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).