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)
• Normal or ↑FEV₁/FVC ratio → there is no dominant airflow obstruction; both FEV₁ and FVC may fall, with FVC falling proportionally more
• ↑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]

The full triphasic sequence is classic but not required in every attack: some patients show only pallor and cyanosis, or only two phases. The photographed hand in the lecture shows a sharply demarcated pale segment of a digit, reflecting abrupt vasospasm rather than a diffuse colour change. ^[1]

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

Visual discriminator from the slides: Raynaud's produces segmental, sharply demarcated pallor/cyanosis that comes and goes; acrocyanosis produces a diffuse, persistent and usually symmetric blue-purple hand without discrete attacks. ^[1]

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, and review vasoconstrictive medicines (including non-selective β-blockers) individually
• 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 SSc digital ulcers: PDE5 inhibitors and/or IV iloprost may be used for active ulcers; bosentan is used to reduce new ulcer formation, not to heal an established ulcer. ^[7]

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 is a historical lecture quip, not a therapeutic principle. Current management is organ-based and increasingly disease-modifying. ^[1][7][8]

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 over the lower lid margin for 5 min; ≤ 5 mm wetting is the current classification threshold
• 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

In the slide comparison, the normal eye has a largely clear surface, whereas the Sjögren eye shows patchy punctate ocular-surface staining, representing damaged corneal/conjunctival epithelium. The biopsy micrograph shows dense focal lymphocytic aggregates centred around ducts and acini, the visual correlate of focal lymphocytic sialadenitis. ^[1]

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. The lecture's forest plot shows a very large association with clinically amyopathic DM (pooled odds ratio roughly 46, with a wide confidence interval), but the more useful bedside message is the phenotype: anti-MDA5 plus respiratory symptoms warrants urgent assessment for rapidly progressive ILD. ^[1]

The slide's “2 out of 3” rule (enzymes, EMG, biopsy) is a historical teaching heuristic, not a modern stand-alone diagnostic criterion. Current assessment integrates phenotype, strength examination, enzymes, myositis-specific antibodies, MRI/EMG and targeted muscle or skin biopsy when needed.

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

The subtype labels below reproduce the lecture's older ILAR-era shorthand. In current practice and guidelines, use oligoarthritis, RF-positive or RF-negative polyarthritis, systemic JIA, enthesitis-related arthritis, psoriatic arthritis and undifferentiated JIA rather than “pauciarticular type 1/2.” ^[11]

• > 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)

What the photographs add: compare sides rather than asking only whether a joint hurts. The affected knee/ankle shows unilateral swelling, loss of the normal bony contour and a flexed posture; chronic asymmetric synovitis may produce fixed flexion and apparent or true leg-length difference. ^[1]

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

Reading the visual slides: the fever chart shows once-daily spikes with return towards baseline between peaks, rather than continuous fever. The rash is faint, salmon-pink and evanescent, often most visible over the trunk, axillae or waist during fever/heat. Cardiomegaly on the chest radiograph may suggest a pericardial effusion, but echocardiography is needed to confirm it. ^[1]

• Chronic headaches and other neurological symptoms ^[1]

The lecture's lateral cervical radiograph shows apophyseal joint-space loss and bony ankylosis, especially around C2–C3. The quoted “up to 50%” is historical cohort material rather than a figure to generalise to children receiving modern therapy. ^[1]

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]

Management depends on subtype and complications; the lecture's single NSAID-first ladder is no longer adequate. ^[11]

Systemic glucocorticoids are therefore not absolutely prohibited: prolonged exposure is avoided because of toxicity and growth effects, but steroids have an important role in MAS and selected severe organ disease. HSCT is not routine JIA therapy. ^[11]

• 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

The calibre diagram places anti-GBM disease beside the pulmonary–renal small-vessel syndromes for differential diagnosis; anti-GBM disease is not itself a primary vasculitis. ^[1]

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

Photographic recognition: livedo is a fixed, net-like violaceous pattern; palpable purpura is raised and non-blanching, usually dependent; splinter haemorrhages and nailfold erythema are supportive but non-specific; digital infarction/gangrene signifies severe occlusive injury; and vasculitic ulcers are often punched-out or necrotic with slough at lower-limb/pressure sites. ^[1]

A common primary vasculitis in adults aged 50 years or older.

The image sequence shows a thickened, tender/non-pulsatile temporal artery; optic-disc swelling or pallor from anterior ischaemic optic neuropathy; transmural granulomatous arteritis with giant cells; and large-vessel involvement beyond the temporal artery. ^[1]

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

• Symptoms occur due to stenosis of the aorta and its branches; the aortic arch and abdominal aorta are most commonly affected ^[1]

• 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: initial glucocorticoids plus a steroid-sparing non-glucocorticoid immunosuppressive agent; biologic therapy and vascular intervention are selected for refractory disease or critical complications ^[12]

The angiographic slides show long-segment narrowing or occlusion of major aortic branches, rather than the distal small-vessel pruning of a capillaritis. At the bedside, compare both radial pulses and arm blood pressures and listen for subclavian/aortic bruits. ^[1]

On indirect immunofluorescence, cANCA is diffuse granular cytoplasmic staining whereas pANCA accentuates the perinuclear region. Modern interpretation prioritises antigen specificity (PR3 versus MPO). ANCA supports a compatible clinical syndrome but is neither diagnostic by itself nor sufficiently sensitive to exclude disease; tissue biopsy is often needed. ^[13]

• IgA-mediated immune-complex small-vessel vasculitis, often following an upper respiratory infection
• Common in spring, after URTI
• Children 2–10 years more commonly affected; adults can be affected
• Classical clinical cluster:
  1. Palpable purpura
  2. Arthritis
  3. Abdominal pain
• Renal involvement can be delayed; monitor blood pressure and urinalysis after presentation rather than assuming the striking purpura will resolve without consequence

The lecture photograph shows extensive dependent palpable purpura over the legs and buttocks: the rash distribution is a diagnostic clue, but the renal follow-up determines longer-term risk. ^[1]

ANCA-associated vasculitis is potentially life-threatening, but treatment is severity- and phenotype-dependent. For severe GPA/MPA, current ACR/VF guidance generally favours rituximab over cyclophosphamide for remission induction, with glucocorticoid-sparing/reduced-dose strategies where appropriate. Non-severe GPA may use methotrexate-based induction; remission maintenance is separately planned. These are specialist regimens, not a uniform “high-dose steroids for all” rule. ^[13]