic corticosteroids when given for long term have multiple side-effects.
In conclusion dupilumab can be an novel and effective steroid sparing agent for refractory or recalcitrant bullous pemphigoid which could curtail severe side effects of systemic corticosteroids.
Source-
1. Zhang Y, Zhang J, Chen J, Lin M, Gong T, Cheng B, Ji C. Dupilumab successfully treated refractory bullous pemphigoid with early clinical manifestations imitating atopic dermatitis: A case letter. Australas J Dermatol. 2021 Nov;62(4):525-527. doi: 10.1111/ajd.13692. Epub 2021 Aug 26. PMID: 34448201.
2. Teraki Y, Hotta T, Shiohara T. Skin-homing interleukin-4 and -13-producing cells contribute to bullous pemphigoid: remission of disease is associated with increased frequency of interleukin- 10-producing cells. J. Invest. Dermatol. 2001; 117: 1097–102.