To the Editor: Severe pulmonary Langerhans cell histiocytosis (PLCH) is rare but potentially life-threatening, particularly when complicated by recurrent pneumothoraces and tension bullae in infants 1-3. Since severe PLCH has a dramatic and severe clinical course, an understanding of its stage-dependent pulmonary pathology and corresponding management strategies is critical to improving outcomes. We describe an infant with multisystem Langerhans cell histiocytosis (LCH) who developed rapidly progressive PLCH complicated by respiratory failure, recurrent bilateral pneumothoraces, and tension bullae requiring prolonged drainage management. A 3-month-old boy with diffuse papular eruptions, hepatosplenomegaly, and cervical and inguinal lymphadenopathy presented to another hospital with fever and increased respiratory efforts. The patient exhibited tachycardia (160 beats/min), tachypnea (60 breaths/min), and hypoxia (SpO2 88% on room air). Chest radiography revealed granular reticular infiltrates, and computed tomography (CT) showed diffuse nodular and reticular pulmonary infiltrates (Figure 1A). The patient was referred to our hospital for further evaluation and management. The skin biopsy was positive for CD1a and Langerin immunochemistry, thus confirming the diagnosis of LCH. A BRAF-V600E mutation was not detected (Figure S1). On hospital Day 3, the patient developed progressive respiratory failure, therefore, admission to the intensive care unit (ICU) and mechanical ventilation were necessary (Figure 1E). Chemotherapy comprising prednisolone, cytarabine, and vincristine was initiated on the day of ICU admission. High-frequency oscillation and prone positioning significantly improved oxygenation; however, inhaled nitric oxide provided limited improvement. His skin lesions and hepatosplenomegaly also improved and successful extubation was performed 14 days after ICU admission. At 4 and 8 days after extubation, left pneumothorax and right pneumothorax developed, respectively (Figure 1B). During the subsequent 8 weeks, multiple recurrent bilateral pneumothoraces, including episodes of tension pneumothorax that required continuous pleural drainage, developed (Figure 2A). Multiple lung bullae that progressed to multiloculated tension bullae also developed (Figure 1C). Targeted drainage into the bullous compartments resulted in gradual respiratory improvement. All drainage tubes were removed 16 weeks after the initial pneumothorax. The patient was discharged after receiving nirsevimab prophylaxis at 20 weeks of hospitalization. Marked improvement in the lung parenchyma appearance was observed on chest CT (Figure 1D). LCH is an inflammatory myeloid neoplasm with tumorous and immune-dysregulated characteristics 4. PLCH affects only 7% to 11% of pediatric patients with LCH and typically occurs as a part of multisystem LCH 3, 5. Severe pulmonary involvement occurs less frequently, but it is associated with a high mortality risk. One nationwide cohort study in France reported a 5-year survival of 62.7% 2. Detailed descriptions of stage-specific drainage strategies for multiloculated tension bullae in infants with PLCH are limited. This case illustrates how pulmonary pathology of severe infantile PLCH in an infant evolves across distinct stages and how each stage requires different strategies. During the initial stage of severe PLCH, patients experience respiratory failure attributable to lung damage caused by tumor infiltration and inflammation. In such cases, prompt induction of chemotherapy is of most importance to reducing the tumor burden and improving the respiratory condition 2. Supportive care such as mechanical ventilation is also important. Prone positioning significantly improved oxygenation in our patient during mechanical ventilation. Studies of neonates and infants with acute respiratory failure who required ventilation have demonstrated improved ventilation-perfusion matching and oxygenation in the prone position 6. These physiological benefits likely contribute to stabilization during the inflammatory phase of severe PLCH in infants. As chemotherapy reduces the tumor burden, PLCH undergoes cystic transformation, thus predisposing patients to pneumothorax. Continuous drainage from the pleural cavity is essential to preventing tension pneumothorax. During later stages, the cysts may enlarge and become multiloculated giant bullae capable of causing profound compression of the normal residual lung, resulting in tension bullae 7. Tension bullae present with tachypnea, desaturation, and tachycardia and their radiographic findings may closely resemble those of tension pneumothorax. During these episodes in our patient, air could not be drained from the pleural cavity, indicating that decompression required additional direct bullae drainage (Figure 2B). Moreover, because bullae are often separated by thin septa, puncture and drainage of each individual compartment are required. CT was useful for distinguishing pneumothorax from multiple cystic bullae and guiding to appropriate intervention (Figures 1B,C and 2B). Stage-specific management strategies are critical for stabilizing the respiratory condition. In our patient, 16-gauge catheters were initially inserted to allow pleural cavity drainage, followed by fluoroscopy-guided placement of 6–8-Fr catheters under anesthesia to optimize positioning and adequate drainage. Decompression of individual bullous compartments was achieved. Adequate deflation was achieved with negative-pressure drainage at –20 cm H2O, consistent with the previous studies 3. Infants have substantial lung growth potential through 2 to 3 years of age, thus providing a biological basis for structural recovery after extensive parenchymal injury 8. Favorable outcomes of chemotherapy combined with carefully tailored drainage strategies have been described for PLCH 9. Prevention of respiratory infections, particularly respiratory syncytial virus and bacterial pneumonia, is essential for supporting lung recovery and avoiding fatal deterioration during vulnerable stages of treatment 2. In conclusion, recognizing the stage-dependent transition from inflammatory lung injury to cyst formation and multiloculated tension bullae is essential to select appropriate, phase-specific interventions for severe infantile PLCH in infants. We thank all the medical staff at the Kumamoto University Hospital for participating in the patient treatment. We would like to thank Editage (www.editage.com) for English language editing. The authors declare no conflicts of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Kudo et al. (Fri,) studied this question.