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• W3167029861 abstract "We thank Muthu and Agarwal1Muthu V. Agarwal R. Thoracic conidiobolomycosis: invasive or allergic?.J Allergy Clin Immunol Pract. 2021; 9: 2544-2545Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar for their interest in our report.2Yeoh DK, Saunders T, Butters C, Burgner D, Bryant PA, Cain TM, et al. Refractory thoracic conidiobolomycosis treated with mepolizumab immunotherapy. J Allergy Clin Immunol Pract 2021;9:2527-30.Google Scholar In our view, the report illustrates the blurred boundaries between infection and allergic responses to fungal pathogens and a potential role for adjunctive targeted immunotherapy in the multimodal management of complicated cases refractory to conventional approaches. Muthu and Agarwal question whether the primary pathologic process was an allergic reaction with bronchocentric granulomatosis rather than invasive fungal infection. In our patient, baseline computerized tomography imaging of the chest showed a mediastinal mass encasing the pulmonary vessels and causing extrinsic compression of the right main bronchus (Figure 1). The location and scale of the lesion can also be appreciated from the initial fluorodeoxyglucose positron emission tomography/magnetic resonance imaging panel in our report. Fungal hyphae with surrounding eosinophilic inflammatory material (Splendore-Hoeppli phenomena) were apparent on histopathological examination of a biopsy sample, and Conidiobolus incongruous was identified by culture. Fluid collected at the same time by bronchoalveolar lavage was culture negative. These features match previously reported cases of invasive mediastinal conidiobolomycosis.3Khatami A. Outhred A.C. Britton P.N. Huguon E. Lord D.J. Wong M. et al.Mediastinal mass in a healthy adolescent at The Children's Hospital at Westmead, Australia.Thorax. 2015; 70: 194-197Crossref PubMed Scopus (5) Google Scholar,4Vilela R. Mendoza L. Human pathogenic entomophthorales.Clin Microbiol Rev. 2018; 31: e00014-e00018Crossref PubMed Scopus (27) Google Scholar Muthu and Agarwal also highlight that glucocorticoids may be detrimental in the setting of invasive fungal infection. Corticosteroid use is indeed associated with increased susceptibility to fungal and other infections.5Lionakis M.S. Kontoyiannis D.P. Glucocorticoids and invasive fungal infections.Lancet. 2003; 362: 1828-1838Abstract Full Text Full Text PDF PubMed Scopus (400) Google Scholar However, there are a myriad of examples for the use of corticosteroids in an attempt to control a disproportionate and dangerous inflammatory response to invasive infection, including with fungi. Steroids are routinely used for Pneumocystis jiroveci pneumonia in patients with HIV6National Institutes of Health-University of California Expert Panel for Corticosteroids as Adjunctive Therapy for Pneumocystis PneumoniaConsensus statement on the use of corticosteroids as adjunctive therapy for pneumocystis pneumonia in the acquired immunodeficiency syndrome.N Engl J Med. 1990; 323: 1500-1504Crossref PubMed Scopus (324) Google Scholar and for cryptococcal meningitis complicated by immune reconstitution inflammatory syndrome.7Perfect J.R. Dismukes W.E. Dromer F. Goldman D.L. Graybill J.R. Hamill R.J. et al.Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America.Clin Infect Dis. 2010; 50: 291-322Crossref PubMed Scopus (1574) Google Scholar For conidiobolomycosis specifically, proliferation of Th2 lymphocyte subsets during invasive infection is well described and may be a pathogen-directed survival mechanism.4Vilela R. Mendoza L. Human pathogenic entomophthorales.Clin Microbiol Rev. 2018; 31: e00014-e00018Crossref PubMed Scopus (27) Google Scholar In a previous case of an adolescent with disseminated conidiobolomycosis, also associated with characteristic histopathological eosinophilic inflammation, clinical and radiological response occurred after administration of corticosteroids.3Khatami A. Outhred A.C. Britton P.N. Huguon E. Lord D.J. Wong M. et al.Mediastinal mass in a healthy adolescent at The Children's Hospital at Westmead, Australia.Thorax. 2015; 70: 194-197Crossref PubMed Scopus (5) Google Scholar In our report, we postulated that the benefits of corticosteroid therapy were counterbalanced by suppression of Th1, Th17, and innate immune responses, preventing clearance of the fungal infection. Cure coincided with initiation of more selective immunotherapy (mepolizumab) and gradual withdrawal of steroid therapy. A recently reported case of dupilimumab immunotherapy in the successful treatment of a child with refractory disseminated coccidioidomycosis adds further weight to our position that targeted immunotherapy may be beneficial in selected cases of invasive fungal infection.8Tsai M. Thauland T.J. Huang A.Y. Bun C. Fitzwater S. Krogstad P. et al.Disseminated coccidioidomycosis treated with interferon-γ and dupilumab.N Engl J Med. 2020; 382: 2337-2343Crossref PubMed Scopus (9) Google Scholar Thoracic conidiobolomycosis: Invasive or allergic?The Journal of Allergy and Clinical Immunology: In PracticeVol. 9Issue 6PreviewYeoh et al1 describe a challenging case of invasive conidiobolomycosis managed with mepolizumab. However, the index case described by the authors appears to be an allergic inflammatory response to Conidiobolus. A Th2 response to the fungi (elevated eosinophils and total IgE), histopathology showing eosinophil-rich inflammation, a prolonged course lasting for nearly a year, and a good response to glucocorticoids and mepolizumab suggest an allergic inflammation. Also, a lack of progression of invasive infection despite high-dose glucocorticoids and mepolizumab therapy implies otherwise. Full-Text PDF" @default.
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• W3167029861 title "Reply to “Thoracic conidiobolomycosis: Invasive or allergic?”" @default.
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