Abstract Background/Aims Haemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory syndrome that can be triggered by a range of infections, malignancies, and autoimmune conditions. Histoplasmosis, an infection caused by the dimorphic fungus Histoplasma capsulatum, can be a trigger for HLH but may also reactivate following immunosuppression in HLH, particularly in patients with risk factors including travel to/from high-risk regions. Of note, both conditions share similar clinical and laboratory features, including fever, cytopenias, hyperferritinaemia, and hepatosplenomegaly, often complicating the diagnosis. Methods We present the case of a 41-year-old lady from Ghana, who presented with a four-day history of fever, painful cervical lymph nodes, and a skin rash. Initially managed as a viral exanthem, she received a six-day course of oral prednisolone with partial symptom relief. However, inflammatory markers continued to rise, and clinical status did not improve. Rheumatology, microbiology and haematology teams were consulted, and a structured diagnostic approach was initiated, including serial H-scores. Laboratory findings evolved to show worsening anaemia, leukocytosis, thrombocytosis, elevated CRP (peak 447 mg/L), abnormal liver function, and markedly elevated ferritin level peaking at 42,076 µg/L. Additional findings included AST 119, triglycerides 2.29 mmol/L, and fibrinogen 8.8 g/L. Her H-score peaked at 113. Autoimmune screen showed a weakly positive rheumatoid factor, negative ANA and ANCA, and normal CPK. CT chest, abdomen and pelvis, and PET scans, found no malignancy or infectious source, and echocardiography was unremarkable. Bone marrow biopsy demonstrated mild haemophagocytosis but no neoplasia or pathogens. An extensive infection screen was sent. Results This case was discussed at the HLH multidisciplinary team meeting with University College London Hospital, in the presence of local microbiology, haematology and rheumatology teams, and she was treated with methylprednisolone, anakinra, and antimicrobial prophylaxis including amphotericin and acyclovir. Urinary antigen to test for Histoplasma was sent in view of ongoing fevers and her relatively recent move from Ghana. After clinical improvement, antifungal therapy was transitioned to oral posaconazole, pending confirmatory testing from the U.S reference lab - which came back positive confirming Histoplasma antigen - and a suggestion from microbiology to continue posaconazole for an extended period. Steroids were tapered. She was discharged when stable with outpatient follow-up with rheumatology and infectious diseases teams. Conclusion This case highlights the importance of recognizing histoplasmosis as a potential trigger for HLH, but may also complicate it due to reactivation following immunosuppression for HLH, particularly in patients with risk factors. Given the clinical and laboratory overlap between these two conditions, timely diagnosis requires a high index of suspicion and a comprehensive diagnostic approach. Early initiation of appropriate antifungal therapy alongside immunomodulatory treatment for HLH is essential to improve outcomes. Clinicians should maintain awareness of this rare but life-threatening association to avoid delays in management and reduce the risk of fatal complications. Disclosure S. Kalyani: None. B. Rogers: None. M. Malik: None.
Kalyani et al. (Wed,) studied this question.