Incidental amelioration of bullous pemphigoid during ixekizumab treatment for psoriasis

Dear Editor, Although coexistence of psoriasis vulgaris with bullous pemphigoid has been occasionally observed,1 its treatment remains a challenge.2– 4 Here we report a case of bullous pemphigoid associated with psoriasis, in which both dermatoses completely disappeared after treatment with ixekizumab, a monoclonal antibody that targets interleukin (IL)17A. A 37yearold woman, with a 20year history of psoriasis vulgaris treated only with topical corticosteroids, developed a pruritic, disseminated eruption with erythema and blisters for 14 days. She manifested neither any constitutional symptoms, such as fever and arthralgia, nor had a relevant medical history, although her father had a history of psoriasis vulgaris. Physical examination revealed erythematous plaques, tense blisters and erosions predominant on her trunk and limbs (Figure 1a,d,g), as well as scaled erythema on her scalp. We found no evidence of mucosal lesions, and Nikolsky's sign was negative. Histopathological examination of a skin biopsy, taken from a bullous lesion, revealed a subepidermal blister with lymphomonocyte infiltration (Figure 1j), while direct immunofluorescence microscopy revealed linear deposits of C3 at the dermal– epidermal junction (Figure 1k). Enzymelinked immunosorbent assay results revealed IgG autoantibodies against both BP180 (21 U/mL; normal values <9 U/mL) and BP230 (52 U/mL; normal values < 9 U/ml), while routine laboratory tests and Lung CT revealed no remarkable results. Based on previous findings, she was diagnosed with psoriasis vulgaris concurrent with bullous pemphigoid (BP). However, the patient refused to take methotrexate, because of its side effects. Given the persistent clinical activity of both plaque psoriasis (PASI 11.6) and BP, treatment with ixekizumab was initiated (subcutaneously 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks). Psoriatic and BP lesions rapidly improved 2 weeks later, followed by remission of the bullous lesions and fewer erythematous desquamative lesions (PASI 4.4) (Figure 1b,e,h). Remission of psoriasis with residual hyperpigmentation, coupled with healing of blisters and erosions without scarring, was observed twelve weeks after initiation of the treatment (Figure 1c,f,i). Both psoriasis and BP were still in complete clinical remission, after one year of ixekizumab initiation, with neither clinical nor biological adverse events. Nevertheless, a longer followup is needed. Although the exact pathogenic mechanism for expression of a combination of psoriasis vulgaris with BP remains unclear, researchers have speculated that BP antigens are unmasked in psoriasis through enzymatic degradation of the basement membrane zone proteins, which allows them to be accessible by circulating antibodies. Additionally, psoriasis patients may be on a broad spectrum of treatment therapies, of which any agent may be a potential trigger factor for BP in psoriasis.1 In the present case of BP associated with psoriasis, ixekizumab totally controlled both diseases in a short time (12 weeks). The refusal of our patient to take methotrexate provides further justification for the use of ixekizumab to control both psoriasis and BP. So far, both for secukinumab (IL17A inhibitors) and ustekinumab (IL12/IL23 inhibitors) have been successfully used to treat BP.2,3 BP is an inflammatory autoimmune bullous disease involving cytokines and proteases in the process of blister formation.1 Although elevated IL17 levels have been observed in lesional skin and serum of BP patients, and its role in blister formation documented,4 nothing is known regarding IL17's role to autoantibody production in BP. Biologics that target IL17 components may represent an alternative approach for treatment of BP with psoriasis vulgaris, and result in a better satisfactory benefit/risk ratio than methotrexate, systemic corticosteroids or immunosuppressants, which are associated with numerous sideeffects and contraindications. However, the relationship between BP development and IL17 blockade therapies for psoriasis remains elusive. Thus, further observations are required to evaluate the efficacy and tolerance of ixekizumab for treatment of BP associated with psoriasis.