Case presentation:
A 16-years-old female patient presented to our hospital with a generalized bullous eruption. History goes back for five years before when she started complaining from scattered bullae on her trunk and she was treated successfully with prednisolone 15 mg daily that was tapered gradually. One year before she was referred to our center, she started complaining from bullous lesions again. Unfortunately, there was no response to dapsone, IVIG, rituximab and even the previous dose of prednisolone. Later, she was referred to our hospital with generalized bullae. Her physical examination showed multiple tense bullae on both lower and upper extremities, trunk (figures 1, 2, 3), and neck in addition to oral lesions. Skin biopsy was done and the histological findings showed sub-epidermal blisters with eosinophilic perivascular infiltrates. Direct immunofluorescence (DIF) study showed linear C3 and IgG deposits at the dermoepidermal junction. Laboratory findings included hyper eosinophilia (44% in peripheral smear with an absolute eosinophil count). According to internal medicine consult, bone marrow biopsy and aspiration was performed. The results revealed hypercellular bone marrow with 75% eosinophils and blasts. The final diagnosis was bullous pemphigoid associated with hypereosinophilic syndrome. Genetic testing for FIP1L1-PDGFRA fusion gene was negative. So high dose prednisolone 40 mg was initiated. There was complete resolution for her skin lesions. Later prednisolone was tapered gradually.
Discussion :
The skin is the most frequent organ involved in HES affecting more than half of the patients and ranging from urticarial lesions, pruritic papules or nodules, and mucosal ulcers (4). Histopathological studies of papular or nodular lesions usually show abundant eosinophilic perivascular infiltrates in addition to neutrophilic and mononuclear ones, whereas mucosal ulcers histology includes nonspecific mixed cellular infiltrates with no vasculitis (4).
Bullous pemphigoid is the most blistering autoimmune disease with prevalence in elderly population (5). Histopathological studies show subepidermal blister formation rich with eosinophils, whereas direct or indirect immunofluorescence assays demonstrate the presence of IgG and/or C3 deposition along the basement membrane zone (5). The cornerstone in treatment of BP is corticosteroids including topical or oral ones, in addition to treatment with other medications like doxycycline, dapsone and immunosuppressants drugs (5). Recent studies showed a role of eosinophils and IgE autoantibodies in addition to anti-BP180 and BP230 IgG autoantibodies as a pathogenic causative factor in BP (6).
HES is one of the heterogeneous entities characterized by eosinophilic infiltrates especially bone marrow and heart followed by lungs, liver and spleen (7). One of HES cutaneous manifestations is blister formation usually in the epidermis or dermal-epidermal junction making it one of the differential diagnosis of BP (7). Till now, about 9 cases of BP with coexisting HES have been reported in literature (table 1). The coexistence of these two disorders may highlight similar molecular and cellular background (7).
Treatment of HES is based on the presence or absence of the FIP1L1-PDGFRA fusion gene. When the genetic test is positive the best treatment is imatinib, whereas when the test is negative corticosteroids is considered as a first line of treatment (8).
This case report shows the important role of dermatologists in diagnosing every skin manifestation even when cutaneous lesions are limited because it can highlight a life-threatening condition (9). BP is a very common blistering disorder that can be associated with HES (9). HES must be considered especially in patients with atypical response to corticosteroids with blood eosinophilia (9). Our patient presented first with limited bullous lesions that resolved with corticosteroid treatment, but later recurred with a more generalized aggressive course with no response for low dose of corticosteroids. After diagnosing the coexistence with HES, prednisolone 1 mg/kg/day (treatment dose for HES), there was complete resolution and relief for symptoms and skin manifestations.
This report shows the importance of skin manifestations even though when there is localized limited lesions since it may highlight a life-threatening condition where early diagnosis and treatment can improve the prognosis (10).