Pulmonary langerhans cell histiocytosis C96.6

Pulmonary Langerhans cell histiocytosis (PLCH) - older name "eosinophilic granuloma of the lung or pulmonary histiocytosis -X" - is a rare, mostly monorganic, adult disease of unknown etiology (Radzikowska E 2017), affecting almost exclusively younger cigarette smokers (see below eosinophilic granuloma). It is a granulomatous, destructive disease of bronchioles with proliferation of Langerhans cells as well as accumulations of other inflammatory cells in the small airways, with formation of nodular inflammatory foci and consecutive formation of lung cysts and pulmonary fibrosis. PLCH may also occur as a partial manifestation of multiorgan Langerhans cell histiocytosis.

Prevalence and incidence are unknown.

PLCH almost always occurs sporadically. Only a few family cases have been described. The majority of patients with PLCH are smokers. The mechanisms by which smoking induces the disease are not known. Presumably, a combination of different mechanisms leads to increased recruitment and activation of Langerhans cells in the small airways.

Onset of disease between 20 and 40 years of age with dyspnea and nonproductive cough. Isolated cases have also been described in young children ( Wang Q et al. 2012).

In 15-20% of patients dyspnea, fever, sweating and weight loss. Chest pain is usually indicative of a pneumothorax, which occurs in 15% of patients. Hemoptysis is rare. At the time of diagnosis, up to 20% of patients still have normal lung function tests.

The focal round granuIomatous infiltrates consist of Langerhans cells(CD1a-, S-100- and Langerin-positive), lymphocytes and eosinophilic granulocytes. Detectable mutations of BRAFV600E (in about 50% of Langerhans cells - Lorillon G et al. 2017) and/or NRAS and KRAS and MAPK genes are present in Langerhans cells.

The diagnostic suspicion results from the clinical symptoms and the anamnestic evidence of cigarette smoking. The diagnosis is supported in the early phase of the disease by the detection of characteristic reticular-nodular infiltrates in x-rays or high-resolution thoracic CT and in the advanced stage by the detection of cystic changes.

Pulmonary function testing and TCO measurement: Restrictive ventilation disturbance (possibly also peripheral obstruction) with respiratory partial insufficiency and often pathological oxy-ergometry or diffusion disturbance.

Bronchial lavage (> 5% CD1-positive histiocytes).

In cases of doubt a lung biopsy is necessary. The inflammation of the bronchioles may be accompanied by varying involvement of the interstitium and the vessels of the lung. In the early stage of the disease, a cellular inflammatory reaction is the main focus. In more advanced stages, cystic lung destruction, scarring of the airways and remodelling of the pulmonary vessels are impressive.

Depending on the radiographic findings at the time of diagnosis, the differential diagnosis includes all diseases with nodular or cystic lung changes. The most common differential diagnoses are emphysema and cystic lung diseases such as lymphangioleiomyomatosis (LAM) and Birt-Hogg-Dubé syndrome.

Spontaneous pneumothorax (cyst rupture); respiratory insufficiency.

Strict ban on smoking: Abstinence can lead to complete or partial regression of the disease. In some patients progression of the disease despite stopping smoking. There is still no general consensus on the role of immunosuppressive therapy in smokers with PLCH.

Pharmacotherapy (prednisone, chlorodeoxyadenosine, cyclophosphamide; methotrexate and cladribine) may be used in patients with severe disease or progressive disease.

The use of BRAF and MEK (MAPK kinase) inhibitors is experimental.

Accompanying with hypoxemia: oxygen therapy.

Ultima ratio is a lung transplant.

Most patients have a relatively good prognosis, especially if the results of the lung function tests remain stable over time. Over 85% of patients survive 10 years after diagnosis (Radzikowska E 2017). Complications such as pneumothorax and secondary pulomonal hypertension worsen the prognosis.

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