Abstract
Accurate diagnosis of autoimmune rheumatic diseases is essential for optimal patient management, particularly in resource-constrained settings. This article presents a systematic diagnostic algorithm that integrates clinical evaluation, laboratory testing (including cost-effective choices), and targeted autoantibody analysis. Special emphasis is placed on differentiating rheumatoid arthritis (RA) from other autoimmune conditions, with a bypass of the antinuclear antibody (ANA) screening pathway when clinical features strongly suggest RA. A flowchart summarizing the diagnostic steps is provided below. Our approach is consistent with current ACR/EULAR guidelines and is designed for clinical utility in low-resource environments.
Introduction
Autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SjS), systemic sclerosis (SSc), inflammatory myopathies (IM), and mixed connective tissue disease (MCTD), pose significant diagnostic challenges due to overlapping clinical features. In settings with limited resources, a cost-effective diagnostic algorithm is crucial. This article outlines a streamlined approach that incorporates patient history, physical examination, basic laboratory tests, and targeted autoantibody panels to enhance diagnostic accuracy and reduce unnecessary expenses.
Methodology
Our diagnostic protocol begins with a thorough clinical evaluation and the ordering of basic laboratory investigations, including a complete blood count (CBC), comprehensive metabolic panel (CMP), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF). In patients where clinical features are highly suggestive of RA—such as symmetric polyarthritis and morning stiffness—the pathway bypasses the ANA screening and proceeds directly with RA-specific tests (RF and anti-cyclic citrullinated peptide [Anti‑CCP]). For other cases, an ANA screening test (using a cost-effective ELISA with a cutoff of 1:160) is performed, followed by analysis of specific ANA patterns (homogeneous, speckled, nucleolar, centromere, and cytoplasmic) to guide further targeted autoantibody testing.

This diagram visually summarizes the diagnostic pathway—from initial clinical assessment to the decision-making steps for RA and non-RA conditions—and is designed to facilitate rapid understanding among clinicians.
Diagnostic Algorithm
The diagnostic algorithm emphasizes:
- Clinical Differentiation: Detailed history and physical examination to identify key features (e.g., malar rash in SLE, symmetric arthritis in RA, dry eyes/mouth in SjS).
- Laboratory Testing: Basic labs with inclusion of RA Factor, and subsequent decision-making on whether to bypass ANA screening for RA.
- Targeted Autoantibody Testing: Depending on the ANA pattern, further tests such as anti-dsDNA, anti-Sm, ENA panel, and others are ordered to narrow the diagnosis.
Results & Discussion
Applying this systematic approach allows clinicians to efficiently differentiate between autoimmune rheumatic diseases. When RA is clinically evident, early ordering of RF and Anti‑CCP reduces diagnostic delays. In cases where ANA screening is warranted, pattern recognition further refines the diagnostic process, enabling the selection of appropriate, cost-effective confirmatory tests. This methodology aligns with ACR/EULAR recommendations and emphasizes the importance of balancing diagnostic accuracy with cost considerations, particularly in low-resource settings.
Conclusion
A structured diagnostic algorithm that integrates clinical evaluation with targeted laboratory testing is essential for managing autoimmune rheumatic diseases in resource-constrained environments. By prioritizing RA-specific tests when clinical features strongly indicate RA and employing cost-effective ANA screening otherwise, clinicians can enhance diagnostic accuracy while optimizing resource use. The accompanying flowchart (Figure 1) provides a visual summary of this approach, serving as a practical guide for healthcare providers.