Familial autoimmunity and risk of developing immune thrombocytopenia and Evans syndrome.

BACKGROUND: Immune thrombocytopenia (ITP) and Evans syndrome (ES) are manifestations of immune dysregulation. Genetic variants in immune-related genes have been identified in patients with ITP and especially ES. We aimed to explore familial autoimmunity in patients with ITP and ES to understand possible contributions to chronicity. PROCEDURE: We assessed family history in two ways: via patient report for ITP and ES and by population-based analysis using the Utah Population Database (UPDB) for ITP. A total of 266 patients with ITP and 21 patients with ES were identified via chart review, and 252 of the 266 patients with ITP were also identified in the UPDB. RESULTS: Chart review showed familial autoimmunity in 29/182 (15.9%) and 25/84 (29.8%) of patients with newly diagnosed+persistent (nd+p) ITP and chronic ITP (cITP), respectively, (p = .009). The UPDB analysis revealed that autoimmunity in relatives of patients with nd+pITP was higher than in relatives of controls (odds ratio [OR]: 1.69 [1.19-2.41], p = .004), but was not significantly increased in relatives of patients with cITP (OR 1.10 [0.63-1.92], p = .734). Incomplete family history in medical records likely contributed to the observed discrepancy. CONCLUSIONS: The findings suggest that familial autoimmunity may have a stronger association with the development of ITP rather than its duration. Twelve (57.1%) patients with ES reported autoimmunity in their relatives. UPDB analysis was omitted due to the small number of patients with ES. The use of population databases offers a unique opportunity to assess familial health and may provide clues about contributors to immune dysregulation features within families.

Pediatric Digit Replantation: A Nationwide Analysis of Failure Rate, Complications, and Potential Factors Affecting Failure.

Purpose: Function and cosmesis may be improved by replantation following digital amputation in pediatric patients. However, accurate failure and complication rate estimates may be limited as most pertinent studies reflect single center/surgeon experience and therefore are limited by small sample sizes. The primary aim of this study was to assess the rate of failure (amputation) following pediatric digital replantation. Secondary aims include evaluating the rate of complications and associated resource utilization (intensive care unit stays, readmission rate, and hospital length of stay). Methods: Digital replantation patients were identified from 47 pediatric hospitals using the 2004 to 2020 Pediatric Health Information System nationwide database. Using applicable International Classification of Disease 9/10 and Current Procedural Terminology codes, we identified complications after replantation, including revision amputation, infection, surgical complications, medical complications, admission to intensive care unit (ICU), and length of stay. Results: Of the 348 patients who underwent replantation the mean age was 8.3 ± 5.1 years, and 27% were female. Mean hospital length of stay was 5.8 ± 4.7 (range, 1-28) days. Of the 53% of patients who required ICU admission, the mean ICU length of stay was 2.4 ± 3.3 days. Failure/amputation after replantation occurred in 71 (20.4%) patients, at a mean of 9.7 ± 27.2 days postoperatively. Surgical complications occurred in 58 (17%) patients, 30-day hospital readmissions occurred in 5.7% of patients, and 90-day readmissions occurred in 6.3% patients. Conclusion: The estimated rate of failure following pediatric digit replantation was 20%. Our data on failure and complication rates and associated resource utilization may be useful in counseling pediatric replantation patients and their families and provide an update on prior literature. Level of Evidence: IV, Prognosis.

Vitamin D status and latitude predict brain lesions in adrenoleukodystrophy.

Objectives: Approximately 40% of boys with X-linked adrenoleukodystrophy (ALD) develop inflammatory demyelinating brain lesions (cerebral ALD, cALD) and are at risk for death or severe disability. Risk factors for cALD are poorly understood. Our objective was to evaluate whether vitamin D status, which influences immune function, is associated with risk for cALD. Methods: We used two independent cohorts to assess whether low vitamin D status is correlated with cALD. We used complementary proxies for vitamin D status: plasma 25-hydroxyvitamin D levels and latitude. In our first cohort, we measured 25-hydroxyvitamin D in biobanked plasma samples from ALD boys with initially normal brain MRIs followed at two expert centers. In a second cohort, we measured latitude (using home ZIP code) among ALD boys identified in a national administrative database (PHIS) covering 51 US pediatric hospitals. We used logistic regression models to estimate the odds of developing cALD in each cohort. Results: In the first cohort, we identified 20 ALD boys with a total of 53 plasma sample timepoints who met inclusion criteria; 50% (n = 10) subsequently developed cALD. Average 25-hydroxyvitamin D levels were lower among boys who developed cALD than those who did not (median 28.9 vs 36.6 ng/ml); p = 0.019. For each 10 ng/mL decrease in 25-hydroxyvitamin D, the odds ratio for developing cALD was 6.94; p = 0.044. In the second cohort, we identified 230 ALD boys across 28 states; 57% of boys (n = 132) developed cALD. Each 2° increase in latitude conferred an odds ratio of 1.17 (95% confidence interval, 1.01, 1.35); p = 0.036 for developing cALD. Conclusions: Using independent cohorts, we found that ALD boys with lower pre-morbid plasma levels of 25-hydroxyvitamin D, or more northerly latitude of residence, were more likely to develop cALD. These findings offer complementary lines of evidence that vitamin D and/or ultraviolet light exposure influence cALD risk.