In a prospective cohort study of 70 consecutive, asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected adults, splenomegaly was found by physical examination in 23% of patients and by ultrasound in 66%. Patients with concomitant liver disease had a higher prevalence of splenomegaly (RR 1.84; P<.001). During a 1-year follow-up of 66 patients, splenomegaly at enrollment was not predictive of any clinical event, and splenomegaly was not associated with a higher risk of developing AIDS during a median follow-up of 6.1 year

Furrer, Hansjakob

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CID 2000;30 (June) Brief Reports 943vivo and also the fragility of the organism during processingin the laboratory.This is the first case report of disseminated S. vasiformisinfection with endocardial and myocardial involvement con-firmed by postmortem examination.Tom Solano,1 Bridget Atkins,2 Evanthia Tambosis,2Stephen Mann,3 and Thomas Gottlieb2Departments of 1Intensive Care, 2Infectious Diseasesand Microbiology, and 3Anatomical Pathology, Concord Hospital,Sydney, AustraliaReferences1. Holland J. Emerging zygomycoses of humans: Saksenaea vasiformis and Apo-physomyces elegans. Curr Top Med Mycol 1997;8:27–34.2. Ellis DH, Kaminski GW. Laboratory identification of Saksenaea vasiformis:a rare cause of zygomycosis in Australia. Sabouraudia 1985;23:137–40.3. Wilson M, Robson J, Pyke CM, McCormack JG. Saksenaea vasiformis breastabscess related to a gardening injury. Aust N Z J Med 1998;28:845–6.4. Torell J, Cooper BH, Helgeson NG. Disseminated Saksenaea vasiformis in-fection. Am J Clin Pathol 1981;76:116–21.5. Hay RJ, Campbell CK, Marshall WM, Rees BI, Pincott J. Disseminatedzygomycosis (mucormycosis) caused by Saksenaea vasiformis. J Infect 1983;7:162–5.Prevalence and Clinical Significance of Splenomegalyin Asymptomatic Human Immunodeficiency VirusType 1–Infected AdultsIn a prospective cohort study of 70 consecutive, asymp-tomatic human immunodeficiency virus type 1 (HIV-1)–infected adults, splenomegaly was found by physicalexamination in 23% of patients and by ultrasound in 66%.Patients with concomitant liver disease had a higher prev-alence of splenomegaly (RR 1.84; ). During a 1-P ! .001year follow-up of 66 patients, splenomegaly at enrollmentwas not predictive of any clinical event, and splenomegalywas not associated with a higher risk of developing AIDSduring a median follow-up of 6.1 years.Splenomegaly is a frequent finding among HIV-infectedadults [1, 2]. It has been found in up to 70% in a postmortemstudy [3]. However, little is known about the prevalence andclinical significance of this finding in asymptomatic patients.Previous studies have often been biased by referral and includedpatients in different stages of HIV infection [1, 4–6]. Therefore,we conducted a prospective observational study among asymp-tomatic HIV-1–infected outpatients.Our outpatient clinic is one of the 7 centers of the Swiss HIVCohort Study (SHCS). Within this community-based cohortstudy, HIV-infected individuals aged >16 years are followed at6-month intervals according to standardized criteria that havebeen described elsewhere [7].Patients were eligible for the present study if they were inCenters for Disease Control and Prevention (CDC) stage A [8]or if they had thrombocytopenia as the only HIV-associatedclinical manifestation. During a 4-month period in 1993, allInformed consent was obtained from all patients.Grant support: This study was financed by the Swiss Federal Office ofPublic Health (3600.010.1).Reprints or correspondence: Dr. H. Furrer, Division of Infectious Dis-eases, University Hospital, Inselspital PKT2 B, CH-3010 Bern, Switzerland(hansjakob.furrer@insel.ch).Clinical Infectious Diseases 2000;30:943–5q 2000 by the Infectious Diseases Society of America. All rights reserved.1058-4838/2000/3006-0022$03.00consecutive patients in CDC stage A underwent ultrasono-graphic evaluation of spleen size. Sonography was performedonly once. Seventy-six patients were eligible, of which 70 wereanalyzed (5 did not consent to the examination, and 1 patienthad had a splenectomy).Patients underwent physical examination by their physicians(who were aware of the study) and underwent ultrasonographythe same day. Sonography was always done by the same ex-aminer, who was not aware of the results of the clinical ex-amination. Clinical splenomegaly was present if the spleen waspalpable. Splenomegaly was defined by ultrasound as a spleenwith a long axis >120 mm [9]. Sociodemographic data andlaboratory values were extracted from the SHCS database andfrom patients’ charts. Clinical events were recorded prospec-tively for 1 year after the examination to evaluate the clinicalimportance of splenomegaly.Of the 70 patients in our cohort, 50 (71%) were male and 20were female; the median age was 31 years (range, 21–51 years).With respect to the mode of HIV-1 transmission, 26 patientswere men who have sex with men, 22 were heterosexual, and20 were injection drug users; 2 were infected by other modesof transmission. Peripheral lymphadenopathy was found in 40patients (58%). The median CD4 cell count was 417 cells/mL(range, 35–890 cells/mL). Seven patients (10%) had plateletcounts cells/L. Twenty-nine patients (41%) had liver9! 125 3 10disease, defined as positive hepatitis B surface antigen, positivehepatitis C serology, or alanine aminotransferase (ALT) levelsabove the upper normal limit; 24 (83%) of those 29 had positiveserology for hepatitis C.Statistical analyses included single table analysis, unpaired ttest and univariate regression analysis, Kaplan-Meier estimates,and Cox’s regression analysis; all of these were performed usingEpi Info 6 (CDC; Atlanta, GA) and Stata 6 software (Stata,College Station, TX).Splenomegaly was found in 14 patients (23%) by clinicalexamination and in 46 (66%) by ultrasound examination (figure1). Median spleen size was 125 mm (range, 92–197 mm). In 2of the 14 patients with clinical splenomegaly, this finding wasnot confirmed by ultrasound. An enlarged spleen was suspected944 Brief Reports CID 2000;30 (June)Figure 1. Histogram of long spleen axis (spleen length) measuredby ultrasound in 70 consecutive patients who were infected with HIVbut were asymptomatic.Figure 2. Box plot of measurements of the long axis of the spleenin patients without (left) and with (right) palpable spleen. Horizontallines indicate the 25th, 50th (median), and 75 percentiles; vertical brack-ets indicate the 10th and 90th percentiles, dots (v) indicate values belowthe 10th or above the 90th percentiles.clinically only in 12 (26%) of 46 patients with splenomegaly byusing ultrasound.Spleen size in patients without palpable spleens was signifi-cantly smaller than that in patients with palpable spleens (meanspleen , mm vs. mm;length 5 SD 120 5 13 140 5 25 P =). A box plot of the spleen size for the two groups is shown.001in figure 2.The prevalence of splenomegaly was higher in patients withliver disease (90%) than in those without it (48%; RR, 1.84;95% CI, 1.3–2.6; ). Among patients with a positiveP ! .001serology for hepatitis C, splenomegaly was found in 22 (92%)of 24. Presence of peripheral lymphadenopathy was not asso-ciated with splenomegaly (RR, 0.9; 95% CI, 0.6–1.3). Of the 7patients with thrombocytopenia, 4 had splenomegaly (RR,0.86; 95% CI, 0.4–1.7). There was no correlation between CD4count and spleen size ( ; ).r = .03 P = .8Four participants were lost to follow-up during the following12 months. Of the remaining 66 patients (94%), 14 had pro-gression of HIV-1 infection according to CDC criteria. Twelvepatients had a stage B event (candida stomatitis, 7 patients;multisegmental herpes zoster, 2; oral hairy leukoplakia, 2; andunexplained weight loss, 1). Two participants progressed tostage C (1 had recurrent episodes of bacterial pneumonia and1 had Pneumocystis carinii pneumonia).Patients with progression of HIV-infection during the 1-yearfollow-up did not have a higher prevalence of splenomegaly(RR, 1.1; 95% CI, 0.72–1.55; ), but had lower CD4 cellP = 1.0counts (median 325 cells/mL vs. 460 cells/mL, ) at studyP = .01entry.Sixty-six patients were followed further within the frameworkof the SHCS, and AIDS-defining events and death were re-corded. Data were assessed at the last follow-up visit at ourcenter. Median follow-up was 74 months (interquartile range,60–76 months). Seven patients died during the extended follow-up; 6 of those 7 had had splenomegaly at baseline. The causesof death were AIDS related (4 patients), suicide (1), narcoticdrug overdose (1), and subarachnoid hemorrhage (1). Fourteenpatients progressed to AIDS, of whom 12 had had spleno-megaly at baseline. One patient, whose spleen was 130 mm longat enrollment, had a non-Hodgkin’s lymphoma diagnosed 29months later.Kaplan-Meier estimates for AIDS-free survival did not showa significant difference between patients with or without sple-nomegaly at baseline (log rank test, ). In a Cox’s re-P = .12gression analysis that included baseline CD4 count, age, andsplenomegaly, the hazard ratio for patients with splenomegalyfor developing AIDS was not significantly different than it wasfor patients without splenomegaly at baseline (hazard ratio 3.0;95% CI, 0.66–13.5; ).P = .15In summary, we found splenomegaly (defined as a spleen witha long axis >120 mm) in two-thirds of consecutive asympto-matic HIV-1 infected patients in our study. The sociodemo-graphic characteristics of study participants were similar tothose of asymptomatic HIV-infected patients seen in our clinic,and to the entire asymptomatic SHCS population, as well asto the asymptomatic HIV-1–infected patients in Switzerland[10]. Thus, our study sample appeared to be representative ofasymptomatic HIV-1–infected patients in Switzerland and lessbiased by referral than were previous study populations thataddressed the frequency of splenomegaly in HIV-1–infectedadults.Our findings confirm the observations made by others [11],that clinical examination alone is a poorly sensitive, but rea-sonably specific method for detection of moderate splenomeg-CID 2000;30 (June) Brief Reports 945aly [12]. The prevalence of sonographic splenomegaly washigher in patients with liver disease, which was mostly due tochronic hepatitis C (HCV) infection in our population. ChronicHCV infection without HIV infection can lead to isolated sple-nomegaly in about one-fourth of the patients [13], whereas itwas a nearly universal feature in our patients who were co-infected with HIV-1 and HCV. In contrast, splenomegaly wasnot associated with peripheral lymphadenopathy or with gradeof immunodeficiency, as measured by CD4 cell counts. Throm-bocytopenia was not definitively associated with splenomegaly,but the number of patients with low platelet counts in our studywas too small to draw definitive conclusions.To date, the clinical importance of splenomegaly in asymp-tomatic HIV-1–infected individuals has remained unclear. Wewere able to follow 190% of the patients for at least 1 year.Splenomegaly was not associated with progression of HIV in-fection. Furthermore, during a 1-year follow-up period no pa-tient developed HIV-associated opportunistic infections or ma-lignancies or other non-HIV–related diseases known to betypically preceded by or associated with splenomegaly.A great concern when splenomegaly is found is that it mightbe non-Hodgkin’s lymphoma. One patient in our series devel-oped this disease 29 months after enrollment in the study. It isunlikely that the moderately enlarged spleen at enrollment wasan early manifestation of this malignant disease. On the basisof our data, it does not seem warranted to perform invasivestudies to rule out non-Hodgkin’s lymphoma in otherwiseasymptomatic HIV-infected persons with splenomegaly.During a median follow-up of 16 years, progression to AIDSwas not associated with splenomegaly at baseline. Plasma HIVRNA levels were not available at baseline. Therefore, we couldnot analyze an association of splenomegaly with the most im-portant prognostic marker [14] and could not correct for it inour Cox’s regression analysis. Our population was too smallto find even moderate associations between splenomegaly andprogression to AIDS. Furthermore, the follow-up was extendedinto a period where combination antiretroviral therapies be-came available and these agents had a major influence on mor-bidity and mortality in HIV-infected persons [15]. Therefore,we were not able to study the natural history of HIV infectionwith regard to splenomegaly in our cohort.Extensive evaluation, beyond a search for hepatitis C infec-tion, is not warranted in asymptomatic HIV-1–infected indi-viduals with an incidental finding of splenomegaly. Conversely,given the high prevalence of splenomegaly in asymptomaticHIV-infected adults, HIV infection should be part of the dif-ferential diagnosis of otherwise unexplained splenomegaly inadults with unknown serostatus of HIV infection.AcknowledgementsMembers of the Swiss HIV Cohort Study are as follows: M. Battegay(Co-Chairman of the Scientific Board), E. Bernasconi, Ph. Bu¨rgisser,M. Egger, P. Erb, W. Fierz, M. Flepp (Chairman of the Group Clinics),P. Francioli (President), H. Furrer, P. Grob, B. Hirschel (Chairman ofthe Scientific Board), B. Ledergerber, L. Matter (Chairman of theGroup Laboratories), A. Meynard, M. Opravil, F. Paccaud, G. Pan-taleo, L. Perrin, W. Pichler, J-C. Piffaretti, M. Rickenbach (Head ofthe Data Center), P. Sudre, J. Schupbach, A. Telenti, P. Vernazza, andR. Weber.Hansjakob Furrer, for the Swiss HIV Cohort StudyDivision of Infectious Diseases, University Hospital,Bern, SwitzerlandReferences1. Smith FJ, Mathieson JR, Cooperberg PL. Abdominal abnormalities in AIDS:detection at US in a large population. Radiology 1994;192:691–5.2. Luthen R, Niederau C. Sonographische befunde bei HIV-patienten. Bild-gebung 1995;62:271–80.3. Ansovini R, Barbolini G, Migaldi M, Botticelli L, De Rienzo B. Splenome-galia da AIDS e problematiche siderotiche connesse. Pathologica 1998;90:133–9.4. Radin R. HIV infection: analysis in 259 consecutive patients with abnormalabdominal CT findings. Radiology 1995;197:712–22.5. Erdozain JC, Gonzalez GM, Pintado V, et al. Ecografia abdominal en elpaciente con infecion por el virus de la inmunodeficiencia humana (VIH):utilidad diagnostica en la valoracion de la patologia medico-quirurgicaasociada. Ann Med Interna 1995;12:115–21.6. Zambetti EF, Haramati LB, Jenny-Avital ER, Borczuk AC. Detection andsignificance of splenomegaly on chest radiographs of HIV-infected out-patients. Clin Radiol 1999;54:34–7.7. Ledergerber B, von Overbeck J, Egger M, Lu¨thy R. The Swiss HIV cohortstudy: rationale, organization and selected baseline characteristics. SozPra¨ventivmed 1994;39:387–94.8. Centers for Disease Control and Prevention. 1993 revised classificationsystemfor HIV infection and expanded surveillance case definition for AIDSamong adolescents and adults. MMWR Morb Mortal Wkly Rep 1992;41(RR-17):1–19.9. Dardenne AN. The spleen. In: Cosgrove D, Meire H, Dewbury K, eds.Abdominal and general ultrasound. Edinburgh: Churchill Livingstone,1993:351–65.10. Bundesamt fu¨r Gesundheit, Gebhardt M. AIDS und HIV in der Schweiz:epidemiologische situation ende 1996. Bern, Bundesamt fu¨r Gesundheit,Epidemiologie und Infektionskrankheiten, 199711. Grover SA, Barkun AN, Sackett DL. Does this patient have splenomegaly?JAMA 1993;270:2218–21.12. Tamayo SG, Rickman LS, Mathews WC, et al. Examiner dependence onphysical diagnostic tests for the detection of splenomegaly: a prospectivestudy with multiple observers. J Gen Intern Med 1993;8:69–75.13. Meijer K, Haagsma EB, Kok T, Schirm J, Smid WM, van der MJ. Naturalhistory of hepatitis C in HIV-negative patients with congenital coagulationdisorders. J Hepatol 1999;31:400–6.14. Mellors JW, Munoz A, Giorgi JV, et al. Plasma viral load and CD41 lym-phocytes as prognostic markers of HIV-1 infection. Ann Intern Med1997;126:946–54.15. Egger M, Hirschel B, Francioli P, et al. Impact of new antiretroviral com-bination therapies in HIV infected patients in Switzerland: prospectivemulticentre study. BMJ 1997;315:1194–9.

Prevalence and Clinical Significance of Splenomegaly in Asymptomatic Human Immunodeficiency Virus Type 1-Infected Adults

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