Detection of FIP1L1-PDGFRA fusion gene-positive cells in the skin lesion of a patient with hypereosinophilic syndrome.

Hypereosinophilic syndrome (HES) is a heterogeneous group of diseases, characterized by persistent hypereosinophilia and end-organ damage. The FIP1L1-PDGFRA (F/P) fusion gene is found in 3-25% of patients with HES and is an oncogenic driver of myeloid neoplasms with clonal eosinophilia. Although cutaneous symptoms are the most common type of symptom in patients who have F/P fusion gene-positive HES (F/P HES), histological reports are limited. We herein present the case of a 78-year-old man with erythematous macules and severe pruritus on his trunk and extremities. Laboratory investigations revealed marked eosinophilia and elevated serum vitamin B12. A histological examination showed massive infiltration of eosinophils and mast cells around the vessels in the upper dermis. Fluorescence in situ hybridization revealed F/P fusion genes in nuclei in the peripheral blood and the skin lesion. The patient was diagnosed with F/P HES, and showed an excellent clinical and haematological response to imatinib.

Two cases of Hailey-Hailey disease effectively treated with apremilast and a review of reported cases.

Hailey-Hailey disease (HHD) is an autosomal dominant genetic disease caused by a mutation of the ATP2C1 gene. Corticosteroids, antibiotics or cyclosporine have been administered to reduce inflammation and prevent flare-ups, but the efficacy is not always sufficient. We herein report two cases of HHD effectively treated with apremilast and review the previous literature. Patient 1 was a 28-year-old male and patient 2 was a 35-year-old female. Both patients were diagnosed with HHD based on histological and genetic analyses. Both patients were treated with oral antibiotics or topical corticosteroids, but their symptoms were refractory, therefore apremilast was administered to both patients. Two weeks later, the skin lesion of both patients was improved. No adverse reaction was observed except for mild headache in patient 2. There have been 13 reported cases of HHD treated with apremilast, including our cases. Eight cases showed a good response to apremilast, whereas five cases showed no response. There seems to be no association between the disease severity and efficacy of apremilast, although the reason remains unknown. Interestingly, an early improvement of the HHD lesion was observed in all good response cases. Although digestive symptoms, headache, and myalgia were observed as adverse events, the treatment was well-tolerated. The accumulation of a greater number of similar cases and further research will be required. We hypothesize that apremilast may be a useful therapeutic option for skin lesions of HHD.