Extrinsic allergic alveolitis J67.9

Inhalation of organic dusts in genetically dísposed individuals leads to an inflammatory hypersensitivity reaction of the lungs. Exogenous-allergic alveolitis can be a notifiable occupational disease if the disease is triggered by occupational substances. It must be compensated according to BK No. 4201 (exogenous-allergic alveolitis) or according to BK No. 1315 (isocyanate allergy) (see also occupational diseases of the lung).

Exogenous allergic alveolitis becomes a rare disease (orphan disease). Prevalence <50/100.000. Incidence in Germany at 2,5 new cases/100.000 inhabitants. Familial occurrence is known. The HLA antigens B8, DR3 and DRw6 are moderately elevated.

The cause of the disease is a mostly occupational, more rarely private exposure to various substances in the air we breathe. Described are > 300 triggering antigens. These are plant antigens (often mould fungus proteins e.g. Aspergillus fumigatus - see below). Aspergillose; Pflaenzenzensporen: e.g. spores by Cryptostroma corticalis - maple bark disease) - and bacterial proteins, animal proteins (e.g. excrements or animal fur dusts), but also chemicals such as isocyanides, anhydrides, phthalic anhydride, which are inhaled as dusts or as aerosols. Repellants such as pyrethrum extracts (diagnosis: pyrethrum pneumonitis) can also be causative.

When the substances are inhaled, a combined immune complex and cell-bound (type IV) immune reaction with the formation of precipitating antibodies of the Ig type (type III allergy) occurs, if the genetic disposition is appropriate. Chronic consequence is pulmonary fibrosis with cor pulmonale.

40-50 years. 15% of the sick are children. M:w=1:1; non-smokers are more likely to contract the disease than smokers.

Acute EEA: In case of massive intake of the allergen to which the affected person is sensitized - e.g. when moving moldy hay or cleaning a pigeon loft. Within 4-12 hours, the patient experiences shortness of breath, an irritating cough, a feeling of illness with headache and pain in the limbs, high fever and possibly chills. These acute symptoms subside after a few days without therapy. With avoidance of the allergen, complete cure possible,

Chronic EAA: In case of permanent or intermittent contact with small amounts of allergens (e.g. in the case of keepers of pet birds in the home), chronic symptoms develop with: dyspnea (85%), cough (82%), chills (56%), sputum (51%) as well as other unspecific complaints such as fatigue, loss of appetite, gradual decrease in performance, feeling of illness, fatigue, weight loss.

Different named symptoms depending on the allergen:

Animal proteins:

• Lung of bird keeper/bird breeder (most common): caused by various bird proteins from excrement. Bird proteins from excrements. Sources of antigen are budgies, canaries, turkeys. Dews, chickens are possible.
• Animal dealer's lung: various animal proteins (mostly excrement). Antigen source: rats, voles.
• Laboratory worker's lung: various animal proteins (mostly excrement, also animal fur dusts): Antigen source: various. Laboratory animals.

Microorganisms:

• Farmer's lung (second most common): causative agent is actinomycetes. Antigen source: moldy hay or silage.
• Humidifier lung: causative agents are actinomycetes (e.g. Thermoactinomyces vulgaris). Source of antigen: e.g. contaminated humidifiers, contaminated ornamental fountains, etc.
• Malt and paper workers' lung: mold spores. Antigen source: moldy barley or malt.
• Hot-tub-lung: Mycobacterium avium. Antigen source: hot-tub
• Salami washer's lung: Penicillum candidum.

Plant allergens:

• Plant allergens usually cause IgE-mediated allergy. Less commonly, wood dusts, cereal or soy, onion or potato dusts may trigger exogenous allergic alveolitis.

Chemical agents:

• Chemical worker's lung: isocyanates, anhydrides. Antigen source: polyurethane foam manufacturing, spray paints, two-component adhesives.
• Epoxy lung: phthalic anhydride. Antigen source: heated epoxy resins.

Drugs:

• Drugs: triggering agents are amiodarone, methotrexate (MTX lung), nitrofurantoin. Rarely, vaccines are causative.

Nodular and reticulonodular infiltrates, milky glass-like opacities of the parenchyma. Increasing fibrosis with chronic course

Leukocytosis, BSG elevated.

Detection of IgG antibodies (not IgE antibodies) against the causative antigen. Remark: important criterion in diagnostics (Raulf M et al. 2017) such antibodies can also occur in healthy exposed persons only. No blood eosinophilia!

Bronchoalveolar Lavage (BAL): highly sensitive. A normal BAl excludes the disease. Increased total number of lymphocytes (>30%), furthermore plasma cells and foam cells.

Imaging: in the acute or subacute stage possibly inconspicuous or spotty infiltrates. In the chronic stage evidence of infiltrates.

Lufu: Restrictive ventilation disorder with reduction of vital capacity and diffusion capacity.

Bronchoalveolar lavage (BAL): in acute alveolitis: neutrophil granulcyte infiltrations. In the chronic phase, CD8 lymphocytosis can be found.

Provocation test (controlled inhalation of the suspected antigen): is usually avoided.

Lung biopsy: only in unclear cases

Main and secondary criteria of exogenous-allergic alveolitis (n. Sennekamp et al.)

Main criteria

• Antigen exposure
• Exposure- and/or time-dependent symptoms
• Sclerophony (crackling rattles)
• Specific IgG antibodies in serum
• X-ray sign of the EAA, if necessary in the HRCT
• pO2 at rest and/or during exercise is reduced or DLCO is restricted.

Additional criteria

• Lymphocytes in the BAL
• Histological findings compatible with EAA
• Positive maternity test
• Positive inhalation exposure or provocation test

If all main criteria are met, the diagnosis is considered confirmed. If one of the main criteria is missing, it can be replaced by a secondary criterion.

The most important differential diagnosis is the differentiation from allergic bronchial asthma (asthmatics usually have a positive family history. The clinical symptoms of allergic asthma occur immediately (a few minutes) after antigen contact. The lungs are over-inflated; IgE-type antibodies are usually detectable.

The concordant occurrence of pulmonary changes and leukocytoclastic vasculitis has been described (see case report)

The most important therapeutic measure is the elimination of allergens. For some allergens, not only the occupational exposure should be avoided, but also a possible exposure in the private environment (e.g. with mould allergens). If the cause is found and can be avoided, the prognosis of acute exogenous allergic alveolitis is very good. As a rule, complete healing occurs.

If the cause is not identified or cannot be sufficiently avoided, pulmonary fibrosis with a cor pulmonale may occur in chronic cases.

Occupational effects: If a connection is found with occupational exposure, the responsible professional association must be informed in order to initiate a procedure with the appropriate occupational health and safety measures or, if these are not sufficient, to change profession. In case of an occupational disease according to Bk No.4201, the costs incurred are to be borne by the responsible employer's liability insurance association.

In the chronic form of EAA, the prognosis is worse than in the acute form, as the fibrotic changes in the lung tissue can persist even if the allergen is avoided. In severe cases, EAA can develop into progressive pulmonary fibrosis (see also Interstitial lung diseases/overview).

A 44-year-old man, pigeon breeder, presented with an itchy purpuric rash and paresthesias of the lower limbs, dyspnea on exertion, polymyalgia rheumatica and mixed polyarthralgias. Based on the clinical, paraclinical and laboratory investigations (electroneuromyography, plethysmography, computed tomography, musculocutaneous biopsy, recent laboratory tests and immunoassays), the main diagnoses of extrinsic allergic alveolitis and leukocytoclastic vasculitis were made. The patient was treated with corticosteroids, which resulted in a favorable outcome, but was exacerbated by the appearance of necrotic skin lesions when the patient discontinued corticosteroid therapy on his own initiative. After resuming corticosteroid therapy, the lesions and symptoms improved (Moldovan HR et al. (2019).

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5. Moldovan HR et al. (2019) A rare association of cutaneous leukocytoclastic angiitis (hypersensitivity vasculitis) and hypersensitivity pneumonia (extrinsic allergic alveolitis) in a pigeon breeder - case report and literature review. Rome J Morphol Embryol 60:325-331.

6. Raulf M et al. (2017) Reference values for the specific IgG determination against typical antigens of exogenous allergic alveolitis. Current data from a multi-center study. Allergi J Int 26: 73

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