Kovacsovics, T.

Meylan, P.

Senn, L.

Tarr, P.E.

Serveur académique lausannois

EDITOR’S CORRESPONDENCERESEARCH LETTERSPeritoneal TuberculosisAfter Imatinib TherapyI matinib mesylate, a selective inhibitor of the BCR-ABL tyrosine kinase gene, is now a standard therapyinpatientswith chronicmyeloid leukemia (CML)andgastrointestinal stromal tumor (GIST). Recent studies haveshown that imatinib alters T-cell–mediated immune re-sponses,1-4 raising the possibility of opportunistic infec-tions associated with imatinib therapy. So far, few epide-miological data are available to support this hypothesis.We report herein a case of peritoneal tuberculosis (TB)following 4 months of imatinib therapy for CML.Report of a Case. A 37-year-old Swiss-born man was di-agnosed as having BCR-ABL–positive CML, and ima-tinib mesylate therapy was initiated (400 mg/d). Onemonth later, the imatinib dosage was reduced owing toan elevation in transaminase (3 times the upper limit ofnormal) and alkaline phosphatase (4 times the upper limitof normal) levels. Serologic test results for human im-munodeficiency virus and hepatitis A, B, andC viruswerenegative, and the abnormal liver test results were attrib-uted to imatinib therapy. Four months later, the ima-tinib mesylate dosage was again increased to 400 mg/d.One week later, the patient developed abdominal pain,anorexia, and nausea. Abdominal computed tomogra-phy revealed ascites, hepatosplenomegaly, and diffuseinfiltration of mesenteric fat. An analysis of ascitic fluidrevealed a white blood cell count of 1100/µL (50% lym-phocytes) (to convert to109/L,multiply by 0.001). Stan-dard bacterial cultures remained sterile. Findings fromaZiehl-Neelsen stain andmycobacterial culturewerenega-tive for organisms. Imatinib therapy was discontinued.Exploratory laparoscopy revealed extensive peritonitis,and peritoneal biopsy specimens demonstrated granu-lomatous inflammation, with a negative Ziehl-Neelsenstain result but a positive polymerase chain reaction re-sult for Mycobacterium tuberculosis complex and posi-tive cultures for M tuberculosis. The patient had no his-tory of travel to a TB endemic country, prior TB exposure,homelessness, or substance use. A chest radiograph showno abnormalities. The initiationof antituberculous therapywas followed by clinical improvement. Imatinib therapywas not restarted because of a concern for pharmaco-logical interaction with rifampin. After 6 months of an-tituberculous therapy, the patient underwent a hemo-poietic stemcell transplantationwithout further infectiouscomplications.At the time of TB diagnosis, 1 month after imatinibtherapy discontinuation, there was global lymphopenia(CD3, CD4, and CD8 cells: 190 [76% {percentage oftotal lymphocytes}], 155 [62%], and 39 [16%] cells/µL,respectively) and no evidence of blast transformation ofCML. After 2 months of antituberculous therapy, lym-phopenia was still present but less pronounced (CD3,CD4, and CD8 cells: 846 [92%], 619 [67%], and 222[24%] cells/µL, respectively).Comment. To our knowledge, this is the second reportof TB reactivation in association with imatinib therapy.The incidence of TB in Switzerland is low (10 per100 000 population per year), and the patient had no his-tory of TB exposure. Global lymphopenia might have fa-cilitated TB reactivation, but TB itself may induce tran-sient lymphopenia.5 In fact, lymphocyte counts rose tosubnormal levels after the initiation of antituberculoustherapy. The increased incidence of herpes zoster6 andprevious cases of pulmonary nocardiosis,7 pulmonaryTB,8and fungal pneumonia9 raise the possibility of opportu-nistic infections associated with imatinib therapy, butmore data are needed. It might be prudent to investigatethe presence of latent TB (by purified protein derivativeskin testing or interferon- release assay) before the ini-tiation of imatinib therapy.Correspondence: Dr Senn, Infectious Diseases Service,Department of Medicine, Centre Hospitalier Universi-taire Vaudois (CHUV) and University of Lausanne, RueduBugnon46,CH-1011Lausanne, Switzerland (Laurence.Senn@chuv.ch).Author Contributions: Study concept and design: Senn.Acquisition of data: Senn and Kovacsovics. Analysis andinterpretation of data: Senn, Tarr, and Meylan. Draftingof the manuscript: Senn. Critical revision of the manu-script for important intellectual content:Kovacsovics, Tarr,and Meylan. Study supervision: Kovacsovics, Tarr, andMeylan.Financial Disclosure: None reported.1. Cwynarski K, Laylor R, Macchiarulo E, et al. Imatinib inhibits the activationand proliferation of normal T lymphocytes in vitro. Leukemia. 2004;18(8):1332-1339.2. Dietz AB, Souan L, Knutson GJ, Bulur PA, Litzow MR, Vuk-Pavlovic S. Ima-tinib mesylate inhibits T-cell proliferation in vitro and delayed-type hyper-sensitivity in vivo. Blood. 2004;104(4):1094-1099.3. Gao H, Lee BN, Talpaz M, et al. Imatinib mesylate suppresses cytokine syn-thesis by activatedCD4T cells of patients with chronicmyelogenous leukemia.Leukemia. 2005;19(11):1905-1911.4. Sinai P, Berg RE, Haynie JM, Egorin MJ, Ilaria RL Jr, Forman J. Imatinib me-sylate inhibits antigen-specificmemoryCD8T cell responses in vivo. J Immunol.2007;178(4):2028-2037.Laurence Senn, MDTibor Kovacsovics, MDPhilip E. Tarr, MDPascal Meylan, MD(REPRINTED) ARCH INTERN MED/VOL 169 (NO. 3), FEB 9, 2009 WWW.ARCHINTERNMED.COM312©2009 American Medical Association. All rights reserved.5. Jones BE, Oo MM, Taikwel EK, et al. CD4 cell counts in human immunode-ficiency virus-negative patients with tuberculosis. Clin Infect Dis. 1997;24(5):988-991.6. Mattiuzzi GN, Cortes JE, Talpaz M, et al. Development of Varicella-Zostervirus infection in patients with chronic myelogenous leukemia treated withimatinib mesylate. Clin Cancer Res. 2003;9(3):976-980.7. Lin JT, LeeMY, Hsiao LT, et al. Pulmonary nocardiosis in a patient with CMLrelapse undergoing imatinib therapy after bone marrow transplantation. AnnHematol. 2004;83(7):444-446.8. Takashima M, Igaki N, Matsuda T, et al. Malignant gastrointestinal stromaltumor of the small intestine complicated with pulmonary tuberculosis dur-ing treatment with imatinib mesylate. Intern Med. 2005;44(2):114-119.9. Speletas M, Vyzantiadis TA, Kalala F, et al. Pneumonia caused by Candidakrusei and Candida glabrata in a patient with chronic myeloid leukemia re-ceiving imatinib mesylate treatment. Med Mycol. 2008;46(3):259-263.Underdiagnosis of Obesity in Adultsin US Outpatient SettingsO besity affects nearly 32%—more than 60 mil-lion—American adults.1 The obesity epidemicimposes an enormous cost on the nation’shealth2 and economy.3 Evidence-based clinical guide-lines recommend that treatment for obesity incorpo-rates a 2-step process: assessment andmanagement.4 Rou-tine screening and accurate diagnosis are among the firststeps leading to proper treatment. However, research onobesity screening and diagnosis in US outpatient set-tings is limited.Methods.Weexamined the rates of obesity screening anddiagnosis in a nationally representative sample of visitsby patients 18 years and older to private physician of-fices and hospital outpatient departments across theUnited States. Data were obtained from the 2005 Na-tional Ambulatory Medical Care Surveys conducted bythe National Center for Health Statistics (NCHS) (http://www.cdc.gov/nchs/about/major/ahcd/ahcd1.htm [ac-cessed July 23, 2008]). Patient, physician, and clinicalinformation is collected at each randomly selected visitand is recorded onNCHS standard patient record forms.Measurements of height and weight were captured forthe first time in 2005. Body mass index (BMI) (calcu-lated as weight in kilograms divided by height in meterssquared) and obesity were defined according to ac-cepted standards.4 Physician diagnoses were docu-mented using open-ended responses for (up to 3) visitdiagnoses, whichwere later coded byNCHS staff accord-ing to the International Classification of Diseases, NinthRevision, Clinical Modification and check boxes for a pre-specified list of current medical problems, one of whichwas obesity, regardless of visit diagnoses. The unit ofanalysiswas the patient visit. National estimateswere gen-erated using the SURVEYMEANS procedure (version9.1.3; SAS Institute, Cary, North Carolina) for the num-ber and proportion of patient visits, including 95% con-fidence intervals (CIs), by taking into account the sam-pling weights and multistage-stratified probabilitysampling designs of the surveys.Results. In 2005, American adults 18 years and oldermade an estimated total of 845 million outpatient vis-its (95% CI, 757 million–932 million). Measurementswere recorded during 42% (95% CI, 39%-46%) of totalvisits for height, 65% (95% CI, 62%-68%) for weight,and 41% (95% CI, 37%-45%) for both height andweight. Of the visits for preventive care only, the cor-responding rates were 52% (95% CI, 46%-58%), 75%(95% CI, 71%-80%), and 51% (95% CI, 46%-57%),respectively. Of the total visits in which BMI wasobtainable, 37% (95% CI, 35%-40%) were for patientswith a BMI of 30.0 or greater.Only 29% (95% CI, 25%-32%) of visits by patientswho were obese according to their BMI had a docu-mented diagnosis of obesity (Figure). The proportionof visits during which obesity was diagnosed was 19%(95% CI, 15%-22%) for patients whose BMI wasbetween 30.0 and 34.9, 32% (95% CI, 26%-38%) forthose whose BMI was between 35.0 and 39.9, and 50%(95% CI, 43%-57%) for those whose BMI was 40.0 orgreater. Obesity was diagnosed in less than 2% of visitsby patients whose BMI was less than 30.0. Owing tothe underreporting of clinical obesity, the agreementbetween obesity defined by BMI and that by physiciandiagnosis was low (=0.3).Comment. These results indicate that obesity is under-appreciated in clinical practice throughout the UnitedStates. Health care providers often fail to obtain neededbiophysical patient data and do not clinically identify obe-sity even when data that are obtained suggest this con-dition. Barriers to obesity screening and diagnosis arelikely multiple andmay involve system, health care pro-vider, and patient factors, including but not limited to,the lack of infrastructure to meet the needs of obese pa-tients, lack of time for preventive care, lack of health careprovider skills or financial incentives to address obe-sity, health care provider or patient concerns aboutweightstigma, and antifat bias by health care providers.5,6 Obe-sity is a complex chronic condition, and health care pro-viders have an important role in preventing, identify-ing, and managing obesity.4 Body mass index and waistcircumference are simple, validatedmeasures of body fatthat provide a reliable prediction of disease risk. Re-search aimed at determining the barriers to optimal healthcare for obese patients will guide the development of in-1001020305060709080400All VisitsWith BMI ≥30Class IObesityClass IIObesityClass IIIObesityPhysician-Diagnosed Obesity, %Figure. Association of physician-diagnosed obesity with clinically measuredbody mass index (BMI) (calculated as weight in kilograms divided by heightin meters squared). Error bars indicate 95% confidence intervals.(REPRINTED) ARCH INTERN MED/VOL 169 (NO. 3), FEB 9, 2009 WWW.ARCHINTERNMED.COM313©2009 American Medical Association. All rights reserved.

Peritoneal tuberculosis after imatinib therapy.

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Peritoneal tuberculosis after imatinib therapy.

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