1. In this observational study, idiopathic CD4 lymphocytopenia (ICL) was associated with an increased risk of opportunistic infections, malignancy, and poor response to coronavirus disease 2019 (COVID-19) vaccination.
2. The most common opportunistic infections were related to human papillomavirus, cryptococcosis, molluscum contagiosum, and nontuberculosis mycobacterial disease.
Evidence Rating Level: 2 (Good)
Study Rundown: CD4 T-cell deficiency of unknown cause, known as ICL, is a rare and elusive condition for which the pathophysiology is not well understood. For patients with ICL, the risk of opportunistic infections is significantly increased in comparison to the general population. This study used an observational cohort design to evaluate the clinical, immunologic, and risk factors of patients with ICL to better understand its prognosis and characteristics. The study included a total of 91 adults with ICL. Analysis of the medical records and found that patients with low CD4 counts were at significantly higher risk for both infections but also malignancies. Further, they had poor evidence of serologic response upon receiving the COVID-19 vaccination. The major limitation of this study was the small sample size, which may impact he generalizability of the results. This study presents the aforementioned increased risk of patients with ICL and highlights the need for ongoing discovery of its pathogenesis for the purpose of developing improved therapeutic strategies to minimize its associated morbidity and mortality.
Click here to read the study in NEJM
In-Depth [retrospective cohort study]: This was a retrospective observational study evaluating the disease presentation, genetics and immunologic profile, and prognosticating factors of adult patients with ICL. Patients aged 18 or above were included if they had CD4+ T-cell lymphopenia defined as a count of less than 300 per mm3, or less than 20% total T-cells. Patients were excluded if they had genetic or acquired causes. The primary outcomes of interest were describing the genetic profile, identifying predictors of clinical events such as infection, immunologic studies, response to COVID-19 vaccination, and mortality. After applying the inclusion and exclusion criteria, 91 patients were included in the final analysis. Results of the analysis found that reduced CD4 count as defined by less than 100 cells per mm3 was associated with an increased risk of opportunistic infection (odds ratio [OR], 5.3; 95% Confidence Interval [CI], 2.8-10.7), as well as malignancy (OR 0.5; 95% CI 0.2-0.9). The most common infections were skin or human papillomavirus related (29%). The most common malignancy was squamous-cell carcinoma. Out of 22 included patients who were immunized against COVID-19, 36% (n=8) had no detectable antibodies in their serum. Malignancies were observed in 13 patients (14%). In summary, this study outlined the clinical and genetic characteristics of patients with ICL, identifying that this population continues to be at increased risk for opportunistic infections. It also highlights the ongoing need to uncover its pathogenesis, supporting future longitudinal research with large sample sizes to better elicit the clinical and population characteristics of ICL.
Image: PD
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