Cytophagic histiocytic panniculitis with fatal haemophagocytic lymphohistiocytosis in a paediatric patient with perforin gene mutation

Cytophagic histiocytic panniculitis (CHP), or histiocytic cytophagic panniculitis, is a rare form of panniculitis associated with haemorrhagic diathesis and histiocytic lymphohistiocytosis (HLH), initially described in 1980 as a benign lymphoproliferative disease.1 In 1991 Gonzalez et al reported a unique entity of subcutaneous T-cell lymphoma with haemophagocytosis, later designated as subcutaneous panniculitis-like T-cell lymphoma (SPTL).2 Marzano et al suggested that CHP and SPTL might span a clinicopathological spectrum in which there is a natural progression from CHP to SPTL.3 HLH is a clinical syndrome of immune deregulation with hypercytokinaemia causing dysfunctions of various organs and a high mortality. Familial HLH (FHL) is associated with several hereditary defects. Stepp et al first showed that the mutation in perforin gene (PRF1) at chromosome 10q21 was responsible for 20–40% of FHL patients.4

Case report

An 11-year-old girl with CHP and HLH presented with spiking fever and indurated skin nodules over the left thigh (fig 1A). She had psychomotor retardation and spastic type cerebral palsy at 2 years of age and epilepsy at age 7. Physical examination revealed indurated skin nodules and hepatosplenomegaly without lymphadenopathy. Laboratory tests showed anaemia, thrombocytopenia, impaired liver function, and raised triglyceride level, without coagulopathy. Blood and urine cultures were negative. Her fever and skin lesions responded dramatically to prednisolone and intravenous immunoglobulins. She became prednisolone-dependent despite attempts at tapering off by adding methotrexate and cyclosporine A. Several episodes of HLH and infections led to three additional admissions in three years. Six months later, she developed prominent facial bruising and swelling. Virological surveys revealed prior/remote Epstein-Barr virus …