[Structural quality of rheumatology clinics for children and adolescents. Paper by a task force of the "Society of Pediatric and Adolescent Rheumatology" and of the "Association of Rheumatology Clinics in Germany"]. / Strukturqualität von kinder- und jugendrheumatologischen Akutkliniken und -abteilungen. Projektgruppenarbeit der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) und des Verbandes Rheumatologischer Akutkliniken (VRA).

Rheumatic diseases in childhood and adolescence differ from those of adulthood according to type, manifestation, treatment and course. A specialized therapy, starting as early as possible, improves the prognosis, can prevent long-term damage and saves the costs of long-term care. Only a specialized pediatric care system can guarantee optimum quality of the processes involved and the results for rheumatology in childhood and adolescence within a global financial system. This requires adequate structural quality of the specialized clinics and departments for pediatric rheumatology. The management of rheumatic diseases in childhood and adolescence is comprehensive and requires a multidisciplinary, specialized and engaged team which can cover the whole spectrum of rheumatic diseases with their various age-dependent aspects. In order to guarantee an adequate, cost-efficient routine, a specialized center which concentrates on inpatient care should treat at least 300 patients with pediatric rheumatic diseases per year. The diagnoses should be divided among the various disease categories with at least 70% of them involving inflammatory rheumatic diseases. For the inpatient care of small children, an accompanying person (parent) is necessary, requiring adequate structures and services. Patient rooms as well as diagnostic (radiography, sonography, etc.) and therapeutic services (physiotherapy, occupational therapy, pool, etc.) must be adequate for small children and school children as well as adolescents. Suitable mother-child units must also be provided and a school for patients is required within the clinic. A pediatric rheumatologist must be available 24 h a day, and it must be possible to reach other specialists within a short time. For painful therapeutic procedures, age-appropriate pain management is obligatory. A continuous adjustment of these recommendations to changing conditions in health politics is intended.

Very early spondyloarthritis: where the inflammation in the sacroiliac joints starts.

Involvement of the sacroiliac joints (SIJ) is a major and characteristic feature of the spondyloarthritides (SpA). In early ankylosing spondylitis and undifferentiated SpA (uSpA) sacroiliitis is the most common early clinical finding and the presumed first manifestation of the disease. Magnetic resonance imaging has proved useful for visualising inflammation in the SIJ in adults and children. Recently, initial localisation of the inflammation in the SIJ has been described in some detail, but it has not been completely defined to date--either in imaging or in histopathological studies. This is mainly owing to the lack of data in very early disease and the lack of follow up studies. Here we present a patient with early disease, which may augment our understanding of this stage of SpA.

Burden and cost of illness in patients with juvenile idiopathic arthritis.

OBJECTIVE: To estimate the cost of illness in an incidence based cohort of patients with juvenile idiopathic arthritis. METHODS: Direct costs (healthcare and non-healthcare costs) and indirect costs (productivity loss due to sick leave and work disability) were measured in 215 JIA patients, assessed on an average of 17 years after disease onset. Assessment included a clinical evaluation, a structured interview, and two self completion questionnaires. Annual direct costs were estimated based on the reported use of healthcare services and resources, using average unit prices. Indirect costs were estimated from the number of work days missed-that is, using the human capital approach. RESULTS: The mean total cost of late JIA was estimated to be 3500 per patient and year, of which the direct cost contributed more than half. Patients with still active disease (55%) incurred the major share (90%) of the cost. They had a mean total cost of 5700 per patient year, with those under rheumatological care incurring a cost of 9300. Having a certain JIA subgroup, functional disability, or receipt of specialised care independently contributed to the total cost in active JIA. Highest mean total costs were found in active seropositive polyarthritis (17 000) and extended oligoarthritis (11 000), while the lowest were found in active enthesitis related arthritis (1500) and persistent oligoarthritis (2700). CONCLUSIONS: Estimated 12 month costs in late JIA are considerable, differing among the various JIA subgroups. Treatment strategies in JIA should be analysed for their cost effectiveness in the long term.

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.

[Eye complications in 458 children with rheumatoid arthritis]. / Augenbeteiligung bei 458 Kindern mit Erkrankungen des rheumatischen Formenkreises.

BACKGROUND: Besides arthritis or other systemic manifestations, endogenous inflammation (most commonly uveitis) can be a symptom of rheumatoid arthritis in children. The uveitis of children shows certain differences compared to that in adults. This study will show these differences and their incidences. PATIENTS AND METHODS: Retrospective analysis of the histories of 458 children that were admitted to the pediatric clinic due to rheumatism related diseases. An analysis of the general and pediatric data, laboratory results and therapy were combined with the ophthalmologic data. RESULTS: 45 (9.8%) of the 458 patients suffered from uveitis at least once during the studied time period between 1992 and 1996. Most common complications of the therapy were clouding of the lens up to full cataract (in both eyes in eight out of nine patients). Seven patients underwent cataract operation. Further complications are synechiae, band shaped keratopathy, secondary glaucoma and retinal diseases. CONCLUSION: Since the pediatric uveitis usually does not take an acute course and since children rarely can articulate themselves precisely, a regular ophthalmologic examination of pediatric rheumatology patients is necessary, as well as every uveitis in children should warrant pediatric-rheumatologic diagnostics. The impact of uveitis is much more severe for children when compared to adults, since it not only endangers the vision but the whole development of the child.

[C-reactive protein, Il-6 and procalcitonin as infection parameters in children with oncologic diseases]. / CRP, IL-6 und PCT als Infektionsparameter bei onkologisch kranken Kindern.

BACKGROUND: Due to anti-neoplastic therapy, there is a high incidence of infections and fever in pediatric patients with malignant disease. We have searched for parameters that may be of value in the early diagnosis of infection, in discriminating between bacterial and non-bacterial causes and for monitoring the response to antimicrobiotic therapy. PATIENTS: 46 febrile episodes in 33 children with malignant diseases under anti-neoplastic therapy, aged 0.5 to 17 years, were included. Each patient was supplied with a central venous catheter (Hickman catheter). METHODS: Blood was taken for the evaluation of C-reactive-protein (CRP), Interleukin-6 (IL-6) and Procalcitonin (PCT). Laboratory data included WBC, blood cultures, as well as microbiologic and serologic tests for important infectious agents. Patients were grouped as follows: 1. Patients with febrile diseases and positive blood cultures, 2. Patients with localized bacterial or mycotic infections and negative blood cultures, 3. Patients with fever of unknown origin, 4. Patients with viral infections, 5. Control group. RESULTS: CRP and IL-6 were more sensitive than PCT in detecting bacterial and mycotic diseases in leukopenic children, because of low PCT-levels in patients with localized infections. IL-6 values were high shortly after onset of fever and decreased under sufficient antimicrobiotic therapy until day three. CONCLUSIONS: Because of the quick response, IL-6 may be helpful in monitoring antimicrobiotic therapy. Using Procalcitonin-levels, we were not able to distinguish between localized bacterial and viral infection in leukocytopenic patients.

Use of contrast-enhanced MR imaging to detect sacroiliitis in children.

PURPOSE: To verify the diagnostic value of contrast-enhanced MR imaging compared with conventional radiography in the diagnosis of sacroiliitis in children. DESIGN AND PATIENTS: Radiography and MR imaging of the sacroiliac joints were performed in 185 children subdivided into the following groups according to the modified European Spondyloarthropathy (SpA) Study Group (ESSG) criteria: group 1, undifferentiated spondyloarthropathy (uSpA) (n=53, 94.5% HLA-B27+); group 2, differentiated SpA (n=45, 93.3% HLA-B27+); group 3, patients with no signs of SpA other than oligoarthritis (n=39, 92.3% HLA-B27+); group 4, HLA-B27+ controls with various other non-SpA diagnoses (n=22); and group 5, HLA-B27-controls with various other non-SpA diagnoses (n=26). Radiographs were evaluated on the basis of the modified New York criteria independently by three experienced radiologists masked to the clinical data. In a second step, the same radiologists independently evaluated the MR images without knowledge of the clinical data and radiographic findings using the recently published criteria developed by our group. These criteria allow differentiation of acute and chronic inflammatory changes. RESULTS: Radiography demonstrated sacroiliitis in 18 patients: 4 of 53 in group 1 (7.5%), 14 of 45 in group 2 (31%), but none in groups 3, 4 and 5. In contrast, MR imaging demonstrated acute and/or chronic sacroiliitis in 44 patients: 18 of 53 in group 1 (34%), 21 of 45 in group 2 (46.7%) and 5 of 39 in group 3 (12.8%), but none in groups 4 and 5. The percentage of sacroiliitis detected by MR imaging was significantly higher than that detected by radiography (P<0.001). CONCLUSION: Contrast-enhanced MR imaging is a useful method for detecting sacroiliitis in children. Advantages of contrast-enhanced MR imaging compared with conventional radiography are a higher sensitivity due to the ability to document early and acute changes and the absence of radiation exposure.

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.

Use of dynamic magnetic resonance imaging to detect sacroiliitis in HLA-B27 positive and negative children with juvenile arthritides.

OBJECTIVE: Involvement of the sacroiliac (SI) joints is a hallmark of the spondyloarthropathies (SpA), especially, in early and later stages of ankylosing spondylitis in adults. The significance of sacroiliitis in juvenile SpA is less clear and the diagnosis of juvenile SpA is difficult due to the mostly nonspecific or absent history of back pain in children and the time delay associated with the diagnosis of sacroiliitis by conventional radiographs. Our aim was to evaluate dynamic magnetic resonance imaging (MRI) of the SI joints in children and to assess the frequency and the determinants of SI joint involvement in juvenile SpA and other juvenile arthritides. METHODS: Clinical examinations and dynamic MRI were performed in 130 children < 16 years of age with joint complaints, 100 with probable SpA, and 30 controls. The degree of back pain was assessed by a visual analog scale (VAS) (0 = no pain, 10 = very severe pain). The following groups were defined before MRI investigation according to modified European Spondylarthropathy Study Group (ESSG) criteria for SpA: Group 1: undifferentiated SpA (uSpA, n = 41, 88% B27+); Group 2: differentiated SpA (n = 29, 97% B27+), comprising reactive arthritis (n = 16), ankylosing spondylitis (n = 9), psoriatic arthritis (n = 3), and arthritis in inflammatory bowel disease (n = 1); Group 3: patients with no signs of SpA other than oligoarthritis, here named juvenile chronic arthritis (JCA) II (n = 30, 93% B27+); Group 4: HLA-B27+ controls without arthritis (n = 12); and Group 5: HLA-B27-controls with various other non-SpA diagnoses (n = 18). MRI was evaluated according to published criteria allowing for differentiation between acute and chronic changes in SI joints. RESULTS: Acute sacroiliitis without chronic changes could only be detected by dynamic MRI: in 17 patients (11 in Group 1, 3 in Group 2, 3 in Group 3) together in 14/70 (20%) patients with SpA. All these 17 patients had normal pelvic radiographs. Using MRI acute and/or chronic sacroiliitis were found in 35 patients: 17/41 in Group 1 (41%), 15/29 in Group 2 (52%), and 3/30 (10%) patients in Group 3, but in no patients in Groups 4 and 5. Chronic SI joint changes > grade 1 were detected by MRI in 18/70 patients with SpA (25.7%). In comparison, radiographic changes > grade 1 were less often detected in 14/70 patients with SpA (20%) or 23/210 SI joints examined (11 %), compared to 29/210 SI joints found in the MRI examinations (14%) (p = 0.05). Among the 70 patients with SpA, those with MRI diagnosis of acute sacroiliitis had a significantly longer disease duration (62+/-34 vs 28+/-16 months; p = 0.01) and higher C-reactive protein (12+/-12 vs 9+/-14; p = 0.01), and also reported more back pain on VAS (4.3+/-3.6 vs 1.2+/-2.2; p = 0.001) than those without sacroiliitis. CONCLUSION: Dynamic MRI and MRI are useful to detect acute and chronic sacroiliitis in children. The main advantages in comparison with conventional radiographs are the ability to detect acute changes in the SI joints, the higher sensitivity to detect chronic changes, and clearly, the lack of radiation exposure; while the disadvantages are the high costs and the duration of the procedure. Sacroiliitis is fairly common in juvenile SpA and seems to be associated with disease intensity and duration.

Potential of autologous immunologic effector cells for bone marrow purging in patients with chronic myeloid leukemia.

Relapse is a major concern in autologous bone marrow transplantation (BMT). Therefore, purging of bone marrow to reduce the amount of tumor cells reinfused into the patient is widely used. Immunologic effector cells such as lymphokine activated killer (LAK) cells are attractive for purging of bone marrow since these cells might have an additional in vivo effect on tumor cells in contrast to other purging protocols. In patients with chronic myelogenous leukemia (CML), LAK cells can only be used in some patients for purging bone marrow since LAK cells possess no or only limited cytolytic activity against autologous CML tumor cells in most cases. In this study, we investigated the effect of autologous and allogeneic cytokine-induced killer (CIK) cells on tumor cells from patients with CML. CIK cells have been generated from peripheral blood lymphocytes by incubation with interferon-gamma on day 0, interleukin-1, interleukin-2 and a monoclonal antibody against CD3 on day 1. In contrast to LAK cells, CIK cells were able to lyse both autologous and allogeneic cells from patients with CML as determined by a 51Cr release and a tumor colony assay. The cytotoxicity of CIK cells against CML cells was confined to the CD56+ population. CIK cells showed no major toxic effect on hematopoietic progenitor cells when tested in CFU-GM assays. CIK cells eliminated three orders of magnitude of K562 cells and less than one order of magnitude of progenitor cells (25% reduction). This represents a differential effect of CIK cells on tumor and progenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

[Wegener's granulomatosis and anti-cytoplasm antibodies]. / Wegenersche Granulomatose und antizytoplasmatische Antikörper.

20 patients with biopsy-proven Wegener's granulomatosis (WG) and 95 control patients underwent determination of anticytoplasmic antibodies (ACPA) by the indirect immunofluorescence technique to assess the specificity and sensitivity of ACPA for WG. Of 14 untreated patients with WG, 13 were ACPA-positive. All these patients became ACPA-negative under immunosuppressive treatment. 4 patients treated with immunosuppressive drugs and 2 patients in remission after termination of therapy had a negative ACPA-test. ACPA were detected in 9 patients of the control group (two patients with Henoch Schoenlein purpura, two patients with systemic vasculitis, 2 patients with systemic diseases, and 1 patient with systemic lupus erythematodes). With that we achieved a specificity of 90.5% and a sensitivity 65.0%. In conclusion the ACPA-determination is very helpful for diagnosis and follow-up of WG.

[The irradiation sequelae in children with lymphogranulomatosis]. / Bestrahlungsfolgen bei Kindern mit Lymphogranulomatose.

1. 37 children with M. Hodgkin received radiotherapy to the involved cervical lymph nodes at the II. Children's Hospital in Berlin-Buch during 1971-1986. 2. Localised growth disturbances and muscle atrophies were observed as late effects. 12 children had severe sequelae and 19 patients moderate late effects. 3. The effects were stronger the younger the children were at the time of irradiation.

[Cellular immune response and glomerulonephritis--their detection with the Tetamun intracutaneous test]. / Zellgebundene Immunantwort und Glomerulonephritis--ihre Erfassung mit dem Tetamun-Intrakutantest.

In the considerations of the pathogenesis of glomerulonephritis more importance is attributed to cellular immune reactions. The cell-mediated immune response was examined by means of the Tetamun intracutaneous test in 37 patients with histological verified glomerulonephritis, in 18 patients with non-glomerular renal diseases, and in 25 healthy probands. The influence of main disease, renal insufficiency, nephrotic syndrome and immunosuppressive therapy on the test results could be determined by proper group formation. A significant diminution of cell-mediated immune reactions by the glomerulonephritis was verified. The importance of this finding in the pathogenetic routes and a possible model are discussed.

[Subtypification of acute lymphocytic leukaemia (ALL) in childhood by characterization of immunological surface membrane markers (author's transl)]. / Subtypisierung der akuten lymphatischen Leukämie (ALL) im Kindesalter durch Bestimmung immunologischer Oberflächenmaker.

Leukaemic blast cells isolated from bone marrow or blood of 42 children with ALL were investigated for presence of immunological surface membrane markers. By characterization of 5 surface markers (reaction with an anti-ALL serum for demonstration of a leukaemia-associated antigen, reaction with an anti-thymocyte serum and formation of E-rosettes for demonstration of T-lymphozytes, as well as reaction with an anti-Ig serum and formation of EAC-rosettes for demonstration of B-lymphocytes) the ALL cells of the 42 patients could be divided into 5 subtypes: I. 18 patients (42,7%( O-ALL with common ALL antigen II. 13 patients (31%) O-ALL without common ALL antigen III. 7 patients (16,7%) T-ALL with E-rosette formation IV. 3 patients (7,2) T-ALL without E-rosette formation V. 1 patients (2,4%) B-ALL.