Diagnosis: Mixed Connective Tissue Disorder (MCTD) complicated by Raynaud's phenomenon, sclerodermatous skin changes, fibrosing alveolitis, and low-grade myositis. ^[1]

• ↓VC and ↓TLC → lungs can't expand fully (restriction from fibrosis)
• ↑FEV₁/FVC ratio → airways are not obstructed; the problem is small stiff lungs
• ↑RV/TLC → residual volume makes up a larger proportion of a shrunken total lung capacity
• ↓DLCO → gas transfer impaired because alveolar membrane is thickened by fibrosis

• Young / middle-aged female
• Subacute onset
• Progressive course
• Cold-induced vasospasm
• Multisystem involvement

Raynaud's phenomenon is episodic digital ischaemia provoked by cold or emotional stress, manifesting as triphasic colour change: white → blue → red. ^[1][3]

Why white → blue → red?

1. White (pallor): Intense arterial vasospasm → digital arteries constrict → no blood reaches fingertips → pallor
2. Blue (cyanosis): Vasospasm partially relaxes but venous outflow is still sluggish → deoxygenated blood pools in dilated capillaries → cyanotic appearance ^[4]
3. Red (rubor): Vasospasm fully releases → reactive arterial hyperaemia floods the digits → red flushing, often with throbbing pain ^[3]

The lecture specifically distinguishes these two conditions:

• Raynaud's = episodic, triggered by cold, triphasic, typically affects fingers (can affect toes, ears, nose)
• Acrocyanosis = persistent bluish discolouration, often bilateral, not episodic, typically benign

The lecture lists these causes explicitly:

Keep warm; avoid cigarettes and vasoconstrictors; vasodilators (calcium channel blockers, PGI₂ / analogues / phosphodiesterase inhibitors). ^[1]

• Non-pharmacological: Keep hands warm (gloves), avoid cold exposure, stop smoking, avoid β-blockers and other vasoconstrictors
• Pharmacological first-line: Calcium channel blockers (e.g. nifedipine, amlodipine) — these directly relax vascular smooth muscle
• Second-line: PGI₂ (prostacyclin) analogues (e.g. iloprost), PDE5 inhibitors (e.g. sildenafil)
• For digital ulcers in SSc: endothelin receptor antagonists (e.g. bosentan) ^[2]

A generalised disorder of connective tissue affecting skin and internal organs, characterised by fibrotic arteriosclerosis of peripheral and visceral vasculature, with variable degrees of extracellular matrix accumulation (mainly collagen) in both skin and viscera, associated with specific autoantibodies (anti-centromere and anti-Scl-70). ^[1]

Understanding "why" SSc happens requires grasping three parallel pathological processes:

1. Immunological activation → Autoantibodies + T-cell activation → drives inflammation
2. Occlusive vasculopathy → Endothelial injury → intimal proliferation → vessel narrowing → ischaemia (explains RP, digital ulcers, renal crisis, PAH)
3. Tissue fibrosis → Activated fibroblasts deposit excessive collagen → skin thickening, lung fibrosis, oesophageal dysmotility, cardiac fibrosis

Peak onset 30–50 years, F:M = 4:1, prevalence 10–20/100,000, annual incidence 1–2/100,000, unrestricted geography, possible genetic predisposition (?DR5, DRw52, DR4). ^[1]

C = Calcinosis cutis, R = Raynaud's phenomenon, E = oEsophageal dysmotility, S = Sclerodactyly, T = Telangiectasia. Associated with anti-centromere antibodies. ^[1]

Why "oEsophageal"? — The mnemonic uses "E" for oesophageal because smooth muscle in the lower 2/3 of the oesophagus is replaced by fibrosis → loss of peristalsis → dysmotility → GORD.

"No drug has been proven to be totally useless until it has been tried in systemic sclerosis" — This quote from the lecture emphasises how difficult SSc is to treat. Management is largely symptomatic.

"Some drugs may not be as useless in systemic sclerosis" — SSc-ILD: systemic corticosteroids + cyclophosphamide/MMF; nintedanib (tyrosine kinase inhibitor); tocilizumab (anti-IL6R mAb). ^[1]

A slowly progressive, inflammatory autoimmune disease affecting primarily the exocrine glands, causing keratoconjunctivitis sicca and xerostomia. Lymphocytic infiltrates replace functional epithelium → decreased exocrine secretions (exocrinopathy). Characteristic autoantibodies: Ro (SS-A), La (SS-B), and rheumatoid factor. ^[1]

• 40–50 years; F:M = 9:1
• Primary Sjögren's may be as common as SLE
• Secondary Sjögren's = sicca complex + underlying CTD
• ~30% of RA and SSc patients have at least histologic evidence of Sjögren's

Demonstrating mucosal dryness:

• Schirmer's test — filter paper strip in lower conjunctival fornix for 5 min; < 5 mm wetting = abnormal
• Rose Bengal staining — stains damaged/devitalised epithelium on cornea/conjunctiva
• Slit lamp examination — identifies corneal erosions/ulceration
• Sialography and sialometry — assesses salivary gland structure and flow

Demonstrating lymphocytic infiltration:

• Minor (labial) salivary gland biopsy — focal lymphocytic sialadenitis with focus score ≥ 1

Demonstrating autoimmunity: ^[1]

A CTD characterised by chronic inflammation of striated muscles (polymyositis) and sometimes the skin (dermatomyositis). Autoantibody associations (e.g. anti-Jo-1, anti-Mi-2) define homogeneous clinical subsets. ^[1]

And further classified by context:

• Childhood idiopathic disease
• Adult idiopathic disease
• Associated with other CTDs
• Associated with underlying malignancy

Anti-MDA5 is associated with clinically amyopathic dermatomyositis AND rapid development of interstitial lung disease with high mortality. ^[1]

This is clinically important because these patients may have minimal muscle involvement but devastating lung disease.

Myositis is diagnosed by 2 out of 3 of: elevated muscle enzymes (CPK, LDH, AST); EMG showing inflammatory myopathy; muscle biopsy. ^[1]

Same disease, different names: JCA (EULAR), JRA (ACR), JIA (ILAR — the preferred current term). ^[1]

• > 4 joints affected in first 6 months; 30–40% of JIA
• Female predominance
• Bimodal: peaks at 2–5 years and 10–14 years
• Children < 10: symmetrical involvement (knees, wrists, ankles); uveitis less common than pauciarticular but ANA+ = higher risk
• Children > 10: RF+ follow adult RA pattern; RF− is the larger group

• < 5 joints; F > M; peak at 2–3 years
• Large joints (knees, ankles, wrists, elbows) but virtually never begins in hips
• Systemic manifestations (other than uveitis) are characteristically absent
• Complications: uveitis and leg length discrepancy (chronic synovitis → growth plate stimulation on affected side → leg lengthening)

Most difficult to diagnose — arthritis may not be evident early, constitutional symptoms dominate. ^[1]

Key features:

• Ill-looking child, spiking fever, rashes, high WBC, anaemia
• Fever pattern: high swinging (quotidian) — characteristically ill when febrile, dramatically improves when temperature normalises
• Salmon-pink macular rash — evanescent, brought out by heat, prominent during fever
• Hepatomegaly, splenomegaly, lymphadenopathy
• Serositis: pericardial effusion, pleural effusion

Major differentials: Infection, leukaemia ^[1]

Articular involvement: Any number of joints — wrists, knees, ankles most typical; also hands, hips, cervical spine, TMJ. Micrognathia and cervical spine fusion in chronic disease. ^[1]

• Arthritis resolves in ~40–50% of children
• If well after 6 months → likely to remain well
• ~1/3 with systemic JIA remain ill for prolonged period — guarded prognosis

• Vessel wall destruction → perforation → haemorrhage into adjacent tissues
• Endothelial injury → thrombosis → ischaemia of dependent tissues
• Fever and constitutional symptoms

Commonest form of primary vasculitis.

GCA and PMR often co-exist and may represent clinical subsets of a single disease process. However, treatment is NOT the same — PMR requires lower doses of steroid. ^[1]

• Females of child-bearing age, more common in Asians
• Also known as: pulseless disease, aortic arch syndrome, occlusive thromboaortopathy
• Clinical: bruits (80%), claudication (70%), decreased pulses (60%), arthralgias (50%), asymmetric BP (50%), constitutional symptoms (40%), hypertension (30%)
• Investigations: markers of inflammation, aortography, MR angiography
• Treatment: high-dose corticosteroids, immunosuppressives, anti-IL6

• Hypersensitivity reaction to bacteria or viruses
• Common in spring, after URTI
• Children 2–10 years more commonly affected; adults can be affected
• Classical triad (acute onset, rapid resolution):
  1. Palpable purpura
  2. Arthritis
  3. Abdominal pain
• Renal involvement (IgA nephropathy) can occur

All are rare but potentially life-threatening systemic disorders. Treatment involves high-dose steroids and immunosuppressive drugs. Rituximab (anti-CD20). ^[1]

1. A 45-year-old woman has Raynaud's, dysphagia, and telangiectasia on her face and hands. Which antibody is most likely positive? → Anti-centromere (Limited SSc / CREST)

2. A 60-year-old man with DM develops rapidly progressive ILD. Which antibody should you test? → Anti-MDA5

3. Which vasculitis is most strongly associated with cANCA? → GPA (Wegener's)

4. A child with pauciarticular JIA is at highest risk for which extra-articular complication? → Chronic anterior uveitis (especially if ANA+)

5. Which drug is the treatment of choice for scleroderma renal crisis? → ACEI

6. Describe the pathophysiology of the triphasic colour change in Raynaud's phenomenon. → Vasospasm → pallor; venous congestion with deoxygenated blood → cyanosis; reactive hyperaemia → rubor.

7. List 4 features that distinguish secondary from primary Raynaud's. → Age > 40, severe/asymmetric, digital ulcers, positive ANA, abnormal nailfold capillaroscopy, other CTD features.

8. A patient with SSc-ILD. What PFT pattern would you expect? → Restrictive: ↓FVC, ↓TLC, ↑FEV₁/FVC, ↓DLCO.

9. Name 3 extra-glandular manifestations of Sjögren's syndrome. → Non-erosive polyarthritis, ILD, renal tubular acidosis, vasculitis, lymphoma.

10. How would you investigate suspected dermatomyositis? Describe the diagnostic criteria for myositis. → 2 out of 3: elevated CPK/LDH/AST, EMG showing inflammatory myopathy, muscle biopsy showing inflammatory infiltrate. Also: auto-antibodies, skin biopsy if needed, malignancy screen in elderly.