Induction — Rheumatology

Written by Betra Youhanna, a medical student and not a doctor — check every detail against your own teaching.

7 diseases · 5 criteria · structured C/P · Inves · Mng

C/P — Clinical Presentation

Inves — Investigations

Mng — Management

Special — Pathognomonic / disease-unique

Rheumatic & Autoimmune Disease

7 entries

Rheumatoid Arthritis

C/P

Affects 1% of population (higher >50y)
Female:Male = 3:1
Onset typically 20–50y
Joint destruction → deformity → disability
Life expectancy shortened

Inves

Rheumatoid Factor (RF): antibodies to IgG; sensitivity >80% in RA at high levels; IgA and IgM RF present years before onset; most RF are IgM subtype; high levels = worse prognosis
Anti-CCP (anti-cyclic citrullinated peptide): as sensitive as and more specific than IgM RF in early + established disease; predicts development into RA in undifferentiated arthritis; marker of erosive disease; detectable in healthy individuals years before clinical RA

Mng

— (deck doesn't enumerate RA-specific drugs; TNF role implicated as pivotal cytokine for biologic therapy)

Special

Pathogenesis: abnormal antigen presentation in synovium; immune complex–mediated; T cell + macrophage dysregulation → MMP + RANKL ligand production
TNF = pivotal (but not exclusive) cytokine; acts pro- and anti-inflammatory directly + indirectly via IL-1, IL-6
Citrullinated extracellular fibrin in synovium = major autoantigen; citrullination by PAD (peptidylarginine deiminase)
Plasma cells make RF antibodies in the joint
Major synovial cell types: T lymphocytes, macrophage-like (type A) synoviocytes, fibroblastic (type B) synoviocytes; less abundant — dendritic cells, B cells, plasma cells, mast cells, osteoclasts
Difficult-airway risk factor: RA (cervical spine involvement/surgery; limited mouth opening) → anticipate difficult intubation

Systemic Lupus Erythematosus (SLE)

C/P

ACR 1982 criteria — ≥4 of 11

Malar rash: fixed red rash over cheeks
Discoid rash: red patches with scaling + plugging of hair follicles
Photosensitivity: rash after sunlight exposure
Mucosal ulcers: mouth and nose
Serositis: inflammation of delicate tissues covering internal organs; abdominal pain
Arthritis: very common; joint pain
Renal disorder: detected by routine blood + urine analysis
Neurological disorder: seizures or psychosis
Haematological disorder: haemolytic anaemia, leukopenia, thrombocytopenia
Immunologic disorder: LE cells, anti-DNA, anti-Sm antibodies
ANA positive (not on offending drugs)
Neuropsychiatric SLE — CNS manifestations: peripheral neuropathy (incl. Guillain-Barré), grand mal seizures, chorea/choreoathetosis, cognitive impairment (memory/perception/orientation/intellectual), severe headaches, stroke, B-cell lymphoma, limbic encephalitis-type picture
Psychiatric presentation: most commonly depression + anxiety (esp. recently diagnosed patients or those with disfiguring skin lesions); psychosis rare

Inves

ANA by indirect immunofluorescence (IIF): patterns include homogenous/speckled, high titre
Anti-dsDNA: screen with Crithidia luciliae; monitoring by quantitative ELISA
Direct immunofluorescence (DIF): immune complex deposition in skin + kidney (anti-IgG or C3 antibody with fluorescent probe)
Limitations: ANA can be positive in healthy individuals (esp. elderly); positive ANA in non-CTD has no diagnostic/prognostic value; ANA titre ≠ disease activity

Mng

Rituximab (chimeric monoclonal anti-CD20 antibody) → B-cell depletion lasting 6–9 months; response rate ~60%
- Antibody levels that fall: anti-DNA, anti-nucleosome, anti-C1q, anti-cardiolipin
- Antibody levels that do NOT fall: anti-Ro, anti-La, anti-Sm, anti-RNP, anti-measles, anti-tetanus toxoid

Special

Predominantly women of childbearing age
Environmental factors (anecdotal/suggested): sunlight, pesticides, silica, mercury, EBV infection, hormones
Paradox: ~90% of adults are EBV-infected, yet SLE prevalence remains low → multifactorial pathogenesis
SELENA study: HRT → increase in mild flare but no overall increase in disease activity
Immunopathogenesis: genetic susceptibility + external triggers → B and T cells specific for self-nuclear antigens (failure of self-tolerance) → apoptosis with defective clearance → TLR stimulation of B cells + DCs by antigen-antibody complexes → type I IFN (IFN-α) production → persistent IgG anti-nuclear antibodies
Discoid lupus: imaging shown pre/post B-cell depletion in deck

Systemic Sclerosis (Scleroderma)

C/P

Diffuse, progressive scleroderma: generalised skin thickening with rapidly progressive and often fatal visceral involvement
Limited cutaneous scleroderma (CREST syndrome):
- Calcinosis cutis
- Raynaud's syndrome
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasias
Skin thickening most obvious; also affects kidney, lung, heart, gut

Inves

ANA testing useful in CTD work-up (per general autoimmune section)

Mng

Special

Systemic disease characterised by sclerosis of connective tissue

Sjögren's syndrome

Special

Named as an autoimmune rheumatic disease; a connective-tissue disease (CTD) in which ANA testing is a useful diagnostic tool alongside relevant clinical history/symptoms

Seronegative spondyloarthropathies (incl. ankylosing spondylitis)

Special

Ankylosing spondylitis — HLA-B27, relative risk 87.4, sex ratio 0.3 (male predominance) — the strongest association on the HLA table
Acute anterior uveitis is also HLA-B27 associated (relative risk 10, sex ratio <0.5)

Chronic arthritis in children (juvenile arthritis)

Special

Named as an autoimmune rheumatic disease on the disease-list slide (survey level only)

Polymyositis / dermatomyositis

Special

Named as a connective-tissue disease (CTD) in which ANA testing is useful alongside relevant clinical history/symptoms

Autoimmune & Nutrition

2 entries

ACR 1982 SLE Criteria

Use: Diagnose SLE. Patient must have ≥4 of these 11 manifestations at any time since disease onset.

Malar rash: fixed red rash over the cheeks
Discoid rash: red patches with scaling and plugging of hair follicles
Photosensitivity: rash after sunlight exposure
Mucosal ulcers: small sores in mouth and nose
Serositis: inflammation of delicate tissues covering internal organs; abdominal pain
Arthritis: very common; pain in the joints
Renal disorder: usually detected by routine blood and urine analysis
Neurological disorder: seizures or psychosis
Haematological disorder: haemolytic anaemia, leukopenia, thrombocytopenia
Immunologic disorder: tests on LE cells, anti-DNA, and anti-Sm antibodies
Anti-Nuclear Antibody (ANA): positive (when patient is not taking drugs known to cause a positive test)

Nutritional Severity Score

Impaired nutritional status (short-term = food intake in last week)

Score 1: Decreased within 50–70% of normal requirements
Score 2: 25–60% of normal requirements
Score 3: 0–25% of normal requirements

Impaired nutritional status (longer-term = weight loss & BMI changes)

Score 1: >5% weight loss in 3 months
Score 2: >5% in 2 months · BMI 18.5–25 · impaired general condition
Score 3: >5% in 1 month · BMI <18.5 · impaired general condition

Severity of disease

Score 1: Diabetes; oncology; chronic patients (COPD or cirrhosis) with acute complications; chronic haemodialysis; hip fractures
Score 2: Major surgery; stroke; severe pneumonia; haematological malignancy
Score 3: ICU patients; head injury; bone marrow transplantation

Scoring rules & management

Age adjustment: if age >70, add 1 to give "age-adjusted total score"
Score ≥3: patient nutritionally at risk → initiate nutritional care plan
Score <3: weekly rescreening
Score <3 but scheduled for major operation: consider preventive nutritional care plan

Rheumatic / Autoimmune

3 entries

HLA serotype associations with autoimmune disease

Use: Links each autoimmune disease to its HLA allele, relative risk, and female:male sex ratio

Disease — HLA allele — relative risk — sex ratio (F:M)

Ankylosing spondylitis — B27 — 87.4 — 0.3
Acute anterior uveitis — B27 — 10 — <0.5
Goodpasture's syndrome — DR2 — 15.9 — ~1
Multiple sclerosis — DR2 — 4.8 — 10
Graves' disease — DR3 — 3.7 — 4–5
Myasthenia gravis — DR3 — 2.5 — ~1
Systemic lupus erythematosus — DR3 — 5.8 — 10–20
Type 1 (insulin-dependent) diabetes mellitus — DR3/DR4 heterozygote — ~25 — ~1
Rheumatoid arthritis — DR4 — 4.2 — 3
Pemphigus vulgaris — DR4 — 14.4 — ~1
Hashimoto's thyroiditis — DR5 — 3.2 — 4–5

Central vs peripheral tolerance (When / Where / How)

Use: Classifies self-tolerance by when, where and how self-reactive lymphocytes are controlled

Central tolerance

When: fetal life (setting) + throughout life (maintenance)
Where: thymus (T lymphocytes) / bone marrow (B lymphocytes)
How: apoptotic death (deletion) of immature self-antigen-specific lymphocytes

Peripheral tolerance

When: throughout life
Where: whole organism (except thymus and bone marrow)
How: apoptotic death (deletion) of mature self-antigen-specific lymphocytes, OR functional inactivation (anergy), OR suppression by regulatory T cells (Tregs) / other immunosuppressive effectors (IDO, kynurenines, IL-10, TGF-β1)

Mechanisms of the autoimmune response (6 mechanisms)

Use: Six mechanisms by which self-tolerance breaks down to trigger an autoimmune response

Cross-reactivity / molecular mimicry — microorganisms & viruses share antigens with self, eliciting cross-reactivity
Formation of neoantigens — by chemical binding (e.g. drugs) or tissue damage
Superantigens — microbial; cause stimulation of T-cells and massive cytokine release
Idiotype cross-reaction — epitopes on the antigen-binding portion of the immunoglobulin cross-react with anti-viral antibody
Release of sequestered / cryptic antigens — exposed to the immune system and provoke a reaction
Dendritic-cell apoptosis & clearance deficiency — leads to inappropriate lymphocyte activation