Aggressive Systemic Mastocytosis Presenting as Pyrexia of Unknown Origin and Sclerotic Bone Lesions: An Uncommon Presentation of a Rare Haematological Disorder

Mastocytosis is a heterogeneous disease characterised by mast cell infiltration into various organs. While cutaneous manifestations are easily recognisable, systemic disease is often difficult to diagnose. Systemic mastocytosis (SM) presenting as pyrexia of unknown origin (PUO) and sclerotic bone lesions is uncommon and adds a layer of complexity to an already challenging diagnosis, especially in the elderly where differential diagnoses are broad. We report the case of an 83-year-old man with recurrent hospital admissions due to unexplained fever, weight loss and cytopenias. Notably, the patient had no prior history of skin lesions, anaphylaxis, or other classical signs of mast cell activation. Computed tomography (CT) of chest and abdomen showed sclerotic rib lesions and hepatosplenomegaly. Extensive workup for infectious, autoimmune, and malignant diseases did not yield a diagnosis. Although a wide range of differential diagnoses were considered, serum tryptase was never tested. Eventually a bone marrow biopsy was done and showed multifocal dense mast cell infiltrates expressing CD117, CD25, and CD2 on immunohistochemistry. Serum tryptase done post bone marrow biopsy was elevated at 810 ug/L. The KIT D816V mutation was confirmed on genetic analysis. Disease was classified as aggressive SM on the basis of organ dysfunction, cytopenias and high mast cell burden. The patient responded well to midostaurin and supportive therapy, with quick resolution of fever and systemic symptoms. Tryptase levels declined steadily over a year. This case underscores the value of serum tryptase and early bone marrow examination in the assessment of PUO, especially when extensive investigations have not yielded a diagnosis. SM is an unusual and potentially under-recognised cause of PUO that should be considered early on in its differential diagnosis, especially when conventional workup is unrevealing. A high index of suspicion is required for diagnosis especially in the absence of recognisable symptoms of mast cell activation. Early diagnosis is essential for effective treatment, prognostication and to alleviate its impact on mental wellbeing. Clinicians should consider incorporating serum tryptase into investigation algorithms for PUO in patients with unexplained cytopenias, organomegaly and bone lesions.