Presentation and outcome of histoplasmosis in pediatric inflammatory bowel disease patients treated with antitumor necrosis factor alpha therapy: a case series.

Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
Inflammatory Bowel Diseases (Impact Factor: 5.48). 01/2011; 17(1):56-61. DOI: 10.1002/ibd.21378
Source: PubMed

ABSTRACT Antitumor necrosis factor alpha (aTNF) therapies are commonly used in the treatment of pediatric inflammatory bowel disease (IBD). However, inhibition of the TNF-alpha pathway predisposes to serious infections, including histoplasmosis, which is the most common invasive fungal infection in individuals on aTNF therapy and carries a high mortality rate when associated with delayed diagnosis. Few data exist on the frequency, presentation, and appropriate treatment of pediatric patients with histoplasmosis on aTNF therapy.
Following Institutional Review Board approval, cases were identified then reviewed with their primary gastroenterologist and infectious disease specialists.
Herein we describe histoplasmosis in five pediatric patients receiving aTNF therapy for IBD in an endemic area.
Histoplasmosis is an important complication of treatment with TNF-alpha neutralizing agents. Children with IBD treated with aTNF therapy who develop the infection may present with minimal pulmonary symptoms. While discontinuation of aTNF therapy is important initially, few data exist to determine when and how aTNF therapy can be reinstituted. Recognition of Histoplasma capsulatum is often delayed due to the overlap of symptoms with some of the extraintestinal manifestations of IBD and other more prevalent infectious complications.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Tumor necrosis factor alpha (TNFα) inhibitors are increasingly administered to children and adolescents with juvenile idiopathic arthritis (JIA) and pediatric inflammatory bowel disease (pIBD). Adult studies indicate that TNFα inhibitors lead to an increased risk of serious infections compared to other disease modifying anti-rheumatic drugs (DMARDs). We report herein a systematic literature review detailing the epidemiology and types of infections reported in children with JIA and pIBD treated with TNFα inhibitors. The most frequently reported infections were mild and characterized as viral in etiology. Severe bacterial and fungal infections also occurred, but were less common and possibly associated with intrinsic risk factors and concurrent immunosuppressive therapy. Few pediatric patients developed M. tuberculosis, likely due to effective screening. There were eight infectious fatalities in children treated with TNFα inhibitors. Overall, although rare, serious infections occur in immunocompromised children and adolescents with JIA and pIBD receiving TNFα inhibitors.
    Clinical Infectious Diseases 07/2013; 57(9). DOI:10.1093/cid/cit489 · 9.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context Tumor necrosis factor-alpha (TNF-α) inhibitor therapy plays a pivotal role in the management of moderate to severe inflammatory bowel disease. Because of the role of TNF-α in the host defenses, anti-TNF therapy has been associated with an increase the risks of granulomatous infections. Objective To report the first case of adalimumab-associated invasive histoplasmosis presenting as an acute hepatitis-like syndrome and febrile pneumonitis in a patient with Crohn's disease. Method Case report of a patient with progressive histoplasmosis confirmed by percutaneous fine needle aspiration biopsy lung and urine Histoplasma antigen. Results We present the case of a young man with CD who developed pneumonia and acute hepatitis-like features caused by Histoplasma capsulatum infection during adalimumab therapy. To the best of our knowledge, this acute hepatitis-like manifestation has never been reported as a presentation of the histoplasmosis in patients with Crohn's disease. Conclusions This case underscores the potential risk for serious infection that may arise in this setting and should alert clinicians to the need to consider the histoplasmosis diagnosis in patients presenting with acute hepatitis-like syndrome associated with prolonged febrile illness or pneumonitis during therapy with anti-TNF-α antibodies.
    Arquivos de gastroenterologia 03/2014; 51(1):73-6. DOI:10.1590/S0004-28032014000100015
  • [Show abstract] [Hide abstract]
    ABSTRACT: : The use of biological agents and immunomodulators for inflammatory bowel disease (IBD) has remarkably improved disease management in the current era but at the same time has increased the risk of infectious complications. Patients with IBD on corticosteroids, immunomodulators, and biological agents are considered immunocompromised and are at risk for opportunistic infections. These are infections caused by organisms that take advantage of a weakened immune system, and cause disease, when they ordinarily would cause mild illness or no disease in an immunocompetent host. Risk factors for opportunistic infections include malnutrition, older age, congenital immunodeficiency, HIV infection, chronic diseases, and use of corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha therapy. Apart from immunosuppressive medications and older age, there is only indirect evidence for above risk factors contributing directly to opportunistic infection risk in patients with IBD. Opportunistic infections in patients with IBD include viral infections (herpes viruses, human papillomavirus, influenza virus, and JC virus), bacterial infections (tuberculosis, nocardiosis, Clostridium difficile infection, pneumococcal infection, legionellosis, and listeriosis), fungal infections (histoplasmosis, cryptococcosis, Pneumocystis jirovecii infection, aspergillosis, and candidiasis), and parasite infections (Strongyloides stercoralis). Although these infections lead to high morbidity and mortality, only a minority of patients with IBD develop opportunistic infections. Currently, we lack a test to accurately predict patients at risk of opportunistic infection, and future research needs to focus on biomarkers or predictive models for risk stratification. Until such a test is developed, we need to screen, prevent, diagnose, and treat opportunistic infections in all patients with IBD in a timely manner.
    Inflammatory Bowel Diseases 09/2013; DOI:10.1097/MIB.0b013e3182a827d2 · 5.48 Impact Factor

Full-text (2 Sources)

Available from
Dec 19, 2014