Abstract Introduction Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder often complicated by hemophagocytic lymphohistiocytosis (HLH). Pulmonary arterial hypertension (PAH) in AOSD is uncommon and poorly understood. Case Presentation We report a 26-year-old woman with AOSD complicated by drug-associated immune reactions (DAIRs), recurrent HLH and subsequent PAH. She initially presented with sore throat and cervical lymphadenopathy which was partially responsive to short courses of corticosteroids, but did not completely resolve. Four months later, she developed quotidian fever and lymphadenopathy with neutrophilic leukocytosis, thrombocytosis, elevated liver enzymes, and elevated ferritin (∼5,000 ng/mL), together with a pruritic eruption not typical for AOSD. Infectious studies were negative, and lymph node and bone marrow biopsies were not concerning for malignancy. Yamaguchi criteria for AOSD were met. She was initially treated with anakinra and prednisone with improvement but later developed recurrent fevers prompting a switch to canakinumab. At seventeen months, she developed HLH with persistent fever, hepatosplenomegaly, ferritin 16,000 ng/mL, and elevated sIL2R 5777 U/ml. She was managed with corticosteroids and tocilizumab with incomplete response, and her tocilizumab was changed to tofacitinib. Eighteen months after onset, she developed dyspnea and new oxygen requirement at rest. CT angiography excluded pulmonary embolism and no abnormal parenchymal findings noted. Pulmonary function testing showed reduced DLCO (50%) without other abnormalities. Right heart catheterization confirmed Group 1 PAH and tadalafil was initiated. She was found to be positive for the HLA-DRB1*15 allele. At 22 months, while on steroids and tofacitinib, she was readmitted with fever, rash, and ferritin 10000 ng/ml. Her tofacitinib was discontinued and she was started on etoposide for refractory disease with partial improvement. During an etoposide infusion, she developed fevers and pruritic rash consistent with DAIR. She tolerated an alternative etoposide formulation and ruxolitinib was added to her treatment regimen due to ongoing fevers and elevated inflammatory markers. Discussion This case illustrates coexistence of AOSD, recurrent HLH, DAIRs, and isolated PAH. Severe pulmonary complications such as PAH and interstitial lung disease are increasingly recognized in Still’s disease, particularly in patients with recurrent HLH, carriers of HLA-DRB1*15 alleles, and DAIRs, including anaphylaxis, injection site reactions, and pruritic rashes. Conclusions Patients with AOSD and recurrent HLH may develop PAH, often in the context of HLA-DRB1*15 carriage and DAIRs. This case emphasizes the importance of maintaining high clinical suspicion and a low threshold for evaluating pulmonary disease in AOSD patients who develop dyspnea, new oxygen requirements or drug reactions. This abstract is funded by: None
Chung et al. (Fri,) studied this question.