Rheumatology Flashcards
RA definition
Associations
Clinical presentation
Signs
Extra-articular manifestations
Chronic multisystem inflammatory disorder of unknown cause with characteristic symmetrical, deforming peripheral polyarthritis, chiefly manifesting as synovitis
Associations
• Smoking
• Goes into remission during pregnancy
Clinical presentation
• Symmetrical joint pain, stiffness, swelling – these 3 indicate synovitis
o Stiffness worse in the morning (>1hr)
• Usually small joints of the hand (PIP’s, MCPs, Wrists) and feet (MTPs) followed by larger joints
• Systemic: Malaise, weight loss, low grade pyrexia
• Onset insidious over weeks/months (10-20% acute)
Signs
• Symmetric polyarthritis affecting small joints of hand +/- deformity
• Tenderness/swelling/warmth/redness of joints (synovitis or fluid)
o Synovitis – boggy joint swelling
• Rheumatoid nodules (hands, elbows, ears lungs)
• Later: Ulnar deviation of fingers, dorsal wrist subluxation, Boutonniere and Swan neck, Z thumb
Extra-articular manifestations
Respiratory Pulmonary fibrosis, pleural effusions, Pulmonary nodules
Felty’s syndrome Triad of RA, Splenomegaly + Leukopenia (SANTA)
Skin Nodules, Palmar Erythema, Vasculitis (rare but can have mesenteric, cerebral etc.)
Eyes Keratoconjunctivitis sicca, Episcleritis, Scleritis
Secondary Sjogren’s syndrome (+ dry mouth)
Cardiac Pericarditis/Pericardial effusion
Bone Osteoporosis
Renal Membranous nephropathy, Secondary amyloidosis
Haem Anaemia of chronic disease (normocytic, normochromic)
Felty’s syndrome: Triad of RA, Splenomegaly + Leukopenia
Neuro Carpal tunnel syndrome (entrapment due to synovitis), Peripheral neuropathy, Mononeuritis multiplex
Amyloidosis
Atlanto-axial joint subluxation – endangers spinal cord - must do AP and latera imaging pre-procedures
RA investigations
Diagnostic criteria
Monitoring of RA
• FBC, CRP + ESR (If acutely raised, can suggest a flare)
• RF: Autoantibody (IgM/IgA/IgG) against Fc portion of IgG. +ve in 75% of RA
• Anti CCP(cyclic citrullinated protein): More specific
o Seropositivity indicates a more progressive disease
• LFTs: Medications may have toxicity in liver
• Renal function: Extra articular manifestations, some medication excreted renally
X- Ray o Loss of joint space o Erosions o Soft tissue swelling o Soft bones (osteopenia) US /MRI allow much earlier radiological diagnosis
Diagnosis: ACR/EULAR Criteria - 6/10 (1) Joint distribution (0-5) 1 large joint 0 2-10 large joints 1 1-3 small joints (large joints not counted) 2 4-10 small joints (large joints not counted) 3 >10 joints (at least one small joint) 5 (2)Serology (0-3) -ve RF AND -ve ACPA 0 Low +ve RF OR low +ve ACPA 2 High +ve RF OR high +ve ACPA 3 (3) Symptom duration (0-1) <6 weeks 0 6 weeks 1 (4) Acute phase reactants (0-1) Normal CRP AND normal ESR 0 Abnormal CRP OR abnormal ESR 1
Monitoring: DAS28
RA Management
Initial management
MDT: PT/OT, Podiatry, Rheumatologists, CNS’s, GP, Neuro, Sugeons • Exercise + Physio + OT • Pharmacological o NSAIDS o DMARDs - within 3 months of symptoms o Biologics o Steroids • Surgical: May relieve pain, improve function and prevent deformity
General approach
Early, aggressive approach
Symptom relief: NSAIDs, PT
Acute flare: Corticosteroids
Initial therapy
DMARD monotherapy +/- a short-course of bridging prednisolone. In the past dual DMARD therapy was advocated as the initial step.
OA Management
- MDT + holistic approach
• Weight loss, Exercise, PT
• Paracetamol, TOPICAL NSAIDs
• Podiatry: shoes with good support - Medications - Analgesia
• Oral NSAIDs, Opioids, Capsaican cream – WHO pain ladder
• Intraarticular injections (steroids or hyaluronic acid)
• Capsaicin cream or other topical analgesics - Criteria for referral for Joint Replacement Surgery (arthroplasty) = definitive treatment
1) Pain – limits walking, present at night, dependent on strong analgesia
2) X-rays - significant changes
3) Failed conservative management
What are seronegative spondyloarthropathies?
Name their features and the conditions
RF and ant CCP -ve. 3 key common features:
1) Axial skeleton inflammation e.g. sacrolillitis
2) Enthesitis – inflammation of tendon insertions
3) HLA-B27 association
Conditions
1) AS
2) Psoriatic arthritis
3) Reactive arthritis
4) Enteropathic arthritis
Ankylosing Spondylitis definition
Clinical presentation
Signs
Extra-articular manifestations
Chronic inflammatory disease of the spine, sacroiliac and axial joints
• Chronic Sacroiliitis
• Seronegative as RF -ve
Epidemiology • M:F = 2-3:1 • >95% AS patients are B27+ve • American Indians > Caucasians > Afro Caribbean/Oriental Presents at 20-30yo
Clinical presentation
• Insidious onset of Lower back pain + stiffness peristing >3 months
• Early morning stiffness, worse with rest + improves with exercise
• Reduced spinal movements – hyperextended neck, Loss of lumbar lordosis, Flexed hips and knees
• Peripheral arthritis (rarely at outset) but enthesitis common
o Plantar fasciitis, Achilles Tendonitis
• Fatigue
Signs
• Tender sacroiliac joints
• Restricted lumbar spinal movements (Schober’s test) - a line is drawn 10 cm above and 5 cm below the back dimples (dimples of Venus). The distance between the two lines should increase by more than 5 cm when the patient bends as far forward as possible
• Reduced lateral flexion
• Increased Occiput-Wall distance (>5cm)
• Reduced chest expansion
• Stooped Posture (loss of lumbar lordosis, thoracic kyphosis, cervical extension)
• Peripheral joint arthritis
• Enthesitis (Achilles tendon, plantar fascia)
Extra-articular manifestations • Atlantic axial instability • Anterior uveitis • Atypical lung fibrosis: Also caused by TB, Sarcoid • Aortic regurgitation • AV conduction defects • Amyloidosis - IgA nephropathy • Autoimmune bowel disease and UC?
AS
Investigations
Management
Chronic inflammatory disease of the spine, sacroiliac and axial joints
• Chronic Sacroiliitis
• Seronegative as RF -ve
Investigations • Bloods o Normocytic anaemia o HLA B27 +ve o ESR/CRP: can be normal • Imaging o MRI most useful: Irregularity (erosions), sclerosis of SI joints followed by fusion Squaring of vertebral bodies, Romanus lesion Syndesmophytes (ossification of the annulus fibrosis) Spinal fusion: Bamboo spine • Specialist tests o Slit lamp examination of eyes
Management
• 1st line: Simple analgesic, NSAIDs + PT (crucial), Support group
• Biologics (if BASDAI >4)
o anti-TNF works in most (after 2 NSAIDs tried 12 weeks apart)
o Secukinumab (anti-IL-17 mAb)
• DMARDs and steroids only work for those with peripheral joint disease – don’t work in spine!!
o Periph. Joint Disease Sulphasalazine
• Surgery has little role except occasionally in fusing painful or unstable bits of spine
Psoriatic arthritis definition
Clinical presentation + Signs
Patterns of joint disease
Investigations
Management
Inflammatory arthritis occurring in association with psoriasis
Clinical presentation
• Psoriasis precedes arthritis in 75%, synchronous in 15%, arthritis precedes in 10%
• Psoriasis (may be minor and not apparent)
• Nail changes: Pitting and onycholysis
• Arthritis – pain, stiffness in joints (Severity of arthritis reflects extent of skin disease in some patients)
arthritis mutilans (severe deformity fingers/hand, ‘telescoping fingers’)
Patterns of joint disease – 5 classic types
1) ASYMMETRIC OLIGOARTHRITIS = classic
2) Polyarthritis (mimics RA)
3) DIP joint arthritis (mimics OA)
4) Axial arthritis (mimics AS)
5) Arthritis mutilans – destructive bone eating form, causing ‘telescoping of the digits
Investigations
• Acute phase response – often normal
• RF -ve (usually)
• X-Rays (Depends on the disease pattern)
May be axial disease (similar to AS – sacroiliitis, syndesmophytes etc)
May be peripheral arthritis (similar to RA except DIP joint involvement)
Asymmetric involvement
o May be asymptomatic erosions in feet so x-ray both hands and feet
?Pencil in cup abnormality?
Management
• Peripheral joint disease – mild: PT,OT, Podiatery NSAIDs, consider steroid injections
• Progressive peripheral joint disease: DMARDs, NSAIDs, PT, Steroid injections
o DMARDs:
Methotrexate or Leflunomide (both help skin)
Sulfasalazine
o 2nd line: Biologics - anti-TNF (Adalimumab), Ustekinumab (Anti Il-12 + 23 monoclonal Ab), Secukinumab (Anti Il-17 monoclonal antibody)
o “Targeted synthetics” – Apremilast (PDE4 inhibitor)
Reactive arthritis definition
Clinical presentation + Signs
Patterns of joint disease
Investigations
Management
Sterile joint inflammation initiated by infection in which the CAUSATIVE ORGANISM CANNOT BE ISOLATED FROM JOINT.
Triad: reactive arthritis, urethritis, conjunctivitis.
Clinical presentation + Signs
• Arthritis developing 3-30 days post GI/GU infection
• Usually self-limiting but recurrent episodes may occur – in most resolution within 2-6 months
• Chronic symptoms in up to 20%
• Associated features
o Conjunctivitis
o Urethritis - Burning or stinging passing water,
o Lower back pain (sacroiliitis)
o Painful heels (enthesitis, plantar fasciitis)
o Oral ulcers
o Circinate balanitis
o Keratoderma blennorrhagicum
Investigations
• ESR/CRP may be raised
• RF -ve
• HLA-B27 may or may not be positive
Management
• Simple analgesics, NSAIDs, Opiods
• Steroids – short term use (if relapse on steroid reduction DMARDs may be required e.g. sulfasalazine 1st line)
• Biologics – anti TNF-alpha effective in some patients
Enteropathic arthritis definition
Clinical presentation + Signs
Patterns of joint disease
Investigations
Management
Arthropathies associated with pathology in the large and small bowel
• IBD mainly (Chron’s, UC)
• Infectious enteritis (Reactive Arthritis)
• Intestinal bypass surgery
• Whipple’s disease (Caused by Tropheryma whippelii)
• Coeliac disease
Clinical presentation
• Arthralgia but usually much less arthritis
• Asymmetrical pauci-articular arthritis
• Knee/ankle>Upper limb
• Spondylitis may occur (similar to AS)
• Associated features
o Enthesitis
o Anterior Uveitis
o Skin lesions (erythema nodosum, pyoderma gangrenosum)
o Clubbing and other manifestations of IBD
Investigations
• FBC: May have Fe deficiency or anaemia of chronic disease
• LFTs: May be abnormal in association with iBD
• CRP/ESR: Raised
• RF: -ve usually
• Haematinics (low iron, low ferritin), low vit D (poor absorpition)
• X-Rays: non erosive osteopenia
• Endoscopy
Management
(1) Treat IBD
(2) Medications
Simple analgesics, NSAIDs (may exacerbate IBD), opiods
DMARDs
• Sulfasalazine (mesalazine) useful in IBD because the ‘sulfa’ treats the join and the ‘salazine’ treats the bowels!
• Methotrexate or Azathioprine
‘Biologics’
• Infliximab / adalimumab (etanercept doesn’t work on the bowel)
Steroids only for acute flares
Surgery - colectomy for refractory UC, avoided wherever possible in Crohn’s disease
What is amyloidosis
Types
- Involvement
- Presentation
- Management
Diagnosis
Group of disorders characterised by extracellular deposits of a protein in abnormal fibrillar form, resistant to degradation
Types
(1) AL amyloid (primary amyloidosis)
- kidneys (proteinuria and nephrotic syndrome), heart (restrictive cardiomyopathy, arrhythmia, angina), nerves (peripheral and autonomic neuropathy), cut (macroglossia, malabsorption/weight loss, perforation, haemorrhage, obstruction and hepatomegaly)nerves (peripheral and autonomic neuropathy), GI (macroglossia, malabsorption/weight loss, perforation, haemorrhage, obstruction and hepatomegaly), vascular (Purpura, especially peri-orbital)
- associated with myeloma
- Rx: optimise nutrition; oral melphalan + prednisolone extends median survival from 13 months to 17
(2) AA amyloid (secondary amyloidoses)
Amyloid derived from amyloid A, an acute-phase protein, reflecting chronic inflammation in RA, UC/Chron’s, familial Mediterranean fever and chronic infections - TB, bronchiectasis, osteomyelitisTB, bronchiectasis, osteomyelitis
- kidney, liver, spleen affected
- may present with proteinuria, nephrotic syndrome or hepato-splenomegaly
- Macroglossia not seen and cardiac involvement rare
- Manage the underlying condition optimally
Diagnosis: biopsy of affected tissue and positive conger red stain with a red green birefringence under polarised light microscopy
- isotope scan will also show areas of deposition
What is Behcet’s disease
Features
Diagnosis
Management
Systemic inflammatory disorder of unknown calls, associated with HLA-B5/B51
Features
Cardinal feature equals oral ulceration. Diagnosis requires oral ulceration and any two of:
- Genital ulcers
- Defined eye lesions (including anterior/posterior uveitis or retinal vasculature)
- Defined skin lesions (erythema nodosum, popular pet pustular lesions)
- Positive skin pathergy test
- Oral ulcers – Aphthous or herpetiform
Other manifestations: mono/poly arthritis affecting knees, ankle, wrists and elbows; Gastro symptoms: diarrhoea, Abdo pain and anorexia; pulmonary and renal lesions, thrombophlebitis, vasculitis and a brainstem syndrome
Diagnosis
Mainly clinical
Pathogen test: needle prick leads to papule formation within 48 hours (highly specific)
Bloods: High ESR + CRP but not antibodies
Management
Colchicine for oral/genital ulcers
Azathioprine or Cyclophosphamide for systemic disease
Gout
Definition
Presentation
Causes
Associations
Investigations
Management
Disorder of curing metabolism characterised by hyperuricaemia. Deposition of monosodium urate crystals in joints – acute arthritis
Presentation
Typically acute mono arthropathy with severe joint inflammation
– MTP joint of the big toe (pad agra)
– other joints affected: ankle, foot, small joints of hand, wrist, elbow or knee
- Can be precipitated by trauma, surgery, starvation, infection or diuretics.
Long-term (chronic tophaceous gout). Urate deposits = top e.g. in pinna, tendons and joints + renal disease (stones, interstitial nephritis may occur)
Causes
DART: Diuretics, Acohol, Renal disease, Trauma
Hereditary, high dietary purines, alcohol execess, diuretics, salicyclates, cytotoxic’s
Associations
CVD, HTN, DM, chronic renal failure
Investigations
Light microscopy of synovial fluid: negatively birefringent Urate crystals
Serum urate: May be raised
High WCC + ESR/CRP in acute attack
Radiographs: only soft tissue swelling in early stages. Later, well-defined punched out emotions are seen in juxta articular bone. No sclerosis and joint spaces are preserved until lateonly soft tissue swelling in early stages. Later, well-defined punched out erosions are seen in juxta articular bone. No sclerosis and joint spaces are preserved until late
Gout management
Acute
– NSAIDs e.g. diclofenac - continue until pain and inflammation subsides
– colchicine (if NSAIDs CI) 500 µg 2 to 3 times per day
– corticosteroids if they both don’t work
Chronic
– Allopurinol: xanthene oxidase inhibitor
- Febuxostats - 2nd line xanthene oxidase inhibitor
Pseudogout definition
Presentation
Risk factors
Investigation findings
Management
Features
- typically of larger joints in elderly patients
– usually spontaneous and self-limiting but can be provoked by illness, surgery or trauma
Polarised light microscopy of synovial fluid shows weekly positively birefringent crystals.
- Radiographs: soft tissue calcium deposit (chondrocalcinosis)
– high white cell count and ESR/CRP in acute attack
Risk factors
- Hyperparathyroidism
- Haemochromatosis
- Acromegaly
- Wilson’s disease
Management
- Acute: NSAIDs, PO/Intrarticular steroids, (colchicine doesn’t work as well)
Chronic: As for RA
Vasculitis
Definition
Classification
• Idiopathic Autoimmune-driven inflammation, caused by inflammatory cell infiltration of the blood vessel wall, resulting in fibrinoid necrosis. Often granuloma formation. Can have severe consequences
o Vessel stenosis –> occlusion and distal infarction
o Aneurysm formation –> rupture of vessels and haemorrhage
• ANCA (antineutrophil cytoplasmic antibodies) are specific for vasculitis and help classification. – They bind to enzymes in the cytoplasm of neutrophils. 2 associated antigen/antibody subtypes:
(1) Anti-P3 antibodies (a-ANCA)
(2) Anti-MPO (p-ANCA
Classifications Large: GCA/PMR, Takayasu's arteritis Medium: PAN, Kawasaki Small (ANCA+): MPA, GPA, EGPA Small (ANCA-): HSP, Essential cryoglobulinaemia
GCA
Definition
Epidemiology
Clinical features
Investigation
Management
Definition
Vasculitis of aorta and major branches with a predilection for the branches of the external carotid (especially temporal artery) and internal carotid (especially ophthalmic artery)
Epidemiology
• Occurs in the elderly (>50 but generally >60yo)
• 2x as common in women
• Often co-exists with PMR
Clinical features
• Systemic upset
• Headache (usually unilateral, temporal) + scalp tenderness
• Jaw claudication (pain on chewing food)
• Visual disturbance (blurring/loss of vision)
• Polymyalgia symptoms.
• Temporal artery/scalp tenderness, thickening and/or loss of pulsation
Investigation
The diagnosis is clinical
• Raised CRP: ESR not reliable without CRP here
• Temporal artery biopsy (ideally within 7-14d of starting steroids): Inflammatory cell infiltrates, giant cells and granulomas
o Skip lesions may occur so don’t be put off if -ve (10%)
• Anaemia: Common feature
Management
• Prednisolone
o 60mg/day for GCA
o reduce dose by weekly decrements of 5mg. Once 10mg reached, reduce by 1mg every 2-4 weeks.
• Give prophylaxis against steroid induced osteoporosis: Bisphosphonates, Calcium and Vit D + GI protection
• Monitor bloods and clinical symptoms
• Consider steroid sparing agent (eg methotrexate or azathioprine) if significant dose of prednisolone required to control disease activity
PMR
Definition
Epidemiology
Clinical features
Investigation
Management
Clinical syndrome of proximal limb girdle pain and stiffness in middle-aged/elderly patients associated with an acute phase response and a rapid response to steroids
Epidemiology
• Mean age 70
• Female: male of 2:1.
Clinical features
• Onset usually sudden but sometimes insidious
• Systemic - fever, fatigue, anorexia, weight loss
• Bilateral proximal muscle pains (shoulder girdle and pelvis) and early morning stiffness
• Synovitis sometimes can occur.
• Muscle strength normal but difficult to assess because of pain
Investigation
• No specific test – combination of clinical findings, raised inflammatory markers
• Raised CRP, (ESR), ALP, normochromic normocytic anaemia etc
Management
• Prednisolone 15mg daily - rapid improvement (24-48 hours) with subsequent normalisation of abnormal blood tests.
• If poor response, alternative diagnosis should be considered.
• Gradually reduce steroids, titrating dose with symptoms and CRP
• Be aware of steroid toxicity - bone and GI protection, diabetes, hypertension
Takayasu’s arteritis
Definition
Epidemiology
Clinical features
Investigation
Management
A granulomatous arteritis of the aorta and great vessels causing stenosis, occlusion or aneurysm of the artery.
–> HTN, Absent peripheral pulses, strokes and HF
LARGE VESSEL VASCULITIS
Epidemiology
• Most common in Asia, particularly Japan.
• 9 x more common in female
• Seen in young adults up to the age of 40.
Clinical features
• Systemic: fever, weight loss, arthralgia
• Occlusive symptoms due to ischaemia
• Vascular: Claudication of affected limb; HTN
• Neuro: Dizziness, headaches, visual disturbance, TIA/Stroke
• Cardiac: Angina, dyspnoea (HF)
• Other: Peripheral pulses may not be palpable, arterial bruits over any large artery
Investigation
KEY = BP DIFFERENCE >10mmHg between arms
• Raised inflammatory markers
• MR-angiography
• PET scan – used FDG as a marker for tissue with high glucose uptake
• Biopsy (temporal artery may be involved sub clinically)
Management
• Prednisolone, usually at a starting dose 1 mg/kg/day – gradually tapered
• Steroid sparing agents eg methotrexate, azathioprine
• Tocilizumab – refractory disease
• Surgical intervention of vascular stenoses: should not be attempted until immunosuppression given and inflammation controlled.
POLYARTERITIS NODOSA
Definition
Epidemiology
Clinical features
Investigation
Management
Necrotising arteritis of medium sized vessels (main visceral arteries) – associated with microaneurysm formation, thrombosis and infarction
Epidemiology
• Predominantly middle aged men.
• Association with Hepatitis B (or less commonly C) infection
Clinical features
• Constitutional: Fever, malaise
• CNS: CVA, mononeuritis multiplex
• Cardiac: MI
• GI: GI perforation, haemorrhage
• Renal: Haematuria, malignant hypertension
• Skin: Infarcts, nodules
• Testes: Pain
• Perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with ‘classic’ PAN
• Hepatitis B serology positive in 30% of patients
Systemic vasculitic symptoms in the presence of hepatitis B signs and in the absence of pulmonary symptoms/signs suggests a diagnosis polyarteritis nodosa
Investigation
• Angiography: Microaneurysms in hepatic, intestinal or renal vessels
• Biopsy: Of affected organ, often kidney
• Raised inflammatory markers
• ANCA -ve
Management
• Control BP and refer
• High dose steroids
• Cyclophosphamide (severe life threatening disease)
• DMARDs (azathioprine, MTX, leflunomide)
• Hep B related PAN – plasma exchange + lamivudine
Granulomatosis with Polyangitis
Definition
Clinical features
Investigation
Management
Necrotising granulomatous vasculitis affecting small vessels usually with involvement of the upper and lower respiratory tract.
Previously called Wegener’s granulomatosis
Clinical features
• ENT:
o Nasal discharge, sinusitis, nasal mucosal ulceration (saddle nose)
o Otitis media, deafness
o Hoarseness, stridor
• Lungs:Cough, haemoptysis, pleuritic pain
• Renal: Glomerulonephritis
Investigation
• cANCA +ve ; Anti-PR3 (proteinase 3) antibodies +ve
• CXR (infiltrates, nodules, cavitation)
• Biopsy of kidney/lung/nasal tissue shows necrotising granulomas
Management
• Systemic immunosuppression and support of affected organs such as the kidneys.
• Induction treatment: steroids, cyclophosphamide/rituximab (organ threatening disease), plasma exchange (life threatening disease)
• Maintenance treatment: azathioprine / mycophenolate mofetil / methotrexate
Microscopic polyangitis
Definition
Epidemiology
Clinical features
Investigation
Management
Necrotising vasculitis of small vessels. No granulomas.
Glomerulonephritis and pulmonary capillaritis common.
Clinical features • Constitutional Fever, malaise • Lung: Pulmonary infiltrates, alveolar haemorrhage • Renal: Glomerulonephritis • Nerves: Mononeuritis multiplex
Investigation
• pANCA +ve; Anti-MPO (myeloperoxidase) antibodies +ve
• Biopsy of affected organ
Management
Systemic immunosuppression and support of affected organs such as the kidneys.
• Induction treatment: steroids, cyclophosphamide/rituximab (organ threatening disease), plasma exchange (life threatening disease)
• Maintenance treatment: azathioprine / mycophenolate mofetil / methotrexate
EGPA
Definition
Clinical features
Investigation
Management
Necrotising granulomatous vasculitis affecting small vessels with involvement of the respiratory tract and associated with asthma and eosinophilia.
Previously called Chrug Strauss syndrome
Clinical features • Lungs: Asthma, rhinitis, nasal polyps, history of atopy • Skin: Purpuric rash • Nerves: Mononeuritis multiplex • Blood: Peripheral eosinophilia
Investigation
• pANCA +ve; Anti-MPO (myeloperoxidase) antibodies +ve
• CXR (infiltrates, nodules)
• Biopsy (eosinophilic necrotising granulomas)
Management
Systemic immunosuppression and support of affected organs such as the kidneys.
• Induction treatment: steroids, cyclophosphamide/rituximab (organ threatening disease), plasma exchange (life threatening disease)
• Maintenance treatment: azathioprine / mycophenolate mofetil / methotrexate
Dupuytren contracture
Definition
Incidence
Causes
Features
Dupuytren contracture is a common condition, characterized by fibromatosis of the palmar fascia, resulting in flexion contractures of the metacarpophalangeal and interphalangeal joints of one or more fingers.
Incidence
Before the age of 55 years, the incidence of Dupuytren contracture is much higher in men than in women. After this age, the incidence is equal.
Causes - Family history of Dupuytren contracture - Hepatic cirrhosis - Diabetes mellitus = Anticonvulsant therapy
Features
The ulnar side of the hand is most commonly affected.
- Inability to extend one or more fingers, usually the ring and little fingers. It is rarely (perhaps never) painful. The fibromatosis may remain stable or progress. Progressive cases can result in marked deformity and loss of function, with the fingers held in a fixed position curled into the palm.
In early cases, nodules may be felt in the palm or on the palmar surface of the finger.
- In more advanced cases, flexion at the metacarpophalangeal joints is seen and the palm of the hand cannot be placed flat on a table (positive tabletop test).
- In severe cases, the proximal and distal interphalangeal joints are involved.
Management
Surgery = most effective treatment.
The decision to progress to surgery can either be made when the patient has a positive tabletop test or when the deformity starts to affect the patient’s quality of life. Palmar fasciectomy is the most commonly performed procedure. Complete correction of the deformity is more difficult the more advanced the disease. There is a risk of recurrence postoperatively.
Fibromyalgia
Definition
Chronic widespread pain symptoms associated. with fibromyalgia are often nonspecific and many patients suffer for a long time between onset of symptoms and establishing a diagnosis. Associated symptoms of fatigue, depression, insomnia, altered bowel habits and poor concentration are accompanied by a widespread soft tissue tenderness localized over a number of trigger points. However, the existence of fibromyalgia as an organic disease remains controversial. Many clinicians recognize the above symptoms and clinical features but feel that labelling patients may reinforce their illness. However, there is evidence that referral rates and investigations lessen once patients have been diagnosed.
Causes
Poorly understood.
Several theories: including a postviral trigger and up-regulation of pain receptor sensitivity. Elements recognized to be indicative of being at risk include:
• Women
• Middle age
• Stressful life events
There is considerable overlap between fibromyalgia and several other conditions that have a functional component:
- IBS, Fibromyalgia, chronic fatigue syndrome
Features • Fatigue • Sleep disturbance • Poor concentration, sometimes referred to as ‘fibro fog’ • Headache • Paraesthesia • Anxiety/depression • Altered bowel habit • Widespread pain
The only significant finding on examination is the presence of soft-tissue tenderness, usually in multiple sites.
Fibromyalgia
Diagnosis
Management
Diagnosis depends on pain that is chronic (>3 months) and widespread (involves left and right sides, above and below the waist, and the axial skeleton). Profound fatigue is almost universal with complaint of unrefreshing sleep and significant fatigue and pain with small increases in physical exertion. Additional features: morning stiffness (~80–90%), paraesthesiae (without underlying cause), headaches (migraine and tension), poor concentration, low mood, and sleep disturbance (~70%). Widespread and severe tender points.
Education
• Inform patients about their condition.
• Reassure them they do not have a destructive arthritis.
• Explain why further investigations might not be useful.
• Emphasize that exercise will not cause harm to their joints.
Physiotherapy/exercise
A graded exercise programme can improve fitness and reduce pain and fatigue.
CBT
This encourages patients to develop coping mechanisms to deal with their symptoms.
Drug therapy
Many types of drugs have been trialled with varying success. Tricyclic antidepressants such as amitriptyline, dual reuptake inhibitors (duloextine), anticonvulsants (pregabalin, gabapentin) and analgesics such as tramadol are all used with varying success. There is no role for antiinflammatory drugs.
Complex regional pain syndrome
AKA
Features
Management
AKA reflex sympathetic dystrophy and is a long-term complex pain syndrome that worsens over time.
Features
It is an uncommon cause of regional pain that typically affects the upper limb, particularly the distal forearm and hand. The pain experienced is usually severe and out-of-context of the original injury, with key features of pain, hypersensitivity, skin changes and autonomic disturbance. Allodynia is often present (pain from a stimulus that would not normally produce pain, e.g., light touch).
Management
Challenging but usually involves bisphosphonates and neuropathic pain killers.
Osteoporosis
Definition
Risk factors
Causes of 2ndary Osteoporosis
Presentation
Investigations
Weeakness of the bones, due to lower than normal bone mass or greater than normal bone loss. Increased risk of fractures.
Bone mineral density (BMD) is used to measure bone strength and is expressed as a T-score. This is the number of standard deviations by which the BMD varies in relation to the mean density of young adults.
Osteoporosis = T-score of less than –2.5. Osteopenia = T-score of between –1 and –2.5.
Normal bone density is expressed as a T-score greater than or equal to –1.
Risk factors
- Non-modifiable: Age, Race (Caucasian, Asian), Female, Early menopause, Small size, +ve FH
- Modifiable: Poor calcium and vitamin D intake, Lack of exercise, Smoking, Alcohol excess
Causes of 2ndary osteoporosis • Hyperthyroidism • Hyperparathyroidism • Hypogonadism • Cushing syndrome • Rheumatoid arthritis • Inflammatory bowel disease • Coeliac disease and malabsorption states • Renal failure • Multiple myeloma • Anorexia nervosa • Medications:corticosteroids, anticonvulsants, heparin
Presentation The three typical fragility fractures are 1) Colles fracture of the wrist 2) NOF fracture 3) vertebral body fracture
Investigations
Serum biochemistry = normal
DEXA = T score
Osteoporosis management
Aim = reduce risk of fractures
(1) Modification of risk factors
e. g stopping smoking or by increasing weight-bearing exercise.
(2) Drug therapies to increase bone mass
1) Bisphosphonates
1st line used in combination with calcium supplements and vitamin D. Antiresorptive and work by inhibiting osteoclast activity. Daily, weekly, monthly and yearly preparations are available and have good efficacy. Gastrointestinal intolerance is a problem for some patients.
2) Denosumab
This is a second line monoclonal antibody directed against RANK-L. RANK-L is a ligand produced by osteoblasts that upregulates osteoclast formation, activity and survival, which in turn causes loss of BMD. It is useful in patients who are intolerant to bisphosphonates. (SC every 6 months)
3) Teriparatide
This is a parathyroid hormone analogue. It is very expensive but useful in patients intolerant to other treatments. Intermittent parathyroid hormone exposure causes an increase in osteoblast activation (above that of osteoclasts) and therefore results in net BMD increases.
Other drugs
Raloxifene, a selective oestrogen receptor modulator, is sometimes used in postmenopausal women but its popularity has significantly decreased. Calcitonin is an antagonistic hormone to parathyroid hormone, reducing osteoclast activity and therefore increasing BMD.
(3)Prevention of falls
Various interventions and often involve a MDT approach. PT/OT/, specialist nurses and social workers
Steroids and assessing osteoporosis risk/management
Individuals requiring continuous oral glucocorticoid therapy for 3 months or more (at any dose) should be assessed for osteoporotic risk factors.
Post- menopausal women, men aged over 50 years and anyone with a previous fragility fracture should receive bisphosphonate treatment without waiting for DXA scanning.
- Fracture risk assessment and DXA results guide treatment for other patients.
Where possible, glucocorticoid doses should be minimized and consideration given to use of steroid-sparing immunosuppressants and alternative routes of steroid administration (e.g. rectal steroids for distal ulcerative colitis).
Paget’s disease of bone
Definition
Cause
Clinical features
Investigation findings
Management
Focal disorder of bone remodelling with increased osteoclastic bone resorption followed by formation of weaker new bone, increased local blood flow and fibrous tissue
Cause
- Unknown
Clinical features
PELVIS, femur, lumbar spine, skull and tibia most affected
- Most cases asymptomatic
- Pain in bone or nearby joint
- Deformities: Enlarged skull, bowing of tibia
- Complications: Nerve compression (deafness, paraparesis), pathological fractures, rarely high CO, Osteogenic sarcoma
Investigation findings
- ALP raised often >1000, normal Ca and phosphate
- Urinary hydroxyproline exertion raised (marker of disease activity)
- X-rays: Boney enlargement + distortion, sclerotic changes and osteolytic areas
Management
- Bisphosphonates (inhibit bone resorption) = Mainstay of treatment
Osteomalacia definition
Inadequate mineralisation of bone - due to vit D deficiency
Causes
- Pigmented skin
- Malabsorption
- Short bowel
- Renal disease (inadequate hydroxylation of vit D)
- Cholestatic liver disease
- Anticonvulsants
Features
- Proximal muscle weakness and pain
- Hypocalcaemia, tetany and seizures
- Rickets in children
Investigations
- Low vit D
- ALP usually high, Ca normal or low, PTH raised
Radiology: Looser’s pseudo fractures (low density bands running perpendicular to the cortex)
Management
- Calcium 1000-1200mg/day
- Vit D 50,000 U/ week for 8 weeks
- Regilar vit D supplementation 800-1000 units
SLE
Definition
Epidemiology
Causes
Clinical features
Investigation findings
Management
Systemic inflammatory disease characterised by autoantibody to nuclear material
Epidemiology
• F:M 9:1
• Disease onset 15-50 yrs
• Afro Caribbean > Asian > White
Causes
- May be induced by drugs e.g. OCP, hydralazine (mild if drug induced), ISONIAZID - confirm drug induced by anti-histone
- UVB light
- Viruses e.g. EBV
Clinical features S : Serositis (pleuritis, pericarditis) O: Oral ulcers A: Arthritis P: Photosensitivity
B: Blood (all low - anaemia, leukopenia, thrombocytopenia) R: Renal (protein) A: ANA I: Immunological (DS DNA) N: Neurological (Psych, Seizures)
M: Malar rash
D: Discoid rash
Investigation findings
- Anti dsDNA: Homogenous staining
- Urine dip: ALWAYS do (quantify blood and protein)
- FBC
- U&Es
- ESR/CRP
- C3/C4
- Coombs test: +ve in autoimmune haemolytic anaemia
- Skin biopsy
- Renal biopsy
Management
(1) Conservative: Educate, avioid sun, stop smoking
(2) Analgesia e.g. NSAIDs: Arthritis, myalgias, serositis
(3) Steroids: When NSAIDs and hydroxychloroquine inadequate
(4) Immunosuppressants: Hydroxychloroquine; Azathioprine, Methotrexate (with folic acid), Mycophenolate motel; Cyclophosphamide
(5) Biologics: Rituximab, Belimumab
Adjunct Rx
- HTN tx if nephritis
- IVIg if needed
- Anti-platelet drugs/warfarin if antiphospholipid syndrome
Antiphospholipid syndrome
Definition
Clinical features
Investigations
Clinical features
(1) Major
• Venous thrombosis: DVT + PE but other veins can be affected (e.g. IVC, pelvic, renal, portal, hepatic)
• Arterial thrombosis: Cerebral ischaemia (stroke, TIA), Peripheral ischaemia
• Fetal complications: Spontaneous abortion, Premature births
• Thrombocytopenia: Not severe enough to cause haemorrhage
(2) Minor • Livedo reticularis • Leg ulcers • Cardiac valve abnormalities • Chorea • Epilepsy • Migraine • Haemolytic anaemia
Investigations
• Lupus anticoagulant/ anticardiolipin antibodies: +ve on 2 occasions, 12 weeks apart
— Check in all pts with SLE! (secondary APS)
• ANA, dsDNA and ENA antibodies: may suggest underlying associated SLE
• FBC: may show thrombocytopenia
• Creatinine and urea: if nephropathy present
• Prolonged APTT
Management
• Initial venous thromboembolic events: evidence currently supports use of warfarin with a target INR of 2-3 for 6 months
• Recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin then increase target INR to 3-4
• Arterial thrombosis: lifelong warfarin with target INR 2-3
Don’t treat if no clinical features
Systemic sclerosis
AKA
Definition
Aka Slceroderma
Multi-system autoimmune disorder of unknown cause characterised by fibrosis of the skin, blood vessels and internal organs.
Investigations
• ANA +ve in 95% (nucleolar pattern)
• Antitopisomerase-1 (Scl-70) antibodies: Associated with DcSSc
• Anticentromere antibodies: Associated with LcSSc
Features (1) Skin • Sclerodactyly (thickening and tightness of skin on fingers and toes) • Microstomia (small mouth) + Furrowing of skin around lips • Loss of normal skin creases • Tethering of skin to underlying structures • Skin hypo-hyperpigmentation • Flexion contractures of joints • Thinning and atrophy (2) CVS • Raynaud phenomenon • Myocardial fibrosis --> HF + arrhythmia (3) Pulmonary • ILD (35% with CREST + 40% with diffuse cutaneous) • Pulmonary HTN (4) Renal disease (5) GI problems (6) MSK: Arthralgia + joint stiffness (7) Neuro: • Peripheral neuropathy • Central neuropathy
Types of systemic sclerosis
Management
Localised Disease
• Linear morphoea, usually occurs in childhood, on one side of body
• Morphea – localised or generalised patches of sclerotic skin
• Guttate morphea – multiple small patches with minimal sclerosis
Systemic disease
(1) Diffuse cutaneous systemic sclerosis (DcSSc)
• Have extensive skin sclerosis and are at a greater risk for the development of significant renal, lung, and cardiac disease.
• The central criterion for the diagnosis of dcSSc is the extension of skin sclerosis proximal to the wrists (particularly over the proximal limbs and trunk but commonly sparing the upper back)
(1) Limited cutaneous scleroderma (LsSSc)
• Skin sclerosis restricted to the hands and, to a lesser extent, to the face and neck.
• They also have prominent vascular manifestations-associated with capillary nail fold dilation, pulmonary hypertension and CREST syndrome variant (Calcinosis, Raynaud’s, Esophageal symptoms, Sclerodactyly, Telangiectasia)
Management
Raynaud phenomenon
• Hand warmers
• Vasodilators (oral nifedipine is first line, topical GTN, intravenous iloprost, bosentan)
• Sympathectomy - severe disease / critical ischaemia
Pulmonary HTN
• Suspected on echocardiography / PFTs
• Confirmed on right heart catheterisation
• Mild disease treated with CCB (eg amlodipine),
• More severe disease can use prostacyclin analogues (e.g. IV epoprostenol), oral bosentan or sildenafil (phosphodiesterase 5 inhibitor)
Pulmonary fibrosis
• MMF or Cyclophosphamide
• Rituximab (conflicting evidence, refractory disease only)
GI problems
• PPI for GORD
• Antibiotics for small bowel overgrowth
• Bulk forming agents for constipation
Skin
• Methotrexate or mycophenolate for early diffuse SSc.
• Refractory or aggressive disease: Cyclophosphamide, rituximab, or IVIg
Screening for complications
• Monitoring pulmonary function tests, echocardiography, BP and renal function help control long-term lung and systemic complications
Sjogren’s syndrome
Definition
Epidemiology
An Autoimmune disorder affecting exocrine glands resulting in dry mucosal surfaces
It may be primary (PSS) or secondary to rheumatoid arthritis or other connective tissue disorders, where it usually develops around 10 years after
Epidemiology
More common in females
40-60x increased risk of lymphoid malignancy
Clinical features
• Dry eyes: keratoconjunctivitis sicca
• Dry mouth swallowing difficulties, dry mucosa, tongue fissured. Dental caries common, oral candidiasis common. Recurrent episodes of parotitis
• Arthralgia
• Raynaud’s, myalgia
• Sensory polyneuropathy
• Renal tubular acidosis (usually subclinical)
• Lack of GI mucus secretions –> Oesophagitis or gastritis
• Vaginal dryness –> Dyspareunia
Risk of lymphoma (NHL relative risk of 44)
Investigations
• Rheumatoid factor (RF) positive in nearly 100% of patients
• ANA positive in 70%
• Anti-Ro (SSA) antibodies in 70% of patients with PSS
• Anti-La (SSB) antibodies in 30% of patients with PSS
• Hypergammaglobulinemia, low C4
• Schirmer’s test
• ROse bengal staining: for keratoconjunctivitis sicca
• Biopsy: Focal lymphocytic infiltration
Management
• Education: Maintain good oral hygiene, avoid OTC anticholinergic medication e.g. cold and cough remedies, avoid irritants e.g. smoking, carbonated drinks, remedies
• Symptomatic: Artificial saliva and tears
• Muscarinic agents: Pilocarpine or Cevimeline may stimulate saliva production
o But cause cholinergic side effects e.g. sweating, abdo cramps
• Hydroxychloroquine can help the arthritis/rash
• Corticosteroids for serious complications like vasculitis and neuro problems
Myositis definition
Pathology
Group of inflammatory myopathies that share the common feature of immune mediated muscle injury causing muscle weakness, including:
Polymyositis (PM) , Dermatomyositis (DM)
Pathology
• Muscle fibres infiltrated by inflammatory cells –> subsequent degeneration, necrosis and phagocytosis
• Pattern of infiltration and predominant cell type allows PM to be distinguished from DM
o Skin biopsy in DM shows the same histological features as Lupus
Clinical features
• Symmetrical proximal muscle weakness (usually subacute)
o Difficulty rising from a chair, climbing stairs or reaching for things above head height
• Dysphagia and regurgitation of food (from weakness of pharyngeal muscles and upper 1/3 of oesophagus)
• Breathlessness, cough (Interstitial lung disease and involvement of intercostal muscles and diaphragm T2 resp failure)
• Musculoskeletal features – arthralgias/arthritis
• Systemic upset – weight loss, fever, fatigue
- Gottron’s papules – Erythematous, scaly papules or plaques over the MCP and PIP and the extensor surfaces of knees and elbows
- Heliotrope rash – Lilac coloured rash affecting eye lids, malar region, forehead and nasolabial folds
- V-sign rash – Confluent erythematous rash over anterior chest and neck
- Shawl-sign rash – Erythematous rash over shoulders and proximal arms
- Mechanic hands – Cracking and fissuring of the skin over the skin pads
- Nailfold abnormalities – Periungual erythema, dilated capillary loops
Myositis
Investigations
Management
Investigations • CK raised • ESR (usually raised) • Autoantibodies: antisynthestase, SRP, Mi2 • Muscle biopsy: Definitive • EMG + Nerve conduction: • MRI
Management
• Physiotherapy and rehabilitation measures should begin early in course of disease
• High dose steroids (1mg/kg) for 4-6 weeks and reduce
• Immunosuppressive (Azathioprine/Methotrexate) as steroid-sparing agents
• IV immunoglobulin or rituximab (refractory cases)
Marfan syndrome
Inheritance + what gene involved
Features
Life expectancy
Management
AD connective tissue disorder. It is caused by a defect in the FBN1 gene on chromosome 15 that codes for the protein fibrillin-1.
Features
Tall stature with arm span to height ratio > 1.05
HIGH ARCHED PALATE
Arachnodactyly (long fingers)
pectus EXCAVATUM
pes planus
scoliosis of > 20 degrees
Heart: dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm, aortic dissection, AORTIC REGURGITATION, mitral valve prolapse (75%),
lungs: repeated pneumothoraces
Eyes: upwards lens dislocation (superotemporal ectopia lentis), blue sclera, myopia
Dural ectasia (ballooning of the dural sac at the lumbosacral level)
The life expectancy of patients used to be around 40-50 years. With the advent of regular echocardiography monitoring and beta-blocker/ACE-inhibitor therapy this has improved significantly over recent years. Aortic dissection and other cardiovascular problems remain the leading cause of death however.
Methotrexate
MOA
Indications
Side effects
Pregnancy
Monitoring
Co-prescription<
Interactions?
Methotrexate toxicity
Inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and pyrimidines. It is considered an ‘important’ drug as whilst it can be very effective in controlling disease the side-effects may be potentially life-threatening - careful prescribing and close monitoring is essential.
Indications
inflammatory arthritis, especially rheumatoid arthritis
psoriasis
some chemotherapy acute lymphoblastic leukaemia
Adverse effects mucositis myelosuppression pneumonitis pulmonary fibrosis liver fibrosis
Pregnancy
women should avoid pregnancy for at least 6 months after treatment has stopped
the BNF also advises that men using methotrexate need to use effective contraception for at least 6 months after treatment
Prescribing methotrexate
methotrexate is a drug with a high potential for patient harm. It is therefore important that you are familiar with guidelines relating to its use
methotrexate is taken weekly, rather than daily
FBC, U&E and LFTs need to be regularly monitored. The Committee on Safety of Medicines recommend ‘FBC and renal and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months’
folic acid 5mg once weekly should be co-prescribed, taken more than 24 hours after methotrexate dose
the starting dose of methotrexate is 7.5 mg weekly (source: BNF)
only one strength of methotrexate tablet should be prescribed (usually 2.5 mg)
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
Methotrexate toxicity
the treatment of choice is folinic acid
RA poor prognosis features
Rheumatoid factor positive poor functional status at presentation HLA DR4 X-ray: early erosions (e.g. after < 2 years) Axtra articular features e.g. nodules Insidious onset Anti-CCP antibodies
Anti-TNF therapy
Examples
- route of adminitstration
- risks
Use
What to check before starting
Biologic therapy
E.g.
1) Etanercept: recombinant human protein, acts as a decoy receptor for TNF-α, subcutaneous administration, can cause demyelination, risks include reactivation of tuberculosis
2) Infliximab: monoclonal antibody, binds to TNF-α and prevents it from binding with TNF receptors, intravenous administration, risks include reactivation of tuberculosis
3) Adalimumab: monoclonal antibody, subcutaneous administration
Use
- RA - after DMARDs x 2 tried
Check before starting
leads to an increased risk of opportunistic infections and re-activation of latent infections, such as tuberculosis (TB). !!!CXR!! is required to look for TB prior to starting biologics.
Lumbar spine pain
Examination will show what
Femoral nerve compression may cause referred pain in the hip
Femoral nerve stretch test may be positive - lie the patient prone. Extend the hip joint with a straight leg then bend the knee. This stretches the femoral nerve and will cause pain if it is trapped
What is Ehler Danlos syndome
Features
Ehler-Danlos syndrome is an AD connective tissue disorder that mostly affects type III collagen.
–> This results in the tissue being more elastic than normal leading to joint hypermobility and increased elasticity of the skin.
Features and complications
ELATSTIC, fragile skin
Joint hypermobility: recurrent joint dislocation
easy bruising
Aortic regurgitation, mitral valve prolapse and aortic dissection
SAH
Angioid retinal streaks
Bisphosphonates
Examples
Use
Side effects
Contraindications
Alendronate, risedronate and etidronate are all licensed for the prevention and treatment of post-menopausal and glucocorticoid-induced osteoporosis
All reduce the risk of both vertebral and non-vertebral - Alendronate, risedronate may be superior to etidronate in preventing hip fractures
ibandronate is a once-monthly oral bisphosphonate
Uses Prevention and treatment of osteoporosis Hypercalcaemia Paget's disease Pain from bone metatases
Side effects
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
Hypocalcaemia: due to reduced calcium efflux from bone. Usually clinically unimportant
Colchicine
MOA
Use
Side effects
Use
- Acute exacerbational of gout
Side effects
- Diarrhoea
When to start urate lowering therapy for Gout
the British Society of Rheumatology Guidelines now advocate offering urate-lowering therapy to all patients after their first attack of gout
ULT is particularly recommended if:
→ >= 2 attacks in 12 months
→ tophi
→ renal disease
→ uric acid renal stones
→ prophylaxis if on cytotoxics or diuretics
Allopurinol = 1st line
Febuxostat
What is type 2 hypersensitivity
Examples
IgG or IgM binds to antigen on cell surface
- Autoimmune haemolytic anaemia
- ITP
- Goodpasture’s syndrome
- Pernicious anaemia
- Acute haemolytic transfusion reactions
- Rheumatic fever
- Pemphigus vulgaris / bullous pemphigoid
Hydroxychloroquine
Use
Adverse effects
Use
- RA
- SLE
Adverse effects
bull’s eye retinopathy - may result in severe and permanent visual loss
-recent data suggest that retinopathy caused by hydroxychloroquine is more common than previously thought and the most recent RCOphth guidelines (March 2018) suggest colour retinal photography and spectral domain optical coherence tomography scanning of the macula
Baseline ophthalmological examination and annual screening is generally recommened
may be used in pregnancy if needed
Still’s disease in adults
epidemiology
Features
Management
Still’s disease in adults
Epidemiology
has a bimodal age distribution - 15-25 yrs and 35-46 yrs
Features Arthralgia Elevated serum ferritin Rash: salmon-pink, maculopapular pyrexia - typically rises in the late afternoon/early evening in a daily pattern and accompanies a worsening of joint symptoms and rash Lymphadenopathy rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative
The diagnosis of Still’s disease in adults can be challenging. The Yamaguchi criteria is the most widely used criteria and has a sensitivity of 93.5%.
Management
NSAIDs
should be used first-line to manage fever, joint pain and serositis ( trialled for at least a week before steroids are added)
Steroids
may control symptoms but won’t improve prognosis
if symptoms persist, the use of methotrexate, IL-1 or anti-TNF therapy can be considered
Septic arthritis
Causative organisms
Criteria for diagnosis
Management
Overview
Most common = Staphylococcus aureus
in young adults who are sexually active Neisseria gonorrhoeae should also be considered
in adults, the most common location is the knee
The Kocher criteria for the diagnosis of septic arthritis: fever >38.5 degrees C non-weight bearing raised ESR raised WCC
Management
synovial fluid should be obtained before starting treatment
Intravenous antibiotics which cover Gram-positive cocci are indicated. The BNF currently recommends flucloxacillin or clindamycin if penicillin allergic
antibiotic treatment is normally be given for several weeks (BNF states 6-12 weeks)
needle aspiration should be used to decompress the joint
arthroscopic lavage may be required
What is meralgia paraesthetica
Presentation
Caused by compression of lateral cutaneous nerve of thigh
Typically burning sensation over antero-lateral aspect of thigh
Sulfasalazine
MOA
Use
Cautions
Adverse effects
Pregnancy
Sulfasalazine is a disease modifying anti-rheumatic drug (DMARDs) used in the management of inflammatory arthritis, especially rheumatoid arthritis. It is also used in the management of inflammatory bowel disease.
Sulfasalazine is a prodrug for 5-ASA which works through decreasing neutrophil chemotaxis alongside suppressing proliferation of lymphocytes and pro-inflammatory cytokines.
Cautions
G6PD deficiency
allergy to aspirin or sulphonamides (cross-sensitivity)
Adverse effects
oligospermia
Stevens-Johnson syndrome
pneumonitis / lung fibrosis
myelosuppression, Heinz body anaemia, megaloblastic anaemia
may colour tears → stained contact lenses
In contrast to other DMARDs, sulfasalazine is considered safe to use in both pregnancy and breastfeeding.
Interferon therapy
Types
use
Interferons (IFN) are cytokines released by the body in response to viral infections and neoplasia. They are classified according to cellular origin and the type of receptor they bind to. IFN-alpha and IFN-beta bind to type 1 receptors whilst IFN-gamma binds only to type 2 receptors.
Interferon-alpha
produced by leucocytes
antiviral action
useful in hepatitis B & C, Kaposi’s sarcoma, metastatic renal cell cancer, hairy cell leukaemia
adverse effects include flu-like symptoms and depression
Interferon-beta
produced by fibroblasts
antiviral action
reduces the frequency of exacerbations in patients with relapsing-remitting MS
Interferon-gamma
predominately natural killer cells. Also by T helper cells
weaker antiviral action, more of a role in immunomodulation particularly macrophage activation
may be useful in chronic granulomatous disease and osteopetrosis
