Linear scleroderma “en coup de sabre” with extensive brain involvement—Clinicopathologic correlations and response to anti-Interleukin-6 therapy

Linear scleroderma “en coup de sabre” (LSES) variant is a cephalic subtype of localized scleroderma that can be associated with extracutaneous stigmata, such as epilepsy, dementia syndromes, as well as focal central nervous system neurologic deficits. While the pathophysiology of cutaneous linear scleroderma includes endothelial cell injury and up regulation of pro-fibrogenic pathways, the basis of LSES-associated neurologic complications is largely unknown. We report a patient with a history of LSES who developed intractable epilepsy and cognitive decline. Magnetic resonance imaging (MRI) of the brain exhibited numerous persistently enhancing brain lesions. Due to progressive neurologic deterioration over a period of 7 years, despite interventional therapy, a brain biopsy was performed. Neuropathologic analysis exhibited acute and chronic cortical ischemia associated with a small vessel lymphocytic vasculitis. Direct immunofluorescent studies showed C5b-9 and IgG deposition on endothelium while indirect immunofluorescent studies demonstrated reactivity of the patient’s serum with the microvasculature of the patient’s own brain tissue and generic human umbilical vein endothelial cells indicative of anti-endothelial cell antibodies. Therapy focusing on damaged endothelium was implemented. The interleukin-6 (IL-6) receptor inhibitor tocilizumab was used and the patient improved dramatically, likely reflecting the drug’s effect on the replenishment of endothelial progenitor cells.