Chiefs’ Inquiry Corner – 4/25/22

April 25, 2022

Chief residents of the NYU Langone Internal Medicine Residency give quick-and-easy, evidence-based answers to interesting questions posed by house staff, both in their clinics and on the wards.

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 Serum sickness is an immune-complex-mediated type III hypersensitivity reaction that results from the formation of immune complexes due to immunization of a human host with a foreign protein. It classically presents with fever, rash, polyarthritis or polyarthralgias. A variety of foreign proteins (e.g., equine anti-thymocyte globulin, rituximab, infliximab) can cause serum sickness. Serum sickness-like reactions (SSLRs) refer to a constellation of symptoms clinically resembling classic serum sickness but typically caused by drugs (e.g., penicillins, macrolides, sulfonamides, cephalosporins, rifampin, bupropion, fluoxetine, thiouracil) or by infection (e.g., hepatitis B, streptococcus). The pathogenesis of SSLRs is not well understood. Patients with serum sickness generally have decreased complement levels (CH50, C3, and C4) due to activation and consumption of complement and may have multi-organ system involvement while patients with SSLRs typically lack hypocomplementemia.

References: Serum Sickness
 A recent umbrella study (read: like a meta-analysis of meta-analyses) looked at whether vitamin D supplementation was associated with change in fracture incidence. There was a trend towards benefit (AKA fracture risk reduction) among studies who looked at vitamin D and calcium supplementation together, but notably effect sizes were small. Above all else, this umbrella review highlighted the heterogeneity of the data (in terms of dosages, study populations, follow-up period) and outcomes (in terms of effect size, overall significance, kind of fracture prevented) with vitamin D supplementation. The study unfortunately does little to answer the age-old question of who might stand to benefit most from vit D supplementation. There is also the question of whether or not we should even be screening for deficiency. This simple question is in and of itself fraught with complications. First, assays used to measure vitamin D levels are notoriously inconsistent and variable both within and between different manufacturers. Second, there is a fair amount of controversy regarding what even counts as a vitamin D deficiency based on lab cutoffs. Third, in a 46-study USPSTF literature review, there was no impact of vitamin D therapy on mortality, falls, fractures, or any other adverse outcomes. Furthermore, none of these 46 studies looked at the direct harms or benefits of even screening for vitamin D deficiency.

References: Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review of Meta-Analyses of Controlled Trials
 Uterus-owners with post-menopausal bleeding have a 6-9% baseline risk of underlying malignancy (averaged among multiple studies which predominantly look at cisgender women). A TVUS can help refine that risk further. An endometrial stripe < 4mm drops the risk of malignancy significantly (as low as <0.3%). Thus, pending a shared decision-maknig conversation with your patient, thin stripes can prompt the route of careful observation (for recurrent episodes of post-menopausal bleeding).

References: Is an endometrial thickness of ≥4 mm on transvaginal ultrasound scan an appropriate threshold for investigation of postmenopausal bleeding?