Paschalis Vergidis1, Robin K Avery2, L Joseph Wheat3, Jennifer L Dotson4, Maha A Assi5, Smyrna A Antoun5, Kassem A Hamoud6, Steven D Burdette7, Alison G Freifeld8, David S McKinsey9, Mary E Money10, Thein Myint11, David R Andes12, Cynthia A Hoey13, Daniel A Kaul14, Jana K Dickter15, David E Liebers16, Rachel A Miller17, William E Muth18, Vidhya Prakash19, Frederick T Steiner20, Randall C Walker21, Chadi A Hage22. 1. Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania. 2. Division of Infectious Disease, Johns Hopkins Hospital, Baltimore, Maryland. 3. MiraVista Diagnostics and Mirabella Technologies, Indianapolis, Indiana. 4. Division of Pediatric Gastroenterology, Hepatology and Nutrition, and Center for Innovation in Pediatric Practice, The Research Institute, Nationwide Children's Hospital, Columbus, Ohio. 5. Department of Internal Medicine, University of Kansas School of Medicine, Wichita. 6. Division of Infectious Diseases, University of Kansas Medical Center, Kansas City. 7. Division of Infectious Disease, Wright State University Boonshoft School of Medicine, Dayton, Ohio. 8. Division of Infectious Diseases, University of Nebraska Medical Center, Omaha. 9. Infectious Disease Associates of Kansas City, Missouri. 10. Department of Medicine, Meritus Medical Center, Hagerstown, Maryland. 11. Division of Infectious Disease, University of Kentucky, Lexington. 12. Department of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison. 13. Long Island Infectious Disease Associates, Huntington, New York. 14. Division of Infectious Disease, University of Michigan Medical School, Ann Arbor. 15. Division of Infectious Diseases, Kaiser Permanente, Fontana, California. 16. Ellis Hospital Schenectady, New York. 17. Division of Infectious Diseases, University of Iowa, Iowa City. 18. Samaritan Infectious Disease, Corvallis, Oregon. 19. Division of Infectious Diseases, Southern Illinois University School of Medicine, Springfield. 20. Indiana University Health Ball Memorial Hospital, Muncie. 21. Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota. 22. Pulmonary-Critical Care Medicine, Indiana University, Indianapolis.
Abstract
BACKGROUND: Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.
BACKGROUND:Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.
Authors: Jong-Hoon Lee; Nancy R Slifman; Sharon K Gershon; Evelyne T Edwards; William D Schwieterman; Jeffrey N Siegel; Robert P Wise; S Lori Brown; John N Udall; M Miles Braun Journal: Arthritis Rheum Date: 2002-10
Authors: Maha Assi; Stanley Martin; L Joseph Wheat; Chadi Hage; Alison Freifeld; Robin Avery; John W Baddley; Paschalis Vergidis; Rachel Miller; David Andes; Jo-Anne H Young; Kassem Hammoud; Shirish Huprikar; David McKinsey; Thein Myint; Julia Garcia-Diaz; Eden Esguerra; E J Kwak; Michele Morris; Kathleen M Mullane; Vidhya Prakash; Steven D Burdette; Mohammad Sandid; Jana Dickter; Darin Ostrander; Smyrna Abou Antoun; Daniel R Kaul Journal: Clin Infect Dis Date: 2013-09-17 Impact factor: 9.079
Authors: Chadi A Hage; Julie A Ribes; Nancy L Wengenack; Larry M Baddour; Maha Assi; David S McKinsey; Kassem Hammoud; Daisy Alapat; N Esther Babady; Michelle Parker; DeAnna Fuller; Aliya Noor; Thomas E Davis; Mark Rodgers; Patricia A Connolly; Boutros El Haddad; L Joseph Wheat Journal: Clin Infect Dis Date: 2011-08-02 Impact factor: 9.079
Authors: Sengwee Toh; Lingling Li; Leslie R Harrold; Elizabeth A Bayliss; Jeffrey R Curtis; Liyan Liu; Lang Chen; Carlos G Grijalva; Lisa J Herrinton Journal: Pharmacoepidemiol Drug Saf Date: 2012-03-13 Impact factor: 2.890
Authors: Karen L Wood; Chadi A Hage; Kenneth S Knox; Martin B Kleiman; Aruna Sannuti; Richard B Day; L Joseph Wheat; Homer L Twigg Journal: Am J Respir Crit Care Med Date: 2003-02-13 Impact factor: 21.405
Authors: Timothy C Olson; Tim Bongartz; Cynthia S Crowson; Glenn D Roberts; Robert Orenstein; Eric L Matteson Journal: BMC Infect Dis Date: 2011-05-23 Impact factor: 3.090
Authors: Adrián Sánchez-Montalvá; Fernando Salvador; Isabel Ruiz-Camps; Pere Barba; David Valcárcel; Elena Sulleiro; Enrique Sanz-García; Israel Molina Journal: Am J Trop Med Hyg Date: 2016-10-17 Impact factor: 2.345