How I manage pulmonary Langerhans cell histiocytosis

Abstract

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare sporadic cystic lung disease of unknown aetiology that is characterised by the infiltration and destruction of the wall of distal bronchioles by CD1a + Langerhans-like cells. In adults, PLCH is frequently isolated and affects young smokers of both sexes. Recent multicentre studies have led to the more standardised management of patients in clinical practice. Smoking cessation is essential and is occasionally the only suitable intervention. Serial lung function testing is important because a significant proportion of patients may experience an early decline in forced expiratory volume in 1 s and develop airflow obstruction. Cladribine was reported to dramatically improve progressive PLCH in some patients. Its efficacy and tolerance are currently being evaluated. Patients who complain of unexplained dyspnoea with decreased diffusing capacity of the lung for carbon monoxide should be screened for pulmonary hypertension by Doppler echocardiography, which must be confirmed by right heart catheterisation. Lung transplantation is a therapeutic option for patients with advanced PLCH.The identification of the BRAF V600E mutation in approximately half of Langerhans cell histiocytosis lesions, including PLCH, and other mutations of the mitogen-activated protein kinase (MAPK) pathway in a subset of lesions has led to targeted treatments (BRAF and MEK (MAPK kinase) inhibitors). These treatments need to be rigorously evaluated because of their potentially severe side-effects.

Pulmonary Langerhans Cell Histiocytosis

“…16 It is estimated that PLCH accounts for 3 to 5% of all diffuse lung diseases in adults. [17][18][19] A national survey of hospital discharges conducted in Japan estimated the prevalence of PLCH to be 0.27 per 100,000 males and 0.07 per 100,000 females in the Japanese population. 12 Extrapolating these numbers to the current population estimates suggests that there are 1,100 patients with PLCH in the United States and 26,000 worldwide.…”

“…The CD1a þ DCs in PLCH express multiple costimulatory molecules, and by producing cytokines such as interleukin 1-β, granulocyte macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-α, they help in secondary recruitment of other immune cells, forming cellular nodules comprised DCs, T-cells, B-cells, fibroblasts, eosinophils, neutrophils, plasma cells, and pigmented macrophages. 18,29,30 As the disease progresses, the nodules are gradually replaced by fibroblastic proliferation with central scarring and peripheral cellular tentacles. 31…”

Recurrent pneumothorax, skin lesions and frequent urination

“…Recurrent pneumothorax, skin lesions and frequent urination is needed to detect bony lesions and lesions at other sites [14]. Bronchoalveolar lavage may show ≥5% CD1a + cells but has low sensitivity.…”

“…Biopsies should be obtained from nodular areas [15,16]. Histopathological examination shows loosely formed granulomas containing CD1a + / CD207 + cells especially around small airways [14]. CD1a and CD207 are present on Langerhans cells and they are used as specific markers to distinguish Langerhans cells from other dendritic cell subtypes [17].…”

Rare pulmonary diseases: a common fight

“…Moreover, also in the current issue of the ERR, LORILLON and TAZI [9] illustrate the current management of PLCH. Abdellatif Tazi is the leader of the French national reference centre for Langerhans cell histiocytosis, and this Frontiers in Clinical Practice article describes several clinical cases as well as key features of PLCH.…”