Pulmonary langerhans cell histiocytosis in a young man complaining of a dry cough and exertional dyspnea

History of present illness

A 38-year-old man went to a pulmonary outpatient clinic complaining of a dry cough and exertional dyspnea without wheezing that began about 1 year earlier. He also reported a recent onset of left-sided chest pain exacerbated by coughing. He had no fever or other notable symptoms in the month leading up to the visit. On the recommendation of the general practitioner, he underwent blood tests and a chest radiograph.

Past medical history

The patient was a current smoker (> 20 cigarettes/day since he was 18 years of age; 20 pack-years) and worked as a tiler. He had no family history of lung diseases or malignancies. He had hypertension and usually took β-blocker therapy (nebivolol 5 mg once daily).

Physical examination and early clinical findings

At the time of the visit, the patient was eupneic at rest, with normal oxygen saturation level (SpO ₂ 97% on room air). On physical evaluation, no significant clinical signs were found in the chest or elsewhere. Blood tests ruled out anemia (hemoglobin level was 15.1 g/dL) and did not suggest an ongoing infection: white blood cell count was normal (8,860 cells/μL) as was the differential count; C-reactive protein was 5 mg/L (normal levels < 10 mg/L).

The electrocardiogram showed sinus tachycardia with a heart rate of 105 beats/min. Chest radiograph revealed a slight reticulonodular pattern in both lungs ( Fig. 7.1 ). Pulmonary function tests ( Fig. 7.2 ) indicated normal lung volumes and diffusion capacity for carbon monoxide.

Clinical course

The plasma D-dimer level was normal, and further diagnostic workup was scheduled on an outpatient basis. The patient returned to the pulmonology clinic 1 month later and provided results of the tests requested by the doctors. Symptoms and clinical evaluation were unchanged.

Mantoux tuberculin skin test was negative. An HRCT scan of the chest ( Fig. 7.3 ) revealed the presence of bilateral cavitary nodules and cysts predominantly in a centrilobular and peribronchovascular distribution, with complete sparing of the bases. Some small subpleural bullae were also evident. There was no mediastinal or hilar lymphadenopathy and no pleural effusion.

Echocardiography showed no significant changes in atrial and ventricular size, morphology, and function. Left ventricular ejection fraction and estimated pulmonary arterial pressure were normal.

Skin prick tests showed no allergy to inhalants. The methacholine challenge test was negative (no airway hyperreactivity).

During a 6-minute walk test in ambient air, the patient covered a distance of 560 m, corresponding to 80% of predicted, in the absence of oxygen desaturation (nadir SpO ₂ 96%). However, he perceived somewhat severe shortness of breath (score 4 on the modified 10-point Borg scale).

Bronchoscopy with BAL of the middle lobe was performed. Five aliquots of normal saline (30 mL each) were sequentially instilled, and about 60 mL of BAL fluid were recovered and analyzed. High cellularity (698,000 cells/mL) and a low ratio (1.8%) between squamous epithelial and ciliated columnar epithelial cells were indicative of an optimal sample.

Leukocyte differential count revealed a mild increase in neutrophils (8%) and eosinophils (6%); lymphocytes were 10%, and macrophages were 76%. Lymphocyte subsets analyses showed a CD4 ⁺ :CD8 ⁺ ratio of 1.8 (normal range 0.9–2.5). The amount of CD1a-positive cells was 5% of the total.

The cultures were negative for common pathogens, as well as microscopy for acid-fast bacilli and polymerase chain reaction for Mycobacterium tuberculosis. The cytological analysis of BAL fluid did not reveal malignant cells.

After bronchoscopy, a multidisciplinary team discussed the case. The team included a pulmonologist, a thoracic radiologist, and a pathologist with great experience in interstitial lung diseases (ILDs).

Recommended therapy and further indications

Since all clinical, radiological, and laboratory data were highly suggestive of PLCH and the main alternative diagnoses were excluded, the multidisciplinary team decided not to continue with invasive investigations. The patient had no signs or symptoms suggesting the coexistence of diabetes insipidus and had no musculoskeletal pain; therefore, he did not undergo further tests.

The doctors advised him of the absolute need to quit smoking and offered him an individualized program with counseling and pharmacological support. Due to his occupational exposure to harmful dust, he was also recommended to use personal protective equipment at work.

Follow-up and outcomes

The patient was monitored from a clinical point of view at 3, 6, and 12 months. He quit cigarette smoking without using medications. Cough and dyspnea subsided and finally disappeared in 3 months. A control HRCT scan of the chest, performed about 6 months later, showed a significant improvement with disappearance of most nodules and cysts ( Fig. 7.4 ). Lung volumes were stable at 6 and 12 months. Further pulmonary function tests were scheduled every 6 months in the following year.