Severe, Therapy-Resistant Generalized Lichen Sclerosus with Morphea Overlap Successfully Treated with Intravenous...

Generalized extragenital lichen sclerosus with morphea overlap is a rare inflammatory and fibrosing dermatosis. Severe bullous-ulcerative disease remains therapeutically challenging and can cause major morbidity.

We report a 54-year-old woman with decade-long progressive generalized extragenital lichen sclerosus-morphea overlap, causing disabling hand sclerosis and widespread painful bullous-ulcerative leg lesions. Conventional first-line and extended immunomodulatory or immunosuppressive treatments, including potent topical corticosteroids, UVA-1 phototherapy, extracorporeal photopheresis, methotrexate, hydroxychloroquine, multiple biologics, and JAK inhibitors, showed little sustained benefit and were sometimes associated with deterioration or relevant immunosuppression. Intravenous immunoglobulin, initiated for secondary antibody deficiency, was associated with disease stabilization and complete ulcer healing; rituximab was subsequently continued as part of B-cell-directed background therapy. Persistent cutaneous inflammation under IVIG and rituximab was accompanied by elevated interferon-associated mediators, including interleukin-18, CXCL9, and CXCL10. Addition of anifrolumab, a type I interferon receptor antagonist, led to marked suppression of inflammatory activity, softening of sclerotic skin, normalization or reduction of several cytokine and chemokine abnormalities, and improved quality of life.

In severe therapy-refractory lichen sclerosus-morphea overlap, combined IVIG, rituximab, and anifrolumab may help control skin inflammation, sclerosis, and skin ulceration. This case supports cytokine-guided, mechanism-based salvage therapy in selected therapy-refractory patients.