When pressed, Mr. W admitted to having a “nagging flu.” Specifically, he had been coughing on and off for several months and more recently had become increasingly short of breath. Previously in good health, he had developed a nonproductive cough without a clear precipitating event. When his symptoms persisted, he was treated by his primary-care physician with a course of oral trimethoprim/
sulfamethoxazole. Despite this therapy, he developed a low-grade fever and myalgias and was switched to oral cefuroxime. He seemed to get better, but the cough returned, along with shortness of breath, primarily with exertion. Symptoms occurred both during the day and at night.
Mr. W tried his son’s albuterol inhaler without obvious benefit. On a follow-up visit, his physician did not hear any wheezes but did hear crackles. Chest x-ray showed bilateral patchy infiltrates. Mr. W was given a prescription for erythromycin, which he took for two weeks, along with an expectorant. He seemed to be getting better, but when symptoms returned and he had difficulty working, Mr. W reluctantly agreed to accompany his son and seek further evaluation.
Mr. W’s medical history was negative for asthma, exercise-induced bronchospasm, hay fever, and sinusitis, although he remembered having had pneumonia once during childhood. He did not smoke and had not received influenza vaccine. For the most part, he worked outdoors and in a barn with horses and hay. However, he was not exposed to animals in the home and did not sleep with a feather pillow or down comforter. No wood-burning stove, evaporative cooler, or humidifier was used in his house. His hobbies included horseback riding and woodworking. He reported no weight loss, sputum production, hemoptysis, arthralgias, or swollen lymph nodes.
On examination, Mr. W appeared fairly comfortable. He was afebrile with normal vital signs and oxygen saturation by pulse oximetry of 96 percent on room air. Bibasilar crackles could be heard, but his examination was otherwise unremarkable. A chest x-ray showed bilateral patchy infiltrates, predominantly in the lower lobes. Pulmonary function testing demonstrated reductions in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), with a normal FEV1/FVC ratio; decreased lung volumes; and diffusion capacity consistent with a restrictive process. A treadmill challenge induced cough and dyspnea along with oxygen desaturation.
Based on his history, pulmonary function tests, and radiologic findings, we suspected that Mr. W had a fairly classic case of farmer’s lung due to exposure to moldy hay in the barn. This form of hypersensitivity pneumonitis is caused by inhalation of thermophilic actinomycetes. To our surprise, a hypersensitivity panel measuring serum precipitins was negative for the suspected antigens but strongly positive to pigeon antigens. These results were confirmed by repeat testing. On further questioning, Mr. W said that his workshop was located in the barn and he recalled seeing an occasional pigeon while doing his woodworking. An inspection of the barn by his son revealed a number of pigeons nesting in the rafters; there were droppings and feathers in the open workshop area.
Hypersensitivity pneumonitis, or extrinsic allergic alveolitis, is caused by inhalation of a number of organic dusts that affect the distal airways. This syndrome may occur in several forms, depending on the amount and duration of exposure to the offending antigen and the patient’s immunologic response. The most frequently implicated organisms are the thermophilic actinomycetes that cause farmer’s lung. “Bird-fancier’s disease,” also known as “pigeon breeder’s disease,” is second only to farmer’s lung as a cause of hypersensitivity pneumonitis. Parakeets and pigeons are the birds most commonly responsible.
A majority of patients have intense contact with birds and their droppings, although a number of cases have involved exposure to a single bird only. The commonly implicated antigens are in the bird droppings, serum, and feathers.
The pathophysiology of hypersensitivity pneumonitis is complex and still not well-understood; there is evidence for both immune-complex and delayed-hypersensitivity reactions. Cytotoxic and suppressor CD8+ T cells are the primary cells found in bronchoalveolar lavage fluid; histology shows a predominance of mononuclear cells and granulomatous reactions. Serum immunoglobulin E is not elevated, and atopy is not a risk factor.
Hypersensitivity pneumonitis can present as an acute, subacute, or chronic illness. Acute symptoms develop four to eight hours after exposure to antigen. Patients present with cough and dyspnea, as well as fever, chills, and malaise, and may mistake their symptoms for pneumonia or a flulike illness. Physical findings on presentation may be normal or include fever, tachypnea, crackles, or rales, possibly progressing to respiratory failure. Wheezing is not typical. Symptoms resolve if the antigen source is removed.
The subacute presentation may be more insidious, with cough, exertional dyspnea, malaise, fatigue, and weight loss developing over the course of days or weeks. Diffuse rales are the primary physical finding. Chronic disease is usually associated with low-dose exposure to the antigen and may not become evident for months or even years after initial exposure. These patients may develop irreversible lung damage with respiratory failure.
The WBC count and erythrocyte sedimentation rate are typically elevated in the acute process. In the symptomatic patient, arterial blood gases generally demonstrate hypoxemia, which is accentuated by exercise. Chest x-rays may be normal but usually show a diffuse reticulonodular pattern or patchy infiltrates. In chronic disease, chest x-rays may demonstrate diffuse interstitial fibrosis. CT scans may further define alveolar involvement, but findings are not specific for hypersensitivity pneumonitis. Pulmonary function testing typically shows a restrictive pattern, with a decrease in FVC and FEV1 and a normal FEV1/FVC ratio. Lung volumes are reduced, and the diffusion capacity may also be low, especially during exercise.
Approximately six hours after exposure, patients classically have a decrease in their pulmonary function, which recovers in parallel with their clinical improvement. The presence of serum precipitins measured by gel diffusion or enzyme-linked immunosorbent assay is suggestive but not diagnostic because they may also be present in asymptomatic subjects. Diagnosis is based on a history of exposure along with the finding of serum precipitins in a symptomatic patient.
Several other syndromes should be considered when evaluating patients for hypersensitivity pneumonitis. Humidifier fever occurs when recirculated water for humidification or cooling becomes contaminated with endotoxin-producing gram-negative organisms. Patients may develop fever, malaise, and a mild cough with chest tightness four to eight hours following exposure to the offending agent. Chest x-rays are normal, and pulmonary function tests are either normal or show mild airway obstruction without impairment of gas transfer. The symptoms clear completely in a few hours.
Grain fever, which is due to inhalation of grain dust and exposure to dusts in animal facilities, can cause similar symptoms. Chronic exposure to cotton dust causes the chronic obstructive lung disease byssinosis. Endotoxin in the cotton dust probably contributes to the acute symptoms called “Monday morning fever.” Heavy exposure to mold spores, which may occur while working in a silo, can cause an acute pneumonitis termed “mycotoxicosis.” Sick building syndrome may be due to increased levels of air contaminants, such as volatile organic compounds and bioaerosols, with inadequate ventilation. Patients complain of mucous membrane irritation, respiratory symptoms, headaches, and problems concentrating. The differential diagnosis of hypersensitivity pneumonitis should include other conditions that may cause interstitial lung disease (ILD).
Complete avoidance of exposure to the offending antigen is usually necessary to prevent progressive pulmonary damage. Although patients with the acute form of hypersensitivity pneumonitis respond well to avoidance and corticosteroids, patients with chronic exposure have less return of pulmonary function, most likely because of irreversible structural damage. Early diagnosis, along with identification and subsequent avoidance of the offending antigen, is therefore critical to effective management.
Hypersensitivity pneumonitis should be considered in patients with intermittent pulmonary and systemic symptoms and those with progressive unexplained pulmonary symptoms and ILD. A thorough history looking for a temporal relationship between onset of symptoms and exposures in the home, at work, or, as in this patient, through a hobby, may expose the cause of the “nagging” symptoms. Mr. W’s cough, dyspnea, and infiltrates on chest x-ray resolved, and his pulmonary function normalized after he was placed on an extended course of prednisone. While he was undergoing treatment, the barn was cleaned up, and the pigeons were evicted.