What Is Pulmonary Langerhans Cell Histiocytosis?

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease that commonly develops in young adult smokers. It is also known as eosinophilic granuloma of the lung, pulmonary Langerhans cell granulomatosis, and pulmonary histiocytosis X.

Langerhans cells are a type of immune cell that normally destroy foreign substances to protect the body. In PLCH, abnormal infiltration of Langerhans cells destroys the tips of lung airway branches (distal bronchioles) progressively. It first causes cysts (sacs filled with liquid or air) to form, followed by granulomas (masses of inflamed tissue).

PLCH can lead to symptoms of chronic dry cough, chest pain, shortness of breath, and exercise intolerance, although up to a quarter of people show no symptoms at all. The cause of PLCH is unknown. 

Signs and Symptoms of Pulmonary Langerhans Cell Histiocytosis

PLCH most commonly presents with a constellation of symptoms, including dry cough, fatigue, chest pain while breathing (pleuritic chest pain), and shortness of breath. But some people may present with no symptoms at all, and may only find out that they have PLCH after getting a chest X-ray for some other reason.

The following symptoms may also be associated with PLCH:

• Collapsed lung (pneumothorax): In 15–30% of cases, lung collapse occurs and leads to the diagnosis of PLCH, occurring during the course of PLCH in 30–45% of cases
• Fever
• Sweating
• Unexplained weight loss
• Skin lesions
• Bone lesions

Causes

The exact cause of PLCH remains a mystery, but it is more common in those who smoke or have a history of smoking. Up to 95% of people with PLCH smoke tobacco.

Some theories point to viral infection or exposure to lung-harming antigens (substances that may trigger an allergic reaction) as possible causes of PLCH. But these theories fail to explain why some people get this disease while others do not.

It's not known whether PLCH is a type of cancer or a cancer-like disease. Research suggests that there might be a neoplastic nature to this condition (in which cells divide and grow at an abnormally high rate)—at least in a subset of people. This is due to the presence of a high number of mutated cells (including mutation of the BRAF V600E gene).

Diagnosis

Pulmonary Langerhans cell histiocytosis is suspected based on history and chest X-rays. It is confirmed by high-resolution computed tomography (CT) and bronchoscopy (a process by which a narrow tube with a camera is inserted through the mouth into the airways of the lungs) with biopsy (which entails taking a tissue sample to examine in a lab) and bronchoalveolar lavage (which entails introducing and suctioning sterile water for a lab to examine).

The following imaging tools and tests may be used in the diagnosis of PLCH:

• Chest X-ray (CXR): A chest X-ray is a quick and widely available imaging tool that can help detect the presence of infiltrates, such as Langerhans cell granulomas, in the lung. Also, a CXR may show cystic changes in the middle and upper lobes, increased lung volume, and pneumothorax (collapsed lung). 
• High-resolution computed tomography (HRCT): This imaging can detect a combination of nodules and cysts that form a star-shaped pattern, predominantly in the upper lung. A biopsy (which consists of taking a sample to analyze in a lab) of these lesions can detect Langerhans cell granulomas, providing a definitive diagnosis of PLCH.
• Pulmonary function tests (PFTs): Pulmonary function tests can provide your healthcare provider with insight into the lung’s ability to reach its maximum volume, diffusion capacity (DLCO), and volume capacity, 
• Bronchoscopy with biopsy and bronchoalveolar lavage: These are used in conjunction with HRCT to confirm the diagnosis of PLCH. The presence of inflammatory cells on bronchoalveolar lavage and inflammatory cells (eosinophils) plus Langerhan cells on biopsy are diagnostic of the disease. 

Prognosis

A European study of adult PLCH found a five-year survival rate of 94% and a 10-year survival rate of 93%. The study found worse outcomes for people who had chronic respiratory failure or pulmonary hypertension (higher than normal pressure in the pulmonary artery).

The National Cancer Institute notes favorable prognostic factors for adult PLCH include having minimal symptoms, smoking cessation, and lung transplant. Unfavorable prognostic factors include altered pulmonary function, age older than 26 years, and smoking.

Researchers have yet to uncover why people have a wide range of clinical presentations. Some people have rapidly progressive cases, while others have more mild cases.

Treatment

PLCH is highly unpredictable, with some people showing stable disease that may even remit with smoking cessation. In contrast, others develop chronic, progressive lung disease that may continue to damage the lungs even after successful smoking cessation.

Currently, there is no standard of treatment for PLCH, although corticosteroids may help manage your symptoms. Chemotherapy has been studied because it can treat childhood Langerhans cell histiocytosis, though it hasn't had much success in adult PLCH.

Targeted therapies in people who have BRAF mutations continue to undergo studies. These include BRAF inhibitors Zelboraf (vemurafenib) and Tafinlar (dabrafenib).

In the most severe cases, lung transplantation may be required.

Summary

Pulmonary Langerhans cell histiocytosis is a lung disease that occurs primarily in young smokers. It may have no symptoms at first and appear incidentally with a chest X-ray or after it has caused a collapsed lung. Symptoms may include a dry cough, fatigue, chest pain while breathing, and shortness of breath.

The cause is unclear, but smoking is a primary risk factor. It can be associated with genetic mutations in the Langerhans cells.

Treatment includes smoking cessation, and corticosteroids may help to manage symptoms. The disease can progress to impair lung function and quality of life and cause loss of life. Continued smoking is associated with worse outcomes, including the progression of the disease.

A Word From Verywell

PLCH is a mysterious disease that can quickly become worse without treatment, but because the symptoms of PLCH mimic those of many other conditions, getting a timely diagnosis is often difficult. If you are a current or past smoker and develop any of the aforementioned symptoms, you should consult a healthcare provider. 

Smoking is a major trigger of PLCH and contributes to many other lung conditions. Quitting smoking is not easy, but healthcare providers are equipped with tools that will help you formulate a plan to quit successfully.