title: Histoplasmosis complicating tumor necrosis factor-α blocker therapy: a retrospective analysis of 98 cases.
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.
authors: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors: Paschalis
authors: P
authors: Vergidis
authors: Division of Infectious Disease, Johns Hopkins Hospital, Baltimore, Maryland.
authors: Robin K
authors: RK
authors: Avery
authors: MiraVista Diagnostics and Mirabella Technologies, Indianapolis, Indiana.
authors: L Joseph
authors: LJ
authors: Wheat
authors: Division of Pediatric Gastroenterology, Hepatology and Nutrition, and Center for Innovation in Pediatric Practice, The Research Institute, Nationwide Children's Hospital, Columbus, Ohio.
authors: Jennifer L
authors: JL
authors: Dotson
authors: Department of Internal Medicine, University of Kansas School of Medicine, Wichita.
authors: Maha A
authors: MA
authors: Assi
authors: Department of Internal Medicine, University of Kansas School of Medicine, Wichita.
authors: Smyrna A
authors: SA
authors: Antoun
authors: Division of Infectious Diseases, University of Kansas Medical Center, Kansas City.
authors: Kassem A
authors: KA
authors: Hamoud
authors: Division of Infectious Disease, Wright State University Boonshoft School of Medicine, Dayton, Ohio.
authors: Steven D
authors: SD
authors: Burdette
authors: Division of Infectious Diseases, University of Nebraska Medical Center, Omaha.
authors: Alison G
authors: AG
authors: Freifeld
authors: Infectious Disease Associates of Kansas City, Missouri.
authors: David S
authors: DS
authors: McKinsey
authors: Department of Medicine, Meritus Medical Center, Hagerstown, Maryland.
authors: Mary E
authors: ME
authors: Money
authors: Division of Infectious Disease, University of Kentucky, Lexington.
authors: Thein
authors: T
authors: Myint
authors: Department of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison.
authors: David R
authors: DR
authors: Andes
authors: Long Island Infectious Disease Associates, Huntington, New York.
authors: Cynthia A
authors: CA
authors: Hoey
authors: Division of Infectious Disease, University of Michigan Medical School, Ann Arbor.
authors: Daniel A
authors: DA
authors: Kaul
authors: Division of Infectious Diseases, Kaiser Permanente, Fontana, California.
authors: Jana K
authors: JK
authors: Dickter
authors: Ellis Hospital Schenectady, New York.
authors: David E
authors: DE
authors: Liebers
authors: Division of Infectious Diseases, University of Iowa, Iowa City.
authors: Rachel A
authors: RA
authors: Miller
authors: Samaritan Infectious Disease, Corvallis, Oregon.
authors: William E
authors: WE
authors: Muth
authors: Division of Infectious Diseases, Southern Illinois University School of Medicine, Springfield.
authors: Vidhya
authors: V
authors: Prakash
authors: Indiana University Health Ball Memorial Hospital, Muncie.
authors: Frederick T
authors: FT
authors: Steiner
authors: Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota.
authors: Randall C
authors: RC
authors: Walker
authors: Pulmonary-Critical Care Medicine, Indiana University, Indianapolis.
authors: Chadi A
authors: CA
authors: Hage
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy; D002648:Child; D000068800:Etanercept / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006660:Histoplasmosis / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome; D000069285:Infliximab / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000935:Antifungal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept
keywords: adalimumab; etanercept; histoplasmosis; immune reconstitution syndrome; infliximab