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Abstract
ABSTRACT
BACKGROUND
There is increasing use of immunosuppressive drugs (ID) in sub-Saharan Africa as new indications emerge in this region, known for its high infection rates. Few data are available on infectious complications of ID in chronic rheumatic diseases (CRD) in Africa
OBJECTIVES
To describe the pattern of serious infections (SI) in CRD patients treated with ID in the Douala General Hospital, Cameroon
PATIENTS AND METHODS
After prior ethical clearance, we reviewed medical records of adult patients treated with ID for at least 6 months in the rheumatology unit of the Douala General Hospital from January 1999 to December 2009. The types of ID, dosage, and treatment duration as well as the indication were recorded. All cases of serious infections were identified. SI were defined as requiring hospitalization, intravenous antibiotic, withdrawal of the drugs or resulting in death.
RESULTS
Sixty-four patients (43 females and 21 male) were enrolled. Indications for use of ID included rheumatoid arthritis, systemic lupus erythematosus and dermatomyositis. ID used included Prednisone (used in all the patients), Methotrexate, Cyclophosphamide, and Azathioprine. Seventeen (26.6%) patients developed at least one SI: pulmonary tuberculosis (n=5), non-tuberculous pneumonia (n=6), febrile enteritis (n=5), and upper respiratory tract (n=2). Five patients presented more than one infection. Infections were increased for patients aged more than 60, cumulated dose of Prednisone more than 700 mg, combination of prednisone and Methotrexate.
CONCLUSION
Pulmonary infections are frequent in CRD patients treated by ID. Prospective studies are needed to better evaluate the burden and risk factors of this complication in sub-Saharan Africa
RÉSUMÉ
INTRODUCTION
Le risque d’infections sévères (IS) est augmenté sous traitement immunosuppresseur (TI), chez les patients souffrant de rhumatismes inflammatoires chroniques (RIC). OBJECTIF
Identifier et décrire les aspects cliniques des IS chez les patients atteints de RIC et traités par immunosuppresseurs. A l’Hôpital Général de Douala.
METHODOLOGIE
Etude transversale descriptive incluant tous les patients souffrant de RIC suivis à l’HGD de janvier 1999 à décembre 2009 et traités par TI pendant au moins 06 mois. Etaient recueillis et analysés : le type, la durée, la dose et l’indication du TI ; la survenue d’une IS. L’IS était définie comme infection nécessitant une hospitalisation, un traitement antibiotique par voie parentérale, l’arrêt du TI, et/ou responsable du décès du patient.
RESULTATS
64 patients (43 femmes et 21 hommes) ont été inclus. Les RIC recensés étaient : Polyarthrite rhumatoïde, lupus érythémateux systémique et dermatomyosite. Les TI utilisés comportaient : Prednisone (n=64) ; Méthotrexate (n=49) ; Cyclophosphamide (n=7) ; azathioprine (n= 3).
Treize (25,5%) patients ont développé au moins une IS ; les IS recensées étaient : tuberculose pulmonaire (n=7), pneumopathie non tuberculeuse (n=7), entérite fébrile (n=5), infections des voies respiratoires hautes (n=2). Les infections étaient plus fréquentes chez les sujets de plus de 60 ans, une dose cumulée de prednisone >700 mg, l’association méthotrexate et prednisone. Cinq patients ont développé plus d’une IS.
CONCLUSION
Les IS pulmonaires sont fréquentes chez les patients souffrant de RIC et traités par TI. La prévention et la prise en charge des complications liées à ces traitements sont essentielles. Des études prospectives sont nécessaires en Afrique où le contexte infectieux endémique pourrait induire une augmentation du risque infectieux lié aux TI.
Keywords
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References
- Zdanowicz MM. The pharmacology of immunosuppression. Am J Pharm Educ. 2009 Dec 17;73(8):144.
- Regazzi MB, Alessiani M, Rinaldi M. New strategies in immunosuppression.Transplant Proc. 2005 Jul-Aug;37(6):2675-8.
- Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23.
- Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. 1989 Nov-Dec;11(6):954-63.
- Prudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, et al Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med 2010; 363:2511-21.
- Ndongo S, Ka MM, Pouye A, Ka EF, Diallo S, Diop TM. Undesirable effects of methothrexate during treatment of rheumatoid arthritis. Dakar Med 2007; 52:37-40.
- Taylor HG, Stein CM. Systemic lupus erythematosus in Zimbabwe. Ann Rheum Dis 1986; 45:645-8.
- Dessein PH, Gledhill RF, Rossouw DS. Systemic lupus erythematosus in black South Africans. S Afr Med J. 1988 Oct 15;74(8):387-9.
- Toruner M, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Orenstein R, Sandborn WJ, and al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008; 134:929-36.
- Dixon WG, Abrahamowicz M, Beauchamp ME, Ray DW, Bernatsky S, Suissa S,Sylvestre MP. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis. Ann Rheum Dis. 2012 Jul;71(7):1128-33.
- slangul E, Le Jeunne C. [Role of corticosteroids in infectious disease].Presse Med. 2012 Apr;41(4):400-5.
- Dussauze H, Bourgault I, Doleris LM, Prinseau J, Baglin A, Hanslik T.[Systemic corticosteroid treatment and risk of infectious diseases]. Rev Med Interne. 2007 Dec;28(12):841-51.
- Glück T, Kiefmann B, Grohmann M, Falk W, Straub RH, Schölmerich J. Immune status and risk for infection in patients receiving chronic immunosuppressive therapy. J Rheumatol. 2005 Aug;32(8):1473-80.
- Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford). 2013 Jan;52(1):53-61.
- Kamen DL. How can we reduce the risk of serious infection for patients with systemic lupus erythematosus? Arthritis Res Ther. 2009;11(5):129.
- Ahuja J, Kanne JP. Thoracic infections in immunocompromised patients. Radiol Clin North Am. 2014 Jan;52(1):121-36.
- Marques ID, Azevedo LS, Pierrotti LC, Caires RA, Sato VA, Carmo LP, and al. Clinical features and outcomes of tuberculosis in kidney transplant recipients in Brazil: a report of the last decade. Clin Transplant. 2013 Mar-Apr;27(2):E169-76.
- Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM,and al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012 May;64(5):625-39.
- Lienhardt C, Fielding K, Hane AA, Niang A, Ndao CT, Karam F, et al. Evaluation of the prognostic value of IFN-gamma release assay and tuberculin skin test in household contacts of infectious tuberculosis cases in Senegal. PLoS One 2010; 5:e10508
References
Zdanowicz MM. The pharmacology of immunosuppression. Am J Pharm Educ. 2009 Dec 17;73(8):144.
Regazzi MB, Alessiani M, Rinaldi M. New strategies in immunosuppression.Transplant Proc. 2005 Jul-Aug;37(6):2675-8.
Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids—new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23.
Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis. 1989 Nov-Dec;11(6):954-63.
Prudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, et al Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med 2010; 363:2511-21.
Ndongo S, Ka MM, Pouye A, Ka EF, Diallo S, Diop TM. Undesirable effects of methothrexate during treatment of rheumatoid arthritis. Dakar Med 2007; 52:37-40.
Taylor HG, Stein CM. Systemic lupus erythematosus in Zimbabwe. Ann Rheum Dis 1986; 45:645-8.
Dessein PH, Gledhill RF, Rossouw DS. Systemic lupus erythematosus in black South Africans. S Afr Med J. 1988 Oct 15;74(8):387-9.
Toruner M, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Orenstein R, Sandborn WJ, and al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008; 134:929-36.
Dixon WG, Abrahamowicz M, Beauchamp ME, Ray DW, Bernatsky S, Suissa S,Sylvestre MP. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested case-control analysis. Ann Rheum Dis. 2012 Jul;71(7):1128-33.
slangul E, Le Jeunne C. [Role of corticosteroids in infectious disease].Presse Med. 2012 Apr;41(4):400-5.
Dussauze H, Bourgault I, Doleris LM, Prinseau J, Baglin A, Hanslik T.[Systemic corticosteroid treatment and risk of infectious diseases]. Rev Med Interne. 2007 Dec;28(12):841-51.
Glück T, Kiefmann B, Grohmann M, Falk W, Straub RH, Schölmerich J. Immune status and risk for infection in patients receiving chronic immunosuppressive therapy. J Rheumatol. 2005 Aug;32(8):1473-80.
Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford). 2013 Jan;52(1):53-61.
Kamen DL. How can we reduce the risk of serious infection for patients with systemic lupus erythematosus? Arthritis Res Ther. 2009;11(5):129.
Ahuja J, Kanne JP. Thoracic infections in immunocompromised patients. Radiol Clin North Am. 2014 Jan;52(1):121-36.
Marques ID, Azevedo LS, Pierrotti LC, Caires RA, Sato VA, Carmo LP, and al. Clinical features and outcomes of tuberculosis in kidney transplant recipients in Brazil: a report of the last decade. Clin Transplant. 2013 Mar-Apr;27(2):E169-76.
Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM,and al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012 May;64(5):625-39.
Lienhardt C, Fielding K, Hane AA, Niang A, Ndao CT, Karam F, et al. Evaluation of the prognostic value of IFN-gamma release assay and tuberculin skin test in household contacts of infectious tuberculosis cases in Senegal. PLoS One 2010; 5:e10508