Original contributionDistinct histopathology of acute onset or abrupt exacerbation of hypersensitivity pneumonitis
Introduction
Hypersensitivity pneumonitis (HSP) is a form of inflammatory lung disease, characterized by an inflammatory response involving the small airways, alveoli, and interstitium in response to an inhaled antigen, particularly from mold or birds. Clinically, it can be categorized into 3 forms, acute, subacute, and chronic, which are distinguished by duration of exposure to the antigen, interval between exposure to onset of symptoms, duration of symptoms, and clinical presentation [1], [2], [3], [4], [5], [6].
Subacute and chronic HSPs occur in response to repetitive exposure to inhaled antigen, presenting with an insidious onset of dyspnea lasting a few weeks to months with associated radiologic and pathologic evidence of interstitial lung disease. The pathologic features of subacute HSP have been well defined in the literature, consisting of a bronchiolocentric chronic inflammatory infiltrate with associated loosely formed histiocyte aggregates and/or giant cells [1], [2], [3]. Chronic HSP has been characterized by the same pathologic features as subacute HSP with the addition of a fibrosing interstitial pneumonitis, which has been correlated with a worse prognosis. Many patterns of fibrosis have been described, including prominent peribronchiolar fibrosis, usual interstitial pneumonitis–like pattern, and nonspecific interstitial pneumonitis–like fibrosis [7], [8], [9], [10], [11], [12], [13], [14].
Patients with acute HSP classically present with the abrupt onset of fever, chills, and cough of several hours' duration, typically peaking 6 to 23 hours after an acute exposure to large quantities of antigen. Symptoms resolve quickly after avoidance of further exposure to the inciting agent [15]. In the setting of repeated exposure, the diagnosis is usually made within a month after the initial onset. As a result of the rapid recovery, biopsies are rarely performed, and thus, there is little in the literature about the histopathology in acute HSP.
We recently encountered a patient with clinically confirmed HSP who presented with rapid onset of symptoms and had a lung biopsy that showed acute fibrinous and organizing pneumonia (AFOP) along with features of subacute HSP. Prompted by this case, we have analyzed 5 HSP cases (the index case and 4 additional cases) with acute onset of symptoms to identify the histopathologic features of acute HSP. We also studied 3 cases with clinically confirmed subacute or chronic HSP that showed similar histopathologic features and well-documented, abrupt exacerbation of symptoms.
A 55-year-old woman presented with a 1-week history of an acute onset of cough, shortness of breath, fever, chills, and fatigue shortly after cleaning her recently flooded basement and car. Computer tomography of the chest revealed multifocal consolidation in both peribronchovascular and subpleural distributions with extensive patchy ground glass opacities. The radiologic differential diagnosis included cryptogenic organizing pneumonia, aspiration pneumonia, or multifocal infectious pneumonia, but HSP was suspected based on the patient's clinical history. An HSP panel was performed and showed reactivity to 3 forms of Aspergillus fumigatus. A video-assisted thorascopic wedge biopsy was performed 11 days after the onset of symptoms. Microscopic evaluation revealed regions of AFOP along with features consistent with HSP (Fig. 1). She was treated with corticosteroids. There was also abatement of molds in her home and car. Her symptoms resolved completely.
Section snippets
Case selection
Sixty-four surgical or transbronchial biopsies with a possible clinical and/or pathologic diagnosis of HSP were identified in the pathology database of Massachusetts General Hospital and from the consultations of one of the authors (E.J.M.). Acquisition of the tissue specimens was approved by the Institutional Review Board of Massachusetts General Hospital and performed in accordance with Health Insurance Portability and Accountability Act regulations. Upon reviewing the histology and the
Clinical features
Table 1 summarizes the clinical features and exposure characteristics for the 5 cases of acute HSP and 3 cases of HSP with acute HSP-like histology. The average age was 45.9 years (range, 9-68 years). Seven patients were female, and 1 was male. Information on definite or possible sensitizing agents was available for 7 cases. There was exposure to mold in 6 patients and to birds in 1 patient. One patient had no identifiable antigenic exposure. Two patients (cases 3 and 4) also had chronic
Discussion
Literature on the pathologic features of acute HSP is scant. This is probably due to the rarity of biopsy in patients whose disease usually resolves quickly. Two of the few cases in the literature happen to appear in the same issue of Thorax in 1968 [16], [17]. One report [16] had 1 acute and 4 subacute or chronic cases. The other report [17] was a fatal case described as farmer's lung in a 17-year-old where the pathology had features of acute disease as well as granulomatous and organizing
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The authors equally contributed to this study.