When should a patient with suspected lupus be referred to secondary care in the UK, as per National Institute for Health and Care Excellence (NICE) guidelines?

When to Refer for Possible Lupus to Secondary Care in the UK NICE

Patients with suspected lupus should be referred to secondary care when they present with persistently abnormal urinalysis or raised serum creatinine, neuropsychological symptoms, or have positive autoantibodies with clinical features suggestive of lupus. 1

Specific Referral Criteria

Laboratory Abnormalities Requiring Referral

• Renal involvement:

  • Persistently abnormal urinalysis
  • Raised serum creatinine
  • Proteinuria (measured by urine protein/creatinine ratio)
  • Abnormal renal ultrasound findings 1

• Immunological abnormalities with clinical features suggestive of lupus:

  • Positive ANA (anti-nuclear antibodies)
  • Positive anti-dsDNA antibodies
  • Low complement levels (C3, C4)
  • Positive anti-Ro, anti-La, anti-RNP, anti-Sm antibodies
  • Positive anti-phospholipid antibodies 1

Clinical Presentations Requiring Referral

1. Neuropsychiatric manifestations:

   • Seizures
   • Paresthesiae
   • Numbness
   • Weakness
   • Headache
   • Cognitive impairment (attention, concentration, word finding and memory difficulties) 1

2. Mucocutaneous manifestations that are:

   • LE specific
   • Persistent despite treatment
   • Causing significant damage or cosmetic concerns 1

3. Kidney involvement:

   • Any signs of nephropathy require prompt referral for consideration of renal biopsy 1

4. Multi-system involvement:

   • Constitutional symptoms (fever, fatigue) plus involvement of two or more organ systems 2, 3

Monitoring Parameters Before Referral

Primary care physicians should consider obtaining the following tests when lupus is suspected, to facilitate appropriate referral:

• Complete blood count
• Erythrocyte sedimentation rate
• C-reactive protein
• Serum albumin
• Serum creatinine (or eGFR)
• Urinalysis and urine protein/creatinine ratio
• ANA and other autoantibody testing 1

Urgency of Referral

• Urgent referral (within 2 weeks) for:

  • Abnormal renal function
  • Neurological symptoms
  • Severe cytopenias
  • Multi-system involvement with constitutional symptoms

• Routine referral for:

  • Stable, mild symptoms
  • Positive serology without significant organ involvement
  • Isolated skin or joint manifestations without systemic features

Common Pitfalls to Avoid

1. Delayed diagnosis: The average time to diagnosis from first symptom is 6.4 years, with 47% of patients initially receiving a different diagnosis 4. Early referral can reduce this delay.

2. Missing renal involvement: Kidney disease may be asymptomatic initially but requires prompt intervention to prevent progression to end-stage renal disease, which occurs in approximately 10% of people with lupus nephritis after 10 years 3.

3. Overlooking neuropsychiatric manifestations: Cognitive symptoms may be subtle and attributed to other causes. Any unexplained neurological symptoms in a patient with suspected lupus warrant referral 1.

4. Failure to recognize the importance of fatigue: Fatigue affects 91% of lupus patients and significantly impacts daily activities 4, but may be dismissed as non-specific.

Post-Referral Management

After diagnosis in secondary care, patients will typically require lifelong monitoring:

• Visits every 2-4 weeks for the first 2-4 months after diagnosis or flare
• Then according to response to treatment
• Lifelong monitoring at least every 3-6 months for renal and extra-renal disease activity 1

Hydroxychloroquine is the standard first-line treatment for most patients with lupus, with additional immunosuppressive agents added based on organ involvement and disease severity 3, 5.