Rheumatic disease mimics in childhood.

Aches and pains in children can arise from multiple problems, varying from a reaction to minor intercurrent infection that rapidly improves to the presence of severe skeletal lesions such as malignancy; they can also be part of a skeletal dysplasia. All cases require a good history (including family history), a full examination, and basic blood tests, which include the erythrocyte sedimentation rate, hemoglobin, white count, platelets, rheumatoid factor, and antinuclear factor. Other tests need be performed only when suspicion has been aroused. Recognition of unusual syndromes is important; no child should be labeled as having juvenile idiopathic arthritis unless there is a clear history with the presence of soft tissue swelling in appropriate sites and other causes for joint pain have been excluded. The conditions that most frequently mimic systemic onset juvenile arthritis are infections, which may have been partially treated, inflammatory bowel disease, malignancy, familial Mediterranean Fever, and the rarer connective tissue diseases, in particular systemic lupus erythematosus. Bacterial infection should be suspected in a child who is feverish and toxic, with a single hot swollen joint that has limited movement and is often rigidly guarded. Should such a child have already received antibiotics, general symptoms may well be minimal, so one is left with the history and a swollen and painful joint. Aspiration for investigation of the synovial fluid as well as blood tests should be undertaken immediately to establish the nature of any underlying infection.

Bone mineral content and bone mineral metabolism: changes after growth hormone treatment in juvenile chronic arthritis.

OBJECTIVE: To determine whether growth hormone (rhGH) affects bone mineral metabolism and bone mineral content (BMC, g/cm) in a therapeutic trial of recombinant growth hormone in growth retarded children with juvenile chronic arthritis (JCA) treated with steroid. METHODS: BMC was measured in 20 children (of whom 17 were treated with corticosteroid) before and after one year of rhGH. Children were randomized to receive either low dose (12 IU/m2/week) or high dose (24 IU/m2/week) for one year. Three monthly assessments were made of disease activity and anthropomorphic measurements. Blood and urine samples were also obtained to measure indicators of disease activity, bone remodeling, and vitamin D and parathyroid hormone (PTH) status. RESULTS: BMC increased during the treatment period and correlated with increasing height. Osteocalcin levels, normally indicators of bone formation, increased after rhGH treatment and correlated significantly with height velocity, particularly for the high dose treatment group. In contrast, osteocalcin levels were negatively correlated with C-reactive protein levels, both before and during treatment. Height velocity, vitamin D, PTH, and osteocalcin levels were significantly lower than age matched controls before treatment. CONCLUSION: Steroid treated children with both JCA and severe growth retardation have reduced vitamin D, PTH, and osteocalcin levels. After treatment with rhGH, height velocity increased, as did BMC. Growth hormone might be a useful adjunct in the treatment of severe growth retardation and osteoporosis in children with JCA. The longterm benefits of rhGH in the treatment of osteoporosis remain unclear.

Prognosis in juvenile arthritis.

Juvenile arthritis implies an onset of disease under 16 years with arthritis persisting in one or more joints for at least six weeks, and with the active exclusion of well defined illnesses, such as systemic lupus erythematosus. Prognosis implies the ability to predict outcome. Its accuracy depends on many factors with early recognition and appropriate care being important. However, response to treatment may be variable. In general, those with involvement of a few joints do better than those with systemic disease or seropositive juvenile rheumatoid arthritis both with regard to persistence of disease activity and complications. These include not just joint deformities, but osteoporosis, amyloidosis, alterations in growth with overall failure and local anomalies, chronic iridocyclitis and psychosocial problems. More aggressive therapy was only introduced in the 1990's, so it is important that multicentre studies are properly assessed in the context of the suggested International diagnostic criteria. One hundred years ago, George Fredric Still drew attention to the systemic form of the disease as distinct from pure polyarthritis [1], but it was only in the 1970s, as follow-up proceeded, that the separate identity of variants became clinically evident [2]. At the Park City meeting [3] and at the EULAR meeting in 1977 [4] when three subgroups (notably systemic, polyarthritis and pauci-articular onset) were defined, that subclassification became regularly used. However, since there were no absolute diagnostic tests there had to be exclusions. At that time the most common medications were aspirin and corticosteroids, although a few patients received gold or penicillamine. In their large group Wallace and Levinson (1990) [5] found that at the 10 year follow-up between 31% and 55% still had active disease. Girls appeared to have a five-fold greater risk for persistent activity than boys; disease duration was probably the most important factor influencing disease activity at follow-up as suggested previously [6]. It was not until the 1990's that the more aggressive therapy in the form of methotrexate--which Giannini had shown to be effective when given in appropriate dosage [7]--and sulphasalazine [8] and the long acting local corticosteroid triamcinolone hexatonide became regularly employed [9, 10]. At the ILAR Meeting in 1993 an international task force was set up under the chairmanship of Dr. C. Fink [11] to develop a classification for the idiopathic arthritides in children, defining childhood as up to 16 years of age. Active exclusion of well-recognised disorders such as rheumatic fever or systemic lupus erythematosus, still had to be made. The first proposed types, which are mutually exclusive, are shown in Table 1. A more recent meeting in Durban under the chairmanship of Dr. R. Petty is yet to be published, but considerable advances have been made, particularly in the definition of subgroups.

Children with chronic arthritis: the management of transition to adulthood.

Idiopathic juvenile arthritis occurs throughout childhood; the young child needs a major paediatric input while the adolescent, at whatever age the disease started, will need help in achieving a satisfactory transfer to adulthood, perhaps using the 'young adult team'. Throughout, an appropriate team of paediatrician, rheumatologist, physiotherapists, occupational therapists and social workers is important in dealing with such young people and their families. They not only treat the disease but give information to parents and children that will aid the day-to-day management of the condition, and help maintain normal education (progressing to further and higher education) and training leading, hopefully, to an acceptable adult lifestyle.

Juvenile rheumatoid arthritis. Effects of disease activity and recombinant human growth hormone on insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, and osteocalcin.

OBJECTIVE: To investigate possible mechanisms of growth impairment in children with juvenile rheumatoid arthritis (JRA). METHODS: Eighteen prepubertal children with JRA and growth retardation received recombinant human growth hormone (rHuGH) for 1 year. Growth hormone profiles over 24 hours were obtained before treatment in 12 patients; the levels did not differ from those in "short normal" children. Levels of insulin-like growth factor 1 (IGF-1), IGF binding proteins (IGFBPs) 1 and 3, insulin, osteocalcin, and C-reactive protein (CRP), as well as the erythrocyte sedimentation rate were measured serially. Pretreatment levels were compared with control levels. RESULTS: In JRA patients, IGF-1, IGFBP-3, and osteocalcin levels were significantly lower and insulin levels significantly higher than those in controls, but there was no significant difference in the level of IGFBP-1. With rHuGH treatment, height velocity and mean levels of IGF-1, osteocalcin, and insulin increased significantly, while mean levels of IGFBP-1 fell significantly. Levels of IGFBP-3 correlated with those of IGF-1. The height velocity correlated positively with IGF-1 and osteocalcin, and negatively with IGFBP-1. Levels of IGFBP-1 were inversely related to those of insulin and IGF-1. There was a significant negative correlation between the CRP and height velocity, IGF-1 level, and osteocalcin level. CONCLUSION: IGF-1 production is impaired in children with active JRA. Treatment with a therapeutic dose of rHuGH can rectify the IGF-1 deficiency within 4 days, but its effect is adversely influenced by the acute-phase response, as reflected by an elevated CRP level.

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.

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.

Juvenile psoriatic arthritis.

From two studies (Lambert et al, 1976; Shore and Ansell, 1982), it was concluded that juvenile psoriatic arthritis is a distinct entity with one group of patients virtually indistinguishable from those with juvenile chronic arthritis initially, while all the patterns of psoriatic arthritis recorded in adults were seen in the remainder. A family history of psoriasis occurs in about half the patients, and one of arthritis in 20%. A swollen tendon sheath of a single finger or toe associated with synovitis in two or three joints of the digits is highly characteristic. Accurate diagnosis is important because these patients tend to go on to develop an asymmetrical destructive polyarthritis. This needs to be recognized early to utilize effective slow-acting drugs. Southwood and colleagues (1989) have defined two quite distinct groups of juvenile psoriatic arthritis: those young at onset, who are usually girls, and those in adolescence, who are more frequently boys. It is possible that there are other variants, including girls aged 8-10 years with a polyarthritic onset who may go on to develop arthritis mutilans. The concept of 'probable juvenile psoriatic arthritis' is supported by follow-up, in that a significant proportion of such patients do pass into the definite group. It is highly desirable that the suggested Vancouver criteria are validated by a long-term prospective study, which will probably need to be multicentred to ensure that the subgroups are large enough for satisfactory conclusions to be drawn. In the management of this serious arthritis in childhood, it is important to consider long-acting drugs early, before undue damage to joints has occurred. Again, multicentre studies are needed to determine which is the most useful. Presently, methotrexate appears to be the drug of choice.

Treatment of growth retardation in juvenile chronic arthritis with recombinant human growth hormone.

OBJECTIVE: To evaluate the effect of recombinant human growth hormone (rhGH) on the linear growth of children with persistently active juvenile chronic arthritis (JCA), most of whom were receiving steroid therapy. All of them were severely growth retarded, but had adequate GH secretion. METHODS: After monitoring height velocity for one year, children were treated for the following year with either 12 IU/m2 or 24 IU/m2 of rhGH. During this period disease activity, drug treatment, dietary intake and bone maturation as well as linear growth were documented. RESULTS: There was a significant increase in height velocity in almost all children during the treatment period. Children with mild to moderate disease activity grew at a better rate than those with very active disease. Children with polyarticular disease responded better than those with systemic JCA. Those children receiving high dose rhGH grew significantly more than those on the low dose regimen. Bone maturation did not exceed chronological age. CONCLUSION: We conclude the rhGH significantly increases the height velocity during one year of treatment. However, its effect on ultimate adult height remains unknown. Thus extensive longterm studies are required to evaluate the risk benefit ratio of this costly treatment.

Polyarteritis nodosa associated with streptococcus.

Twelve children are described with an essentially benign vasculitic illness in association with streptococcal infection. They demonstrated characteristic clinical features of nodular cutaneous polyarteritis with fever. Laboratory findings showed an acute phase response associated with raised antistreptolysin and antihyaluronidase titres in all patients and a positive throat culture for beta haemolytic streptococcus in three patients. Ten required corticosteroids. Two patients had systemic involvement with abnormal arteriography; both had appreciably raised white cell counts (> 40 x 10(9)/l). They may represent a subset of poststreptococcal vasculitis, requiring cytotoxic treatment for effective disease control.

Biochemical prediction of changes in spinal bone mass in juvenile chronic (or rheumatoid) arthritis treated with glucocorticoids.

OBJECTIVE: To identify biochemical predictors of spinal bone mineral growth and the development of spinal osteoporosis in children with juvenile chronic arthritis (JCA) treated with glucocorticoids. METHODS: Bone mass measurements were made at 3 monthly intervals for one year in 31 children. At each visit, blood and urine were obtained for assessment of laboratory indices related to the acute phase response and bone remodelling rates. Assessments were also made of joint inflammation (simple joint count). RESULTS: Plasma albumin and C-reactive protein (CRP) concentrations contributed independently of height velocity to the prediction of lumbar spinal bone mineral growth, but only when averaged over the year of observation. The simple joint count did not usefully predict spinal bone mineral changes in the individual patient, nor did any measured index normally related to bone turnover (plasma osteocalcin, 25 (OH) vitamin D, urinary hydroxyproline). Mean values of the simple joint count were predicted by mean CRP and CRP trends. Joint count trends were predicted by hemoglobin trends. None of these relationships, although statistically significant, was strong enough to predict individual outcomes precisely. CONCLUSIONS: Failure of spinal bone mineral growth is related to failure of growth in height and weight but also to biochemical markers for the activation of the acute phase response. Failure of bone growth to correlate with increased hydroxyprolinuria or plasma osteocalcin concentrations may be attributed to the confounding effect of glucocorticoid treatment on plasma osteocalcin levels in children whose bone resorption is little changed from normal levels despite their reduced growth. Biochemical measurements are weak substitutes for bone densitometry in monitoring spinal growth in these children.

Drug-induced systemic lupus erythematosus in a nine-year-old boy.

After a series of intercurrent infections, a 9-year-old boy on ethosuximide for pefit mal developed typical drug-induced systemic lupus erythematosus. After ethosuximide was stopped, he continued to deteriorate and was treated with corticosteroid therapy, which could be only gradually tapered off over many months. Follow-up 4 years later showed him to be completely well.

Deflazacort in juvenile chronic arthritis.

Vertebral crush fracture associated with glucocorticoid therapy causes major morbidity in juvenile chronic arthritis (JCA). Deflazacort (DFZ) may have an advantage over prednisone (PRED) because of its alleged bone sparing properties. Of 34 children with JCA receiving more than 5 mg PRED/day, 31 completed a 1-year, double blind, randomized, comparative trial of DFZ and PRED. Patient characteristics at trial entry were well matched. DFZ and PRED were prescribed in equivalent amounts. DFZ achieved similar disease control to PRED, and was not associated with untoward effects. Joint counts, hematological indices and biochemical values did not differ between treatment groups initially or during the trial. Bone density trends (velocities) in the lumbar spine were measured using dual photon absorptiometry at 3-monthly intervals and trends in bone and soft tissue growth calculated. Lumbar spine bone growth correlated with indices of somatic growth, with wide ranges in each group. Co-variance analysis showed a significant advantage (p < 0.007) of DFZ over PRED when spinal bone density was compared to body surface area and weight. Children taking DFZ showed less weight gain but similar height gain to children taking PRED. Children with poor or no somatic growth showed significant lumbar bone loss only in the PRED group. Of the children originally treated with PRED; 11 were switched to DFZ after completing the double blind study. Data for 26 children treated with DFZ for 1 year were thus available and confirmed a significantly greater rate of spinal bone growth relative to somatic growth, p < 0.002.(ABSTRACT TRUNCATED AT 250 WORDS)