# Intravenous Immunoglobulin Treatment in Patients With Streptococcal Toxic Shock Syndrome in Southern Sweden: A Retrospective Population-Based Study

## TL;DR

A study in southern Sweden found no clear evidence that IVIG treatment improves survival in patients with streptococcal toxic shock syndrome.

## Contribution

This is the first population-based study evaluating IVIG's effect on STSS mortality in a real-world setting.

## Key findings

- IVIG-treated patients were younger and had fewer comorbidities but higher disease severity.
- Crude analysis suggested lower mortality in IVIG-treated patients, but adjusted analysis showed no significant benefit.
- The study highlights risks of bias in observational research for rare diseases.

## Abstract

Intravenous immunoglobulins (IVIGs) have been suggested as an adjunctive treatment in streptococcal toxic shock syndrome (STSS), but there are no conclusive trials. In southern Sweden, IVIG is routinely used in certain hospitals but not others. We hypothesized that this would resemble a natural experiment, and we aimed to evaluate the effect of IVIG in patients with STSS.

We conducted a population-based retrospective cohort study on STSS cases in southern Sweden from 2017 to 2024. The main exposure was any IVIG treatment, and the primary outcome was 30-day mortality. Cox regression was used, adjusted for lactate, Sequential Organ Failure Assessment score, Charlson Comorbidity Index, and concurrent clindamycin treatment. We modeled IVIG as a time-dependent variable to address immortal time bias.

In total, 106 patients fulfilled STSS criteria, of which 56 (53%) were treated with IVIG. Despite geographic differences, the IVIG group was younger and had fewer comorbidities but higher disease severity at baseline. Crude analysis suggested lower mortality in the IVIG group (hazard ratio, 0.69; 95% CI, .34–1.41). However, after adjusting for covariates and accounting for immortal time bias, the hazard ratio was estimated at 1.69 (95% CI, .66–4.30).

Although our study included a large population of patients with STSS, our results were inconclusive regarding the effect of IVIG on 30-day mortality. This study highlights the risk of bias in observational studies in rare conditions. Prospective interventional studies are needed to determine the efficacy of IVIG in patients with STSS.

In this population-based study of 106 cases with streptococcal toxic shock syndrome, our results were inconclusive regarding the effect of intravenous immunoglobulin on 30-day mortality. Cautious interpretation is warranted due to the risk of remaining bias. Prospective studies are needed.

Graphical AbstractThis graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/intravenous-immunoglobulin-treatment-in-patients-with-streptococcal-toxic-shock-syndrome-in-southern-sweden-a-retrospective-population-based-study-b705d7fd-0403-4929-a5db-5625b763cfe4For image description, please refer to the figure legend and surrounding text.

This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/intravenous-immunoglobulin-treatment-in-patients-with-streptococcal-toxic-shock-syndrome-in-southern-sweden-a-retrospective-population-based-study-b705d7fd-0403-4929-a5db-5625b763cfe4