P24 Recurrent skin ulcerations as an isolated manifestation of ISG15 deficiency

Abstract

Abstract Type I interferonopathies are characterized by a very broad phenotypic spectrum; however, some overlapping clinical features are seen across the type I interferonopathies, most particularly brain and skin involvement. We report a female patient presenting at 7 months of age with ulcerations in her groin and axilla. The lesions in her axilla healed; however, she continued having recurrent ulcerations in both sides of her groin and she developed lipoatrophy of the lower abdomen. Skin biopsy revealed deep-seated inflammation with abnormal adipose tissue; no bacteria were isolated. Extensive immunology blood work-up did not reveal any abnormalities, and the inflammatory markers were normal. Because of the extent of the clinical findings and pending results of genetic screening with targeted next-generation sequencing, we commenced methotrexate at 1 year of age (15 mg m–2). Following the initiation of methotrexate, there was marked improvement in the clinical features, with resolution of active skin ulceration. Genetic screening revealed a homozygous stop mutation in ISG15 p.Q16X. A CT scan of her head did not show any calcifications. Methotrexate was stopped at age 3 years. She remains well with no further skin ulcerations, and her development continues to be age appropriate. ISG15 deficiency is a type I interferonopathy, previously described in association with intracranial calcifications and increased susceptibility to mycobacteria infections. However, more recent reports have described skin ulcerations as a main finding in addition to neurological and immunological manifestations. Our patient is not showing any signs of neurological or other immunological manifestations but remains under careful monitoring.