Successful treatment of multicentric reticulohistiocytosis with JAK inhibitor: a case series

Multicentric reticulohistiocytosis (MRH) is a rare non-Langerhans cell histiocytosis characterised by erosive arthritis and papulonodular skin lesions, frequently associated with autoimmune features. Therapeutic strategies remain empirical despite the potentially severe and disabling course. We report three cases of MRH with heterogeneous systemic involvement, all showing sustained, multidomain responses to Janus kinase (JAK) inhibitors.All patients developed inflammatory arthritis, ranging from arthralgia to destructive arthropathy, and early cutaneous papules predominantly affecting the face and trunk. Systemic manifestations included digital microangiopathy with a scleroderma-like capillaroscopic pattern in one patient and interstitial lung disease with lymphocytic alveolitis in another. Two patients fulfilled criteria for Sjögren's syndrome, and all were positive for anti-Sjögren's-syndrome-related antigen A/Ro52kD antibodies, highlighting the autoimmune overlap of MRH.Diagnosis was confirmed histologically by CD68-positive histiocytic and multinucleated giant cell infiltration. Conventional synthetic disease-modifying antirheumatic drugs and tumour necrosis factor inhibitors were ineffective or poorly tolerated, whereas tofacitinib and upadacitinib induced rapid and durable improvement across articular, cutaneous, vascular and pulmonary domains. These observations support a role for JAK-STAT signalling in MRH and suggest JAK inhibition as a rational therapeutic option in refractory multisystem disease.