Eosinophilic Granuloma (Histiocytosis X)
- Author: Eleanor M Summerhill, MD, FACP, FCCP; Chief Editor: Zab Mosenifar, MD more...
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.[1]
See also Eosinophilic Granuloma, Skeletal and Eosinophilic Granuloma, Thoracic for a radiological perspective.
Pathophysiology
Pulmonary Langerhans cell histiocytosis X (PLCH) is histologically characterized by parenchymal 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-Sch ü ller-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 of Langerhans cells 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.
Epidemiology
Frequency
United States
Pulmonary Langerhans cell histiocytosis X (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.[2] At another center, 15 cases of PLCH were found after lung biopsy, compared with 274 cases of sarcoidosis.[3]
International
In Belgium, 3% of patients evaluated at 20 pulmonary referral centers were diagnosed with PLCH.[4] A large Japanese study estimated the prevalence of pulmonary Langerhans cell histiocytosis X (PLCH) at 0.27 males and 0.07 females per 100,000 population based on hospital discharge diagnoses over a 1-year period.[5] Scant epidemiologic data are available regarding this disease in the developing world.
Mortality/Morbidity
- Pulmonary Langerhans cell histiocytosis X (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.
- 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 pulmonary Langerhans cell histiocytosis X (PLCH) , no definitive epidemiologic data related to racial background are available.
Sex
No sex predilection is recognized for pulmonary Langerhans cell histiocytosis X (PLCH).
Age
The peak incidence of pulmonary Langerhans cell histiocytosis X (PLCH) occurs in the 20- to 40-year age bracket.
Podbielski FJ, Worley TA, Korn JM, Connolly MM. Eosinophilic granuloma of the lung and rib. Asian Cardiovasc Thorac Ann. Apr 2009;17(2):194-5. [Medline].
Gaensler EA, Carrington CB. Open biopsy for chronic diffuse infiltrative lung disease: clinical, roentgenographic, and physiological correlations in 502 patients. Ann Thorac Surg. Nov 1980;30(5):411-26. [Medline].
Colby TV, Lombard C. Histiocytosis X in the lung. Hum Pathol. Oct 1983;14(10):847-56. [Medline].
Thomeer M, Demedts M, Vandeurzen K. Registration of interstitial lung diseases by 20 centres of respiratory medicine in Flanders. Acta Clin Belg. May-Jun 2001;56(3):163-72. [Medline].
Watanabe R, Tatsumi K, Hashimoto S, Tamakoshi A, Kuriyama T. Clinico-epidemiological features of pulmonary histiocytosis X. Intern Med. Oct 2001;40(10):998-1003. [Medline].
Vassallo R, Ryu JH, Schroeder DR, Decker PA, Limper AH. Clinical outcomes of pulmonary Langerhans'-cell histiocytosis in adults. N Engl J Med. Feb 14 2002;346(7):484-90. [Medline].
Delobbe A, Durieu J, Duhamel A, Wallaert B. Determinants of survival in pulmonary Langerhans' cell granulomatosis (histiocytosis X). Groupe d'Etude en Pathologie Interstitielle de la Société de Pathologie Thoracique du Nord. Eur Respir J. Oct 1996;9(10):2002-6. [Medline].
[Guideline] Prakash UB. Uncommon causes of cough: ACCP evidence-based clinical practice guidelines. Chest. Jan 2006;129(1 Suppl):206S-219S. [Medline].
Stacher E, Beham-Schmid C, Terpe HJ, Simiantonaki N, Popper HH. Pulmonary histiocytic sarcoma mimicking pulmonary Langerhans cell histiocytosis in a young adult presenting with spontaneous pneumothorax: a potential diagnostic pitfall. Virchows Arch. Aug 2009;455(2):187-90. [Medline].
Alalawi R, Whelan T, Bajwa RS, Hodges TN. Lung transplantation and interstitial lung disease. Curr Opin Pulm Med. Sep 2005;11(5):461-6. [Medline].
Misaki H, Yamauchi T, Arai H, et al. Secondary malignant fibrous histiocytoma following refractory langerhans cell histiocytosis. J Clin Exp Hematop. May 2009;49(1):33-7. [Medline].
Arico M. Langerhans cell histiocytosis in adults: more questions than answers?. Eur J Cancer. Jul 2004;40(10):1467-73. [Medline].
Chaowalit N, Pellikka PA, Decker PA, et al. Echocardiographic and clinical characteristics of pulmonary hypertension complicating pulmonary Langerhans cell histiocytosis. Mayo Clin Proc. Oct 2004;79(10):1269-75. [Medline].
Crausman RS, Jennings CA, Tuder RM, Ackerson LM, Irvin CG, King TE Jr. Pulmonary histiocytosis X: pulmonary function and exercise pathophysiology. Am J Respir Crit Care Med. Jan 1996;153(1):426-35. [Medline].
Dacic S, Trusky C, Bakker A, Finkelstein SD, Yousem SA. Genotypic analysis of pulmonary Langerhans cell histiocytosis. Hum Pathol. Dec 2003;34(12):1345-9. [Medline].
King TE, Crausman RS. Pulmonary histiocytosis X. In: Fishman AP, ed. Fishman's Pulmonary Diseases and Disorders. Vol 1. 3rd ed. New York, NY: Mc-Graw Hill; 1998:1163-70.
Sundar KM, Gosselin MV, Chung HL, Cahill BC. Pulmonary Langerhans cell histiocytosis: emerging concepts in pathobiology, radiology, and clinical evolution of disease. Chest. May 2003;123(5):1673-83. [Medline].
Tazi A. Adult pulmonary Langerhans' cell histiocytosis. Eur Respir J. Jun 2006;27(6):1272-85. [Medline].
Vassallo R, Ryu JH. Pulmonary Langerhans' cell histiocytosis. Clin Chest Med. Sep 2004;25(3):561-71, vii. [Medline].
Print
