Syphilis and Tuberculosis as Mimickers of Autoimmune Diseases: Diagnostic Overlap and Surveillance Implications in Mexico

TL;DR

Syphilis and tuberculosis in Mexico can mimic autoimmune diseases, leading to misdiagnosis and flawed surveillance due to overlapping symptoms.

Contribution

The paper proposes integrating differential diagnostic algorithms and expanded lab criteria into surveillance systems to address diagnostic mimicry.

Findings

Syphilis and tuberculosis can present autoimmune-like features such as elevated acute phase reactants and positive autoantibodies.

Current surveillance systems in Mexico misclassify cases due to a lack of autoimmune disease tracking and diagnostic overlap.

Proposed solutions include syndromic and etiological approaches to improve diagnostic accuracy and reporting.

Abstract

In Mexico, syphilis and tuberculosis are infectious diseases subject to mandatory and immediate epidemiological surveillance, both with special systems that allow nominal follow-up for either variant. Surveillance uses the operational definitions of probable and confirmed cases established in the manual for epidemiological surveillance issued by the General Directorate of Epidemiology of the Ministry of Health. However, both diseases, mainly in the chronic state, present challenges because of their ability to mimic autoimmune disorders. This review explores the phenomenon of clinical and immunological mimicry in secondary and tertiary syphilis, as well as in extrapulmonary tuberculosis, and analyzes its implications for the accuracy of case reporting at the national level. Evidence shows that both infections can present systemic inflammatory features, such as elevated acute phase reactants, positive autoantibodies, and alterations in cerebrospinal fluid that resemble autoimmune profiles. These overlaps can lead to misdiagnosis, inappropriate immunosuppressive treatment and misclassification of confirmed cases within the Mexican surveillance system. Surveillance of these conditions is robust; however, current operational definitions have weaknesses, particularly when atypical or autoimmune conditions are present, as they only focus on cases with the highest prevalence or public health impact. This manuscript proposes the integration of differential diagnostic algorithms and expanded laboratory criteria, including autoimmune markers and molecular tests, into surveillance protocols. Although individual efforts exist in health institutions, in our country, the absence of autoimmune diseases in the national register of obligatory notification stands out, contrasting with surveillance models in other countries, where autoimmune diseases are tracked systematically. To improve diagnostic accuracy and reporting, surveillance systems should incorporate a syndromic and etiological approach, recognizing infectious autoimmune mimicry as a factor in the final recording of confirmed cases to avoid epidemiological silence.

Figures