Musculoskeletal

Systemic Lupus Erythematosus

A lifelong multisystem autoimmune disease in which loss of tolerance produces autoantibodies and inflammation across skin, joints, kidneys, blood, serosa and the nervous system.

In a nutshell

Suspect SLE when multisystem features cluster: inflammatory joint symptoms, photosensitive or cutaneous disease, oral ulcers, cytopenia, serositis, renal disease, thrombosis or neurological symptoms. ANA is a sensitive test when clinical suspicion is present, but diagnosis is clinical and specialist; anti-dsDNA, anti-Smith and low complement support it. Always check blood pressure and urine, distinguish flare from infection or thrombosis, and treat to remission or low disease activity with hydroxychloroquine and organ-directed steroid-sparing therapy.

Classic presentation

A person, often a woman in the reproductive years, with fatigue, inflammatory small-joint symptoms, photosensitive rash or oral ulcers and unexplained cytopenia or renal findings. The diagnostic clue is the combination of clinical features and supportive autoantibodies, not ANA positivity alone.

Key points

SLE should be diagnosed by clinicians experienced in its management; SLICC and EULAR/ACR criteria support structured thinking but are not diagnostic criteria.
Request ANA only with reasonable clinical suspicion. A negative ANA makes SLE unlikely, while a positive ANA alone is non-specific.
Supportive tests include anti-dsDNA, extractable nuclear antigens including anti-Smith, C3/C4, full blood count, renal function and antiphospholipid antibodies.
Blood pressure and urinalysis belong at every visit. Proteinuria, haematuria, falling eGFR or hypertension can indicate lupus nephritis even when the patient feels well.
Rising anti-dsDNA and falling complement may support impending activity, but assess the patient for infection, drug toxicity, damage and thrombosis rather than treating numbers alone.
Hydroxychloroquine is recommended unless contraindicated; minimise cumulative glucocorticoids and use specialist steroid-sparing therapy for persistent or organ-threatening disease.
Pregnancy planning matters: review teratogenic drugs and check antiphospholipid, anti-Ro/SSA and anti-La/SSB status with specialist and obstetric input.

First-line investigation

When the clinical pattern supports SLE, request ANA with full blood count, renal function, urinalysis and blood pressure assessment; then add anti-dsDNA, extractable nuclear antigens, C3/C4 and antiphospholipid testing with specialist referral.

Management

Recognise the multisystem pattern and refer

Refer suspected SLE to experienced secondary or tertiary clinicians; urgently escalate renal, neurological, respiratory, cardiac, haematological, thrombotic or severe infectious features.^1,2

Confirm the diagnosis and screen every organ

Use clinical assessment with ANA-directed serology, full blood count, renal function, urinalysis, protein quantification, blood pressure, complement and antiphospholipid testing; classification criteria are not diagnostic criteria.¹

Start hydroxychloroquine and reduce preventable risk

Offer hydroxychloroquine unless contraindicated, arrange retinal monitoring, minimise UV exposure and smoking, encourage appropriate activity and vaccination, and address cardiovascular and bone health.^1,6

Control active disease without prolonged steroid exposure

Use glucocorticoids as a short-term bridge and add specialist-selected immunosuppression for moderate or organ-threatening disease; discuss biologics with a specialist lupus MDT when disease remains active or steroid-dependent.^1,5,6

Treat lupus nephritis as a renal emergency pathway

Arrange timely biopsy and combined renal-rheumatology care; choose histology-directed immunosuppression and NICE-approved options such as mycophenolate combinations only within specialist and NHS treatment pathways.^1,3,4

Treat to target and plan pregnancy safely

Aim for remission or low disease activity, monitor renal and systemic response, taper glucocorticoids where possible, coordinate complex care through an MDT, and provide pre-pregnancy counselling with review of teratogenic therapy and anti-Ro/La and antiphospholipid status.^1,5,3,4

Exam traps

ANA is sensitive but not specific: a positive ANA does not diagnose SLE and a negative ANA makes it unlikely rather than absolutely impossible.
A flare is not the only explanation for fever, cytopenia, confusion or chest pain; infection, thrombosis, drug toxicity and damage may be more dangerous.
Normal CRP does not exclude active SLE, but inflammatory markers must be interpreted with the clinical picture; a disproportionate CRP rise should prompt consideration of infection or serositis.
Do not wait for a dramatic renal presentation: repeat urinalysis, blood pressure, protein quantification and renal function at every review.
Do not describe belimumab, voclosporin or obinutuzumab as routine primary-care options; their use depends on specialist assessment, histology, licensing and NICE/NHS arrangements.

Illustrations

Immune complex deposition mechanismDiagram showing autoantibody binding to nuclear antigen forming immune complexes that deposit in skin, joint, renal and serosal tissue and activate complement.PassFinals · original

Lupus nephritis on renal biopsyHistology image of immune complex glomerulonephritis with characteristic full-house immunofluorescence staining seen in lupus nephritis.Nephron, Wikimedia Commons · CC-BY-SA-3.0

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.