MEDICIN

2024
E
RHEUMATOLOGY

Rasheed Mohammed

RHEUMATOLOGY | Medicine 1
 Title No.

Rheumatoid Arthritis 3
Systemic Lupus Erythematosus 7
Gout 11

RHEUMATOLOGY | Medicine 2
 Rheumatoid Arthritis
• Pathology:
- Chronic autoimmune inflammation of synovium
- Systemic disease with extraarticular complications
- More common in women
- Usual age of onset 20 to 40 years
- Disease course may wax and wane with flares

• Association:
- HLA DR4, DR1
- IHD (RA = Type II DM)

• Clinical features
1. Constitutional symptoms: Fever, malaise, weight loss, and myalgias

2. Arthritis:
▪ Polyarthritis ≥ 3 joints
▪ Symmetric joint inflammation
▪ Gradual onset of Pain, stiffness, swelling
▪ Classically “morning stiffness”
▪ Joint stiffness >1 hour after rising
▪ Improves with use
▪ Most often involves wrists and hands
▪ Classically affects MCP and PIP joints of hands
▪ DIP joints spared (Contrast with osteoarthritis – DIP joints involved)
▪ Lumbar spine usually spared (Also a contrast with osteoarthritis)

3. Deformity:
▪ Ulnar deviation
▪ Swelling of MCP joints → deviation
▪ Swan neck deformity
▪ Hyperextended PIP joint with Flexed DIP
▪ Boutonnière deformity
▪ Flexed PIP joint with Hyperextended DIP
▪ Rheumatoid nodules
▪ Palpable nodules common in 20 to 35% patients
▪ Pathognomonic for rheumatoid arthritis
▪ Common on elbow although can occur anywhere
▪ Usually no specific treatment

4. Baker's cyst (popliteal cyst)

▪ Swelling of gastrocnemius-semimembranosus bursa
▪ Common in patients with OA or RA of knee
▪ Often asymptomatic bulge behind knee
▪ If ruptures → symptoms similar to DVT (Posterior knee pain, swelling, ecchymosis)
▪ Usually a clinical diagnosis, May need to rule out DVT

RHEUMATOLOGY | Medicine 3
 5. Extraarticular features
▪ Serositis – inflammation of serosal surfaces
▪ Pleuritis→ pleural effusion
▪ Pericarditis → pericardial effusion
▪ Parenchymal lung disease
▪ Interstitial fibrosis
▪ Pulmonary nodules
▪ Carpal tunnel syndrome
▪ Anemia of chronic disease
▪ Episcleritis and scleritis: Red eye, Eye pain, Discharge
▪ Sjogren’s syndrome: Common in patients with RA

• Investigation
1. CBC: Anemia of chronic disease
2. Acute phase reactant: ESR ↑CRP
3. Rheumatoid factor (RF)
▪ 70 to 80% of patients
▪ Low specificity – elevated in some normal patients and other conditions
4. Anticyclic citrullinated peptide antibodies (anti-CCP)
▪ More specific 98%
5. Arthrocentesis (Sampling of synovial fluid)
o WBC 20k to 50k (inflammatory “RA, gout”)
o WBC 2K – 20K (Osteoarthritis “non-inflammatory”)
o WBC > 50K = Septic Arthritis
6. Joint X-ray
o Early: Periarticular osteopenia
o Late: bony erosions, subluxation

• Diagnostic criteria: Scores ≥6 are diagnostic

A. Joint involvement (swelling or tenderness ± imaging evidence)
▪ 1 large joint =0
▪ 2–10 large joints =1
▪ 1–3 small* joints =2
▪ 4–10 small* joints =3
▪ > 10 joints (at least 1 small joint) =5
B. Serology (at least 1 test result needed)
▪ Negative RF and negative anti-CCP =0 Low +ve RF or low +ve anti-CCP =2
▪ High +ve RF or high +ve anti-CCP =3 C
C. Acute phase reactants (at least 1 test result needed)
▪ Normal CRP and normal ESR =0
▪ Abnormal CRP or abnormal ESR =1
D. Duration of symptoms:
▪ <6 weeks =0
▪ ≥6 weeks =1

• Long Term Complications

1. Increased risk of infections (Proteus mirabilis)
2. Increased risk of coronary disease (Leading cause of mortality)
3. Secondary (AA) amyloidosis

RHEUMATOLOGY | Medicine 4
 4. Felty Syndrome: Syndrome of splenomegaly and neutropenia in RA
6. Atlantoaxial joint arthritis (C1 to C2)
▪ Occurs with longstanding disease
▪ Neck pain and stiffness
▪ Complication → Cervical subluxation
o Possible life-threatening spinal cord compression
o May require surgical treatment
o Limited by DMARD therapy
▪ Cervical spine X-ray before surgery in RA patients
▪ Risk of neurologic injury with intubation
5. Osteoporosis
▪ Accelerated by RA
▪ Also often worsened by steroid treatment
▪ 30 percent ↑ risk of major fracture
▪ 40 percent ↑ risk hip fracture

• Treatment
• Acute flare:
▪ NSAIDS are good for symptom relief, but have no effect on disease progression.
▪ Corticosteroids: rapidly reduce symptoms and inflammation (Oral prednisolone or IM depot
methylprednisolone)
• Long term management:
▪ Disease-modifying antirheumatic drugs (DMARDs) + short course of corticosteroids

• Disease-modifying antirheumatic drugs (DMARDs)

- Protect joints from destruction
- Reduce disease progression and complications
- Slow onset of effect over weeks
- Usually given as oral drugs
- They include:
• Methotrexate
▪ Best initial DMARD
▪ May cause bone marrow suppression
▪ Co-administered with folic acid
▪ Also causes hepatotoxicity and stomatitis
▪ Monitor CBC, LFTs and creatinine
• Sulfasalazine (rash, ↓sperm, oral ulcers)
• Hydroxychloroquine (Eye involvement; retinopathy … annual screening)
• Lefluonimde (teratogenicity)

• Biological Therapy
▪ Antibody-based treatments
▪ Infusions or injections
▪ Used when resistance to 2 DMARDs (including methotrexate)
▪ Anti-TNF alpha therapy: infliximab
▪ Non-TNF biologics: Rituximab, Tocilizumab, Abatacept
▪ Pre-treatment screening for latent TB, hepatitis B and C

RHEUMATOLOGY | Medicine 5
 • Poor prognostic feature:
1. Female
2. Insidious onset
3. HLA DR4 +ve
4. +ve RhF, Anti-CCP, Radiological changes
5. Extra articular features

RHEUMATOLOGY | Medicine 6
 Systemic Lupus Erythematosus
• Pathology:
- Autoimmune disease with antibodies against nuclear components, e.g., dsDNA.
- Antibody-antigen complexes circulate in plasma (Type III HSR)
- Deposit in MANY tissues → diffuse symptoms
- Most patients (90%) are women
- Usually develops age 15 to 45

• Clinical features
- Flares and remissions common
- Systemic symposia: Fever, weight loss, fatigue, lymphadenopathy
- Malar rash
o Classic lupus skin finding
o “Butterfly” rash
o Common on sunlight exposure
- Discoid skin lesions
o Circular skin patches
o Classically on forearm
- Oral or nasal ulcers
- Raynaud Phenomenon
o White/blue fingertips
o Painful on exposure to cold
o Vasospasm of the artery → ischemia
o Can lead to fingertip ulcers
- Polyarthritis (monoarthritis unusual)
o Symmetric, Migratory
o Symptoms come/go over 24 hours
o Brief morning stiffness (< RA)
o Knees and hands most common
o Pain out of proportion to objective findings; Mild swelling, minimal X-ray abnormalities
- Serositis
o Inflammation of pleura (pain with inspiration)
o Inflammation of pericardium (pericarditis)
- Cytopenias
o Anemia, thrombocytopenia, leukopenia
o Antibody deposition on blood cells → destruction
o Immune dysfunction and ↑ infection risk
- CNS Involvement
o Cognitive dysfunction, Confusion, Memory loss
o Stroke, Seizures
- Cardiac Manifestations
o Libman-Sacks (marantic) endocarditis
o Nonbacterial inflammation of valves
o Increased risk of coronary artery disease

RHEUMATOLOGY | Medicine 7
 - Lupus Nephropathy
o Common (50% in first year, 75% overall).
o Common cause of death in lupus
o Can present as nephritic or nephrotic syndrome or both
o Requires renal Biopsy to diagnose.
o 6 histological stages:
▪ I: Minimal mesangial
▪ II: Mesangioproliferative
▪ III: Focal proliferative glomerulonephritis (<50% of glomeruli)
▪ IV: Diffuse proliferative glomerulonephritis (>50% of glomeruli) (Most
common/most severe)
▪ V: Membranous glomerulonephritis
-
▪ VI: Advanced Sclerosing lupus nephritis (ESRD)

• Laboratory findings
1. Anti-nuclear antibodies (ANA)
▪ Sensitive but not specific [present in many other autoimmune disorders]
▪ Negative test = disease very unlikely
▪ Reported as titer: 1:20 or 1:200
▪ Often 1:160 considered positive
2. Anti-double stranded DNA (anti-dsDNA)
▪ Specific for SLE
▪ Associated with disease activity (↑ in flares)
▪ Associated with renal involvement (glomerulonephritis)
3. Anti-smith (anti-Sm)
▪ Specific for SLE
4. Antiphospholipid antibodies
▪ Antibodies against proteins in phospholipids
▪ Can lead to antiphospholipid syndrome
▪ May cause venous or arterial thrombosis with ↑ PTT
5. Complement levels
▪ Low C3/C4 levels (hypocomplementemia)
▪ Antibody-antigen complexes activate complement
6. Inflammatory markers:
▪ ESR: increase with flares
▪ CRP: usually normal
▪ Multisystemic disorder + ↑ ESR but Normal CRP → think of SLE

• Diagnosis
- American College of Rheumatology (ACR) criteria
- Need four of 11 criteria
- At least 1 clinical + 1 laboratory or biopsy proven lupus-nephritis with +ve ANA or Anti-DNA

1. Malar Rash 2. Cerebritis

3. Discoid Rash 4. Renal disease;
5. Photosensitivity 6. Cytopenias
7. Oral ulcers 8. + ANA
9. Arthritis 10. Anti-dsDNA or Anti-Sm or antiphosphid
11. Serositis

RHEUMATOLOGY | Medicine 8
 • For monitoring & follow up:
1. Anti-dsDNA
2. Complement levels
3. ESR

• Treatment:
• Acute flare:
▪ Mild: (No serious organ damage.) Hydroxychloroquine or low-dose steroids.
▪ Moderate: (Organ involvement.) Mycophenolate.
▪ Severe flares: If life- or organ-threatening, eg haemolytic anaemia, nephritis, severe pericarditis
or CNS disease; high-dose IV steroids, IV cyclophosphamide.
▪ Lupus nephritis:
o Classes I and II
▪ Show mild histological changes with little risk of renal disease progression
▪ ACEI/ARB for renal protection
▪ Hydroxychloroquine for extra-renal disease.
o Classes III-V
▪ Mycophenolate, glucocorticoids, cyclophosphamide, rituximab.
▪ BP control vital (e.g., ACEI).
▪ Renal replacement therapy may be needed if disease progresses
▪ Neuropsychiatric lupus
o MDT working; psychometric testing, lumbar puncture may be indicated
• Maintenance:
1. NSAIDs: unless renal disease
2. Hydroxychloroquine
▪ Anti-malarial drug with immunosuppressant properties
▪ Common first line therapy
▪ Rare, feared adverse outcome: corneal deposits, retinopathy and vision loss
▪ Routine eye exams required
3. Glucocorticoids
▪ Added to hydroxychloroquine for more severe forms
▪ Oral prednisone or intravenous methylprednisolone
4. Steroid-sparing agents
▪ Azathioprine, methotrexate, and mycophenolate.
• General measures:
1. Avoid sunlight
▪ Many patients photosensitive → Can trigger flares
▪ Use sunblock
2. Pregnancy counseling
▪ May exacerbate disease
▪ Associated with higher risk of complications
▪ Usually avoided until disease quiescent 6 months
3. Screen for co-morbidities and medication toxicity.

RHEUMATOLOGY | Medicine 9
 • Drug-Induced Lupus
- Lupus-like syndrome after taking a drug
- Classic drugs: isoniazid, hydralazine, procainamide
- Often rash, arthritis, penias, ANA +ve, Anti dsDNA –ve
- Kidney or CNS involvement rare
- Key features: anti-histone antibodies >95% of cases.
- Resolves on stopping the drug

• Raynaud Phenomenon
* Seen in other autoimmune disorders (RA, scleroderma)
* Can be Isolated disorder
* Treatments: avoid cold, Dihydropyridine calcium blockers (amlodipine)

• Avascular Necrosis
* Osteonecrosis → Bone collapse
* Most commonly femoral head
* Mechanism poorly understood
* Associated with glucocorticoid use and SLE
* Also occurs in sickle cell disease

RHEUMATOLOGY | Medicine 10
 Gout

• Definition:
- Deposition of monosodium urate deposition in joints
- Triggers inflammatory response
- Recurrent attacks of acute monoarthritis

• Pathology:
- Combination of Hyperuricemia + genes predistortion + cool temperatures
- Usually monoarthritis
- 60% in the 1st metatarsophalangeal joint (base of great toe; podagra)
- Also often occurs in knee

• Assassination
- More common in obese males
- Associated with hypertension, HTN, IHD, metabolic Syndrome

• Triggers
A. Overproduction of uric acid:
1. Red meat, seafood
2. Trauma/surgery: tissue breakdown
3. Myeloproliferative disorders: CML, ET, PV associated with high cell turnover
4. Tumor Lysis syndrome: increase cell turnover
B. Decreased excretion by kidneys
1. Renal failure, Volume depletion
2. Thiazides, loop diuretics: ↓ uric acid secretion in urine
3. Alcohol: Metabolism leads to lactic acid production → increase renal reabsorption of urate
C. Genetic enzyme defects
1. Lesch-Nyhan Syndrome: X-linked absence of HGPRT → “juvenile gout”
2. Von Gierke’s Disease: G6P-deficiency → lactic acidosis → Promotes urate reabsorption

• Clinical course/ features

• Gout flares
▪ Acute arthritis; redness, hotness, swelling
▪ Usually monoarticular
▪ Often associated with a trigger: red meat, alcohol, surgery, drugs , etc …
• Intercritical period
▪ The time between gout flares
• Tophaceous gout
▪ Tophi: urate collections in connective tissue
▪ Most common in the Ears, tendons, bursa
▪ Slowly-enlarging hard masses, not painful or tender
▪ Seen with longstanding hyperuricemia
▪ Don’t confuse with RA nodules
o History of symmetric polyarthritis in RA
o History of recurrent bouts of monoarthritis in gout

RHEUMATOLOGY | Medicine 11
 • Complication:
1. Urate Nephropathy
▪ Consequence of longstanding hyperuricemia
▪ Uric acid crystals in urine → Uric acid stones → Chronic renal failure
2. Tophi

• Diagnosis
1. Arthrocentesis (Sampling of synovial fluid)
▪ WBC 20k to 50k
▪ Polarized light microscopy: Needle-shaped, “negatively birefringent” crystals
2. Serum urate level:
▪ Normal 3 to 8
▪ During gout flares normal or low serum urate may be present
o Cytokines may lower urate levels
o Urate deposits in joints
▪ Therefor testing for serum urate not helpful for diagnosis of gout
▪ Most accurate testing for urate is two weeks or more after a flare
3. X-rays
▪ May show evidence of joint destruction
▪ Particularly in advanced, chronic disease

• Treatment
• Acute attacks
1. Oral glucocorticoids: prednisolone
▪ Avoided with infection, post-op (wound healing), brittle diabetes
2. NSAIDs
▪ Usually high-dose potent NSAIDs; Naproxen or indomethacin
▪ Avoided with high bleeding risk (anticoagulant use), CKD, peptic ulcer disease
3. Colchicine
▪ Anti-inflammatory: inhibits white blood cell activity
▪ Alternative to glucocorticoids or NSAIDs
4. Glucocorticoid intraarticular injection
▪ Used when flare involves only one or two joints
• Prevention of acute attacks
1. Lifestyle modification
▪ Weight loss and exercise: ↓ serum urate and risk of flares
▪ Moderation of animal/seafood protein intake and alcohol
2. Allopurinol
▪ Xanthine oxidase inhibitor → ↓ uric acid production
▪ Goal urate level < 6 mg/dL (normal 3 to 8)
▪ May cause rash, leukopenia/thrombocytopenia or diarrhea
▪ Must be given under cover of NSAID/colchicine during the first few months of treatment
because allopurinol precipitates attack first
▪ Indication of allopurinol:
1. Frequent or disabling attacks (more than 2/year)
2. Tophi or structural joint damage
3. Renal insufficiency (CrCl <60 mL/minute)

RHEUMATOLOGY | Medicine 12
 3. Other drugs:
▪ Probenecid: Uricosuric drug – promotes urate excretion
▪ Pegloticase
o Recombinant form of uricase enzyme that breaks down urate
o Used for severe, refractory gout

• Deferential diagnosis for gout:

1. Pseudogout
2. Septic arthritis

• Pseudogout (Calcium Pyrophosphate Deposition Disease)

• Definition: Calcium pyrophosphate deposition in joints
• Association:
▪ Occurs in older patients (average age: 72)
▪ Common in patients with hemochromatosis, hypercalcemia and hyperparathyroidism
• Triggers: by trauma, surgery, medical illness, parathyroidectomy
• Clinical picture:
▪ Acute attacks of inflammatory arthritis
▪ Resemble attacks of gout
▪ Knee involved in 50% of cases
• Diagnosis:
▪ Polarized light microscopy Rhomboid crystals positively birefringent
▪ X-ray: Chondrocalcinosis
• Treatment:
▪ Acute attack: NSAIDs, Colchicine, Intraarticular glucocorticoid injection
▪ Prophylaxis for pseudogout: colchicine

RHEUMATOLOGY | Medicine 13