Spotlight on the diagnosis of extrinsic allergic alveolitis (hypersensitivity pneumonitis)

Abstract

Repeated inhalative exposures to antigenic material from a variety of sources, mainly from moulds, thermophilic Actinomycetes, and avians, respectively, can induce immune responses with the clinical picture of extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis. Delays of years or even decades till the diagnosis is made are not uncommon; frequent misdiagnoses include allergic asthma, COPD, recurrent flue and other infections. We provide here the state of the art references, a detailed case description and recommend a current diagnostics schema.

Extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis is an immunologically mediated disease caused by sensitization to repeated inhalation of antigenic organic material derived from a variety of sources, such as mouldy hay, mouldy wood bark, bacterially contaminated metal working fluid or humidifier water (Figures 1, 2, 3 and 4), avian bloom proteins, but also chemicals such as isocyanates may cause this disorder [1-8], (Table 1). EAA is predominantly an occupational disease with most common antigens from thermophilic Actinomycetes species, various moulds and avian proteins. The prevalence of extrinsic allergic alveolitis varies depending on the climate, geographic conditions, occupational and industry factors, and is mostly is in the range of 0.1-3 [9-11] percent with farmer's lung or bird fancier’s lung as the prevailing one in most regions. Sensitized subjects may develop an acute, subacute (intermittent), and chronic progressive course depending on degree of sensitisation, intensity and duration of exposure.

Figure 1

Agents causing extrinsic allergic alveolitis, specific inhalative challenge testing, and bronchoalveolar lavage cells. A. Mouldy hay causing farmer’s lung disease in the subject shown in Figure 1D and Figure 4 B. Bronchoalveolar lavage with extensive neutrophilia present six hours post challenge in an subject with pigeon breeder’s lung. C. Water and sediment of a humidifier water of a printing plant (of the subject shown in Figure 3). Microscopic examinations demonstrated a variety of bacteria and moulds in this specimen. D. Occupational type specific inhalative challenge test with mouldy hay (Figure 1A).

Figure 2

Acute extrinsic allergic alveolitis after indicative challenge by mouldy hay. The figure shows a summary of the clinical diagnostic findings of the patient described as case 1. Clinical evidence: Several hours post challenge, fever, malaise, cough, associated with a restrictive ventilation pattern, and impaired gas exchange. The data shows lung function and other clinical findings in a time scale after the challenge [h]: f: Vital capacity VC [L], e: P_a,O2 arterial oxygen pressure [mmHg], d. Diffusion capacity/transfer coefficient for carbon monoxide (T_L,CO) factor [mL/min*kPa], c: Specific airway resistance (sRaw) measured by whole body plethysmography [kPa*s]; Further parameter shown are: b: Temperature profile gradation [°C], a. Blood leukocytes counts *1000/mm³].

Figure 3

Chest x-ray of a 33 year old worker of a printing plant, suffering from subacute humidifier lung disease. For details see text. There are patchy infiltrates predominantly in the lower and middle lung fields.

Figure 4

Presence of specific IgG antibodies in blood sera of 23 subjects suffering from isocyanate alveolitis. Note that all but five subjects show significant levels of such antibodies. The diisocyanates toluylene disocyanate (TDI), methylene diphenyl diisocyanate (MDI) and hexamethylene diisocyanate (HDI) bound to human serum albumin (HSA) were used for immune absorbent assay (CAP immunoanalysis) as described. For methodological details see Baur [4], Budnik et al. [18]. Specific IgG antibodies in blood sera from a patient suffering from humidifier lung due to exposure to contaminated humidifier water (Figure 1C). Shown is ELISA assay with anti IgG antibodies recognising dose specific reaction to various concentrations of workplace related humidifier water antigens. The negative and positive controls show lab intern positive and negative samples from patients with strong signal (positive reaction) and pool serum from healthy subjects without contact with humidifier aerosols (negative control, unspecific binding).

Table 1 Sources and major antigens of extrinsic allergic alveolitis (hypersensitivity pneumonitis)

EAA is associated with diffuse inflammation of lung parenchyma and airways in sensitized subjects including non-caseating interstitial granulomas and peribronchial mononuclear cell infiltration with giant cells. Although most affected subjects typically have high serum concentrations of circulating immunoglobulin G antibodies specific for the causative antigen(s), the diagnosis may be difficult as the symptoms are often non-specific, have typically a latency period of several hours, or may appear constitutional with malaise and weight loss; frequently they are gradually progressive over years, finally with persisting respiratory distress independent of the inducing exposure (Figures 1, 2, 3 and 4). Delays of years or even decades till the diagnosis is made are not uncommon, misdiagnoses include allergic asthma, COPD, recurrent flue and other infections. We recommend the following diagnostics schema for the disease pattern.