Primary and secondary Sjögren's syndrome in children--a comparative study.

Sjögren's syndrome is a chronic inflammatory systemic autoimmune disease mainly affecting the exocrine and, particularly, the salivary and lacrimal glands. The condition usually occurs in adults. In 1994, the criteria for this syndrome were redefined in a multicenter European study. In children, Sjögren's syndrome is a rare and probably underdiagnosed disease. To date, Sjögren's syndrome in children has only been described in case reports and in the comparative presentation of various study results. So far, no study of a comparative classification into primary and secondary Sjögren's syndrome has been carried out in a patient population of any size. Sjögren's syndrome should be considered in the differential diagnosis of children with recurrent parotitis, keratoconjunctivitis sicca, or pronounced and early tooth decay associated with xerostomia. In this study of 23 children and adolescents under the age of 16 with the clinical symptoms and laboratory findings of Sjögren's syndrome, we differentiate between primary and secondary Sjögren's syndrome. The value of the individual methods of assessing the oral and the ophthalmological components and the manifestation of the underlying rheumatic condition are discussed on the basis of the EULAR criteria. The EULAR diagnostic criteria are of limited applicability in children because reliable anamnestic data are frequently lacking. Another problem in diagnosing Sjögren's syndrome is the short-term detection of serological alterations and clinical symptoms. Even if young patients do not completely fulfill the required criteria, Sjögren's syndrome can be assumed or confirmed in the presence of positive testing for oral and ocular manifestations and recurrent salivary gland enlargement.

Prognosis of patients with juvenile chronic arthritis and juvenile spondyloarthropathy.

OBJECTIVE: Evaluation of the course and the prognosis of juvenile chronic arthritis (JCA) and juvenile spondyloarthropathy (JSpA). METHODS: The entire medical histories of 171 patients with JCA or JSpA were reviewed. The study cohort comprised 102 patients with oligoarticular, 17 with systemic, and 24 with polyarticular onset of JCA; 28 patients had a SpA; 91 patients with JCA from a population based cohort were included in that study cohort. The mean period of followup was 7.4 years. The probability of remission was estimated by survival analysis methods (Kaplan-Meier method). RESULTS: After a disease duration of 10 years the highest probability of complete remission was estimated for patients with oligoarticular or systemic onset of JCA (54% and 38%, respectively). In the oligoarthritis group with late onset of JCA, a lower probability of remission was found for the HLA-B27+ patients compared with HLA-B27- patients. Patients with polyarticular onset of JCA had the poorest prognosis, with a significantly lower probability of complete remission (15%) within 10 years, more secondary injuries, and a lower functional capacity at followup. Patients with JSpA showed a 17% probability of remission after a disease duration of 5 years and ranged between the remission rates for oligoarticular and polyarticular JCA. The estimated remission rates for the patients with JCA in the population based cohort and in the whole cohort were quite similar. CONCLUSION: Our data suggest a favorable prognosis for JCA and JSpA in general, but with differences among the subtypes. It seems that more than 50% of the patients with JCA and JSpA reach adulthood with active arthritis and need further rheumatological care.

Diagnostic value of sialography with both the conventional and digital subtraction techniques in children with primary and secondary Sjögren's syndrome.

OBJECTIVE: The application of anamnestic data on siccative symptoms required for classifying adult Sjögren's syndrome is limited in childhood. Instrumental test procedures are therefore necessary for objectively recording the oral and ophthalmologic manifestations of the disease. The aim of this study was to clarify the sialographic changes that occur in Sjögren's syndrome in children. STUDY DESIGN: A total of 23 sialograms were obtained with both conventional and digital subtraction techniques in 21 children with primary (10 girls and 1 boy) or secondary Sjögren's syndrome (10 girls). The films were assessed by 3 physicians and submitted for a consensus analysis if necessary. RESULTS: The pathologic features observed in the children varied from a slightly narrowed ductal system to multiple peripheral ductal ectasias and completely destroyed parenchyma. Sialographic examinations demonstrate that, with progressing disease, regression of acinar dilatations and rarification of the ductal system occur. CONCLUSION: The results show that the spectrum of sialographically recordable lesions in Sjögren's syndrome in children is greater than is described thus far in the literature.

Incidence and prevalence of juvenile chronic arthritis in East Berlin 1980-88.

OBJECTIVE: To estimate the incidence and prevalence rates of juvenile chronic arthritis (JCA). METHODS: The study population was children under 16 years of age living in the East Berlin area (part of the former German Democratic Republic). By admission order that was effective up to 1990, all children with symptoms of a rheumatic disease living in the East Berlin area had to be referred to the 2nd Children's Hospital at Berlin-Buch. This specific condition allowed us to ascertain cases from the clinical records and to calculate population rates. Based upon this data, the results of surveys with different methods of case ascertainment are compared. RESULTS: An incidence rate of 3.5 per 100,000 and a prevalence rate of 2.0 per 10,000 children were calculated. The frequency of JCA is higher for girls, with an incidence of 4.3 per 100,000 and a prevalence of 2.3 per 10,000. The figures for boys are 2.7 per 100,000 and 1.7 per 10,000, respectively. CONCLUSION: Because of the specific prerequisites, the population rates of prevalence and incidence that were based on clinical records can be regarded as valid in this study. Deviant results of other surveys can be explained by differences in the study design or in the diagnostic procedures used.

Nested polymerase chain reaction strategy simultaneously targeting DNA sequences of multiple bacterial species in inflammatory joint diseases. I. Screening of synovial fluid samples of patients with spondyloarthropathies and other arthritides.

OBJECTIVE: Bacteria play a crucial pathogenetic role in Lyme arthritis (LA), reactive arthritis (ReA), other forms of spondyloarthropathy (SpA), and possibly in undifferentiated oligoarthritis (uOligo). Polymerase chain reaction (PCR) technology has been applied to detect bacterial DNA of individual microbes in synovial fluid (SF) of patients with arthritides. We screened for DNA sequences of 8 bacterial species simultaneously in SF of patients with inflammatory joint disease. METHODS: We examined 104 SF samples of 96 patients with ReA (n = 13), undifferentiated SpA (uSpA, n = 10), uOligo (n = 50), juvenile chronic arthritis (JCA, n = 13), and rheumatoid arthritis (RA, n = 10). A nested PCR approach was developed to detect DNA sequences of 8 bacteria: Chlamydia trachomatis, C. pneumoniae, Yersinia enterocolitica, Salmonella enteritidis, Campylobacter jejuni, Shigella flexneri, Klebsiella pneumoniae, and Borrelia burgdorferi. The detection limit was determined at 10 bacterial/sample. Serology and lymphocyte proliferation assay were done in parallel in most patients. RESULTS: In 12 cases bacterial DNA of B. burgdorferi (n = 7), C. trachomatis (n = 2), C. jejuni (n = 2), and C. pneumoniae (n = 1) was detected in patients with uOligo (n = 9) and JCA (n = 3), while no evidence of bacterial DNA was found in patients with ReA, uSpA, and RA. Shigella flexneri DNA was detected in 4 cases, but the significance of this finding remains uncertain due to the high sequence homology of this species with Escherichia coli. DNA of Y. enterocolitica, S. enteritidis, or K. pneumoniae was not found. A positive serologic response was found in 7/9 PCR positive patients. In 11/96 cases antibodies to 2 or more bacteria were found in parallel (11.5%). Antigen specific lymphocyte proliferation was observed in 5/9 PCR positive patients. CONCLUSION: Bacterial DNA was detected in peripheral joint of patients with uOligo and JCA, but not in ReA, uSpA, or RA in this study. The detection of bacterial DNA in synovial material by PCR technology gives useful diagnostic information, especially when antibodies against several microbes are present or antibodies are not detectable. Failure to detect bacterial DNA in patients with ReA and uSpA with longstanding disease suggests that in later stages autoimmune mechanisms may operate.

Lyme arthritis in European children and adolescents. The Pediatric Rheumatology Collaborative Group.

OBJECTIVE: To evaluate and describe Lyme arthritis in European children and adolescents. METHODS: This was a prospective multicenter study. The diagnosis of Lyme arthritis required the exclusion of other diseases and positive findings on serology for IgG antibodies to Borrelia burgdorferi. Enzyme-linked immunosorbent assay, immunoblotting, and polymerase chain reaction techniques to identify infection by B burgdorferi were used. RESULTS: Among 62 children and adolescents with Lyme arthritis, only 1 had a preceding erythema migrans. Arthritis was episodic in 62% and was chronic at onset in 18%. The most common manifestation was monarthritis of the knee. Joint involvement in patients with oligoarthritis was predominantly unilateral or symmetric. Arthralgia was very rare. Treatment with 1 or 2 courses of different antibiotics resulted in disappearance of the arthritis in 77% of the patients. CONCLUSION: The clinical presentation of Lyme arthritis in children is different from that in adults. The calculated incidence of Lyme arthritis in persons under the age of 17 years (4/100,000) exceeds previous estimations.

Identification and characterization of a TNF alpha antagonist derived from a monoclonal antibody.

Peptides derived from the CDRs of the anti-TNF alpha monoclonal antibody Di62 were tested for inhibition of binding of Di62 to TNF alpha as well as of TNF alpha to its 55 and 75 kDa receptor. A peptide derived from the CDR1 of the light chain was shown to specifically inhibit Di62 binding to TNF alpha with markedly higher activity (Ki = 4 microM) than all other CDR-derived peptides. This peptide also significantly inhibited binding of TNF alpha to its 55 and 75 kDa receptor and protected L929 cells from the cytotoxic effect of TNF alpha (IC50 = 6 microM). The C-terminal region of this peptide, which is homologous to the 55 and 75 kDa TNF receptor, was found to be essential for activity.

[Synovial cellular immune response to bacterial pathogens in patients with chronic juvenile arthritis]. / Synoviale zelluläre Immunantwort auf bakterielle Erreger bei Patienten mit juveniler chronischer Arthritis.

Juvenile chronic arthritis is a heterogenous disease with an ill-defined pathogenesis. In our study, synovial fluid (SF) and peripheral blood (PB) of 70 children with oligoarthritis were investigated; bacteria-specific lymphocyte proliferation and antibodies to arthritogenic bacteria were determined. Specific cellular immune responses in SF but not in PB were found in 4/7 patients with either Lyme- or reactive arthritis (60%). In comparison, in subgroup JCA II (n = 45) encompassing mainly elder HLA B27 positive boys, a specific response in SF but again not in PB was detected in 10 children to Yersinia enterocolitica (YE), in four children either to Borrelia burgdorferi (BB) and Chlamydia trachomatis (CT), and in one child to Campylobacter jejuni (CJ). In contrast, in subgroup JCA I (n = 17) encompassing mainly young ANA-positive girls with chronic iridocyclitis, no specific response was found. The correlation of the synovial cellular and the humoral immune responses was 100% in the case of BB and 50% for YE; no antibodies against CT or CJ were detectable. Neither specific cellular nor humoral immune responses were detected against Salmonella or Shigella. We conclude that, in the pathogenesis of some patients with JCA, bacterial microbes have a triggering role. Mainly YE, but also BB and CT are responsible for cases of JCA in which no symptomatic infection preceded.

Aetiological role of bacteria associated with reactive arthritis in pauciarticular juvenile chronic arthritis.

BACKGROUND: The cause of juvenile chronic arthritis (JCA) is unknown. Pauciarticular JCA is the most common subtype and can be subdivided into early (type I) and late onset (type II) forms, the latter clinically resembling reactive arthritis. METHODS: The cellular immune responses to bacteria associated with reactive arthritis in blood and synovial fluid from 39 children with pauciarticular JCA, three children with classical reactive arthritis, and two children with psoriatic arthritis were examined. Specific titres of antibodies to bacteria in serum samples were measured in all patients. RESULTS: A bacteria specific synovial cellular immune response was found in two of three (67%) patients with reactive arthritis and 14 of 28 (50%) patients with pauciarticular JCA type II but only in one of 11 (9%) patients with pauciarticular JCA type I and none in patients with psoriatic arthritis. Six patients responded specifically to Chlamydia trachomatis and 11 to Yersinia enterocolitica. Antigen specific lymphocyte proliferation correlated poorly with the specific antibody response. CONCLUSIONS: These findings suggest that bacteria with associated reactive arthritis may have a causative role in pauciarticular JCA type II but not in JCA type I.

[Sonography of fetal growth behavior in maternal diabetes mellitus]. / Sonographische Untersuchungen über das fetale Wachstumsverhalten bei mütterlichem Diabetes mellitus.

In the Gynaecological Hospital affiliated to the District Hospital of Karl-Marx-Stadt, which is a care centre for pregnant diabetic women, 363 diabetic women of classes White A-F 1779 were subjected to ultrasonic examinations between 1982 and 1988. In this connection, nominal-value graphs were prepared to show the biparietal diameter (BIP), the medium thorax diameter and the head-thorax index in dependence upon the gestational age. These nominal-value graphs give a general idea of the specific fetal growth behaviour in case of diabetes mellitus. They permit to reliably diagnose a fetal hypertrophy or hypotrophy. Moreover, they provide a starting point for a more effective coverage of gestational diabetics and open up new prospects for insulinisation.

Influence of cholecystokinin on the synaptosomal dopamine uptake in the nucleus accumbens of rats.

The influence of the sulfated cholecystokinin octapeptide (CCK-8S) on the synaptosomal high-affinity [(3)H]dopamine (DA) uptake was investigated in the medial and lateral part of nucleus accumbens in rats. CCK-8S induced a concentration-dependent biphasic inhibition of [(3)H]-DA uptake in both subregions. After preincubation of CCK-8S with the synaptosomes the inhibitory effect was completely abolished. Kinetic analysis of the uptake influence suggests an uncompetitive inhibition by CCK-8S; this means that CCK-8S attacks only the DA-uptake carrier complex by inhibitory manner. The possible regulatory relevance of this mechanism is discussed.

[Circulating immune complexes and age]. / Zirkulierende Immunkomplexe und Alter.

The circulating immune complexes were quantitatively determined by PEG-precipitation in the serum samples of 413 from the clinical point of view healthy persons subdivided into several age groups. In comparison with the other age groups the age group of 0-15 years showed the lowest immune complex values (mean = 3.14 +/- 0.96 mg protein/ml) with a significant higher distribution (p = 5%). Significant differences between the persons of the age of 16-30, 31-45 and 46-60 years were not traceable. The average values of the circulating immune complexes amounted to 3.82 +/- 0.75, 3.9 +/- 0.67 respectively 3.91 +/- 0.38 mg protein/ml. In comparison with these three age groups the circulating immune complexes showed with an average value of 3.62 +/- 0.75 mg protein/ml a falling tendency for the persons more than 60 years old. There existed a statistical significant difference (p = 5%) for the persons of the age of 31-45 years. A sexual dependence of the immune complexes could not be found within the age groups. Autoantibodies (ANF, anti-dsDNA antibodies) were traceable in the serum of 23 (24.7%) of the persons more than 60 years old. The comparison of the sera with and without autoantibodies didn't show any significant difference with regard to the immune complexes.