Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders.

OBJECTIVE: Vertebral fractures are an under-recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy. METHODS: Children were categorized as follows: juvenile dermatomyositis (n = 30), juvenile idiopathic arthritis (n = 28), systemic lupus erythematosus and related conditions (n = 26), systemic arthritis (n = 22), systemic vasculitis (n = 16), and other conditions (n = 12). Thoracolumbar spine radiograph and dual x-ray absorptiometry for lumbar spine (L-spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L-spine BMD Z score, and back pain were analyzed for association with vertebral fracture. RESULTS: Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2-3 fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean +/- SD L-spine BMD Z score was significantly different from zero (-0.55 +/- 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 +/- 1.0, P = 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1-53.8], P = 0.004). CONCLUSION: In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

Cytokine genotypes correlate with pain and radiologically defined joint damage in patients with juvenile rheumatoid arthritis.

OBJECTIVES: Single nucleotide polymorphisms (SNPs) in cytokine genes have been associated with risk of a number of autoimmune diseases. Moreover, some SNPs are associated with variations in rates of in vitro gene expression, and it is therefore possible that these functional polymorphisms may differentially affect inflammatory processes and disease outcome. This project's objective was to determine whether cytokine genotypes correlate with disease outcomes in patients with juvenile rheumatoid arthritis (JRA). METHODS: Genotypes of SNPs of pro-inflammatory cytokines, tumour necrosis factor-alpha -308G -->A, interleukin-6 (IL-6) -174G -->C and interferon-gamma +874G -->A, and anti-inflammatory, immunosuppressive cytokines, interleukin-10 -1082G -->A, -819C -->T and -592A -->C and transforming growth factor-beta1 (TGF-beta1) codon 10T -->C and codon 25G -->C, were determined for patients with JRA who previously participated in a long-term outcome study. Cytokine genotypes and clinical variables showing significant correlations with clinical outcomes at the alpha = 0.100 level in univariate analyses were entered in multivariate tests. RESULTS: In multivariate tests, the IL-6 genotype -174G/G was positively correlated with pain [regression coefficient B = 0.899, 95% confidence intervals (CI) 0.185, 1.612, P = 0.014]. The homozygous TGF-beta1 codon 25G/G genotype showed a protective effect against joint space narrowing on radiographs taken within 2 yr of disease onset, but confidence intervals were wide [odds ratio (OR) 0.176, 95% CI 0.037, 0.837 P = 0.029]. CONCLUSIONS: The correlation of IL-6 genotype with pain and the possible association of the TGF-beta1 codon 25 genotype with short-term radiographic damage (G/C with greater risk and G/G with decreased risk) suggests that both these polymorphisms may be useful early prognostic indicators. Further studies of the relation between cytokine genotypes and outcomes in patients with all forms of juvenile idiopathic arthritis (JIA) are warranted.

Lipodystrophy in patients with juvenile dermatomyositis--evaluation of clinical and metabolic abnormalities.

OBJECTIVE: Lipodystrophy and associated metabolic abnormalities are being increasingly recognized as complications of juvenile dermatomyositis (JDM). We investigated the prevalence of lipodystrophy and the extent of metabolic abnormalities related to lipoatrophic diabetes mellitus in patients with JDM. METHODS: Twenty patients with JDM were evaluated for evidence of lipodystrophy and associated lipoatrophic diabetes mellitus. All patients underwent clinical assessment, laboratory investigations, and metabolic studies (oral glucose tolerance test, lipid studies, insulin antibodies). RESULTS: We found clinical evidence of lipodystrophy and lipoatrophic diabetes mellitus in 4 of 20 patients with JDM and metabolic abnormalities known to be associated with lipodystrophy in another 8 patients. The 20 patients with JDM were categorized as follows: Group 1 (Patients 1-4) consisted of patients with lipodystrophy and either diabetes mellitus (2 patients) or impaired glucose tolerance (2 patients); Group 2 (Patients 5-12): no lipodystrophy but abnormal glucose and/or lipid studies; Group 3 (Patients 13-20): no lipodystrophy and no abnormalities of glucose and lipid studies. CONCLUSION: We found 25% of patients with JDM have lipodystrophy, and 50% present with hypertriglyceridemia and insulin resistance. Screening for metabolic abnormalities in JDM should be included in routine followup because of the effect of lipodystrophy on longterm prognosis.

Echocardiography and pulmonary function testing in childhood onset systemic lupus erythematosus.

The aim of this paper was to investigate the frequency of echocardiography (ECHO) and pulmonary function test (PFT) abnormalities in childhood onset systemic lupus erythematosus (SLE), and to determine the relationship of these abnormalities to disease activity. The charts of 50 patients with childhood onset SLE attending a pediatric rheumatology clinic were reviewed for ECHO and PFT studies. The frequency and description of ECHO and PFT abnormalities were documented. Possible associations of PFT and ECHO abnormalities with clinical cardiopulmonary disease, radiographic findings, and measures of lupus disease activity were evaluated. Forty patients (80%) had at least one ECHO study. Twenty-seven (68%) had an abnormal initial study. Nine of 14 patients with an initial abnormal ECHO had normal findings on repeated study. Three abnormalities were considered moderately severe. Thirty-three patients (66%) had at least one PFT performed. Sixteen (48%) were abnormal initially. Four of these 'abnormal' studies were repeated and the abnormalities persisted. Nine patients (27%) were considered to have a severe abnormality. Thirty-one children (62%) had both studies performed. An initial abnormal ECHO and abnormal PFT was found in 10 (32%) of these children. No relationship between ECHO or PFT abnormality and any measure of disease activity (physician's global assessment, anti DNA, C3 or ESR) could be found. Occult cardiac and pulmonary disease as demonstrated by ECHO or PFT occurs frequently in childhood onset SLE. If we wish to understand the natural history of these abnormal heart and lung findings, it will be necessary to do serial testing with ECHO and PFTs in this population.

Isolated tuberculous monoarthritis mimicking oligoarticular juvenile rheumatoid arthritis.

Isolated monoarthritis caused by Mycobacterium tuberculosis in the absence of clinical pulmonary disease is extremely rare in North America. After decades of consistent declines in incidence, a remarkable resurgence of tuberculosis (TB) is occurring in North America. It must always be considered in the differential diagnosis of chronic monoarthritis if devastating sequelae are to be avoided. We describe 2 cases of tuberculous arthritis in young children presenting with monoarthritis of the knee. The presumptive diagnosis in each case was oligoarticular onset juvenile rheumatoid arthritis (JRA). Each had an atypical course for JRA, with lack of response to intraarticular corticosteroid. The diagnosis of TB arthritis was made only with synovial biopsy.

Comparison of criteria for the classification of childhood arthritis.

OBJECTIVE: To evaluate the applicability of the ILAR criteria for classification of childhood arthritis in an outpatient pediatric rheumatology clinic population, and to determine the proportion of children who met standard classification criteria, but failed to meet ILAR criteria for specific arthritides, and therefore became unclassifiable. METHODS: We reviewed the charts of 70 consecutive patients who had arthritis for at least 6 months, and attended the clinic between September and November 1997. Sixty-nine patients were categorized according to one of the traditional classifications [ACR for juvenile rheumatoid arthritis (JRA), European Spondylarthropathy Study Group (ESSG) for spondyloarthropathy, Vancouver Criteria for juvenile psoriatic arthritis (JPsA)], and the ILAR classification system. RESULTS: Sixty-one patients (88.4%) were classifiable by the ILAR system; 8 others failed to fulfill ILAR criteria for any specific category, and were assigned to the "other arthritis" category. Of the 29 patients with oligoarticular onset JRA, 6 were unclassified, 5 because of exclusions, and one because he fulfilled criteria for 2 categories. Presence of a family history of psoriasis accounted for most of the exclusions in the oligoarthritis and enthesitis related arthritis categories. All patients with polyarticular onset or systemic onset JRA were classified in the corresponding category in the ILAR system. One 9-year-old patient with spondyloarthropathy was reclassified as "other arthritis" because of exclusions. All 6 children with definite JPsA met ILAR criteria for PsA. Of 4 patients with probable JPsA, only 2 met ILAR criteria for PsA, a third was classified as rheumatoid factor negative polyarthritis, and the fourth was classified as "other arthritis" because of exclusions. CONCLUSION: The ILAR classification criteria applied to a group of children with chronic arthritis classified by traditional criteria results in reassignment of 11.6% of the patients, predominantly in the oligoarticular group. It will be important to determine the role of the presence of a family history of psoriasis in classifying these patients.

Knee magnetic resonance imaging in childhood chronic monarthritis.

OBJECTIVE: To describe the usefulness of magnetic resonance imaging (MRI) of the knee in the evaluation of chronic monarthritis of uncertain cause in childhood. METHODS: We retrospectively reviewed 21 children referred to our clinic with a putative diagnosis of chronic inflammatory monarthritis of the knee who had MRI performed between May 1993 and June 1997. The median age was 13 years (range 2-17) and 11 were girls. RESULTS: The clinical diagnosis prior to MRI assessment was inflammatory arthritis in 16 patients, and a primary noninflammatory cause in 5. MRI was done in the patients with presumptive inflammatory arthritis when there were atypical symptoms, signs, or radiographs (n = 14), or when they failed to respond to therapy (n = 2). In the patients with a presumptive noninflammatory diagnosis, MRI was performed to clarify the diagnosis. Twelve children (57%) had MRI evidence of a noninflammatory diagnosis. In 4 children (19%) the MRI study indicated the presence of arthritis, and in 5 children (24%) the MRI studies were normal. The noninflammatory diagnoses included: lipoma arborescens (n = 1), vascular malformation [intraarticular (n = 1), extraarticular (n = 1)], synovial chondromatosis (n = 2), partial anterior cruciate ligament tear (n = 2), traumatic bone contusion (n = 2), possible meniscal tear (n = 1), osteochondritis dissecans (n = 1), and a soft tissue mass of uncertain significance in the suprapatellar pouch (n = 1). CONCLUSION: Inflammatory arthritis is usually diagnosed by clinical assessment alone. Uncommonly, when a single joint is involved, and atypical features are identified by a pediatric rheumatologist, other causes of chronic pain and swelling need to be excluded. In this selected patient population, MRI is a useful tool either to confirm the presence of inflammatory arthritis or to investigate a wide range of pathology that can mimic knee joint arthritis.

Malignancies in children who initially present with rheumatic complaints.

OBJECTIVE: Children ultimately diagnosed with malignancy are referred to pediatric rheumatology clinics with provisional rheumatic diagnoses. We aimed to distinguish the features in these patients that lead to the correct diagnosis of malignancy. STUDY DESIGN: A retrospective review of the case records of 29 children (19 boys and 10 girls, aged 1 to 15.5 years) with malignancy who were referred to 2 pediatric rheumatology centers between 1983 and 1997. RESULTS: The suspected diagnoses on referral were: juvenile rheumatoid arthritis (12), nonspecific connective tissue disease (4), discitis (3), spondyloarthropathy (3), systemic lupus erythematosus (2), Kawasaki disease (2), Lyme disease (1), mixed connective tissue disease (1), and dermatomyositis (1). The final diagnoses were leukemia (13), neuroblastoma (6), lymphoma (3), Ewing's sarcoma (3), ependymoma (1), thalamic glioma (1), epithelioma (1), and sarcoma (1). Patients had features typical of many rheumatic disorders including musculoskeletal pains (82%), fever (54%), fatigue (50%), weight loss (42%), hepatomegaly (29%), and arthritis (25%). Features that were suggestive of malignancy included nonarticular "bone" pain (68%), back pain as a major presenting feature (32%), bone tenderness (29%), severe constitutional symptoms (32%), clinical features "atypical" of most rheumatic disease (48%), and abnormal initial investigations (68%). The atypical features included night sweats (14%), ecchymoses and bruising (14%), abnormal neurologic signs (10%), abnormal masses (7%), and ptosis (3%). Initial investigations with abnormal findings included complete blood count/smear (31%), discordant erythrocyte sedimentation rate and platelet count (28%), elevated lactate dehydrognease level (24%), plain skeletal x-ray films (28%), bone scan (21%), and abdominal ultrasonography (17%). Findings of investigations done before referral to the rheumatology clinic were not recognized as abnormal in 11 (40%) patients. CONCLUSIONS: Patients with a diverse group of malignancies, other than leukemia, may present to the pediatric rheumatologist. Pediatric care providers should be familiar with typical features of childhood rheumatic disorders, and rheumatic diagnoses should be reevaluated in the presence of any atypical or discordant clinical features.

Anti-RNP antibody in a child with undifferentiated carcinoma and no evidence of mixed connective tissue disease.

We describe a young girl who presented with musculoskeletal symptoms and who was found to have high titres of antinuclear antibody with anti-RNP antibody. She was initially suspected of having mixed connective tissue disease, but ultimately was found to have metastatic undifferentiated carcinoma with an unknown primary site. This is a very uncommon malignancy of childhood and an association with anti-RNP antibody has, to our knowledge, not been described. The clinical significance of this finding is discussed.

Pneumocystis carinii pneumonia in childhood systemic lupus erythematosus.

OBJECTIVE: Although Pneumocystis carinii pneumonia (PCP) is known to occur in adults with systemic lupus erythematosus (SLE), this infection has rarely been described in childhood SLE. We describe 3 children with SLE who developed PCP and describe risk factors for this complication. METHODS: A retrospective case review. RESULTS: All 3 children had severe active SLE with organ involvement requiring immunosuppressive therapy, but the clinical presentations of PCP differed in each patient. They shared some of the known risk factors for opportunistic infection in adults with SLE, including lymphopenia, but severe lymphopenia (< 0.35 x 10(9)/1) was not seen. CONCLUSION: PCP is an uncommon but serious complication of childhood SLE, and should be considered in the presence of respiratory symptoms, however subtle. The role of oral chemoprophylaxis is discussed.

Juvenile psoriatic arthritis: followup and evaluation of diagnostic criteria.

OBJECTIVE: To describe the course of juvenile psoriatic arthritis (JPsA) defined by the "Vancouver Criteria." METHODS: A retrospective review of JPsA in 63 children, (44 girls, median age at onset 4.5 yrs; 19 boys, median age at onset 10.1 yrs) who fulfilled the Vancouver Criteria, as follows. Definite JPsA: arthritis with psoriasis, or arthritis with 3 of 4 minor criteria (nail pits, dactylitis, psoriasis-like rash, family history of psoriasis); probable JPsA: arthritis with 2 of the minor criteria. RESULTS: At last followup, 50 children had definite JPsA and 13 had probable JPsA. Rheumatoid factor was absent in all; antinuclear antibody was present in 50%. Thirty-eight children were followed for > 5 yrs, 18 for > 10 yrs, and 7 for > 15 yrs. Forty-four children had active arthritis; 32% were in functional class I, 38% in class II, 22% in class III, and 8% in class IV. Of the 46 patients with oligoarticular onset, 21 remained oligoarticular, and 25 became polyarticular. Arthritis in the small joints of the hands and feet increased in frequency, with arthritis eventually occurring in proximal interphalangeal joints in 63%, metacarpophalangeal or metatarsophalangeal joints in 55%, and distal interphalangeal joints in 27%. Dactylitis occurred in 35%, most commonly in 2nd toes and index fingers. Nine patients (14%) developed chronic anterior uveitis. Eleven of 24 patients (46%) who initially had probable JPsA evolved to definite JPsA after a median of 2.1 yrs. Five developed psoriasis and the remainder developed additional minor criteria. The 13 patients with a current diagnosis of probable JPsA did not differ significantly from the 50 patients with definite JPsA with respect to number of joints involved at onset or during the disease course. Patients with psoriasis (n = 41) did not differ from those with definite JPsA without psoriasis (n = 9) with respect to the number of joints involved at onset or during the disease course, functional class, or need for 2nd line therapy. CONCLUSION: JPsA defined by the Vancouver Criteria is a relatively common chronic arthropathy of childhood that differs clinically, serologically, and genetically from both juvenile rheumatoid arthritis and juvenile ankylosing spondylitis.

Spondyloarthropathies of childhood.

The term spondyloarthropathy, currently used to describe some forms of idiopathic arthritis of childhood, may be inappropriate because most children included in this category do not have arthritis of the spine, and inflammatory disease of the sacroiliac joints is an infrequent or late finding. Juvenile AS, the archetype, or "complete" disease may account for only one fifth of the so-called "spondyloarthropathies". "Incomplete" or "early" spondyloarthropathies are most frequent. Such children may not develop axial symptoms and signs for 5 to 10 years after onset, and they may be better characterized as having enthesitis-related arthritis, a term proposed by a recent task force of the International League Against Rheumatism (ILAR). Reactive arthritis, although etiologically linked with the spondyloarthropathies, uncommonly progresses to AS in childhood; most patients have peripheral arthritis with or without enthesitis resolving in the relatively short term. The arthritis associated with IBD is more commonly peripheral than axial. Although axial disease undoubtedly occurs in JPsA, in the authors' experience it is very uncommon.

An unusual case of mixed sclerosing bone dystrophy presenting with morning stiffness and joint swelling in childhood: a case report.

We describe a case of a 16 year old native Indian girl with pain, morning stiffness and foot swelling who had radiographic changes consistent with mixed sclerosing bone dystrophy (MSBD) combined with fibrous dysplasia.

Atlantoaxial subluxation in children with seronegative enthesopathy and arthropathy syndrome: 2 case reports and a review of the literature.

We describe 2 HLA-B27 positive children with seronegative enthesopathy and arthropathy (SEA) syndrome who developed spontaneous (nontraumatic) atlantoaxial subluxation early in their disease course. Neither child had evidence of spinal cord compression but both had progressive atlantoaxial subluxation in spite of conservative treatment. Both underwent elective posterior cervical (C1-C2) fusion.

Visual prognosis in children with chronic anterior uveitis and arthritis.

OBJECTIVE: To determine the visual and ocular prognosis for children with uveitis and chronic arthritis and in patients with uveitis with juvenile rheumatoid arthritis (JRA) or juvenile psoriatic arthritis (JPsA) and to evaluate risk factors associated with ocular complications. METHODS: We studied 49 children with chronic arthritis having greater than 2 years ophthalmological followup from onset of uveitis. Visual acuity and ocular complications (band keratopathy, synechiae, cataracts, glaucoma, or phthisis bulbi) were documented. For the 45 patients with JRA/JPsA, the antinuclear antibody and HLA status, time and mode of onset, and the course of uveitis, were evaluated as risk factors for developing complications. RESULTS: Mean followup was 9.4 years from diagnosis of uveitis (82 affected eyes). Ocular complications developed in 27 eyes (33%). Visual impairment (corrected acuity 20/50 or worse), occurring only in the presence of complicated uveitis, was present in 12 eyes (15%). Of 45 patients with JRA/JPsA, over 95% developed uveitis within 5 years of onset of arthritis. Those with complicated uveitis (n = 13, mean followup 8.6 years) and uncomplicated uveitis (n = 32, mean followup 10 years) were compared: factors significantly associated with complicated uveitis were (1) a chronic course of uveitis (2) JPsA (3) diagnosis of uveitis prior to, or at the time of arthritis onset (4) symptomatic onset. CONCLUSION: The risk of developing uveitis 5 years after the onset of JRA/JPsA is small. Although ocular complications were common (33%) among patients with uveitis, normal vision was maintained or correctable for over half of them. Those with uveitis and risk factors for developing ocular complications may need close ophthalmological scrutiny.

SEA syndrome revisited: a longterm followup of children with a syndrome of seronegative enthesopathy and arthropathy.

Thirty-six of the 39 children originally described with the syndrome of seronegative enthesopathy and arthropathy, followed for a mean of 11 years after symptom onset, were found to have had a widely varied clinical course. Twelve of the 23 patients (52%) who originally did not have a seronegative spondyloarthropathy developed definite (6) or possible (6) seronegative spondyloarthropathies. The development of a seronegative spondyloarthropathy was associated with HLA-B27 (p = 0.0004) and the presence of arthritis (rather than arthralgia only) at the time of the original report (p = 0.05). For patients with arthritis, the development of a seronegative spondyloarthropathy was associated with arthritis onset after 5 years of age (p = 0.01).