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Hypersensitivity pneumonitis caused by a hidden antigen
Abstract
We present the case of a 28-year-old patient suffering from progressive exertional dyspnea for about 5 months. A previous atypical pneumonia had taken a prolonged course in spite of antibiotic therapy. Main symptoms were tachypnea, cyanosis and inspiratory crackles. The chest X-ray showed interstitial pneumonia, and lung function testing showed a severe hypoxemia and a reduced diffusing capacity. In the bronchoalvealar lavage, performed within the first 24 hours after exacerbation, an neutrophilic alveolitis was found. The CT thorax showed a diffuse groundglass shadow with partial fibrotic changes. Serologically, specific IgG against moulds were found, particularly against Aspergillus fumigatus. Although the patient showed the clinical findings of hypersensitivity pneumonitis and serological evidence sensitization against Aspergilli, there was no visible mould infestation in the patient's environment. The diagnosis of hypersensitivity pneumonitis, the hidden causative allergen, could be confirmed when measurements in the patient's environment revealed a hidden focus of Aspergillus fumigatus.
Bronchoalveolar lavage (BAL) was carried out before and after antigen inhalation in ten hypersensitivity pneumonitis (HP) and five control subjects. Control subjects did not show any significant variation in BAL cells after challenge with diluted pigeon serum. In HP patients, the total number of BAL cells increased from (41.5 +/- 16.8) X 10(4) cells/ml before challenge to (84.0 +/- 28.9) X 10(4) cells/ml after challenge. Of greater interest, the values of polymorphonuclear neutrophils in patients increased from 8.3 +/- 9.7 percent before challenge to 41.2 +/- 24.35 percent, 24 hours after antigen challenge (p - 0.0001). Another BAL, carried out a week later, recovered a persistently high number of cells, (74.67 +/- 33.36) X 10(4) cells/ml. However, the percentage of polymorphonuclear neutrophils and lymphocytes did not differ from the initial pre-challenge BAL. Our study demonstrates an immediate and transient neutrophil alveolitis after antigen inhalation in patients with acute hypersensitivity pneumonitis.
We report of three children with the suspected diagnosis of extrinsic allergic alveolitis. Two suffered from dyspnea on exertion and lived close to birds, and the third was first taken ill with a pneumonia. The subsequent deterioration with severely restricted ventilation during the convalescence lead to further examinations. All patients improved under Prednisolon. But in two cases the recovery was incomplete: 1. because of a non-compliant reduction of the steroid dosage and 2. due to renewed antigen exposure after normalisation of the lung function. Central medical task in the extrinsic allergic alveolitis are: Identification of the antigen, reliable instruction, short-term control of lung function, and compliance as well as avoidance of reexposure.
A 62-year-old woman was directed to our hospital by the diagnosis 'bronchiolitis obliterans'. Diffusing capacity was reduced, blood gas analysis showed an arterial hypoxemia and X-ray an interstitial infiltration. She was treated with an antibiotic and dismissed 21 days later. Six days after dismission the patient was directed to our hospital again with the same symptoms. At home she had spent long time at her couch beside plants with mouldy humus. Bronchoalveolar lavage showed lymphocytosis with a low CD4/CD8 ratio, the serum showed high IgG titers against mould fungi. In fungi traps there was much growth of aspergilli. After short time of treatment by steroids and allergen avoidance the patient was asymptomatic.
Clinical, pathologic, roentgenologic and immunologic findings in twenty-four cases of farmer's lung are presented. The findings are correlated with the three stages of the disease.
Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease of inhaled antigens. HP is not a uniform disease but rather a clinical complex syndrome characterized by varying intensities of responsiveness to different organic antigens. The main aetiological agents include thermophilic bacteria, fungi, animal proteins, and chemical compounds. A combination of host and environmental factors should be considered as a requisite to developing this disease. Although the antigens differ widely, the clinical syndromes that results are very similar. HP occurs mainly in non-smokers, and clinically it may be in acute, subacute, or chronic forms. The diagnosis of HP requires a constellation of clinic, radiographic, physiologic, pathologic, and immunologic criteria. HP is characterized by a diffuse and predominantly mononuclear cell inflammation, a partly granulomatous, immune disorder of alveolar regions that often involves the small airway. A strong evidence supports that delayed cell-mediated hypersensitivity mechanisms play a role in pathogenesis of HP. Studies performed on lung cells have demonstrated that cells bearing suppressor/cytotoxic phenotype characterize the lymphocytic alveolitis in patients with hypersensitivity pneumonitis. And also recently evidence has been provided indicating that a prominent role of T-helper 1 cell-mediated hypersensitivity with an imbalance in T-lymphocyte subsets, although the deposit of immune complex may participate in an acute form of the disease as well as in the early phase of the chronic form. Microsc. Res. Tech. 53:307–312, 2001. © 2001 Wiley-Liss, Inc.
Das Spektrum der Erkrankungen, die zu pulmonalen Komplikationen in Form einer respiratorischen Insuffizienz führen können,
ist groß und reicht von internistischen Krankheitsbildern wie Herz- oder Niereninsuffizienz über chirurgisch-orthopädische
Probleme wie Traumen und Operationsfolgen zu der großen Gruppe der zentralnervös bedingten und neuromuskulären Erkrankungen.
Bereits bei Diagnose dieser Erkrankungen sollte eine sorgfältige pneumologische Untersuchung erfolgen, die durch ein verlaufsbegleitendes
Monitoring ergänzt werden muss. Dieses Vorgehen stellt die Grundlage für eine adäquate Therapie einer sich entwickelnden respiratorischen
Insuffizienz dar, die neben der Behandlung der Grunderkrankung symptomatische Maßnahmen bis hin zur Durchführung der nicht-invasiven
und invasiven Beatmung umfassen muss.
Farmer's lung is rare in Australia whereas allergic alveolitis due to domestic fungal exposure ("domestic allergic alveolitis") is common. However there has been no systematic analysis of the fungi responsible for domestic allergic alveolitis in Australia. The aim of this study was to determine the sources and types of fungi that cause this type of alveolitis in Australia. Twelve subjects with recently diagnosed, biopsy proved, alveolitis thought on clinical grounds to be due to domestic fungal exposure were studied. The houses of all subjects were inspected, and fungal samples were taken. All lived in substandard inner city dwellings. Extensive wood decay was found in 10/12 while 4/12 also had obvious fungal growth on damp walls. Twelve fungal species were identified including Serpula lacrymans (8/12), Paecilomyces variottii (6/12), Aspergillus fumigatus (5/12), and Leucogyrophana pinastri (2/12). No single fungal group predominated. Nine of 12 patients showed positive precipitin results to one or more of the isolated fungi. Inhalation tests were done with extracts of Serpula lacrymans, Geotrichum candidum, and Aspergillus fumigatus in six of the patients and a positive late response to one or more of the fungi was observed in five of these. Relocation of the patients to a new dwelling resulted in improvement in each case.
Farmer's lung is a hypersensitivity reaction to fungal spores in mouldy hay, most commonly Micropolyspora faeni. The type of immunological reaction is debated but a high dose of antigen is necessary and the inflammation may result from activation of the alternative pathway of complement, linked to a type 3 response. Detection of serum precipitins to fungal antigens is used as a diagnostic aid but it is unclear why up to 18% of men with sufficient exposure to antigen and with the serum precipitins do not develop symptoms. Two Cornish men are described who had long term exposure to dusty hay but who developed symptoms of farmer's lung only after infection with Mycoplasma pneumoniae.
A 23-year-old woman patient became seriously ill with the typical signs and symptoms of allergic alveolitis and with deep hypoxemia during exercise. A broad spectrum of positive precipitating antibodies was found in the serum, mainly against Penicillium casei and Aureobasidium pullulans. Although she was intensively questioned on hobbies and on possible antigens at home and at work, it was only possible to trace an antigen source after a controlled antigen free period away from home in another environment and after a controlled reexposure experiment at home: it proved to be a patch of mould of 0.5 m2 on the bedroom wall. The filaments and the spores of the fungi of the mould were shown directly by microscope. Precipitating antibodies were also present against these fungi. After several antigen-free months (the patient moved into a dry and sunny new apartment) the threatening respiratory failure (severe hypoxemia during exercise) disappeared completely together with the clinical signs and symptoms. Thus, mould on bedroom walls may constitute a threat and should be considered in cases of allergic alveolitis of apparently unknown origin.
Clinical, pathologic, roentgenologic and immunologic findings in twenty-four cases of farmer's lung are presented. The findings are correlated with the three stages of the disease. Pathologically, farmer's lung is generally considered an interstitial pneumonitis with granuloma formation. Our study indicates a much greater variety of histopathologic changes than previously described. This includes interstitial pneumonitis without granuloma formation, organizing endobronchial exudate and the finding of foreign material in many biopsy specimens. This foreign body material may be of etiologic importance. Circulating antibodies can be demonstrated by the agar gel diffusion technic in patients with recent and active disease. This procedure may afford a simple diagnostic test for the confirmation of farmer's lung. The disease is reversible in the early stages. Progressive pulmonary fibrosis and emphysema can develop with repeated exposure and was the cause of death in four of the twenty-four patients. The only known cure is removal of the patient from his environment.