Rheumatology Flashcards
(340 cards)
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
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
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)
4
Q
What criteria scoring system is used to diagnose gout?
A
The Nijmegen criteria (score >7 = 80% chance of gout)
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
6
Q
How is a definitive diagnosis of gout made?
A
Identification of urate crystals in synovial fluid or tophi aspirate
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).
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
9
Q
Mechanism of action of allopurinol
A
Xanthine oxidase inhibitor (XO prolongs activity of 6-mercptopurine)
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
11
Q
Which patients should allopurinol doses be reduced in?
A
Elderly patients
Patients with impaired renal function
Patients with impaired hepatic function
12
Q
Mechanism of action of Benzbromarone
A
Uricosuric - urate excretion therapy
13
Q
Why can benzbromarone only be used in hospital?
A
Rare side effect of hepatotoxicity
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
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
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
17
Q
What are the side effects of colchicine?
A
Diarrhoea, colic
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
19
Q
What medication should be used to treat gout in patients intolerant of colchicine?
A
Low dose NSAIDs
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
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
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
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) +
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
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
```
339
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
340
Management of Paget's
Bisphosphonates - pamidronate, risedronate or zolendronic acid
