This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gaughan, D. M. Articles by Oleske, J. M. Search for Related Content PubMed PubMed Citation Articles by Gaughan, D. M. Articles by Oleske, J. M. Related Collections Infectious Disease & Immunity Related AAP Red Book topics: Human Immunodeficiency Virus... Social Bookmarking                         What's this?

PEDIATRICS Vol. 109 No. 5 May 2002, pp. e74

ELECTRONIC ARTICLE

Osteonecrosis of the Hip (Legg-Calvé-Perthes Disease) in Human Immunodeficiency Virus-Infected Children

Denise M. Gaughan, MPH^*, Lynne M. Mofenson, MD, Michael D. Hughes, PhD^*, George R. Seage, III, DSc, MPH^*,, Gregory L. Ciupak, BS^||, James M. Oleske, MD, MPH^¶, for the Pediatric AIDS Clinical Trials Group Protocol 219 Team

^* Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts
National Institute of Child Health and Human Development, National Institutes of Health, Rockville, Maryland
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
^|| Frontier Science and Technology Research Foundation, Amherst, New York
^¶ Department of Pediatrics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey

--> Objective. Osteonecrosis of the hip has been reported in human immunodeficiency virus (HIV)-infected adults; whether this is related to HIV infection or its treatment is unknown. There has been 1 report of osteonecrosis among HIV-infected children. Specifically, avascular necrosis of the hip consistent with Legg-Calvé-Perthes disease (LCPD) was reported in 3 HIV-infected children with AIDS from Spain in 1992. We evaluated the prevalence and incidence of LCPD, the pediatric equivalent of adult osteonecrosis of the hip, in HIV-infected children participating in a prospective cohort study of long-term outcomes in HIV-infected and HIV-exposed children—Pediatric AIDS Clinical Trials Group (PACTG) protocol 219.

Methods. PACTG 219 enrolled 2014 HIV-infected and 849 HIV-exposed, uninfected children between April 1993 and September 2000. Children had periodic examinations with collection of clinical and laboratory data. The database was reviewed for reports of LCPD and other bone disorders. A prevalent case was defined as LCPD diagnosis preceding PACTG 219 enrollment and an incident case had to have occurred between enrollment and September 2000. A case-control study (matching on age, gender, and race/ethnicity, which are known to be associated with risk of LCPD and HIV infection status) was performed to investigate factors possibly associated with LCPD.

Results. Six cases of LCPD (4 prevalent cases reported at study entry; 2 diagnosed during 5837 person-years of follow-up) were observed; LCPD was seen only in children with perinatal HIV infection. LCPD prevalence was 199 per 100 000 compared with an estimated general pediatric population prevalence of 23 per 100 000. Based on age-adjusted general population rates, the expected number of prevalent cases at PACTG 219 study entry would have been 0.44; the age-adjusted LCPD prevalence rate ratio was 9.0 (95% confidence interval [CI]: 8.3–9.7) for HIV-infected children compared with the general population. LCPD incidence was 34 per 100 000 person-years (95% CI: 0.42–124) compared with the estimated general population incidence of 6 per 100 000 person-years (95% CI: 5–7). Based on age-adjusted general population rates, the expected incidence of LCPD in PACTG 219 would have been 0.42; the age-adjusted relative risk of LCPD in HIV-infected PACTG 219 children was 4.8 (95% CI: 0.56–10.4). No cases were observed in uninfected children during 1919 person-years of follow-up on PACTG 219; the age-adjusted expected number of cases was 0.09. Median onset age was 7 years; 67% were of Hispanic or black race/ethnicity and 33% were female. Four of the 6 LCPD cases had received antiretroviral therapy before diagnosis; treatment was primarily with nucleoside reverse transcriptase inhibitors, and 2 had received protease inhibitors. Three of the LCPD cases had corticosteroid exposure before the diagnosis, but only 1 child had systemic exposure and the remaining 2 had topical exposure exclusively. In the case-control study, antiretroviral and corticosteroid therapy, CD4 cell percentage, birth weight, height for age and gender percentile, and triglyceride levels were not significantly associated with LCPD. However, the case-control study had limited power to evaluate possible associations.

Conclusion. Similar to HIV-infected adults, children with perinatal HIV infection have an increased risk for osteonecrosis of the hip, and clinicians should be alert to this diagnosis when HIV-infected children present with limp or hip pain. Whether LCPD is attributable to HIV infection itself, HIV-associated complications that could predispose to hypercoagulopathy, HIV-related therapies, or to the growth abnormalities in HIV-infected children is unknown and deserves additional evaluation.

Key Words: osteonecrosis • Legg-Calvé-Perthes disease • perinatal human immunodeficiency virus infection

Abbreviations: HIV, human immunodeficiency virus • LCPD, Legg-Calvé-Perthes disease • AIDS, acquired immune deficiency syndrome • PACTG, Pediatric AIDS Clinical Trials Group • NRTI, nucleoside reverse transcriptase inhibitors • NNRTI, nonnucleoside reverse transcriptase inhibitors • PI, protease inhibitors • ZDV, zidovudine • DDI, didanosine, 3TC, lamivudine • D4T, stavudine

---

Received for publication Oct 19, 2001; Accepted Jan 9, 2002.

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?