Connective Tissue Disorders

Systemic lupus erythematosus (SLE):

• •Female-to-male ~9:1; peak onset 15-45 years; more prevalent and severe in Afro-Caribbean and South Asian populations.
• •Constitutional: fatigue (often dominant), fever, lymphadenopathy.
• •MSK (>90%): non-erosive arthritis of small joints. Jaccoud''s arthropathy produces correctable deformities from ligamentous laxity and tenosynovitis - distinct from RA''s fixed erosive disease. Myalgia is common; AVN is corticosteroid-related.
• •Skin (>80%): malar (butterfly) rash sparing nasolabial folds, photosensitive; discoid lesions; oral or nasal ulcers (often painless); alopecia; livedo reticularis (APS).
• •Renal: lupus nephritis affects ~50% (ISN/RPS class I to VI; class IV is the most severe). Proteinuria, haematuria, hypertension, falling eGFR - often asymptomatic early.
• •Haematological: anaemia of chronic disease or Coombs-positive haemolysis, leucopenia/lymphopenia, immune thrombocytopenia.
• •Serositis: pleuritis (most common), pericarditis.
• •Neuropsychiatric: headache, cognitive dysfunction, seizures, psychosis, cerebrovascular disease (especially with APS).
• •ESR-CRP dissociation (raised ESR, relatively normal CRP unless serositis or infection) is a useful clue.

2019 EULAR/ACR classification criteria require positive ANA at 1:80 or above (HEp-2) as the entry criterion, followed by weighted clinical and immunological domains; classification at a total score of 10 or more.

Systemic sclerosis (SSc) - two phenotypes with distinct timing and complication profiles:

• •Limited cutaneous SSc (lcSSc): skin thickening distal to elbows and knees and on the face; CREST features (Calcinosis, Raynaud''s, oEsophageal dysmotility, Sclerodactyly, Telangiectasia); anti-centromere; Raynaud''s typically precedes systemic disease by years to decades; pulmonary arterial hypertension (PAH) is the dominant serious complication. Annual screening echocardiography and DLCO.
• •Diffuse cutaneous SSc (dcSSc): skin thickening extending proximal to elbows or knees and onto the trunk; anti-Scl-70 (ILD) and anti-RNA polymerase III (renal crisis); Raynaud''s typically starts concurrently with skin and organ involvement (rapid onset is a key diagnostic clue). ILD and scleroderma renal crisis are the major complications.
• •Raynaud''s is almost universal (>95%). Tendon friction rubs (palpable crepitus) are nearly pathognomonic for dcSSc. Nailfold capillaroscopy distinguishes secondary Raynaud''s (early: giant dilated capillary loops and microhaemorrhages; late: avascular dropout) from primary (normal). A dermatoscope is enough in primary care.

Idiopathic inflammatory myopathies (IIMs):

• •Cardinal feature: progressive, symmetrical, proximal weakness (difficulty rising from a chair, climbing stairs, lifting overhead) with markedly elevated CK (often >10 times upper limit).
• •Dermatomyositis (DM): heliotrope rash of the upper eyelids and Gottron''s papules over MCP and PIP knuckles (both pathognomonic), shawl sign, V-sign, and mechanic''s hands. DM (and to a lesser extent PM) is associated with underlying malignancy (ovarian, lung, breast, GI, nasopharyngeal) - screen at diagnosis, especially over 40.
• •Antisynthetase syndrome (anti-Jo-1 the commonest antibody): myositis + ILD + mechanic''s hands + arthritis + Raynaud''s + fever. ILD drives morbidity.
• •Immune-mediated necrotising myopathy (anti-SRP, anti-HMGCR - the latter statin-associated): very high CK, severe weakness, minimal inflammation on biopsy.
• •Inclusion body myositis: distal AND proximal weakness (finger flexors, quadriceps), insidious onset, men over 50, poor response to immunosuppression.

Sjogren''s syndrome: dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia); anti-Ro/SSA and anti-La/SSB; Schirmer''s test under 5 mm wetting in 5 minutes is abnormal. Significantly increased non-Hodgkin lymphoma risk (MALT of parotid) - watch for persistent parotid swelling, lymphadenopathy, falling C4, falling rheumatoid factor, and rising beta-2 microglobulin.

Mixed connective tissue disease (MCTD): Raynaud''s, swollen hands, and a myositis-like overlap with high-titre anti-U1 RNP as the defining antibody.

Antiphospholipid syndrome (APS): arterial and venous thrombosis plus pregnancy morbidity. Persistently positive (at least 12 weeks apart) lupus anticoagulant, anti-cardiolipin, or anti-beta-2-glycoprotein-1 with a clinical thrombotic or obstetric event. Long-term anticoagulation is indicated.

SEM relevance: Raynaud''s complicates cold-exposure activities (winter running, climbing, water sports); ILD/PAH limits exercise tolerance and altitude tolerance; long-term corticosteroids elevate AVN, tendinopathy, and fracture risk; return-to-sport is individualised after each flare with attention to fatigue, fitness loss, and medication side effects.

Investigation is targeted to clinical suspicion, never a blanket 'autoimmune screen'. First-line work-up when a CTD is suspected: ANA (sensitive but ~5-15% of healthy adults positive), FBC (cytopenias in SLE; eosinophilia in EGPA), CRP and ESR (look for ESR-CRP dissociation in SLE), CK (if proximal weakness), renal function and urinalysis (screening for lupus nephritis and vasculitis), complement (low C3/C4 in active SLE), and immunoglobulins (polyclonal hypergammaglobulinaemia in Sjogren's and SLE).

Specific autoantibodies are guided by clinical picture (see the Anatomy pearl). Request urgent ANCA testing if rapidly progressive glomerulonephritis or pulmonary haemorrhage is suspected - these are medical emergencies. Antiphospholipid antibodies are tested when thrombosis or pregnancy morbidity is suspected.

Imaging: CXR for pleural disease and ILD; HRCT thorax for ILD characterisation (ground-glass, honeycombing, fibrosis); echocardiography for PAH screening (especially lcSSc) and pericardial effusion; MRI muscle for active myositis and biopsy planning; nailfold capillaroscopy for Raynaud''s evaluation.

Specialist confirmation: renal biopsy for lupus nephritis ISN/RPS classification; muscle biopsy for IIM subtype and to distinguish IBM from PM; salivary gland biopsy for Sjogren''s (focal lymphocytic sialadenitis); EMG (myopathic pattern); pulmonary function tests with DLCO (early ILD and PAH marker, serial monitoring in SSc).

CTD management is rheumatology-led with multidisciplinary input (renal, respiratory, dermatology, ophthalmology, obstetrics, physiotherapy, psychology). The MSK clinician''s role: recognise, refer urgently, understand treatment principles, and manage MSK complications.

General principles: rigorous UV protection in SLE (SPF 50+, protective clothing, avoid midday sun); aggressive cardiovascular risk management (markedly increased CV risk); bone protection on long-term corticosteroids per NICE NG223/NOGG; vaccinations up to date with live vaccines contraindicated during immunosuppression; pre-conception counselling (methotrexate, mycophenolate, and cyclophosphamide are teratogenic; anti-Ro positive women need fetal cardiac monitoring for congenital heart block).

SLE: hydroxychloroquine is recommended for all SLE patients (BSR maximum dose <5 mg/kg actual body weight/day; annual retinal screening from 5 years, or from 1 year if high risk; safe in pregnancy and breastfeeding). NSAIDs for mild MSK and serositis. Corticosteroids for flares and active organ disease at the lowest effective dose, with IV methylprednisolone for severe disease. Steroid-sparing agents: mycophenolate mofetil (induction and maintenance of lupus nephritis, also non-renal disease), cyclophosphamide (severe lupus nephritis with greater toxicity), and azathioprine (maintenance, check TPMT, safe in pregnancy). Biologics: belimumab (NICE-approved), rituximab (off-label), and anifrolumab.

SSc: keep warm; nifedipine first-line for Raynaud''s; sildenafil for refractory disease; IV iloprost for critical digital ischaemia. AVOID high-dose corticosteroids (>15 mg prednisolone/day) - they precipitate scleroderma renal crisis, especially in dcSSc. ILD: mycophenolate or cyclophosphamide; nintedanib as antifibrotic. PAH: specialist pulmonary hypertension centre using endothelin receptor antagonists, PDE5 inhibitors, and prostacyclin analogues, often in combination. Scleroderma renal crisis: ACE inhibitors are the specific treatment, used even in AKI (the exception to the usual rule of withdrawing ACE inhibitors in AKI).

Inflammatory myopathies: high-dose prednisolone first-line (1 mg/kg, tapered) with IV methylprednisolone for severe disease; steroid-sparing with methotrexate, azathioprine, mycophenolate, IVIG (particularly for DM skin or dysphagia), or rituximab. Malignancy screen at diagnosis. IBM is steroid-resistant; management is supportive (physiotherapy, OT, falls prevention, swallowing assessment).

Sjogren''s: artificial tears (preservative-free), saliva substitutes, pilocarpine; hydroxychloroquine for arthralgia and fatigue; immunosuppression for severe systemic disease; lymphoma surveillance.

APS: long-term warfarin (NOT DOACs) for arterial events or triple-positive APS; low-dose aspirin with LMWH for obstetric APS.

Exercise is safe and beneficial across all CTDs when individualised. In SLE, exercise improves fatigue, fitness, mood, and function and does not worsen disease - UV precautions during outdoor sessions (SPF 50+, protective clothing, indoor/shaded exercise during photosensitive flares). Aquatic exercise is often well tolerated during flares.

In inflammatory myopathies, progressive resistance training is safe in stable, treated disease and improves strength without flaring activity - a significant shift from older teaching. In active untreated disease, begin with gentle ROM until inflammation is controlled. IBM is steroid-unresponsive: physiotherapy is the mainstay, with falls prevention and swallowing assessment.

In SSc, daily hand exercises preserve grip and finger extension; oral and facial exercises maintain mouth opening (microstomia is progressive); paraffin wax baths may improve stiffness; cardiopulmonary rehabilitation is adapted to ILD/PAH limits.

Fatigue management across all CTDs uses exercise (paradoxically beneficial), pacing, energy conservation, sleep hygiene, and psychological support, while addressing contributors (anaemia, hypothyroidism, depression, medication side effects). Lupus UK, SRUK, and Myositis UK are valuable peer-support resources to signpost.

• •2019 EULAR/ACR SLE classification criteria - ANA at least 1:80 (HEp-2) as the entry criterion, weighted clinical and immunological domains, classification at a total score of 10 or more.
• •BSR guidelines on SLE, hydroxychloroquine monitoring, scleroderma renal crisis, and biologic eligibility - the UK standard for diagnosis and treatment.
• •2017 EULAR/ACR IIM classification criteria - replaces the older Bohan and Peter criteria; includes DM, PM, antisynthetase, IMNM, and IBM subtypes.
• •BSR scleroderma renal crisis guidance - ACE inhibitors as specific treatment even in AKI; high-dose corticosteroids should be avoided in SSc.
• •ACR/EULAR APS classification criteria (2023 update) - clinical and laboratory domains; lupus anticoagulant, anti-cardiolipin, and anti-beta-2-glycoprotein-1 at sustained titre.

• •ANA 1:80 or above is the 2019 EULAR/ACR SLE entry criterion.
• •Anti-Scl-70 = diffuse SSc/ILD; anti-centromere = limited SSc/PAH; anti-RNA pol III = renal crisis.
• •DM Gottron''s papules and heliotrope rash are pathognomonic; screen for malignancy over 40.
• •High-dose steroids in SSc risk renal crisis; ACE inhibitors treat it even in AKI.
• •Anti-Jo-1 = antisynthetase syndrome with myositis, ILD, and mechanic''s hands.
• •Triple-positive APS or arterial events: warfarin, not DOACs.