The pathogenesis of FHP is complex. An allergic mechanism is most likely, but the disease does not fit
neatly with one of the four types of allergic reaction. The presence of precipitating antibodies, immune complexes (suggestive of a type III reaction) and granuloma formation (more in keeping with a cell-mediated type IV reaction) have all been well documented. Lymphocytic infiltration of the alveoli is typical of the acute phase of the disease, but, with progression, fibrotic changes are seen on X-ray. Among studies that have followed up farmers with FHP, 30% of a group of cases in Orkney developed further acute attacks over 10 years [38] and 25% of a group of cases in the USA (with an average disease duration of 14 years) described shortness of breath when walking with people of their own age [39].
Despite a large number of epidemiological studies of this disease, it has been difficult to assess the extent of the problem. There is a lack of consistency in case ascertainment and prevalence estimates vary according to whether cases are defined by symptoms alone, by tests for precipitating antibodies in serum or by more sophisticated investigations, including chest X-ray and bronchoalveolar lavage. Prevalence surveys based solely on symptoms are likely to overestimate the problem, since the symptoms can be relatively non-specific and some misdiagnosis of toxic febrile reactions will occur. On the other hand, surveys based on modern imaging and biopsy or lavage specimens are likely to lead to underestimation, since milder cases are unlikely to be admitted to hospital for investigation or treatment.