Idiopathic pleuroparenchymal fibroelastosis in a never-smoker woman with a history of hypersensitivity pneumonitis

History of present illness

A never-smoker, 57-year-old woman complained of increasing shortness of breath and a persistent cough, producing only sporadically white-gray sputum, without hemoptysis and without a specific circadian rhythm. Moreover, she had a considerable weight loss exceeding 4 kg in the last 6 months in combination with a compromised quality of life (7/10 on a visual analogue scale) related to limited exercise tolerance. Manifest shortness of breath only occurred upon high-intensity physical exercise (Modified Medical Research Council [mMRC] dyspnea scale = 0) but was reported as progressively increased over the past 2 years. The patient denied chest pain when resting or taking deep breaths. She had no fever or other signs of infection, no symptoms in organs or systems other than the respiratory, and no recent hospital admissions.

Past medical history

The patient worked as a travel consultant in a regional travel office. Her familial history was negative for interstitial lung diseases (ILDs) or other chronic respiratory diseases. She had no prior exposition to either radiation or chemotherapy. Twenty years before the current presentation, the patient was diagnosed with hypersensitivity pneumonitis (HP), following manifestation of a dry persistent cough. In this context, exposure to avian dust was identified back then, as the patient held two budgerigars ( Melopsittacus undulatus ) in her flat. Corresponding precipitins against avian antigens turned positive, and an immunosuppressive treatment with corticosteroids had been initiated. The respiratory symptoms were largely resolved, and the patient had a good quality of life for many years. However, 2 years before the current presentation, the symptoms recurred. She denied recent long-distance travels or contact to dust or mold or continued exposure to birds. An antigen screening questionnaire revealed no ongoing exposure to known relevant pulmonary antigens. Chest computed tomography (CT) imaging findings were interpreted as a nonspecific ILD, whereas a bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies showed a marginal lymphocytosis and a nonspecific fibroelastic remodeling of the parabronchial parenchyma. Her pulmonologist prescribed a second course of prednisolone in suspicion of relapsed HP. However, this had no significant effects on either shortness of breath or cough, and she was also prescribed long-term oxygen therapy during exertion. Physical tolerance further deteriorated in the following months, when the patient was finally referred to the outpatient clinic for ILD for further differential diagnostics.

Physical examination and early clinical findings

At presentation, the patient had a body mass index (BMI) of 21.5 kg/m ² . A flat chest and a prominent suprasternal notch ( Fig. 17.1 ) were noticed. Fine crackles were absent upon auscultation as was no wheezing; percussion was damped over the upper lung lobes. She was able to climb two flights of stairs with the use of oxygen 2 L/min with mild shortness of breath (New York Heart Association class II), while the resting pulse oximetry values were sufficient without supplemental oxygen. The screening for fatigue (Fatigue Assessment Scale [FAS]), major depression (Patient Health Questionnaire-9 [PHQ]), and anxiety (Generalized Anxiety Disorder 2-item [GAD-2]) remained negative. The remainder of the physical examination and particularly the evaluation of the ankles, joints, and skin revealed no signs suggestive of rheumatological disease.

On chest radiograph, a pronounced bilateral reticulation pattern, predominating in the upper lobes, with no signs of pleural effusions became evident. A reduction in the anteroposterior chest diameter (platythorax) was also noticed.

Clinical course

The patient underwent pulmonary function tests (PFTs) that depicted a restrictive ventilation pattern with preserved Tiffeneau index, forced expiratory volume in 1 second (FEV ₁ ) of 1.52 L = 54% predicted, vital capacity. (VC) of 1.74 L = 51% predicted, total lung capacity (TLC) of 2.87 L = 53% predicted, and a compromised gas transfer factor (DLCO 4.49 mmol = 50% predicted). Of note, CO uptake after correction for the alveolar volume remained preserved with 1.8 mmol (112% predicted), indicating an additional feature of extrapulmonary restriction. The 6-minute walk test (6MWT) revealed a slight exercise-induced limited oxygenation ( Fig. 17.2 ).

Antinuclear antibody (ANA) screening showed a slight speckled staining pattern (titer 1:640). A subsequently performed extractable nuclear antigen screening (ENA-Screen) remained negative. Since the preexisting diagnosis of hypersensitivity pneumonitis with sensitization against birds, antigen-specific IgG against avian and mold antigens were tested ( Table 17.1 ). While IgG anti dove and budgerigar tested only marginally positive, IgG anti aspergillus antigens tested positive. Further laboratory workup depicted no signs of lymphocytic or neutrophilic inflammation. Rheuma factor and anticitrullinated antibodies testing showed no titer elevation.

TABLE 17.1 ■

Laboratory Testing of Precipitins Against Various Frequently Detected Pulmonary Antigens Driving Development of Hypersensitivity Pneumonitis

IgG CAP Antigen	Reference, mAg/L	Result, mAg/L	Interpretation
Pigeon	< 16	17.2	Borderline positive
Budgerigar	< 8	17.2	Weak positive
Saccharoplyspora rectivirgula	< 13	5.74	Negative
Aspergillus fumigatus	< 64	107	Intermediate positive
Penicillium chrysogenum	< 64	58.4	Negative
Aureobasidium pullulans	< 22	14.1	Negative
Cephalosporium acremonium	< 23	18.0	Negative
Fusarium proliferatum	< 46	14.4	Negative

HRCT of the chest was added for complementation of the initial diagnostic workup ( Fig. 17.3 and 17.4 ). This revealed marked bilateral apical pleural fibrosis with marked involvement of the pulmonary fissures, with intraalveolar fibrotic reticulations of the subpleural lung parenchyma and patchy consolidations with upper lobe predominance. Traction bronchiectasis was noted, predominating in the upper lobes, together with a diverticulum of the distal trachea. Meanwhile, lower lobes showed subtle pleural thickening and volume loss. Moreover, a posteroanterior gradient of interstitial change was noted together with a deviation of the trachea. Ground-glass opacities documented in former CT scans of the patients were absent.