Pediatric Psoriasis Comorbidity Screening Guidelines.

Importance: Psoriasis is a complex inflammatory skin condition associated with serious medical comorbidities in adults, including obesity, hypertension, dyslipidemia, type 2 diabetes mellitus, psoriatic arthritis, nonalcoholic fatty liver disease, depression, anxiety, and decreased quality of life. Because psoriasis begins in childhood in almost one-third of patients, early identification of risk may be critical to minimizing effects on future health. Objective: To develop the first set of guidelines for comorbidity screening for patients with pediatric psoriasis based on current evidence. Evidence Review: A literature review was performed using PubMed from January 1999 through December 2015. Limiting the search to human studies published in English and removing reviews and editorials produced 153 relevant manuscripts. An expert panel in psoriasis, pediatric dermatology, pediatric rheumatology, pediatric gastroenterology, pediatric endocrinology, and adult and pediatric cardiology used the patient-centered Strength of Recommendation Taxonomy (SORT) method to evaluate and grade the quality of evidence. Findings: Because of the limited number of pediatric studies published on these topics, the strength of the panel's recommendations is classified as SORT level C expert consensus recommendations. The majority of recommendations coincide with those endorsed by the American Academy of Pediatrics for the general pediatric patient but with added attention to signs and symptoms of arthritis, depression, and anxiety. The panel also identified key areas for further investigation. Conclusions and Relevance: Patients with pediatric psoriasis should receive routine screening and identification of risk factors for associated comorbidities. These guidelines are relevant for all health care providers caring for patients with pediatric psoriasis, including primary care clinicians, dermatologists, and pediatric specialists. Because these are the first pediatric guidelines, re-review and refinement will be necessary as studies further detail, and possibly stratify, risk in affected children.

Use of Glucuronidated Mycophenolic Acid Levels for Therapeutic Monitoring in Pediatric Lupus Nephritis Patients.

BACKGROUND/OBJECTIVES: Mycophenolate mofetil (MMF) is used to treat pediatric-onset lupus nephritis (pLN). Data are equivocal on the use of plasma mycophenolic acid (MPA) levels as a measure of efficacy and predictor of therapeutic outcomes in pLN. Glucuronidated MPA (MPA-G) is an inactive metabolite that is a marker of adequate absorption and normal metabolism of MMF. We evaluated the use of MPA and MPA-G levels in routine care of pLN. METHODS: This was a retrospective study of pLN patients treated with MMF dosed at 600 mg/m. Clinical renal remission (CR) was defined as proteinuria of less than 500 mg/24 h. Midinterval MPA and MPA-G plasma levels were drawn during routine follow-up, approximately 6 hours after the previous dose of MMF. Steady-state levels of MPA were calculated using pharmacokinetics and compared with routine midinterval plasma MPA levels. RESULTS: Seventeen pLN patients treated with MMF had MPA and MPA-G levels. Eleven patients were in CR; 6 were not in CR at the time of evaluation and had not responded to MMF after more than 3 months of therapy. The mean MPA level for patients in CR was 3.26 ± 2.02 µg/mL compared with 3.02 ± 1.76 µg/mL for patients not in CR. Three patients in CR did not have detectable levels of MPA. Calculated steady-state levels of MPA did not reflect the observed levels. Glucuronidated MPA levels were therapeutic (44.2 ± 26.7 µg/mL) in patients in CR, but low (29.88 ± 22 µg/mL) in patients not in CR (not statistically significant). CONCLUSIONS: Midinterval plasma levels of MPA do not reflect predicted steady-state levels in pLN and do not correlate with clinical response. Midinterval plasma levels of MPA-G indicate adequate absorption and may correlate better with clinical pLN activity.

Safety and Efficacy of Belimumab to Treat Systemic Lupus Erythematosus in Academic Clinical Practices.

OBJECTIVE: To evaluate the use and efficacy of belimumab in academic practices. Belimumab is a human monoclonal antibody that inhibits soluble B lymphocyte stimulator and has been approved for the treatment of adults with systemic lupus erythematosus (SLE). METHODS: Invitations to participate and complete a 1-page questionnaire for each patient prescribed belimumab were sent to 16 physicians experienced in SLE phase III clinical trials. The outcome was defined as the physician's impression of improvement in the initial manifestation(s) being treated without worsening in other organ systems. RESULTS: Of 195 patients treated with belimumab at 10 academic centers, 96% were taking background medications for SLE at initiation of belimumab, with 74% taking corticosteroids. The main indications for initiation of belimumab were arthritis, rash, and/or worsening serologic activity, with 30% of patients unable to taper corticosteroids. Of the 120 patients taking belimumab for at least 6 months, 51% responded clinically and 67% had ≥ 25% improvement in laboratory values. While numbers are limited, black patients showed improvement at 6 months. In a subset of 39 patients with childhood-onset SLE, 65% responded favorably at 6 months, and 35% discontinued corticosteroids. CONCLUSION: Our data demonstrate favorable clinical and laboratory outcomes in patients with SLE at 6 months across all racial and ethnic groups, with similar improvement seen among patients with childhood-onset SLE.

Major infections in a cohort of 120 patients with juvenile-onset systemic lupus erythematosus.

In order to describe the incidence and characteristics of major infections in juvenile-onset systemic lupus erythematosus (jSLE), we studied a cohort of 120 patients (51% Hispanic and 28% African American, 49% with renal involvement and 12% with neuropsychiatric manifestations). There were 101 major infections affecting 44 patients (37%) for an incidence of 169/1000 patient-years of follow-up. Active disease at jSLE diagnosis, renal involvement, neuropsychiatric manifestations, higher cumulative dose of prednisone, and treatment with cyclophosphamide or mycophenolate mofetil were all associated with major infection (p<0.05). By logistic regression, the combined effect of treatment with cyclophosphamide and cumulative dose of prednisone was associated with major infection (p=0.04). Two patients died, one due to cytomegalovirus infection. Major infection was associated with damage (p=0.004). In conclusion, in a large cohort of jSLE patients, major infections were common, were associated with active disease and its treatment, and resulted in noteworthy morbidity.

Consensus treatment plans for induction therapy of newly diagnosed proliferative lupus nephritis in juvenile systemic lupus erythematosus.

OBJECTIVE: To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE). METHODS: A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance after considering the existing medical evidence and current treatment approaches. RESULTS: After an initial Delphi survey (response rate = 70%), a 2-day consensus conference, and 2 followup Delphi surveys (response rates = 63-79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypical patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized dosages for 6 months. Additionally, the CTPs describe 3 options for standardized use of glucocorticoids, including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs. CONCLUSION: CTPs for induction therapy of proliferative LN in juvenile SLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in juvenile SLE.

Neurocognitive impairment in childhood-onset systemic lupus erythematosus: measurement issues in diagnosis.

OBJECTIVE: To assess the prevalence of neurocognitive impairment (NCI) in childhood-onset systemic lupus erythematosus (cSLE) by comparing published classification criteria, and to examine associations between NCI, disease characteristics, psychosocial well-being, and intelligence. METHODS: cSLE patients and ethnicity- and age-matched healthy controls completed a neuropsychological research battery, and results were categorized by 3 different NCI classification criteria with different cutoff scores (e.g., >2, 1.5, or 1 SD below the mean) and the number of required abnormal tests or domains. RESULTS: Forty-one cSLE subjects and 22 controls were included. Subjects were predominantly female (~70%) and Hispanic (∼70%). Executive functioning, psychomotor speed, and fine motor speed were most commonly affected. Method 1 classified 34.1% of cSLE subjects with NCI compared to method 2 (14.6% with decline and 7.3% with NCI) and method 3 (63.4% with NCI). The prevalence of NCI was not significantly different between the controls and patients using any of the categorization methods. NCI was not associated with SLE disease activity or characteristics or with depression. Using method 3, patients in the cognitive impairment group reported significantly lower quality of life estimates (69.7 versus 79.3; P = 0.03). Below average intellectual functioning (intelligence quotient <90) differentiated the number of test scores >1 and >1.5 SDs, but not >2 SDs below the mean. CONCLUSION: NCI was prevalent in cSLE, but varied according to the chosen categorization method. A similar proportion of cSLE patients and controls had NCI, reinforcing the importance of studying an appropriate control group. Categorical classification (i.e., impaired/nonimpaired) may oversimplify the commonly observed deficits in cSLE.

Favorable outcome of juvenile dermatomyositis treated without systemic corticosteroids.

OBJECTIVE: To describe the course of patients with juvenile dermatomyositis (JDM) treated effectively without systemic corticosteroids. STUDY DESIGN: A retrospective study of 38 patients with JDM treated at a tertiary care children's hospital identified 8 patients who had never received corticosteroids. Disease presentation and course, pharmacologic, and ancillary treatments were recorded. RESULTS: Patients in the no corticosteroid group were followed for a median of 2.8 years (range, 2.1 to 9.5 years). Treatment was primarily with intravenous immunoglobulin (IVIG) (75%) and methotrexate (50%), with favorable response in all. No serious treatment complications were observed; headaches were reported by 3 patients receiving IVIG. Two patients had a myositis flare after discontinuing all medications for more than 1 year; complete resolution of symptoms was observed after either 1 or 2 further doses of IVIG. Two patients had calcinosis (at 1 and 9 years of disease); however, no patient had joint contractures, muscle atrophy, lipodystrophy, or functional limitations. CONCLUSIONS: Systemic corticosteroids can be avoided in a select group of patients with JDM. Alternative agents such as methotrexate and IVIG may be prescribed to effectively treat JDM and prevent complications.