36-Year-Old Woman with Chronic Cough and Pulmonary Nodules

A 36-year-old Caucasian woman presented to her primary care physician complaining of approximately 12 months of nonproductive cough. She also reported intermittent sharp, pleuritic anterior chest pain. She has had night sweats for the past year without documented fevers and she also reported weight loss. She had received antibiotics in the past with no improvement of her symptoms. She denied shortness of breath or hemoptysis and she denied tuberculosis exposure. A previous PPD was negative. The rest of the review of systems was negative.

Her past medical history was significant for thyroid carcinoma diagnosed 5 years ago. Her past surgical history included thyroidectomy and hysterectomy.

Family History was significant for her father dying of a myocardial infarction at age 40 and her mother who had hypertension. She smoked 1-2 packs per day for the past 24 years. She denied alcohol and drug abuse. She had been a New Jersey resident all her life. She was a maintenance person and worked as a plumber and electrician but did not report any significant exposures. She was not married and had no children. She denied foreign travel and history of sexually transmitted diseases. 

Her medications included levothyroxine 75 mg daily and sertraline 25 mg daily. She had no known drug allergies.

She had a normal complete blood count and basic metabolic panel. TSH was 1.4. ESR was 20. ANA, C-ANCA and anti GBM were negative. Rheumatoid Factor was normal, and alpha-1 antitrypsin level was normal. The sputum culture grew normal respiratory flora, fungal sputum culture had no growth, and three sputum samples were negative for acid fast bacilli. CT scan of the lungs is shown in Figure 1.

Pulmonary Langerhans cell histiocytosis (PLCH), also known as histiocytosis X and eosinophilic granuloma, is an uncommon interstitial lung disease (ILD) that primarily afflicts young Caucasian cigarette smokers. The exact incidence and prevalence of this disease are unknown, but it probably represents 5% of all ILD (1). Young adults between the ages of 20 and 40 years old are usually affected, and the gender distribution varies among studies. Some studies report male predominance, others suggest that women are more frequently affected than men and others report equal distribution (1,2). The vast majority of patients are smokers (90% or more) and there are no known occupational exposures or known predisposing genetic factors (3). The most common symptoms are nonproductive cough and dyspnea, although patients may also complain of constitutional symptoms such as fatigue and weight loss. Twenty-five percent of the patients are asymptomatic and approximately 15% present with spontaneous pneumothorax (3). The chest radiograph is abnormal in most patients. Findings in the early stages of the disease include nodules in the upper and middle lung zones with sparing of the lung bases and costophrenic angles. As the disease progresses, a reticulonodular pattern predominates followed by cystic changes (2, 4). In end-stage PLCH, reticular areas of opacity in the upper and middle lung zones and honeycomb lung can be found (4). HRCT scan is more sensitive than radiography. Findings include nodules of varying size, some may have cavities like the ones seen in this patient, and they are usually found in the upper and middle lung zones with relative sparing of the lung bases(3, 4). Cystic lesions are the most common feature and usually measure less than 10 mm in diameter. The demonstration of nodules and cysts in a characteristic distribution is highly suggestive of PLHC (5). However, when only nodules or cysts are present, the specificity decreases and other diseases should be considered (4).

Centrilobular emphysema is less likely in this patient given the CT scan findings. Blebs can be seen in emphysema but not nodules. When cystic lesions predominate such as in advance PLHC, it may be difficult to distinguish from emphysema, but that is not the case in this patient (6). Other diseases to consider in predominantly cystic PLHC are lymphangioleioyomatosis, idiopathic pulmonary fibrosis and Pneumocystis jiroveci pneumonia (4). Lymphangioleiomyomatosis occurs almost exclusively in women of childbearing age and affects the lungs diffusely rather than the upper lung zones like in PLHC(4).  The cystic lesions of idiopathic pulmonary fibrosis have a subpleural and basilar distribution and patients have decreased lung volumes (4). Patients with Pneumocystis jirovecii pneumonia may also develop lung cysts that may be indistinguishable from cystic lesions of PLHC (4).

Respiratory bronchiolitis-associated interstitial lung disease is a rare disease that occurs in young smoking adults in their third through sixth decades of life such as this patient. The most common symptoms are chronic cough and dyspnea. CT scan findings include fine centrilobular nodules and areas of ground glass bilaterally. Both upper and lower lung fields are affected. Emphysematous changes can coexist (4, 6).

Silicosis is a lung disease caused by inhalation of mineral dust. Patients may be asymptomatic or present with exertional dyspnea and productive cough. Some patients may also have constitutional symptoms such as weight loss and malaise. CT scan manifestations include multiple small (<10 mm) nodules that are scattered diffusely throughout the lungs (but may be more prominent in the upper lung fields), and pleural thickening. The nodules in PLHC follow a centrilobular distribution whereas the nodules in silicosis have a perilymphatic distribution (7).

Multiple pulmonary nodules can be seen in metastatic cancer but they are usually localized in the better perfused lung bases and not the upper lobes like the nodules seen in this patient. Cavitation of metastatic lesions occurs in less than 5% of the cases (8). Patients with PLCH are at increased risk of developing malignant neoplasm but it does not seem to be related to tobacco exposure. Lymphoma, myeloproliferative disorders, lung, prostate and breast cancer and are some of the malignancies that have been described (9-11).