Pulmonary Langerhans cell histiocytosis (PLCH) is a cigarette smoking-related interstitial lung disease （ILD） that mostly occurs in adults, and is clinically rare. The lesions are characterized by granulomatous changes formed by Langerhans cell exudation in the center of the bronchioles, and asteroid fibrotic lesions accompanied by cyst formation are pathological changes.
Etiology and pathogenesis
PLCH usually occurs in young individuals, and the etiology of the disease is unclear. It was thought that it might be related to clonal proliferation of precursor cells, cytokine-mediated diseases, viral infections, and immune disorders. It is currently believed that PLCH is a form of excessive immune response of lung tissue related to cigarette smoking, caused by chronic inflammatory lesions ultimately leading to the deposition of Langerhans cells in the interstitial area of the small airways.
Clinical manifestations
The clinical manifestations of PLCH are non-specific, and the onset is insidious. The most common symptoms are dry cough, chest tightness, dyspnea, thoracodynia, fatigue, and emaciation, and there may be no symptoms. Some patients present spontaneous pneumothorax as the first symptom, and some patients may also develop pulmonary hypertension due to long-term hypoxia. Pulmonary function test may be normal in the early stage, and is manifested by restrictive, mixed ventilation function and diffusion dysfunction in the late stage. Typical pulmonary function test reveals decreased vital capacity and normal or increased residual volume.
Chest x-ray shows nodules or reticulonodular exudative lesions, often in the upper and middle lobes of the lungs, and the costophrenic angles are clear. HRCT characteristically shows multiple irregular cysts with varying wall thickness, often accompanied by peribronchiolar nodules (1 - 4mm in diameter) in the early stage, mainly in the upper and middle lung fields.
Diagnosis
Multiple cysts and nodules mainly in the upper and middle lung fields or Langerhans cells in BALF (positive OKT6 or anti-CD1a antibody staining) exceeding 5% are highly suggestive of PLCH.
Differential diagnosis
Chronic eosinophilic pneumonia
The normal structure and contour of the alveoli have not been completely destroyed. Eosinophil aggregation is mainly in the alveolar cavities; while the eosinophil infiltration of PLCH in the cellular phase is mainly in the interstitium.
Desquamative interstitial pneumonia (DIP)
The typical feature is the massive accumulation of macrophages in the alveolar cavities. There may be localized DIP-like reactions around the lesions of PLCH in the cellular phase, but they are not as diffuse as DIP lesions.
Usual interstitial pneumonia (UIP)
The fibrotic lesions are heterogeneously distributed, often in the subpleural area, peripheral lobules, or peripheral lungs, fibroblastic foci are the main feature, and honeycomb lung can also be formed. The focal fibrous scars of PLCH in the fibrotic phase tend to be in the center of the bronchus, and the edge of the lesion extends radially to the periphery.
Pulmonary lymphangiomyomatosis (PLAM)
PLAM histopathologically reveals nodular proliferation of smooth muscle cells around lymphatic vessels and small airways, and positive immunohistochemical HMB45 and SMA, which is significantly different from PLCH.
Treatment
Smoking cessation should be the top priority in the initial treatment of PLCH. Patients with wheezing and obstructive lung disease can be treated with inhaled corticosteroids and bronchodilators. In non-smokers or patients with progressive exacerbation of clinical symptoms after smoking cessation, systemic treatment should be selected. Cladribine can improve lung function, relieve lung nodules and cystic changes, and is used for salvage treatment of advanced PLCH, while vinblastine and radiotherapy are not effective in pulmonary PLCH. Patients with recurrent pneumothorax usually require pleurodesis. Patients with pulmonary hypertension in the late stage may consider vasodilators such as endothelin receptor antagonists and phosphodiesterase 5 inhibitors. Lung transplantation should be considered for terminal patients. The 1-year survival after transplantation is > 75%, but the disease may still relapse after transplantation. Other auxiliary treatments include oxygen therapy, influenza vaccination, and prompt control of lung infection.