What more can we learn from muscle histopathology in children with dermatomyositis/polymyositis?

OBJECTIVE: To correlate disease course and complications in children with juvenile dermatomyositis (JDM) and polymyositis (JPM) with specific features of muscle pathology on biopsy. METHODS: This is a retrospective cohort analysis of 59 children diagnosed with JDM or JPM between 1965 and 1998 and followed at the Cincinnati Children's Hospital Medical Center (CCHMC) for a mean duration of 7.3 years (range 1.1-24.5 years). Disease course was characterized as limited, chronic non-ulcerative or chronic ulcerative, similar to previously defined disease course subtypes reported by Crowe et al.(1). All subjects had diagnostic muscle biopsies performed at CCHMC and had disease for at least two years' duration in order to classify their disease course as either limited or chronic. Features of muscle histopathology that were evaluated included loss of the intramuscular capillary bed, infarct, perifascicular myopathy, direct immunofluorescence (DIF) staining of the intramuscular vasculature and specifically, the locale of DIF staining, i.e., small arteries or capillaries. Disease complications that were assessed included calcinosis, contractures, muscle atrophy, lipodystrophy, gastrointestinal ulceration, cutaneous ulceration and death. Data analysis was completed using Chi-square or Fisher's exact tests and logistic regression modeling. RESULTS: Twenty-two children (37%) had limited disease, 24 (41%) had chronic non-ulcerative disease and 13 (22%) had chronic ulcerative disease. Neither loss of the intramuscular capillary bed nor perifascicular myopathy on muscle biopsy significantly correlated with disease course or the various complications evaluated in this study. DIF staining of intramuscular vessels overall was not significantly associated with clinical disease course, but the localization of DIF staining to intramuscular arteries (rather than to capillaries) was significantly associated with the outcome of chronic ulcerative disease. Nine of the 13 children with chronic ulcerative disease had DIF-arterial staining on muscle biopsy (69%), significantly greater than DIF-arterial staining in children with limited disease (32% had DIF-arterial staining) (p = 0.04), chronic non-ulcerative disease (8% had DIF-arterial staining) (p = 0.0002), and non-ulcerative disease overall (limited + chronic non-ulcerative disease groups combined) (20% had DIF-arterial staining), with p = 0.001. Additionally, lack of DIF-arterial staining on biopsy was significantly correlated with patients not having gastrointestinal ulceration (p = 0.002), cutaneous ulceration (p = 0.004) and/or death (p = 0.02) as disease-related complications. Infarct on muscle biopsy was significantly associated with the development of chronic ulcerative disease (p = 0.02), being present on biopsy in 23% of children with chronic ulcerative disease compared with none of the patients with chronic non-ulcerative disease and 4% of those with limited disease. Infarct on muscle biopsy correlated with the outcomes of death (p = 0.01) and gastrointestinal ulceration (p = 0.03), but not with the development of cutaneous ulceration (p = 0.18). CONCLUSION: DIF-arterial staining and infarct on muscle biopsy are significantly associated with the development of chronic ulcerative disease in JDM and JPM, while perifascicular myopathy and loss of the intramuscular capillary network are not associated with disease course. The presence of DIF-arterial staining and infarct on biopsy should suggest early use of second-line therapeutic agents to more quickly bring disease activity under control.

Long-term outcome among patients with juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis (JRA) is a chronic inflammatory disease primarily affecting the joints but also extra articular tissue. The long-term outcome of JRA has different aspects, which include disease outcome, mortality, iridocyclitis and stature. Several studies, which have addressed these issues, are reviewed in this article. In addition, functional, educational and employment status of patients with JRA are also reviewed. To facilitate better understanding of these various studies, a description of the terminology used in defining disease is provided. Several of the instruments that are available for assessing outcome among patients are described. The role of laboratory and radiological evaluation in predicting outcome is also addressed.

Magnetic resonance imaging in juvenile rheumatoid arthritis.

OBJECTIVES: This study was undertaken to examine the role of magnetic resonance imaging (MRI) in the management of patients with juvenile rheumatoid arthritis (JRA). METHODS: A Medline search was performed to identify all publications pertaining to MRI in JRA. Further searches and identification of articles from bibliographies identified articles pertaining to plain radiograph imaging in JRA and MRI in adult rheumatoid arthritis. RESULTS: Studies in both children and adults have shown superiority of MRI to plain radiography in detecting synovial hypertrophy and articular cartilage abnormalities. Several studies in adults have shown a good correlation of MR images with gross anatomic as well as histological findings at arthroscopy. Biochemical changes that occur before structural changes within the joint may even be detectable with magnetic resonance spectroscopy. CONCLUSIONS: MRI holds promise for the assessment of disease progression in JRA and may be useful in serial evaluation, as in clinical trials.

Improving rheumatologists' screening for alcohol use and sexual activity.

OBJECTIVES: To design, implement, and assess the impact of an office-based intervention designed to improve rheumatologists' identification of risk behaviors, especially alcohol use and sexual activity, among adolescents and young adults with chronic rheumatologic conditions. DESIGNS: Prospective intervention study. SETTING: Midwestern academic pediatric rheumatology practice. PARTICIPANTS: Ten attending rheumatologists and fellows and 178 patients (mean age, 18.1 years; 67% female; 88% white; 69% with juvenile rheumatoid arthritis) seen in the practice during the baseline and intervention years. MAIN OUTCOME MEASURES: Change in the rate of screening for alcohol use and sexual activity from the baseline to the intervention year, and physician perceptions of the intervention. RESULTS: Screening for alcohol use increased from 4.2% (9/208) at baseline to 31.6% (56/177) after the intervention (P<.001). Of those patients undergoing screening at follow-up, 20 (36%) of 56 patients reported any alcohol use and 11 (20%) reported current alcohol use. Of those reporting current use, 7 (64%) were counseled or referred. Methotrexate use increased the likelihood of alcohol screening (43% [33/76] vs 26% 123/871; P = .02). Screening for sexual activity increased from 12.4% (27/ 218) to 36.2% (64/177) (P<.001) from baseline to follow-up. Of 52 females undergoing screening at follow-up, 31 (60%) were sexually active. Eleven (41%) of 27 sexually active females were not using contraception other than condoms (4 were not asked about contraception); 7 (82%) of these were referred for contraceptive counseling. Seven rheumatologists completed in-depth semistructured interviews after the intervention. All reported time as a main barrier to screening. Other barriers included logistical problems, discomfort with the subject area, ambivalence about whether risk behavior screening is the province of pediatric rheumatologists, and perceived lack of applicability to their patients. CONCLUSIONS: Despite knowledge and concern about the interaction of immunosuppressive therapy and risk behaviors, few rheumatologists adequately screen the behavior of their adolescent and young adult patients. Time constraints, organizational issues, and physician beliefs remain barriers to widespread screening.

Substance use among adolescents with juvenile rheumatoid arthritis.

OBJECTIVE: To determine the prevalence of substance use among adolescents with juvenile rheumatoid arthritis and to assess available opportunities for rheumatologists to identify high risk teens. METHODS: Fifty-two teens (mean age 13.9 years, 86% female) completed questionnaires regarding substance use (alcohol, tobacco, marijuana, and other illicit substances), functional disability, and frequency of health care contacts. RESULTS: Alcohol use was reported by 30.7% of teens, including 23.5% of those for whom methotrexate was prescribed; 15.4% reported tobacco use in the last year, and 13.4% reported other illicit substance use in their lifetime, although most use was experimental. No teen reported marijuana use. The majority reported regular contact with their rheumatologist but only 26.9% were ever interviewed alone. CONCLUSION: Many teens with juvenile rheumatoid arthritis, including those prescribed methotrexate, used substances, especially alcohol. When rheumatologists see adolescents, particularly in situations where methotrexate may be prescribed, a clinical setting conductive to confidentially, physician comfort in asking about sensitive topics such as substance abuse, and referral relationships with skilled adolescent health and substance abuse counseling providers are essential.

Functional measures in children with rheumatic diseases.

The measurement of function in children with rheumatic diseases is an intimate part of not only the initial diagnostic work-up, but also of every clinic visit during the course of these chronic diseases. This article focuses on the development of specific and general instruments used to systematically measure function and thus, outcome of the rheumatic diseases and their treatments. Reference is made to instruments developed for use in the general pediatric and adult rheumatology population as a basis for the discussion of the instruments in use in pediatric rheumatology. Specifically, the dimensions of physical function, psychosocial impact, economic impact and quality of life are addressed.

School problems and teacher responsibilities in juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis (JRA) may cause a variety of school problems. Twenty-four children with JRA, 24 of their parents, and 14 of their teachers completed questionnaires regarding the frequency of 40 potential school problems and the extent of the teacher's responsibility in helping children deal with 28 medical, academic, or social issues. Though respondents viewed school problems as occurring infrequently, parents and children more frequently than teachers noted that problems occurred (p less than .05). Children felt problems with self-concept and peer relationships occurred most frequently, while parents and teachers emphasized physical health and activity-related problems. Children's ratings regarding extent of teacher's responsibility were lower than those of parents' or teachers' ratings (p less than .05). While parents and teachers viewed the teacher as responsible for helping children deal with psychosocial issues, children felt that teachers should deal primarily with academic areas. Children viewed teachers as being responsible for withholding information about arthritis from their classmates, and did not want their teacher to encourage peer interaction. Results indicate major differences exist between perceptions of children with JRA, and their parents and teachers, regarding frequency of problems and extent of the teacher's responsibility. Since children may resist assistance from teachers in psychosocial areas, their views should be considered before planning interventions to resolve such problems.

The Cutaneous Assessment Tool: development and reliability in juvenile idiopathic inflammatory myopathy.

OBJECTIVES: Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) was designed to measure skin activity and damage in IIM. We describe the development and inter-rater reliability of the CAT, and the frequency of lesions endorsed in a large population of juvenile IIM patients. METHODS: The CAT includes 10 activity, 4 damage and 7 combined lesions. Thirty-two photographic slides depicting IIM skin lesions were assessed by 11 raters. One hundred and twenty-three children were assessed by 11 paediatric rheumatologists at 10 centres. Inter-rater reliability was assessed using simple agreements and intra-class correlation coefficients (ICC). RESULTS: Simple agreements in recognizing lesions as present or absent were generally high (0.5-1.0). ICCs for CAT lesions were moderate (0.4-0.75) in both slides and real patients. ICCs for the CAT activity and damage scores were 0.71 and 0.81, respectively. CAT activity scores ranged from 0 to 44 (median 7, potential range 0-96) and CAT damage scores ranged from 0 to 13 (median 1, potential range 0-22). The most common cutaneous lesions endorsed were periungual capillary loop changes (63%), Gottron's papules/sign (53%), heliotrope rash (49%) and malar/facial erythema (49%). CONCLUSIONS: Total CAT activity and damage scores have moderate to good reliability. Assessors generally agree on the presence of a variety of cutaneous lesions. The CAT is a promising, semi-quantitative tool to comprehensively assess skin disease activity and damage in IIM.

Disease outcomes and ovarian function of childhood-onset systemic lupus erythematosus.

The objective of this study was to determine the medical outcomes including the ovarian function childhood-onset SLE (cSLE). The medical records of all patients diagnosed with cSLE in the Greater Cincinnati area between 1981 and 2002 were reviewed. Patient interviews were performed to obtain additional information on current medication regimens, disease activity [SLE Disease Activity Index (SLEDAI-2k)], and damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)]. The occurence of premature ovarian failure (POF) and reduction of the ovarian reserve was assessed by timed gonadotropin levels. There were 77 patients (F : M = 70 : 7, 53% Caucasian, 45% African-American and 2% Asian) with a mean age at diagnosis of 14.6 years. Nine patients died (88.3% survival) during the mean follow-up of 7.1 years (standard deviation [SD] 5.6) and 88% of the patients continued to have active disease (SLEDAI-2k mean/SD: 6.6/6.7), with 42% of them having disease damage (SDI mean/SD: 1.62/2.1); Non-Caucasian patients had higher disease activity (mean SLEDAI-2k: 10 versus 3.4; P < 0.0001) and more disease damage (mean SDI : 2.1 versus 1.2; P < 0.02) than Caucasian patients. Cyclophosphamide was given to 47% of the patients during the course of their disease and associated with the presence of significantly reduced ovarian reserve (RR = 2.8; 95% CI: 1.7-4.8; P = 0.026). Patient mortality and disease damage with cSLE continue to be high. Although overt POF with cyclophosphamide exposure is rare, it is a risk factor for significantly decreased ovarian reserve cSLE.

Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies.

OBJECTIVE: To assess for novel markers of muscle damage using urinary muscle metabolites by 1H magnetic resonance spectroscopy in patients with juvenile idiopathic inflammatory myopathy (IIM). METHODS: Creatine (Cr), choline (Cho), betaine (Bet), glycine (Gly), trimethylamine oxide (TMAO), and several other metabolites were measured in first morning void urine samples from 45 patients with juvenile IIM and from 35 healthy age-matched controls, and correlated with measures of myositis disease activity and damage. Urinary metabolite to age-adjusted creatinine (Cn) ratios were examined. RESULTS: Age-adjusted initial Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios were higher in patients with juvenile IIM than controls (P < 0.01). Cr:Cn ratios showed significant correlations with physician-assessed global disease damage (Spearman rs = 0.37; P = 0.01), Steinbrocker functional class (rs = 0.35; P = 0.02), serum Cr (rs = 0.72; P = 0.001), and lactate dehydrogenase (rs = 0.34; P = 0.03) levels. Cho:Cn (rs = 0.3; P = 0.05), Gly:Cn (rs = 0.33; P = 0.03), and TMAO:Cn (rs = 0.36; P = 0.02) ratios showed a significant correlation with serum aldolase levels. Cho:Cn ratios also showed a significant correlation with aspartate aminotransferase levels (rs = 0.35; P = 0.02). A linear regression model was used to evaluate the factors influencing urinary Cr:Cn ratios in the 43 patients with data sets available at the initial visit. The regression model explained 73% of the variation in Cr:Cn ratios. The most significant factor was the physician-assessed global disease damage (R2 = 0.50, P = 0.015). CONCLUSION: Urinary Cr:Cn, Cho:Cn, Bet:Cn, Gly:Cn, and TMAO:Cn ratios are elevated in juvenile IIM and Cr:Cn correlates strongly with global disease damage. The Cr:Cn ratio may have potential utility as a marker of myositis disease damage.

Use of methotrexate in children.

Methotrexate continues to be the safest and most efficacious second-line drug for the treatment of JRA. In addition, it is useful in other inflammatory conditions in children. Careful education is necessary, particularly with regard to the importance of laboratory tests and the avoidance of comorbidity such as pregnancy and alcohol-induced liver injury. Health care providers should be comfortable discussing these issues with children and adolescents.

MRI findings of lipoma arborescens of the knee in a child: case report.

Lipoma arborescens is an intraarticular lesion characterized by a frond-like mass of mature fat cells, usually involving the suprapatellar bursa. It is a rare lesion in adults and extremely rare in children. Because of the fatty nature of the lesion, the MRI findings of lipoma arborescens are specific. We present the MRI findings of lipoma arborescens of the knee in a 9-year-old girl.

Arthritis associated with inflammatory bowel disease in children. Relationship of joint disease to activity and severity of bowel lesion.

The records of 102 children with inflammatory bowel disease (44 with ulcerative colitis, 58 with Crohn's disease) were reviewed for evidence of joint disease unassociated with erythema nodosum. Thirteen children had arthritis, four had ulcerative colitis, and nine had Crohn's disease. Arthritis tended to be pauciarticular; ankles, knees, elbows and hips were most commonly affected. In three patients arthritis preceded bowel symptoms, in two the onset of arthritis and bowel disease was concurrent, and in eight arthritis appeared after the onset of bowel symptoms. The relationship between arthritis and specific features reflecting activity and severity of the bowel disease was examined in detail. Twenty-one attacks of arthritis, ranging in duration from two days to 12 weeks (mean, 31 days) were documented. Thirteen attacks occurred when the bowel disease was symptomatic; nine occurred within one month of a flare of the bowel disease. Most exacerbations of bowel disease in patients who had arthritis were unaccompanied by joint complaints. None of the features reflecting activity or severity of the bowel disease was more common in patients with arthritis than in those without arthritis.

Coronary artery disease in systemic lupus erythematosus: risk factors, assessment, and prevention.

The 10-year survival rate of patients with systemic lupus erythematosus (SLE) currently is more than 85|X%; the greater longevity permits late complications to emerge. Recent studies have shown an increased incidence of coronary artery disease (CAD), frequently in young adults. CAD currently is among the most common causes of death in patients with SLE who survive longer than 5 years. Multiple risk factors, some specific to SLE, are implicated in premature development of CAD. These include coronary artery vasculitis, hypertension and hyperlipidemia, corticosteroid therapy, and antiphospholipid antibodies, which may result in coronary thrombotic events. Therefore, risk factors for CAD should be actively sought as part of routine care of patients with SLE, and appropriate modification strategies, including medications if necessary, should be employed. Noninvasive cardiac tests should be used early in the evaluation of any symptoms consistent with myocardial ischemia, heart failure, or cardiac arrhythmias.

Chemotherapy-associated Raynaud's phenomenon in a two-year-old girl.

Raynaud's phenomenon occurred in a 2-year-old girl 17 months after starting multiagent chemotherapy for an endodermal sinus tumor of the vagina. Symptoms began 2 months after receiving her final dose of bleomycin, and gradually resolved over a 6-month period despite continuing vinblastine. Chemotherapy-associated Raynaud's phenomenon appears to be unusual in young children, although mild episodes of vasospasm may not be reported by children or their parents. Specific questions regarding symptoms of Raynaud's phenomenon should be asked of all children receiving vinblastine and bleomycin therapy.

Methylprednisolone pulse therapy for nonrenal lupus erythematosus.

High-dose intravenous methylprednisolone therapy has previously been shown to be efficacious in the treatment of renal lupus erythematosus. The present report presents 2 patients with life-threatening, nonrenal lupus erythematosus. One patient had coma and seizures, while the other had sever thrombocytopenia and anaemia. Both had failed to respond to oral corticosteroid therapy in high doses but had dramatic clinical responses with intravenous methylprednisolone given in 'pulses.' Possible mechanisms of clinical improvement are discussed.

Proliferative response of peripheral blood mononuclear cells to autologous and allogeneic muscle in patients with polymyositis/dermatomyositis.

We examined the proliferative responses of peripheral blood mononuclear cells (PBMC) to autologous and homologous muscle homogenates in 21 patients with early, active, untreated polymyositis/dermatomyositis (PM/DM), 8 patients with chronic PM/DM, 10 patients with myopathies other than PM/DM, 7 patients with connective tissue diseases without myositis, and 12 healthy individuals. PBMC from patients with PM/DM and from control subjects were incubated with various dilutions of autologous and homologous muscle homogenates. PBMC from patients with active PM/DM underwent significant proliferation on exposure to both the autologous muscle and the homologous muscle homogenates. In contrast, PBMC from patients with chronic PM/DM, other myopathies, connective tissue diseases without myositis, and from healthy individuals did not respond to either autologous or homologous muscle. Our findings demonstrate that the PBMC of patients with PM/DM are sensitized to muscle.