1. Definition
2. Aetiology
3. Types
4. Predisposing Factors
5. Pathogenesis
6. Clinical Features & Signs
7. Diagnosis / Investigations
8. Complications

Ankylosing Spondylitis (AS)

1. Definition

2. Aetiology

• Genetic: The strongest association is with HLA-B27 - approximately 90% of AS patients are HLA-B27 positive. More than 30 subtypes of B27 exist; HLA-B2705 is the primordial subtype. Subtypes B2706 and B2709 do NOT confer susceptibility. Non-MHC genes also contribute - aminopeptidase genes (ERAP1, ERAP2), IL-23 receptor gene, IL-1 receptor, and others.
• Molecular mimicry: Sequence homology between HLA-B27 and gram-negative enteric bacteria (e.g., Klebsiella pneumoniae, Salmonella, Shigella) may trigger autoimmunity.
• Gut inflammation: Subclinical gut inflammation is common in AS; microbial translocation from the gut is thought to drive systemic inflammation.
• Cytokines: TNF-alpha and IL-17/IL-23 axis play central roles in driving inflammation and new bone formation.

3. Types / Classification

• Primary AS - idiopathic, HLA-B27-related
• Juvenile AS - onset before age 16 (up to 15% of juvenile idiopathic arthritis cases)
• Late-onset AS - small subset; presents with sacroiliitis and oligoarthritis in older adults

4. Predisposing Factors

5. Pathogenesis

1. HLA-B27 and antigen presentation: HLA-B27 presents arthrogenic peptides (possibly derived from self or bacterial proteins) to CD8+ cytotoxic T cells, initiating an autoimmune response.
2. Misfolding hypothesis: HLA-B27 heavy chains can misfold and form homodimers, activating unfolded protein response (UPR) and promoting IL-23 production.
3. Enthesitis: Primary site of pathology is the enthesis (bone-tendon/ligament junction), especially at the annulus fibrosus attachment to vertebral bodies.
4. Inflammatory cascade: TNF-alpha, IL-17, IL-23 drive synovitis, osteitis, and enthesitis.
5. Bony erosion then new bone formation: Initial inflammation causes erosion at corners of vertebral bodies ("Romanus lesion" or "shiny corners"). This is followed by reactive new bone formation - syndesmophytes form at the annulus fibrosus.
6. Ankylosis: Progressive syndesmophyte bridging of adjacent vertebrae leads to the classic "bamboo spine."
7. Sacroiliitis: Begins in the lower iliac portion of the SI joint (richest in hyaline cartilage), progressing to total joint obliteration.

6. Clinical Features and Signs

Spinal / Axial Features

• Inflammatory low back pain: Onset insidious, persists >3 months, worse at rest and at night, improved by exercise - a key distinguishing feature from mechanical back pain
• Early-morning stiffness lasting >30 minutes
• Pain in SI joint region, with or without radiation to the buttock
• Midthoracic and cervical pain (suggests inflammatory pathology)
• Fatigue - often a major complaint in young male patients

Signs on Examination

• Schober's test: <5 cm increase in lumbar flexion (tests lumbar spine mobility)
• Chest expansion reduced (<5 cm at 4th intercostal space) - due to costovertebral joint involvement
• Occiput-to-wall distance increased - due to cervical rigidity
• Tragus-to-wall distance increased
• Loss of normal lumbar lordosis - early finding
• Kyphotic posture - late finding ("question mark" posture)
• Sacroiliac tenderness on direct compression
• FABER (Patrick's) test positive - pain on Flexion, ABduction, External Rotation of hip

Extra-Articular Features

• Anterior uveitis (25-30%) - acute, unilateral, painful red eye; recurrent
• Cardiovascular: Aortitis, aortic regurgitation, conduction defects (AV block)
• Pulmonary: Upper lobe bilateral reticulonodular infiltrates with cyst formation (apical fibrobullous disease)
• Skin: Psoriasis (in some overlap patients)
• Bowel: Subclinical ileocolitis (~60% at colonoscopy)
• Peripheral arthritis: Asymmetric, predominantly lower extremity large-joint oligoarthritis (hip, knee, ankle)
• Enthesitis: Heel pain (Achilles/plantar fascia), chest wall tenderness

7. Diagnosis / Investigations

Classification Criteria - Modified New York Criteria (1984)

1. Low back pain and stiffness >3 months, improved by exercise but NOT by rest
2. Limitation of lumbar spine motion in sagittal AND frontal planes
3. Limitation of chest expansion

• Sacroiliitis grade ≥2 bilateral, OR grade 3-4 unilateral

• Definite AS: Radiological criterion + at least 1 clinical criterion
• Probable AS: 3 clinical criteria alone, OR radiological criterion alone

Investigations

8. Complications

Sjögren's Syndrome

1. Definition

• Primary Sjögren's - sicca features occur in isolation, without another underlying autoimmune disease
• Secondary Sjögren's - sicca features occur in the setting of another autoimmune disease (e.g., rheumatoid arthritis, SLE, scleroderma)

2. Aetiology

• Genetic: Associations with HLA-B8 and HLA-DR3 alleles; also linked to other MHC alleles and non-MHC immune-regulatory genes
• Viral triggers: An initial inciting viral infection (e.g., Epstein-Barr virus, hepatitis C virus, HTLV-1, Coxsackievirus) is thought to trigger an aberrant autoimmune response in genetically susceptible individuals
• Immune dysregulation: Overstimulation of B cells leading to polyclonal hypergammaglobulinaemia and autoantibody production (anti-Ro/SS-A and anti-La/SS-B)
• Epithelial activation: Salivary gland epithelial cells adopt an activated phenotype and drive chronic inflammation via type I interferons and chemokine expression
• Hormonal: Oestrogen's immunomodulatory role may explain the striking female predominance (>90% women)

3. Types

4. Predisposing Factors

5. Pathogenesis

1. Inciting event: A viral infection (likely) triggers innate immune activation in genetically predisposed individuals
2. Epithelial activation: Salivary and lacrimal gland epithelial cells upregulate MHC class II molecules, adhesion molecules, and produce pro-inflammatory cytokines (IFN-alpha/beta, BAFF)
3. T-cell infiltration: CD4+ T cells (predominantly) and CD8+ T cells infiltrate the glands; follicular helper T cells (Tfh) are increased and promote B-cell activation
4. B-cell overstimulation: Chronic B-cell activation leads to:
   • Polyclonal hypergammaglobulinaemia
   • Production of anti-Ro/SS-A and anti-La/SS-B autoantibodies
   • Ectopic germinal centre formation within glands
   • Autoreactive B-cell clones escape tolerance checkpoints
5. Glandular destruction: Progressive lymphocytic infiltration replaces acinar cells, causing hypofunction and dryness
6. Systemic spread: Immune complexes, cryoglobulins, and autoreactive lymphocytes cause extraglandular manifestations
7. Lymphomagenesis: Chronic B-cell stimulation and clonal expansion can evolve into marginal zone B-cell lymphoma (in salivary/lacrimal glands)

6. Clinical Features and Signs

Glandular Features

• Dry mouth, soreness, burning sensation of mouth and lips
• Difficulty chewing, swallowing, and speaking
• Food sticking to buccal mucosa; intolerance to acidic/spicy foods
• Signs: Absent sublingual salivary pool, cloudy/stringy saliva, smooth fissured tongue with filiform papillae atrophy
• Bilateral parotid gland enlargement in 25-66% (may be episodic or chronic)
• Dental caries - especially along the gingival margin

• Foreign body / "gritty" or "sandy" sensation in eyes
• Dryness, redness, photophobia, pain
• Signs: Dilated bulbar conjunctival vessels, periorbital injection, corneal surface irregularity, lacrimal gland enlargement

• Vaginal dryness - burning, dyspareunia (especially peri-/postmenopausal women)
• Dry nose, throat, skin (xerosis/pruritus)
• Dryness of trachea/bronchi: chronic dry cough

Systemic / Extra-glandular Features

7. Diagnosis / Investigations

ACR/EULAR 2016 Classification Criteria for Primary Sjögren's Syndrome

Investigations

8. Complications

Osteomyelitis

1. Definition

2. Aetiology

By Route of Infection

By Causative Organism

3. Types / Classification

By Duration

By Mechanism / Cierny-Mader Classification (Adults)

By Pathogen Type

• Pyogenic (bacterial) - most common
• Mycobacterial (TB, non-tuberculous mycobacteria)
• Fungal (Aspergillus, Candida, Blastomyces, Coccidioides)
• Viral/parasitic - rare

4. Predisposing Factors

5. Pathogenesis

Acute (Haematogenous) Osteomyelitis - Stages

1. Bacteraemia: Organisms enter the bloodstream from a focus of infection (e.g., skin, throat, GI tract) or IV drug use
2. Metaphyseal seeding: The metaphyses of long bones are preferentially affected due to:
   • Slow, turbulent blood flow through looped sinusoidal vessels
   • Relative lack of phagocytic cells in these vascular loops
   • Microtrauma creates foci for bacterial adherence
   • S. aureus binds bone matrix collagen via surface adhesins
3. Acute inflammatory phase (0-48 hours): Bacteria proliferate; intense neutrophilic response; bone cell necrosis begins within 48 hours
4. Abscess formation: Pus accumulates under pressure; spreads longitudinally along Haversian canals and radially through cortex
5. Periosteal elevation: Pus tracks through cortex, lifts periosteum - creates subperiosteal abscess which:
   • Disrupts blood supply to cortex (ischaemic necrosis)
   • Acts as a powerful stimulus for new bone formation (involucrum)
6. Soft tissue extension: Periosteum ruptures → soft tissue abscess → draining sinus tract to skin surface
7. Chronic phase (>1 week): Chronic inflammatory cells release cytokines → osteoclast activation → bone resorption
   • Sequestrum: Fragment of dead, devascularised, infected bone; acts as a persistent nidus for infection
   • Involucrum: Shell of new living periosteal bone surrounding the sequestrum
   • Cloaca: Opening in involucrum through which pus drains
   • This creates a "bone-within-a-bone" appearance on imaging
8. Joint involvement: Epiphyseal infection may spread into the joint → septic arthritis (especially in neonates where epiphyseal vessels traverse the physis)

6. Clinical Features and Signs

Acute Osteomyelitis

• Fever, rigors, malaise, anorexia (systemic illness)
• Severe throbbing, constant pain over the affected bone
• Refusal to use the limb (particularly in children - "pseudoparalysis")
• Unexplained fever in infants; localised pain in adults

• Localised tenderness over the affected metaphysis
• Swelling, warmth, erythema of overlying soft tissues
• Restricted movement of adjacent joint (sympathetic effusion)
• Lymphadenopathy (regional)
• In neonates: irritability, poor feeding, swollen limb

Subacute Osteomyelitis

• More insidious; milder systemic features
• Localised pain and mild tenderness
• May present as Brodie's abscess (tender metaphyseal lytic lesion)

Chronic Osteomyelitis

• Persistent low-grade pain and tenderness
• Discharging sinus tract through skin (pathognomonic)
• Intermittent acute flare-ups after years of dormancy
• Soft tissue fibrosis and scarring
• Bone deformity, shortening, or thickening
• May be surprisingly asymptomatic between flares

Vertebral (Spinal) Osteomyelitis - Pott's Disease (TB)

• Insidious back pain, low-grade fever, night sweats, weight loss
• Spinal tenderness
• Psoas abscess (may point to inguinal region)
• Gibbous deformity (angular kyphosis) - from vertebral collapse
• Neurological deficits from cord compression

7. Diagnosis / Investigations

8. Complications

Cervical Spondylosis

1. Definition

2. Aetiology

3. Types (Clinical Entities)

• "Soft" disc: Acute herniation of nucleus pulposus without osteophytes
• "Hard" disc: Disc-osteophyte complex (chronic; more common in spondylosis)

4. Predisposing Factors

• Age >40 years
• Male sex
• Genetic predisposition (early disc degeneration)
• Occupational: frequent lifting, excessive driving, prolonged neck posture
• Cigarette smoking
• Prior cervical trauma or surgery
• Congenitally narrow cervical spinal canal (Torg/Pavlov ratio <0.8)
• Obesity (increased axial load)
• Rheumatoid arthritis (accelerates cervical joint destruction)

5. Pathogenesis

Flowchart

AGEING + MECHANICAL STRESS + GENETIC PREDISPOSITION
                    │
                    ▼
     ┌─────────────────────────────────┐
     │  Nucleus Pulposus Dehydration   │
     │  (loss of proteoglycans/water)  │
     └─────────────┬───────────────────┘
                   │
                   ▼
     ┌─────────────────────────────────┐
     │  Disc Height Loss               │
     │  + Annular Tears / Fissures     │
     └─────────────┬───────────────────┘
                   │
                   ▼
     ┌─────────────────────────────────┐
     │  Increased Load on              │
     │  - Facet joints                 │
     │  - Uncovertebral joints (Luschka│
     └─────────────┬───────────────────┘
                   │
                   ▼
     ┌─────────────────────────────────┐
     │  Reactive Osteophyte Formation  │
     │  (vertebral endplates, facets,  │
     │   uncovertebral joints)         │
     └─────────────┬───────────────────┘
                   │
                   ▼
     ┌─────────────────────────────────┐
     │  Loss of Cervical Lordosis      │
     │  + Ligamentum Flavum Hypertrophy│
     └─────────────┬───────────────────┘
                   │
        ┌──────────┴──────────┐
        ▼                     ▼
┌───────────────┐    ┌──────────────────────┐
│ Neural Foramen│    │  Central Spinal Canal │
│ Narrowing     │    │  Narrowing            │
└───────┬───────┘    └──────────┬───────────┘
        │                       │
        ▼                       ▼
┌───────────────┐    ┌──────────────────────┐
│ RADICULOPATHY │    │ MYELOPATHY           │
│ (nerve root   │    │ (spinal cord         │
│ compression)  │    │ compression)         │
└───────────────┘    └──────────────────────┘

6. Clinical Features and Signs

A. Discogenic Neck Pain (Axial)

• Insidious onset neck pain, worse with movement
• Occipital headache (referred pain)
• Restricted cervical range of motion
• No neurological deficit

B. Radiculopathy (Nerve Root Compression)

• Spurling's test (positive): Neck rotation + lateral bend + vertical compression reproduces radicular pain
• Shoulder abduction sign: Relief of pain when patient places hand on head (decompresses root)
• Dermatomal sensory loss, myotomal weakness, hyporeflexia

C. Cervical Myelopathy (Cord Compression) - Most Serious Form

• Finger clumsiness - difficulty with buttons, writing (most common early symptom)
• Clumsy, wide-based gait, leg heaviness, difficulty with tandem walk
• Bilateral upper extremity numbness and paresthesias (especially hands)
• Neck/arm/leg pain
• Urinary dysfunction - urgency, frequency, or retention
• Lower extremity weakness (corticospinal tract involvement = worse prognosis)

• Hyperreflexia in lower limbs (UMN); may have hyporeflexia at level of compression (LMN)
• Hoffman's sign positive (flicking middle finger → thumb flexes) - UMN sign
• Babinski sign positive
• Inverted radial reflex: Tapping brachioradialis → finger flexion instead of forearm flexion (C5-6 lesion)
• Lhermitte's sign: Electric shock-like sensation down spine on neck flexion
• Grip and release test: Inability to open/close fist >20 times in 10 seconds
• Romberg sign positive (posterior column involvement)
• Spastic paraparesis / quadriparesis in advanced cases

• Stepwise deterioration then stable period: 65-80% (most common)
• Slowly progressive over months-years: 20-25%
• Rapidly progressive over days-weeks: 3-5%

7. Diagnosis / Investigations

8. Complications

Lumbar Spondylosis

1. Definition

2. Aetiology

3. Types / Clinical Entities

Stenosis subtypes:

• Central stenosis - thecal sac compression (neurogenic claudication)
• Lateral recess stenosis - nerve root compressed before it exits the foramen
• Foraminal stenosis - nerve root compressed at exit foramen
• Tandem stenosis - both cervical and lumbar stenosis coexist

4. Predisposing Factors

• Age >40 years (prevalence rises steeply with age)
• Male sex (canal smaller at L3-L5 in men)
• Genetic predisposition
• Occupation: heavy lifting, driving, repetitive spinal loading
• Obesity
• Cigarette smoking
• Previous lumbar surgery or trauma
• Congenitally narrow lumbar canal
• Scoliosis or kyphosis (abnormal spinal mechanics)
• Metabolic diseases: Paget's, acromegaly, fluorosis
• Spondylolisthesis (isthmic or degenerative)

5. Pathogenesis

Flowchart

AGEING + GENETIC FACTORS + MECHANICAL OVERLOAD
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  Nucleus Pulposus Desiccation    │
     │  (loss of water, proteoglycans)  │
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  Disc Height Loss                │
     │  + Annular Tears / Fissures      │
     │  + Endplate Changes (Modic)      │
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  Increased Load Transferred to:  │
     │  - Posterior facet joints        │
     │  - Posterior longitudinal lig.   │
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  Facet Osteoarthritis            │
     │  + Vertebral Endplate Osteophytes│
     │  + Disc Bulge / Annular Retropul │
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  Ligamentum Flavum Hypertrophy   │
     │  + Facet Capsule Hypertrophy     │
     │  (40% of canal compression from  │
     │   soft tissues alone)            │
     └──────────────┬───────────────────┘
                    │
         ┌──────────┼──────────────┐
         ▼          ▼              ▼
   ┌──────────┐ ┌──────────┐ ┌────────────┐
   │ Discogen-│ │ Foraminal│ │  Central   │
   │ ic Pain  │ │ Narrowing│ │  Stenosis  │
   └──────────┘ └────┬─────┘ └─────┬──────┘
                     │             │
                     ▼             ▼
               ┌──────────┐ ┌───────────────┐
               │RADICULOP-│ │ NEUROGENIC    │
               │ATHY      │ │ CLAUDICATION  │
               │(sciatica)│ │ / Cauda equina│
               └──────────┘ └───────────────┘

NOTE: On EXTENSION → ligamentum flavum buckles
inward + disc bulges anteriorly = WORST compression.
On FLEXION → canal opens = RELIEF (e.g., leaning
forward on shopping cart = "shopping cart sign").

6. Clinical Features and Signs

A. Discogenic Low Back Pain

• Axial low back pain - insidious onset, dull/aching
• Worse with prolonged sitting, bending, lifting
• Back pain > leg pain
• No neurological deficit, no tension signs
• Restricted lumbar flexion, paravertebral muscle spasm
• May radiate to buttocks but not below the knee

B. Lumbar Radiculopathy (Disc Herniation / Foraminal Stenosis)

• Straight Leg Raise (SLR) / Lasegue's test (positive if pain reproduces at <70°): stretches L4-S1 roots
• Crossed SLR (positive): contralateral leg raise reproduces ipsilateral sciatica - highly specific for disc herniation
• Femoral stretch test: hip extension stretches L2-L4 roots - for upper lumbar disc
• Kemp's test: extension + lateral flexion + rotation reproduces radicular pain
• Dermatomal sensory loss, myotomal weakness, diminished or absent reflexes

C. Neurogenic Claudication (Lumbar Spinal Stenosis)

• Bilateral leg pain, aching, heaviness, numbness brought on by walking or standing
• Relieved by sitting, squatting, or spinal flexion ("shopping cart sign" / "stoop test")
• Symptoms worsen going downhill (extension position), improve going uphill (flexed posture)
• Variable walking distance before symptoms force patient to stop
• Buttock and thigh > calf distribution
• Normal peripheral pulses (differentiates from vascular claudication)

• May have minimal findings at rest
• Wide-based gait, reduced lumbar extension
• UMN signs absent (cauda equina = LMN lesion)
• Hyporeflexia at ankle and knee
• Sensory loss in dermatomal pattern
• Schober's test: reduced lumbar flexion

D. Cauda Equina Syndrome (Surgical Emergency)

• Saddle anaesthesia (perianal, perineal, inner thigh numbness)
• Urinary retention (most reliable sign) or incontinence
• Faecal incontinence
• Bilateral leg weakness
• Bilateral absent ankle jerks
• Must be decompressed within 24-48 hours to preserve function

7. Diagnosis / Investigations

• Normal: >100 mm² cross-sectional area / AP diameter >12 mm
• Relative stenosis: 100-75 mm²
• Absolute stenosis: <100 mm² / AP diameter <10 mm

8. Complications

Systemic Lupus Erythematosus (SLE)

1. Definition

2. Aetiology

3. Types

4. Predisposing Factors

5. Pathogenesis

Flowchart

GENETIC SUSCEPTIBILITY (HLA-DR2/DR3, complement deficiency)
+ ENVIRONMENTAL TRIGGERS (UV, infections, drugs)
+ HORMONAL FACTORS (oestrogen)
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  Increased Apoptosis / Impaired  │
     │  Clearance of Apoptotic Debris   │
     │  → Release of nuclear antigens   │
     │    (dsDNA, histones, Sm, Ro, La) │
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  Dendritic Cells Activated       │
     │  → TYPE I INTERFERON (IFN-α/β)  │
     │    overproduction ("IFN signature")│
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  B-cell Hyperactivation          │
     │  + Defective T-regulatory cells  │
     │  + Autoreactive T helper cells   │
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  AUTOANTIBODY PRODUCTION         │
     │  • Anti-dsDNA (specific for SLE) │
     │  • Anti-Sm (specific for SLE)    │
     │  • Anti-Ro/SS-A, Anti-La/SS-B    │
     │  • Anti-histone (drug-induced)   │
     │  • Antiphospholipid antibodies   │
     │  • Anti-C1q                      │
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  IMMUNE COMPLEX FORMATION        │
     │  (Ag-Ab complexes)               │
     │  → Deposited in tissues:         │
     │    kidneys, skin, joints, vessels│
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  COMPLEMENT ACTIVATION           │
     │  (C3a, C5a - anaphylatoxins)     │
     │  → Neutrophil/macrophage recruit.│
     │  → Inflammatory cytokines (IL-1, │
     │    IL-6, TNF-α)                  │
     └──────────────┬───────────────────┘
                    │
                    ▼
     ┌──────────────────────────────────┐
     │  TISSUE INJURY                   │
     │  • Glomerulonephritis (wire-loop)│
     │  • Vasculitis                    │
     │  • Serositis                     │
     │  • Haematological cytopenias     │
     │  • CNS injury                    │
     └──────────────────────────────────┘

6. Clinical Features and Signs

Constitutional (>90%)

• Fever, fatigue, malaise, weight loss, lymphadenopathy

Musculoskeletal (~95%)

• Arthralgia - most common and earliest symptom
• Non-erosive, migratory polyarthritis (resembles RA but non-destructive)
• Jaccoud's arthropathy - deforming but non-erosive arthropathy
• Myalgia, myopathy
• Avascular necrosis of femoral head (even without steroids)

Cutaneous (~80%)

• Malar (butterfly) rash - erythema over cheeks and nose bridge, SPARING nasolabial folds; lasts days to weeks; resolves without scarring
• Discoid lupus - scarring plaques on face/scalp; can cause permanent alopecia
• Photosensitivity - rash or systemic flare on UV exposure
• Oral/nasal ulcers - painless (or mildly painful); hard palate, buccal mucosa
• Subacute cutaneous LE (SCLE) - annular or papulosquamous rash on sun-exposed areas
• Bullous LE - subepidermal blisters; responds dramatically to dapsone
• Alopecia - diffuse, non-scarring; "lupus hairs" (short fragile frontal hairs)
• Livedo reticularis - marker for CNS involvement and antiphospholipid syndrome
• Vasculitic lesions: palpable purpura, leg ulcers, periungual telangiectasia
• Raynaud's phenomenon (~15%; associated with less renal disease)

Renal (~50%) - Lupus Nephritis

• Proteinuria (>0.5 g/day), haematuria, RBC casts
• Nephrotic or nephritic syndrome
• Hypertension
• Progression to chronic kidney disease/ESRD
• WHO/ISN-RPS Classes: I-VI (Class III/IV = proliferative = worst prognosis; Class V = membranous)
• "Wire-loop" lesion on light microscopy (subendothelial immune complex deposits) in Class IV
• Active nephritis virtually never occurs without positive anti-dsDNA

Cardiovascular

• Pericarditis - most common cardiac manifestation (pleuritic chest pain, friction rub)
• Myocarditis (cardiomegaly, gallop)
• Libman-Sacks endocarditis - non-bacterial verrucous vegetations on mitral valve; associated with APL antibodies
• Accelerated atherosclerosis - major cause of death in long-standing SLE
• Thrombosis (arterial and venous) - due to antiphospholipid antibodies

Pulmonary

• Pleuritis with effusion (most common; pleuritic chest pain)
• Acute lupus pneumonitis
• Interstitial lung disease
• Shrinking lung syndrome (diaphragm dysfunction)
• Pulmonary arterial hypertension (anti-RNP antibodies)
• Pulmonary embolism (from antiphospholipid syndrome)

Neuropsychiatric (NPSLE)

• Seizures (in absence of other causes)
• Psychosis (in absence of other causes)
• Cognitive dysfunction, "lupus fog"
• Depression, anxiety
• Cerebrovascular disease (stroke - from vasculitis or antiphospholipid syndrome)
• Transverse myelitis, optic neuritis, chorea
• Cranial neuropathies, peripheral neuropathy
• Aseptic meningitis

Haematological

• Haemolytic anaemia (Coombs-positive)
• Leucopenia / Lymphopenia (<4000/μL; <1000/μL)
• Thrombocytopenia (<100,000/μL); ITP may precede SLE
• Elevated ESR; CRP often normal (CRP rises only with serositis or infection in SLE)

Gastrointestinal

• Nausea, vomiting, diarrhoea
• Mesenteric vasculitis / intestinal pseudo-obstruction
• Lupus hepatitis, pancreatitis (rare)

Other

• Sjögren's syndrome overlap (keratoconjunctivitis sicca)
• Hashimoto's thyroiditis association
• Antiphospholipid syndrome: recurrent miscarriages, DVT, stroke, thrombocytopenia

7. Diagnosis / Investigations

Classification Criteria

1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Non-erosive arthritis
6. Serositis (pleuritis/pericarditis)
7. Renal disorder (proteinuria >0.5g/day or cellular casts)
8. Neurological disorder (seizures/psychosis)
9. Haematological disorder (haemolytic anaemia / leukopenia / lymphopenia / thrombocytopenia)
10. Immunological disorder (anti-dsDNA / anti-Sm / APL antibodies)
11. Positive ANA

Laboratory Investigations

8. Complications