Prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in juvenile chronic arthritis.

OBJECTIVE: Sera from 66 children with active JCA of oligoarticular, polyarticular or systemic onset, 13 sera from patients in disease remission, 15 sera from patients with reactive arthritis, and 11 from Lyme arthritis patients were tested for the presence of anti-neutrophil cytoplasmic antibodies (ANCA) in order to evaluate their diagnostic significance in JCA. RESULTS: ANCA were found in 21% (14/66) of the active JCA sera, all showing an atypical pANCA staining pattern using indirect immunofluorescence on ethanol fixed granulocytes. 71% of these sera also showed antinuclear antibodies (ANA) on HEp-2 cells. By additional staining on paraformaldehyde fixed granulocytes to exclude staining artefacts due to ethanol fixation, 2 of the pANCA positive sera showed cytoplasmic staining. In no case did we find nuclear fluorescence suggesting a true cytoplasmic localization of the involved antigens. All ANCA positive sera were negative for anti-MPO and anti-LF antibodies. ANCA prevalence in our study group did not correlate with the disease subgroup, disease duration or other clinical characteristics. However, we found ANCA only in active disease. CONCLUSION: Our data suggest that the diagnostic importance of ANCA in JCA is restricted to only a few JCA patients. In these cases, however, ANCA positivity supports the diagnosis of JCA. Further studies are needed to substantiate this finding, as well as possible subgroup specificities. Standardized techniques of granulocyte fixation and antigen specific tests are needed to produce comparable results in different study groups.

Five year follow-up of a prospective cohort of juvenile chronic arthritis with recent onset.

One hundred and fifty children with unsuspected juvenile chronic arthritis (JCA) and a disease duration of 3-6 months entered a prospective study. Diagnosis of JCA could be verified in 107 patients according to the WHO-EULAR criteria. After 5.0 +/- 0.9 years 66 of the 107 patients showed no disease activity, 24 of them for more than 2 years, 23 for less than 2 years without any drug therapy. Nineteen patients were still on NSAIDs and/or long acting drugs, 14 patients with unfavourable morphologic outcome (greater than stage II) and 17 patients with severe functional impairment (greater than or equal to stage III) all belonged to the 41 children with still active disease after 5 years follow-up. The disease course was polyarticular in 10 of the 14 patients with severe radiologic changes and in 14 of the 17 with unfavourable functional results. The wrist joint proved especially vulnerable since 46% of the severe radiologic changes concerned this joint. All 4 children with positive rheumatoid factor followed a polyarticular course with severe radiologic changes (stage greater than II), 3 of them together with unfavourable functional outcome. Risk factors for morphologically and functionally unfavourable course are therefore seen in a still active disease after 5 years, a polyarticular joint involvement and a positive rheumatoid factor. Extra-articular complications concerned chronic iridocyclitis in 7 patients, acute iridocyclitis in 2, amyloidosis in 1 and growth retardation in 2 children. -The prospective study is to be continued.

[Juvenile fibromyalgia syndrome]. / Fibromyalgiesyndrom bei Kindern und Jugendlichen.

OBJECTIVE: The aim was to develop a guideline for diagnostic procedures and treatment of juvenile fibromyalgia syndrome (JFMS) in cooperation with 10 German medical and psychological associations and 2 patient self-help groups. METHODS: A systematic literature search, including all controlled studies evaluating diagnosis and treatment of JFMS, was performed in the Cochran Collaboration Reviews (1993-12/2006), Medline (1980-12/2006), PsychInfo (1966-12/2006) and Scopus (1980-12/2006). Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. Grading of the strengths of recommendations was performed according to the German program for disease management guidelines. Standardized procedures to reach a consensus on recommendations were used. RESULTS: Pain in children/adolescents involving several body areas and lasting >3 months without an obvious somatic cause is called JFMS or pain amplification syndrome. Therapeutically, a multidisciplinary concept with psychotherapy and physiotherapy, relaxation techniques and patient education is recommended. CONCLUSION: These guideline will contribute to a better recognition and standardized care of patients with JFMS and facilitate clinical studies.

[MCTD (Sharp) syndrome in childhood (author's transl)]. / Das Sharp-Syndrom (MCTD), eine besondere Form der Kollagenose im Kindesalter.

Clinical course and prognosis of children with MCTD-Syndrome are described and six own cases are compared with the cases reported by other authors. The immunological and histological findings would seem to confirm the independence of the disease or, at least, reveal it as a particular clinical course of other connective tissue diseases. On the other hand, the initial conception, that the course of the disease can be viewed as favourable on account of the absence of kidney and CNS findings, must not be reevaluated according to our experiences of the last few years. This applies particularly to the cases of MCTD in childhood, since authors in the U.S.A. have, in the meantime, reported instances of death. One patient in our own hospital was diagnosed through biopsy as having a severe membrano-proliferative glomerulonephritis, another patient has had a severe myo-pericarditis in 1978.

[Nuclear spin tomography studies (MRI) of joints in juvenile chronic arthritis]. / Kernspintomographische Untersuchungen (MRT) von Gelenken bei juveniler chronischer Arthritis (JCA).

MRT (magnetic resonance imaging) is a new method of producing pictures of internal organs; the main advantage compared to radiography is the ability to subtly differentiate soft tissues. 14 children suffering from juvenile chronic arthritis of different subgroups are described. MRT pictures of knee joints show clearly the structure and form of the articular cartilage, ligaments as well as the nature, density and thickness of the inflammatory tissue. MRT permits a very early diagnosis of a progression in the inflammatory articular process without accompanying ionising radiation, an advantage in childhood.

[Persistent (chronic active) Epstein-Barr virus infection and arthritis in childhood]. / Persistierende (chronisch-aktive) Epstein-Barr-Virus-Infektion und Arthritis im Kindesalter.

Between 1981 und 1983 some 1300 patients with the primary diagnosis of juvenile chronic arthritis were admitted. In 9 of them a persistent EBV-infection was simultaneously evident. The course of disease was primarily systemic with the characteristic criteria: high septic intermittent fever, rheumatic exanthema, hepatosplenomegaly and lymphadenopathy. It is still unclear whether a replication of virus in the synovia or a precipiation of immune complexes is involved. A common cause for the persistent EBV-infection and arthritis via an immune-suppressive agent is possible.

[A case of cobalamin-dependent methylmalonic acidemia. Biochemical aspects, diagnosis and possible treatment (author's transl)]. / Eine cobalaminabhängige Methylmalonacidämie. Biochemische Grundlagen, Diagnostik und Therapiemöglichkeiten.

A case of methylmalonic acidemia with intermittend homocystinuria is described. Special attention is given to the early symptoms of this inborn error of metabolism, like lethargy, muscular hypotony, poor feeding, ketoacidosis, and recurrent vomiting. Furthermore, the necessary diagnostic steps, the pertinent differential diagnosis (septicemia, duodenal stenosis, other inborn errors of metabolism), and the possible treatment are discussed.

[Chronic juvenile arthritis--difficult early diagnosis--differentiation of arthropathies in the patient case load of a juvenile arthritis hospital]. / Juvenile chronische Arthritis (JCA)--eine schwierige Frühdiagnose--Differenzierung der Gelenkserkrankungen im Krankengut einer Rheuma-Kinderklinik.

Among 2369 children who had been admitted and treated in the Rheumatic Children's Hospital Garmisch-Partenkirchen between 1952 and 1979 under the diagnosis "juvenile chronic arthritis (JCA)" or, "collagenosis", there were 244 patients (= 10.3%) for whom in the end a different diagnosis was set. The major part of these children suffered from arthritides where there was proof of a direct or an indirect connection with bacterial infections or where there existed a corresponding suspected diagnosis (altogether 162 out of these 244 children, = 66.4%). The remaining 82 cases differentiated into 26 further diagnoses with various frequencies. Our examinations show that six criteria are found relatively frequently in arthropathies not caused by juvenile chronic arthritis. These require special consideration in the differential diagnosis: oligoarthritic onset of the disease, high fever - especially septic intermittent fever, erythema nodosum, endomyocarditis, no (or only very slight) functional resp. morphological changes of the joints.

[Postinfectious (reactive) arthritis--an important differential diagnosis to juvenile chronic arthritis (JCA) (author's transl)]. / Die postinfektiöse (reaktive) Arthritis, eine wichtige Differentialdiagnose zur juvenilen chronischen Arthritis (JCA).

Symptoms, laboratory findings and clinical course of 10 pediatric patients suffering from postinfectious arthritis are described. The postinfectious arthritis is caused by an infection with Salmonella, Versina, Brucella or Shigella. The illness results from a preceding enteritis accompanied by fever. It differs from the juvenile chronic arthritis by the more clarified etiology and pathogenesis and particularly by the markedly shorter course, the lack of functional deterioration and by normal X-ray findings of the joint structure. In the parainfectious cases a similar pathogenesis is suggested, but the time relation is not as clear; the arthritis is diagnosed ahead of the enteritis. The human leucocyte antigen HLA-B 27 can frequently (90%) be proven in patients suffering from postinfectious arthritis. This is related to a genetic disposition of this type of arthritis as it can be observed in juvenile spondylitis ankylosans and in Reiter-syndrome, which can be considered as a special type of postinfectious arthritis.

[Connatal leukaemia and pseudoleukaemia--two cases with cytochemical findings (author's transl)]. / Konnatale Leukämie und Pseudoleukämie--Zwei Fälle mit zytochemischen Befunden.

Two newborn infants with hyperleukocytosis and blast cells in the peripheral blood are compared. Case 1 represents a connatal leukemia, which could be characterized as monocytic by the naphthol-ASesterase reaction, which was inhibited by NaF. The child died after a few hours. Case 2 must be diagnosed as "pseudoleukemia" in mongolism. The blast cells were classified as lymphoblastic on the basis of a strong granular beta-glucuronidase reaction. The patient achieved spontaneous remission.

[Hyperammonemia due to ornithine transcarbamylase deficiency--a cause of lethal metabolic crisis during the newborn period and infancy (author's transl)]. / Hyperammonämie durch Ornithin- Transcarbamylase-Mangel--Ursache letaler metabolischer Krisen im Säuglingsalter.

A severe hyperammonemia is the characteristic finding in patients with enzyme defects in urea cycle and one of the main causes of the acute metabolic crisis dsuring the newborn period and infancy. A case report is given about two male infants, who died in the age of one and of seven months respectively. In the second child the blood ammonia concentration raised up to 833 micrograms/100 ml, and, OTC deficiency was diagnosed due to enzyme determination in liver biopsie. Probably, the first child, that also died as newborn, suffered from the same disease. In this case, only post mortem findings are available.

[Tuberculous arthritis--a rare, but important differential diagnosis in juvenile chronic arthritis]. / Arthritis tuberculosa--eine seltene, aber wichtige Differentialdiagnose zur juvenilen chronischen Arthritis (JCA).

We observed a 13 year old Turkish boy suffering from chronic arthritis of the left knee since 1983. Clinical symptoms as slow progression of the disease and laboratory data including a positive HLA B 27 test suggests the diagnosis of juvenile chronic arthritis. A tuberculous arthritis was initially excluded by X-ray examination of the chest. The positive tuberculin test was attributed to the BCG vaccination. Because of insufficient response to antiinflammatory drug therapy a synovectomy was performed for diagnostic as well as therapeutic reasons. Histopathological results suggested sarcoidosis. A second synovial biopsy of the affected joint revealed granulomas combined with multiple necrosis typical for tuberculous infection. The animal experiments showed positive results. Tuberculostatic therapy was successful with INH, myambutol and rifampicin. Joint function and MRI results markedly improved.

[Prospective observation study on the clinical course of chronic juvenile arthritis (JCA)]. / Prospektive Beobachtungsstudie zum klinischen Verlauf der juvenilen chronischen Arthritis (JCA).

A non-randomized follow-up study of 106 children with juvenile chronic arthritis was conducted for two years starting from the onset of the disease. All subgroups - with the exception of seropositive polyarthritis - showed a decrease in the number of joints affected, and activity of the disease in a number of patients. Instant remission and therapeutic effects cannot distinctly be differentiated. Radiological changes are proper criteria for early diagnosis in children with intense progressive joint-findings. X-ray examinations of the joints affected are therefore indicated at regular intervals especially, in the seropositive, occasionally in the seronegative polyarthritic subgroup.

[Differentiation of juvenile chronic arthritis--diagnostic significance of HLA associations]. / Differenzierung der Juvenilen Chronischen Arthritis (JCA)--Diagnostische Bedeutung der HLA-Assoziationen.

From January 1980 to June 1982, 150 children with primary onset of a joint disease during the previous 6 months were entered into a prospective non-randomized observation study. 106 of the 150 children were diagnosed as juvenile chronic arthritis cases according to the EULAR-criteria. Nine children of this group belonged to the systemic subgroup (7 girls, 2 boys). HLA-typing was performed in 100 of the 106 children: HLA-B27 was evident in the total patient group with significantly increased 41% versus 8.9% of the control group. This antigen is significantly evident in all subgroups with variously increased frequency, except in the systemic and early-onset (pauciarticular) subgroups; the frequency in the rheumatoid-factor-negative polyarticular type of juvenile chronic arthritis (JCA) was 37.9%, in the rheumatoid-factor-positive polyarticular form 33.3%, and in the oligoarthritis/sacroiliitis-group 72.2%. DR5 was significantly present in the total patient group with 32% (control group 13.4%) and in the early-onset oligoarthritis group (43.7%). The rheumatoid-factor-positive (50%) and negative polyarticular group (31%) showed a pronounced slightly significant increase.

[Rheumatic iridocyclitis in childhood--differentiation on the basis of clinical and immunological parameters (author's transl)]. / Die rheumatische Iridocyclitis im Kindesalter--Differenzierung nach klinischen und immunologischen Gesichtspunkten.

In approximately 10% of the children suffering from juvenile chronic arthritis (JCA), rheumatic iridocyclitis was also diagnosed. In 90 JCA and iridocyclitis patients we studied relative risk, clinical course and prognosis by means of several clinical and immunological parameters. Antinuclear antibodies (ANA), selective IgA-deficiency, oligoarthritis type of onset of the disease and manifestation of JCA during infancy--predominantly in girls--were quite often accompanied by a pronounced susceptibility to rheumatic iridocyclitis, while seropositivity (RF-positivity) and systemic onset of juvenile chronic arthritis normally rule out rheumatic iridocyclitis. Among HLA-B27-positive boys of school age, the acute course of rheumatic iridocyclitis, which rarely results in serious and lasting complications, is more frequent; in some cases juvenile sacroiliitis or ankylosing spondylitis are evident. The evaluation of the risk factors makes it possible to systematically define subgroups likely to develop chronic iridocyclitis and less susceptible groups of patients, thus facilitating early diagnosis and treatment as well as clinical observation of the development of chronic iridocyclitis.

[Amyloidosis-a dreaded complication of juvenile chronic arthritis (JCA). (author's transl)]. / Die Amyloidose-eine gefürchtete Folgekrankheit der juvenilen chronischen Arthritis (JCA).

Our studies describe symptoms, clinical course and prognosis of 60 children (out of a total of 2063 patients) suffering from chronic arthritis complicated with amyloidosis. Amyloidosis is predominantly caused by the systemic subgroup of juvenile chronic arthritis, which is characterized by high inflammation activity. The amyloidosis and the sequelae are one of the main causes of death in JCA (27 of the 90 lethal cases in our juvenile chronic arthritis unit were connected with amyloidosis). Proteinuria is the most frequent sign in the early stage of the amyloidosis. Early diagnose and treatment by cytostatic drugs like chlorambucil seems to improve the prognosis. The cumulative survival results in the existence of two different subgroup of amyloidosis.

[Chronic infantile lactate acidosis]. / Chronische Laktatazidose bei einem Säugling.

A baby with congenital lactic acidosis is described. The blood levels of lactic acid and alanine as well as the excretion of these compounds in the urine were largely elevated. Clinically the illness presented with vomiting, poor feeding, areflexia, muscular hypotonia and hepatomegaly. The baby died at the age of three months. The pyruvate dehydrogenase complex in cultured fibroblasts showed an activity of 14% of normal values.

Trisomy 10p due to t(5;10)(p15;p11) segregating in a large sibship.

A family is reported with a segregating t(5;10)(p15;p11) translocation resulting in a child carrying trisomy 10p. The clinical findings of the patient are compared with trisomy 10p and the Cri-du-Chat syndrome.

Increased serum urate in galactosemia patients after a galactose load: a possible role of nucleotide deficiency in galactosemic liver injury.

Five galactosemic and 5 normal children received an oral load of galactose under standardized conditions. The maximal blood galactose level after 1.5 hours was 12.6 +/- 2.0 (S.D.) mmol/l in individuals with a deficiency of uridylyl transferase (EC2.7.7.12) as compared to 5.8 +/- 1.2 (S.D.) mmol/l in the controls. The concentration of serum urate in galactosemics increased to 155% of the fasting level (P less than 0.005); no rise was detectable in the controls. The elimination of urate with the urine was augmented by the same amount in both groups. Our studies provide evidence for an increased catabolism of hepatic nucleotides. This may lead to a deficiency of nucleotides which is proposed as a cause of galactosemic liver injury.