Journal of the Louisiana State Medical Society
DISCUSSION Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare lung disease caused by the accumulation of inflamma- tory cells in small airways of the lung, leading to nodular granulomatous changes of the lung parenchyma, which over time, progress to reticular and cystic changes. There are no data regarding the overall prevalence of PLCH in the adult population. However, two series of patients under- going lung biopsy for diffuse interstitial disease reported PLCH in 3%-5% of all diffuse lung disease biopsies, in comparison with sarcoidosis, which was found in 12.5% of the same patients. 1,2 It has been hypothesized that PLCH is likely underdiagnosed because it can be asymptomatic and sometimes undergoes spontaneous remission. 3 The incidence of PLCH peaks in young adults between ages 20-40. 4 Gender distribution of PLCH has recently been shown to be equal. As the rates of smoking between men and women have evened out over the past few decades, so has the incidence of the disease. 3,5 PLCH is strongly associated with smoking tobacco cigarettes. More than 90% of adult patients are smokers. 6,7 It has been suggested that cigarette smoke may irritate the small airways, leading to injury and inflammation. 7 Langerhans cells are a subgroup of antigen-presenting dendritic cells found in the skin and in the epithelium of the tracheobronchial tree. Their normal function is to survey antigens that are deposited in the airway during inhala- tion. Activation of Langerhans cells leads to a cascade of signaling, leading to an adaptive immune response. PCLH is characterized by peribronchiolar proliferation of Langer- hans cells, forming stellate nodules that cavitate and form cysts. The advanced disease is characterized by scarring of airways and pulmonary vascular remodeling. The etiology of PLCH is poorly understood. It has been proposed that PLCH is an immune response to an unknown antigen, leading to T-cell activation. The unknown antigen likely is related to cigarette smoking. However, there are also host factors involved, as only a small percentage of cigarette smokers develop PLCH. 8 Theories that have been proposed include a viral origin, neoplastic proliferation, and immune system dysregulation. 8 PLCH has also been shown to be associated with lym- phoma and is more likely to be diagnosed in a patient pre- viously treated with chemotherapy and radiation therapy, usually for Hodgkin’s disease. 3 Many patients with PLCH are asymptomatic, leading to diagnosis based on chest radiograph for other indications. Symptomatic patients typically present with a nonproduc- tive cough, dyspnea, an abnormal chest radiograph, or recurrent spontaneous pneumothorax. 3 Diagnosis of PLCH is difficult based on these nonspecific symptoms. A minor- ity of patients may also experience fever, weight loss, and malaise. 4 Laboratory findings tend to be within normal limits in PLCH patients, with the exception of a possibly moder- ately elevated erythrocyte sedimentation rate. 8 Pulmonary
function tests can show an obstructive, restrictive, or mixed pattern. Vital capacity is often low, and residual volume is often normal or increased, leading to a total lung capacity that is relatively normal. 8 In most adult patients, LCH affects only the lungs. 3 However, the most likely extrapulmonary findings in PLCH are cystic bone lesions, diabetes insipidus (DI), and skin le- sions. 4 Patients should be carefully examined for these other signs with a skeletal survey and physical exam if diagnosed with PLCH. PLCH is not typically a strictly nodular or cystic disease but a spectrumof varying degrees of granulomatous nodular changes, which predominate earlier in the disease process and cystic changes which predominate later in the disease process. 3,6,9,10 Brauner proposed that the initial nodules eventually cavitate, leading to thick-walled cysts, which thenmature to thin-walled and ultimately confluent cysts. 9,10 Imaging is fundamental for diagnosis of PLCH, as symptoms are non-specific. Early nodular PLCH is charac- terized by radiography, computed tomography (CT), and high-resolution CT as bilateral mid- to upper-lung zone distribution of pulmonary nodules with relative sparing of the lung bases, especially the costophrenic sulci, and normal to increased lung volumes. The nodules are typically irregu- larly marginated, 1 to 10 mm in size, and can range from a few scattered nodules to innumerous and/or confluent nodules. A chest radiograph is the initial imaging modality of choice; however, high-resolution CT (HRCT) is markedly more sensitive and specific for PLCH. 3,6,9 The differential diagnosis for nodular PLCH includes sarcoidosis, silicosis, metastasis, and hematogenous infec- tious processes such as military tuberculosis. HRCT is utilized to narrow the diagnosis by distinguishing the cen- trilobular distribution of PLCHnodules from the periphym- phatic distribution of sarcoidosis, silicosis, and lymphangitic carcinomatosis. 6,9 Cystic lesions of PLCH can also be difficult to distin- guish from bullous emphysema, lymphangioleiomyoma- tosis (LAM), bronchiectasis, and honeycombing associated with end stage fibrotic lung diseases. However, an emphy- sematous bulla is typically a focus of parenchymal destruc- tion lacking a cyst wall. LAM occurs almost exclusively in females and has a diffuse bilateral distribution and more uniform appearing cysts. Cystic bronchiectasis has a com- municating branching pattern. Honeycombing tends to be peripheral and basilar in distributionwith associated ground glass opacity and parenchymal architectural distortion. HRCT can often be utilized to reach an accurate diagnosis in 84% of cases and can preclude the need for an invasive lung biopsy. 6,9 Pneumothorax can occur as a complication of PLCH and may be the initial presenting clinical and imaging finding. Lymphadenopathy, air-space consolidation, and a solitary pulmonary nodule are rare imaging findings of PLCH. 9 Advanced disease can be associatedwith pulmonary hypertension. 3 First-line treatment for PLCH is immediate cessation
180 J La State Med Soc VOL 166 July/August 2014
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