A peripheral blood eosinophilia of greater than 1.0×109 /L is relatively unusual and offers a clue to the underlying diagnosis. In 2003, we established a specialist service to diagnose unexplained eosinophilia. To describe the causes of an eosinophilia in our service and the diagnostic algorithm we developed. Subjects were referred by physician colleagues across a range of specialties and undertook standard investigations following a semi-structured protocol. Data were extracted from a bespoke database. Three hundred and eighty two subjects were referred over a 17-year period. Average age was 54years and 183 (48%) of subjects were female, with 21 of 25 (84%) females in the idiopathic eosinophilic pneumonia group (p<0001), 22 of 30 (73%) females in the gastrointestinal disease group (p<.008), but 11 of 37 (30%) females in the eosinophilic granulomatosis with polyangiitis group (p<.04). A diagnosis was assigned after systematic evaluation using a pre-defined algorithm in 361 (94.5%) of cases. Fungal allergy (82 subjects: 21%), parasitic infection (61 subjects: 16%) and severe eosinophilic asthma (50 subjects: 13%) were the three commonest individual diagnoses. Hypereosinophilic syndrome (HES) disease including eosinophilic granulomatosis with polyangiitis (EGPA) accounted for 85 subjects (20%) of which seven subjects (2%) had myeloproliferative disease (M-HES). A high IgE was common, and 79 (91%) of subjects with complete data who had an IgE of ≥1000IU/L had fungal allergy or parasite infection. The serum tryptase was raised in 44 of 302 (14.5%) of individuals across all diagnostic groups, though none had mastocytosis. A diagnosis of an unexplained eosinophilia can usually be determined using as semi-structured algorithm. Parasitic infection and fungal allergy often with severe eosinophilic asthma were common causes, whereas HES, particularly myeloproliferative, disease was relatively rare.
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