eMedicine Specialties > Pulmonology > Interstitial Lung Diseases
Eosinophilic Granuloma (Histiocytosis X)
Updated: Mar 3, 2008
Introduction
Background
Eosinophilic granuloma, also known as pulmonary histiocytosis X (PHX) or pulmonary Langerhans cell histiocytosis X (PLCH), is an uncommon interstitial lung disease that is epidemiologically related to tobacco smoking. It chiefly affects young adults, primarily occurring in the third or fourth decades of life.
See also Eosinophilic Granuloma, Skeletal and Eosinophilic Granuloma, Thoracic for a radiological perspective. Additionally, the Medscape General Medicine article Lymphangioleiomyomatosis may be helpful, as may a reader comment and author response related to this article.
Pathophysiology
PLCH is histologically characterized by abnormal infiltration of the lungs by activated Langerhans cells. Langerhans cells are differentiated cells of the dendritic cell system and are closely related to the monocyte-macrophage line. These antigen-presenting cells are normally found in the skin, reticuloendothelial system, heart, pleura, and lungs. They may be identified by immunohistochemical staining or by the presence of Birbeck granules via electron microscopy.
PLCH is similar to pediatric histiocytic disorders (Letterer-Siwe disease and Hand-Schuller-Christian disease). However, in contrast to pediatric histiocytoses, which involve multiple organs, PLCH usually manifests in a single organ; the lung. About 4-20% of patients with PLCH also have cystic lesions in the bones. Other organ systems are only rarely affected.
The accumulation found in the lungs is hypothesized to occur in response to exposure to cigarette smoke. Supporting this hypothesis is the finding that the initial histologic and radiographic findings are peribronchiolar. In addition, the disease is most prominent in the upper and middle lung zones, as seen in other smoking-related lung diseases. The granulomatous infiltrates seen in PLCH are composed of Langerhans cells, eosinophils, lymphocytes, macrophages, plasma cells, and fibroblasts, which form nodules centered on the terminal and respiratory bronchioles, causing destruction of the airway walls. In late stages of the disease, fibrotic stellate scarring occurs, and end-stage PLCH is characterized by this scarring along with cystic spaces and honeycombing.
Frequency
United States
PLCH is a rare disorder and the true prevalence is unknown. At 1 specialty referral center in the United States, PLCH was identified in less than 5% of patients who underwent lung biopsy for the diagnosis of interstitial lung disease.1 At another center, 15 cases of PLCH were found after lung biopsy, compared with 274 cases of sarcoidosis.2
International
In Belgium, 3% of patients evaluated at 20 pulmonary referral centers were diagnosed with PLCH.3 A large Japanese study estimated the prevalence of PLCH at 0.27 males and 0.07 females per 100,000 population based on hospital discharge diagnoses over a 1-year period.4 Scant epidemiologic data are available regarding this disease in the developing world.
Mortality/Morbidity
- PLCH has a highly variable course. Some patients have spontaneous remissions, especially when they stop cigarette smoking, whereas others progress to end-stage fibrotic lung disease.
- In 1 retrospective study, median survival was 12.5 years after diagnosis.5 A European study showed similar findings, with a median survival of 13 years.6
- Factors associated with a poorer prognosis include multisystem involvement other than bone (including diabetes insipidus related to pituitary involvement), recurrent pneumothorax, severe pulmonary artery hypertension, older age at diagnosis, severe pulmonary function test abnormalities, and more widespread cystic changes on imaging studies.
- Cigarette smoking is important to disease activity. Smoking worsens morbidity and mortality. Smoking cessation frequently stabilizes the disease and sometimes leads to its regression.
Race
Because of the rarity of the disease, no definitive epidemiologic data related to racial background are available.
Sex
No sex predilection is recognized.
Age
The peak incidence occurs in the 20- to 40-year age bracket.
Clinical
History
Presentations are variable. Approximately 25% of patients are asymptomatic, and their disease is diagnosed after an evaluation of incidental findings on chest radiographs. Others present with respiratory or constitutional symptoms. In order of decreasing frequency, common presenting symptoms are as follows:
- Nonproductive cough (56-70%)
- Dyspnea (40%)
- Fatigue (30%)
- Weight loss (20-30%)
- Chest pain (21%)
- Spontaneous pneumothorax, which may be recurrent, is a classic presentation found in 10-20% of patients.
- Fever (15%)
- Cystic bone lesions (4-20%): These may be painful and may predispose the patient to pathologic fracture.
Physical
Patients with PLCH present with nonspecific physical findings. Neither inspiratory rales (crackles) nor clubbing is common. Cor pulmonale may develop; therefore, the following related findings may be present:
- Loud second heart sound with accentuated pulmonic component
- Tricuspid regurgitation murmur
- Right ventricular lift
- Peripheral edema
Causes
No occupational causes or geographic predispositions are recognized. People with PLCH, almost invariably, are cigarette smokers. Antigenic stimulation from 1 or more components of tobacco smoke is likely responsible for the disease. Because only a few tobacco smokers develop the disease, other susceptibility factors, such as host genetics and environmental exposures, most likely play an important role in pathogenesis. Some reports in the literature also describe PLCH developing following radiation and/or chemotherapy for lymphoma. Additional investigation is needed to further our understanding of this disease process.
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References
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Keywords
eosinophilic granulomatosis, EG, pulmonary histiocytosis X, PHX, pulmonary Langerhans cell histiocytosis, PLCH, pulmonary histiocytosis, histiocytosis, cigarette smoking, end-stage fibrotic lung disease, fibrotic lung disease
