Slow-acting antirheumatic drug use in systemic onset juvenile chronic arthritis.

The records of patients with systemic onset juvenile chronic arthritis were reviewed to study the effects of slow-acting antirheumatic drugs on systemic features of the disease and joint manifestations. Frequency and severity of side effects were also evaluated. The following conclusions resulted from this study. Most children could be treated with an alternate-day corticosteroid regimen. Gold and D-penicillamine treatment was not effective or tolerated during the systemic phase. However, after that phase, joint disease was controlled in 42% and 60% of children, respectively. Chlorambucil treatment was helpful in patients with amyloidosis and in those patients in whom all other drugs had failed. The incidence of side effects of chlorambucil are high, however. Antimalarial drug treatment was well tolerated but ineffective during the systemic phase. It was effective on joint disease alone in 44% of a small number of patients. Azathioprine treatment was well tolerated and effective in 50% of patients.

Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort.

Thirty-four children with juvenile chronic (rheumatoid) arthritis were recruited to a randomized, double-blind study of deflazacort (an oxazolone derivative of prednisone) vs prednisone. All had been receiving glucocorticoid therapy for at least 1 year and required at least 5 mg/d of prednisolone (usually as 10 mg every 2 days). Thirty-one children completed the study. Bone density trends were measured in the spine by dual photon absorptiometry and in the forearm by single photon quantitative computed tomography at 3-monthly intervals. Trends (velocities) in bone and soft tissue growth were calculated. In the spine, bone growth correlated well with indices of soft tissue growth, but covariance analysis showed a significant advantage (P less than .007) of deflazacort when spinal bone mineral growth was compared to body surface area and weight. In part this was due to a temporary interruption in weight by children receiving deflazacort, whose gain in height was comparable with that of the prednisone group. Some children in both groups improved clinically and showed catch-up growth; in these children relative spinal bone mineral growth velocities were about twice those observed for height and weight. It is concluded that during the first year of deflazacort, their spinal bone mineral content at a level that was appropriate for their height and weight. Further observations are required to establish whether this advantage can be maintained subsequently. The anti-inflammatory effects of the two glucocorticoids appeared similar.

Juvenile dermatomyositis.

Juvenile dermatomyositis is a multisystem disease characterized by muscular inflammation affecting primarily the skin and muscle; it presents as a nonsuppurative myositis causing symmetrical weakness and typical skin rashes that affect the face and hands in particular, but can occur at any site. In the last few years, a number of reviews have been published, this article only highlights some points of interest.

Vasculitis in children and adolescents.

Vasculitis can present in childhood. There is a wide spectrum of disease in vasculitis, with Henoch-Schönlein purpura and Kawasaki disease occurring most commonly; however, macroscopic and microscopic polyarteritis, Wegener's granulomatosis, Takayasu's disease, cutaneous polyarteritis, hypersensitivity angiitis; vasculitis associated with connective tissue disorders, such as dermatomyositis, and a number of other miscellaneous vasculitides are seen. With the current range of investigative and therapeutic tools, it is possible to diagnose and treat the majority of patients although morbidity and mortality is not inconsequential.

Circulating immune complexes in subacute infective endocarditis and post-streptococcal glomerulonephritis.

Two out of five patients with subacute infective endocarditis and two patients with post-streptococcal glomerulonephritis had large amounts of soluble circulating immune complexes in their sera. The three others with endocarditis had less severe disease and minimal evidence of circulating immune complexes. Low serum complement was also found in two of the cases.

Naproxen absorption in children.

A study was carried out in 9 children (mean age 10.8 years) suffering from rheumatic disorders to determine peak plasma levels and plasma curve of naproxen following the administration of a single oral dose of a suspension formulation. The results suggest that there is no significant difference in naproxen peak blood levels and half-life between adults and children and a twice-daily dosage regime, as in adults, should be suitable, therefore, for therapeutic use in children. The formulation was well-tolerated and no untoward effects were noted.

The visualization and characterization of two immunological forms of alpha 2 macroglobulin by immunoelectrophoretic methods.

Two peaks of alpha 2 macroglobulin (alpha 2M) were demonstrated in serum or plasma treated with trypsin using crossed immunoelectro-phoresis (CIEP). Both peaks moved the same distance in the first dimension and separated only when electrophoresed into antibody containing gel. The double peak phenomenon was shown not to be an artefact of the antiserum used and that the sample had to be fresh for both peaks to be visualised. Using the methods of staggered well CIEP and crossed thin layer gel chromatography (CTLGC) both peaks were shown to be of very similar antigenicity and molecular size. The technique of line immunoelectrophoresis (LIEP) demonstrated that the newly described lower peak was the alpha 2M/protease complex. The lowest concentration of alpha 2M/protease complexes that could be detected was 0.03 g/l. The two peaks of alpha 2M do not follow the theory of rocket immunoelectrophoresis (RIEP) and this is discussed.

Hypertrophic osteoarthropathy in the paediatric age.

Hypertrophic osteoarthropathy should be considered in any child who presents with a non-inflammatory synovitis of the knees, ankles and wrists and particularly if there is finger clubbing or soft tissue hypertrophy of the fingers. It is rare to get the typical facial appearances until after adolescence. Alteration in epiphyseal growth is associated with the periosteal reaction, as is change in the shape of the patella; whether this leads to premature osteoarthrosis is not yet certain. Secondary disease is common in cyanotic congenital heart disease, but its frequency appears to be decreasing with early treatment of such children. Chest infections are also better controlled so again it is less common, but does still occur, particularly in cystic fibrosis in the older age group who have intractable chest infections. It is seen but rarely in disorders such as inflammatory bowel disease or pulmonary metastases, particularly from bone tumours.

How should pediatric rheumatology be delivered?

In all forms of rheumatic disease in childhood, early and accurate diagnosis is essential. The aims of therapy in juvenile arthritis are pain relief and the preservation of joint function while maintaining normal growth and psychological development. As management is complex it will require a coordinated, multi-disciplinary team in which good communication between all members is a priority. Many families will need some form of counselling, whether it be from a social worker, the paediatrician involved, or a psychologist. This is particularly important in adolescence, whether the disease has commenced at this time or whether the child has gone into adolescence with a chronic illness.

Acute leukaemia related to chlorambucil therapy for juvenile chronic arthritis.

We report the case history of a boy with juvenile chronic arthritis, complicated by amyloidosis, who was treated with chlorambucil. He later developed an acute leukaemia and died. The published reports of malignancies developing in children following the use of this drug are reviewed and it was seen from these that cytotoxic drugs should be reserved for treating the life threatening complications of non-malignant diseases of childhood.

Rheumatoid arthritis with periarticular calcifications.

A rare case of rheumatoid arthritis with periarticular calcifications, lung involvement, pericarditis, nodules, Sjögren's syndrome and various drug side-effects is described. Over a period of more than 10 years of observation, the patient's arthritis has been characterized by remissions and exacerbations.

Indoprofen in juvenile chronic arthritis.

Indoprofen at 10-12 mg/kg body weight was compared with aloxiprin at 80 mg/kg body weight in children suffering from juvenile chronic arthritis. Indoprofen was significantly superior to aloxiprin in reducing soft tissue swelling and joint limitation and was effective in relieving pain and morning slowness and improving grip strength. The drug was well tolerated and is a satisfactory agent for the treatment of chronic arthritis in children.

Amyloidosis in juvenile chronic arthritis: a morbidity and mortality study.

A retrospective study of 79 juvenile arthritic patients with reactive amyloidosis for a mean of 10 years (3 months-24.25 years) from the onset of amyloidosis was performed. Eighty percent of those treated with chlorambucil (n = 57) were alive compared with 23.5% of patients not treated with chlorambucil (n = 19) 10 years after diagnosis. Renal failure was the cause of death in 82.3% and infection in 11.7%. Side effects included one chlorambucil-treated patient who developed acute leukaemia, and seven patients who developed severe leucopenia and four thrombocytopenia. Fifteen patients are no longer on cytotoxic therapy and are in remission. Analysis of their fertility status showed that there were 5 normal births in 3 women and 2 terminations of pregnancy in 23 chlorambucil-treated women of child bearing age. Six women had ovarian failure. None of the male patients fathered a child.

Increased frequency of DR4 in systemic onset juvenile chronic arthritis.

Eighty-one patients with systemic onset juvenile chronic arthritis (JCA) have been tested for HLA-A, -B, -C, and -DR antigens. This study confirms previous reports of an increased incidence of DR4 in these patients. Subdivision of the patients according to their disease course over ten years showed different HLA associations with different disease courses. The frequency of DR4 tended to be greater in patients with less severe disease. There was also an increased incidence of HLA B27 in patients in whom relapses of disease were associated with intercurrent infections.

Triamcinolone into the knee joint in juvenile chronic arthritis.

Sixty children aged less than 10 years with pauci-articular onset juvenile chronic arthritis and knee joint involvement received local injections with triamcinolone hexacetonide into the knee (total 83 knees). One year after injection, 77% of knees were excellent with no soft tissue swelling, no deformity and full range of movement, or good with slight swelling or deformity, but functioning well. Eleven knees which had relapsed within one year improved after a second injection and 2 after a third. Complications were limited to small areas of subcutaneous tissue atrophy in 2 patients. Intra-articular injection of long-acting steroids is a useful means of controlling disease activity in the knee joints of young children with pauci-articular juvenile chronic arthritis.

Sacroiliitis in juvenile chronic arthritis. A 10-year follow-up.

66 children with early juvenile chronic arthritis underwent HLA A and B typing in 1974; 16 carried HLA B27. Ten of these had a pauciarticular onset, 3 systemic and 3 poly-articular. At follow-up 10 years later bilateral sacroiliitis had developed in 9 of the 16 B27 positive children, all of whom had a pauciarticular onset. Males predominated and these children had an older age of onset and a predominantly lower limb arthropathy. Enthesopathy and acute iritis further distinguished this group clinically. Other sacroiliac changes, usually simple fusion associated with severe hip involvement, were seen in 7 of the patients, 6 were girls and 6 were HLA B27 negative. Back pain and limitation had developed in 5 children, 4 of whom were B27 positive, after an average of 8 years' disease and at a mean age of 17.3 years. It is concluded that the presence of HLA B27 in boys aged 9 or over, with an onset of pauciarticular disease, signifies that they belong to the spondylitic group.

HLA antigen frequencies among patients with juvenile chronic arthritis and amyloidosis: a brief report.

Amyloidosis is seen in a small number of patients with juvenile chronic arthritis (JCA). In order to determine whether particular HLA markers might predispose to the development of amyloid in JCA a group of 45 patients with amyloidosis confirmed by biopsy was typed for the HLA-A, B, C and DR loci. The results confirmed previous smaller studies that no HLA antigen detected by standard serological techniques was associated specifically with the development of amyloidosis. Those antigens which showed an altered frequency (ie. DR4 and DRw8) were known to be associated with the different types of JCA onset represented in this group.

A crossover study of naproxen, diclofenac and tolmetin in seronegative juvenile chronic arthritis.

Nonsteroidal anti-inflammatory drugs (NSAID) are useful in the management of juvenile chronic arthritis (JCA) and efficacy has usually been compared with aspirin. The disadvantages of aspirin include the frequency of dosage, monitoring of salicylate levels and concern about Reye's syndrome. We have performed a single blind crossover study comparing naproxen 10 mg/kg/day, tolmetin 25 mg/kg/day and diclofenac 2 mg/kg/day in 28 children with seronegative JCA over 12 weeks. Clinical and laboratory assessments were made after 4 weeks of treatment on each drug. Clinical improvement was seen with all three NSAID compared to baseline after a 24-hour washout period, but statistical significance was reached in only 2 or 3 of the clinical parameters for each drug. Side effects were mild and typical of NSAID, but occurred less frequently with naproxen (5) and tolmetin (5) than with diclofenac (7). Thus the anti-inflammatory effect of all three drugs was confirmed with no significant differences between them in terms of efficacy and tolerance. Tolmetin 200 mg tablets are now only available in France and N. America, therefore naproxen or diclofenac are recommended as the first line of treatment in children with chronic arthritis over the age of 5.

Spinal and somatic growth in patients with juvenile chronic arthritis treated for up to 2 years with deflazacort.

We previously reported a double-blind controlled trial of Deflazacort vs Prednisone in patients with Juvenile Chronic Arthritis who had required corticosteroid therapy for at least one year. This paper presents further results on an additional 11 patients, making 26 altogether, who were treated for one year with deflazacort. Fourteen of these went on to a second year of deflazacort treatment. As previously reported, the relative rate of spinal bone mineral growth in the first year was greater for the spinal bone mineral content than for the body surface by about 70%. In the second year of treatment spinal bone mineral continued, with wide variations, to grow at the same or a very slightly greater rate. However, somatic growth recovered so that there was no significant difference between the relative growth rates in the spinal bone mineral and the body surface area in year 2 (P = 0.78). Deflazacort therapy appears to permit appropriate growth of the spine in relation to the rest of the body against a background of variable growth impairment due to the disease process and the treatment required to control it.

Serum IGF-I levels and growth failure in juvenile chronic arthritis.

The association between growth failure and serum IGF-I levels has been assessed in 32 children with Juvenile Chronic Arthritis (JCA) aged 5-16 years. A spectrum from normal growth to severe growth failure was included in the study population. Height Standard Deviation Score (SDS) ranged from -5.79 to +1.41 (median -1.22) and Height Velocity from 0.72-8.85 cm/yr (median 3.81 cm/yr). Known risk factors for growth failure (disease activity, steroid treatment, vertebral collapse) were confirmed. Additionally, height SDS was significantly correlated with serum IGF-I levels (rs = 0.49; p = 0.008); height velocity was significantly, although less strongly correlated with IGF-I levels (rs = 0.41; p = 0.027). There was no correlation between IGF-I levels and either of two indices of nutritional status, or between IGF-I levels and current steroid dose. The correlation of serum IGF-I with parameters of growth failure may be due to either insufficient secretion of growth hormone (GH) or defective GH action. In view of the recently increased availability of GH for treatment of short stature, it is important to distinguish between these two mechanisms.