Rheumatology Flashcards

1
Q

What features in the history would you expect to see in a patient with gout?

A
Severe pain in a single joint (usually big toe)
Acute onset (typically <24 hours, often overnight) with episodes lasting 1-2 weeks
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2
Q

What features would you expect to see on examination of a patient with gout?

A

Tender, red, hot, swollen joint
Tophi (chalky deposits) typically in the digits or over the elbow
Marked swelling with red, shiny skin

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3
Q

What investigations would you carry out in a patient with suspected gout?

A
Baseline LFT and renal function
Serum rate levels
X-ray of symptomatic joints
Screen patients for cardiovascular risk factors
Synovial aspirate (in secondary care)
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4
Q

What criteria scoring system is used to diagnose gout?

A

The Nijmegen criteria (score >7 = 80% chance of gout)

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5
Q

Describe the factors and scores used in the Nijmegen criteria

A

Male sex: 2
Previous reported arthritis attack: 2
Onset within 1 day: 0.5
Joint redness: 1
First metatarsophalangeal joint involvement: 2.5
Hypertension/>1 cardiovascular risk factor: 1.5
Serum uric acid >0.35mmol: 3.5

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6
Q

How is a definitive diagnosis of gout made?

A

Identification of urate crystals in synovial fluid or tophi aspirate

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7
Q

Name 3 key differential diagnoses for gout

A
Septic arthritis
Pseudo-gout (secondary to chondrocalcinosis)
Psoriatic arthritis (severe psoriasis can cause elevated urate).
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8
Q

When would you refer a patient with suspected gout?

A

You are unsure if they have septic arthritis/other differential
Patient is resistant to treatment

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9
Q

Mechanism of action of allopurinol

A

Xanthine oxidase inhibitor (XO prolongs activity of 6-mercptopurine)

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10
Q

When is urate lowering therapy indicated?

A

Patients with tophi, erosions or recurrent gout attacks (>2/year), renal impairment, nephrolithiasis or on diuretics

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11
Q

Which patients should allopurinol doses be reduced in?

A

Elderly patients
Patients with impaired renal function
Patients with impaired hepatic function

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12
Q

Mechanism of action of Benzbromarone

A

Uricosuric - urate excretion therapy

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13
Q

Why can benzbromarone only be used in hospital?

A

Rare side effect of hepatotoxicity

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14
Q

Guidelines state that serum urate levels should be ?? to achieve rapid clearance of urate crystals and ?? to achieve adequate maintenance

A

<0.3mmol/L

<0.36mmol/L

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15
Q

How long should you wait after starting urate lowering therapy to recheck serum urate levels, and why?

A

2 weeks, as 50% of gout patients will have normal urate levels during an attach due to the effect of inflammation on urate excretion

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16
Q

What is the prophylactic treatment used to prevent gout flares?

A

Allopurinol 100mg daily increased by 100mg every 4 weeks until target serum uric acid reached, side effects occur or maximum dose is reached

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17
Q

What are the side effects of colchicine?

A

Diarrhoea, colic

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18
Q

What patients is colchicine contra-inidicated in?

A

Patients with renal or hepatic impairment who are taking a P-glycoprotein inhibitor or a strong CYP34A inhibitor

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19
Q

What medication should be used to treat gout in patients intolerant of colchicine?

A

Low dose NSAIDs

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20
Q

What lifestyle changes can be made to prevent gout attacks?

A

Reduce/remove diuretics
Reduce alcohol intake to within recommended limits
Gradual weight loss to ideal body weight
Avoid sweetened, sugary beverages and rich foods

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21
Q

What features would you expect to see in the history of someone with a connective tissue disorder?

A
Photosensitive skin rash
Polyarthritis/polyarthralgia affecting small joints
Pleurisy 
Pericarditis
Muscle pain/weakness
Dyspnoea
Severe Raynaud's
Seizures/focal neurological defects
Psychosis
Mouth ulcers
Dry mouth, dry eyes
Hair loss
Recurrent miscariage
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22
Q

What features would you expect to see on examination a patient with a connective tissue disorder?

A
Skin rash
Synovitis
Mouth ulcers
Scarring alopecia
Sclerodactyly
Raynaud's (with digital ulceration)
Telangiectasia
Pleural or pericardial effusion
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23
Q

What investigations would you perform in a patient with suspected connective tissue disease?

A

FBC & ESR (will show raised ESR, anaemia, leukopenia and thrombocytopenia)
Immunology (will show ANA +++, anti dsDNA +, extricable nuclear antigen (ENA) +

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24
Q

When should you consider referral of a patient with suspected connective tissue disorder

A

Patient with several (<4) symptoms

Patient with signs and have a + ANA and sDNA antibody

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25
What features would you expect to see in the history of a patient with fibromyalgia?
``` Generalised musculoskeletal pain Fatiguability Disability Constant fatigue, poor sleep Poor concentration Irritability Associated facial pain, IBS, irritable bladder, allodynia, chemical sensitivity and tension headaches History of stressful events often dating back to childhood ```
26
What features would you expect to see on examination in a patient with fibromyalgia
Multiple tender spots on the back and anterior trunk with moderate digital pressure
27
What investigations would you perform in a patient with suspected fibromyalgia?
``` Routine bloods (should be normal) Inflammatory markers TFTs Bone profile (calcium, vit D, etc) Anti-CCP antibodies (to rule out RA, should be negative) Imaging (to exclude other disease) ```
28
How would you manage a patient with fibromyalgia?
Education Pain control - gabapentin, amitryptilline, nortriptylline, fluoxetine Sleep disturbance - guidance on getting a good night's sleep Physiotherapy CBT
29
What features would you expect to see in the history of a patient with ankylosing spondylitis?
Low back pain and stiffness in sacroiliac region, sometimes radiating to buttocks Marked early morning stiffness, improving as day goes on Onset in the late teens/early 20s Associated iritis and IBD
30
What features would you expect to find on examination of a patient with ankylosing spondylitis?
Reduced range of spinal movements | Reduced chest expansion
31
What investigations would you carry out in a patient with suspected ankylosing spondylitis?
ESR & CRP (often raised but may be normal) | Pelvic and lumbar spine X-rays (sacroileitis and possible syndesmophytes)
32
What differential diagnoses would you consider in a patient with suspected ankylosing spondylitis?
Prolapsed intervertebral disc (pain will follow nerve root distribution) Mechanical back pain (worse on movement, relieved by rest)
33
What features would you expect to see in the history of a patient with giant cell arteritis and polymyalgia rheumatica?
``` New onset headache (usually unilateral in the temporal or occipital area) Jaw claudication Scalp tenderness/pain Visual disturbances Neurological involvement (rare) ``` Symmetrical pain and stiffness affecting shoulder and pelvic girdle Difficulty raising from chair unaided and brushing hair General malaise Age >50
34
What features would you expect to see on examination in a patient with giant cell arteritis?
Usually unremarkable on examination Occasionally focal tenderness or thickening over temporal artery Visual field defects or reduced visual acuity
35
What investigations would you perform in a patient with suspected giant cell arteritis/PMR?
``` Routine bloods (will show mild anaemia, elevated ESR & CRP) Temporal artery biopsy (can be negative) ```
36
What are the indications for referral of a patient with GCA?
Unusual presentation (suggestive symptoms but normal ESR, age <50) Patient fails to respond adequately to corticosteroid treatment (suggests diagnosis is wrong) Symptoms cannot be controlled with <10mg daily prednisolone (may need to consider immunosuppressive therapy)
37
Describe the management plan for a patient diagnosed with GCA
1. Check FBC & ESR before commencing treatment 2. 40-60mg daily prednisolone (>0.75mg/kg/day) 3. Review after a week of treatment and recheck FBC & ESR - symptoms should dramatically improve and ESR should fall in 2-3 days 4. Continue high-dose steroid therapy for 4 weeks 5. Step-down steroid therapy by 10mg every 2 weeks until 20mg daily dose is reached 6. Step-down steroid therapy by 2.5mg every 2 weeks until 10mg daily dose is reached 7. Step-down steroid therapy by 1mg every month until the steroids can be completely withdrawn
38
In a patient with GCA, you should treat an asymptomatic patient with steroids if their ESR is high (true/false)
False - steroid dose should be titrated against ESR and symptom presence
39
What should you do if symptoms reoccur during the steroid step-down process in a patient with GCA?
Increase the prednisolone dose to the one which was last controlling symptoms and recommence the program of reduction.
40
What two medications should all patients undergoing GCA treatment receive?
Calcium and Vitamin D supplements. Additional bone protection (bisphosphonates) should be considered in all patients >65 or patients <65 with a T-score of <1.5.
41
What features would you expect to see in the history of a patient with Hypermobility syndromes?
Generalised joint pain Increased joint laxity Back pain Dislocations (uncommon) ``` Fibromyalgia-like syndromes Easy bruising Abdominal symptoms Mitral valve prolapse Postural tachycardia symptoms ```
42
Describe the test and scores used to calculate a modified Beighton score for patients with suspected hyper mobility?
Extend 5th finger by 90o: 1 point for each side Extend thumb back to touch forearm or lie parallel to forearm: 1 point for each side Extend elbow by >10o: 1 point for each side Extend knee by >10o: 1 point for each side Bend over and tough floor with flat of hands with legs straight: 1 point
43
How would a diagnosis of hyper mobility be made?
A score >3 on the modified Beighton test alongside pain for >3 months in >3 joints.
44
How is hypermobility managed?
Patient education Pain relief - analgesics, NSAIDs, gabapentin, amitryptilline, fluoxetine Physiotherapy - muscle strengthening to improve joint stability
45
Describe the management algorithm for a patient with OA?
1) Disease education, weigh loss and physiotherapy 2) Topical NSAIDs, paracetamol 3) Oral NSAIDs 4) Substitute compound analgesic for paracetamol 5) Add gabapentin or low dose amitryptilline 6) Consider tramadol 7) Consider strong opiate
46
What features would you expect to see in the history of a patient with polymyalgia rheumatica?
``` Symmetrical pain and stiffness affecting shoulder and pelvic girdle Difficulty rising from chair unaided Difficulty combing hair General malaise Age >50 ```
47
What features would you expect to see on examination of a patient with polymyalgia rheumatica?
Nothing (trick question lol)
48
What investigations would you perform in a patient with suspected polymyalgia rheumatica?
Routine bloods (normally normal except raised ESR)
49
When would you consider referring a patient with polymyalgia rheumatica to rheumatology?
When the patient fails to respond adequately to corticosteroid treatment When symptoms can not be controlled with <10mg prednisolone daily (consider immunosuppressive treatment)
50
Describe the management plan of a patient with polymyalgia rheumatica
1. Check FBC and ESR 2. Prescribe 15-20mg prednisolone daily 3. Review after 1 week - assess symptomatic response and recheck ESR - symptoms should improve dramatically and ESR should have fallen 4. Reduce steroid dose by 2.5mg/month until daily dose is 10mg 5. Reduce steroid dose by 1mg/month until treatment can be withdrawn (usually 1-2 years)
51
What should you do if a patient symptoms recur during treatment for polymyalgia rheumatica?
Increase prednisolone dose by 5mg daily then resume dose reduction at 1mg/month
52
What additional medications should you consider in patients on steroid therapy for polymyalgia rheumatica?
Bisphosphonates in patients >65 taking >7.5mg prednisolone for >3 months, or patients <65 with a DEXA scan T-score <1.5.
53
What features would you expect to see in the history of a patient with psoriatic arthritis?
Joint pain, stiffness and swelling in an asymmetrical distribution affecting the PIP and DIP joints of the hands, feet and large joints Early morning joint stiffness (typically <30 mins) Inactivity gelling History of psoriasis
54
What features would you expect to see on examination of a patient with psoriatic arthritis?
Soft tissue swelling, tenderness of affected joints Nail pitting and nail dystrophy Skin rash
55
What investigations would you perform in a patient with suspected psoriatic arthritis?
FBC & ESR (ESR raised) Anti-CCP antibodies (typically negative) X-ray of affected joints
56
What is the main differential diagnosis to consider in a patient with suspected psoriatic arthritis?
Osteoarthritis in a patient with concurrent psoriasis.
57
How would you differentiate between a patient with psoriatic arthritis and a patient with osteoarthritis and concurrent psoriasis?
Patients with OA and psoriasis will have bony swelling of the DIP, PIP and MCPJs rather than synovitis, and stiffness will not be limited to the morning. OA will show joint changes and no erosions on X-ray.
58
What features would you expect to see in the history of a patient with rheumatoid arthritis?
Joint pain, stiffness and swelling in a symmetrical distribution affecting wrists, MCPJ/MTPJ and PIPs in the hands and feet. Large joints may also be affected. Early morning stiffness (typically >30 mins) Inactivity gelling
59
What features would you expect to see on examination of a patient with rheumatoid arthritis
Soft tissue swelling and tenderness of affected joints | Painful squeeze test
60
What investigations would you carry out in a patient with suspected rheumatoid arthritis?
FBC, ESR, LFTs Anti-CCP antibodies X-ray of affected joints
61
How is the severity of rheumatoid arthritis assessed?
Das28 score
62
Describe the factors and scores considered in the DAS28 test
``` Joints affected: 1 large joint - 0 2-10 large joints - 1 1-3 small joints - 2 4-10 small joints - 3 ``` ESR & CRP Normal - 0 Raised - 1 Duration of symptoms: <6 wks - 0 >6 wk - 1 Immunology: Negative CCP - 0 Low positive CCP - 2 High positive CCP - 3
63
A DAS28 score of >? is definitive of rheumatoid arthritis
>6 Score <4 - consider other diagnosis Score 4-5 - potential RA
64
What are the differential diagnoses which should be considered in a patient with suspected rheumatoid arthritis?
Viral arthritis Osteoarthritis Psoriatic arthritis
65
What features would you expect to see in the history of a patient with Osteogenesis Imperfecta?
``` Multiple low trauma fractures during childhood/adolescence continued into adult life Back pain Height loss Deafness Soft tissue injury Family history ```
66
What features would you expect to find on examination of a patient with Osteogenesis Imperfecta?
Blue sclera Hypermobility Bone deformity (in severe cases)
67
What investigations would you carry out in a patient with suspected Osteogenesis Imperfecta?
Routine bloods and Vitamin D levels X-ray of thoracic and lumbar spine DEXA scan (unless already done in last 5 years)
68
What features would you expect to see in the history of a patient with Paget's Disease of the Bone
``` Bone pain Pathological fracture Bone deformity Deafness Osteoarthritis ```
69
What features would you expect to see on examination of a patient with Paget's disease of the bone
``` No abnormalities Bone deformities (usually affecting the tibia, skull and fibula) ```
70
What investigations would you perform in a patient with suspected Paget's disease of the bone?
``` Routine bloods (Raised ALP) X-ray lumbar spine and pelvis (Abnormal in 70% of patients) ```
71
What treatment would you recommend in a patient with symptomatic Paget's disease which is not controlled by simple analgesics?
IV bisphosphonates (single IV zolendronate infusion) to suppress bone turnover and reduce pain.
72
What is the prevalence of RA?
1%
73
What is the female: male ratio of RA?
3:1
74
How much does RA decrease life expectancy by in males and females
Males - 4 years | Females - 10 years
75
How many loci have been associated with RA, and which ones show the strongest association?
~100 loci | HLA-DRB1, HLA-B and HLA-DPB1
76
What is the main risk factor for RA?
Smoking
77
What is the main protective factor for RA?
Pregnancy - many people enter remission due to immunosuppression and hormonal changes
78
What cells invade the synovial membrane in RA?
Lymphocytes Plasma cells Dendritic cells Macrophages
79
What is the role of lymphoid follicles in RA?
Lymphoid follicles form in the synovial membrane and activate T-cells to produce cytokines, and B-cells to produce antibodies (RF and ACPA).
80
Describe the role of T-cells in RA
T-cells produce TNFa and INF-y which activate synovial macrophages which activate synovial fibroblasts to produce further cytokines
81
Describe the role of synovial fibroblasts in RA
Synovial fibroblasts proliferate, causing synovial hypertrophy and produce matrix metalloproteinases which degrade soft tissue and cartilage. The inflamed synonym produces PGs and NO which causes vasodilation resulting in swelling and pain.
82
Systemic release of ... triggers production of the acute phase response proteins by the liver in RA?
IL6
83
What are the pathological features of RA?
Inflamed synovial membrane T-lymphohyctes, macrophages and fibroblasts in the panes Neutrophils in the synovial fluid
84
Describe the typical presentation of a patient with undiagnosed RA
Symptoms >6 weeks duration Symmetrical polyarticular joint pain, swelling Morning stiffness lasting >1 hour Systemic symptoms (weight loss, fatigue, fever, susceptibility to infection) Extra-articular symptoms
85
Describe the MSK features of RA
Muscle wasting Tenosynovitis Bursitis Osteoporosis
86
Describe the haematological features of RA
Anaemia Thrombocytosis Eosinophilia
87
Describe the lymphatic features of RA
Felty's syndrome | Splenomegaly
88
What is Felty's syndrome?
Presence of RA, splenomegaly and a low WCC
89
Describe the ocular features of RA
Episcleritis/scleritis Scleromalacia Keratoconjuctivis sicca
90
Describe the vascular features of RA
``` Digital arteritis Ulcers Pyoderma gangrenosum Mononeuritis multiplex Visceral arteritis ```
91
Describe the cardiac features of RA
Pericarditis/myocarditis/endocarditis Conduction defects Coronary vasculitis Granulomatous aortitis
92
Describe the pulmonary features of RA
Nodules/Caplan syndrome Pleural effusion Fibrosing alveolitis Bronchiolitis
93
Describe the neurological features of RA
Cervical cord compression Compression neuropathies Peripheral neuropathies Mononeuritis multiplex
94
Name some deformities characteristic of RA
Ulnar deviation Swan neck Boutonniere Z-thumb
95
What is the main indication for X-ray in RA patients?
Assess for structural damage
96
What is the DAS28 score used to assess, and how is it calculated?
Used to assess disease activity, response to treatment and need for biologic therapy. Calculated by counting the number of involved joints, the ESR and the patient global health.
97
What tests could you do to help you establish a diagnosis of RA?
``` Clinical picture CRP ACPA RF Ultrasound/MRI ```
98
What tests could you do to help you monitor disease activity/drug efficacy in RA?
DAS28 score
99
What tests could you do to help you monitor drug safety in RA?
``` Urinalysis FBC Chest X-ray U&Es LFTs ```
100
Describe the typical management plan in RA patients
1) Initiate steroid step down therapy (30mg, reduce by 5mg every 2 weeks) 2) Initiate methotrexate (15mg weekly) and folic acid (5 mg weekly) - can escalate to 25mg depending on response 3) Commence additional DMARD - usually triple therapy 4) Commence additional/subsitute DMARD or glucocorticoids 5) Commence biologic - reduce dose after 12 months of remission
101
What is the triple therapy used for RA?
Methotrexate Hydroxychloroquine Sulfasalazine
102
What could you use to treat a transient RA flare?
Intra-articular glucocorticoid injections OR a short course of oral glucocorticoids
103
Mechanism of action of methotrexate
Dihydrofolate reductase inhibitor
104
Side effects of methotrexate
``` Hair loss GI upset Pneumonitis Hepatotoxicity Reduced WCC/platelets ```
105
What advice would you give to a woman of reproductive age on methotrexate?
Discontinue >3 months before conception | Don't use during breast-feeding
106
Side effects of sulfasalazine
``` Skin rashes GI upset Reversible azoospermia Anaphylaxis Reduced folic acid levels Abnormal LFTs Reduced WCC/platelets ```
107
What monitoring would you do in an RA patient on methotrexate?
Regular FBC, LFTs and U&Es
108
What advice would you give to an RA patient on sulfasalazine?
Get regular FBC and LFTs | Report unexplained bleeding/bruising/purpura/sore throat or fever
109
Side effects of leflunomide
Hepatotoxicity | Reduced WCC/platelets
110
What advice would you give to an RA patient on leflunomide?
Get regular FBC, LFTs and U&Es Discontinue >24 months before conception Don't use in breast-feeding
111
Side effects of azathioprine
``` Myelosuppression GI symptoms Skin eruptions Hepatotoxicity Reduced WCC/platelets Increased cancer risk with long term use ```
112
Mechanism of action of azathioprine
Purine analogue which inhibits DNA synthesis
113
Mechanism of action of Infliximab
TNFa inhibitor
114
Side effects of Infliximab
``` Hypotension Chest pain SOB Rash/itching Fever/chills TB/Hep B reactivation Hepatosplenic T-cell lymphoma Drug-induced lymphoma Demyelinating CNS disorders Vitiligo ```
115
Mechanism of action of tocilizumab
Anti-IL6
116
Mechanism of action of abatercept
Prevents T-cell activation
117
Mechanism of action of Rituximab
B-cell inhibitor
118
What could you consider in patients who fail to respond to biologics or intra-articular injections?
Synovectomy Joint replacement Metatarsal head excision Fusion of wrist/ankle
119
List the potential complications of RA
Osteoporosis Amyloidosis Microcytic anaemia - caused by NSAID-induced GI bleed Normochromic normocytic anaemia/thrombocytosis Felty's syndrome Lymphadenopathy
120
Mechanism of action of hydroxychloroquine
Decreases TLR signalling (by increasing lysosomal pH in antigen-presenting cells)
121
Side effects of hydroxychloroquine
``` Eye problems GI upset Acne Blisters Blood disorders Convulsions Vision difficulties Diminished reflexes Emotional changes Pigmentation changes Hepatotoxicity ```
122
Mechanism of action of leflunomide
Dihydroorotate inhibitor - inhibits synthesis of pyrimidines
123
When is leflunomide contra-indicated?
Pregnancy/breast-feeding Liver disease Hepatitis B/C infection Serious infection
124
What monitoring would you do regularly in patients on DMARDs for RA?
Monthly FBC Regular LFTs Regular U&Es Regular CRP
125
What monitoring would you do regularly in patients on biologics for RA?
Regular FBC, LFTs, lipid panel Annual skin examination TB/Hep B monitoring Blood pressure and heart monitoring
126
Side effects of Tocilizumab
``` Hepatotoxicity Reduced WCC Upper respiratory tract infections Headache Hypertension Hypercholesterolaemia ```
127
Side effects of Abatercept
Infection Anaphylaxis Increased progression of slow growing cancer URTIs
128
Side effects of Rituximab
``` Infection Rash/itching Hypotension SOB Hep B reactivation Leukoencephalopathy Toxic epidermal necrosis ```
129
Side effects of Baricitinib
URTIs | Hypercholesterolaemia
130
Mechanism of action of Baricitinib
JAK Kinase inhibitor
131
Mechanism of action of cyclophosphamide
Alkylating agent - interferes with DNA duplication
132
Side effects of cyclophosphamide
``` GI upset Bone marrow suppression Hemorrhagic cystitis Pigmentation changes Hair loss/changes Lethargy ```
133
When is cyclophosphamide contra-indicated?
Pregnancy/breast-feeding Active infection Neutropenia Bladder toxicity
134
Side effects of glucocorticoids
``` Immunodefifiency Hyperglycaemia Easy bruising Thin skin Reduced calcium absorption and OP Weight gain Impaired memory/attention span Muscle/tendon breakdown ```
135
Side effects of paracetamol
Hepatotoxicity | Rash
136
Side effects of NSAIDs
GI upset/ulcers Kidney disease Adverse cardiovascular events Asthma
137
When are NSAIDs contra-indicated?
``` >50s GI upset Uncontrolled hypertension Kidney disease IBD Past TIA/stroke Asthma 3rd trimester of pregnancy ```
138
??? is the most common inflammatory arthritis in men and older women
Gout
139
Prevalence of gout
1-2%
140
Gout shows a ?:1 male:female ratio
5:1
141
Risk factors for gout
``` Obesity Metabolic syndrome High alcohol intake Generalised OA Diet high in game/offal/seafood, low in Vit C Age Male Ethnicity (Pacific and Maoris islanders) High serum uric acid levels Lead poisoning ```
142
Describe the pathophysiology of gout
Gout is caused by deposition of monosodium urate monohydrate crystals in the synovial joint. The body's uric acid concentration depends on the balance between purine synthesis (2/3) and dietary intake (1/3) and elimination by the kidney and gut. Purine synthesis is regulated by xanthine oxidase.
143
in 90% of gout patients, the main abnormality is ...?
Renal uric acid excretion, which is genetically determined
144
List some causes of diminished renal uric acid excretion
``` Increased renal tubular absorption Renal failure Lead toxicity Lactic acidosis Alcohol Drugs (thiazides, aspirin, cyclosporin, pyrazinamide) ```
145
List some causes of increased uric acid production
``` Myeloproliferative disease Lymphoproliferative disease Psoriasis High fructose intake Glycogen storage disease Inherited disorders (Lesch-Nyhan syndrome, Phosphoribosyl pyrophosphate synthetase 1 mutations) ```
146
First line treatment for an acute flare up of gout
Colchicine
147
Mechanism of action of colchicine
Inhibits microtubule assembly in neutrophils
148
Side effects and contra-indications of colchicine
GI upset CI in renal impairment, hepatic impairment and patients taking P-glycoprotein inhibitors or CYP34A inhibitors
149
2nd line treatment for a gout flare up
NSAIDs
150
1st line treatment for gout prophylaxis
Allopurinol
151
2nd line treatment for gout prophylaxis
Febuxostat
152
Mechanism of action of Febuxostat
Xanthine oxidase inhibitor
153
List 3 uricosurics which can be used to prevent gout
Probenecid Sulfinpyrazone Benzbromarone
154
List some considerations that have to be taken into account with uricosurics
CI in over-producers of uric acid CI in renal impairment or urolithiasis Require patients to maintain high fluid intake Can only be initiated in hospital due to high toxicity
155
Mechanism of action of pegloticase
Enhance uric acid breakdown
156
When is pegloticase indicated?
Tophaceous gout reistant to standard therapy
157
What lifestyle measures should be recommended to a gout patient?
Weight loss Reduce alcohol intake Avoid seafood and offal Substitute anti-hypertensives for losartan if possible
158
Prevalence of fibromyalgia
2-3%, reaches a peak of 7% in women >70
159
Fibromyalgia shows a ??:1 female: male ratio
10:1
160
Risk factors for fibromyalgia
Female sex | Life events causing psychosocial distress
161
Two interrelated abnormalities in fibromyalgia
1) Non-restorative sleep | 2) Pain sensitisation
162
Average age of onset of PMR and GCA
>70
163
GCA and PMR affect females and males in a ?:1 ratio
3
164
What is the overall prevalence of GCA and PMR in >50s?
~2 in 10,000 people affected
165
What may you see on a fundoscopy in a patient with GCA?
Pale/swollen optic disc 24-36 hours after event
166
What 3 tests could you do to definitively diagnose GCA?
1) Temporal artery biopsy 2) Temporal artery ultrasound 3) Fluorodeoxyglucose PET scan
167
What would you see on a temporal artery biopsy in a patient with GCA?
Fragmentation of the internal elastic lamina, with necrosis of the media, in combination with mixed inflammatory cell infiltrate
168
What would you see on a temporal artery ultrasound in a patient with GCA?
'Halo' sign around affected arteries
169
What would you see on a Fluorodeoxyglucose PET Scan in a patient with GCA?
Strongly positive result
170
1st line management of GCA/PMR?
Prednisolone (with oral bisphosphonate, calcium and vitamin D supplementation)
171
When should symptoms resolve after starting steroid treatment in a PMR/GCA patient?
48-72 hours after starting treatment
172
Higher doses of prednisolone are required in PMR compared to GCA (true/false)
False
173
What rate of reduction is suggested in steroid step down therapy in patients with GCA/PMR?
1mg per month
174
Prevalence of pseudogout in 65-75 year olds, and >585s
10-15% of 65-75 year olds | 30-60% of >85s
175
Risk factors for pseudogout
``` Age OA Primary hyperparathyroidism Familial factors Haemochromotosis hypophosphatasia Hypomagnesemia Wilson's disease ```
176
Triggers for an attack of pseudogout
Trauma Intercurrent illness Dehydration Surgery
177
Describe the pathophysiology of pseudogout
Condition associated with deposition of calcium pyrophosphate dihydrate crystals within the articular and hyaline cartilage. The underlying mechanisms are poorly understood.
178
Clinical features of pseudogout
``` Can be asymptomatic Swollen, tender joint Large joint effusion (warm, erythematous) Fever Confusion/Malaise ```
179
Clinical features of chronic arthropathy caused by pseudogout
``` Chronic joint pain Early morning stiffness Inactivity gelling Functional impairment OA features with varying degrees of synovitis ```
180
What is the 1st line investigation in pseudogout? And what other investigations would you consider?
1st line: join aspiration and synovial fluid examination (to demonstrate CPPD crystals and differentiate from gout) Gram stain and culture of fluid to rule out co-existing sepsis X-rays - may show calcification in the cartilage Screening for secondary causes of pseudogout
181
What does synovial joint aspirate look like in patients with pseudogout?
Turbid and blood-stained
182
List the potential treatment options for a patient with pseudogout
1) Joint aspiration = may provide symptomatic relief 2) Intra-articular glucocorticoids injections, colchicine or NSAIDs 3) Early active mobilisation
183
Most common form of arthritis
OA
184
What percentage of people develop knee and hip OA?
45% develop knee OA | 25% develop hip OA
185
Risk factors for OA
``` Family history - Multiple epiphyseal dysplasia - Polygenic inheritance Developmental abnormalities - SUFE -DDH Limb deformities Repetitive loading - Famers - hip OA - Miners - knee OA - Athletes - knee/ankle OA Destabilising injuries - Cruciate ligament tear - Meniscectomy Obesity Trauma Hormonal - Oestrogen deficiency - Aromatase inhibitors ```
186
List the 4 characteristic pathological features of OA
1) Focal loss of cartilage 2) Subchondral osteosclerosis 3) Osteophyte formation 4) Remodelling of joint contour Also see increased bone mineral density, capsule thickening and surrounding muscle wasting.
187
Describe the pathophysiology of OA
Chondrocytes start to divide and produce nests of metabolically active cells - these increase production of matrix components but also accelerate the breakdown of major structural components of the collagen matrix. This makes the cartilage vulnerable to load-bearing injury. Fissuring occurs and deep vertical clefts develop, localised chondrocyte death and decreased cartilage thickness occurs.
188
Clinical features of OA
Characteristic joint involvement - PIPs, DIPs, knees, hips, neck, lumbar spine Painful and functional joint restriction Pain - insidious onset - intermittent nature - mainly related to movement/weight-bearing -only brief (<15 min) morning stiffness and inactivity gelling ``` Examination shows: Restricted movement Palpable crepitus Bony swelling Deformities Joint line/peri-articular tenderness Muscle weakness/wasting Mild/absent synovitis ```
189
Generalised nodal OA has a weak genetic predisposition (true/false)
False - strong genetic predisposition
190
Generalised nodal OA shows a marked female preponderance (true/false)
True
191
Describe the characteristic features of generalised nodal OA
``` Polyarticular DIP and PIP joint involvement Heberden's/Bouchard's nodes Good functional outcome for hands Lateral deviation Predisposition to OA at other joints ```
192
Which 2 joints does knee OA typically originate in?
1) patellofemoral | 2) medial tibiofemoral
193
What is an important risk factor which can lead to unilateral OA in men?
Trauma
194
Describe the characteristic features of knee OA
Bilateral and symmetrical knee involvement Pain localised to anterior or medial aspects of knee and upper tibia Pain usually worse on stairs/inclines Difficulty with prolonged walking, rising from a chair, bending over ``` Examination: Jerky, antalgic gait Varus or fixed flexion deformity Joint line/peri-articular tenderness Quadriceps weakness/wasting Restricted movements with crepitus Bony swelling ```
195
Which part of the hip does hip OA commonly affect?
The superior aspect of the joint - it is often unilateral and frequently progresses with superolateral migration of the femoral head, which has a poor prognosis.
196
Which part of the hip does hip OA less commonly affect?
Medial OA - this shows more central cartilage loss and is largely confined to women. It is often bilateral at presentation but has a better prognosis as axial migration of the femoral head is uncommon.
197
Obesity is associated with a more rapid progression of hip OA (true/false)
true
198
List the characteristic features of hip OA
Anterior groin pain Functional difficulties Examination: Antalgic gait Quadriceps/gluteal wasting and weakness Pain and restriction of internal rotation with hip flexed Fixed flexion, external rotation deformity Ipsilateral leg deformity
199
Which parts of the spine are most commonly affected by OA?
Cervical and lumbar spine
200
List the characteristic features of spine OA
``` Pain localised to lower back or neck Pain relieved by rest and worsened by movement Limited range of movement Loss of lumbar lordosis Positive straight leg raise test ```
201
Describe the typical features of early-onset OA
Onset before 45 years old Monoarthritic Clear history of previous trauma
202
List the causes of early-onset OA
``` Previous trauma Localised instability Juvenile idiopathic arthritis Haemochromotosis Ochronosis Acromegaly Spondyloepiphyseal dysplasia Late avascular necrosis Neuropathic joint Kashin-Beck disease ```
203
Describe erosive OA
A group of patients with hand OA who have a more prolonged inflammatory response, more overt inflammation, more disability and worse outcome than nodal OA
204
List the distinguishing features of erosive OA
Preferential targeting of PIP joints Subchondral erosions on X-ray Occasional ankylosis of affected joints Lack of association with OA in other joints
205
What investigations would you perform in a patient with suspected OA?
1) Plain x-ray of affected joints - hip = non-weightbearing posteroanterior - knee = weight-bearing anteroposterior & flexed skyline - spine = weight-bearing anteroposterior 2) Routine biochemistry, haematology, auto-antibodies (moderate acute phase response seen) 3) Synovial fluid aspirate (viscous with low cell count) 4) Additional investigations in early-onset OA to determine cause
206
List the management options for OA patients
``` Education Lifestyle advice - Weight loss - Strengthening and aerobic exercise - Pacing of activities - Walking aids Non-pharmalogical measures - Acupuncture - TENS - Heat/cold compress ``` ``` Pharmalogical measures - Paracetamol - Topical NSAID - Topical Capsaicin - Oral NSAID - Antineuropthic drug Intra-articular glucocorticoid injections Nutraceuticals ``` Surgery Total joint replacement Osteotomy Cartilage repair
207
What is the most rapid and destructive joint disease?
Septic arthritis
208
Prevalence of septic arthritis
2-10 per 100,000 in the general population | 30-70 per 100,000 in those with pre-existing joint disease or joint replacement
209
Morality of septic arthritis
~10%
210
Risk factors for septic arthritis
``` Age Pre-existing joint disease Diabetes Immunosuppression IVDU ```
211
Most common route of spread of infection in septic arthritis
Haematogenous spread from skin infections or upper respiratory tract infections
212
What organisms would you suspect in an adult with septic arthritis?
Staphylococcus Aureus
213
What organism would you suspect in a young, sexually active adult with septic arthritis?
``` Gonococcus (from untreated gonorrhoea). Presents with: Migratory arthralgia Low-grade fever Tenosynovitis Painful pustular skin lesions ```
214
Which organisms would you suspect in an elderly patient with septic arthritis?
Gram negative bacilli | Group B/C/G streptococci
215
Which organisms would you suspect in an IVDU with septic arthritis?
Gram negative bacilli | Group B/C/G streptococci
216
Name 4 less common organisms which can cause septic arthritis
Group A streptococci Pneumococci Meningococci Haemophilus Influenzae
217
Describe the clinical features of septic arthritis
Acute/sub-acute mono arthritis Fever Swollen, hot, red joint Pain on rest and movement
218
What investigations would you perform in a patient with suspected septic arthritis?
1) Joint aspiration --> send for Gram stain and culture (synovial fluid usually turbid and blood-stained) 2) Blood cultures 3) CRP --> may not be raised in elderly or immunocompromised patients or early in disease course
219
Describe the management protocol for a patient with suspected septic arthritis
1) Joint aspirate --> Gram stain and culture Blood cultures Routine biochemistry and haematology (Consider other cultures to determine primary source of infection) 2) Commence IV antibiotics --> usually IV Flucloxacillin (covers most Staph and Streps). Use IV Vancomycin if MRSA suspected or IV Gentamicin if you suspect a gram- sepsis. 3) Pain relief 4) Daily joint aspiration 5) Early physiotherapy
220
Which conditions does the term 'Juvenile Idiopathic Arthritis' encompass?
``` Systemic JIA (5%) Oligoarthritis (60%) Polyarthritis (20%) Anthesis-Related arthritis (5%) RF+ arthritis (5%) Psoriatic arthritis (5%) ```
221
Prevalence of JIA
1 in 1000 <16s
222
Incidence of JIA
1 in 10,000 people a year
223
Immunology of JIA
``` Systemic JIA - autoantibody - Oligoarthritis/polyarthritis - ANA+ Anthesis-Related arthritis - HLAB27+ RF+ arthritis - RF+, ACPA+ Psoriatic arthritis - autoantibody negative ```
224
Describe the clinical features of systemic JIA
``` Fever Rash Arthralgia Hepatosplenomegaly Haemophagocytic syndrome ```
225
What is the investigation of choice to confirm synovitis or tenosynovitis in children with JIA?
Ultrasound
226
1st line treatment for JIA?
Methotrexate
227
Name 2 treatments which could be considered in JIA patients with uveitis?
Azathioprine | Cyclosporin
228
Name the 5 conditions which are considered spondyloarthropathies
1) Axial spondyloarthritis 2) Ankylosing spondylitis 3) Reactive arthritis 4) Psoriatic arthritis 5) Enteropathic spondyloarthritis
229
Define spondyloarthropathies
A group of related inflammatory MSK diseases that show overlap in their clinical features and have a share immunogenic associated with HLA-B27
230
Describe the clinical features common to spondyloarthropathies
``` Asymmetrical inflammatory oligoarthritis (more common in lower limb) History of inflammatory back pain Sacroileitis and spinal osteitis Enthesitis Tendency for familial aggregation HLA-B27 association Psoriasis Uveitis Sterile urethritis or prostatitis IBD Aortic root lesions ```
231
Prevalence of spondyloarthropathies
1%
232
Describe the suggested pathophysiology of spondyloarthropathies
Aberrant host response to infection and abnormal mucosal immunity mediated through changes in IL12, IL23 and Th17
233
Ankylosing spondylitis affects males: females in a ?:1 ratio
3
234
Prevalence of ankylosing spondylitis
<0.5%
235
Describe the suspected pathophysiology of axial spondyloarthropathies
Abnormal host response to intestinal microbiota with Th17 cell involvement - this leads to production of inflammatory cytokines. HLA-B27 is also involved - it can activate leucocytes, and misfiled to cause inflammatory response.
236
List the clinical features of axial spondyloarthropathies
Inflammatory back pain, radiating to buttocks and posterior thighs Early morning stiffness Symptoms exacerbated by rest and received by movement Often have history of IBD and psoriasis Reduced lumbar spine range of movement in all directions Pain on sacroiliac stressing High enthesitis index
237
Extra-articular features of axial spondyloarthropathy
``` Fatigue, anaemia Anterior uveitis Prostatitis, sterile urethritis IBD Osteoporosis CVD Amyloidosis (rare) Atypical upper lobe pulmonary fibrosis ```
238
What investigation would you perform in someone with suspected axial spondyloarthropathy?
MRI/Ultrasound
239
What is the diagnostic criteria for Axial Spondyloarthritis
1) Sacroilitis on MRI AND 1 other feature in history, clinical examination or investigation OR 2) HLA-B27+ patients with one other clinical feature
240
What is the diagnostic criteria for Ankylosing Spondylitis?
X-ray evidence of sacroileitis AND 1 other feature on clinical history, exam or investigation
241
Describe the management of a patient with axial spondyloarthropathy
1) Patient education 2) NSAID (can progress to TNF inhibitor or Secukinumab) 3) Physical therapy 4) Consider Sulfasalazine/Methotrexate for severe/persistent MSK features 5) Consider local glucocorticoid injections for persistent plantar fascitits, peripheral arthritis and other enthesopathies
242
Sexually acquired reactive arthritis shows a male: female predominance of ??:1?
15:1
243
??% of patients attending a sexual health clinic with non-specific urethritis have sexually acquired reactive arthritis?
1-2%
244
List the common bacterial causes of reactive arthritis
``` Chlamydia Campylobacter Salmonella Shigella Yersinia ```
245
List the common causes of non-spondylo- reactive arthritis
``` Many viruses Mycoplasma Borrelia Streptococci Mycobacter ```
246
Describe the clinical features of non-spondylo- reactive arthritis
Acute monoarthalgia not associated with HLA-B27
247
Describe the typical features of reactive arthritis
Acute onset Inflammatory enthesitis, oligoarthritis, and/or spinal inflammation Lower limbs predominantly affected Systemic features
248
Describe the extra-articular features of reactive arthritis
``` Circinate balanitis Keratoderma blennorrhagica Pustular psoriasis Nail dystrophy Mouth ulcers Conjunctivitis Uveitis ```
249
??% of patients still have active disease 20 years after initial presentation with reactive arthritis
10%
250
List some rare complications of reactive arthritis
``` Aortic incompetence Conduction defects Pleuropericarditis Peripheral neuropathy Seizures Meningoencephalitis ```
251
What investigations would you consider doing in a patient with suspected reactive arthritis?
1) Joint aspiration --> exclude gout, sept arthritis 2) ESR --> raised 3) 'two glass' test --> demonstration of mucoid threads in first void specimen that clear in the second to confirm urethritis 4) High vaginal swabs --> test for chlamydia 5) Stool culture --> usually negative except in Salmonella, but may show previous dysentery 6) RF, ACPA, ANA --> negative
252
What features would you see on the X-ray of a patient with chronic or recurrent reactive arthritis?
1) Periarticular osteoporosis 2) Proliferative erosions 3) Periostitis 4) Large 'fluffy' calcaneal spurs 5) Asymmetrical and often unilateral sacroiliitis 6) Coarse and asymmetrical syndesmophytes
253
1st line treatment for reactive arthritis
Rest NSAIDs Analgesia
254
What treatments could you consider in a reactive arthritis patient when 1st line options have been exhausted?
1) Intra-articular or systemic glucocorticoids 2) DMARDs - in patients with marked persistent symptoms or chronic/recurrent disease 3) Anti-TNF therapy in DMARD resistance 4) Treat cause e.g. doxycycline or azithromycin for chlamydia
255
Prevalence of psoriatic arthritis in general population
0.2%
256
Prevalence of psoriatic arthritis in patients with psoriasis
40%
257
What age does psoriatic arthritis usually onset?
25-40 years
258
Studies suggest that heritability of psoriatic arthritis may exceed ??%?
80%
259
What two gene variants are the strongest genetic risk factors for psoriatic arthritis?
HLA-B | HLA-C
260
Where do the genetic variants involved in psoriatic arthritis tend to lie?
Within or close to IL12, IL23 and NFkB signalling pathways
261
Describe the typical clinical features of psoriatic arthritis
Pain and stiffness affecting joints, spine, tendons and enthesis without synovitis
262
List the 6 patterns of psoriatic arthritis
1) Asymmetrical inflammatory mono/oligoarthritis --> typically in hands and feet, 'sausage digits' 2) Symmetrical polyarthritis --> mainly in women, resembles pattern of RA 3) DIPJ arthritis --> similar to generalised nodal OA, associated with psoriatic nail disease 4) Psoriatic spondylitis --> back/neck pain and stiffness 5) Arthritis Mutilans --> targets fingers and toes, 'telescoping' 6) Enthesitis-predominant --> enthesitis and nail changes
263
What is the CASPAR criteria used to diagnose?
Psoriatic arthritis - inflammatory articular disease with 3 or more points
264
What criteria does the CASPAR grading system include?
``` Current psoriasis (2 points) History of psoriasis in 1st/2nd degree relative Psoriatic nail dystrophy Negative RF IgM Current dactylitis History of dactylitis Juxta-articular new bone ```
265
How is a diagnosis of psoriatic arthritis made?
Clinical features (Antibodies usually negative) X-rays may be normal or show erosive changes - features that favour psoriatic arthritis over RA include: - Characteristic distribution of proliferative erosions - New bone formation - Absence of periarticular osteoporosis and osteosclerosis MRI and Doppler US are increasingly used to detect synovial and enthesis inflammation
266
Describe the management protocol for psoriatic arthritis
1) NSAIDs Analgesia 2) Intra-articular glucocorticoid injections 3) DMARDs - usually methotrexate (Can also use sulfasalazine, cyclosporin or leflunomide) - pay attention to LFTs as abnormalities are common in psoriatic arthritis 4) Anti-TNF therapy OR Secukinumab (IL17 inhibitor) Ustekinumab (IL12/23 inhibitor) can be used to improve joint, dactylitis and enthesitis OR Apremilast (PDE4 inhibitor) but not as effective as biologics
267
What treatments are contra-indicated in psoriatic arthritis and why?
1) Splints and prolonged rest --> tendency to fibrous and bony ankylosis 2) Hydroxychloroquine --> can cause exfoliative skin reactions
268
Side effects of Apremilast
Weight loss Depression Suicidal thoughts
269
Prevalence of SLE
0.02 - 0.3%
270
??% of SLE patients are male?
10%
271
SLE is associated with a ?x increased mortality
5x, mainly due to increased risk of premature CVD
272
Describe the pathophysiology of SLE
Main pathophysiology is autoantibody production, mainly directed against antigens within the cell or nucleus - this leads to defects in apoptosis or apoptotic cell clearance which leads to inappropriate exposure of intracellular antigens on the cell surface and polyclonal T and B-cell activation
273
List the typical features of SLE
``` Systemic symptoms - fever, weight loss, lymphadenopathy, fatigue Arthralgia and early-morning stiffness Secondary Raynauds Rash Proliferative glomerulonephritis Pericarditis Increased risk of CVD Pleurtic pain Pleual effusion Pneumonitis Atelactasis Reduced lung volume Pulmonary fiborosis Headache Poor concentration Visual hallucinations Chorea Organic psychosis Transverse myelitis Lymphocytic meningitis Blood abnormalities Mouth ulcers Perionteal serositis ```
274
? out of 11 criteria have to be met to be diagnosed with SLE
4
275
List the 11 criteria used to diagnose SLE
1) Malar rash 2) Discoid rash 3) Photosensitivity 4) Oral ulcers 5) Arthritis 6) Serositis 7) Renal disorder 8) Neurological disorder 9) Haematological disorder 10) Immunological evidence 11) ANA
276
What are the 3 mandatory tests needed in a SLE diagnosis?
1) ANA --> + 2) ENAs and complement antibodies 3) Routine haematology, biochemistry and urinalysis
277
Describe the management of mild-moderate SLE
1) Analgesics NSAIDs Hydroxychloroquine 2) Glucocorticoids Methotrexate/Azathioprine/Mycophenolate mofetil 3) Belimumab
278
Describe the management of severe-life-threatening SLE
High dose glucocorticoids e.g. methylprednisolone | High dose immunosuppression e.g. cyclophosphamide
279
Describe the maintenance protocol for SLE
Oral prednisolone Azathioprine/Methotrexate/Mycophenolate mofetil Control CVD risk factors Smoking cessation Warfarin (if antiphospholipid antibodies present)
280
Peak age of onset of systemic sclerosis
40-50 year olds
281
Prevalence of systemic sclerosis
10-20 per 100,000
282
Systemic sclerosis affects females: males in a ?:1 ratio
4:1
283
Name the two types of systemic sclerosis
1) Diffuse cutaneous systemic sclerosis (30%) | 2) Limited cutaneous systemic sclerosis (70%)
284
List the factors associated with poor prognosis in diffuse systemic sclerosis
``` Older age Diffuse skin disease Proteinuria High ESR Low gas transfer for carbon monoxide Pulmonary hypertension ```
285
Describe the pathophysiology of systemic sclerosis
Autoimmune disorder of connective tissue which results in fibrosis of skin, internal organs and vasculature. T-lymphocytes infiltrate the skin and lead to abnormal fibroblast activation, which leads to excess production of ECM in the dermis. This causes symmetrical thickening, tightening and induration of the skin, arterial narrowing and endothelial injury.
286
List the typical features of systemic sclerosis
``` Non-pitting oedema of fingers and flexor tendon sheather Thinning lips Raynauds Digital ischaemia Sclerodactyly Calcinosis Telangiectasia ``` Arthralgia Flexor tenosynovitis Muscle weakness/wasting ``` Erosive oesophagitis Dysphagia Odynophagia Early satiety Outlet obstruction 'Watermelon' stomach Bacterial overgrowth Pseudo-obstruction ``` Pulmonary hypertension Interstitial lung disease Hypertensive renal crisis
287
What investigations would you perform in a patient with suspected systemic sclerosis?
1) Routine haematology, renal, liver and bone function tests Urinalysis 2) Chest X-ray, trans-thoracic echocardiography and lung function tests --> assess for interstitial lung disease and pulmonary hypertension High-resolution CT --> ?interstitial lung disease Right heart catheter measurements --> ?pulmonary hypertension 3) Barium swallow --> assess oesophageal involvement Hydrogen breath test --> indicate bacterial overgrowth
288
Describe the management of systemic sclerosis
Raynauds/digital ulcers: - Avoidance of cold exposure, thermal insulation - Calcium channel blockers/losartan/fluoxetine/sildenafil - IV prostacyclin --> severe disease/critical ischaemia - Bosentan --> ischaemic digital ulcers - Fucidin-hydrocortisone cream --> digital tip health GI complications: - PPIs/anti-reflux agents - Rifaximin/tetracycline/metronidazole --> bacterial overgrowth - Metroclopramide/domperidone --> dysmotility/pseudo-obstruction Hypertension - ACE inhibitors Joint involvement: - Analgesics - NSAIDS - Methotrexate Pulmonary hypertension: - Bosentan Interstitial lung disease: - Glucocorticoids and IV cyclophosphamide
289
Which 3 conditions make up a mixed connective tissue disorder?
1) Systemic sclerosis 2) Myositis 3) SLE
290
List the 3 typical features of a mixed connective tissue disorder
1) Indolent finger puffiness 2) Raynaud's 3) Myalgia
291
Which antibody is present in most patients with mixed connective tissue disorder?
Anti-RNP antibodies
292
Primary Sjogren's typically onsets between ??-?? years?
40-50
293
Primary Sjogren's affects females: males in a ?:1 ratio
9:1
294
Describe the pathophysiology of Sjogren's syndrome
Lymphocytic infiltration of the salivary and lacrimal glands, leading to glandular fibrosis and exocrine failure.
295
Describe the typical features of Sjogren's
``` Dry eyes Conjunctivitis Blepharitis Filamentary keratitis Xerostomia Dental caries Salivary gland enlargement Rashes Non-erosive arthralgia Generalised OA Raynauds Fatigue ```
296
Which autoimmune conditions is Sjogren's commonly associated with?
``` SLE Systemic sclerosis Coeliac disease Primary biliary cholangitis Chronic active hepatits Myasthenia Gravis ```
297
What test would you do to initially establish a diagnosis of Sjogren's syndrome?
Schirmer tear test - measure tear flow over 5 minutes using absorbent paper strips placed on lower eye lid (>6mm is normal).
298
What test would you do if the diagnosis of Sjogren's remained in doubt after initial tests?
Minor salivary gland biopsy - to demonstrate lymphocytic infiltrate
299
What blood test results would be present in a patient with Sjogren's?
``` Raised ESR Hypergammagobulinaemia One or more antibodies: - RF - ANA - SS-A (anti-Ro) - SS-B (anti-La) - Gastric parietal cell antibody - Thyroid antibody ```
300
What two complications do Sjogren's patients need to be screened for?
1) Interstitial lung disease (chest x-ray and lung function tests) 2) Interstitial nephritis
301
Describe the symptomatic management of Sjogren's
Dry eyes --> lacrimal substitutes Filamentary keratitis --> soft contact lenses, lacrimal duct occlusion Xerostomia --> chewing gum, artificial salvia Dental caries --> post-prandial oral hygiene, prompt treatment of oral candidiasis Vaginal dryness --> lubricants
302
Name the treatment which can be considered in early Sjogren's disease
Systemic pilocarpine - to amplify disease activity
303
What can be used to treat skin and MSK features of Sjogrens?
Hydroxychloroquine
304
When would you consider immunosuppressant use in Sjogren's?
Interstitial lung disease (glucocorticoids and cyclophosphamide) and interstitial nephritis (if Hydroxychloroquine alone is not sufficient)
305
What test would you do in a patient with Sjogren's who had non-resolving lymphadenopathy or salivary gland enlargement, and why?
Biopsy to exclude malignancy
306
Incidence of polymyositis and dermatomyositis
2-10 per million/year
307
Typical age of onset of Polymyositis and dermatomyositis
40-60
308
Pathophysiology of polymyositis and dermatomyositis
Skeletal, cardiac and gut smooth muscle inflammation
309
Typical features of polymyositis and dermatomyositis
Symmetrical proximal muscle weakness affecting mainly lower limbs and occurring over a few weeks Difficulty rising from chair/climbing stairs/lifting Muscle pain Systemic symptoms Skin lesions - Gottron's papules - Heliotrope rash - Periorbital oedema - 'Shawl' rash - Enlarged, tortuous periungal nail-fold capillaries
310
Interstitial lung disease occurs in ??% of polymyositis and dermatomyositis patients, and is strongly associated with the ??? antibody
30% | Antisynthetase
311
What is the pivotal investigation in polymyositis/dermatomyositis and what does it show?
Muscle biopsy - shows fibre necrosis, regneration and inflammatory cell infiltrate. MRI should be used to identify abnormal muscle for biopsy
312
What blood test is a good marker of disease activity in polymyositis/dermatomyositis?
Serum CK - should be raised
313
What is the initial management of polymyositis/dermatomyositis?
Oral glucocorticoids (or IV in respiratory/pharyngeal weakness), then reduced by 25% each month to a maintenance dose Can consider immunosuppressive therapy (methotrexate or MMF) Can consider IV Ig therapy in refractory disease Mepacrine or Hydroxychloroquine can be used in skin-predominant disease
314
Main risk of glucocorticoid treatment in polymyositis/dermatomyositis?
Glucocorticoid-induced myopathy - biopsy shows type II fibre atrophy and treatment response is poor.
315
Most common inflammatory arthropathy in children
Juvenile dermatomyositis
316
Incidence of juvenile dermatomyositis
2-4 per million
317
Median age of onset of juvenile dermatomyositis
7
318
Management of juvenile dermatomyositis
1) IV methylprednisolone 2) Oral glucocorticoids and methotrexate 3) Cyclophosphamide for lesional ulceration IV immunoglobulins in resistant disease
319
Clinical features of Adult-onset Still's disease
``` Intermittent fever Rash Arthlagia Splenomegaly Hepatomegaly Lymphadenopathy ```
320
What would investigations reveal in a patient with adult-onset Still's disease?
1) Acute phase response 2) Elevated serum ferritin 3) Negative RF and ANA
321
Management protocol for adult-onset Still's disease
1) Glucocorticoids 2) Azathioprine or MMF 3) Canakinumab or anakinra
322
What is the most common bone disease?
Osteoporosis
323
Risk factors for osteoporosis
``` Genetics - LRP5 mutations, oestrogen receptor mutations Hypogonadism Hyperthyroidism Hyperparathyroidism Cushing's IBD Ankylosing spondylitits Rheumatoid arthritis Drug Malabsorption Chronic liver disease COPD CF Myeloma Low BMI HIV Immobilisation Heavy smoking ```
324
What does and duration of glucocorticoid treatment substantially increases osteoporosis risk?
>7.5mg daily for >3 months
325
Symptoms of osteoporosis
Osteoporosis is asymptomatic until a fracture occurs. Fracture symptoms: - Pain - Local tenderness - Deformity
326
List 4 common osteoporotic fractures
1) Vertebral fracture 2) Colle's fracture 3) Hip 4) Humerus
327
Define a fragility fracture
'A fracture which occurs from a fall of standing height or less'
328
What investigation would you carry out in a patient with suspected osteoporosis?
Hip and lumbar spine DEXA scan
329
Indications for DEXA scan
``` Fragility fracture in patient >50 Clinical risk factors Increased fracture risk assessment score Glucocorticoid therapy Assessment of response to treatment Assessment of progression from osteopenia to osteoporosis Age <50 but strong risk factors ```
330
Management of osteoporosis
Non-pharmalogical - Smoking cessation - Alcohol reduction - Adequate dietary calcium - Exercise Pharmacological 1) Allendronic acid 2) IV zolendronate
331
What advice would you give to someone taking an oral bisphosphonate?
Take on an empty stomach with water, sitting upright Side effects include: GI upset, worsening of GORD, jaw osteonecrosis Report any dysphagia - oesophageal ulceration and perforation can occur
332
What would you do after a patient with osteoporosis had been on an oral bisphosphonate for 3 years?
Review with a DEXA scan 1) Stop treatment 2) Continue treatment for 5 more years 3) Switch to IV bisphosphonate
333
Causes of osteomalacia/rickets
``` Vitamin D deficiency Chronic renal failure Vitamin-D resistance Vitamin D receptor defects Hyophosphatemia Bisphosphonate therapy Aluminium Fluoride ```
334
Clinical features of osteomalacia
``` Fractures Bone pain Generalised malaise Proximal muscle weakness Bone/muscle tenderness on pressure ```
335
What investigations would you do in a patient with suspected osteomalacia?
Serum vitamin D Serum PTH, calcium, phosphate, ALP X-rays Bone biopsy
336
How would you manage a patient with osteomalacia?
Cholecalciferol - high doses for 2-4 weeks then reduce to maintenance dose
337
Prevalence of Paget's disease
1% of >55s, but prevalence doubles each decade so affects 8% of >85s
338
Clinical features of Paget's
``` Axial skeleton involvement Bone pain Bone deformity or expansion Increased warmth over affected bone Neurological problems - Deafness - Cranial nerve defects - Nerve root problem - Spinal cord compression/spinal stenosis ```
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What investigations would you do if you suspected Pagets? What would they show?
Isolated rise in ALP X-ray - bone expansion with alternating radiolucucenfcy and osteosclerosis. Radionucleotide bone scan - used to identify affected sites Bone biopsy (rare) - exclude bony metastasis
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Management of Paget's
Bisphosphonates - pamidronate, risedronate or zolendronic acid