Ruxolitinib combined with azithromycin for scrub typhus-associated hemophagocytic lymphohistiocytosis in a child: a case report and narrative literature review.

BACKGROUND: Scrub typhus-associated hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening complication in children, with reported mortality of 11.9%-30%. Conventional immunomodulation with corticosteroids and intravenous immunoglobulin often provides insufficient control of the hyperinflammatory state, while etoposide-based chemotherapy carries significant toxicity. JAK1/2 inhibition targeting the interferon-gamma pathway represents a promising therapeutic strategy, but its application in scrub typhus-associated HLH has not been previously reported.

CASE PRESENTATION: A 5-year-11-month-old girl with no prior medical history presented with persistent fever, tachypnea, hepatosplenomegaly, and a 0.5 cm eschar in the left axilla after travel to Yunnan Province, China. Laboratory findings revealed pancytopenia (platelets 40× 109/L), hyperferritinemia (>2,000 ng/mL), hypofibrinogenemia (1 g/L), and elevated interferon-gamma (135.48 pg/mL). Bone marrow aspiration demonstrated hemophagocytosis. Metagenomic next-generation sequencing confirmed Orientia tsutsugamushi infection. The patient met six of eight HLH-2004 diagnostic criteria. She was treated with oral ruxolitinib (5 mg twice daily) initiated on the day of admission, followed by intravenous azithromycin (10 mg/kg once daily) after confirmatory testing. Fever resolved within 72 h. Ruxolitinib was temporally associated with rapid clinical improvement, although causal attribution cannot be established due to concurrent therapies. By day 8, platelet count normalized to 240× 109/L, ferritin declined to 1,246 ng/mL, and fibrinogen recovered to 2.4 g/L. The patient was discharged on day 13 with ruxolitinib tapered to 2.5 mg daily. At 3-month follow-up, she remained well with normal laboratory parameters.

LITERATURE REVIEW: Narrative literature review of 66 previously reported pediatric cases from Chinese and English databases (inception to May 2026) plus the present case revealed an overall mortality of 11.94% (8/67). Among these patients, 43 (64.2%) received corticosteroids, 34 (50.7%) received intravenous immunoglobulin, and only 3 (4.5%) received etoposide. The published cases suggest that absence or delay of anti-rickettsial therapy is associated with poor outcomes, though the evidence is limited by case-report bias and confounding.

CONCLUSION: This is the first report of successful JAK1/2 inhibitor therapy in scrub typhus-associated HLH. This case raises a hypothesis worth investigating further-that ruxolitinib combined with azithromycin may achieve rapid disease control with good tolerability. Prospective studies are needed to evaluate the role of targeted JAK inhibition in infection-triggered HLH.