Pulmonary Langerhans cell histiocytosis (PLCH): a smoking-related lung disease

Langerhans cells are a kind of immune cell. In Langerhans cell histiocytosis (LCH), these cells accumulate in tissues where they do not belong. A published review explains that LCH may affect a single organ or be a multisystem illness, and that lung involvement, which it calls PLCH, is more common in adults and may be the only organ involved or part of multisystem disease. In adults, isolated lung disease is the usual pattern.

In PLCH the cells gather around the small airways and form nodular inflammatory lesions. The review says that cellular inflammation is prominent in early disease, whereas more advanced stages are characterised by cystic lung destruction, scarring of airways and changes in the lung blood vessels. That sequence of nodules, then cavitating nodules and cysts, is what shows on a CT scan.

PLCH is rare. The review notes that precise prevalence data are not available, but it was found in 4 to 5% of surgical lung biopsies taken for diffuse lung disease in one large series, which is probably an under-estimate because many people never have a biopsy.

The review states there are convincing data supporting a causal relationship between cigarette smoke and PLCH in adults, with more than 90% of adult patients smoking or having had substantial second-hand smoke exposure. The mechanism is not fully understood, but the evidence suggests cigarette smoke acts as a direct stimulant of airway factors that promote the recruitment and activation of Langerhans cells. The review also notes that the lack of a current or past smoking history makes the diagnosis less likely.

Because of this link, the practical message is the same for everyone: if you smoke and have been diagnosed with PLCH, stopping is the single most important thing you can do. This is true whether the disease is mild or advanced. The review describes smoking cessation as the main and first-line therapy in all adult smokers.

According to the review, about two-thirds of patients are symptomatic at diagnosis. Breathlessness and an unproductive (dry) cough are the most common symptoms. Constitutional symptoms including fever, sweats and weight loss occur in 15 to 20%. In 10 to 15% of adults there are symptoms from disease outside the lungs, such as passing a lot of urine and excessive thirst from diabetes insipidus, bone pain from skeletal involvement, or skin rashes.

Chest pain usually signifies a collapsed lung (pneumothorax) or rib involvement. The review notes that coughing up blood is uncommon and suggests an alternative cause, such as a chest infection, lung cancer or a fungal ball in a cavity. Because the picture can resemble other lung conditions, some people are diagnosed after a chest X-ray for another reason or after a collapsed lung.

Diagnosis begins with a clinical history, including smoking, and chest imaging. The review says that a high-resolution CT scan of the chest should be obtained in every patient because in many instances it can distinguish PLCH from other cystic lung diseases such as lymphangioleiomyomatosis, Birt-Hogg-Dube syndrome or emphysema, with characteristic nodules and cysts in the upper and mid lung zones.

Lung function tests are usually done too. The review reports that up to 20% of patients have normal pulmonary function at diagnosis and about 70% have a reduced diffusing capacity for carbon monoxide, which is the most common abnormality. A restrictive pattern is more frequent in earlier stages and an obstructive pattern more common as the disease advances.

A biopsy gives a definite diagnosis but is not always needed. The review says that lung biopsy is necessary for definitive diagnosis although it may not be required when imaging findings are highly characteristic, particularly in mildly symptomatic patients in whom no specific therapy is contemplated other than smoking cessation. When CT findings are non-diagnostic, bronchoscopy or surgical lung biopsy may be indicated. Because LCH can involve other sites, doctors may also look for bone, skin or pituitary involvement with X-rays or MRI.

The cornerstone is stopping smoking. The review says all smokers must be counselled on the importance of smoking cessation, which may result in regression of disease and obviate the need for systemic immunosuppressive therapy. It adds that there is no general consensus about immunosuppressive therapy in smokers with PLCH, and that although corticosteroids have historically been used for progressive disease, it remains unclear whether patients objectively respond to them. Other agents, including cladribine, cyclophosphamide and methotrexate, have been used in progressive disease, and their role is not well defined.

In the UK the NHS offers free support to quit. The NHS Better Health pages describe local Stop Smoking Services, which are free and offer expert professional support in person, online or by phone, and say that talking to a professional helps you choose the right product. Options include nicotine replacement therapies (patches, gum, sprays or lozenges), nicotine-free medicines such as varenicline, and nicotine vapes for adult smokers to support quitting. The NHS says combining nicotine-free medicine with nicotine replacement can make you over 5 times more likely to quit for good, and that the general advice is to use products for at least 12 weeks, or longer if needed. Ask your GP or lung specialist about local services.

Complications are managed individually. The review says that recurrent pneumothorax is best managed with surgical pleurodesis, which does not preclude later lung transplantation, and that lung transplantation should be considered in patients with progressive lung disease.

The review calls pulmonary hypertension, raised pressure in the blood vessels of the lungs, a common and under-recognised complication in PLCH that is associated with poor survival. Pneumothorax, as above, is another important complication. Respiratory failure accounts for a substantial proportion of deaths in end-stage disease.

Even so, the review says the course in adults is variable and unpredictable, ranging from no symptoms to progressive, disabling disease. Several factors have been associated with a poorer outcome, including extensive cysts, severely reduced diffusing capacity, obstructive lung function, multi-organ involvement and prolonged steroid therapy, but only pulmonary hypertension reliably predicts prognosis in an individual. The overall message is that the outlook for most people is relatively good, particularly if lung function remains stable and they stop smoking.

Regular follow-up with lung function testing and, when needed, repeat CT scans is used to monitor stability.

Sudden sharp chest pain with breathlessness may mean a collapsed lung and needs urgent assessment: call 999 or go to A&E. See your GP promptly for worsening breathlessness, persistent cough, unexplained weight loss, fever or sweats, or coughing up blood. If you have been diagnosed with PLCH and develop increasing swelling of the ankles or breathlessness on minimal effort, tell your specialist, as this can be a sign of pulmonary hypertension.

No NHS or UK charity patient page on PLCH was found at the time of writing, so the account of the disease draws mainly on a review article by US authors. The NHS Better Health pages are cited for UK stop-smoking support. A specialist respiratory team will advise on your own care.