John W. Moohr

Sickle cell disease as a cause of osteonecrosis of the femoral head.

BACKGROUND AND METHODS Osteonecrosis of the femoral head is an important complication of sickle cell disease. We studied 2590 patients who were over 5 years of age at entry and followed them for an average of 5.6 years. Patients were examined twice a year, and radiographs of the hips were taken at least twice: at study entry and approximately three years later. RESULTS At study entry, 9.8 percent of patients were found to have osteonecrosis of one or both femoral heads. On follow-up, patients with the hemoglobin SS genotype and alpha-thalassemia were at the greatest risk for osteonecrosis (age-adjusted incidence rate, 4.5 cases per 100 patient-years, as compared with 2.4 in patients with the hemoglobin SS genotype without alpha-thalassemia and 1.9 in those with the hemoglobin SC genotype). Although the rate of osteonecrosis in patients with the hemoglobin SC genotype did not differ significantly from that in patients with the hemoglobin SS genotype without alpha-thalassemia, osteonecrosis tended to develop in these patients later in life. Intermediate rates of osteonecrosis were observed among patients with the hemoglobin S-beta zero-thalassemia and the hemoglobin S-beta(+)-thalassemia genotypes (3.6 and 3.3 cases per 100 patient-years, respectively). Osteonecrosis was found in patients as young as five years old (1.8 cases per 100 patient-years for all genotypes). The frequency of painful crises and the hematocrit were positively associated with osteonecrosis. The mean corpuscular volume and serum aspartate aminotransferase level were negatively associated. Twenty-seven patients had hip arthroplasty during the study; 10 were under 25 years of age. Five of the 27 required reoperation 11 to 53 months after the initial operation. CONCLUSIONS Osteonecrosis of the femoral head is common in patients with sickle cell disease, with an incidence ranging from about 2 to 4.5 cases per 100 patient-years. Patients with the hemoglobin SS genotype and alpha-thalassemia and those with frequent painful crises are at highest risk. The overall prevalence is about 10 percent. The results of hip arthroplasty are poor.

Acyclovir-Resistant Varicella Zoster Virus Infection after Chronic Oral Acyclovir Therapy in Patients with the Acquired Immunodeficiency Syndrome (AIDS)

Abstract Four patients with human immunodeficiency virus (HIV) infection who received chronic oral acyclovir therapy for suppression of recurrent varicella zoster or herpes simplex virus infection ...

Osteonecrosis of the humeral head in sickle cell disease

The prevalence and incidence of osteonecrosis (ON) of the humeral head in sickle cell disease was determined by a study of 2524 patients who were entered into a prospective study and followed for an average of 5.6 years. At entry, 5.6% had roentgenographic evidence of ON in one or both shoulders. There was little difference in age-adjusted prevalence among genotypes, but there were striking differences in age-specific rates. Observed at ages ranging from five to 24 years, 3.25% of sickle cell anemia (S/S) patients, but only 1.1% of sickle cell disease (S/C) patients, had ON. No S/beta+ thalassemia patients younger than 25 years of age had ON on entry. The highest age-adjusted incidence rate was found in S/S patients with concomitant alpha-thalassemia (4.85 per hundred patient-years), followed by S/beta zero-thalassemia (4.84 per hundred patient-years), S/beta+ thalassemia (2.61 per hundred patient-years), S/S without alpha-thalassemia (2.54 per hundred patient-years), and S/C (1.66 per hundred patient-years). Only 20.9% of patients reported pain or had limited range of movement at the time of diagnosis. Sickle cell disease is a frequent cause of ON of the humeral head, especially in children and young adults.

Childhood leukemia presenting as a diaphyseal radiolucency.

A 41-month-old black child with a symtomatic diaphyseal destructive lesion of the femur, and a corresponding area of increased uptake on a technetium99m bone scan, had an upper respiratory tract infection. An open biopsy was performed because of an initial clinical diagnosis of osteomyelitis, histiocytosis X or a round cell sarcoma. The biopsy showed numerous blast cells compatible with acute lymphocytic leukemia. Acute leukemia should be included in the differential diagnosis of symptomatic diaphyseal destructive lesions in children. A peripheral blood smear should be carefully interpreted prior to any other invasive diagnostic tests.

THROMBOCYTOPENIA IN CHILDREN WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION

Thrombocytopenia was found in five (12.5%)of 40 children with evidence of HIV infection, Age of the patients at time of diagnosis of thrombocytopenia ranged from two months to two years; platelet counts were less than 50,000/cmm in all and less than 10,000/cmm in three. Two of five patients had thrombocytopenia at the time of diagnosis of HIV infection while three others developed it during the course of their illness. Three of five patients manifested bleeding (petechiae, echymosis, and epistaxis). Bone marrow examination revealed increased numbers of megakaryocytes in all. Increased levels of platelet associated antibody (PAIgG) were found in 2/2 patients tested. Four patients received intravenous gamma globulin (IVGG) in a dose of 2-3 g/kg over a 3-5 day period. Only one patient had a significant increase in platelet count (from 32,000 to 350,000 /cmm)two days after a five day course of IVGG therapy, but the count returned to 40,000/cmm in two weeks. Two patients whose platelet count did not improve after IVGG received prednisone and in one there was a moderate but transient increase in the platelet count. We conclude that immune thrombocytopenia occurs in children with HIV infection and that the rate of response to IVGG appears to be lower than that reported in HIV associated ITP in adults or non-HIV associated ITP in children.

199 CARDIAC STATUS OF CHILDREN WITH SICKLE CELL ANEMIA (SS)

Echocardiograms (E) were obtained from 44 children with SS and from 54 normal Blacks (Nl). Equations for predicting the normal values (PN) for 12 echo parameters were derived (PN = A . BSAb . HRc ± K), and the observed values from SS then expressed as standard deviation from normal (O PN). Increased cardiac output, LVEDD, LVESD, wall thickness, LAmax and Ao diameter were observed in SS (p < 0.001); however, the functional parameters %MAS, VCF and PEP/ET did not differ from Nl. Density function curves (DFC), derived by discriminant regression analysis using 7 echo parameters were obtained with equation: Ydv = K1 OPN1 + K2 OPN2 + Kn OPNn ± X, where Ydv = discriminating value and K, X = constants. There was clear separation of the DFC of SS and Nl. Eleven children with SS underwent hypertransfusion therapy (HT) for 3/12-3 yrs (packed RBC q 2-3 weeks) to achieve Hgb ≥ 10 gm %, % S Hgb < 20%. E were obtained periodically before/after, and during HT. Mean values during HT/off HT were: Hgb 9.7/7.2 (p < .001), % S Hgb 12.1/88.2 (p < .001). The DFC and Ydv before and after HT did not differ from those of 44 untreated SS (P = NS); during HT, there was significant shift (p < 0.001) of DFC and Ydv towards Nl. We conclude that cardiac size and function are abnormal in SS children, improve during HT, but revert back to abnormal state after discontinuing the HT.

132 CARDIAC EFFECTS OF HYPERTRANSFUSION THERAPY IN SICKLE CELL DISEASE (SS)

Serial echocardiography was used to assess cardiac size and function of 5 children (0. 9 to 16 years) on hypertransfusion therapy (HT) for clinical problems related to SS. Satisfactory HT status, defined as total Hb levels maintained at ≥10 gm% and Hb-S at <10%, was achieved with washed packed RBC transfusion every 2-3 weeks. Iron status was monitored. Echo measurements of LV dimension (LVD), LA dimension (LAD), LV wall thickness (W), LV mass (M), cardiac output (Q), PEP/ET ratio and circumferential fiber shortening velocity (VCF) were obtained every 2-4 months during HT. These were compared to those of 100 normal children (48 Blacks, 52 Whites). Clinical improvement was dramatic. In one child (age 1 yr), the echo data remained normal before and during HT. The values in the other 4, expressed as % of predicted normal, before (C) and during HT for 8-10 mos are as follows:The improved clinical status during HT is accompanied by diminution of cardiac size and of the high-output state. These changes may reverse after HT is discontinued.

131 ECHO EVALUATION OF CARDIAC STATUS IN HOMOZYGOUS SICKLE CELL DISEASE (SS)

Cardiac size and function were evaluated in 47 clinically-well non-hypertransfused children with SS, age 0. 6 to 19 years, using echocardiography. Steady-state hemoglobin ranged from 5. 5 to 10. 0 gm%; in 29, ≥7 gm% (gp A) and in 16, <7 gm% (gp B). Age-matched normal children (48 Blacks, 52 Whites) were controls (N). Echo parameters included: RV dimension (RVD), LA dimension (LAD), LV dimension (LVD), LV wall thickness (W), LV mass (M), cardiac output (Q), and LV function parameters including circumferential fiber shortening velocity (VCF) and LV pre-ejection/ejection time ratio (PEP/ET). The 1n of BSA was plotted against In echo parameters except in VCF where In heart rate was used. Data were expressed in percent of predicted normal. Increased values (>2 SD from N mean) were observed for RVD (in 22%), LAD (in 54%), LVD (in 52%), W (in 28%), M (in 61%), Q (in 50%), VCF (in 7%) and PEP/ET (in 34%). Group t-tests vs N showed significant differences (p<0. 001) except for VCF. Gp B had greater LVD, M, and LAD than gp A (p<0.01 to <0.05). The degree of abnormality did not correlate with age. Children with SS have cardiac volume overload and a compensated high-output state. The abnormal LV wall and PEP/ET seen in certain patients may suggest secondary myocardial disease.