The prevalence of human leukocyte antigen (HLA) DR/DQ/DP alleles in Kuwaiti children with oligoarticular juvenile idiopathic arthritis.

We have determined the prevalence of human leukocyte antigen (HLA)-DR, DQ and DP alleles in Kuwaiti children with oligoarticular juvenile idiopathic arthritis (OA-JIA) and healthy controls using the PCR-SSP (sequence specific primers) method. The analysis took into account the presence of antinuclear antibodies and chronic anterior uveitis. DRB1*03 (RR 2.20, P<0.001), DRB1*08 (RR 5.280, P<0.026), DQA1*0501 (RR 1.930, P<0.001), DQB1*0304 (RR 7.920, P<0.002), DQB1*0501 (RR 3.080, P<0.007) and DPB1*0101 (RR 8.8, P<0.001) were the main HLA alleles associated with OA-JIA in Kuwaiti Arabs in this study. DRB1*03 was detected in 71% of children with positive ANA, and in 50% of children with anterior uveitis. DQA1 alleles *0501, *0103 and *0105 (P<0.001; 0.029 and 0.024 respectively) were found to be associated with OA-JIA. In contrast, DQA1*0301 and DQA1*0302 alleles appear to be protective in Kuwaiti children (RR 0.153, P<0.001 and RR 0.278, P<0.016 respectively). The DQB1 alleles *0304 and *0501 were associated with OA-JIA (P<0.002 and P<0.007 respectively). In the case of DPB1, only one allele (*0101) was associated with OA-JIA (P<0.001). Most Kuwaiti Arab patients with OA-JIA who carried a DQ or DP susceptibility allele also had an accompanying DRB1*03 or *8 allele.

Role of human leukocyte antigen DRB1*0307 and DRB1*0308 in susceptibility to juvenile rheumatoid arthritis.

OBJECTIVE: To study the prevalence of Human Leukocyte Antigen (HLA) DR alleles in children with juvenile rheumatoid arthritis (JRA). METHODS: DNA samples from 64 children with oligoarticular and seronegative polyarticular JRA and 64 controls of the same ethnic background were analyzed using PCR-sequence specific primers (PCR-SSP) method. Analysis took into account the onset subtype, the presence of antinuclear antibodies (ANA) and the presence of chronic anterior uveitis, a recognised serious complication of JRA. RESULTS: A high prevalence of DR3 alleles were detected in children with oligoarticular JRA compared to controls (p < 0.05). DR3 alleles were the commonest also in patients with positive ANA as well as those with chronic anterior uveitis. The interesting finding in this study is the absence of two DR3 alleles, namely DRB1*0307 and DRB1 *0308 in the control group while present in significant proportion in children with JRA. DRB1*0307 was present in 16% of children with oligoarticular subtype and 15% of those with polyarticular JRA. DRB1*0308 was only detected in children with oligoarticular JRA, none of the children with polyarticular JRA or the controls had this allele. CONCLUSION: These findings support earlier observations linking these two DR3 alleles, namely 0307 and 0308, to the genetic susceptibility to JRA.

Prevalence of human leukocyte antigen (HLA) DRB1 alleles in Kuwaiti children with juvenile rheumatoid arthritis.

The prevalence of human leukocyte antigen (HLA) DR alleles has been determined in 69 Kuwaiti Arab children with juvenile rheumatoid arthritis (JRA) and compared to that in 212 ethnically matched normal healthy controls using a PCR-sequence specific primers (PCR-SSP) method. A very high incidence of DR3 was detected in JRA patients compared to the controls (P < 0.0001, RR = 2.235). The high incidence of HLA-DR3 in JRA patients was accounted for mainly by an excess of DRB1*0307 (P < 0.05, RR = 3.072) and DRB1*0308 (P < 0.009, RR = 2.663) compared to the controls. Moreover, DR3 was more prevalent when patients with ANA-positive JRA were analysed separately; 73% compared to 58% for the whole JRA patient group. The frequency of DR1 was also higher in the JRA group compared to controls (P = 0.019, RR = 3.585). Although the incidence of some alleles was higher in the control group (DR13 and DR7), none reached a statistically significant level. All the patients with iridocyclitis had either a DR1 or DR3 allele, except for one child. The frequency of DRB1*03 was found to be much higher in the polyarticular subtype of Kuwaiti JRA cases compared to the oligoarticular subgroup and the controls. Also, a non-significant increase in the frequency of the DRB1*04, *11 and *15 alleles was detected in the polyarticular subtype of the Kuwaiti JRA cases compared to the controls.

Poststreptococcal reactive arthritis.

The occurrence of an entity designated poststreptococcal reactive arthritis (PSReA) has been highlighted in recent reports. The syndrome was considered part of the spectrum of acute rheumatic fever by some, whereas others stressed the differences between the two diseases. As distinct from acute rheumatic fever, PSReA is characterized by a shorter latency period between the inciting streptococcal infection and the onset of arthritis, a higher frequency of involvement of the small joints and axial skeleton, poor response to aspirin and other nonsteroidal anti-inflammatory drugs, a protracted course of arthritis, a low incidence of carditis, and absence of other major manifestations of acute rheumatic fever. Recent studies have demonstrated an increased frequency of DRB1*01 in patients with PSReA, which contrasts with the increased frequency of DRB1*16 in rheumatic fever. Because 6% of patients with PSReA have been reported to have late onset carditis, it is judicious to recommend that patients with PSReA receive prophylactic antimicrobials for a minimum period of 5 years or until the age of 21 years, whichever is longer.

On defining Sydenham's chorea: where do we draw the line?

Sydenham's chorea (SC) is a major manifestation of rheumatic fever characterized by an array of neuropsychiatric symptoms that vary in severity, timing, and character. Some of the same symptoms are seen in Tourette's syndrome and childhood-onset obsessive-compulsive disorder. Genetic vulnerability appears to play a role in all three conditions. The term PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcus) has been introduced to describe a putative subset of obsessive-compulsive disorder and Tourette's syndrome that bears some resemblance to Sydenham's chorea. This article discusses whether PANDAS should be subsumed under Sydenham's chorea, thus expanding the diagnostic boundaries of Sydenham's chorea to include primarily neuropsychiatric presentations now classified as cases of obsessive-compulsive disorder or Tourette's syndrome. We conclude that PANDAS is a useful construct, but that it would be premature to view it as a subset of Sydenham's chorea-whether defined narrowly or broadly.

Filariasis and erisipela in Santo Domingo.

This study examined acute-convalescent changes in diagnostic anti-streptococcal antibodies by the anti-streptolysin O (ASO) and anti-DNAase B (ADAB) tests among patients (n 28) with lymphedema and recurrent erisipela of the lower limb, comparing them with endemic normal control residents (n=25). The study was based in Villa Francisca, an urban focus of Bancroftian filariasis in eastern Santo Domingo, capital of the Dominican Republic. The acute signs and symptoms of erisipela were consistent with a diagnosis of bacterial cellulitis. The ASO test was especially successful at demonstrating a rise in mean titer during convalescence, whereas the ADAB produced about the same frequency of significant increases (0.2 log titer) as did the ASO. When subjects were scored as responders if mounting a minimal titer increase by either test, patients were found more frequently positive than were controls (chi2=5.3, P=0.02). About half (54%) of all patients mounted at least a minimal antibody increase. Filaria-specific IgG4 antibodies were absent from all sera of 20 residents of a nonendemic Dominican mountain town but appeared in about two-thirds of the sampled residents of the endemic barrio. Notably however, levels did not change between the acute phase and convalescence. These findings are consistent with the hypothesis that recurrent streptococcal invasion of the lymphatics may be a significant factor triggering or amplifying lymphedema and elephantiasis in patients with chronic filariasis.

Poststreptococcal reactive arthritis: clinical characteristics and association with HLA-DR alleles.

OBJECTIVE: To assess the relationship of poststreptococcal reactive arthritis (ReA) to other forms of ReA and rheumatic fever by comparing the frequency of HLA-B27 and DRB1 alleles in these diseases. METHODS: The diagnosis of poststreptococcal ReA was established in 25 children seen in a pediatric rheumatology clinic. HLA-B27 and DRB1 genotyping was performed in 18 of the white American patients. The DRB1 genotyping results were compared with those in 33 patients with rheumatic fever and 190 normal individuals. RESULTS: HLA-B27 was positive in 3 of the 18 poststreptococcal ReA patients, a frequency not different from that found in normal individuals. Compared with normal controls, the frequency of the DRB1*01 allele was higher in poststreptococcal ReA patients (odds ratio [OR] 2.7, P=0.044), while DRB1*16 was increased in patients with rheumatic fever (OR 4.3, P=0.028). CONCLUSION: The association of poststreptococcal ReA with HLA-DRB1*01, but not with HLA-B27, suggests that its pathogenesis may be more similar to that of rheumatic fever than to that of ReA associated with enteric pathogens.

Antiphospholipid antibodies in pediatric lupus nephritis.

Antiphospholipid antibodies (aPL) of various isotypes are known to occur in systemic lupus erythematosus (SLE), but the significance of this finding in the pediatric population remains unclear. Our aim was to determine whether children with lupus nephritis have an increased risk of thrombosis and whether antiphosphatidylserine (APS) or antiphosphatidylinositol (API) antibodies were predictive of thrombotic complications. Thirty-six children (27 girls/9 boys; 44% black) with SLE nephritis (WHO II, 1; WHO III, 7; WHO IV, 21; WHO V, 7) were evaluated for antiphosphatidylserine, antiphosphatidylinositol, and anticardiolipin immunoglobulin (Ig) G and IgM isotypes, using a modified solid-phase enzyme-linked immunoassay (ELISA). Twenty-four patients (67%) had at least one positive aPL. Longitudinal data on 26 patients showed fluctuations in the degree of positivity. Eight patients experienced thrombotic complications, with equal distribution between arterial and venous events. Other clinical manifestations included thrombocytopenia in seven patients (19%), hemolytic anemia (44%), lupus anticoagulant (6%) and false-positive Venereal Disease Research Laboratory (VDRL) test results (11%). Comparisons between those with and without a thrombotic event showed no detectable difference in the incidence of aPL positivity between the two groups. We conclude that neither APS, API, nor anticardiolipin (ACL) activity was predictive of thrombotic complications in our subset of patients with lupus nephritis.

B lymphocyte antigen D8/17: a peripheral marker for childhood-onset obsessive-compulsive disorder and Tourette's syndrome?

OBJECTIVE: It has been hypothesized that Sydenham's chorea, a major manifestation of rheumatic fever, may provide a medical model for obsessive-compulsive disorder and associated conditions, such as Tourette's syndrome. Monoclonal antibody D8/17 identifies a B lymphocyte antigen with expanded expression in nearly all patients with rheumatic fever and is thought to be a trait marker for susceptibility to this complication of group A streptococcal infection. The authors investigated whether D8/17 expression is greater than normal in some forms of obsessive-compulsive disorder and Tourette's syndrome. METHOD: By immunofluorescence techniques, 31 patients with childhood-onset obsessive-compulsive disorder and/or Tourette's syndrome or chronic tic disorder and 21 healthy comparison subjects were evaluated for percentage of D8/17-positive B cells. None had rheumatic fever or Sydenham's chorea. Levels of antineuronal antibodies and streptococcal antibodies were also determined. RESULTS: The average percentage of B cells expressing the D8/17 antigen was significantly higher in the patients (mean = 22%, SD = 5%) than in the comparison subjects (mean = 9%, SD = 2%). When classified categorically, all patients but only one comparison subject were D8/17 positive. No difference between groups in the presence of antineuronal antibodies or high streptococcal titers was found. CONCLUSIONS: Patients with childhood-onset obsessive-compulsive disorder or Tourette's syndrome had significantly greater B cell D8/17 expression than comparison subjects despite the absence of documented Sydenham's chorea or rheumatic fever. These findings suggest that D8/17 may serve as a marker for susceptibility among some forms of childhood-onset obsessive-compulsive disorder and Tourette's syndrome, as well as rheumatic fever or Sydenham's chorea.

Juvenile rheumatoid arthritis in velo-cardio-facial syndrome: coincidence or unusual complication?

We report on two patients with velo-cardio-facial syndrome (VCFS) and juvenile rheumatoid arthritis (JRA). The first, a 9-year-old girl, presented with microcephaly, characteristic face, congenital heart disease, and velopharyngeal insufficiency. Fluorescence in situ hybridization (FISH) study showed deletion of D22S75 (N25), confirming the diagnosis of VCFS. At age 7, she developed joint pain, and polyarticular JRA was diagnosed. Awareness of this case led to the subsequent diagnosis of VCFS (also confirmed by FISH) in another, unrelated 12-year-old girl with characteristic face, hypernasal speech, and obesity. JRA was first diagnosed in this case at age 5 years, and she subsequently developed severe polyarticular disease. Neither patient had clinical or laboratory evidence of immunodeficiency. This observation represents the first report of the association of JRA with VCFS and raises the question of whether this is a coincidental association or a rare complication of this condition.

Cost-effectiveness of Haemophilus influenzae type b conjugate vaccine program in Florida.

Introduction of Haemophilus influenzae type b (Hib) vaccine has significantly decreased this disease's incidence in childhood. The cost-effectiveness and economic impact of the Hib immunization program in Florida were investigated and three periods compared: I = 1984-1988; II = 1989-1990; and III = 1991-1992. The cost per year of Hib disease in Period I was $27.48 million while that in Periods II and III was $15.95 million and $.88 million respectively. The total savings in millions were: Periods I and II = $11.53; Periods II and III = $11.07; and Periods I and III = $22.6. The greatest saving was realized between Periods I and III because of the initiation of immunization with the Hib vaccine starting at two months of age during Period III. Hib immunization is cost-effective and significant savings would more than pay for the cost of the program.

Active systemic lupus erythematosus is associated with depletion of the natural generic anti-idiotype (anti-F(ab')2) system.

OBJECTIVE: To study the relationship of serum IgG anti-F(ab')2 and clinical disease activity in 108 patients with systemic lupus erythematosus (SLE) and to determine whether low serum anti-F(ab')2 with active renal disease is accompanied by deposition of anti-F(ab')2 in renal immune complex lesions. METHODS: We studied 108 patients with definite SLE over a 5 yr period and assayed serum anti-F(ab')2 levels in relation to degree of clinical disease activity. Renal biopsy eluates of 26 patients with SLE were examined by enzyme linked immunosorbent assay (ELISA) for relative amounts of IgG, anti-DNA, and IgG anti-F(ab')2. RESULTS: Active SLE was strongly associated with low serum anti-F(ab')2. SLE renal biopsy eluates frequently contained high levels of IgG and IgG anti-DNA and lower, but definite, IgG anti-F(ab')2 activity. When specific activity of IgG anti-DNA and IgG anti-F(ab')2 was compared between kidney biopsy eluates and concomitant serum, marked relative renal concentration was found for both anti-DNA (19-fold) and anti-F(ab')2 (74-fold). Some biopsy eluates contained IgG antibodies bearing apparent double specificity for both DNA and F(ab')2. CONCLUSION: Active SLE is often associated with low serum anti-F(ab')2. Relative enrichment over specific activity in serum of both IgG anti-F(ab')2 and anti-DNA in SLE kidney biopsy eluates may indicate participation of both reactants in the glomerular disease process. Low serum anti-F(ab')2 in active SLE may reflect down modulation of failure of idiotypic control mechanisms associated with disease progression.

Latex particle agglutination tests on the cerebrospinal fluid. A reappraisal.

Rapid diagnostic tests are often used to identify microbial etiology of infection early. Latex particle agglutination (LPA) tests on the cerebrospinal fluid (CSF) are frequently used for purpose of rapid diagnosis. We evaluated their usefulness in management of patients with suspected meningitis. We also evaluated the cost effectiveness of LPAs during an 11-month period; 1,540 CSF specimens were tested for H. influenzae type b, Group B streptococcal (GBS), N. meningitidis and S. pneumoniae using LPAs. Only 27 were positive. LPAs were useful in management of only the neonates with GBS infection. On the whole, LPAs were very expensive and not cost-effective.

Haemophilus influenzae type B invasive disease in urban and rural children: immunization patterns and prevalence of disease.

To examine the impact of the introduction of Haemophilus influenzae type b (Hib) conjugate vaccine, we reviewed the incidence of Hib invasive disease in the state of Florida from 1984 to 1992. We analyzed the incidence of disease in two populations of children, one residing in an urban area and the other in a rural area. This study was designed to compare incidence rates prior to and following the introduction of Hib vaccine for children. Our data show a > 80% decrease in the incidence of Hib invasive disease in the state of Florida and a similar decrease in both the urban and rural populations examined. Analysis of the data revealed that the majority of children contracting Haemophilus influenzae type b invasive disease in both populations were either not immunized or were only partially immunized.