Clinical and Immunological Characteristics of Overlap Syndromes in Pediatric Patients at a Tertiary Care Hospital in Mexico

Abstract

Introduction

Overlap syndromes in pediatric rheumatology represent a challenge in diagnosis and treatment due to the coexistence of clinical and immunological features of two or more systemic autoimmune diseases such as systemic lupus erythematosus (SLE), juvenile dermatomyositis (JDM) and juvenile idiopathic arthritis (JIA), among others. The information available at the international level is limited and no specific epidemiological data are available for the pediatric population in Mexico.

Objective

To clinically and immunologically characterize patients with a confirmed diagnosis of overlap syndrome seen at the Federico Gómez Children's Hospital of Mexico.

Methodology

Retrospective longitudinal study. Information was obtained from the records of patients who attended between 2014 and 2024. Clinical and immunological variables and 12-month evolution were recorded. Patients were classified into complete remission, partial remission, or persistence of activity according to criteria for each disease. Univariable and multivariable analysis was performed to explore baseline factors associated with presenting the most frequent overlap diagnosis and associated with complete remission of activity or partial remission/persistence at 1 year.

Results
A total of 188 files were reviewed, of which 30 met the inclusion criteria. Female sex was predominant (66.7%), with a median age at initial diagnosis of 11 years. With a time interval between first and second diagnosis of 12.8 months (ICR 25%-75% 11-16 months). The most frequent initial diagnoses were SLE in 40%, JIA in 23.3% and JDM in 16.7%. JDM was the most frequent overlapping diagnosis (33.3%). Being older at initial diagnosis (MR 1.88, 95% CI 1.04-3.39) and the presence of heliotrope rash (MR 40.8, 95% CI 2.09-797.8) were found to be associated with subsequent diagnosis of JDM in the multivariable analysis adjusted for sex. In univariable analysis comparing disease activity groups, the presence of symptoms such as heliotrope rash, sclerodactyly and muscle weakness were associated with achieving complete remission at 12 months (p=0.03). Patients with a first diagnosis of SLE, pleural effusion, and low complement C3-C4 levels more frequently presented partial or persistent remission (p=0.04, p=0.02, and p=0.03, respectively) (Table). However, these associations did not persist in age-adjusted multivariable analysis.

Conclusions
Age and the presence of specific clinical manifestations at diagnosis of a first systemic autoimmune disease are associated with the overlap of a second disease. Manifestations such as pleural effusion or complement consumption could help to predict the clinical course of the disease in pediatric patients diagnosed with overlap syndrome.