Mycoplasma pneumoniae-triggered hemophagocytic lymphohistiocytosis complicated by type I plastic bronchitis in a child: a case report

Background Hemophagocytic lymphohistiocytosis (HLH) triggered by Mycoplasma pneumoniae (MP) is exceptionally rare in children, with fewer than 25 pediatric cases reported. Its concurrence with plastic bronchitis (PB) has not been well characterized, and host factors predisposing to recurrent infection-triggered hyperinflammation remain poorly understood. Case presentation A 6-year-old previously healthy girl experienced two hyperinflammatory episodes separated by 7 months. The first episode (August 2023) featured fever, lymphadenopathy, hepatosplenomegaly, hyperferritinemia (4,184 ng/mL), elevated cytokines, and declining blood counts but did not fulfill complete HLH-2004 criteria; it resolved with hepatoprotective therapy and a short corticosteroid course. The second episode (March 2024), triggered by confirmed M. pneumoniae infection (targeted next-generation sequencing), fulfilled 7 of 8 HLH-2004 criteria: fever, splenomegaly, pancytopenia (hemoglobin nadir 72 g/L, platelets 32 × 10 9 /L, ANC 0.86 × 10 9 /L), hypertriglyceridemia/hypofibrinogenemia (0.748 g/L), hyperferritinemia (31,905 ng/mL), decreased NK-cell activity, and bone marrow hemophagocytosis, with elevated soluble CD25 (9,249 pg/mL, approximately 2,312 U/mL—marginally below the 2,400 U/mL threshold but indicative of significant T-cell activation) and an HScore of 231 (>99% probability). Complications included severe hepatic injury (AST 4,017 U/L), consumptive coagulopathy, toxic–metabolic encephalopathy with seizure, and histologically confirmed type I plastic bronchitis requiring two bronchoscopies for bilateral cast extraction. Immunological evaluation revealed borderline NK-cell degranulation (ΔCD107a 5.68%; severe impairment threshold ≤5%) with normal CTL degranulation and preserved perforin, MUNC13-4, SAP, and XIAP expression. Quantitative NK-cell deficiency had been documented during the first episode. Treatment with modified HLH-2004 protocol (dexamethasone and IVIG without etoposide), doxycycline, and supportive care achieved complete recovery. Conclusion This case demonstrates that MP-HLH can present with exceptional severity including type I PB and multiorgan failure, particularly in children with prior hyperinflammatory episodes suggesting underlying immune vulnerability. Borderline NK-cell degranulation combined with quantitative NK-cell deficiency and recurrent hyperinflammation supports a threshold model of HLH susceptibility. Functional immune screening including CD107a degranulation assays should be performed in children with recurrent or unusually severe infection-triggered hyperinflammation, even without a definitive monogenic diagnosis.