Severe Prolonged Cough as Presenting Manifestation of <b><i>FIP1L1-PDGFRA</i></b>+ Chronic Eosinophilic Leukaemia: A Widely Ignored Association

Abstract

Chronic eosinophilic leukaemia associated with the FIP1L1-PDGFRA fusion gene (F/P+ CEL) is a rare cause of marked persistent hypereosinophilia, arising almost exclusively in male patients. Clinical presentations are heterogeneous with a higher incidence of eosinophil-mediated cardiomyopathy than in other hypereosinophilic syndrome variants. Features of chronic myeloproliferative disease are often present, including splenomegaly and elevated serum vitamin B₁₂ levels. The diagnosis is made by fluorescence in situ hybridization (FISH) showing the deletion of the CHIC2 locus and/or RT-PCR showing the FIP1L1-PDGFRA fusion transcript. Treatment with imatinib mesylate, a tyrosine kinase inhibitor, results in rapid and complete resolution of hypereosinophilia and associated symptoms, except for those related to sub-endocardial fibrosis that may be irreversible. We report the case of a male patient in whom isolated intractable cough remained the only clinical manifestation of F/P+ CEL for 4 years. Furthermore, eosinophil autofluorescence, an as yet unreported artefact in this setting, precluded the detection of the CHIC2 deletion and further delayed diagnosis, underlining that both FISH and RT-PCR should be performed when this disease is suspected.

Rare Case of Primary Hypereosinophilic Syndrome

“…There have been some cases where patients had minimal symptoms with little to no disease progression over several years. 5 First-line therapy for all patients with the FIP1L1-PDGFRA mutation is a tyrosine kinase inhibitor called imatinib mesylate and should be initiated immediately upon diagnosis of this subtype in order to prevent the progression of end-organ damage. If mutational analysis is not readily available, certain lab values can be used as surrogate markers for the presence of the mutation including markedly elevated serum Vitamin B12 levels (>2000 pg/mL), elevated serum tryptase level (>11.5 ng/mL), and/or splenomegaly.…”

Cough in hypereosinophilic syndrome: case report and literature review

“…It is important to clarify whether there is a rearrangement of the fusion gene by early fluorescence in situ hybridization (FISH) or nested RT-PCR testing [31] after eliminating secondary causes of eosinophilia. Because eosinophil autofluorescence may interfere with FISH, Roufosse et al [7] recommended that both FISH and RT-PCR should be performed when this disease is suspected. Imatinib was curative in HES patients with a positive PDGFRA fusion gene, and there was no relapse report.…”

“…We found 16 HES cases [7,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] with cough as the main or only symptom (Case 3-18, Table 2). The overall clinical information is summarized in Table 2.…”

“…HES patients may have eosinophilic infiltrates in the airways, and are often misdiagnosed as CVA, asthma, or other eosinophilic lung diseases. Chronic cough as presenting manifestation of platelet-derived growth factor receptor alpha (PDGFRA) + chronic eosinophilic leukaemia is being increasingly recognized [7]. Recently, we successfully treated 2 patients with HES, eosinophilic airway inflammation, and chronic cough, in whom one was PDGFRA +, but the other was not.…”

Uncommon causes of chronic cough associated with airway eosinophilia

“…Chronic cough associated with HES has been associated particularly with presence of the FIP1L1-PDGFRA fusion gene (11). Recently, we reported (10) 2 patients with HES, eosinophilic airway inflammation, bronchial hyperreactivity and chronic cough, among which one was PDGFRA+, but the second patient was PDGFRA− HES with features suggestive of myeloproliferative neoplasm (MHES) (12,13).…”