MuscleSkeleton and roomatology 2 Flashcards
1
Q
What is osteoarthritis?
A
Non-inflammatory wear and tear of joints resulting from loss of cartilage
2
Q
Describe the epidemiology of osteoarthritis
A
- Most common type of arthritis- More common in females- More common in elderly
3
Q
What are 6 risk factors for osteoarthritis?
A
- Obesity2. Age3. Female4. Family history5. Trauma6. Occupations associated with manual labour
4
Q
Describe the pathophysiology of osteoarthritis
A
- Imbalance between cartilage being worn down and the chondrocytes replacing it- Usually occurs in larger, weight-bearing synovial joints e.g. hips and knees
5
Q
What are 3 common symptoms of osteoarthritis?
A
- Joint pain exacerbated by exercise2. Joint stiffness after rest (transient in morning)3. Reduced functionality (limited joint movement)
6
Q
What are 2 additional symptoms of osteoarthritis?
A
Bone swellings in fingers:- Herberden’s node (in distal interphalangeal joints)- Bouchard’s node (in proximal interphalangeal joints)
7
Q
What is the investigation for patients with osteoarthritis and the 4 most common findings?
A
X ray (LOSS):- L - loss of joint space- O - osteophytes formation- S - subchondral sclerosis (increased density of bone along joint)- S - subchondral cysts (fluid-filled holes in bone)
8
Q
What is the treatment for osteoarthritis?
A
- Pain relief (start with paracetamol and work up analgesics ladder)- Cortisol injections- Physiotherapy- Weight loss- Joint replacement (must lose weight)
9
Q
What is the difference between pain in patients with osteoarthritis vs rheumatoid arthritis?
A
Osteoarthritis - worse during/after exerciseRheumatoid arthritis - better during/after exercise
10
Q
What is rheumatoid arthritis?
A
Autoimmune inflammation of synovial joints - symmetrical polyarthritis
11
Q
Describe the epidemiology of rheumatoid arthritis
A
- More common in females (3:1)- Most often develops younger/middle age
12
Q
What are 4 risk factors for rheumatoid arthritis?
A
- Genetics - HLA DR4 gene (often present in RF positive patients)2. Genetics - HLA DR1 (often present in RA patients)3. Rheumatoid factor (RF)4. Cyclic citrullinated peptide antibodies (anti-CCP)
13
Q
What does rheumatoid factor (RF) do?
A
Autoantibody that targets Fc portion of IgG antibody, triggering activation of the immune system
14
Q
Describe the pathophysiology of rheumatoid arthritis
A
- Autoimmune destruction of synovium - Inflammation causes damage to bone cartilage, tendons and ligaments- Most common joints affected are PIP joints and MCP joints (HARDLY EVER DIP JOINTS - if these are affected, it is usually always osteoarthritis)
15
Q
What are 5 signs of rheumatoid arthritis?
A
- ‘Boggy’ feeling when palpating synovium around joints2. Z-shaped deformity of thumb3. Swan neck deformity (hyperextended PIP with flexed DIP)4. Boutonnieres deformity (hyperextended DIP with flexed PIP)5. Ulnar deviation of fingers at knuckle
16
Q
What are 5 symptoms of rheumatoid arthritis?
A
- Joint pain/swelling/stiffness (pain worse after rest/in the mornings and improves with activity)2. Fatigue3. Weight loss4. Flu-like illness5. Muscle aches/weakness
17
Q
What is palindromic rheumatism?
A
- Self-limiting short episodes of inflammatory arthritis with joint pain/stiffness/swelling- Lasts 1-2 days and then completely resolves itself- May progress to full RA (greater risk if have RF and anti-CCP antibodies)
18
Q
What are 2 investigations for patients with rheumatoid arthritis?
A
- X-ray2. Bloods
19
Q
What does an x-ray show in patients with rheumatoid arthritis?
A
LOSE:
- L - lost joint space
- O - osteopenia (reduced bone density)
- S - soft tissue swelling
- E - erosion
20
Q
What do bloods show in patients with rheumatoid arthritis?
A
- Anti-CCP antibodies (more sensitive and specific than RF)- RF- Raised ESR/CRP
21
Q
What is the treatment for rheumatoid arthritis?
A
- Physiotherapy- Ibuprofen/NSAIDs- Steroids- Methotrexate- Rituximab (if others not working)
22
Q
What are 3 complications of rheumatoid arthritis?
A
- Atlantoaxial subluxation –> cervical spinal cord compression2. Inflammation of tendons increases risk of tendon rupture3. Lung involvement e.g. interstitial lung disease, fibrosis etc.
23
Q
Describe atlantoaxial subluxation
A
- Local synovitis and damage to ligaments and bursa around odontoid peg of axis (C2) and atlas (C1)- This causes the axis (C2) and odontoid peg to shift within the atlas (C1)- Subluxation causes cervical spinal cord compression (weakness/loss of sensation) and is an EMERGENCY
24
Q
What must be excluded when investigating patients with gout/pseudogout?
A
Septic arthritis (life threatening - medical emergency)
25
What is the difference between gout and pseudogout?
Both crystal arthropathiesGout - deposition of monosodium urate crystals within jointsPseudogout - deposition of calcium pyrophosphate crystals within joints
26
What is crystal arthropathy/arthritis?
Joint disorder caused by deposits of crystals in joints and soft tissues around them
27
Describe the difference in epidemiology between gout and pseudogout
Gout - more common in malesPseudogout - more common in females
28
What are 7 risk factors for gout?
1. Male2. Obesity3. High purine diet (meat/seafood)4. Alcohol5. Diuretics6. Existing CVD/kidney disease7. Family history
29
What are 4 risk factors for pseudogout?
1. Hyperthyroidism2. Hyperparathyroidism3. Excess iron/calcium4. Female
30
Describe the pathophysiology of gout
- Deposition of monosodium urate crystals within joints- Most affected joints are metatarsophalangeal/carpometacarpal joints and wrists
31
Describe the pathophysiology of pseudogout
- Damage to joints causes deposition of calcium pyrophosphate crystals within joints- Most affected joints are knees, shoulders, wrists and hips
32
What is the main sign of gout?
Gouty tophi:- Subcutaneous deposits of uric acid- Most commonly in small joints (DIP joints) and connective tissue of hands, elbows and ears
33
What is the main symptom of gout and pseudogout?
Hot, swollen, painful, stiff joint (gout - 1st metatarsal/DIP joint, pseudogout - knee)
34
What are 3 investigations for patients with gout and pseudogout?
1. Joint aspiration (both)2. X-ray (both)3. Bloods (gout)
35
Describe the difference in joint aspiration results between gout and pseudogout
- No bacterial growth (both)- Monosodium crystals (gout)/calcium pyrophosphate crystals (pseudogout)- Crystals are needle shaped (gout)/rhomboid shaped (pseudogout)- Birefringence (under polarised light) = negative (gout), positive (pseudogout)
36
What do bloods show in patients with gout?
Hyperuricaemia
37
What does an x-ray look like in patients with gout?
- Space between joint is typically maintained- Lytic lesions in bone- Punched out erosions (which may have sclerotic borders with overhanging edges)
38
What does an x-ray look like in patients with pseudogout?
- Chondrocalcinosis (thin white line in the middle of the joint space due to calcium deposition)- LOSS (loss of joint space, osteophytes, subarticular sclerosis, subchondral cysts)
39
What is the treatment for gout?
- Lifestyle changes (e.g. losing weight, staying hydrated, reducing alcohol/purine-based food intake)- NSAIDs (first line)- Colchicine- Allopurinol
40
What is the treatment for pseudogout?
Symptoms usually resolve spontaneously over several weeksSymptomatic management:- NSAIDs- Colchicine- Joint aspiration- Steroid injections/oral steroids- Joint washout (arthrocentesis - in severe cases)
41
When is colchicine used in patients with gout/pseudogout?
Used in patients that cannot have NSAIDs e.g. patients with renal impairment or significant heart disease
42
What is allopurinol and what does it do?
Xanthine oxidase inhibitor - reduces uric acid production
43
What are 2 complications of gout?
1. Infection in gouty tophi2. Destruction of joint
44
What is osteoporosis/osteopenia?
Osteoporosis - reduction in bone densityOsteopenia - less severe reduction in bone density than osteoporosis
45
Describe the epidemiology of osteoporosis/osteopenia
- More common in females- More common in elderly
46
What are 9 risk factors for osteoporosis/osteopenia?
SHATTERED:S - steroid useH - hyperthyroidism, hyperparathyroidism, hypercalciuriaA - alcohol/tobacco useT - thin (BMI <18.5)T - testosterone lowE - early menopauseR - renal/liver failureE - erosive/inflammatory bone diseaseD - dietary low calcium/malabsorption & Diabetes type I
47
What are 4 other groups of medications that can increase the risk of osteoporosis/osteopenia?
1. SSRIs2. PPIs3. Anti-epileptics4. Anti-oestrogens
48
Describe the pathophysiology of osteoporosis/osteopenia
- Decreased bone mass/density and micro-architectural deterioration- Increase in bone fragility and susceptibility to fracture
49
What are 2 investigations for patients with osteoporosis/osteopenia?
1. FRAX score 2. Bone mineral density (BMD) using DEXA (dual-energy x-ray absorptiometry) scan
50
What does a FRAX score tell us?
Predicts the risk of a major osteoporotic or hip fracture over the next 10 years
51
DEXA scans look at BMD and calculate a Z score and a T score, what is a Z score?
Tells us the number of standard deviations that a patient's bone density falls below the mean for their age
52
DEXA scans look at BMD and calculate a Z score and a T score, what is a T score?
Tells us the number of standard deviations that a patient's bone density falls below the mean for a healthy young adult T score at hip:- >-1 = normal- -1 to -2.5 = osteopenia- <-2.5 = osteoporosis
53
What is the treatment for osteoporosis/osteopenia?
- Lifestyle changes (exercise, maintain healthy weight, avoid falls, smoking cessation, reducing alcohol consumption)- Vitamin D and calcium supplements- Bisphosphonates e.g. alendronate, risendronate, zolendronic acid- Denosumab (alternative to bisphosphonates)- HRT
54
What do bisphosphonates do?
Interfere with osteoclasts and reduce their activity which slows down the breakdown of bone (slows down bone reabsorption)
55
What are 4 key side effects of bisphosphonates?
1. Reflux and oesophageal erosions2. Atypical fractures3. Osteonecrosis of jaw4. Osteonecrosis of external auditory canal
56
How are reflux and oesophageal erosions prevented in patients taking bisphosphonates?
Patients advised to take them on an empty stomach, sitting upright for 30 minutes before moving/eating
57
What is fibromyalgia?
Chronic persistent musculoskeletal pain with unknown cause (non-specific muscular disorder)
58
Describe the epidemiology of fibromyalgia
- More common in women- Usually presents around ages 20-50- More common in people with poorer socioeconomic statuses
59
What are 8 risk factors/associations for fibromyalgia?
1. Female2. Middle aged3. Low household income4. Divorced5. IBS6. Chronic headache7. Depression8. Chronic fatigue syndrome
60
What are 4 symptoms of fibromyalgia?
1. Fatigue2. Brain fog3. Pain (worse with stress and cold weather)4. Morning stiffness
61
What are 2 investigations for patients with fibromyalgia?
1. Exclude all other differentials with bloods and imaging2. 11 tender points in 9 pairs of sites for >6 months
62
What is the treatment for fibromyalgia?
- Exercise- Relaxation- Analgesia e.g. paracetamol, tramadol, codeine- CBT- TCAs e.g. amitriptyline- Pregabalin (anti-convulsant)
63
What are 4 complications of fibromyalgia?
1. Worse quality of life2. Anxiety/depression3. Insomnia4. Opiate addiction
64
What is Sjogren's syndrome?
Autoimmune destruction of exocrine glands (especially lacrimal and salivary glands)
65
Describe the epidemiology of Sjogren's syndrome
More common in females
66
What are 3 causes of Sjogren's syndrome?
Primary = idiopathicSecondary = develops as a complication of SLE or RA
67
What are 3 risk factors for Sjogren's syndrome?
1. Family history (first degree relative = 7x increased risk)2. Female3. >40 years
68
What is the main symptom of Sjogren's syndrome?
Dry mucous membranes i.e. dry mouth/eyes/vagina
69
What are 2 investigations for patients with Sjogren's syndrome?
1. Anti-Ro and anti-La antibodies2. Schirmer test (tears travel <10mm on filter paper = lack of tears)
70
What is the treatment for Sjogren's syndrome?
- Artificial tears/saliva- Vaginal lubricants- Hydroxychloroquine (used to halt progression)
71
What are 3 common complications of Sjogren's syndrome?
1. Eye infections (conjunctivitis, corneal ulcers)2. Oral problems (dental cavities, candida infections)3. Vaginal problems (candidiasis, sexual dysfunction)
72
What are 5 rare complications of Sjogren's syndrome?
1. Pneumonia and bronchiectasis2. Non-Hodgkin's lymphoma3. Peripheral neuropathy4. Vasculitis5. Renal impairment
73
What is vasculitis?
Autoimmune disease that causes inflammation of the blood vessel walls
74
What are the 4 types of small vessel vasculitis?
1. Henoch-Schonlein Purpura (HSP)2. Microscopic polyangiitis3. Granulomatosis with polyangiitis (Wegner's granulomatosis)4. Eosinophilic granulomatosis with polyangiitis (Churg-Straus syndrome)
75
What are the 3 types of medium vessel vasculitis?
1. Eosinophilic granulomatosis with polyangiitis (Churg-Straus syndrome)2. Polyarteritis nodosa3. Kawasaki disease
76
What are the 2 types of large vessel vasculitis?
1. Giant cell arteritis2. Takayasu's arteritis
77
What are 3 general signs of vasculitis?
1. Renal impairment2. Anterior uveitis and scleritis3. Hypertension
78
What are 4 general symptoms of vasculitis?
1. Purpura2. Joint/muscle pain3. Peripheral neuropathy4. GI disturbances (diarrhoea, bleeding, abdominal pain)
79
What are 5 systemic presentations of vasculitis?
1. Fever2. Malaise3. Fatigue4. Weight loss/anorexia5. Anaemia
80
What investigation is usually done for all types of vasculitis?
Bloods = inflammatory markers ESR and CRP = raised
81
What is the standard treatment for vasculitis?
Corticosteroids and immunosuppressants e.g. prednisolone + cyclophosphamide
82
What are the main steroid options for vasculitis?
- Oral e.g. prednisolone- IV e.g. hydrocortisone- Nasal spray for nasal symptoms- Inhaled for lung involvement
83
What are the main immunosuppressant options for vasculitis?
- Cyclophosphamide- Methotrexate- Azathioprine- Rituximab (and other monoclonal antibodies)
84
Which 2 types of vasculitis are usually treated differently and why?
Henoch-Schonlein Purpura (HSP) and Kawasaki disease --> most often affects children
85
What is Henoch-Schonlein Purpura (HSP)?
Small vessel vasculitis that occurs due to IgA deposits in blood vessels
86
Describe the epidemiology of HSP
Commonly presents in children <10 years
87
Describe the pathophysiology of HSP
- IgA deposits in the blood vessels of organs e.g. skin, kidneys, GI tract- Often triggered by gastroenteritis or an upper airway infection (e.g. tonsilitis)
88
What are 4 clinical presentations of HSP?
1. Symmetrical purpura on lower limbs/buttocks2. Joint pain3. Abdominal pain4. Renal involvement (HTN)
89
What is the treatment for HSP?
- Typically supportive e.g. analgesia, rest, hydration- Patients without kidney involvement usually recover within 4-6 weeks
90
What are 2 complications of HSP?
1. 1/3 of patients have a recurrence within 6 months2. 1% of patients go on to develop end stage renal failure
91
What is microscopic polyangiitis?
A type of small vessel vasculitis
92
What are 3 clinical presentations of microscopic polyangiitis?
1. Renal failure (main feature)2. Shortness of breath3. Haemoptysis
93
What are 2 investigations for microscopic polyangiitis?
1. Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) blood tests (a.k.a anti-MPO antibodies)2. No granulomas on histology
94
What is granulomatosis with polyangiitis?
Small vessel vasculitis that affects the respiratory tract and kidneys
95
What is granulomatosis with polyangiitis also known as?
Wegener's Granulomatosis
96
What are 5 clinical presentations of granulomatosis with polyangiitis in the upper respiratory tract?
1. Saddle-shaped nose (due to perforated nasal septum - MAIN SIGN)2. Epistaxis3. Crusty nasal secretions4. Hearing loss5. Sinusitis
97
What are 4 clinical presentations of granulomatosis with polyangiitis in the lungs/kidneys?
1. Cough2. Wheezing3. Haemoptysis 4. Rapidly progressing glomerulonephritis(Often misdiagnosed as pneumonia in lungs)
98
What are 2 investigations for granulomatosis with polyangiitis?
1. Anti-neutrophil cytoplasmic antibodies antibodies (c-ANCA) blood tests (a.k.a anti-PR3 antibodies)2. Histology shows granulomas
99
What is eosinophilic granulomatosis with polyangiitis?
Small and medium vessel vasculitis most often associated with lung and skin problems (can also affect kidneys)
100
What is eosinophilic granulomatosis with polyangiitis also known as?
Churg-Straus syndrome
101
Describe the epidemiology of eosinophilic granulomatosis with polyangiitis
Usually presents in late teenage years/early adulthood
102
What is a clinical presentation of eosinophilic granulomatosis with polyangiitis?
Severe asthma
103
What are 2 investigations for eosinophilic granulomatosis with polyangiitis?
1. Anti-neutrophil cytoplasmic antibodies (p-ANCA) blood tests (a.k.a anti-MPO antibodies)2. FBC = elevated eosinophil levels
104
What is polyarteritis nodosa?
Medium vessel vasculitis that affects the skin, GI tract, kidneys and heart
105
Describe the epidemiology of polyarteritis nodosa
- Associated with hepatitis B (also Hep C/HIV)- More common in developing countries
106
What are 5 clinical presentations of polyarteritis nodosa?
1. Livedo reticularis (mottled purple rash)2. Cutaneous/subcut nodules3. Unilateral orchitis4. Abdominal pain5. Hypertension
107
What are 2 investigations for polyarteritis nodosa?
1. HbsAg2. Biopsy = shows transmural fibrinoid necrosis
108
What is the treatment for polyarteritis nodosa?
- Hep B negative = usual vasculitis treatment- Hep B positive = antiviral agent, plasma exchange and corticosteroids
109
What are 5 complications of polyarteritis nodosa?
1. Renal impairment2. Stroke3. Myocardial infarction4. GI perforation and haemorrhages5. Arthritis
110
What is Kawasaki Disease?
Medium vessel vasculitis (arteritis) associated with mucocutaneous lymph nodes
111
Describe the epidemiology of Kawasaki Disease
1. Commonly presents ages <5 years2. 1.5 x more common in males3. More common in children of Japanese descent
112
What are 2 risk factors for Kawasaki Disease?
1. Male2. Japanese
113
What does Kawasaki Disease most commonly affect?
Coronary arteries
114
What are 4 clinical presentations of Kawasaki Disease?
1. Fever for >5 days2. Non-purulent bilateral conjunctivitis3. Strawberry tongue4. Erythema and desquamation (skin peeling) of palms and soles
115
What is an investigation for Kawasaki Disease?
Echo
116
What is the treatment for Kawasaki Disease?
Aspirin and IV immunoglobulins
117
What is a complication of Kawasaki Disease?
Coronary artery aneurysm
118
What is giant cell arteritis?
Large vessel vasculitis (arteritis) that affects the aorta and/or its major branches (carotid and vertebral arteries)
119
What is Takayasu's arteritis?
Large vessel vasculitis (arteritis) that mainly affects the aorta and its branches (also pulmonary arteries - a.k.a pulseless disease)
120
What is the difference between giant cell arteritis and Takayasu's arteritis?
Very similar - Takayasu's arteritis usually affects younger patients (<40 years) than giant cell arteritis (>50 years)
121
Describe the epidemiology of giant cell arteritis
- 2-3 x more common in females- More common in people of Northern European descent- Often presents in patients >50 years
122
What are 3 risk factors for giant cell arteritis?
1. Female2. Northern European3. Family history of polymyalgia rheumatica
123
What are 6 clinical presentations of giant cell arteritis?
1. Headache over temporal area (typically unilateral)2. Scalp tenderness 3. Jaw claudication4. Blurred vision5. Diplopia (double vision)6. Amaurosis fugax (blindness in one/both eyes)
124
What are 2 investigations for giant cell arteritis?
1. Temporal artery biopsy (GOLD standard) = shows giant cells and granulomatous inflammation
2. Raised ESR and CRP (ESR raised more often)
125
What is the treatment for giant cell arteritis?
High dose glucocorticoid ASAP (usually prednisolone 40mg-60mg)
126
What are 2 complications of giant cell arteritis?
1. Blindness2. Irreversible neuropathy
127
Describe the epidemiology of Takayasu's arteritis
Usually presents before the age of 40
128
What are 2 specific symptoms of Takayasu's arteritis?
1. Arm claudication2. Syncope
129
What are 3 non-specific symptoms of Takayasu's arteritis?
1. Fever2. Malaise3. Muscle aches
130
What are 3 investigations for Takayasu's arteritis?
1. CT/MRI angiography (GOLD STANDARD)2. Granulomatous inflammation on histology3. Doppler ultrasound of carotids (used to detect carotid disease)
131
What is a complication of Takayasu's arteritis?
Aortic aneurysm
132
What is Paget's disease?
Disorder of bone turnover
133
Describe the epidemiology of Paget's disease
Affects up to 10% of individuals by the age of 90
134
Describe the pathophysiology of Paget's disease
- Excessive bone formation and resorption due to excessive osteoblast and osteoclast activity- Leads to patchy areas of high density (sclerosis) and low density (lysis)- Causes enlarged, misshapen, weak bones- Particularly affects axial skeleton (bones of head/spine)
135
What are 5 clinical presentations of Paget's disease?
60-80% are asymptomatic1. Bone deformity e.g. bowed tibia, skull changes2. Fractures3. Hydrocephalus (due to blockage of aqueduct of sylvius)4. Bone pain5. Hearing loss (due to nerve compressive of 8th cranial nerve)
136
What are 2 investigations for patients with Paget's disease?
1. X-ray2. Bloods
137
What does an x-ray look like in patients with Paget's disease?
- Bone enlargement and deformity- Osteoporosis circumscripta (well defined osteolytic lesions)- Cotton wool appearance of skull (poorly defined areas of sclerosis and lysis)- V-shaped defects in long bones
138
What are the results of bloods in patients with Paget's disease?
- Raised ALP (alkaline phosphate)- Normal calcium and phosphate
139
What is the treatment for Paget's disease?
- Bisphosphonates- NSAIDs for bone pain- Calcium and vitamin D supplements
140
What are 2 complications of Paget's disease?
1. Osteosarcoma2. Spinal stenosis and cord compression
141
What are spondyloarthropathies?
Chronic inflammatory diseases that most commonly affect the sacroiliac (SI) joints and axial skeleton
142
Describe the epidemiology of spondyloarthropathies
- All conditions associated with HLA-B27 gene- Seronegative (RF -ve)
143
What are the 5 types of spondyloarthropathies?
1. Ankylosing arthritis2. Psoriatic arthritis3. Reactive arthritis4. Enteropathic arthritis (a.k.a IBD associated arthritis)5. Juvenile idiopathic arthritis
144
What are the features of spondyloarthropathies?
SPINEACHES - sausage digitsP - psoriasisI - inflammatory back painN - NSAIDs (good response)E - enthesitis (heel)A - arthritisC - crohn's/colitis/elevated CRPH - HLA-B27E - eye (uveitis)
145
What is ankylosing spondylitis?
Inflammatory condition that mainly affects the sacroiliac joints and axial skeleton
146
Describe the epidemiology of ankylosing spondylitis
- Typically presents in late teens/20s- Used to think it was 3 x more common in males but now seem to think it affects both equally
147
What is a risk factor for ankylosing spondylitis?
1. HLA-B27 gene2. Male?
148
Describe the pathophysiology of ankylosing spondylitis
- Inflammatory arthritis of spine and rib cage- Leads to new bone formation and fusion of joints
149
What are 3 symptoms of ankylosing spondylitis?
1. Lower back pain and stiffness - worse with rest and improves with movement2. Sacroiliac pain3. Flares of worsening symptoms
150
What are 6 investigations for patients with ankylosing spondylitis?
1. X-ray2. HLA-B27 genetic test3. Rheumatoid factor -ve4. CRP and ESR = raised5. MRI of spine (bone marrow oedema)6. Schober's test
151
What does an x-ray look like in patients with ankylosing spondylitis?
- Bamboo spine- Squaring of vertebral - Subchondral sclerosis and erosions- Syndesmophytes (bony outgrowths from spinal ligaments)- Ossification of ligaments, discs and joints- Fusion of facet, sacroiliac and costovertebral joints
152
What is Schober's test?
- Used to assess how much mobility there is in the spine- Patient stands straight- Find L5 vertebrae and mark a point 10cm above and 5cm below - Ask the patient to bend forward as far as they can and measure the distance between the points- Distance <20cm = indicates restriction in lumbar movement
153
What is the treatment for ankylosing spondylitis?
- NSAIDs- Steroids- Anti-TNF drugs e.g. etanercept- Monoclonal antibodies against TNF e.g. infliximab, adalimumab- Physiotherapy and lifestyle advice- Surgery for deformities
154
What is a complication of ankylosing spondylitis?
Vertebral fractures
155
What is psoriatic arthritis?
Inflammatory arthritis associated with psoriasis
156
Describe the epidemiology of psoriatic arthritis
1 in 5 patients with psoriasis have psoriatic arthritis
157
What is a risk factor for psoriatic arthritis?
HLA-B27 gene
158
What are 5 clinical presentations of psoriatic arthritis?
1. Inflammatory joint pain2. Plaques of psoriasis3. Onycholysis (separation of nail from nail bed)4. Dactylitis (inflammation of full finger)5. Enthesitis (inflammation of entheses - point of insertion of tendons into bone)
159
What are 3 patterns of psoriatic arthritis?
1. Symmetrical polyarthritis2. Asymmetrical polyarthritis3. Spondylitic pattern
160
Describe symmetrical polyarthritis
- Presents similarly to rheumatoid arthritis- More common in women- Most affected = hands, wrists, ankles and DIP joints- MCP joints less commonly affected
161
Describe asymmetrical polyarthritis
Mainly affects the digits and feet
162
Describe spondylitic pattern
- More common in men- Back stiffness- Sacroiliitis- Atlanto-axial joint involvement
163
What are 6 investigations for patients with psoriatic arthritis?
1. X-ray2. ESR and CRP = raised3. HLA-B27 genetic test4. Rheumatoid factor -ve5. Negative for anti-CCP6. Joint aspiration (no bacteria/crystals)
164
What does an x-ray look like in patients with psoriatic arthritis?
- Erosion in distal interphalangeal (DIP) joint- Periarticular new bone formation- Osteolysis- Pencil-in-cup deformity
165
What is the treatment for psoriatic arthritis?
- NSAIDs- Physiotherapy - Steroid injection- DMARDs (disease-modifying anti-rheumatic drugs) e.g. methotrexate, sulfasalazine- TNF inhibitors/monoclonal antibodies e.g. etanercept, infliximab, adalimumab- Ustekinumab (last line - monoclonal antibody that targets interleukins 12 and 23)
166
What is the main complication of psoriatic arthritis?
Arthritis mutilans:- Severe form of psoriatic arthritis (joint is completed destroyed)- Occurs in phalanxes- Osteolysis of bones around the joints in the digits- Leads to progressive shortening of the digit- Skin then folds as the digit shortens, giving an appearance of 'telescopic finger'
167
What is reactive arthritis?
Inflammatory arthritis (synovitis) that occurs after exposure to certain GI or GU infections (used to be known as Reiter syndrome)
168
What are 5 common causes of reactive arthritis?
1. Chlamydia2. Gastroenteritis3. Campylobacter jejuni4. Salmonella enteritidis5. Shigella
169
What is a risk factor for reactive arthritis?
HLA-B27 gene
170
What are 5 clinical presentations of reactive arthritis?
1. Often mistaken for septic arthritis as present similarly2. Begins 1-4 weeks after onset of infection3. Asymmetrical oligoarthritis4. Painful, swollen, warm, red and stiff joints5. Dactylitis (inflammation of full finger)
171
What is the classic triad of clinical presentation for reactive arthritis?
"Can't see, can't pee, can't climb a tree"- Conjunctivitis- Urethritis- Arthritis
172
What are 6 investigations for patients with reactive arthritis?
1. X-ray (sacroiliitis or enthesopathy)2. Joint aspiration (negative - exclude septic arthritis and gout)3. ESR and CRP = raised4. HLA-B27 genetic test5. Rheumatoid factor -ve6. Negative for ANA
173
What is the treatment for reactive arthritis?
- NSAIDs- Corticosteroids- DMARDs e.g. methotrexate (for chronic)
174
What is septic arthritis?
Infection of one or more joints causes by pathogenic inoculation of microbes
175
Describe the epidemiology of septic arthritis
Common complication of joint replacement - occurs in around 1% of straight forward hip or knee replacements
176
What are 5 causes of septic arthritis?
1. Staphylococcus aureus (most common)2. Neisseria gonorrhoea 3. Streptococcus pyogenes (Group A streptococcus)4. Haemophilus influenza5. Escherichia coli (E. Coli)
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How is septic arthritis spread?
Via direct inoculation or via haematogenous spread
178
What are 8 risk factors for septic arthritis?
1. Pre-existing joint disease e.g. OA/RA2. Joint prostheses3. IVDU4. Immunosuppression5. Alcohol misuse6. Diabetes7. Intra-articular corticosteroid injection8. Recent joint surgery
179
What does septic arthritis most commonly affect?
Usually only affects a single joint - most common is knee
180
What are 5 symptoms of septic arthritis?
1 Hot, red, swollen and painful joint2. Stiffness and reduced range of motionSystemic symptoms:3. Fever4. Lethargy5. Sepsis
181
What are 3 investigations for septic arthritis?
1. Joint aspiration (fluid may be purulent)2. Blood culture3. Bloods (WCC, ESR, CRP = raised)
182
What are joint aspiration samples sent for in patients with septic arthritis?
- Gram staining- Crystal microscopy- Culture- Antibiotic sensitives
183
What is the treatment for septic arthritis?
- IV antibiotics for 3-6 weeks- Aspirate joint- Analgesia
184
What are 3 antibiotic options for septic arthritis?
1. First line = flucloxacillin + rifampicin2. Vancomycin = vancomycin + rifampicin (if allergic to penicillin, MRSA or prosthetic joint)3. Clindamycin
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What is osteomyelitis?
Infection in the bone and bone marrow
186
Describe the epidemiology of osteomyelitis
- More common in males- Commonly presents in children <10 years
187
What are the 2 most common causes of osteomyelitis?
1. Staphylococcus aureus2. Salmonella (if the patient has sickle cell anaemia)
188
What are 7 risk factors for osteomyelitis?
1. Male2. Open bone fracture3. Orthopaedic surgery4. Immunocompromised5. Sickle cell anaemia6. HIV7. TB
189
What are 3 ways of entry for osteomyelitis?
1. Hematogenously (through blood)2. Open wound3. Contiguously (skin into blood)
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What are 6 symptoms of osteomyelitis?
1. Afebrile/low grade fever2. Pain3. Swelling4. Tenderness5. Malaise/fatigue6. Refusal to use limb or weight bear
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What are 5 investigations for patients with osteomyelitis?
1. X-ray2. MRI3. Bloods (WCC, ESR, CRP = raised)4. Blood culture5. Bone marrow aspiration/bone biopsy with histology and culture
192
What is the treatment for osteomyelitis?
- Extensive and prolonged antibiotic therapy- Surgery for drainage and debridement of infected bone
193
What is systemic lupus erythematosus (SLE)?
Inflammatory multisystem autoimmune connective tissue disease
194
Describe the epidemiology of SLE
- More common in women- More common in Asian people- Commonly presents in 20s-40s
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Describe the pathophysiology of SLE
Type III hypersensitivity reaction - Anti-nuclear antibodies and anti double stranded DNA antibodies trigger inflammatory response
196
What is the most specific symptom of SLE?
Photosensitive malar rash across face ('butterfly' shaped)
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What are 6 non-specific symptoms of SLE?
1. Fatigue2. Weight loss3. Fever4. SOB5. Mouth ulcers6. Hair loss
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What are 6 investigations for patients with SLE?
1. Antibodies (ANA, anti-dsDNA)2. FBC (normocytic anaemia in chronic)3. C3 and C4 = decreased4. Raised ESR but normal (or slightly elevated) CRP5. Immunoglobulins = raised6. Urinalysis = proteinuria
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What is the treatment for SLE?
- Hydroxychloroquine (first line for mild)- NSAIDs- Steroids e.g. prednisolone- Immunosuppressants e.g. methotrexate, azathioprine, cyclosporin- Monoclonal antibodies e.g. rituximab- Suncream and sun avoidance for rash
200
What are 9 complications of SLE?
1. CVD2. Infection3. Anaemia of chronic disease4. Pericarditis 5. Pleuritis6. Interstitial lung disease7. Lupus nephritis8. Venous thromboembolism9. Recurrent miscarriage
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What is antiphospholipid syndrome?
Autoimmune disease associated with antiphospholipid antibodies causing the blood to become more prone to clotting
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Describe the epidemiology of antiphospholipid syndrome
More common in females
203
What are the causes of antiphospholipid syndrome?
Can occur on its own or secondary to an autoimmune condition, especially SLE
204
What are 7 risk factors for antiphospholipid syndrome?
1. Diabetes2. HTN3. Obesity4. Female5. Smoking6. Oestrogen therapy for menopause7. Underlying systemic autoimmune disease
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Describe the pathophysiology of antiphospholipid syndrome
- Associated with antiphospholipid antibodies- These interfere with coagulation and create a hypercoagulable state where the blood is more prone to clotting
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What are the 3 antiphospholipid antibodies?
1. Lupus anticoagulant2. Anticardiolipin antibodies3. Anti-beta-2 glycoprotein I antibodies
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What are 4 clinical presentations of antiphospholipid syndrome?
1. Thrombosis2. Recurrent miscarriage3. Livedo reticularis (purple rash)4. Thrombocytopenia
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How is antiphospholipid syndrome diagnosed?
History of thrombosis/pregnancy complication + persistent antiphospholipid antibodies
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What is the treatment for antiphospholipid syndrome?
- Long-term warfarin- Low molecular weight heparin + aspirin (in pregnancy)
210
What are 3 complications of antiphospholipid syndrome?
1. Venous thromboembolism e.g. DVT, PE2. Arterial thrombosis e.g. stroke, MI, renal thrombosis3. Pregnancy complications e.g. recurrent miscarriages, pre-eclampsia, stillbrith
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What is Raynaud's phenomenon?
Intermittent spasm in the arteries supplying the fingers and toes usually precipitated by cold and relieved by heat
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What 4 conditions are most commonly associated with Raynaud's phenomenon?
1. SLE2. Systemic sclerosis3. Rheumatoid arthritis4. Dermatomyositis
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What is dermatomyositis?
Autoimmune connective tissue disorder involving chronic inflammation of the skin and muscles
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What is polymyositis?
Autoimmune disorder involving chronic inflammation of the muscles
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What are causes of dermatomyositis/polymyositis?
Usually as a result of underlying malignancy - paraneoplastic syndromeCommonly associated with cancers:- Lung- Breast- Ovarian- Gastric
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What are 2 symptoms of both dermatomyositis and polymyositis?
Symptoms develop over weeks1. Bilateral muscle pain, mostly affecting proximal muscles in shoulder and pelvic girdle2. Fatigue/weakness
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What are 5 skin involvement symptoms of dermatomyositis?
1. Gottron lesions2. Photosensitive erythematous rash on back, shoulders and neck3. Purple rash on face/eyelids4. Periorbital oedema5. Subcutaneous calcinosis
218
What are 2 investigations for patients with dermatomyositis/polymyositis?
1. Creatine kinase blood test (<300U/L)2. Autoantibodies
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Which autoantibodies are usually present in patients with dermatomyositis?
1. Anti-Jo-1 antibodies2. Anti-Mi-2 antibodies 3. Anti-nuclear antibodies
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Which autoantibodies are usually present in patients with polymyositis?
Anti-Jo-1 antibodies
221
What is the treatment for dermatomyositis/polymyositis?
- Corticosteroids- Immunosuppressants e.g. azathioprine- IV immunoglobulins- Biological therapy e.g. infliximab, etanercept
222
What is scleroderma/systemic sclerosis?
Autoimmune inflammatory and fibrotic connective tissue disease causing hardening of the skin
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Describe the pathophysiology of scleroderma/systemic sclerosis
- Increased fibroblast activity- Leads to increased collagen deposition- Results in abnormal growth of connective tissue
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What is the characteristic presentation of scleroderma/systemic sclerosis?
'Beak'-like nose and small mouth
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What are the 2 main patterns of disease for scleroderma/systemic sclerosis?
1. Limited cutaneous systemic sclerosis2. Diffuse cutaneous systemic sclerosis
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Describe limited cutaneous systemic sclerosis
Used to be called CREST syndromeC - calcinosis (calcium deposits under skin in fingertips)R - Raynaud's phenomenon (white/blue fingertips in response to cold)E - oEsophageal dysmotility (swallowing difficulties, acid reflux, oesophagitis)S - sclerodactyly (shiny, tight skin without normal folds in hands)T - telangiectasia (dilated small blood vessels in skin))
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Describe diffuse cutaneous systemic sclerosis
Features of CREST syndrome plus:- Cardiovascular problems e.g. HTN, CAD- Lung problems e.g. pulmonary hypertension, pulmonary fibrosis- Kidney problems e.g. glomerulonephritis, scleroderma renal crisis
228
What are 2 investigations for scleroderma/systemic sclerosis?
1. Autoantibodies2. Nailfold capillaroscopy
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Which autoantibodies are found in patients with limited cutaneous systemic sclerosis?
- Anti-nuclear antibodies- Anti-centromere antibodies
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Which autoantibodies are found in patients with diffuse cutaneous systemic sclerosis?
- Anti-nuclear antibodies- Anti-Scl-70 antibodies
231
What is nailfold capillaroscopy?
- Magnify and examine area where the skin meets the fingernails- Allows us to examine the health of peripheral capillaries- Indications of scleroderma/systemic sclerosis = abnormal capillaries, avascular areas and micro-haemorrhages
232
What is the treatment for scleroderma/systemic sclerosis?
- Steroids and immunosuppressants- Avoid smoking- Gentle skin stretching to maintain range of motion- Emollients- Treat symptoms e.g. nifedipine for symptoms of Raymaud's phenomenon
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What is polymyalgia rheumatica?
Inflammatory condition causing pain and stiffness in the shoulders, pelvic girdle and neck
234
Describe the epidemiology of polymyalgia rheumatica
- Strong association with giant cell arteritis- More common in women- More common in Caucasians- Usually affects older adults >50 years
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What are 4 systemic symptoms of polymyalgia rheumatica?
1. Weight loss2. Fatigue3. Fever4. Low mood
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What are 3 other clinical presentations of polymyalgia rheumatica?
1. Upper arm tenderness2. Carpel tunnel syndrome3. Pitting oedema
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What are 5 main clinical presentations of polymyalgia rheumatica?
1. Bilateral shoulder pain that may radiate to elbow2. Bilateral pelvic girdle pain3. Worse with movement4. Interferes with sleep5. Stiffness for at least 45 minutes in the morning
238
What are 2 investigations for patients with polymyalgia rheumatica?
1. ESR and CRP = raised2. Exclude other conditions (FBC, urinalysis, LFTs etc.)
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What is the treatment for polymyalgia rheumatica?
Steroids - initially 15mg prednisolone
240
How is a diagnosis of polymyalgia rheumatica confirmed?
After 3-4 weeks of steroids, should expect to see a 70% improvement in symptoms and inflammatory markers to return to normal
241
How are patients with polymyalgia rheumatica typically weaned off steroids?
- 15mg prednisolone until symptoms are fully controlled- 12.5 mg for 3 weeks- 10mg for 4-6 weeks- reduce by 1mg every 4-8 weeks- Can take 1-2 years to fully wean off
242
What is mechanical lower back pain?
Pain related to movements of the lumbar and sacral regions of the spine associated with no specific disease
243
Describe the epidemiology of mechanical lower back pain
- Most common form of back pain- More common in females
244
What are 7 causes of mechanical lower back pain?
1. Muscle/ligament sprain2. Facet joint dysfunction3. Sacroiliac joint dysfunction4. Herniated disc5. Spondylolisthesis (anterior displacement of a vertebra out of line with the one below)6. Scoliosis7. Degenerative changes e.g. arthritis
245
What are 7 risk factors for mechanical lower back pain?
1. Manual labour2. Smoking3. Low socioeconomic status4. Poor working conditions5. Female6. Psychological disorder7. Pre-existing chronic widespread pain
246
What are 2 signs for serious pathology in patients with mechanical lower back pain?
1. Elderly (myeloma)2. Neuropathic pain (spinal cord compression)
247
What are 2 symptoms of mechanical lower back pain?
1. Unilateral back pain often helped by rest, worse in evenings and aggregated by exercise2. Muscular spasm causing local pain and tenderness
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What are red flag symptoms in patients with mechanical lower back pain?
TUNAFISHT - traumaU - unexplained weight loss and night sweatsN - neurological deficits, bowel/bladder incontinenceA - age <20 or >55F - feverI - IVDUS - steroid use/immunosuppressionH - history of cancer
249
What are 2 investigations for patients with mechanical lower back pain?
1. Bloods (ESR, CRP, FBC, ALP)2. Imaging e.g. DEXA scan/MRI
250
What is the treatment for mechanical lower back pain?
- Often self-limiting- Analgesia ladder- Lifestyle advice- Physiotherapy
251
What is lumbar spondylosis?
Degeneration of the intervertebral disc due to it losing its compliance and thinning over time
252
Describe the epidemiology of lumbar spondylosis
Affects older patients
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What are the symptoms of lumbar spondylosis?
Initially asymptomatic and progressively worsens:- Pain in lower back/buttocks/thighs- Numbness/tingling spreading from lower back down a leg (sciatica)- L4/L5 most common
254
What is the treatment for lumbar spondylosis?
- Analgesia- Physiotherapy
255
What is osteomalacia?
Defective bone mineralisation leading to soft bone due to a lack of Ca2+
256
What is Rickets?
Inadequate mineralisation of bone and epiphyseal cartilage in the growing skeleton of children
257
What are 4 causes of osteomalacia/rickets?
1. Malnutrition2. Drug induced3. Defective 1-alpha hydroxylation4. Liver/kidney disease
258
Describe the pathophysiology of osteomalacia
- Vitamin D deficiency- Lack of vitamin D reduces calcium and phosphate absorption from the intestines and kidneys- Lack of calcium and phosphate in the blood- = defective bone mineralisation
259
What are 4 symptoms of osteomalacia?
1. Fatigue2. Bone pain3. Muscle weakness/aches4. Pathological or abnormal fractures
260
What are 6 symptoms of Ricket's?
1. Leg bowing and knock knees2. Tender swollen joints3. Growth retardation4. Bone and joint pain5. Dental deformities (delayed formation of teeth, enamel hypoplasia)6. Enlargement of end of ribs (rachitic rosary)
261
What are 4 investigations for patients with osteomalacia?
1. Serum 25-hydroxyvitamin D (insufficiency = 25-50nmol/L, deficiency = <25nmol/L)2. Low serum calcium and phosphate3. DEXA = low BMD4. X-ray = loss of cortical bone
262
What is the treatment for osteomalacia?
Supplementary vitamin D (cholecalciferol)
263
Describe the epidemiology of primary bone tumours
- More common in males- More common in children
264
Describe the epidemiology of osteosarcomas
- Most sarcoma- Usually presents in adolescents and younger adults 10-20 years
265
Describe the epidemiology of ewing sarcomas
- Very rare- Usually presents in teens
266
Describe the epidemiology of osteochondroma
Common in males <25 years
267
What are 4 risk factors for primary bone tumours?
1. Previous radiotherapy2. Previous cancer3. Paget's disease (associated with osteosarcoma)4. Benign bone lesions
268
Describe the pathophysiology of osteosarcomas
Originates from metaphysis of long bones - most commonly affects femur, tibia and humerus
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Describe the pathophysiology of ewing sarcomas
Originates from mesenchymal stem cells in long bones
270
Describe the pathophysiology of osteochondromas/chondrosarcoma
Originates from cartilage - overproduction of bone which deposits on metaphysis
271
What is the difference between osteochondromas/chondrosarcomas?
Osteochondroma = benignChondrosarcoma = malignant
272
Where are primary bone tumours most common?
Long bones
273
What are 5 clinical presentations of primary bone tumours?
1. Persistent bone pain, worse at night2. Bone swelling3. Palpable mass4. Easy bruising5. Mobility issues e.g. limp, joint stiffness, reduced range of movement
274
What are 3 investigations of primary bone tumours?
1. Biopsy (gold standard)2. X-ray (first line)3. Bloods (raised ALP)
275
What does an x-ray look like in patients with primary bone tumours?
- Poorly defined lesion in the bone- Destruction of normal bone- 'Fluffy' bone- 'Sunburst' appearance
276
What is the treatment for primary bone tumours?
- Surgical resection of lesion, often with limb amputation- Chemotherapy- Radiotherapy
277
What are 2 complications of primary bone tumours?
1. Pathological bone fractures2. Metastasis
278
Describe the epidemiology of secondary bone tumours
More common than primary bone tumours
279
Tumours where are most likely to metastasise to bone?
PBKTL (lead kettle):- Prostate- Breast- Kidney- Thyroid- Lungs
280
What are 5 clinical presentations of secondary bone tumours?
1. Severe bone pain, worse at night2. Weight loss3. Fatigue4. Fever5. Malaise
281
What are 2 investigations for secondary bone tumours?
1. X-ray = lytic lesions2. CT scans = metastases
282
What is the treatment of secondary bone tumours?
- Chemotherapy- Radiotherapy- Surgery- Bisphosphonates
283
What is Marfan's syndrome?
Autosomal dominant condition affecting the gene responsible for creating fibrillin
284
What is a risk factor for Marfan's syndrome?
Family history
285
Describe the pathophysiology of Marfan's syndrome
- Fibrillin is an important component of connective tissue- People with Marfan's syndrome lack this and so have features resulting from abnormal connective tissue
286
What are 8 clinical presentations of Marfan's syndrome?
1. Tall stature2. Long neck3. Long limbs4. Long fingers (arachnodactyly)5. High arch palate6. Hypermobility7. Pectus carinatum or pectus excavatum8. Downward sloping palpable fissures
287
What are 2 investigations for patients with Marfan's syndrome?
1. Ask patients to cross their thumb across their palm (thumb tip goes past opposite edges of hand = indicates arachnodactyly)2. Ask patients to wrap the thumb and fingers of one hand around the other wrist (thumb and fingers overlap = indicates arachnodactyly)
288
What is the treatment for Marfan's syndrome?
- Lifestyle changes (avoid intense exercise, caffeine, stimulants)- Drugs e.g. beta blockers, angiotensin II receptor antagonists- Physiotherapy- Yearly echo and ophthalmologist review
289
What is the main aim of treatment for Marfan's syndrome?
Minimise blood pressure and heart rate
290
What are 6 complications of Marfan's syndrome?
1. Valve prolapse2. Aortic aneurysms3. Lens dislocation4. Pneumothorax5. GORD6. Scoliosis
291
What is Ehlers-Danlos Syndrome (EDS)?
Group of autosomal dominant conditions that cause defects in collagen
292
Describe the epidemiology of Ehlers-Danlos Syndrome (EDS)
Hypermobile EDS = most common and least severe type of EDSVascular EDS = most dangerous type
293
What is a risk factor for Ehlers-Danlos Syndrome (EDS)?
Family history
294
What are 5 clinical presentations of Ehlers-Danlos Syndrome (EDS)?
1. Hypermobility of joints2. Easily stretched skin (hyperextensibility)3. Easy bruising4. Chronic joint pain5. Re-occurring dislocations
295
What are 3 clinical presentations of classical Ehlers-Danlos Syndrome (EDS)?
1. Joint pain2. Abnormal wound healing3. Lumps over pressure points
296
What is a clinical presentation of vascular Ehlers-Danlos Syndrome (EDS)?
Thin, translucent skin
297
What is the investigation for Ehlers-Danlos Syndrome (EDS)?
Beighton score (used to assess extent of hypermobility)
298
What is the Beighton score?
One point scored for each side of the body:- Palms flat on floor with straight legs (score 1)- Elbows hyperextend- Knees hyperextend- Thumb can bend to touch forearm- Little finger hyperextends past 90 degrees
299
What is the treatment for Ehlers-Danlos Syndrome (EDS)?
- Physiotherapy- Occupational therapy- Psychological support
300
What are 4 complications of classical Ehlers-Danlos Syndrome (EDS)?
1. Hernias2. Prolapse3. Aortic root dilation4. Mitral regurgitation
301
What is a complication of vascular Ehlers-Danlos Syndrome (EDS)?
Skin, internal organs and vessels prone to rupture
302
What is a complication of hypermobile Ehlers-Danlos Syndrome (EDS)?
Postural orthostatic tachycardia syndrome (POTS)
303
What is postural orthostatic tachycardia syndrome (POTS)?
Result of autonomic dysfunction that causes appropriate tachycardia on sitting or standing up
304
What are 6 symptoms of postural orthostatic tachycardia syndrome (POTS)?
1. Pre syncope2. Syncope3. Headaches4. Disorientation5. Nausea6. Tremor
