DP12: An 11-year mystery

Maneh Farazmand,¹ Janice Ferguson,¹ Ruth Green² and John Goodlad³

¹Manchester Foundation Trust, Manchester, UK; ²Salford Royal Hospital, Manchester, UK; and ³Queen Elizabeth University Hospital, Glasgow, UK

A 45-year-old man presented with several small, well-demarcated dermal plaques on the right thigh in April 2007. He had no systemic symptoms and no lymphadenopathy. He had travelled extensively in the Far East and South America in the preceding 2 months. Routine bloods and screening tests for coeliac disease, syphilis, HIV and Epstein–Barr virus were negative; HbA^1c was normal. He had a chronic normocytic normochromic anaemia. A school of tropical medicine found no evidence of tropical disease. The first of four biopsies showed features of necrobiosis lipoidica. He was treated with topical steroids, tacrolimus and occluded steroids with no improvement. The plaques slowly became more numerous and thicker on both legs. A second biopsy 4 years later was reported as granuloma annulare. After 10 years, knee flexion was restricted and painful owing to enlargement of a thick plaque in the popliteal fossa. He had a modest response to intralesional triamcinolone. The plaques began to enlarge more rapidly in all areas. A third biopsy showed atypical granuloma annulare with a differential diagnosis of interstitial granulomatous dermatitis. A multidisciplinary team review concluded that there was no evidence of lymphoma. Treatment with photodynamic therapy, psoralen + ultraviolet A (24 sessions) and dapsone for 6 months was unsuccessful. A fourth biopsy in 2019 showed a dense, diffuse infiltrate of histiocytes throughout the dermis with abundant pale eosinophilic foamy cytoplasm, suggestive of non-Langerhans cell histiocytosis. He was screened for systemic disease and had a normal computed tomography of the thorax, abdomen and pelvis, and magnetic resonance imaging of the head with contrast. A positron emission tomography (PET) scan showed increased activity in the skin and subcutaneous lesions, which were reported to be compatible with a non-Langerhans histiocytosis such as Erdheim-Chester disease (ECD). No noncutaneous manifestations were identified. Methotrexate (25 mg weekly) for 16 weeks had only a modest effect and he has progressed to cytarabine under the care of the oncology team. Although this case seems to be a histiocytosis of some type, it lacks the systemic manifestations and the BRAF mutation that would give more certainty to a specific diagnosis of ECD or a Langerhans histiocytosis (Goyal G, Heaney ML, Collin M et al. Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era. Blood 2020; 135: 1929–45; Diamond EL, Dagna L, Hyman DM et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood 2014; 124: 483–92). It has taken 11 years and four biopsies to arrive at the possibility of ECD, and repeated sampling for oncogenic mutations and follow-up PET may provide a more certain diagnosis in the future.