EED is a rare cutaneous leukocytoclastic vasculitis involving the papillary dermis and mid-dermal vessels that results in a dense neutrophilic infiltrate with fibrinoid necrosis. Its diverse manifestations make early diagnosis extremely challenging. Although typical cutaneous lesions at atypical sites or atypical cutaneous lesions at typical sites have been reported (5), EED rarely presents itself as blisters, especially on the limbs and trunk. We reviewed the literature regarding variants that presented as blisters (Table 1) (4, 6-9). Cases presenting as vesicles (pustule or not) that underwent direct immunofluorescence were excluded. We observed that the histopathological presentation of EED with bullae comprised subepidermal blisters. Direct immunofluorescence test results were not relevant or diagnostic of EED; however, they were important for diagnosing autoimmune bullous disorders. There have been 16 reported cases of vesicles, and almost all of them were pathologically manifested as epidermal vesicles.
Our current case presented as blisters with a transparent area that formed under epidermal oedema; however, they were not bullous. One of the mechanisms of blister formation is the release of enzymatic granules from neutrophils, resulting in alterations of the basal membrane (10). We inferred that the blisters on the lower limbs were subepidermal blisters due to the negative Nikolsky sign. We determined that the blisters formed during the acute phase because of the intense inflammatory response that occurs; this response is different than the pseudovesiculation of papillary dermal oedema that occurs during the early stage of EED. Because the characteristics of cutaneous lesions appear to mimic Sweet’s syndrome, the diagnosis is challenging to pathologists. However, it has been reported that the bullous type of Sweet’s syndrome is more prone to epidermal blisters. Although Sweet’s syndrome and EED are related clinical entities in the spectrum of neutrophilic dermatosis (11), bullous EED should be considered as the differential diagnosis of bullous diseases.
Various hypotheses regarding the pathogenesis of EED remain unproven. Paraproteinaemia is strongly associated with EED (11) , but no causative relationship has been established. We performed an evaluation to determine the presence of immunoglobulin in the blood and found no evidence of paraproteinaemia.
Treatment with 16 mg methylprednisolone daily and 200 mg hydroxychloroquine twice daily for 2 weeks significantly improved the lesions. Dapsone was not used because the patient declined the glucose hexaphosphate dehydrogenase test. Both hydroxychloroquine and glucocorticoids are recommended as second-line medications for the treatment of EED, but such anti-inflammatory regimens should be encouraged. This combination was significantly advantageous for our case, resulting in rapid symptom improvement and recurrence prevention.
In conclusion, EED is a chronic condition with a diverse clinical presentation involving the face, extremities, and trunk. In rare cases, EED can present as a blister that pathologically manifests itself as a subepidermal blister.