Rheumatology Flashcards
Causes of acute monoarthritis?
Crystal-induced?
Trauma?
- Infection- streptococcal
- Gout -often men. Pseudogout -often elderly women with severe OA
- Haemarthrosis (bleeding into joint spaces. It is a common feature of hemophilia)
What is Haemophilia?
Hemophilia A, also called factor VIII (FVIII) deficiency or classic hemophilia, is a genetic disorder caused by missing or defective factor VIII, a clotting protein
Causes of chronic monarthritis
Infections - TB
Inflammatory - Psoriatic arthritis (PsA), Reactive arthritis, Foreign body
Non-inflammatory - Osteoarthritis (OA), Traumatic e.g. meniscal tear, Osteonecrosis (associated with prednisolone use), Neuropathic – Charcot’s joint
Tumours- All are rare
Causes of acute polyarthritis
Inflammatory arthritis - RA, PsA, reactive arthritis
Autoimmune arthritis - e.g. SLE, vasculitis
Viral infection - e.g. HIV, Chikungunya, parvovirus
Crystal arthritis - Uncontrolled gout
Chikungunya (mosquitoes - joint pain, fever)
Rx- acetaminophen, do not take NSAIDs
Causes of chronic ( >3 months) polyarthritis
Inflammatory arthritis - RA, PsA, reactive arthritis
Autoimmune arthritis - SLE, vasculitis
Crystal arthritis - Uncontrolled gout
Causes of arthritis of the DIPJs
PsA - will also be nail dystrophy (pitting) on the affected digit
OA - is the commonest disorder affecting this joint (Heberden’s nodes)
Fibromyalgia
- Symptoms?
- Treatment tends to be a combination of:
- Cause?
- Condition appears to be triggered by?
- Epidemology
1.
- WIDESPREAD PAIN
- Increased sensitivity to pain
- extreme tiredness (fatigue)
- muscle stiffness
- difficulty sleeping
- problems with mental processes (known as “fibro-fog”), e.g. problems with memory and concentration
- headaches
- IBS – a digestive condition that causes stomach pain and bloating
- Medications: antidepressants and painkillers
Talking therapies: CBT and counselling
Lifestyle changes: exercise programmes and relaxation techniques
- thought to be related to abnormal levels of certain chemicals in the brain and changes in the way the CNS (brain, spinal cord and nerves) processes pain messages carried around the body.
4.
- an injury or infection
- giving birth
- having an operation
- the breakdown of a relationship/ death of a loved one
- F>M (females 7x more than males)
Extra-articular symptoms and signs
Extra articular signs:
Neurology
Cardio-respiratory
Haematological
Gastro-intestinal
SLE symptoms
What is gals?
GALS (gait, arms, legs, spine) assessment
State the abnormal gaits and causes of the abnormalities
HEMPIPLEGIC - pt cannot dorsiflex foot, foot drop, common peroneal nerve
What is valgus and varus knee deformity?
How do you asses hypermobility syndrome
Bow legs are due to medial compartment arthritis usually OA as the medial compartment takes most load. Knock knees are much less common, and are indicative of both compartments being involved in inflammatory arthritis.
Flat feet may be idiopathic, but are a feature of joint hypermobility syndromes and of inflammatory arthritis. If the forefoot is widened, with irregular gaps between toes which do not sit on the ground, this is likely to be inflammatory arthritis.
Hand exam
Look: Look at both the dorsal and palmar aspects. Inspect for deformities, scars, swellings and wasting. Look at the skin (calcinosis, telangiectasia, psoriasis) and nails (psoriasis). Do not forget to check for rheumatoid nodules or tophi on extensor aspects of elbows.
Feel: Check for joint tenderness. MCPJs and wrists are key sites affected by RA. Thumb bases and DIPJs are key sites affected by OA. Swellings may be warm in RA. OA swellings are bony. RA swellings are soft. Tendon swellings with tendon crepitus are seen in RA. Thickening of the skin in the palm causing digit contracture, usually of the ring finger may be Dupuytren’s.
Move: Ask the patient to make a fist. This screens for problems with flexion at the MCPJs, PIPJs and DIPJs. Ask the patient to fully extend their fingers. Check wrist flexion/extension and radial/ulnar deviation. Check supination/pronation.
Function: Ask the patient to undo a button, pick up and write with a pen etc.
Additional examination: Check thumb abduction (median nerve). Check little finger abduction (ulnar nerve). If carpal tunnel syndrome is suspected, perform Phalen’s and Tinel’s tests. If numbness is reported, check light touch and pin prick sensation. Be able to explain the ulnar nerve and medial nerve distributions in the hand.
Professionalism: Maintain patient dignity, communicate sensitively to the patient and examiner. Clean your hands.
What is tinnels test?
What is phalens test?
This is used to help diagnose carpal tunnel syndrome (CTS), the most common peripheral neuropathy of the upper limb. Any type of arthritis at the wrist can predispose to this.
Tap over the carpal tunnel with your index and middle fingers for 30-60 seconds. If the patient develops tingling in the thumb and radial two and a half fingers, this suggests median nerve irritation.
If the history suggests carpal tunnel syndrome, Phalen’s test may be used..
Ask the patient to hold their wrist in complete and forced flexion (pushing the dorsal surfaces of both hands together) for 60 seconds. If the patient’s symptom develop then the test is positive.
Motor nerve supply to the hand: median nerve
All muscles of anterior compartment of forearm EXCEPT flexor carpi ulnaris and the medial two parts of flexor digitorum profundus
pronator teres and pronator quadratus – pronate forearm flexor carpi radialis – flexes and abducts wrist
palmaris longus – flexes wrist and tenses palmar aponeurosis flexor digitorum superficialis – flexes fingers at PIPJs
lateral two parts of flexor digitorum profundus – flex index and middle fingers at DIPJs
flexor pollicis longus – flexes thumb at IPJintrinsic muscles of hand – LOAF muscles
lateral two lumbricals – flex MCPJs and extend IPJs of index and middle fingeropponens pollicis – opposes thumb
abductor pollicis brevis – abducts thumb
flexor pollicis brevis – flexes thumb at MCPJ
- Sensory nerve supply to the hand: ulnar nerve
- Motor nerve supply to the hand: ulnar nerve
- skin over hypothenar eminence
- medial 1⁄3 palm of hand
- palmar aspect of lateral 11⁄2 fingers
- medial 1⁄3 dorsum of hand
- dorsal aspect of medial 11⁄2 fingers (little finger and half of ring finger)
Two muscles of forearm:
flexor carpi ulnaris – flexes and adducts wrist; medial two parts of flexor digitorum profundus – flex ring and little fingers at DIPJs
Most of the intrinsic muscles of the hand – interossei and the adductor pollicis.
These include numbness over hypothenar eminence and in the ulnar nerve distribution of hand.
Paralysis of flexor carpi ulnaris causes weak wrist flexion and adduction. Paralysis of medial two parts of flexor digitorum profundus causes weak flexion of ring and little finger DIPJs. Paralysis of most of the intrinsic muscles of the hand results in weak MCPJ flexion and IPJ extension of ring and little fingers, loss of finger abduction and adduction, and loss of opposition of little finger.
To test adductor pollicis, ask the patient to grip a piece of card between the thumb and the side of the index finger (Froment’s test). In ulnar nerve palsy, the IPJ and MCPJ of the thumb will flex as the patient tries to grip the card. Test adduction by asking the patient to grip the card between the little and ring fingers whilst holding the fingers extended. Test the first dorsal interosseus muscle by asking the patient to abduct the extended index finger against resistance.
paradox: The ulnar nerve also innervates the ulnar (medial) half of the flexor digitorum profundus muscle (FDP). If the ulnar nerve lesion occurs more proximally (closer to the elbow), the flexor digitorum profundus muscle may also be denervated. As a result, flexion of the IP joints is weakened, which reduces the claw-like appearance of the hand.
appearance is most pronounced when the nerve is injured at the wrist, for example by compression in Guyon’s canal, as the function of flexor digitorum profundus will be preserved.
Interpreting blood tests in rheumatic diseases
Hb: Anaemia of chronic disease most common in RA, Fe deficiency may be due to NSAIDs
platelets: Rise with inflammation or bleeding, fall in SLE
neutrophils: Rise with inflammation, sepsis and prednisolone usage; Fall in SLEor with DMARD toxicity
lymphocytes: Fall in SLE or DMARD induced
U&E: Rise due to NSAIDs, renal disease in lupus/vasculitis or gout
Uric acid: Elevated in gout, but falls with inflammation
LFTs: Hepatitic rise due to DMARD toxicity
CK, ALT, LDH: Rise in myositis
How do we test for rheumatoid arthritis?
- RF Ab against the Fc fragment of igG.
Seropositive patients (RF +) tend to have more severe disease.
- anti-CCP more specific for RA than RF.
Neither of these antibodies rises during disease flare.
- ANAs
most commonly SLE
Dermatomyositis and polymyositis
- What are these?
- Symptoms and signs
- Diagnostic criteria
- Investigations
- Treatment
- Did you know….?
- Types of myositis
- Rare idiopathic muscle diseases that are characterized by inflammation of striated muscle. M:F is similar and peak age of onset is 40-50 years.
polymyositis – affects many different muscles, particularly the shoulders, hips and thigh muscles; F>M, 30-60
dermatomyositis – muscles + rash; F>M and affects both adults and children
- Insidious onset of muscle proximal weakness, often painless. May be with SOB or rash. Raynaud’s syndrome is common.
3.
- Symmetrical proximal muscle weakness
- Raised serum muscle enzyme levels e.g.
- Typical electromyographic (EMG) changes
- Biopsy evidence of myositis
- Typical rash of dermatomyositis
- PM if >= 3 of the first 4 above criteria
- DM if rash and >= 2 of the first 3 above criteria
4.
- Some patients have raised inflammatory markers.
- The FBC is usually normal.
- The kidney is not affected.
- Raised ALT (from muscle) with the “liver” enzymes being normal may be a clue.
- 80% patients are antinuclear antibody positive.
- anti-Jo-1 and anti-Mi2 extended muscle auto-antibody panel
- MRI
- Speech and language therapy
5.
- High dose corticosteroids are the mainstay in the first few weeks.
- Monitoring: inflammatory markers and CK
- Repeat EMG studies/MRI or biopsy may be needed.
- Long term: MTX or AZA.
- Rituximab can be effective.
- Intravenous immunoglobulin is also effective
- DM, sun-protection is important and HCQ may also reduce the rash.
For most patients, DM and PM are long-term conditions
6.
- ~ normal inflammatory markers
- upper oesophagus has striated muscle so swallowing may be affected (risk of aspiration pneumonia)
- Diaphragmatic involvement may lead to respiratory failure
- Many patients also develop inflammatory lung disease
- DM: inc risk of malignancy especially in the 2-3 years before and after the diagnosis of DM
- DM rash is photosensitive and often leads to post inflammatory hyper- or hypo- pigmentation. It initially appears in light exposed areas such as the scalp, face and neck.
- It takes the form of linear plaques on the dorsal aspects of the hands (Gottron’s papules). Patients may also have dilated nail-fold capillaries, dry cracked palms and fingers (“mechanics hands”)
- Periorbital oedema is common, and a violet rash to the eyelids (heliotrope rash) is less common.
- Patients with scleroderma and SLE can develop myositis
7.
- polymyositis – shoulders, hips and thigh muscles
- dermatomyositis – muscles + rash
- post-infectious reactive myositis – post viral infections and causes the muscles to become inflamed; this type of myositis is usually mild and settles without treatment
- inclusion body myositis (IBM) – weakness in the quadriceps (main thigh muscles), weakness in the forearm muscles that flex the fingers, and weakness in the muscles below the knee, which can cause foot drop, making it difficult to lift the front part of your foot and toes and causing the foot to drag on the ground when walking; IBM is more common in men and tends to occur after the age of 50
Fibromyalgia
- What is it?
- Pathogenesis
- Symptoms and signs
- Risk factors
- Treatment
- Investigations
- disorder of central pain processing characterized by chronic widespread pain in all 4 quadrants of the body (both sides and above and below the waist). Allodynia, a heightened and painful response to innocuous stimuli, is often present.
2.
- Induced by deliberate sleep deprivation - EEG studies show reduced REM sleep and delta wave sleep.
- This causes hyper-activation in response to noxious stimulation, and neural activation in brain regions associated with pain perception in response to non-painful stimuli.
- Not restricted to pain
- joint/muscle stiffness
- profound fatigue
- unrefreshed sleep
- numbness
- headaches
- irritable bowel/bladder syndrome
- depression and anxiety
- poor concentration and memory “fibrofog”
- female:male=9:1
peak age of onset 40-50
onset may have an obvious trigger – emotional or physical e.g. painful arthritis
- depression, fatigue, and sleep disturbance.
- simple measures to improve sleep and PAL
- Drug treatment is mainly with low dose amitrypytline
- Pregabalin may be effective
- Opiates are not recommended. Cognitive behavioural therapy is effective too
- Blood tests:
ESR, CRP, FBC, U+E, LFT, Ca, CK and TFT
Giant cell arteritis/temporal arteritis
a. symptoms
b. management
1. What is Giant cell arteritis and who is affected?
2. What are the risk factors?
3. What are the symptoms?
4. How is diagnosis made?
5. How is it treated
- Chronic vasculitis of large- and medium-sized vessels, >50
- Median age of onset is 72
- ~ causes inflammation of arteries originating from the arch of the aorta
- Anterior ischemic optic neuropathy (AION) & acute visual loss
- Visual symptoms (emergency)
- jaw claudication and tongue discomfort
- GCA may present as CVA
- Chronic vasculitis of large- and medium-sized vessels, >50
- >90% are >60 yr old
50% have PMR
F>M
-
Headache 70%
- Often localized, unilateral, boring, or lancinating in quality over the temple
- Jaw claudication upon mastication is highly suggestive
- Constitutional symptoms are common
-
Headache 70%
- Visual symptoms include amaurosis fugax, blindness, diplopia and blurring
-
Scalp tenderness, especially over the temporal artery
4. Presence of any 2 or more of the following in patients >50 years with: - Raised ESR, CRP or PV (plasma viscosity)
- New onset of localized headache
- Tenderness or decreased pulsation of temporal artery
- New visual symptoms
- Biopsy revealing necrotizing arteritis
-
Prednisolone 60–100 mg PO per day for at least 2 weeks before considering tapering down slowly
- For acute onset visual symptoms, consider 1g methylprednisolone IV pulse therapy for the 1–3 days
- Low-dose aspirin therapy to reduce thrombotic risks
-
Prednisolone 60–100 mg PO per day for at least 2 weeks before considering tapering down slowly
Gout
- What is gout and what causes it?
- What are the risk factors for gout?
- How is it treated?
- Did you know….?
- crystal? effects? Causes of pseudogout? Cause? Light microscopy? Xray findings?
- what are tophi?
- What do you see in gout
- Ix
- inflammatory arthritis, hyperuricemia
1st metatarsophalangeal joint is most commonly involved at presentation (podagra)
Deposition of monosodium urate:
- acute and chronic arthritis
- soft-tissue masses called tophi
- urate nephropathy
- uric acid nephrolithiasis
After an initial flare, a second flare occurs in ~60% of patients within 1 year and 78% within 2 years of the initial attack.
Gout is associated with a high risk of CVD.
- Non-modifiable factors
Age >40 years, Male
Modifiable factors
Increased purine uptake (meats and seafood) Alcohol intake (especially beer)
High fructose intake
Obesity
Congestive heart failure
Coronary artery disease
Dyslipidemia
Renal disease
Organ transplant
Hypertension
Smoking
Diabetes mellitus
Urate-elevating medications e.g. diuretic, ACE inhibitors, beta-blockers, ciclosporin, diuretics, pyrazinamide, ritanovir, tacrolimus, and lead exposure.
-
General Prevention:
Maintain optimal wt
Regular exercise
Diet modification (reduce purine-rich foods)
Reduce alcohol consumption (beer and liquor), Smoking cessation
Maintain fluid intake and avoid dehydration
Specific approach:
- 1st in acute gout: NSAIDs, oral/IM steroids, colchicine
- Chronic: allopurinol and febuxostat (both are xanthine oxidase inhibitors and reduce urate formation)
Benzbromarone and sulfinpyrazone are used less commonly as more s/e. They act to increase renal excretion of uric acid.
Aim to reduce SUA to < 360micromol/L
- MSU crystals found in synovial fluid aspirate are pathognomonic for gout.
Pharmacologic treatment should begin within 24 hours of acute gout flare
Asymptomatic hyperuricemia does not require treatment
negatively birefringent needles
- Calcium pyrophosphate crystals, mainly occurs in older women with OA, negative bifringement rhomboid, chondrocalcinosis
- Tophi (firm, white nodules under translucent skin).
~10 years after the first attack of acute gout for tophi to develop
extensor joint aspects e.g. elbow or knee, or Achilles tendon. They can occur in other areas such as the helix of the ears or dorsum of hands or feet.
They are usually pain-free but can become inflamed, infected or ulcerated, or discharge white material.
No initial investigations are required -> with typical gout-like symptoms + no suspicion of other conditions, e.g. septic arthritis
Ongoing follow up of people with gout-like symptoms:
Joint fluid MS&C:
Serum uric acid (SUA) ~ measured 4–6wksafter an acute attack of gout to confirm hyperuricaemia:
The formation and deposition of monosodium urate crystalsoccur when urate levels are > 380 micromol/L.
Gout may be present without hyperuricaemia and a normal level of urate does not exclude the diagnosis. Normal levels are often found during an acute flare of gout, when plasma urate levels may fall to normal.
Joint X-ray:
Plain radiographs are often normal.
Non specific soft tissue swelling and subcortical cystsmay be present.
Advanced disease may demonstrate bone erosion.
Screen for CVS risk factors and renal disease
- normal joint space, PUNCHED OUT/periarticualr erosions, soft tissue swelling
Management of acute gout?
When does it resolve?
Follow up?
2 wks (if treated, significant improvement in pain is usually experienced within 24 hrs, and resolution is often within 2-7 days)
Follow up (4-6wks)
+ Check SUAL
+ Measure BP & repeat blood testing for HbA1c, renal function, & lipid profile (manage & lower)
+ Discuss the use of urate-lowering therapy (ULT) ULT = allopurinol & febuxostat
- Who should be considered for urate lowering therapy
- DD for gout
- Management using rapriop
+ Septic arthritis: any person who is systemically unwell (with or without a temperature) and an acutely painful, hot, swollen joint.
+ Bursitis, cellulitis, tenosynovitis.
+ Non-urate crystal-induced arthropathy, e.g. pseudogout
+ OA
+ Psoriatic arthritis
+ Reactive arthritis
+ Rheumatoid arthritis
+ Haemochromatosis
+ Trauma
- R: uric acis deposits in joint space
A: maintain healthy wt, avoid sugary foods, alchol, smoking, hydration, Vit C supplementation, ice,
P: stop Bendroflumethiazide
R:
I: xray of joint joint aspirate and cytp;ogy
O: BP 3mnthly
Serum UAL 6wks after flare up, U&Es, LFTs, lipids, HbAC1
P: manage CVD risk
What is the most important Ix for monoarthritic presentation?
How can the pattern of joint involvement provide clues?
- What is hypermobility spectrum disorder?
- Who gets it?
- Symptoms and signs
- Rx
- What is the Beighton score
- The heritable connective tissue disorders include
- Pain syndrome in people with joints that move beyond normal limits (“double-jointed”).
It is due to laxity of ligaments, capsules and tendons. It is thought that the origin of pain is from microtrauma.There is no genetic test for this.
- Often familial.
More common in women and Asian people.
It usually presents in childhood or young adulthood. Recurrent subluxations or dislocations may feature. - Pain around the joints, worse after activity
Other features:
- soft tissue rheumatism e.g. epicondylitis
- abnormal skin: papyraceous scars,
- hyperextensible, thin, striae
- marfanoid habitus
- arachnodactyly
- drooping eyelids, myopia
- hernias and uterine/rectal prolapses
4.
Non-drug therapy
- strengthening exercises to reduce joint subluxation
- Work on posture and balance may also be needed.
- Splinting and even surgical interventions may be needed.
- Advice on pacing and goal setting may be helpful.
- Specialist pain management input is often needed.
Pharmacological therapy
- Paracetamol should be the mainstay.
6. HSD, Marfan syndrome and Ehlers Danlos syndrome
- What is osteoarthritis?
- Cause
- RF
- Symptoms and signs
- Ix
- Rx
- degenerative,
progressive loss of articular cartilage,
new bone formation and capsular fibrosis
- Failure of normal cartilage subject to abnormal or
incongruous loading for long periods
Damaged/defective cartilage failing under normal conditions of loading
Break up of cartilage due to defective stiffened subchondral bone passing more load to it
Key features of cartilage in OA:
loss of elasticity with a reduced tensile strength
cellularity and proteoglycan content are reduced
- >65
Women > men
Obesity
Trauma
- The hip, knee and spine most commonly affected. Pain is provoked by movement and by weight- bearing. At first it is intermittent, but later may be constant. At the knee, inactivity gelling and a feeling that the joint will give way are common.
- Xray: loss of joint space, osteophytes, subchondral cysts, sclerosis
- wt loss, insoles, walking stick
PT
Topical NSAIDs and topical rubefacients and capsaicin can be helpful.
Intra- articular corticosteroids can be offered.
Features of vasculitis
PMR
Features
Ix
Rx
- What is it?
- Who is affected?
- What are the symptoms?
- How is diagnosis made?
- Treatment
- pain and stiffness of the shoulder, hip girdles, and neck
- Incidence increases with age.
- Average age of onset ~70 years
- Rare in people <50 years of age
- Is associated with GCA
- Incidence increases with age.
- History:
- Suspect PMR in elderly patients with new sudden onset of proximal limb pain and stiffness (neck, shoulders, hips).
- Difficulty rising from chair or combing hair (proximal muscle involvement)
- Night time pain
- Systemic symptoms in ~25% (fatigue, weight loss, low-grade fever)
Physical exam:
- Decreased ROM of shoulders, neck, and hips
- Muscle strength is usually normal—may be limited by pain and/or stiffness.
- Muscle tenderness
4. Typical history and exam supported by finding raised inflammatory markers
Check either ESR or PV as well as CRP
Consider temporal artery biopsy if symptoms of GCA
5.
- Expect a dramatic (diagnostic) response within 5 days of starting prednisolone.
- 15 mg of prednisolone daily
- Methotrexate can be steroid-sparing in relapsing patients.
- Most patients require 18 months of treatment with prednisolone
What are yellow flags
- What is Raynaud’s’ phenomenon?
- What is Raynaud’s syndrome?
- What diseases are associated with Raynauds phenomenon
- Rx
- Complications
- Did you know….?
1.
- Vasospasm
- Painful
- sequence of colour changes in response to a cold stimulus
- precipitated by stress.
- white- inadequate blood flow
- blue -venous stasis
- red -re-warming hyperaemia
- term is used when Raynaud’s phenomenon is idiopathic.
Common in young women and may improve as they get older. It may be familial.
Treatment comprises measures to keep warm and to avoid smoking.
- picture - dermatomyositis and polymyositis
4.
keep warm and to avoid smoking
CCB (1st) NIFEDIPINE
Phosphodiesterase-5 inhibitors, and prostacyclins are usually effective. (sildenafil)
- digital ulcers, severe digital ischaemia and infection
6.
- Episodes usually last minutes. Pattern is symmetrical and bilateral; tissue necrosis is rare.
- Underlying disease, episodes may last for hours and the pattern is often asymmetrical, with only a few digits affected
- Nail-fold capillaroscopy is non-invasive and available in many rheumatology units. It is useful in diagnosis of scleroderma and DM. This imaging tool enables evaluation
Rheumatoid arthritis
- Pathophysiology
- Hx
- Examination
- Ix
- image
- Usually female (3:1), 30 – 50 years old, presenting with progressive, peripheral and symmetrical polyarthritis. Usually affects MCPs/PIPs/MTPs and typically spares DIPs (cf OA) but may affect any joint inc hips/knees/shoulders/c-spine. Must have hx ≥ 6 weeks for ∆.Morning stiffness > 30 mins duration.Commonly c/o fatigue/malaise.
3.
- Soft tissue swelling and tenderness first.
- Ulnar deviation/palmar subluxation of MCPs.
- Swan-neck & Boutonnière deformity to digits.
- Rheumatoid nodules – most common at the elbow.
- Check median nerve – carpal tunnel association.
4.
- RF & anti-CCP
- FBC – normocytic anaemia (chronic disease),
WCC if concerns re septic arthritis.
- Inflammatory markers – elevated
- X-ray changes apparent in established disease –
USS/MRI more sensitive in early disease
- Other investigation guided by history & exam e.g.
may need PFTs and HRCT chest if lung involvement (e.g. pulmonary fibrosis).
RA
- Diagnostic criteria
- Rx
RA
managment
etanercept TB
all DMARDS myelosupression
if giving methotraxate (inhibits dihydrofolate reductase no purines/pyrimadines) must give folic acid
remember that woman who had shingles in the clinic and she said she couldnt take aspirin because of her having RA
Interactions
avoid prescribing trimethoprim or co-trimoxazole concurrently - increases risk of marrow aplasia
high-dose aspirin increases the risk of methotrexate toxicity secondary to reduced excretion
DMARDS take 6-12wks to start working so then give steroids
RA
extraarticular manifestations
Sjogren’s syndrome
- what is it?
- Common symptoms and signs
- Ix
- Rx
- The most common diseases associated with SS are?
Associated with other autoimmune conditions- ?
5-10% life time risk of ?
Pregnant patients with anti Ro/SS-A anti bodies are at risk of ?
Biopsy is characteristic - focal lymphocytic infiltration of exocrine glands.
- Chronic autoimmune inflammatory disorder
dec lacrimal and salivary gland secretion
Primary form - not associated with other diseases
Secondary form- associated with another underlying rheumatic disease
More than 80% are women
- Madfred!
Myalgia
Arthralgia
Dry Mouth
Fatigue
Raynaud’s phenomenon
Enlarged parotids
Dry eyes
Most patients present with sicca symptoms- xerophthalmia (dry eyes), xerostomia (dry mouth), and fatigue.
- Anti Ro and Anti La Antibodies – 90% of patients RF & anti ds-DNA antibodies may be seen
Schirmer’s test- measures tear volume
Salivary gland biopsy may be needed
- Essentially symptomatic
Avoid dry or smoky atmospheres
Dry eyes–artificial tears
Dry mouth -artificial saliva, sugar free gum/pastilles
Skin emollients,
vaginal lubricants
Immunosuppressants/steroids rarely needed
- RA and SLE
Coeliac disease, Primary Biliary Cirrhosis, Auto immune thyroid disease
B cell lymphoma!
fetal loss, complete heart block in the fetus, and neonatal lupus syndrome in the newborn
- What are the spondyloarthropathies?
- What is Schobers test?
- Ankylosing spondylitis Ix & Rx
- Psoriatic arthritis
Affects ? of patients with psoriasis (M = F)
Exam findings: oligo-arthritis with ? or “sausage” digit.
Can be symmetrical arthritis like RA, or mono-arthritis.
Severe deformities (arthritis mutilans in 5%).
Investigations: ?
Rx:
- Reactive arthritis what is it?
Presentation:
Other features: skin (circinate balanitis, keratoderma blennorrhagica), eye (conjunctivitis, uveitis), enthesitis.
Ix:
Rx:
- Enteropathic arthritis
10 - 20% of those with IBD develop arthropathy. Of these 2/3 = peripheral arthritis and 1/3 develop axial disease.
2 types of peripheral disease: ?
Rx:
- Extra-articular manifestations of Ankylosing spondylitis – All the As!
These are a group of conditions that affect the spine and peripheral joints and are associated with the presence of HLA-B27.
They comprise: PEAR
- Ankylosing spondylitis (most common)
- Enteropathic arthritis
- Psoriatic arthritis
- Reactive arthritis
common clinical features:
- Sacroiliac/axial disease (back/buttock pain)
- Inflammatory arthropathy of peripheral joints
- Enthesitis (inflammation at tendon insertions)
- Extra-articular features (skin/gut/eye)
Ankylosing spondylitis
- mark skin 10cm above and 5cm below PSIS, bend forward with straight legs, distance increase to >20cm is normal), reduced chest expansion
- Ix: MRI spine and SI joints (more sensitive than X-ray).
Rx: NSAIDs and PT, TNF inhibitors, IL-17 inhibitors
MISS DMARDS STRAIGHT ONTO BIOLOGICS
- 10%
dactylitis: inflammation of an entire digit (a finger or toe), and can be painful
CRP often raised. Central joint erosions seen early on u/sd or MRI leading to ‘pencil in cup’ x-ray appearance.
NSAIDs, DMARDs, TNF inhibitors, IL-17 inhibitors, IL12/23 inhibitors.
- Sterile synovitis developing after a distant infection either post dysentery (Salmonella / Shigella / Campylobacter) or following urethritis/cervicitis (Chlamydia trachomatis)
few days – 2 wks post infection, acute asymmetrical lower limb arthritis develops.
skin (circinate balanitis, keratoderma blennorrhagica), eye (conjunctivitis, uveitis), enthesitis
serology/microbiology, inflammatory markers raised, may need joint aspirate to rule out septic/crystal arthritis
Rx: treat infection (this may not improve arthritis). NSAIDs and joint injections. Most will resolve within 2 years. Those that do not (esp if HLA-B27+) may need DMARDs.
- Type 1 = oligoarticular, asymmetric and has a correlation with IBD flares
Type 2 = polyarticular symmetrical and less correlation with IBD flares
Rx: Remember NSAIDs may flare IBD. Consider DMARDs. TNF inhibitors will treat both the bowel disease and the arthritis.
SLE
- Ix
- Rx:
- Fx9 > M
Peak age of onset is in early adulthood
Estrogens are thought to be permissive for autoimmunity.
Estradiol may prolong the life of autoreactive B and T lymphocytes.
UV light triggers SLE: it alters the structure of DNA in the dermis which renders it more immunogenic.
Drugs that trigger an SLE-like syndrome include isoniazid, minocycline and TNF inhibitors
FBC is a simple diagnostic clue because it is abnormal in most patients
ESR and plasma viscosity are raised in most patients but CRP is normal
People of colour have a worse prognosis SLE is associated with a high CVD risk
1.
- raised ESR or plasma viscosity
- Anaemia and leukopenia are common
- 95% patients are antinuclear antibody positive Anti-Ro, Anti-La are common
- Anti- dsDNA titre rises with disease activity
- Antiphospholipid antibodies increase the risk of pregnancy loss and thrombosis
- C3 and C4 fall with disease activity
- Urinalysis is vital for detecting renal disease
- Skin biopsy can be diagnostic
- Renal biopsy can be diagnostic and can help prognosticate
2.
- Sun protection
- Advice on healthy lifestyle in view of cardiovascular risk
- Hydroxychloroquine is helpful for rash and arthralgia
- Mycophenolate mofetil, azathioprine and rituximab are commonly used too
- Short courses of prednisolone for flares
Systemic sclerosis/ scleroderma
- What is systemic sclerosis
- Common symptoms and signs
- Multisystem autoimmune disease.
Increased fibroblast activity resulting in abnormal growth of CT which leads to vascular damage and fibrosis.
2 main sub types:
limited SSc diffuse SSc
- Limited Scleroderma
Also known as CREST syndrome.
Usually many years of Raynaud’s symptoms before any scleroderma (skin thickening). Development of PA hypertension after a mean of 10 years of symptoms.
CREST syndrome
- Calcinosis Cutis
- Raynaud’s phenomenon
- Eosophageal dysmotility
- Sclerodactyly
- Telangiectasia
Diffuse Scleroderma
Less common. Higher risk of mortality. Characterised by sudden onset of skin involvement, and is proximal to the elbows and knees
Osteoporosis
- What is OP
- RF
- How is diagnosis made?
- What is a Z score?
What pathologies on an Xray may make you query osteoporosis
- Rx
- s/e of alendronic acid
- Reduced bone density
-
Non-modifiable
- Advanced age (>65 years)
- Female
- Caucasian or south Asians
- FHx of osteoporosis-genetic
- History of low trauma fracture (fall from standing height or less, at walking speed or less)
Modifiable
- Low body weight (58 kg or body mass index [BMI] <21)
- Premature menopause (age<45)
- Calcium/vitamin D deficiency
- Inadequate physical activity
- Cigarette smoking
- Excessive alcohol intake (>3 drinks/day)
- Iatrogenic: e.g. corticosteroids, aromatase inhibitors
3.
- Dual energy x-ray absorptiometry (DEXA) of the lumbar spine and hip is considered the gold standard for the diagnosis of osteoporosis.
- T-score is the number of SDs from the mean bone density of persons of same gender at age of peak density (25 years)
- T-score -2.5 or less = osteoporosis
- Normal BMD = T-score ≥ −1
-
Osteopenia = T-score between −1 and −2.5
4. - The Z-score is a comparison of the patient’s BMD with an age- & gender-matched population. - A Z-score <−2 should prompt evaluation forcauses of secondary osteoporosis.
- Plain radiographs lack sensitivity to diagnose osteoporosis, but rib fractures or vertebral compression fractures without trauma history should prompt evaluation for osteoporosis.
5.
Risk modification: weight-bearing exercise, vitamin D3 supplementation (800-2000 IU/day), limiting alcohol, and smoking cessation. Dietary advice regarding calcium intake; supplements if needed.
For osteoporosis
Vitamin D ± calcium supplementation plus:
1st line: Oral bisphosphonates, or IV if oral not tolerated.
2nd line: Denosumab or teriparatide
Bisphosphonates e.g. alendronate, risedronate and etidronate
MOA: inhibit osteoclasts
s/e:
- oesophageal reactions: oesophagitis, oesophageal ulcers (especially alendronate)
- osteonecrosis of the jaw
- increased risk of atypical stress fractures of the proximal femoral shaft in patients taking alendronate
- acute phase response: fever, myalgia and arthralgia may occur following administration
Strontium ranelate
MOA: ‘dual action bone agent’ - increases deposition of new bone by osteoblasts (promotes differentiation of pre-osteoblast to osteoblast) and reduces the resorption of bone by inhibiting osteoclasts
increased risk of cardiovascular events, thromboembolic events, Stevens Johnson syndrome
Raloxifene - selective oestrogen receptor modulator (SERM)
has been shown to prevent bone loss and to reduce the risk of vertebral fractures, but has not yet been shown to reduce the risk of non-vertebral fractures
has been shown to increase bone density in the spine and proximal femur
may worsen menopausal symptoms
increased risk of thromboembolic events
may decrease risk of breast cancer
Denosumab
human monoclonal antibody that inhibits RANK ligand, which in turn inhibits the maturation of osteoclasts
given as a single subcutaneous injection every 6 months
initial trial data suggests that it is effective and well tolerated
Teriparatide
recombinant form of parathyroid hormone
very effective at increasing bone mineral density but role in the management of osteoporosis yet to be clearly defined
Hormone replacement therapy
has been shown to reduce the incidence of vertebral fracture and non-vertebral fractures
due to concerns about increased rates of cardiovascular disease and breast cancer it is no longer recommended for primary or secondary prevention of osteoporosis unless the woman is suffering from vasomotor symptoms
Hip protectors
evidence to suggest significantly reduce hip fractures in nursing home patients
compliance is a problem
Falls risk assessment
no evidence to suggest reduced fracture rates
however, do reduce rate of falls and should be considered in management of high risk patients
Osteoporosis - prevention of fragility fractures
Who should I assess for fragility fracture risk?
- Consider assessing fracture risk for people taking the following medication, especially in the presence of other Risk factors:
Additional investigations to exclude an underlying cause for fragility fractures and osteoporosis.
The QFracture® and FRAX® risk assessment tools predict the absolute risk of hip fracture, and major osteoporotic fractures (spine, wrist, or shoulder) over 10 years.
women 11.1%
2.6%
QFracture risk
