What is the most likely diagnosis for a patient presenting with oral ulcers, fever and fatigue, polyarthritis, microscopic hematuria, and a painful rash over the trunk and face?

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Most Likely Diagnosis: Systemic Lupus Erythematosus (SLE)

The most likely diagnosis is SLE (Option A), as this patient presents with the classic constellation of oral ulcers, polyarthritis, microscopic hematuria (indicating renal involvement), fever/fatigue, and a painful rash—all cardinal features of lupus that collectively point toward multisystem autoimmune disease rather than the more limited manifestations of Behçet disease or IgA vasculitis.

Clinical Reasoning

Why SLE is the Primary Diagnosis

  • Multisystem involvement is the key distinguishing feature: The combination of oral ulcers, polyarthritis, renal involvement (microscopic hematuria), constitutional symptoms (fever/fatigue), and cutaneous manifestations represents the typical multiorgan pattern of SLE 1.

  • Oral ulcers in SLE are well-documented and occur in the majority of patients, representing one of the ACR diagnostic criteria 2, 3.

  • Polyarthritis affecting multiple joints is a hallmark of SLE, occurring in the vast majority of patients and typically presenting as symmetric joint involvement 1.

  • Microscopic hematuria indicates lupus nephritis, a serious manifestation that occurs in approximately 50% of SLE patients and represents immune complex-mediated glomerular injury 1.

  • Painful rash over trunk and face is consistent with lupus cutaneous manifestations, which can include malar rash, photosensitive eruptions, or other inflammatory skin lesions 2, 1.

Why NOT Behçet Disease (Option B)

  • Behçet disease is characterized by recurrent bipolar aphthosis (oral AND genital ulcers), which is not described in this patient 4.

  • The renal involvement (microscopic hematuria) is uncommon in Behçet disease, whereas it is a cardinal feature of SLE 1.

  • While Behçet can cause arthritis, the combination of renal disease, polyarthritis, and systemic features more strongly suggests SLE.

Why NOT IgA Vasculitis (Option C)

  • IgA vasculitis (Henoch-Schönlein purpura) typically presents with palpable purpura on the lower extremities, not a painful rash on the trunk and face 5.

  • While IgA vasculitis can cause microscopic hematuria, oral ulcers are not a typical feature of this condition 5.

  • IgA vasculitis is more common in children and typically follows an upper respiratory infection.

Diagnostic Approach

Immediate Laboratory Evaluation

  • Antinuclear antibody (ANA) testing is the first-line screening test for SLE 2, 3.

  • Complete blood count to assess for cytopenias (anemia, thrombocytopenia, leukopenia) which are common in SLE 1.

  • Urinalysis with microscopy to quantify hematuria and assess for proteinuria and cellular casts indicating active nephritis 1.

  • Complement levels (C3, C4) are typically low in active SLE, particularly with renal involvement 1.

  • Anti-dsDNA and anti-Smith antibodies are highly specific for SLE and should be obtained if ANA is positive 2, 3.

  • Renal function tests (creatinine, BUN) to assess kidney function 1.

Critical Pitfalls to Avoid

  • Do not dismiss oral ulcers as simple aphthous ulcers without considering systemic disease when accompanied by other symptoms 3.

  • Do not delay diagnosis by treating symptoms in isolation—the combination of features demands immediate comprehensive evaluation, as diagnostic delay is associated with increased organ damage 3.

  • Do not overlook renal involvement—microscopic hematuria in the context of systemic symptoms requires urgent nephrology consultation, as lupus nephritis requires aggressive immunosuppression to prevent irreversible kidney damage 1.

  • Recognize that oral ulcers in SLE do NOT represent vasculitis histologically, but rather interface mucositis, so the absence of vasculitis on biopsy does not exclude SLE 6.

Management Implications

  • Immediate rheumatology referral is essential for patients with suspected SLE presenting with multisystem involvement 3.

  • Nephrology consultation should be obtained urgently given the microscopic hematuria, as renal biopsy may be needed to classify lupus nephritis and guide treatment 1.

  • Early diagnosis and treatment within 6 months of symptom onset is associated with less organ damage accrual, making prompt recognition critical 3.

References

Research

Pleural and pulmonary involvement in systemic lupus erythematosus.

Presse medicale (Paris, France : 1983), 2011

Guideline

Diagnostic Approach to Soft Palate Ulcers

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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