Rheumatology Flashcards
1
Q
What type of arthritis is Rheumatoid Arthritis?
A
It is a Chronic Symmetrical Inflammatory Polyarthritis of unknown origin
2
Q
Which HLA types have been identified in Rheumatoid Arthritis?
A
HLA- DR4 and HLA-DR1
3
Q
Which sex is most commonly affected by Rheumatoid Arthritis?
A
Young Females are more affected than males
4
Q
What environmental factors are hypothesized to play a role in the pathogenesis of Rheumatoid Arthritis?
A
- Smoking (esp women who are RF + or APCA +)
- Others: stress or infections: EBV, CMV, Proteus, E. Coli, Porphyromonas Gingivalis. ACPA → Anti-Citrullinated Protein Antibody
5
Q
What is the pathogenesis of RA
A
Unknown Trigger → triggers immune system → Inflammatory Cascade → Cytokines (TNF-α, IL-1, IL-6) → Synovium produces Pannus (Type of granulation tissue with inflammatory cells) → Cytokines release proteolytic enzymes and activate osteoclasts → Destruction of cartilage and bone NB → also have activated B-Lymphocytes which produce Ab, which maintain the inflammatory response → most relevant = RF & ACPA
NB → the main target of RA is the Synovium
6
Q
What is the classical clinical picture of Rheumatoid Arthritis? (i.e epidemiology)
A
Young Women
Insiduous onset of pain and early morning stiffness → wrist and hands (typically)
Constitutional Sx (Lethargy, Fatigued, Low grade fever)
Loss of function of joints
7
Q
Which joints can be affected in Rheumatoid arthritis?
A
Most common = Wrists, Proximal IPJ’s, MCPJ’s & MTPJ’s, knees, ankles
Less common = Elbows, cervical spine (C1/C2), Shoulders, Hips Rarely → Crico-Arytenoid, Temporomandibular
8
Q
What is the classical course of Rheumatoid Arthritis?
A
Chronic Condition characterisedby flares (Acute on Chronic)
Persistant inflammation is characterised by gradual loss of function due to progressive joint damage Vast majority of RA patients are forced to make work and lifestyle changes
9
Q
The hallmark of Rheumatoid arthritis is
A
The hallmark of Rheumatoid arthritis is Synovitis best seen around the hands
10
Q
What are the clincial signs which raise suspicion for Rheumatoid arthritis? (5) (early signs)
[…]
A
- Boggy Tender soft tissue swelling palpable & visible around MCP and PIP joints
- Inability to make a fully closed fist
- Loss of grip strength
- Swelling over dorsal wrist (these tendons are often at risk of rupturing - Extensor tendons 4/5)
- Wasting of intrinsic muscles may occur early in disease - due to cytokines and disuse due to pain or entrapment neuropathy
11
Q
What deformities can occur in the hands in advanced Rheumatoid Arthritis?
A
1, Swan neck Deformity
2. Boutonniere Deformity
3. Z Deformity of the Thumb
4. Ulnar deviation and later subluxation and dislocation of the MCPJ
12
Q
What does the Swan Neck Deformity in Rheumatoid Arthritis entail?
A
Flexion of the MCP and DIPJs with Extension of the PIPJs
Occurs due to shortening/abnormal tone of intrinsic hand muscles and tendons
13
Q
What does the Boutonniere Deformity in Rheumatoid Arthritis entail?
A
PIPJ flexion and DIPJ hyperextension
14
Q
What does the Z-Thumb deformity in Rheumatoid Arthritis entail?
A
MCPJ flexion and IPJ hyperextension
15
Q
What does Ulnar deviation and Subluxation in Rheumatoid Arthritis deformity entail?
A
d.t extensor tendon malalignemnt and progressive MCPJ destruction
16
Q
What features in Rheumatoid Arthritis are suggestive of a Poor prognosis?
A
- Early appearance of erosions
- RF/ACPA Positivity
- Rheumatoid Nodules
17
Q
What Peri-articular Manifestations of RA are there? (2)
A
- Rheumatoid Nodules (Usually in RF+ patients) - Occurs on extensor surfaces of the forearm
- Tenosynovitis - common since synovium is targeted in RA
18
Q
What are the ocular manifestations of RA? (4)
A
- Scleritis/Episcleritis resulting in scleromalacia = blindness if untreated
- Secondary Sjögrens syndrome Any RA patient with a red eye needs an urgent opthalmalogical opinion
19
Q
What are the pulmonary manifestations of RA? (3)
A
Pleurisy/Effusions are the most common manifestations
ILD (Fibrosis) also occurs commonly
Nodules (Rheumatoid) may occur in Lung/Pleura (coal miners + RA+ pulmonary nodules»_space; extensive fibrosis»_space; Caplan syndrome)
20
Q
What are the cardiac manifestations of RA? (1)
A
Pericardial effusions
21
Q
What are the Skin Manifestations of RA? (1)
A
Leg ulcers due to vasculitis
22
Q
What is the pathogenesis of Rheumatoid nodules?
A
It has been observed that rheumatoid nodules frequently form over extensor sites and areas vulnerable to trauma. The trauma causes inflammatory particles to build up and leads to a secondary inflammatory response which ultimately causes fibrin release and necrosis.
23
Q
What are the Haematological Manifestations of RA? (2)
A
Anaemia → Anaemia of chronic disease or due to NSAID’s use (PU)
Felty’s Syndrome → Triad of RA, Spleenomegaly and Neutropenia = susceptible to severe disease
23
Q
What are the Neurological Manifestations of RA? (2)
A
Carpal Tunnel Syndrome
Cervical Myelopathy with UMN signs due to spinal cord compression due to RA of C1/C2
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What special investigations can be done to Confirm your RA Dx?
(Bloods) - 5
(Fluids) - 1 (look for 6)
(Imaging) -3
Bloods:
- FBC → Anaemia, Thrombocytosis (Acute phase response)
ESR/CRP → Often Elevated
Serology → RF/APCA
U+e → To get a baseline in the pt before Rx administration
- If considering Biologicals >> TB GXP
Fluids- Synovial Fluid → Straw Coloured/Cloudy (Polymorphonuclearcytes and ↑WBC, RF+, No Crystals, No Cultures, ZN negative, low glucose)
Imaging
Radiology → Soft tissue swelling, peri-articular osteopenia, erosions
U/S → Picks up early erosions
MRI → Sensitive to both erosions and synovitis but expensive
25
What are the medical options for RA treatment?
Non-medical
Medical - (5)
NON MEDICAL
1. Patient education
2. Physiotherapy -Exercises to maintain mobility
3. Occupational therapy - esp if still employed and to prevent contractures
4. Social worker - counseling and disability grant forms
MEDICAL
1. Disease Modifying Antirheumatic drugs (DMARDs)
2. Biological Therapies
3. Steroids
4. Anti-inflammatories (NSAIDs - Diclofenac, Ibuprofen, Idomethacin)
5. Analgesics (Paracetamol & Amytriptyline)
SURGICAL
26
What Surgical Options are available for RA patients? (3)
1. Joint Replacement (Pain not responding to medical treatment, restoration of movement)
2. Synovectomy (single joint not responding to adequate treatment of DMARDs especially if threatening tendon rupture)
3. Carpal Tunnel Release (If necessary)
27
What drug is used as the cornerstone for treatment of RA?
Methotrexate - a DMARD Use it weekly
Other options include: Sulfasalazine & Chloroquine (Daily use)
All these drugs are slow acting and youll only see results and improvement after 2-4 months
28
What is the prognosis of RA?
RA is a debilitating condition that produces significant disability.
More than 30% will leave workforce within 5 years
life expectancy is shortened by 10 years
Increased mortality due to:
1. Cardiovascular Complications (accelerated Atherosclerosis)
2. infections, Malignancies (Lymphoma)
3. RA itself (vasculitis,lung involvement, medication-related)
29
- What is the RF
- What does a + RF suggest?
- However, RF has poor specificity. List 4 other conditions where it is +
Auto-antibody against the FC portion of the body's own immunoglobulins.
A + RF suggests a poor prognosis
1. Old age
2. TB, HIV, hepatitis B/C
3. Infective endocarditis
4. Other rheumatic diseases >> SLE, Sjogrens
30
- What is Anti-CCP
- What does Anti-CCP suggest?
- What is the advantage of using anti-CCP vs RF
- What are the main disadvantages of anti-CCP?
-Anti-CCP is a group of Ab directed against citrullinated peptides (modified proteins). Citrillunation of peptides is normal, but in the genetically susceptible pts, it is associated with Ab formation and persistent inflammation and synovitis
- Pro: 98% specificity ; may predict the development of RF way before clinical signs appear.
- Cons: Also + in HIV, TB, and other CTDs
31
List 3 drugs that are disease modifiying in RFA
1. DMARDS
2. Biologicals
3. Steroids
32
Which group do the following drugs belong to:
Infliximab, adulimab
Rituximab
Tocilizumab
Biologicals
1. TNF-a blockers
IL-6 blockers
B-lymphocyte blockers
33
What is the dose of steroids for short-term use (week)vs for maintenance (i.e when used in combination with DMARDS to gain better control of the disease)
short-term: 0.5 mg/kg
Maintenance: < 10 mg/day
34
List 5 complications of steroids
1. Diabetogenic, HPT
2. Osteoporosis
3. Increase susceptibility to infections
4. AVN risk higher
5. Cataract (EYE! )
35
What is Osteoarthritis (OA)?
OA is defined pathologically or radiologically as the loss of articular cartilage, sclerosis of subchondral bone and osteophytosis. It represents the end result of numerous pathways resulting in structural failure of a joint
36
What are the important epidemiological aspects of OA?
Very common : 2-3% of populatoin
Increase with age
Male = Female (Female more severe)
37
What are the main aetiological causes of OA?
PRIMARY
- Localised
- Generalised
SECONDARY
Congenital
= Untreated Congenital dislocation of the hip
= Perthes Disease
= SUFE
Traumatic
Fracture, internal derangement, neuropathic joint (DM), occupational
Inflammatory
Septic
Rheumatoid
Seronegative arthropathies
Metabolic
(Crystal arthritis,
hemochromatosis
alkaptonuria)
Endocrine
(Acromegaly, DM, Hyperparathyroidism, Hypothyroidism)
37
What is the nature of pain in OA?
Deep pain, worse on movement, relieved by rest
Pain may be referred (to knee from hip) Pain is due to microfractures of subchondral bone, low grade synovitis, increased venous pressure, osteophytes or from surrounding soft tissue
37
Describe the basic Pathological mechansims behind OA
Biochemical & Mechanical changes = cartilage damage
Focal Softening of articular cartilage
Focal Develops → clefts and crevices
Subchondral Bone exposure → Sclerosis & Cyst formation [synovial fluid by pressure of joint is forced into bone = cyst]
Chondrocytes [ ] ↓ (Die)
Destruction of cartilage → Joint destruction
Osteophytes = late attempt to stabilise joint (Hypertrophy of subchondral bone and remodelling results in sclerosis and osteophyte "spur" formation
38
What are the main symptoms for OA?
No Systemic Symptoms (constitutional)
1. Pain
2. Stiffness which lasts 15-30min, morning and after immobilization
3. Muscle Spasm
4. Pain worse with movement
39
Which joints are commonly involved in OA? (9)
DIP
PIP
1st Carpometacarpal joint
Acromioclavicular
Knees
Hips
Spine (Lumbar & lower cervical)
1st MTP If outside this list, look deeper to exclude another cause
40
What are common signs for OA? [this is now when you are examining this patient] - 7
1. Swelling due to capsular thickening, bony enlargement, effusion or synovitis
2. Tenderness @ joint margin
3. Crepitus
4. Warmth
5. Palpable osteophytes (herbeden and bouchards)
6. Deformity (Impaired function)
7. Muscle atrophy due to disuse
41
What laboratory tests can be done for OA?
There are no specific lab tests for OA, unless you looking for secondary causes.
Synovial fluid is essentially normal
42
What are the 8 modes of OA treatment? Explain each modality
Non-pharma - 3
Pharma - 3
Surgical - 2
NON-PHARMA
1. Weight reduction> reduce load on joints.
2. Exercise> Increases mobility.> symptom relief
3. Heat/ massage > eases painful,, stiff joints > symptom relief
PHARMA
1. Analgesics- simple> panado
2. NSAIDS (or Cox-2 inhibitors to decrease GI risk)
3. Steroids - intra-articular
SURGICAL
- Arthroplasty - re-alignment > relive painful movement and increase mobility
- Osteotomy > joint replacement. >> mobility >> functionality
42
What radiological features suggest OA? (6)
Radiologically, specific joints are affected by OA >> DIP, PIP, 1ST CMC, Hip, knee, acromio-clav, certain parts of the spine (lower cervical and lumbar)
1. Loss of joint space
2. Subchondral Sclerosis
3. Bone cysts
4. osteophyte formation
5. Malalignment/Deformity
6. HAND X-RAY: Gullwing sign in DIPs and PIPs
43
What are the indications for Arthoplasty in OA? (2)
1. Severe pain, unresponsive to medical therapy, constantly awakens from sleep, cannot stand in one place for >20/30 min
2. Loss of joint function >> cannot walk more than 1 block, effect on ADLs
44
What supplements can be given for OA? (3)
1. Glucosamine >> glycosaminoglycans
2. Chondroitin: from bovine trachea
3. Viscosupplementation> Hyaluronan (glycosaminoglycan)
45
PRIMARY GENERALISED OA (> or more than 4 joints involved )
- Describe the inheritance pattern in males vs females
- What is the pathology in this type of OA?
- T/F These pts get OA with episodic course with mild inflammatory phases.
- Females: dominant inheritance, Males: recessive
- Defect in type 2 or 9 cartilage
- True
46
NODULAR ARTHRITIS/ INFLAMMATORY OA
- This is common, worst on which side?
- Describe the pattern of involvement
- Describe the clinical signs
- List 3 conditions with which it is commonly misdiagnosed
- Dominant side
- DIP, PIP, 1st CMC, 1st MTP
- Herbeden and Bouchard's nodes, flexion and/or lateral deviation of distal phalanx
- RA, Acute gout/ pseudogout
46
OA OF HIP
- 80% of these cases are due to?
- Describe the loss of ROM
- Where does the pt feel the pain?
- Developmental defects.
- Loss of internal rotation first, then decreased extension, abduction and flexion
- Pain in groin/ buttock or knee.
46
OA OF KNEE
- Which 2 compartments of the knee may be affected?
- Describe findings of patellofemoral OA on examination
- List 2 commonly associated symptoms
1. tibiofemoral and patellofemotal compartment
2. Crepitus on passive flexion / extension
3. quadriceps wastign + effusions
46
OA OF SPINE
- Which part in the spine is affected by OA
- TRUE OR FALSE: There is good clinical and radiologic correlation
- Describe how the pt may present (3)
- Lower cervical and lower lumbar spine
- False- poor correlation
1. Pain (may be radiated to buttocks or shoulder or localized)
2. neurological symptoms
3. Decreased ROM d/t pain and stiffness
46
What are the Crystal Arthropathies?
A group of pathological conditions in which crystals contribute to tissue damage Main mechanism is crystal formation within joint capsules and hence an inflammatory response
47
What are the 3 important crystals that cause crystal arthropathies, and what conditions cause them?
Uric Acid Crystals → Gout
Calcium Pyrophosphate Crystals → Pseudo-Gout & Chondrocalcinosis
Calcium Hydroxyapatite Crystals → Calcifying Peri-Arthritis & Tendinitis
48
What is Uric Acid?
What is the normal Uric acid in men and women, respectively?
Uric acid is the chief end product of purine metabolism (Humans do not have the enzyme uricase, this oxidases ua to a highly soluble compound allantoin).
We get 10-30% of uric acid from dietary purines (adenine and guanine). 60-90% from endogenous liver excretion
Men: < 0.45 mmol/L
Women < 0.35 mmol/L
48
Interaction between Crystals & Plasma Proteins may cause 3 things, namely?
Complement Activation
Release of Cellular Mediators (eg. Histamine)
Phagocytosis - Free Radicals and Lysosomal Enzymes
49
What is Gout?
Inflammatory reaction in Synovial Joints &/or Periarticular tissues due to the Deposition of Urate Crystals due to Hyperuricemia.
Gout is the commonest inflammatory arthritis is men > 40y/o (+ postmenopausal women)
49
What are the primary causes for Hyperuricaemia?
OVERPRODUCTION
- With or without enzyme abnormality
→ Superactivity of PRPP Synthase
→ Deficiency of HGPRT
UNDER SECRETION
→ Low GFR
→ Abnormal Tubular Management of Uric Acid
OR
Combination of the two
49
What are the Secondary Causes for Hyperuricemia?
DRUGS: CAN'T LEAP }All decrease renal excretion of uric acid
Cyclosporine;
Alcohol;
Nicotinic acid;
Thiazides;
Lasix;
Ethambutol;
Aspirin (low dose);
Pyrazinamide
OVERPRODUCTION
- Purine Rich Food
- Increased Cell Turnover, Myelo & Lymphoproliferative Disorders, - Psoriasis
- Increased ATP Breakdown with Alcohol Abuse, fructose ingestion, and Obesity
UNDER SECRETION
- Keto & Lactic Acidosis,
- Renal Disease, Polycystic Kidney Disease,
Lead Nephropathy, Hypothyroidism, Hyperparathyroidism
49
What is the spectrum of manifestations that come with Hyperuricemia? (5)
1 → Asymptomatic Hyperuricaemia
2 → Acute Gout
3 → Interval/intercritical Gout (ASx intervals between acute attacks)
4 → Chronic Tophaceous Gout
5 → Complications: Gouty Nephropathy, Kidney Stones
50
Asymptomatic Hyperuricaemia
- What is meant/ how is this entity diagnosed?
- What is an important step in your management? Exclude __
- Discuss the management of these patients (4)
Definitoin= Pt demonstrates hyperuricaemia at least 3 times with monthly intervals (NB never Rx on grounds of one result)
Exclude Secondary Causes
Management:
1. Dietary Adjustments
2. 24h Uric Acid Excretion test (>800mg/24 hr production =over producer. < 800mg/24 hrs excreted = underexcreter)
3. Determine renal function
4. Evaluate for metabolic syndrome- HPT. DM,
Rx is controversial → most do not develop acute gout
51
ASYMPTOMATIC HYPERURICAEMIA
If Uric Acid levels are persistently above 0.54mmol/L what is the patient at high risk of? (4)
THEREFORE, we treat if uric acid values are persistently> 0.5 mmol/L or > 12 mg/dL
Acute Gout
Kidney Stones
Gouty nephropathy
CVS complications
52
ACUTE GOUT ATTACK
Describe the clinical picture of an Acute Gout Attack.
Middle aged man, awakens early in the morning, metabolic profile
Severe pain and swelling and redness of affected joint, mostly mono-articular (or Oligoarticular) or acute gout of 1st MTP= pogadra
Pyrexia, Malaise, Raised WCC, and Raised ESR
53
ACUTE GOUTY ATTACK
What are some precipitating factors for Acute Gout? (6)
1. Trauma
2. Surgery - 3-5 days post op
3. Drugs
4. Excessive alcohol/food binge
6. Bleeding
7. Acute medical illness (Infection, radiation etc.)
54
ACUTE GOUTY ATTACK
What are some associated conditions with Acute Gout?
1. Acute Tenosynovitis
( Other sites: Olecranon Bursa, Prepatellar bursa, Achilles tendon
2. History of/current uric acid kidney stones
3. Tophi
55
What special investigations are used to confirm a diagnosis of acute gout? (Labs, Imaging, Fluids)
LABS
Serum Uric A. >> Raised/Normal
U+e > Renal impaired? low GFR?
ESR/WCC > raised
FLUIDS
Synovial Fluid microscopy for crystals
IMAGING
X-Rays show soft tissue swelling
Sonar
DECT
55
What condition does acute gout mimic?
Cellulitis - periarticular edema and swelling
56
DDX of MONOARTHRITIC acute gout (5)
1. Cellulitis
2. Septic Arthritis
3. Pseudogout (CPPD)
4. Reactive Arthritis
56
DDX of POLYARTHRITIC acute gout (2)
1. RA
2. CPPD
57
What is the average interval duration between attacks in interval gout?
On average 6-9 months → interval becomes shorter with increased frequency of attacks
57
Which conditions can co-exist with gout? - 4
RA, OA, CPPD, Sepsis
58
CHRONIC TOPHACEOUS GOUT
What is chronic tophaceous gout ?
This is gout which is characteristic of having acute attacks which last a little longer as well as chronic polyarticular arthritis with secondary degenerrative changes
59
What are Tophi (wrt. Gout)?
Tophi are seen in Chronic Tophaceous Gout
ASx
Limit Joint Movement/Nerve Impingement
Can Ulcerate → Material is released
Secondary Infection
Tophi are stone-like deposits of monosodium urate in the soft tissues, synovial tissues, or in bones near the joints.
60
What Renal Complications are seen in Hyperuricemia? (3)
1. Stones → Urate stones are radio transparent & Calcium stones are radio-opaque
2. Kidney Pathology → Interstitial fibrosis (Slow progressive renal failure)
3. Acute Urate Nephropathy
61
How is Acute Gout managed? (3)
In acute gout, you treat the inflammation. Not the Raised Uric Acid
1. Colchicine - 1 mg stat, then 0.5 mg 2 hrs later, then 0.5 mg 12 hrs later, then 0.5 mg 2-3x dly if normal kidney function (If AbN kidney, no more than 0.5 mg/day )
2. NSAID (or COX2- celebrex)
3. Corticosteroids (IMI or IAI)
or a Combo of the above
62
How is Interval/Chronic Gout managed?
Removal of precipitating factors and secondary causes
Treat metabolic syndrome
Change medication where needed e.g. HCTZ
63
What is the main indication for gout prophylaxis?
What is the 1st line and 2nd line gout prophylaxis medication
All pts that are going on uric acid-lowering therapy
→ 1st Line - Colchecine, Low Dose NSAID & PPI
→ 2nd Line - Low dose Prednisone PO
64
What are the indications for Uric Acid lowering therapy? (List 6)
1) > 2 attacks of acute gout / year
2) Tophi
3) Gout with chronic kidney disease
4) Uric acid kidney stones past or present
5) [Very raised uric acid levels >0,55 mmol/l or 12mg/dl]
6) [ X ray changes of gout ]
65
What are the 2 main Uric Acid Lowering Medications used in Gout?
Uricosuric Drug → Probenecid
Xantine Oxidase Inhibitor → Allopurinol
66
TRUE OR FALSE:
Drugs that are lipid-lowering must ONLY be started AFTER the resolution of the acute attack. BUT if the pt is already on this medication, you should NOT stop it during the attack.
True
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