Rheumatology Revision 4 Flashcards

(56 cards)

1
Q
A
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2
Q

Describe the basic pathophysiology of RA

A

current theory for the pathophysiology of RA is that exposure to an external trigger in a genetically predisposed individual leads to an abnormal, autoimmune response, which targets synovial joints resulting in chronic inflammation and joint damage

Following a suspected triggering event, there is development of self-citrullination: alteration of a positively charged arginine amino acid into the neutral citrulline
- The immune system then reacts to these citrullinated proteins, which is characterised by development of anti-cyclic citrullinated peptide (anti-CCP) antibodies.

Also get infiltration of synovial joints with immune cells and a subsequent pro-inflammatory response causing the classic synovitis

At joint level: synovial membrane hyperplasia, or ‘thickening’, which subsequently damages cartilage - called a pannus. There is subsequent boney loss, which manifests as localised and periarticular boney erosions.

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3
Q

Describe the clinical features of RA

A

Polyarthropathy:
- multiple joints affected, usually in symmetrical distribution; typically the small joints of hands or feet (MCP most common; PIP; MTP)
- On palpation of the joints, there will be tenderness and synovial thickening, giving them a “boggy” feeling.
- Morning stiffness lasting more than 30 mins
- Joint swelling
- Cervical (but not lumbar) spine can be affected
- Knees, ankle, hips and shoulders
- Pain on palpitation

Muscle atrophy:
- may see ‘guttering’ between extensor tendons in hands due to wasting of the interossei muscles

Systemic symptoms
- myalgia
- fatigue
- low-grade fever
- weight loss
- low mood

TOM TIP: Rheumatoid arthritis very rarely affects the distal interphalangeal joints. Enlarged and painful distal interphalangeal joints are more likely to represent Heberden’s nodes due to osteoarthritis.

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4
Q

Describe what is meant by a boutonniere and swan-neck deformity [2]

A

Boutonniere deformity:
- flexion at the PIP joint with hyperextension of the distal interphalangeal (DIP) joint
- caused by a tear in the central slip of the extensor components at the proximal interphalangeal (PIP) joint.

Swan-neck deformity:
- hyperextension at the PIP joint with flexion of the DIP joint

Boutonniere - same positions are buttoning up a shirt

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5
Q

Name two other hand signs of RA (asides from swan-neck and Boutonniere deformities) [2]

Name a foot sign [1]

A

Ulnar deviation at MCPs:
- subluxation of the MCP joints with deviation of the fingers towards the ulnar bone due to dislocation of flexor tendons and disruption of extensor tendons.

Z-deformity at wrist:
- hyperextension of interphalangeal joint of thumb in association with carpal bone rotation and radial deviation as well as ulnar deviation at MCPs
- deformity to the thumb

Hammer toes:
- compensatory flexion of the toes due to weakening and subluxation of surrounding tendons.

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6
Q

Describe why RA can lead to spinal cord compression [1]

A

Atlantoaxial subluxation occurs in the cervical spine.:
- Synovitis and damage to the ligaments around the odontoid peg of the axis (C2) allow it to shift within the atlas (C1).

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7
Q

Describe the extra articular manifestations of RA:
- occular [4]
- oral [2]

A

Ocular
* Keratoconjunctivitis sicca: refers to dry eyes. Seen in 10%. If accompanied with xerostomia (dry mouth) suggestive of secondary Sjögren’s syndrome.
* Episcleritis: inflammation of superficial layer of sclera
* Scleritis: more aggressive inflammation of the whole sclera
* Scleromalacia perforans

Oral
* Xerostoma (dry mouth): If accompanied with keratoconjunctivitis sicca (dry eyes) suggestive of secondary Sjögren’s syndrome.
* Oral ulcers

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8
Q

Describe the extra articular manifestations of RA:
- pulmonary [3]
- cardiac [4]

A

Pulmonary
* Interstitial lung disease
* Serositis: inflammation of serous membranes (i.e. pleural, pericardium, peritoneum)
* Costochrondritis

Cardiac
* Pericarditis: as part of serositis
* Myocarditis
* Non-infective endocarditis
* Increased risk of ischaemic heart disease

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9
Q

Describe the extra articular manifestations of RA:
- Renal [1]
- Neurological [3]
- Haemotological [3]

A

Renal
* Glomerulonephritis (uncommon in the absence of vasculitis)

Neurological
* Peripheral neuropathy: diffuse sensorimotor neuropathy or mononeuritis multiplex
* Entrapment mononeuropathies: carpal tunnel syndrome
* Cervical myelopathy: typically due to cervical spin involvement or atlantoaxial subluxation

Haematological
* Neutropenia: if combined with splenomegaly known as Felty’s syndrome
* Thrombocytopaenia or thrombocytosis
* Haematological malignancies

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10
Q

Describe 3 dermatological mainfestations of RA [3]

A

Rheumatoid nodules:
- most present skin complaint (20%). Found on extensor surfaces of upper limb at pressure points (e.g. elbow) as hard nodule. Composed of central fibrinoid necrosis with surrounding fibroblasts. Usually in seropositive patients.

Vasculitis skin rash:
- ulcers, digital gangrene, periungual infarcts, splinter haemorrhages

Pyoderma gangrenosum

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11
Q

How do you differentiate PsA to RA? [3]

A
  • PsA often demonstrates an asymmetric oligoarticular pattern.
  • Dactylitis (sausage digits) and enthesitis are also unique features of PsA that help differentiate from RA.
  • Radiographic findings such as pencil-in-cup deformity or periostitis could aid differentiation; these are NOT typical for RA.
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12
Q

Which factors indicate a worse prognosis in RA?

A

Poor prognostic features
* rheumatoid factor positive
* poor functional status at presentation
* HLA DR4
* X-ray: early erosions (e.g. after < 2 years)
* extra articular features e.g. nodules
* insidious onset
* anti-CCP antibodies

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13
Q
A

Rheumatoid arthritis seen in adults of all ages

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14
Q

Which is the most common occular complication of RA? [1]

A

keratoconjunctivitis sicca

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15
Q

What are iatrogenic occular complications seen in RA? [2]

A
  • steroid-induced cataracts
  • chloroquine retinopathy
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16
Q

What is the difference between epi- and slceritis? [2]

A

episcleritis (erythema)
scleritis (erythema and pain)

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17
Q
A

HLA DR4

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18
Q

Lung fibrosis caused by rheumatoid arthritis typically affects the:
* Upper zone
* Lower zone

A

lower zones

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19
Q
A

DAS28

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20
Q

State why synovial joints are susceptible to inflammatory injury [2]

A

Presence of rich network of fenestrated capillaries
* Fenestrated capillaries: become more leaky so plasma and immune cells can enter synovial membrane and joint cavity

Limited ways it can respond

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21
Q

DAS28 is used to monitor RA; treat to target is the aim.

What DAS28 scores would indicate:
- disease remission [1]
- low severity [1]
- medium severity [1]
- high severity [1]

A
  • disease remission: < 2.6
  • low severity: 2.6 - 3.2
  • medium severity 3.2 - 5.1
  • high severity: > 5.1
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22
Q

Name this deformity seen in the hand associated with RA [1]

Describe the changes in hand position that occurs [2]

A
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23
Q

Describe the initial treatment plan for RA with MILD disease activity at initial presentation: not pregnant or planning pregnancy

A

1st Line: conventional DMARD:
- hydroxychloroquine - it is better tolerated and has a more favourable risk profile than other DMARDs

Consider: Corticosteroid
- Prednisolone

Consider: non-steroidal anti-inflammatory drug (NSAID)
- ibuprofen

NB: hydroxychloroquine: should only be considered for initial therapy if mild

BMJBP

24
Q

State 5 side effects of corticosteroids

A

Osteoporosis; weight gain; DM; HTN

25
Methotrexate: 1. MoA? 2. Advantages [3] 3. Disadvantages [6]
**MoA**: - Folic acid inhibitor (due to inhibition of dihydrofolate reductase) which stops cell proliferation; impacts rapidly dividing cells **Advantages**: - Inexpensive - Oral or injection - Well established safety profile **Disadvantages** - N&V - Mouth sores - Hair loss - Liver toxicity - Bone marrow suppresion - Lung toxicity
26
How do you manage / monitor ongoing methotrexate; SSZ and LEF prescription? [3]
**FBC** and **LFTs** are to be **monitored every 2 weeks** for the first **6 weeks (induction phase)** and with any **increased dose**, and then **monthly for 3 months**.
27
What important AE do you need to monitor for with hydroxychloroquine tx? [1]
**Retinal toxicity** - requires regular eye exams Also: gastrointestinal upset, skin rash
28
Describe the MoA [1] and AEs [3] of MMF
**MoA**: - **Inhibits** enzyme used for de novo **purine synthesis** - effects **T & B cells** **AEs**: - GI upset - Infections - Bone marrow suppression
29
What do you screen for **prior to starting** methotrexate; SSZ and LEF tx? [3]
- **FBC; UEs; LFTs** - **Viral serology screen** - **Baseline** **CXR** - for **MTX** as can cause PF - **Baseline BP** for **LEF**
30
What should you offer women prior to cyclophosphamide treatment? [1]
Egg harvesting treatment as causes infertility
31
Describe the MoA and side effects of cyclophosphamide
**MoA**: - Alkylating agent - cross links DNA strands, leading to cell death **Effects**: - Bone marrow suppression - Bladder inflammation - hamorrhagic cystitis - Infertility - N&V
32
Describe some of the unwanted effects of blocking TNFa
TNFa is essential for granuloma formation, organisation and maintenance - **risk of TB reactivation** AND **increased risk of infection** **Autoimmune reactions:** - paradoxical psoriasis (new onset or worsening) - drug induced lupus - MS or optic neuritis **Allergic reactions** **HF exacerbations** **Blood abnormalities** (anaemia; neutropenia) **Liver toxicity** **Increased risk of malignancies**
33
What should you screen for prior to anti-TNF tx? [4]
**FBC ++** **Serology for HIV, HBV & HCV** **CXR and TB Elispot** **Exclude** **infections**, **pregnancy**, **malignancy**, **NYHA Class III/IV and EF < 50%**
34
antibodies to antibodies
Can produce antibodies agaisnt
35
Name an anti-TNF that can be used in pregnancy [1]
**Certolizumab**
36
Name an anti-TNF that might cause less chance of infection [1]
**Etanercept**
37
Whats an overall JAK inhibitor MoA? [1]
JAKs are inside the cells (block the messages delivered by cytokines inside the cells) There are different JAKs
38
Name an advantage of JAK inhibitors tx [1]
Can be taken orally (c.f. biologics are often infusions)
39
Name some side effects of JAK inhibitors [4]
**Increased risk of serious infections** - use in caution with > 65 **Risk of MACE** - caution with CVD **Malignancy** - particularly increased risk of **lymphoma and lunger cancer** **Thrombotic events; GI side effects and anaemia**
40
Describe the treatment pathway for RA
41
Which alternative drug should be used if pregnant or pregnancy planning? [1]
**Sulfasalazine**
42
How often do you perform blood tests for methotrexate monitoring? [1]
43
How do you assess response to methotrexate use? [1]
Assess using **DAS28 = disease activity score of 28 joints**
44
45
What needs to be checked before starting DMARDs?
**Hepatitis B and C status, purified protein derivative (PPD), FBC, and LFT**s need to be checked before starting DMARDs.
46
Describe the initial treatment plan for RA with **MODERATE-SEVERE disease activity at initial presentation** *not pregnant or planning pregnancy*
**1st line cDMARD:** - **methotrexate** (primary option) with **folic acid supplementation** - sulfasalazine (secondary option) - hydroxychloroquine (secondary option) - leflunomide (secondary option) - bridged with corticosteroid - **prednisolone for 2/3 months until methotrexate starts working** **2nd line: Combination treatment with multiple cDMARDs** **3rd line: bDMARDs** - **etanercept** (primary option) - **infliximab** - **adalimumab** **4th line: Rituximab** ## Footnote Double check with lecture
47
How do you treat a flare of RA? [1]
flares of RA are often managed with corticosteroids - oral or intramuscular - **methylprednisolone**
48
Which RA medication has a risk of reactivating TB? [1]
**Etanercept** and also adalimumab, infliximab, golimumab and certolizumab
49
Which RA medication has a risk of an infusion reaction? [1]
**Rituximab**
50
**TOM TIP**: The main biologics to remember are **[3]** (TNF inhibitors), and **[1]** (a monoclonal antibody that targets the CD20 proteins on the surface of B cells).
TOM TIP: The main biologics to remember are **adalimumab, infliximab and etanercept (TNF inhibitors)**, and **rituximab** (a monoclonal antibody that targets the CD20 proteins on the surface of B cells). **They cause immunosuppression, increasing the risk of infection, certain cancers (e.g., skin) and reactivation of latent TB.**
51
Describe the dosing regimen for methotrexate [1]
**Methotrexate** interferes with folate metabolism and suppresses the immune system. **It is given once a week** **Folic acid 5mg** is taken once a week (on a different day to the methotrexate)
52
Describe the MoA of Leflunomide [1] Name 5 side effects [5]
**Leflunomide** is an immunosuppressant medication that interferes with the production of pyrimidine. **Side effects:** * **Mouth** **ulcers** and mucositis * **Increased** **blood** **pressure** * **Liver toxicity** * **Bone marrow suppression and leukopenia** (low white blood cells) * **Teratogenic** (harmful to pregnancy) and needs to be avoided before conception in both women and men * **Peripheral neuropathy**
53
**TOM TIP: The unique side effects worth remembering are**: - Methotrexate [3] - Leflunomide [2] - Sulfasalazine [3]
**TOM TIP: The unique side effects worth remembering are**: **Methotrexate:** * Bone marrow suppression * leukopenia * highly teratogenic **Leflunomide**: - Hypertension - peripheral neuropathy **Sulfasalazine**: - Orange urine - male infertility (reduces sperm count)
54
**TOM TIP: The unique side effects worth remembering are**: - Hydroxychloroquine [3] - Anti-TNF medications [2] - Rituximab [2]
**Hydroxychloroquine**: - Retinal toxicity - blue-grey skin pigmentation - hair bleaching **Anti-TNF medications:** - Reactivation of tuberculosis **Rituximab**: - Night sweats - thrombocytopenia
55
**[2]** are considered the safest DMARDs in pregnancy
**Hydroxychloroquine and sulfasalazine** are considered the safest DMARDs in pregnancy
56
3-monthly monitoring for MTX, SSZ, and LEF includes..? [5]
3 monthly **FBC; ALT; AST; ALP; Albumin; U&Es**