The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3.

IPEX is a fatal disorder characterized by immune dysregulation, polyendocrinopathy, enteropathy and X-linked inheritance (MIM 304930). We present genetic evidence that different mutations of the human gene FOXP3, the ortholog of the gene mutated in scurfy mice (Foxp3), causes IPEX syndrome. Recent linkage analysis studies mapped the gene mutated in IPEX to an interval of 17-20-cM at Xp11. 23-Xq13.3.

A novel mutation in TNFRSF1A associated with overlapping features of tumor necrosis factor receptor-associated periodic syndrome and hyper-IgD syndrome.

We describe a 10-year-old child with a novel mutation, c.352A>G/p.Thr118Ala (T89A) in the tumour necrosis factor receptor superfamily 1A (TNFRSF1A) gene. The patient presented with periodic fevers beginning at 2 years of age. He had overlapping clinical and laboratory features of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and hyper-IgD syndrome (HIDS). This patient expands the clinical and genetic spectrum of TRAPS.

Henoch-Schönlein purpura in children. Report of 100 patients and review of the literature.

Henoch-Schönlein purpura (HSP) is an acute leukocytoclastic vasculitis that primarily affects children. In the current report, the author presents the clinical features of 100 children with HSP and reviews the literature, placing particular emphasis on new information concerning the etiology, immunopathogenesis, and treatment of HSP. The dominant clinical features of HSP are cutaneous purpura (100%), arthritis (82%), abdominal pain (63%), gastrointestinal bleeding (33%), and nephritis (40%). The etiology of HSP remains unknown, but it is clear that IgA plays a critical role in the immunopathogenesis of HSP, as evidenced by increased serum IgA concentrations, IgA-containing circulating immune complexes, and IgA deposition in vessel walls and renal mesangium. There are 2 subclasses of IgA, but HSP is associated with abnormalities involving IgA1 exclusively, and not IgA2. This finding may be a consequence of abnormal glycosylation of O-linked oligosaccharides unique to the hinge region of IgA1 molecules. Although several lines of evidence suggest a genetic susceptibility to HSP, the fundamental basis for the abnormalities involving IgA remain unclear. In general, HSP is an acute, self-limited illness, but one-third of patients will have 1 or more recurrences of symptoms. Corticosteroid therapy may hasten the resolution of arthritis and abdominal pain, but does not prevent recurrences. To date, no form of therapy has been shown to shorten appreciably the duration of HSP. The long-term prognosis of HSP is directly dependent on the severity of renal involvement. Corticosteroids in usual doses have no effect on established nephritis. Evidence is emerging that treatment with high-dose intravenous pulse methylprednisolone coupled with azathioprine or cyclophosphamide may be beneficial in patients with severe nephritis.

Intentional ipecac poisoning: Munchausen syndrome by proxy.

The intentional poisoning of two children with ipecac by their mothers is described. Intractable vomiting and diarrhea were the initial symptoms in both patients. In addition, one patient had clinical and laboratory evidence of skeletal and cardiac myopathy. Both children were subjected to extensive and invasive diagnostic evaluations before the correct diagnosis of chronic ipecac poisoning was made. These cases illustrate the toxic effects of ipecac ingestion and serve to alert physicians to child abuse by ipecac poisoning.

Prophylactic antibiotics in pediatric surgery.

The frequency and appropriateness of prophylactic antibiotic use in children less than 6 years of age who received surgery were examined. Antibiotics were prescribed for 62% of children who had surgery, and prophylaxis was the sole reason for antibiotic use in 73% of the patients. Prophylactic antibiotics were administered inappropriately with respect to timing or duration to 42% of the children receiving preoperative prophylaxis, 67% receiving intraoperative prophylaxis, and 55% receiving postoperative prophylaxis. Thus, prophylaxis alone is the major indication for antibiotic use in pediatric surgical patients, and prophylactic antibiotics are frequently administered inappropriately.

Reflex sympathetic dystrophy in children: treatment with transcutaneous electric nerve stimulation.

During the past 6 years, ten children with reflex sympathetic dystrophy were treated. Pain in an extremity was the initial complaint in all patients. The pain was unilateral in 90% of the patients; upper and lower extremities were affected with equal frequency. Tenderness to palpation, extreme hyperesthesia, and dysesthesia were other dominant features. All patients had some evidence of autonomic nervous system dysfunction in the affected extremity (swelling, color change, decreased temperature, and/or hyperhidrosis). The median duration of symptoms prior to referral and diagnosis was 5 months. All children were treated as outpatients with a transcutaneous electric nerve stimulator and home-based physical therapy. With this regimen, seven patients had complete remission within 2 months. Two other patients improved with transcutaneous electric nerve stimulation therapy, and one patient had no response to transcutaneous electric nerve stimulation. Reflex sympathetic dystrophy is frequently underdiagnosed in children. Increased awareness of this syndrome is important because accurate diagnosis is crucial and transcutaneous electric nerve stimulation offers a safe, simple, and effective outpatient therapy for reflex sympathetic dystrophy in children.

Manifestations and linkage analysis in X-linked autoimmunity-immunodeficiency syndrome.

The clinical findings of a kindred with an X-linked disorder are characterized by autoimmune polyendocrinopathy, enteropathy with villous atrophy, chronic dermatitis, and variable immunodeficiency. Linkage analysis was performed on 20 members of the affected kindred to determine the location of the responsible locus. Informative recombinations limited the region to an approximate 20 cM interval bordered by DXS1055 and DXS1196/DXS1050. Multipoint analysis generated a lod score >3 for the region contained between DXS8024 and DXS8031. The candidate region includes the Wiskott-Aldrich syndrome (WAS) locus. Evaluation of the Wiskott-Aldrich syndrome protein gene by single strand conformational analysis, heteroduplex analysis, and direct sequencing of the 12 exons in an affected male and two carrier females revealed no abnormalities. We conclude that this kindred has an X-linked disorder, distinct from WAS, that results in autoimmunity and variable immunodeficiency. The responsible locus maps to the pericentromeric region Xp11.23 to Xq21.1.

Transfusion-acquired human immunodeficiency virus infection in twelve neonates: epidemiologic, clinical and immunologic features.

Twelve neonates in 3 cohorts received blood transfusions from two donors who were infected with human immunodeficiency virus (HIV). All 12 infants developed laboratory and/or clinical evidence of HIV infection, usually in the first year of life. Ten of 12 infants had serum antibody to HIV when tested between 9 and 42 months of age. The two seronegative infants were severely hypogammaglobulinemic when they were tested. Nine infants developed a variety of illnesses attributable to HIV infection, but only 2 fulfilled criteria for the diagnosis of acquired immunodeficiency syndrome. In follow-up ranging from 2 1/2 to 4 years 5 patients (42%) have died. Four patients had HIV-associated illnesses but recovered and now have few if any symptoms attributable to HIV infection. Three children have never had signs or symptoms attributable to HIV. Immunologic abnormalities were present in all patients; the most consistent finding was a decrease in the proportion of T helper cells. Three patients had severe panhypogammaglobulinemia. The hypogammaglobulinemic infants had significantly lower numbers and percentages of T helper cells compared to the remaining patients (P less than 0.01). We conclude that exposure to HIV via transfusion in the neonatal period results in an extremely high rate of infection with substantial mortality and morbidity, but clinical recovery occurs in some patients. Also hypogammaglobulinemia may be more common in infants with HIV infection than previously appreciated.

Information collected during the residency match process does not predict clinical performance.

OBJECTIVE: To determine whether information collected during the National Resident Matching Program (NRMP) predicts clinical performance during residency. METHODS: Ten faculty members rated the overall quality of 69 pediatric house officers as clinicians. After rating by the faculty, folders were reviewed for absolute rank on the NRMP match list; relative ranking (where they ranked in their postgraduate year 1 [PGY-1] group); scores on part I of the National Board of Medical Examiners (NBME) examination; grades during medical school pediatrics and internal medicine rotations; membership in the Alpha Omega Alpha Medical Honor Society; scores of faculty interviews during intern application; scores on the pediatric in-service examination during PGY-1; and scores on the American Board of Pediatrics certification examination. RESULTS: There was substantial agreement among faculty raters as to the overall quality of the residents (agreement rate, 0.60; kappa = 0.50; P = .001). There was little correlation between faculty ratings and absolute (r = 0.19; P = .11) or relative (r = 0.20; P = .09) ranking on the NRMP match list. Individuals ranked in the top 10 of the match list had higher faculty ratings than did their peers (mean +/- SD, 3.66+/-1.22 vs. 3.0+/-1.27; P = .03), as did individuals ranked highest in their PGY-1 group (mean +/- SD, 3.88+/-1.45 vs. 3.04+/-1.24; P = .03). There was no correlation between faculty ratings and scores on part I of the NBME examination (r = 0.10; P = .49) or scores on the American Board of Pediatrics certification examination (r = 0.22; P = . 11). There were weak correlations between faculty ratings and scores of faculty interviews during the intern application process (r = 0.27; P = .02) and scores on the pediatric in-service examination during PGY-1 (r = 0.28; P = .02). There was no difference in faculty ratings of residents who were elected to Alpha Omega Alpha during medical school (mean +/- SD, 3.32+/-1.21) as compared with those who were not (mean +/- SD, 3.08+/-1.34) (P = .25). CONCLUSIONS: There is significant agreement among faculty raters about the clinical competence of pediatric residents. Medical school grades, performance on standardized examinations, interviews during the intern application process, and match-list ranking are not predictors of clinical performance during residency.

Prevalence of IgM, IgA and IgG rheumatoid factors in juvenile rheumatoid arthritis.

Using an enzyme immunoassay, sera from 50 children with juvenile rheumatoid arthritis (JRA) and 39 controls were tested for IgM, IgA and IgG rheumatoid factors (RF). RF of the IgM and IgA isotypes were present in 11 (22%) patients, but in only one control (p = 0.008). IgG RF was present in the sera of 2 (4%) patients and in none of the controls (p = 0.21). Of the 22 patients with IgM RF or IgA RF, only 3 sera (14%) contained RF of both isotypes. IgM RF was more common in patients with polyarticular disease, while IgA RF was more common in patients with pauciarticular disease. These results indicate that IgM and IgA RF are present in a significant minority of JRA patients and suggest that there is independent expression of the respective RF isotypes.

The effect of intravenous immunoglobulin on lymphocyte populations in children with Kawasaki syndrome.

High dose intravenous immunoglobulin (IVIG) is extremely effective therapy for Kawasaki syndrome (KS), but the mechanism of action remains unknown. The present study was performed to determine the effect of IVIG on lymphocyte populations and lymphocyte activation markers in 15 children with KS. Following IVIG, there was a decrease in the percentage of CD19 cells and an increase in the percentage of CD8 cells, but there was no change in the proportion of CD3 or CD4 cells. Moreover, there was no change in the percentage of activated CD4 or CD8 cells, as measured by HLA DR and interleukin-2 receptor expression after IVIG therapy. These results indicate that IVIG is effective treatment for KS via mechanisms other than the direct modulation of T cell activation markers.

Case report: increase in CD4 lymphocyte counts after splenectomy in HIV-infected patients.

The records were reviewed of five human immunodeficiency virus (HIV) type 1-infected patients who underwent splenectomy, four for HIV-associated thrombocytopenia and one for gastric compression secondary to splenomegaly. After splenectomy, the four adult patients all had marked, sustained increases in their absolute CD4 lymphocyte counts; greater increases were observed in CD8 lymphocyte counts, accounting for decreases in the CD4:CD8 ratios. In patients 5 (one of triplets, all of whom were infected with HIV after a blood transfusion), absolute CD4 lymphocyte counts were stabilized after splenectomy; the other siblings manifested a decline in CD4 counts, which was associated with a delay in physical development and recurrent episodes of varicella. Immunohistochemical staining of spleen sections demonstrated significantly higher numbers of CD4 cells in splenic tissue from HIV-infected patients than from patients splenectomized secondary to trauma (2,070 +/- 284 vs. 962 +/- 296; p = 0.025). In addition, the HIV-infected patients had significantly higher percentages of CD4 lymphocytes in splenic tissue than in peripheral blood (49.3 +/- 11.0 vs. 20.3 +/- 7.9; p = 0.005), suggesting that CD4 cells were sequestered in the spleens of these patients. These findings have implications for the management of splenectomized HIV-infected patients with regard to optimal timing of initiation of zidovudine therapy and for prophylaxis of Pneumocystis carinii pneumonia.

Acute leukemia presenting as arthritis in children.

The clinical and laboratory features of six children with arthritis as the presenting manifestation of acute leukemia are reviewed. Asymmetric arthritis involving the large joints of the extremities was the dominant clinical feature in all patients. Despite the presence of antinuclear antibody in three patients, other laboratory features, particularly hematologic abnormalities, served as clues to the diagnosis of leukemic arthropathy in most patients.

Thrombocytosis in Henoch-Schönlein purpura.

The clinical and laboratory features of acute Henoch-Schönlein purpura in 18 patients are presented. Thrombocytosis was noted in 67 per cent of the patients and was significantly associated with the presence of abdominal pain and gastrointestinal bleeding. We found no correlation between increased serum IgA concentrations or elevated sedimentation rates and any of the clinical features of Henoch-Schönlein purpura.

Failure to thrive due to obstructive sleep apnea.

The clinical features of two children with failure to thrive due to obstructive sleep apnea are presented. Both patients had subnormal growth velocities for height and weight for many months before diagnosis; both were underweight for height. Relief of their airway obstruction by adenotonsillectomy was promptly followed by catch-up growth and subsequent normal growth velocities. Obstructive sleep apnea should be considered in the differential diagnosis of failure to thrive in children.