Juvenile systemic lupus erythematosus in multicase families from Saudi Arabia: comparison of clinical and laboratory variables with sporadic cases

The object of this study was to compare patients with familial versus sporadic systemic lupus erythematosus (SLE) with respect to clinical, laboratory variables and outcome. The familial SLE group comprised 12 patients while the comparative group comprised 24 patients selected by systemic sampling from our pediatric rheumatology clinic database. Those patients are listed according to the date of referral, which represents a sampling frame. The first patient was chosen randomly and subsequent patients were chosen at intervals of three. The two groups were compared with respect to: demographic information, age of onset of SLE, disease and follow up duration, clinical and laboratory variables and outcome. The patients from the familial group were younger and had an earlier age of onset of disease (P = 0.03, 0.001 respectively). Seven patients with familial SLE were from the eastern region of Saudi Arabia (P = 0.006). The two groups were comparable with respect to gender, disease duration and follow-up. At diagnosis, the discoid rash was more frequent in the familial group (P = 0.03) while other clinical and laboratory variables including disease activity as measured by SLEDAI did not show significant differences. The mean dose of steroid and use of other immunosuppressive therapy were similar in both groups. Three patients from the familial group died; two of them had unusual complications (one patient had transverse myelitis and pancreatic pseudocyst and the other one had extensive pyoderma gangrenosum). All patients from the sporadic group are alive in stable condition but one patient had severe central nervous system disease. Familial SLE patients tend to be younger and more likely to have discoid rash, in addition a marked difference in the origin of patients was noted. These differences may be helpful in identifying SLE patients with a stronger genetic predisposition. The mortality among familial SLE patients is more frequent which may reflect the disease severity.     

Juvenile idiopathic arthritis in multicase families

OBJECTIVE: To characterize juvenile idiopathic arthritis (JIA) patients from multicase families. METHODS: The study series comprised 80 affected siblings belonging to 37 families. Comparisons were made with a population-based series of JIA patients from Finland and with a sibling series from the United States. RESULTS: The distribution of cases according to onset type was similar in the sibling and population-based series. The age at diagnosis was significantly lower in the sibling series (4.8 years vs 7.4 years; p < 0.001). There was more intra-pair similarity in onset and course types in the United States series compared to the Finnish series and the proportion of girls was higher in the former. CONCLUSION: The only significant difference between familial and sporadic cases with JIA is an earlier onset of disease in familial cases. There is no essential difference in clinical features of the disease between patients in the multicase and sporadic groups. Differences between the Finnish and US series may be due to selection bias in the latter.     

Impact of C1q deficiency on the severity and outcome of childhood systemic lupus erythematosus

Objective: To delineate the clinical and laboratory features of systemic lupus erythematosus (SLE) in C1q‐deficient Saudi children and to compare them with sporadic SLE patients with respect to their clinical and laboratory features and disease outcome. Methods: The C1q‐deficient SLE patient group comprised 14 patients, while the comparative group comprised 11 patients selected by systemic sampling from our pediatric lupus clinic database. The two groups were compared with respect to: demographic, clinical and laboratory variables and outcome. Results: The C1q‐deficient SLE patients had an earlier age of onset of disease (P = 0.003); 43% had familial SLE and none of the comparative group had family histories of SLE. The two groups were comparable with respect to gender, disease duration and follow‐up. Scarring alopecia, discoid rash and nail changes were more frequent in the C1q‐deficient SLE patient group. However, there were no significant differences. The mean white blood cell count was lower (P = 0.04) and the level of anti‐Sm and anti‐phospholipid antibodies were higher (P = 0.04) in the C1q‐deficient SLE patients. Other variables did not show significant differences. Two patients from the C1q‐deficient SLE patient group died due to infection. All patients from the control group are alive. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index mean was higher in the C1q‐deficient SLE patients group but was not statistically significant. Conclusion: C1q‐deficient SLE patients tend to be younger and more likely to have familial disease with severe cutaneous manifestations. The mortality among them is more frequent, which may reflect disease severity.     

Immunogenetic differences between patients with familial and non-familial rheumatoid arthritis

OBJECTIVE: To search for possible immunogenetic differencies between the patients with familial and non-familial rheumatoid arthritis (RA). METHODS: The study compared 129 familial RA patients with 217 non-familial patients for the frequencies of HLA-DR antigens including DR4 subtypes, DR4-DQB1*0301 and DR4-DQB1*0302 haplotypes and HLA-B27 antigen as well as the age of disease onset and existence of rheumatoid factor or joint erosions. RESULTS: Two major differences between familial and non-familial groups were found: firstly, familial RA patients had increased frequency of HLA-DR4 as compared with the non-familial RA group (68.2 v. 54.8%; p = 0.019). Secondly, the mean age at onset of RA was significantly lower in the familial than in the sporadic RA patients (42.0 v. 46.5 years; p = 0.0020) and the difference still remained when the DR4 positive and negative subgroups were compared separately. CONCLUSION: These results confirm the more prominent association with HLA-DR4 in familial than in the non-familial cases and suggest that accumulation of HLA risk genes may, at least partly, explain the familial occurrence of the disease. Other susceptibility genes may also be concentrated in multiplex case families as suggested by an earlier age at the onset of RA in both HLA-DR4 positive and negative familial patients.     

Factors affecting the efficacy of intraarticular corticosteroid injection of knees in juvenile idiopathic arthritis

OBJECTIVE: To determine in a prospective analysis whether baseline demographic, clinical, and laboratory variables predict the outcome of intraarticular corticosteroid (IAC) injection of the knees in children with juvenile idiopathic arthritis (JIA). METHODS: We studied consecutive patients who met the criteria for the diagnosis of JIA and received their initial injection of triamcinolone hexacetonide in one or both knees. Predictor variables included sex, age, age at onset of JIA, onset subtype, disease duration, drug therapy at the time of IAC injection, physician and parent global assessment of disease status, Childhood Health Assessment Questionnaire disability index, erythrocyte sedimentation rate (ESR), C-reactive protein, involvement of other joints besides knees, amount of fluid aspirated, and dose of IAC injected. The primary outcome measure was persistence of complete clinical response at 6 months, i.e., no evidence of synovitis clinically. RESULTS: Ninety-four patients were available for analysis. At 6 months after the IAC injection, 65 (69%) patients showed a sustained complete clinical response, whereas 29 (31%) had had a recurrence of joint inflammation. Univariate statistical analyses showed that patients who had a sustained clinical response had a significantly higher ESR than those who did not (p = 0.023). The ESR was the only variable that remained in the best-fit model from multivariate logistic regression analysis (OR 2.61, p = 0.049). CONCLUSION: Our findings indicate that patients with JIA who have a higher ESR are more likely to benefit from IAC injection of the knees.     

Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study

BACKGROUND: Genetic factors may play a role in determining the development of extraintestinal manifestations (EIMs) and autoimmune diseases (AD) in patients with inflammatory bowel disease (IBD). We sought to determine the association between EIMs and AD in patients with first-degree familial IBD and sporadic IBD. METHODS: All patients evaluated in the IBD Clinic at the Mayo Clinic between January and September 1999 were offered enrollment. One clinic patient who was matched on age, gender, and geographic area of residence to each case served as controls. Information regarding EIMs and AD was obtained from a questionnaire completed by all IBD patients and controls. The adjusted odds ratios (95% CIs) for EIM as a function of first-degree familial IBD compared with sporadic IBD and AD as a function of first-degree familial IBD compared with sporadic IBD were estimated with a matched one-to-one conditional logistic regression model. RESULTS: Two hundred forty-three patients with IBD (47 first-degree familial IBD, 196 sporadic IBD) were enrolled. Forty percent of IBD patients had one or more EIMs compared with 14% matched controls [p < 0.001; OR = 3.1 (95% CI: 1.8 to 5.2)]. A total of 259 of the 1122 IBD patients and their first-degree family members indicated one or more EIM diagnoses (23%). The association between "familial versus sporadic" status and any EIM diagnosis was not significant [p = 0.59, the odds for an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.2 (95% CI: 0.8 to 1.7)]. Ten percent of IBD patients had one or more AD diagnoses compared with 19% matched controls [p = 0.04; OR = 0.4 (95% CI: 0.1 to 0.96)]. A total of 153 of the 1122 IBD patients and their first-degree family members indicated one or more AD diagnoses (14%). The association between disease status ("familial or sporadic") versus any AD diagnosis was not significant [p = 0.68, the odds for any AD in an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.4 (95% CI: 0.9 to 2.3)]. CONCLUSIONS: There was a positive association between IBD status (patient vs control) versus EIM, but not AD. A significant positive association between disease type (familial or sporadic) versus either EIM or AD was not detected.     

Chronic uveitis in children with and without juvenile idiopathic arthritis: differences in patient characteristics and clinical course

OBJECTIVE: Anterior uveitis (AU) in childhood may be the first manifestation of juvenile idiopathic arthritis (JIA). We identified factors that may help to differentiate JIA-associated AU from the more common idiopathic AU (IAU) before the onset of arthritis. METHODS: Children with IAU and with JIA-associated AU were analyzed for their demographics, age at onset of uveitis, uveitis course and complications, ocular surgery, antiinflammatory medication, and best corrected visual acuity (BCVA). RESULTS: AU was associated with JIA in 88 cases, and was idiopathic in another 49. In the JIA group, 60% of patients were female compared to 47% in the IAU group (p = 0.154). Antinuclear antibody (ANA) was significantly more frequent in the JIA group (88% vs 33%; p < 0.001, OR 14.4, 95% CI 5.8-35.6). Insidious uveitis onset occurred more often in JIA than in IAU patients (67% vs 31%; p < 0.001, OR 4.6, 95% CI 2.2-9.8). Persistent uveitis was found in 82% of JIA patients, and in 57% of IAU patients (p = 0.003, OR 3.4, 95% CI 1.5-7.4). Median age of AU onset was 5 years in JIA and 9 years in IAU (p < 0.001). Uveitis complications at first presentation at our institutions were more frequent in JIA than in IAU patients (79% vs 61%; p = 0.027, OR 2.5, 95% CI 1.1-5.3). During followup, 69 surgical procedures (51% of patients, 1.31 per patient) were performed in the JIA group, and 18 in IAU patients (0.57 per patient) (p = 0.008). BCVA was better in the IAU patients at first presentation (p = 0.001). CONCLUSION: The IAU and JIA-associated AU in childhood differ in their clinical course. ANA positivity, presence of uveitis complications at first manifestation, insidious onset, duration over 3 months, BCVA of 20/50 or less, and an age of 3 years or younger might help to detect AU associated with JIA. JIA uveitis manifests earlier, has more complications, and more often requires systemic immunosuppression and surgical intervention.     

Increased prevalence of antithyroid antibodies and subclinical hypothyroidism in children with juvenile idiopathic arthritis

OBJECTIVE: To estimate the occurrence of antithyroid antibodies (ATA) and hypothyroidism in children with juvenile idiopathic arthritis (JIA) compared to matched healthy controls. METHODS: The occurrence of ATA, including antithyroglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies, was evaluated by quantitative immunometric ELISA in children with JIA and in a healthy matched control group. Thyroid function was assessed in both groups. RESULTS: The study group included 66 patients with JIA (50 girls, 16 boys) of mean age 11.7 +/- 4.4 years (range 2-23). The control group included 89 children (71 girls, 18 boys) of mean age 10.8 +/- 4.2 years (range 2-18). Mean age at onset of joint disease was 7.3 +/- 3.6 years (range 1-15). Anti-TG antibodies were found in 7 of 62 patients (11.3%) in the JIA group and 2 of 89 controls (2.2%) (p = 0.03); anti-TPO antibodies were found in 5 of 65 patients (7.9%) and one of 89 controls (1.1%) (p = 0.08). All patients with ATA had oligoarticular type JIA (p = 0.01). Mean thyroid stimulating hormone (TSH) levels were higher in the study group than in controls (2.6 +/- 2.3 vs 1.9 +/- 1.0 mIU/l; p = 0.01); levels were above normal range (0.4-4 mIU/l) in 8 study patients (12%) and 3 controls (3.4%) (p = 0.055). Overall, ATA were found in 9 of the 150 study participants, 4 (44%) of whom had TSH levels above 4 mIU/l (p = 0.001). CONCLUSION: Children with JIA have a higher than normal incidence of ATA and subclinical hypothyroidism and should be routinely screened for these variables.     

Dutch patients with familial and sporadic ankylosing spondylitis do not differ in disease phenotype

OBJECTIVE: To assess potential differences in the phenotypic expression between familial and sporadic ankylosing spondylitis (AS). METHODS: Clinical data from the patient record forms were compared between 55 patients with AS from multicase families (i.e., families in which > or = 2 first-degree relatives have the disease) (familial AS) and 110 sex and age matched patients with AS who did not have a first-degree relative with the disease (sporadic AS). RESULTS: Between familial and sporadic AS no differences were found in age at disease onset, age at diagnosis, or prevalences of peripheral arthritis and acute anterior uveitis. CONCLUSION: Potential differences in genetic makeup are not reflected in differences in the phenotypic expression of familial and sporadic AS.     

Positive family history of psoriasis does not affect the clinical expression and course of juvenile idiopathic arthritis patients with oligoarthritis

OBJECTIVE: In the 1997 revision of the International League of Associations for Rheumatology (ILAR) criteria for juvenile idiopathic arthritis (JIA), a family history of psoriasis is an exclusion for the oligoarthritis category. We investigated whether psoriasis in a first or second degree relative influences the clinical expression and course of JIA patients with oligoarthritis. METHODS: In a cross-sectional study, consecutive oligoarticular-onset JIA patients were investigated. Clinical evaluations included confirmation of a family history of psoriasis and assessment of nail abnormalities, dactylitis, psoriatic rash, variables of JIA activity, and laboratory indicators of inflammation. Retrospective assessments included sex, onset age, disease duration, antinuclear antibodies, HLA-B27, uveitis, ocular complications, second-line therapies, intraarticular corticosteroid injections, radiographic joint lesions, joint involvement over time, and laboratory investigations at disease presentation and first observation. RESULTS: A total of 185 patients were included. Thirty-three had a positive family history of psoriasis (group 2) and 139 did not (group 1). Thirteen patients fulfilled the ILAR criteria for juvenile psoriatic arthritis (group 3). Patients in groups 1 and 2 were comparable for all parameters, except for a higher frequency of females in group 1 (P = 0.04). As compared with group 2, patients in group 3 were less frequently antinuclear antibody positive and had a more severe arthritis and a different distribution of joint involvement. CONCLUSION: We found close similarities in the clinical features and course among patients with oligoarthritis who had a positive family history for psoriasis and those who did not. These findings argue against the exclusion of the former patients from the oligoarthritis category of JIA.     

Clinical characteristics of familial versus sporadic Crohn's disease using the Vienna Classification

BACKGROUND: The etiology of Crohn's disease, an illness protean in its manifestations, may be better resolved through studies involving more homogenous subgroups of patients. Because a strong genetic influence exists, family history of inflammatory bowel disease may be a useful variable for patient classification if patients with familial and sporadic Crohn's disease are clinically different. Our study attempted to define any possible differences. METHODS: The medical records of 552 patients were reviewed, and patients were classified according to guidelines of the Vienna Classification. Patients were then divided based on family history of inflammatory bowel disease, and the familial and sporadic groups were compared. RESULTS: Overall, 422 (78.9%) patients were diagnosed before age 40 years (A1) and 114 (21.1%) at age 40 years or older (A2). There were 141 (26.3%) patients with disease involving the terminal ileum only (L1), 211 (39.4%) in the colon only (L2), 117 (21.9%) in the terminal ileum and colon (L3), and 66 (12.3%) in the upper gastrointestinal tract (L4). Disease behavior, as determined at the time of last visit or telephone contact, was nonstricturing, nonpenetrating (B1) in 149 (27.9%) patients, stricturing (B2) in 50 (9.3%) patients, and penetrating (B3) in 336 (62.8%) patients. Comparisons among the groups of 53 patients with first-degree relatives only, the 96 patients with either first-, second-, or third-degree relatives (familial CD group), and the 439 patients with sporadic disease demonstrated no differences in sex, age at diagnosis, or disease location. There was a difference in disease behavior between the familial and sporadic groups (p = 0.048) that failed to exist when nonstricturing, nonpenetrating cases were excluded. No such difference was observed between the first-degree relatives only group and the sporadic group (p > 0.10). CONCLUSIONS: Using the Vienna Classification, familial and sporadic Crohn's disease differed only in disease behavior. However, this difference failed to exist after patients with nonstricturing, nonpenetrating disease were excluded. Therefore, familial and sporadic groups appear to be quite similar clinically, and family history does not appear to be a variable useful for disease subclassification.     

Clinical and immunological characteristics of elderly onset Sjögren's syndrome: a comparison with younger onset disease

OBJECTIVE: To compare the clinical and laboratory characteristics of patients with primary Sj?gren's syndrome (SS) with an elderly onset to those with a younger onset. METHODS: The study group comprised 85 consecutive patients (79 women and 6 men) attending the Sj?gren's clinic. Primary SS was diagnosed according to the San Diego criteria. Elderly onset disease (EOD) was determined as the appearance of symptoms suggestive of SS after age 65. Clinical and laboratory variables for EOD were compared to those of a younger onset disease (YOD). Salivary and serum samples of all patients were examined for concentrations of interleukin 6 (IL-6) and hyaluronic acid (HA). RESULTS: Seventeen patients with SS (20%) matched the definition of EOD and their median disease onset was 71 years (range 65-80). No significant differences were noted in the clinical disease manifestations between the 2 groups of patients. Rheumatoid factor and anti-Ro(SSA) antibodies were more common in the YOD group (p = 0.012 and p = 0.023, respectively). Significant elevations of salivary IL-6 and HA levels were detected in the YOD group compared to the EOD group with SS (17.3 +/- 3.6 vs 8.8 +/- 2.1 pg/ml and 230.2 +/- 41.1 vs 128.8 +/- 33.3 ng/ml, respectively) (p < 0.0001). CONCLUSION: EOD SS has somewhat milder clinical symptoms with fewer immunological manifestations than YOD. The elevations of salivary IL-6 and HA in the younger group of SS patients support in part the differences in the inflammatory process between the 2 groups.     

Clinical heterogeneity of familial colorectal cancer and its influence on screening protocols.

The age at onset of non-polyposis colorectal cancer (CRC) was investigated in 49 families with at least three relatives affected in two successive generations. Forty one of these families satisfy the accepted minimum criteria for hereditary non-polyposis CRC. The remaining eight families were distinguished by a late age of disease onset and, hence, could not be included in the group. The condition in these latter families has been designated provisionally, as late onset familial CRC. The hereditary non-polyposis CRC families include 194 patients, 110 men and 84 women (mean age at diagnosis: 44 years; range: 16-74 years). Ninety two per cent of the patients were diagnosed by age 60. Colorectal cancer was diagnosed at progressively earlier ages in successive generations (p < 0.0005). The late onset CRC families comprised 30 patients, 20 men and 10 women (mean age at diagnosis: 62 years; range: 51-77 years). Fifty eight per cent of the CRCs in the patients belonging to the hereditary non-polyposis CRC families were located in the right colon compared with 13% in the late onset familial CRC group (p < 0.001). Multiple CRCs were found in 23% of the cases in the former but in only 3% in the latter families (p < 0.05). Adenomas associated with CRC were reported in 14.5% of the cases in the hereditary non-polyposis CRC families and in 30% of the cases in the late onset familial CRC group (p = NS). Extracolonic cancers, frequently encountered in hereditary non-polyposis CRC, were not found in the late onset CRC families. These findings indicate that there is a distinct clinical entity of non-polyposis CRC in which colorectal cancer develops at a more advanced age than in hereditary non-polyposis CRC. Future molecular genetic studies should confirm this hypothesis. In the meantime, recognition of these late onset familial CRC families, which will rest on clinical observations, is important because of the implications for the screening protocol.     

Serum and synovial fluid concentrations of matrix metalloproteinases 3 and its tissue inhibitor 1 in juvenile idiopathic arthritides

OBJECTIVE: Matrix metalloproteinases (MMP) are a large family of proteolytic enzymes involved in the remodeling of extracellular matrix during tissue resorption in idiopathic arthritides. We investigated serum and synovial fluid (SF) concentrations of MMP-3 and its tissue inhibitor (TIMP-1) in juvenile idiopathic arthritides (JIA). METHODS: Sera from 45 patients with active, 15 patients with inactive JIA, and 15 healthy controls were evaluated by ELISA for MMP-3 (stromelysin-1), TIMP-1, and soluble p75 tumor necrosis factor receptor (sTNFR). Paired SF concentrations were evaluated in 19 patients with JIA. RESULTS: MMP-3 serum concentrations were significantly higher in patients with active poly- and oligoarticular JIA versus inactive patients (p = 0.04 and p = 0.02, respectively) and healthy controls (p < 0.001 for both). Serum MMP-3, but not TIMP-1, concentration displayed a variable degree of correlation with clinical and laboratory variables of disease activity and with p75 sTNFR concentrations (r = 0.37, p = 0.005). SF MMP-3 concentrations were 30-300 times higher than those found in paired sera (p < 0.001, Wilcoxon rank test). A clear inversion of MMP-3/TIMP-1 ratio was observed when sera (median 0.31. range 0.02-1.5) were compared with the corresponding SF samples (5.3, range 4.9-5.5; p < 0.001). CONCLUSION: MMP-3 (stromelysin-1) is clearly overexpressed in SF of patients with JIA. An inadequate counter-expression of TIMP-1 may represent a crucial event for the development and perpetuation of tissue damage.     

Is there a role for arthroscopic synovectomy in oligoarticular juvenile idiopathic arthritis?

OBJECTIVE: To evaluate the longterm efficacy and safety of arthroscopic synovectomy (AS) in children with oligoarticular juvenile idiopathic arthritis (JIA). METHODS: Patients with oligoarticular JIA and persistent monoarticular involvement, refractory to nonsteroidal antiinflammatory drugs (NSAID) and/or intraarticular corticosteroid (IAC) treatment underwent AS followed, one month later, by IAC. The efficacy of AS was prospectively evaluated, and a good response was defined as absence of synovitis or > or = 60% decrease in articular score from baseline. Clinical, laboratory, and radiological variables (radiographs, ultrasound, magnetic resonance imaging) were noted to examine possible factors predictive of the result. RESULTS: Twenty-two patients with JIA (15 female, 7 male) entered the study. Age at disease onset was 77 months (range 13-168). Mean disease duration at the time of AS was 50 months (3-324). Nineteen knees, 2 temporomandibular joints, and one shoulder were treated; the mean followup was 57 months (12-168). Thirty-six percent of patients relapsed within 12 months of the procedure, 14% within 24 months, and 14% thereafter. Eight patients (36%) remain in remission after a mean 65 months' followup. Variables found to be predictive of good response were persistent monoarticular course (p = 0.004), short disease duration at the time of AS (p = 0.03), and normal erythrocyte sedimentation rate and C-reactive protein at baseline (p = 0.008 and 0.01, respectively). CONCLUSION: AS is a safe but only partially effective procedure in patients with oligoarticular JIA. Best results are achieved early in the disease course in children with persistent monoarticular involvement and no evidence of systemic inflammation.     

Familial vs sporadic rheumatoid arthritis (RA). A prospective study in an early RA inception cohort

OBJECTIVES: To study potential differences in demographic, process and outcome variables between familial and sporadic rheumatoid arthritis (RA) in an early RA inception cohort. METHODS: In 1998, we ascertained the familial status of all collaborative patients in a large early RA inception cohort at our department. Familial RA was defined by the presence of at least two siblings fulfilling the American College of Rheumatology criteria for RA. Baseline demographic data and prospectively recorded disease activity variables, therapies and radiological damage during the first 6 yr of disease were included in the analysis. A regression analysis was performed to assess whether familial clustering is a prognostic factor. RESULTS: We identified 142 patients with sporadic and 36 with familial RA. The most striking difference between these groups was the larger sibship size in multicase families (8.2 +/- 2.5 vs 5. 5 +/- 2.8; P < 0.0001). Age at onset was similar in both groups, although males with familiar RA were younger at disease onset than those with sporadic RA (median 50 vs 57 yr; P=0.03). No differences were found in gender, presence of rheumatoid factor (RF), antinuclear factor and HLA-DR typing or in disease activity, interventions and outcome over 6 yr of follow-up. Early radiological damage and disease activity, but not familial history of RA were prognostic for X-ray damage. CONCLUSION: We show that sibship size is the only relevant risk factor for familial RA. No differences in genotypic and phenotypic characteristics, disease severity or radiological damage were observed among familial and sporadic RA. Familial history of RA is not a poor prognostic factor. This prospective study confirms previous cross-sectional findings in the Dutch population.     

Early predictors of severe course of uveitis in oligoarticular juvenile idiopathic arthritis

OBJECTIVE: To determine whether demographic, clinical, and laboratory variables at onset of arthritis can predict the development and the severity of anterior uveitis (AU) in oligoarticular juvenile idiopathic arthritis (JIA). METHODS: In a retrospective study, a cohort of 366 patients with oligoarticular onset JIA from 3 pediatric rheumatology centers were evaluated. Patients were classified in 3 groups: severe uveitis (SU) with a mean >/= 2 uveitis relapses/year with complications or need for immunosuppressive therapy; mild uveitis (MU) with a mean 相似文献   

A comparison of clinical and immunogenetic features in familial and sporadic rheumatoid arthritis

Clinical and immunogenetic factors were compared in 214 patients with sporadic rheumatoid arthritis (RA) and 117 patients from 52 multiplex families. Sex distribution, articular disease severity and seropositivity for rheumatoid and antinuclear factors were similar in familial and sporadic disease. There was a trend for Sj?gren's and Felty's syndromes to be more frequent in familial RA but extraarticular disease features were otherwise similar in the 2 RA disease groups. Mean age of onset was 41.1 years in familial and 46.5 years in sporadic RA (p less than 0.0006); 67% of family probands, 74% of affected relatives and 57% of sporadic patients were HLA-DR4 positive (p less than 0.05 affected relatives vs sporadic). The similarity of clinical features found in familial and sporadic RA justifies the use of families with RA to study aspects of disease pathogenesis.     

Transforming growth factor-beta1, interleukin-10 and interferon-gamma cytokine polymorphisms in patients with hereditary, familial and sporadic chronic pancreatitis.

BACKGROUND: The genetic influence is undefined in about 40% of patients with hereditary and familial pancreatitis and in the majority of patients with sporadic chronic pancreatitis. The pathophysiological mechanisms underlying the progression from acute to chronic pancreatitis have not been clarified. Cytokines participate in the immunological progression of pancreatic inflammation and may play an important role in the development of pancreatic fibrosis. AIMS: We determined whether functional polymorphisms in the transforming growth factor-beta1 gene at positions -509, +869 (codon 10) and +915 (codon 25), in the interleukin-10 gene at position -1082, and in the intron 1 of the interferon-gamma gene at position +874 are associated with hereditary, familial or sporadic pancreatitis. METHODS: We investigated 78 patients with hereditary and familial pancreatitis and 62 patients with sporadic pancreatitis that were tested negative for cationic trypsinogen gene mutations, and 73 controls. Mutational analysis was performed by direct DNA sequencing or by amplification refractory mutational system polymerase chain reaction. We used the age at onset as marker of disease severity. RESULTS: The genotype frequencies were similar between patients and controls for all investigated cytokine polymorphisms (p > 0.05). We did not find an association between the different genotypes and the age at onset of the disease, and we did not detect different genotype distributions in patients with morphological alterations on pancreatic imaging after a disease duration of up to 5 years. CONCLUSION: These genetic variants do not play a dominant role in hereditary, familial or sporadic chronic pancreatitis.     

Circulating survivin indicates severe course of juvenile idiopathic arthritis

BACKGROUND: Survivin is an anti-apoptotic protein that has been recently suggested as a predictive marker of joint destruction in adult rheumatoid arthritis. We assessed the presence of extracellular survivin in patients with juvenile idiopathic arthritis (JIA). METHODS: Survivin levels were assessed in the circulation of 46 patients with JIA and in the age- and gender-matched controls (n=46) having no inflammatory disease, by ELISA. Survivin levels were analyzed with respect to the onset type and the activity of the joint disease. The intensity of inflammation and cartilage turnover was measured as levels of IL-6, serum amyloid A protein (SAA), and cartilage oligomeric matrix protein (COMP), respectively. RESULTS: The levels of extracellular survivin were significantly higher in JIA compared to the controls (p=0.0002). High levels of survivin (above mean + 2SD of the controls) were detected in 8/46 (17% JIA patients. High survivin expression was associated with polyarticular onset, active phase of arthritis. In contrast, survivin was neither related to the levels of IL-6, SAA, nor to COMP. CONCLUSION: Circulating survivin is expressed in a significant group of patients with JIA being associated to a severe course of the disease. It may be potentially used to select children with unfavorable prognosis of JIA who are in need of active pharmacologic treatment.