Diagnostic Anchoring on Positive Autoimmune Serologies in Polysymptomatic Patients

Patients with diffuse, longstanding symptoms and a broadly positive review of systems are commonly referred for evaluation of systemic autoimmune rheumatic diseases. When these presentations are coupled with incidental serologic abnormalities, most often a low-titer antinuclear antibody, diagnostic ambiguity can solidify into a persistent but unsupported diagnosis of an autoimmune rheumatic disease. A central error in this process is conflating symptom burden with disease probability, while overlooking the corresponding disease prevalence in the general population, the limited specificity of many reported symptoms, and the absence of objective inflammatory findings. In low-prevalence conditions such as systemic autoimmune rheumatic diseases, the accumulation of numerous non-specific symptoms does not meaningfully increase diagnostic likelihood and instead magnifies false-positive interpretations. This review examines how base-rate neglect, anchoring on positive autoantibodies, and diagnostic momentum converge to drive misdiagnosis and iatrogenic harm. It is recommended that a pan-positive review of systems should prompt diagnostic restraint rather than escalation, underscoring the importance of probabilistic reasoning, pattern recognition, and clear communication in preventing misdiagnosis and low-value care.