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.

Successful treatment of aspergillus brain abscess with itraconazole and interferon-gamma in a patient with chronic granulomatous disease.

This report describes the successful treatment of Aspergillus brain abscess in a boy with chronic granulomatous disease.

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.

Henoch-Schönlein purpura.

Although Henoch-Schönlein purpura (HSP) can occur at any age from infancy to adulthood, it is overwhelmingly a disease of childhood. Indeed, HSP is the most common vasculitis syndrome affecting children. The clinical features of HSP have been well documented, and the diagnosis is generally not difficult. However, there are substantial gaps in our understanding of the etiology, pathogenesis, and treatment of HSP. This article briefly reviews the clinical aspects of HSP and new information concerning therapy. The major focus of this review is recent information concerning abnormalities of immunoglobulin A1 glycosylation and the role of aberrantly glycosylated immunoglobulin A1 in the pathogenesis of HSP.

Acquired Brown's syndrome in a child with poststreptococcal reactive arthritis.

Acquired Brown's syndrome is a disorder of ocular mobility characterized by the inability to elevate the affected eye in full adduction owing to inflammatory tenosynovitis of the superior oblique tendon. We describe a child who developed Brown's syndrome as a complication of poststreptococcal reactive arthritis.

Hypocomplementemic urticarial vasculitis: report of a pediatric case.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is well described in adults but is quite rare in children. We report a pediatric case of HUVS initially diagnosed as juvenile rheumatoid arthritis and then as Henoch-Schönlein purpura. Beginning at 3 years of age, our patient developed polyarthritis with hypocomplementemia. She subsequently experienced an intermittent purpuric rash beginning at age 4 years, and she continued to have episodic arthritis and rash for years. Hematuria and proteinuria were noted at 12 years of age; renal biopsy revealed membranoproliferative glomerulonephritis with membranous features. Serum complement evaluation revealed activation of the classical pathway, consistent with HUVS. Therapy with oral dapsone led to improvement in proteinuria. HUVS should be considered in the differential diagnosis of pediatric patients with glomerulonephritis, urticarial rash, arthritis/arthralgias, and obstructive pulmonary disease.

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.

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.

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.

Remission of juvenile rheumatoid arthritis with varicella infection.

This report describes 2 children with juvenile rheumatoid arthritis (JRA) poorly responsive to therapy. Both patients experienced dramatic improvement in their arthritis coincident with acute, uncomplicated varicella infection. Although remission of JRA has been associated with other viral infections, this phenomenon has not been previously reported with varicella infection.

Hemorrhagic bullous lesions in Henoch-Schönlein purpura.

This report describes two children with Henoch-Schönlein purpura (HSP) associated with hemorrhagic bullous lesions. This unusual cutaneous manifestation of HSP may be a source of diagnostic confusion, but it does not appear to have prognostic implications.

Increased serum IgD concentrations in children with Henoch-Schönlein purpura.

Serum IgD concentrations were measured in 39 children with Henoch Schonlein purpura (HSP) and 40 control children by means of radial immunodiffusion. Serum IgG, IgA and IgM concentrations in the HSP patients were measured by nephelometry. The geometric mean IgD concentration in children with HSP (16.7 microg/ml) was significantly higher than in control children (9.1 microg/ml; P=0.03). Serial testing in 10 HSP patients revealed no significant change in IgD concentrations over periods ranging from 1 to 12 months. There was no relationship between IgD and IgA concentrations in the HSP patients. Nineteen of the 39 HSP patients (49%) had nephritis. The mean IgD concentration in patients with nephritis (10.7 microg/ml) did not differ from control values, but was significantly lower than the mean IgD level in the remaining 20 patients who did not have nephritis (25.4 microg/ml; P=0.02). These results indicate that serum IgD levels are increased in children with HSP who did not have nephritis. IgD concentrations in patients with nephritis were similar to levels in control children.

Petechial gloves and socks syndrome caused by parvovirus B19.

This report describes a 14-year-old boy with petechial gloves and socks syndrome associated with acute parvovirus B19 infection. This represents only the second child reported with this distinctive exanthem.

The clinical course of human immunodeficiency virus infection in genetically identical children.

Human immunodeficiency virus (HIV) infection in children is associated with diverse clinical manifestations and highly variable rates of progression. There is little information concerning the clinical course of HIV infection in genetically identical children. We review the cases of identical triplets who were infected with HIV at 1 day of age via a blood transfusion from a common unit of contaminated blood. The subsequent clinical manifestations of HIV infection in the triplets were remarkably uniform. Moreover, the patients' CD4 cell counts declined at similar rates. These patients enhance our understanding of the role of viral and host factors in determining the clinical progression of HIV infection.

Alterations in the O-linked glycosylation of IgA1 in children with Henoch-Schönlein purpura.

OBJECTIVE: To examine O-linked glycosylation of serum IgA1 in children with acute Henoch-Schönlein purpura (HSP). METHODS: The O-linked oligosaccharides of serum IgA1 from 28 children with acute HSP and 26 control children were examined by enzyme immunoassay using plant lectins with well defined carbohydrate binding specificities. The lectins included Artocarpus integrifolia (jacalin), Arachis hypogaea (peanut lectin), and Sambucus nigra (elderberry lectin). Jacalin binds to galactose-N-acetylgalactosamine (Gal-GalNAc). Jacalin interaction with this oligosaccharide is not influenced by the presence of sialic acid on the galactose moiety. Peanut lectin also interacts with Gal-GalNAc, but binding is inhibited if the galactose residue is sialylated. Elderberry lectin binds to N-acetylneuraminic acid (sialic acid). RESULTS: There was no difference in the binding of jacalin to IgA1 from patients with HSP compared to controls (p = 0.5). The binding of peanut lectin to IgA1 was significantly higher in HSP compared to controls (p = 0.007). Since peanut lectin binding is inhibited by the presence of sialylated galactose, these results suggest diminished sialic content of the O-linked oligosaccharides of IgA1 in HSP compared to controls. Indeed, the binding of the sialic acid-specific elderberry lectin to IgA1 was significantly lower in HSP compared to controls (p = 0.004). CONCLUSION: The O-linked oligosaccharides of serum IgA1 from children with acute HSP are deficient in salic acid compared to serum IgA1 from control children.