Case Description: A lean, 17-year-old Caucasian male with type 1 diabetes diagnosed at age 9 experienced an abrupt increase in his insulin requirements. He was managed on mixed daily injections. ...Daily insulin requirements increased from 1.7 units/kg/day to 3.3 units/kg/day over 6 months. His total insulin level was 7 mcIU/mL with a free insulin level of 4.8 mcIU/mL, indicating exogenous insulin antibodies. Switching from insulin aspart to glulisine, due to presumed antibodies against insulin aspart was unsuccessful, and his insulin requirements continued to increase to 4.4 units/kg/day. Immunosuppressive therapy was commenced with mycophenolate mofetil, decreasing his insulin requirements to 1.1 units/kg/day after 7 months of treatment. Repeat testing revealed an improvement in the discrepancy between total and free insulin levels, with a total insulin level of 5.2 mcIU/mL and free insulin level of 4.6 mcIU/mL.
Discussion: Exogenous insulin antibody syndrome should be considered in patients with poorly controlled diabetes and requiring greater than 2 units/kg/day of insulin without obesity. Classically, antibodies against exogenous insulin were found in patients receiving insulin derived from animal sources; however, recombinant human insulin can very rarely trigger an antibody response in select patients. Immunosuppression using mycophenolate mofetil greatly reduced insulin requirements and this case highlights its novel use in children with diabetes who develop insulin antibody syndrome.
Disclosure
L. Saba: None. A. B. Orandi: None. S. Pittock: None. A. Creo: None.
Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by muscle weakness and cutaneous manifestations in adults and children. Calcinosis, a complication of DM, is the abnormal ...deposition of insoluble calcium salts in tissues, including skin, subcutaneous tissue, tendons, fascia, and muscle. Calcinosis is more commonly seen in juvenile DM (JDM), but also develops in adult DM. Although the mechanism of calcinosis remains unclear, several pathogenic hypotheses have been proposed, including intracellular accumulation of calcium secondary to an alteration of the cellular membrane by trauma and inflammation, local vascular ischemia, dysregulation of mechanisms controlling the deposition and solubility of calcium and phosphate, and mitochondrial damage of muscle cells. Identifying calcinosis biomarkers is important for early disease detection and risk assessment, and may lead to novel therapeutic targets for the prevention and treatment of DM-associated calcinosis. In this review, we summarize myositis autoantibodies associated with calcinosis in DM, histopathology and chemical composition of calcinosis, genetic and inflammatory markers that have been studied in adult DM and JDM-associated calcinosis, as well as potential novel biomarkers.
•Anti-NXP2 autoantibodies have been associated with calcinosis in both adult and juvenile dermatomyositis (DM).•The structure and composition of calcinosis differ from normal trabecular bone, with a mineral content of carbonate apatite.•Inflammation plays a central role in the calcinosis process in DM, with calcium as a chemoattractant for inflammatory cells.•Further research is needed to identify serum biomarkers for calcinosis in DM.
Few risk factors have been identified for the development of calcinosis among patients with Juvenile Dermatomyositis, and currently no clinical phenotype has been associated with its development. We ...analyzed a large database of patients to further elucidate any relationships among patients with and without calcinosis.
The CARRA legacy registry recruited pediatric rheumatology patients from 55 centers across North America from 2010 through 2014, including over 650 subjects with Juvenile Dermatomyositis. We compared the demographic characteristics, clinical disease features and treatment histories of those with and without calcinosis using univariate and multivariate logistic regression.
Of the 631 patients included in the analysis, 84 (13%) had a current or prior history of calcinosis. These patients were statistically more likely to have longer durations of disease prior to diagnosis and treatment, have lipodystrophy and joint contractures, and to have received intravenous immune globulin or rituximab as treatments.
Calcinosis is found more often in patients with prolonged active disease, severe disease, and certain clinical features such as lipodystrophy and joint contractures. When these factors are combined with other known associations and predictors, groups of at-risk patients can be more effectively identified, treated and studied to improve overall outcomes.
Tumor necrosis factor‐alpha inhibitor therapy for inflammatory bowel disease may be associated with paradoxical cutaneous adverse events, most commonly psoriasiform eruptions. We present the case of ...a pediatric female patient with Crohn's disease who developed multiple concurrent cutaneous eruptions while on infliximab treatment, including morphea, psoriasiform dermatitis, and genital lichen sclerosus. Although refractory to skin‐directed treatments, all three conditions resolved upon discontinuation of infliximab, supporting their development as a paradoxical reaction to infliximab therapy.
Objective
To characterize the incidence and prevalence of childhood‐onset systemic lupus erythematosus (SLE), and to estimate the proportion of patients who are diagnosed with SLE during childhood.
...Methods
A cohort of patients with incident childhood‐onset SLE from 1976 to 2018 from an 8‐county region in the US were identified based on comprehensive medical record review. All patients met the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE or the ACR SLE classification criteria from 1997 at or before age 18 years. Incidence rates were estimated using Poisson methods. We estimated the childhood‐onset SLE point prevalence for January 1, 2015. Results were sex and age adjusted to the US 2000 population. Among all the SLE patients living in the 8‐county region on January 1, 2015, the proportion of patients diagnosed at ≤18 years was estimated.
Results
A total of 13 children were diagnosed with childhood‐onset SLE during the study period (using the EULAR/ACR definition; mean age at diagnosis 15.1 years, 85% female, 69% White). Childhood‐onset SLE overall adjusted incidence rate was 0.7 (95% confidence interval 95% CI 0.2–1.1) per 100,000 children. The incidence rate in girls was 1.2 (95% CI 0.5–1.9) per 100,000 children, while in boys it was 0.2 (95% CI 0.0–0.5) per 100,000. The adjusted prevalence of childhood‐onset SLE was 1.1 (95% CI 0.0–3.1) per 100,000 children. The proportion of patients with SLE diagnosed as children was 9% (95% CI 6–13%).
Conclusion
In this population‐based study, both the incidence and prevalence rates of childhood‐onset SLE were ~1 per 100,000 children. One in 10 adults with SLE was diagnosed in childhood. More studies are needed to further characterize the epidemiology of childhood‐onset SLE in minorities.
Objective
Systemic juvenile idiopathic arthritis–associated lung disease (SJIA‐LD) is a life‐threatening disease complication. Key questions remain regarding clinical course and optimal treatment ...approaches. The objectives of the study were to detail management strategies after SJIA‐LD detection, characterize overall disease courses, and measure long‐term outcomes.
Methods
This was a prospective cohort study. Clinical data were ed from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD.
Results
We enrolled 41 patients with SJIA‐LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow‐up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty‐four percent of patients carried the HLA‐DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA‐LD also showed markedly elevated serum interleukin‐18 (IL‐18), variable C‐X‐C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti–IL‐1/6 biologics and addition of other immunomodulatory treatments and lung‐directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time.
Conclusion
Patients with SJIA‐LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.
Child with fever, rash, and abnormal gait Ojukwu, Elizabeth; Anderson, Jana; Orandi, Amir B.
Journal of the American College of Emergency Physicians Open,
August 2020, Letnik:
1, Številka:
4
Journal Article
High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment ...guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing.
We retrospectively reviewed the records at a single tertiary-care children's hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure was time to control of muscle and skin disease. Additional outcome measures included glucocorticoid dosing, effect of treatment on height, frequency of calcinosis, and complications from treatment.
Of the 69 patients followed during the study period, 31 fulfilled inclusion criteria. Median length of follow-up was 4.58 years, (IQR 3-7.5). Myositis control was achieved in a median of 7.1 months (IQR 0.9-63.4). Cutaneous disease control was achieved in a median of 16.7 months (IQR 4.3-89.5). The median starting dose of glucocorticoids was 0.85 mg/kg/day, (IQR 0.5-1.74). The median duration of steroid treatment was 9.1 months, (IQR 4.7-17.4), while the median duration of any pharmacotherapy was 29.2 months (IQR 10.4 to 121.3). Sustained disease control off medications was achieved in 21/31 (68%) patients by the end of review. Persistent calcinosis was identified in only one patient (3%).
Current accepted treatment paradigms for Juvenile Dermatomyositis include oral glucocorticoids beginning at 2 mg/kg/day and reduced over a prolonged time period. However, our results suggest that treatment using reduced doses and duration with early use of steroid-sparing agents is comparably effective in achieving favorable outcomes in Juvenile Dermatomyositis.
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