What is the most likely diagnosis and initial work‑up for a patient presenting with bilateral hand inflammatory arthritis, painful oral ulcers, and acute renal failure?

Most Likely Diagnosis: Systemic Lupus Erythematosus (SLE)

The triad of bilateral hand inflammatory arthritis, painful oral ulcers, and acute renal failure strongly suggests systemic lupus erythematosus (SLE) as the primary diagnosis, requiring urgent serologic testing and renal biopsy to confirm lupus nephritis. 1

Clinical Reasoning

This presentation represents a classic multi-system autoimmune disease pattern. While the provided evidence focuses heavily on rheumatoid arthritis, the combination of features points away from RA:

• Oral ulcers are NOT a feature of rheumatoid arthritis but are a defining criterion of SLE 2
• Acute renal failure is extremely rare in RA but occurs in 50-60% of SLE patients as lupus nephritis 2, 3
• Hand arthritis occurs in both conditions, but SLE arthritis is typically non-erosive, while the acute renal failure distinguishes this case 4, 3

The evidence documents that SLE commonly presents with arthralgia in 68.75% and arthritis in 48.31% of patients, with hand and wrist involvement being most typical 2, 3. Oral ulcers (mucosal ulcers) are among the ACR classification criteria for SLE 2.

Immediate Diagnostic Work-Up

Urgent Laboratory Tests (Order Stat)

• Complete blood count with differential to assess for cytopenias (leukopenia, lymphopenia, thrombocytopenia, hemolytic anemia) which occur commonly in SLE 1, 2
• Comprehensive metabolic panel including creatinine, BUN, electrolytes, liver enzymes, and albumin to quantify renal dysfunction 1, 5
• Urinalysis with microscopy looking for proteinuria, hematuria, cellular casts (RBC casts are pathognomonic for glomerulonephritis), and dysmorphic RBCs 6, 1
• 24-hour urine protein or spot urine protein-to-creatinine ratio to quantify proteinuria severity 2
• ESR and CRP (CRP preferred) to document inflammatory activity, though CRP may be normal in active SLE unlike other inflammatory conditions 6, 1

Essential Autoantibody Panel

• Antinuclear antibody (ANA) with titer and pattern—positive in >95% of SLE patients 1, 2
• Anti-double stranded DNA (anti-dsDNA) antibodies—highly specific for SLE and correlates with disease activity and renal involvement 1, 4
• Anti-Smith (anti-Sm) antibodies—highly specific for SLE though less sensitive 1
• Complement levels (C3, C4, CH50)—low levels indicate active disease and correlate with lupus nephritis 2, 4
• Rheumatoid factor (RF) and anti-CCP to exclude rheumatoid arthritis or identify "rhupus" syndrome (rare overlap) 1, 7

Additional Serologies

• Anti-SSA/Ro and anti-SSB/La antibodies if sicca symptoms present 1
• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) given thrombotic risk in SLE 2
• Direct Coombs test if anemia present to detect autoimmune hemolytic anemia 2

Imaging Studies

• Bilateral hand and wrist radiographs to assess for erosive changes—SLE typically shows non-erosive arthritis unlike RA, though "rhupus" can show erosions 1, 7, 3
• Renal ultrasound to assess kidney size, echogenicity, and exclude obstruction as cause of acute renal failure 5
• Power Doppler ultrasound of hands if clinical synovitis is subtle—superior to examination for detecting inflammation in SLE arthritis 4

Critical Next Steps

Nephrology Consultation (Urgent)

Renal biopsy is indicated urgently to confirm lupus nephritis, determine histologic class (I-VI), guide immunosuppressive therapy intensity, and establish prognosis 2, 5. Lupus nephritis class determines treatment—Class III/IV requires aggressive immunosuppression with cyclophosphamide or mycophenolate mofetil plus high-dose corticosteroids 2.

Rheumatology Referral (Urgent)

Refer within 6 weeks of symptom onset per inflammatory arthritis guidelines, though this case warrants immediate consultation given multi-organ involvement 1.

Differential Diagnoses to Exclude

Rhupus Syndrome (SLE + RA Overlap)

• Rare coexistence showing erosive polyarthritis with SLE features 7
• Would show positive RF, anti-CCP, ANA, and anti-dsDNA simultaneously 7
• Renal involvement less common than pure SLE 7

Drug-Induced Lupus

• Oral ulcers and renal failure are rare in drug-induced lupus, making this less likely 2
• Obtain medication history for hydralazine, procainamide, isoniazid, minocycline 2

ANCA-Associated Vasculitis

• Can cause arthritis, oral ulcers, and rapidly progressive glomerulonephritis 1
• Order ANCA panel (PR3-ANCA, MPO-ANCA) to exclude granulomatosis with polyangiitis or microscopic polyangiitis 1

IgA Vasculitis (Henoch-Schönlein Purpura)

• Typically shows palpable purpura on lower extremities, not just arthritis 8
• Renal involvement occurs but oral ulcers are not characteristic 8

Behçet's Disease

• Recurrent oral and genital ulcers with arthritis 2
• Renal involvement is rare, making this less likely 2

Common Pitfalls to Avoid

• Do not dismiss SLE based on normal CRP—unlike RA, CRP may be normal or only mildly elevated in active SLE despite severe disease 1, 9
• Do not delay renal biopsy—acute renal failure in SLE requires histologic diagnosis within days to prevent irreversible damage 5
• Do not assume seronegative disease excludes SLE—while ANA is positive in >95%, a small percentage are ANA-negative 1, 2
• Do not start NSAIDs empirically—NSAIDs can worsen renal function in lupus nephritis and should be avoided until renal status is clarified 3, 5
• Do not confuse SLE arthritis with RA—SLE arthritis is typically non-erosive and non-deforming, though "Jaccoud's arthropathy" can cause reducible deformities 3

Disease Activity Assessment

Once SLE is confirmed, use SLEDAI (SLE Disease Activity Index) score to quantify disease activity—higher scores correlate with worse outcomes and guide immunosuppression intensity 4. The presence of renal involvement, oral ulcers, and arthritis already indicates moderate-to-high disease activity requiring aggressive treatment 4.