Cross-sectional characteristics of pediatric-onset discoid lupus erythematosus: Results of a multicenter, retrospective cohort study.

BACKGROUND: The incidence of systemic lupus in children with discoid lupus is unknown. OBJECTIVE: This study assessed the baseline characteristics of patients with pediatric discoid lupus erythematosus (pDLE). METHODS: Medical records at 17 sites were reviewed for pediatric dermatology and rheumatology patients with discoid lupus erythematosus. The inclusion criteria were clinical and/or histopathologic diagnosis of discoid lupus erythematosus with an age at onset of <18 years. Baseline data were collected at the first documented visit. Outcomes included diagnosis of systemic lupus erythematosus (SLE) at the baseline visit using the 1997 American College of Rheumatology (primary) and the 2012 Systemic Lupus International Collaborating Clinics (secondary) criteria. RESULTS: Of the >1500 charts reviewed, 438 patients met the inclusion criteria. The cohort was predominantly female (72%) and racially/ethnically diverse. A diagnosis of SLE at the baseline visit (pDLE + SLE) was rendered in 162 (37%) patients using the American College of Rheumatology and in 181 (41%) patients using the Systemic Lupus International Collaborating Clinics criteria. Patients with pDLE + SLE were older at the time of rash onset (median, 12.9 vs 8.9 years; P < .001), with shorter time from discoid lupus erythematosus onset to diagnosis, compared with patients with pDLE-only (median, 2 vs 7 months; P < .001). Patients with pDLE + SLE were more likely to be female (P = .004), with generalized discoid lupus erythematosus and clinically aggressive disease, including end-organ involvement, positive serologies, and higher- titer levels of antinuclear antibodies (P < .001). LIMITATIONS: Retrospective study. CONCLUSION: A diagnosis of discoid lupus erythematosus in adolescence should prompt thorough screening for SLE.

Childhood-onset lupus with clinical neurocognitive dysfunction shows lower streamline density and pairwise connectivity on diffusion tensor imaging.

OBJECTIVES: The objective of this report is to use diffusion-tensor imaging (DTI) for investigating white-matter connectivity changes associated with neurocognitive dysfunction in childhood-onset lupus (cSLE-NCD) as measured by formal neuropsychological testing. METHODS: DTI was performed in six individuals with (cSLE-NCD) and nine without neurocognitive dysfunction (cSLE-noNCD) as well as 14 healthy controls. Presence of neurocognitive deficits was identified by formal neuropsychological testing. The brain was divided into 116 regions, and pairwise connectivity (defined as the number of streamlines with an endpoint in each of those regions) and streamline density (defined as the number of streamlines passing through a region regardless of endpoints) were evaluated. Group comparisons were made for regional and global measures of streamline density and pairwise connectivity. RESULTS: A significant decrease in global streamline density was observed in the cSLE-NCD vs. control group (1189 vs. 1305 p = 0.002) and vs. cSLE-noNCD (1189 vs 1320 p = 0.001). The cSLE-noNCD and control groups had similar streamline density. A similar pattern for pairwise connectivity was observed with a significant decrease in the cSLE-NCD group (217) versus the cSLE-noNCD (236; p = 0.013) and control group (238; p = 0.004). Regional measures of pairwise connectivity displayed mixed results. CONCLUSIONS: The analysis of DTI in this pilot study shows cSLE-NCD is associated with global loss of streamline density and pairwise connectivity, suggesting breakdown of the structural network. These results complement previously reported functional and volumetric findings that suggest cSLE-NCD is associated with measurable changes in gray and white matter. If confirmed in larger cohorts, DTI abnormalities could be used as imaging biomarkers of cSLE-NCD.

Effects of obesity on health-related quality of life in juvenile-onset systemic lupus erythematosus.

OBJECTIVE: This study evaluated the effects of obesity on health-related quality of life (HRQOL) measures in juvenile-onset systemic lupus erythematosus (jSLE). METHODS: Obesity was defined as a body mass index (BMI) ≥ 95 th percentile according to the Sex-specific Center for Disease Control BMI-For-Age Charts and determined in a multicenter cohort of jSLE patients. In this secondary analysis, the domain and summary scores of the Pediatric Quality of Life (PedsQL) Inventory and the Child Health Questionnaire (CHQ) of obese jSLE patients were compared to those of non-obese jSLE patients as well as historical obese and non-obese healthy controls. Mixed-effects modeling was performed to evaluate the relationship between obesity and HRQOL measures. RESULTS: Among the 202 jSLE patients, 25% (n = 51) were obese. Obesity had a significant negative impact on HRQOL in jSLE, even after adjusting for differences in current corticosteroid use, disease activity, disease damage, gender and race between groups. Obese jSLE patients had lower physical functioning compared to non-obese jSLE patients, and to non-obese and obese healthy controls. Compared to their non-obese counterparts, obese jSLE patients also had worse school functioning, more pain, worse social functioning and emotional functioning. Parents of obese jSLE patients worry more. The CHQ scores for obese jSLE patients were also worse compared to non-obese jSLE patients in several other domains. CONCLUSION: Our study demonstrates the detrimental effects of obesity on patient-reported outcomes in jSLE. This supports the importance of weight management for the therapeutic plan of jSLE.

Corticosteroid use in childhood-onset systemic lupus erythematosus-practice patterns at four pediatric rheumatology centers.

OBJECTIVE: To evaluate corticosteroid prescribing patterns in childhood-onset systemic lupus erythematosus (SLE), comparing four academic pediatric rheumatology practices. METHODS: Patients with childhood-onset SLE (n=72) treated at four large pediatric rheumatology centers were studied at 3-month intervals for 18 months. Information on medication use, disease activity as measured by the SLEDAI and the SLAM; and disease damage by the SLICC/ACR Damage Index was collected. RESULTS: At the time of enrollment, patients at each center were similar for disease duration, age, frequency of renal involvement and disease damage. Prednisone (mean 9 mg/day) was continued during 72% of periods of inactive disease for at least 3 months (SLEDAI=0). Centers differed in the use of intravenous pulse methylprednisolone (p<0.0001). Even when adjusted for between-center differences in patient weight, race and disease activity, centers also significantly differed in the dose of prednisone (p<0.05). The center with the largest between-patient variability in the dose of prednisone prescribed to its patients showed the smallest between-patient variance in patient disease activity. CONCLUSIONS: Corticosteroids are commonly used for the treatment of childhood-onset SLE, even when the disease is inactive. There appears to be important between-center differences in the use of intravenous and oral corticosteroids for childhood-onset SLE therapy that cannot be explained by patient disease activity corticosteroid prescribing patterns influence disease control. Further studies are needed to determine whether differences in practice patterns lead to significant differences in longer-term disease outcomes with childhood-onset SLE.

Lupus headaches in childhood-onset systemic lupus erythematosus: relationship to disease activity as measured by the systemic lupus erythematosus disease activity index (SLEDAI) and disease damage.

The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is the most commonly used measure of disease activity for children with systemic lupus erythematosus (SLE). For headaches to be scored in the SLEDAI as a symptom of active disease, they have to be nonresponsive to narcotic analgesia. This may affect the overall estimation of disease activity, especially because headaches are common among children with SLE and narcotic analgesia is rarely used for headache therapy in paediatrics. Moreover, the importance of headaches for the development of damage and their relation to other clinical parameters and outcomes has not been well described for children with SLE. We reviewed the medical charts of an inception cohort of children (n = 63) who were newly diagnosed with SLE. Information on headaches and other disease parameters was obtained. Disease activity and damage were measured using the SLEDAI and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI), respectively. It has been shown that the accumulated burden of active disease as measured by serial SLEDAI scores over time is one of the best predictors of eventual damage to children with SLE. New-onset or significant increase of severe and/or persistent headaches (LHA) were reported in 43% of the patients during a mean follow-up of 3.6 years. LHA occurred preferentially among patients with elevated levels of antiphospholipid antibodies (aPL) (P < 0.02) and only 6% of all LHA episodes were treated with narcotics and thus considered for the measurement of disease activity in the SLEDAI. LHA were unrelated to proxy-measures of disease activity, such as the need to intensify therapies. When used in children, the insensitivity of the SLEDAI to capture LHA did not seem to decrease the responsiveness of the SLEDAI to detect clinically important worsening of disease, or negatively impact on its ability to predict damage.

The economic impact of intermittent high-dose intravenous versus oral corticosteroid treatment of juvenile dermatomyositis.

OBJECTIVE: To perform a cost-identification and cost-effectiveness analysis comparing oral corticosteroids (OCS) with high-dose intermittent intravenous corticosteroid (IVCS) regimens in the treatment of juvenile dermatomyositis (JDM). METHODS: Children previously diagnosed and treated for JDM (without myositis-specific or myositis-associated autoantibodies) at a single medical center by a single provider were identified. Two treatment protocols were compared: OCS and IVCS. Data on initial disease severity, time to remission, resource use, and costs generated were collected from patient records. Incremental cost-effectiveness ratios (ICE) were constructed. RESULTS: Patients treated with IVCS achieved median remission 2 years earlier at median increased cost of $13,736. The ICE ratio comparing IVCS to OCS is $6,868 per year of disease avoided. CONCLUSION: This study suggests that, although IVCS treatments are costly, they are cost-effective.

Intravenous corticosteroids: adverse reactions are more variable than expected in children.

OBJECTIVE: To determine the frequency and severity of adverse reactions associated with high dose intermittent intravenous corticosteroids (IVCS) in children with rheumatic disease. METHODS: Prospective documentation of adverse reactions associated with IVCS given to 213 pediatric rheumatology patients over a 4 year period. RESULTS: Forty-six of the 213 children (22%) reported an adverse reaction. The 46 patients received 2622 doses of IVCS. Twenty-one patients (10% of all patients studied) had behavioral changes, including altered mood (14), hyperactivity (4), psychosis (2), disorientation (1), and sleep disturbances (3). Nonbehavioral adverse reactions included headache (5.2%), abdominal complaints (4.7%), pruritus (4.2%), vomiting (3.8%), hives (2.3%), hypertension (2.3%), bone pain (1.5%), dizziness (1.5%), fatigue (1%), lethargy (1%), hypotension (1%), tachycardia (1%), hyperglycemia (1%), fracture (1%), tremor (0.5%), anaphylaxis (0.5%), ulcer (0.5%), and "gray appearance" (0.5%). Using chi-squared analysis, there were no statistical differences in ethnicity (p = 0.54) or diagnosis (p = 0.46) between patient groups, with or without adverse reactions. There was a significant statistical association between history of drug induced cutaneous reaction and adverse reactions to IVCS (p < 0.01). CONCLUSION: IVCS are associated with a spectrum of adverse reactions in children with rheumatic disease, of which volatile behavior is the most frequent. Children with a history of drug induced cutaneous reaction are more likely to have an adverse reaction to IVCS.

Systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) of childhood is a complex and challenging disease which can occur at any age. Identification of disease early in it's course and aggressive, appropriate management leads to improved outcome for an individual child. The history of SLE indicates how much progress has been made in the last quarter century. A discussion of the etiopathogenesis of SLE demonstrates the complexity of the syndrome. This is followed by a description of clinical manifestations, including diagnostic criteria, differential diagnosis and suggested methods for eliciting important symptoms to make the diagnosis. Evaluation of specific organs is next reviewed highlighting critical organ manifestations that are significant for future prognosis. Treatment of SLE includes a variety of medications, including non-steroidal anti-inflammatory medications, steroids and immuno-suppressive drugs. Attention to physical activity, stress and nutrition is equally important. Signs and symptoms that indicate disease flare or infection are described. Lastly, related syndromes are reviewed.

Disseminated Nocardia brasiliensis infection: an unusual complication of immunosuppressive treatment for childhood dermatomyositis.

The use of steroids combined with cytotoxic drugs has increased in the last decade. The concomitant increase of opportunistic infections has contributed significantly to morbidity and mortality of patients treated with immunosuppressive agents. We describe a child with dermatomyositis who developed disseminated Nocardia brasiliensis infection while receiving steroids and methotrexate. Infectious etiology was established by gram stain. The patient was treated successfully. Disseminated Nocardia brasiliensis infection is rare with a high reported mortality. Diagnosis may be delayed secondary to insidious onset, similarity of clinical manifestations to other pathogens and slow growth in routine culture media. Nocardia should be considered early in the evaluation of infection in patients treated with immunosuppressive agents.