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Pulmonary
Langerhans' cell granulomatosis (histiocytosis) is proliferation
of monoclonal Langerhans' cells in lung interstitium and airspaces.
Etiology is unknown, but cigarette smoking plays a primary role.
Symptoms are dyspnea, cough, fatigue, and/or pleuritic chest pain.
Diagnosis is based on history with imaging tests or bronchoalveolar
lavage and biopsy. Treatment is smoking cessation. Corticosteroids
are given in many cases, but efficacy is unknown. Lung transplantation
is curative when combined with smoking cessation. Prognosis is good
overall, although patients are at increased risk of malignancy.
Pulmonary Langerhans' cell granulomatosis (PLCG) is a disease in which monoclonal CD1a-positive Langerhans' cells (a type of histiocyte) infiltrate the bronchioles and alveolar interstitium, accompanied by lymphocytes, plasma cells, neutrophils, and eosinophils. PLCG is one manifestation of Langerhans' cell histiocytosis (see Histiocytic Syndromes: Langerhans' Cell Histiocytosis), which can affect organs in isolation (most notably the lungs, skin, bones, pituitary, and lymph nodes) or simultaneously. PLCG occurs in isolation ≥ 85% of the time.
The etiology of PLCG is unknown, but the disease occurs almost exclusively in whites 20 to 40 yr who smoke. Men and women are affected equally. Women develop disease later, but any differences in disease presentation by sex may represent differences in smoking behavior. Pathophysiology may involve recruitment and proliferation of Langerhans' cells in response to cytokines and growth factors secreted by alveolar macrophages in response to cigarette smoke.
Symptoms and Signs
Typical symptoms and signs of PLCG are dyspnea, nonproductive cough, fatigue, and/or pleuritic chest pain, and 10 to 25% of patients have sudden, spontaneous pneumothorax (see Mediastinal and Pleural Disorders: Pneumothorax). About 15% of patients are asymptomatic, with disease noted incidentally on a chest x-ray taken for another reason. Bone pain from bone cysts (18%), skin rash (13%), and polyuria from diabetes insipidus (5%) are the most common manifestations of extrapulmonary involvement and occur in up to 15% of patients, rarely being the presenting symptoms of PLCG. There are few signs of PLCG; the physical examination results are usually normal.
Diagnosis
PLCG is suspected based on history, physical examination, and chest x-ray and is confirmed by high-resolution CT (HRCT) and bronchoscopy with biopsy and bronchoalveolar lavage.
Chest x-ray classically demonstrates bilaterally symmetric nodular opacities in the middle and upper lung fields with cystic changes and normal or increased lung volumes. The lung bases are often spared. Appearance may mimic COPD or lymphangioleiomyomatosis (see Interstitial Lung Diseases: Lymphangioleiomyomatosis). Confirmation on HRCT of middle and upper lobe cysts (often with bizarre shapes) and/or nodules with interstitial thickening is considered diagnostic of PLCG. Pulmonary function test findings are normal, restrictive, obstructive, or mixed depending on when the test is performed during the course of the disease. Most commonly, the diffusing capacity for carbon monoxide (DLco) is reduced and exercise is impaired.
Bronchoscopy and biopsy are indicated when imaging and pulmonary function tests are inconclusive. Finding > 5% of CD1a cells in bronchoalveolar lavage fluid is highly suggestive of the disease. Biopsy shows proliferation of Langerhans' cells with occasional clustering of eosinophils (the origin of the outdated term eosinophilic granuloma) in the midst of cellular and fibrotic nodules that may take on a stellate configuration. Immunohistochemical staining is positive for CD1a, S-100 protein, and HLA-DR antigens.
Treatment
The main treatment is smoking cessation, which leads to symptom resolution in up to 1⁄3 of patients. As with other ILDs, empiric use of corticosteroids and cytotoxic drugs is common practice even though their effectiveness is unproven. Lung transplantation is an option for otherwise healthy patients with accelerating respiratory insufficiency, but the disease may recur in the transplanted lung if the patient continues or resumes smoking.
Spontaneous resolution of symptoms occurs in some patients with minimally symptomatic disease; 5-yr survival is about 75%, and median survival is 12 yr. However, some patients develop slowly progressive disease, for which the clinical markers include continued smoking, age extremes, multiorgan involvement, persistent constitutional symptoms, numerous cysts on chest x-ray, reduced DLco, low FEV1/FVC (< 66%), high residual volume (RV)/total lung capacity (TLC) ratio (> 33%), and need for prolonged corticosteroids. Cause of death is respiratory insufficiency or malignancy. Lung cancer risk is increased because of cigarette smoking.
Last full review/revision November 2005
Content last modified November 2005
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