Andrew H. Eichenfield

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

To formulate consensus treatment plans (CTPs) for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (SLE).

Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis

Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy. The initial dose of methotrexate averaged 7.1 mg/m2/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours. Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or D-penicillamine. Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases. Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months. The range of treatment duration was 8 to 39 months (mean 18.5 months). Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts. Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively. No significant toxic effects were observed. Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy. We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy. Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment.

Naproxen-induced pseudoporphyria: A distinctive photodermatitis

A distinctive photodermatitis developed in 22 children who had been receiving naproxen for prolonged periods. The eruption was marked by erythema, vesiculation, or increased skin fragility characterized by easy scarring of sun-exposed skin. Results of biochemical studies for porphyria were normal, and other causes of photosensitivity were believed to be unlikely. Of the 22 patients, 21 had juvenile rheumatoid arthritis; one patient had systemic lupus erythematosus. Twenty of the patients had fair skin and blue eyes. In each case, all findings except scarring resolved when naproxen was discontinued. Attention must be paid to complaints suggesting photosensitivity in children receiving naproxen.

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.

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/ObjectivesMycophenolate 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. MethodsThis was a retrospective study of pLN patients treated with MMF dosed at 600 mg/m2. 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. ResultsSeventeen 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 &mgr;g/mL compared with 3.02 ± 1.76 &mgr;g/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 &mgr;g/mL) in patients in CR, but low (29.88 ± 22 &mgr;g/mL) in patients not in CR (not statistically significant). ConclusionsMidinterval 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.

Usefulness of FaceTime to Improve Medication Adherence in Adolescents and Young Adults with Systemic Lupus Erythematosus: A Case Series

Poor adherence to medications is a ubiquitous problem in patients with chronic diseases such as systemic lupus erythematosus (SLE), and can be associated with higher risk of disease flare and mortality. With the increasingly accessible use of mobile technology in health care, a novel application has emerged: the use of mobile technology to improve medication adherence in patients with chronic disease. We report the use of video-conferencing via FaceTime to improve medication adherence in childhood-onset SLE patients treated with mycophenolate mofetil. All of the patients had an undetectable mycophenolic acid (MPA) level prior to remote directly observed therapy (remote DOT) with FaceTime. The primary outcome was achievement of a therapeutic MPA level after remote DOT with FaceTime, and was met in all patients. This suggests an important role for video-conferencing in the improvement of medication adherence and disease outcomes not only in SLE patients, but in young adults with other chronic diseases.