Infections Associated with Positive ANA Testing
A positive ANA test can occur with numerous infectious diseases, most notably tuberculosis, syphilis, scrub typhus, HIV, hepatitis B and C, Epstein-Barr virus, and various intracellular bacterial infections—though these findings do not indicate autoimmune disease and typically resolve with treatment of the underlying infection. 1
Most Common Infectious Causes
Bacterial Infections
- Mycobacterium tuberculosis is the most frequently identified pathogen associated with positive ANA in infectious disease patients 1
- Treponema pallidum (syphilis) commonly produces positive ANA results, particularly in secondary and tertiary stages 1
- Bartonella henselae (cat scratch disease) can trigger ANA positivity 1
- Escherichia coli and other gram-negative bacterial infections may produce transient ANA positivity 1
Rickettsial Infections
- Orientia tsutsugamushi (scrub typhus) is a significant cause of ANA positivity, with both confirmed infections and seropositive cases showing positive ANA 1
- Rickettsia species can produce positive ANA results during acute infection 1
Viral Infections
- HIV infection is associated with positive ANA testing and should be routinely screened in adults with suspected autoimmune disease regardless of risk factors 2, 1
- Hepatitis C virus (HCV) produces ANA positivity that may be clinically indistinguishable from primary autoimmune disease 2
- Hepatitis B virus (HBV) infection can cause positive ANA, particularly in chronic infection 2
- Epstein-Barr virus can trigger ANA positivity and has been associated with subsequent development of systemic lupus erythematosus 1
- Cytomegalovirus (CMV) and parvovirus can produce thrombocytopenia with positive ANA 2
Clinical Context and Diagnostic Approach
When to Suspect Infection vs. Autoimmune Disease
- Intracellular infections (mycobacterial, syphilis, rickettsial) are particularly associated with positive ANA and should be actively excluded 1
- In patients presenting with rapidly progressive glomerulonephritis, infection must be excluded with as much certainty as possible before significant immunosuppression is given 2
- The diagnostic workup should include culture of skin, tonsils, blood, or cerebrospinal fluid depending on clinical presentation 2
Key Distinguishing Features
- ANA positivity from infection typically occurs in low titers and is transient, resolving with treatment of the underlying infection 3, 4
- Elevated IgG levels, particularly selective IgG elevation without IgA/IgM elevation, is more suggestive of autoimmune hepatitis than infection 2
- In infection-related glomerulonephritis, assess for low complement (C3, C4), rheumatoid factor, cryoglobulins, and factor B antibody levels to help differentiate from primary autoimmune disease 2
Essential Workup When ANA is Positive
Mandatory Infection Screening
- HIV and HCV serologic testing should be performed routinely in all adults with positive ANA and suspected autoimmune disease, as these infections may be clinically indistinguishable from primary autoimmune conditions 2
- Hepatitis B surface antigen (HBsAg) testing is essential before initiating immunosuppression 2
- Helicobacter pylori testing (preferably urea breath test or stool antigen) should be considered in adults with typical immune thrombocytopenia 2
- Blood cultures should be obtained when bacterial infection is suspected, with special attention to fastidious organisms like Candida, Coxiella burnetii, Borrelia, and Bartonella that may require serological diagnosis 2
Additional Testing Based on Clinical Context
- Tuberculosis screening is critical given that M. tuberculosis is the most common pathogen associated with positive ANA in infectious disease patients 1
- Syphilis serology (RPR/VDRL and confirmatory testing) should be performed given the high association with ANA positivity 1
- Rickettsial serology for O. tsutsugamushi and Rickettsia species should be considered in endemic areas or with compatible clinical presentation 1
Critical Clinical Pitfalls
Risk of Misdiagnosis
- ANA positivity occurs in 30-40% of patients with various infections, making it a non-specific finding that requires careful clinical correlation 1, 3
- In one study, 43 of 82 patients (52%) with positive ANA and no prior autoimmune diagnosis were ultimately found to have infectious disease rather than autoimmune conditions 1
- ANA testing in the presence of non-specific symptoms like fever, joint pain, myalgias, fatigue, or rash increases the likelihood of false-positive results, especially in children 3
Consequences of Premature Immunosuppression
- Starting immunosuppression before excluding infection can be catastrophic, particularly with organisms like tuberculosis, HIV, or hepatitis B 2
- Immunosuppressive agents such as cyclophosphamide or rituximab may accelerate viral replication in untreated HBV infection 2
- The infection rate during induction immunosuppressive therapy for ANCA vasculitis is 38-40%, with bacterial pneumonia being the most common complication 5
Special Populations
- Elderly patients, immunocompromised hosts, and those with sub-sanitary living conditions have higher rates of infection-related ANA positivity 2
- Children are more likely than adults to have positive ANA from acute infections rather than autoimmune disease 3
- ANA positivity is more common in women and the elderly even in healthy populations, further complicating interpretation 4
Monitoring After Infection Treatment
- One patient in a large cohort developed systemic lupus erythematosus after EBV-induced infectious mononucleosis, and another developed adult-onset Still's disease after scrub typhus, indicating that some infections may trigger subsequent autoimmune disease 1
- Patients should be observed for an average of 24 weeks to determine whether ANA positivity resolves with infection treatment or represents emerging autoimmune disease 1
- Persistently low C3 beyond 12 weeks after treatment of postinfectious glomerulonephritis may indicate complement C3 glomerulonephritis rather than infection-related disease and warrants kidney biopsy 2