Hypersensitivity pneumonitis (HP) is a diffuse granulomatous interstitial lung disease caused by inhalation of various antigenic organic particles [1]. HP is often difficult to diagnose because the clinical manifestations are nonspecific and the radiologic and histologic patterns can mimic those of other interstitial and small airway diseases [2]. HP traditionally has been classified as manifesting in three phases: acute, subacute, and chronic. Although this classification is helpful, patients often present with both subacute and chronic findings [1, 3]. Acute HP is characterized by abrupt onset of symptoms within a few hours after heavy antigen exposure in a previously sensitized patient. Subacute HP is caused by intermittent or continuous exposure to low doses of antigen. Chronic HP results from very low-level persistent or recurrent exposure to antigen and is differentiated from subacute HP by the presence of fibrosis [1, 3].

A high index of suspicion and meticulous acquisition of an environmental and occupational history are essential in making the diagnosis. In as many as 40% of histologically proven cases of HP, however, the offending agent is not identified [4, 5]. High-resolution CT plays an important role in the diagnosis of HP and frequently shows characteristic findings in patients with normal chest radiographic findings [4]. Early recognition of the disease and prevention of long-term antigen exposure are necessary to avoid progression to irreversible fibrosis [5]. The aim of this pictorial essay is to illustrate the spectrum of high-resolution CT and pathologic findings of HP.

Acute HP is characterized histologically by the presence of neutrophilic infiltration of the respiratory bronchioles and alveoli. A pattern of diffuse alveolar damage and temporally uniform, nonspecific, chronic interstitial pneumonitis may also be seen [1, 3]. Subacute HP is characterized histologically by the presence of cellular bronchiolitis, noncaseating granulomas, and bronchiolocentric interstitial pneumonitis with a predominance of lymphocytes (Fig. 1A, 1B). Areas of organizing pneumonia (bronchiolitis obliterans with organizing pneumonia) may be identified [6]. These findings, however, are not present in all cases. Furthermore, in some patients the predominant histologic pattern is nonspecific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP). Ohtani et al. [6] analyzed the histologic and clinical characteristics of chronic bird fancier's lung in 26 patients. The NSIP pattern was found in 13 patients, eight of them having fibrotic NSIP-like lesions; the UIP-like pattern in 11 patients; and organizing pneumonia (bronchiolitis obliterans with organizing pneumonia reaction) in two patients.

In the presence of a history of exposure and consistent clinical and radiologic findings, the diagnosis of HP can be confirmed by visualization of increased numbers of lymphocytes in bronchoalveolar lavage fluid and occasionally by findings at transbronchial biopsy. Surgical biopsy, however, is often needed for the definitive diagnosis of both subacute and chronic HP and for reliable differentiation of chronic HP from idiopathic interstitial pneumonia [3, 4].

The radiologic manifestations of acute HP are those of acute pulmonary edema. Because of the characteristic clinical manifestations and the rapid resolution of the symptoms, high-resolution CT is seldom performed in the evaluation of these patients [1, 7]. The characteristic high-resolution CT manifestations of subacute HP consist of patchy or diffuse bilateral ground-glass opacities, poorly defined small centrilobular nodules, and lobular areas of decreased attenuation and vascularity on inspiratory images and of air trapping on expiratory images (Figs. 2A, 2B and 3). The ground-glass opacities primarily reflect the presence of diffuse lymphocytic interstitial pneumonitis; minor degrees of organizing pneumonia, when present, also can contribute to this appearance (Fig. 4). The poorly defined centrilobular nodules may be caused by cellular bronchiolitis, the predominantly peribronchiolar distribution of interstitial pneumonitis (Fig. 1A, 1B), or focal areas of organizing pneumonia (Fig. 5). The lobular areas of decreased attenuation and air trapping are presumably caused by small-airway obstruction by cellular bronchiolitis or, less commonly, by constrictive bronchiolitis [3, 7].

Chronic HP is characterized on high-resolution CT by the presence of reticulation and traction bronchiectasis and bronchiolectasis due to fibrosis superimposed on findings of acute or subacute HP [7] (Fig. 6A, 6B, 6C, 6D). The reticulation in chronic HP can be patchy or random or have a predominantly subpleural and peribronchovascular distribution but typically tends to spare the lung bases [7, 8]. In a small percentage of cases, chronic HP results in subpleural honeycombing [3, 7] (Fig. 7A, 7B, 7C).

HP reaction can be seen as a manifestation of drug-induced lung disease (Fig. 3), inhalation of Mycobacterium avium-intracellulare complex organisms (e.g., hot tub lung) (Fig. 18A, 18B), or exposure to low-molecular-weight chemicals [1, 3] (Fig. 7A, 7B, 7C). The histopathologic and radiologic features usually are indistinguishable from those of HP secondary to immunologic reaction to inhaled organic antigens, except for hot tub lung, which characteristically at histologic examination has large numbers of granulomas, sometimes necrotizing, and a relatively minor interstitial inflammatory component.

A confident diagnosis of subacute HP on high-resolution CT is based on the presence of ground-glass opacities, poorly defined centrilobular nodules, and mosaic attenuation on inspiratory images and of air trapping on expiratory CT images. Chronic HP is characterized on high-resolution CT by the presence of reticulation due to fibrosis superimposed on findings of subacute HP. Histologically subacute HP is characterized by the presence of cellular bronchiolitis, noncaseating granulomas, and bronchiolocentric lymphocytic interstitial pneumonitis. High-resolution CT and pathologic features of chronic HP frequently overlap with those of NSIP and usual interstitial pneumonia. Awareness of the various manifestations of HP is important for early diagnosis and management to avoid progression to irreversible fibrosis.

Address correspondence to C. I. S. Silva ([email protected]).