Week 11 - connective tissue Flashcards
Describe the basic epidemiology of polymyalgia rheumatica. (LO1)
- Second most common autoimmune syndrome. 1-5 people in 10,000 affected.
- Risk in women 2.4%, 1.7% in men.
- Rarely affects <50 year olds.
- Most patients >60. Mean age of onset is around 70.
- 15-20% of PMR patients also have giant cell arteritis (GCA).
- Mainly affects white patients. Uncommon in black, Hispanic, Asian and Native American individuals.
Describe the pathophysiology of polymyalgia rheumatica. (LO1)
- Suggested genetic predisposition if white people are more affected.
- Associated with HLA-DR4 gene.
- PMR and GCA may start with the activation of dendritic cells at the adventitia-media border of large vessels, causing IL-1 and IL-6 production. This leads to the suppression of T-regulatory cells, leading to reduction in IFN-γ cytokine.
- If there is no IFN-γ to stimulate macrophages, then GCA arterial inflammation does not stop.
Describe the presentation of polymyalgia rheumatica. (LO1)
- Recent onset of significant stiffness in shoulder/hip girdle and pain in shoulder/hip muscles (proximal limbs) and neck muscles.
- Symmetrical shoulder girdle aching for >2 weeks.
- Morning stiffness >45 minutes.
- Bilateral hip pain/limited range of motion.
- Constitutional symptoms (33-50% patients): fever, anorexia, malaise, headache, myalgia.
- Absence of objective weakness (don’t confuse with muscle guarding).
- Difficulty rising from seat, prone position (lying flat on front).
- Shoulder/hip bursitis.
- Possible oligoarthritis (1-4 joints affected in first 6 months of disease).
- Exclusion of other diagnosis (except GCA).
What do the letters in SECCRET stand for when regarding polymyalgia rheumatica? (LO1)
- S = stiffness and pain.
- E = elderly individuals.
- CC = constitutional symptoms, caucasians.
- R = rheumatism (arthralgias/arthritis).
- E = elevated ESR.
- T = temporal arteritis (GCA particularly at temples.
Describe the findings from a physical examination that would be indicative of polymyalgia rheumatica. (LO1)
- Chronically ill.
- Neck and shoulders tender.
- Limited active range of motion.
- Capsular contracture.
- Muscle atrophy.
- Increased pain on joint movement - felt at proximal extremities.
- Synovitis often in knees, wrists, sternoclavicular joints.
- Objective muscle strength testing should be normal unless atrophy.
- GCA and PMR suggested to be different manifestations of the same disorder so check GCA for temporal/occipital headaches, scalp tenderness, jaw pain and visual disturbances.
Describe the investigations for polymyalgia rheumatica. (LO1)
- CRP - elevated.
- ESR - >40mm/hour (often over 100mm/hour).
- Absence of RF and antibodies to citrullinated antigens (ACPAs).
- Rule out neuromuscular dysfunction with neurological exam - no muscle weakness.
Lab abnormalities:
- Anything showing systemic inflammation (normochromic normocytic anaemia, thrombocytosis, increased gamma globulins).
- Abnormal liver enzymes (33% of cases) - increased alkaline phosphatase (ALP) level.
Synovial fluid:
- Leukocyte 1000-20,000 cell/mm³.
- Negative culture.
- Negative crystal.
Describe the management of polymyalgia rheumatica. (LO1)
- Initially: single daily dose of 12.5-25mg of prednisolone (or other glucocorticoid) OR intramuscular methylprednisolone 120mg every 3 weeks (if can’t take oral prednisolone).
- Early: methotrexate 7.5-10mg/week, especially if it’s not possible to taper glucocorticoids.
- Azathioprine: reduces long-term need for steroids (steroid-sparing agent). Given alongside fast-acting steroids so that when azathioprine has an effect (3-6 months later), the patient can stop taking steroids.
- Tocilizumab is reported to be effective, inhibition of IL-6 in PMR.
Describe the tapering of glucocorticoids in polymyalgia rheumatica. (LO1)
- Only once CRP and ESR are normalised - decrease by 2.5mg every 2-4 weeks until 10mg/day.
- Further tapering by 1mg every 1-2 months while monitoring.
- If CRP and ESR elevate again, don’t increase prednisolone straight away until the cause has been investigated.
- If relapse (65% chance), small increase to dosage before relapse (often 5mg/day).
- After 6-12 months have passed, taper again by 1mg/day every 2 months.
How long does treatment for polymyalgia rheumatica usually last? What could be a reason for treatment lasting a lot longer? (LO1)
Often lasts >2 years.
- If prednisolone 20mg/day does not improve symptoms/normalise ESR and CRP within a month, suspect a giant cell arteritis (GCA).
- If GCA suspected, do temporal artery biopsy/check other diagnosis (malignancy, infection).
- Reassurance, education, regular monitoring, range of motion exercises, especially if muscle atrophying and contracture is present.
- Treat glucocorticoid side effects with vitamin D and calcium supplements + regular dual x-ray absorptiometry screening, check glucose intolerance and hyperlipidaemia.
- Strong no to tumour necrosis factor antagonists and Chinese herbal supplements.
List the differentials for polymyalgia rheumatica. (LO1)
- Chronic pain syndrome, e.g. fibromyalgia.
- Hyper/hypothyroidism.
- Depression.
- Polymyositis.
- Malignancy (lymphoma, myeloma).
- Inflammatory myopathy - including body myositis.
- Lambert-Eaton syndrome.
- Occult infection (TB, HIV, SBE).
- Late onset spondyloarthropathy.
- Late onset rheumatoid arthritis - distinguish with absence of RF and anti-CCP, lack of synovitis of hands and feet, no erosions on x-ray.
- Psoriatic arthritis (enthesopathic).
- Systemic vasculitis.
- Frozen shoulder, rotator cuff, shoulder OA.
- Multiple separate lesions.
Describe the prognosis for polymyalgia rheumatica. (LO1)
- Patients should respond dramatically within a week of starting 20mg/day prednisolone.
- 75% of patients can taper off prednisolone within 2 years.
- 10-20% of patients likely to relapse within months to years.
- 25-35% of patients require low dose glucocorticoids indefinitely due to relapse when tapered off.
Briefly describe systemic lupus erythematosus. (LO2)
- Multi-system autoimmune disease with different presentations.
- Treatments are tailored depending on different organ involvement.
- Rheumatologist primary responsible for lupus patients.
Describe the epidemiology of SLE. (LO2)
- 0.03% prevalence in Caucasians.
- 0.2% prevalence in in Afro-Caribbeans.
- 90% of affected patients are female.
- 20-30 year olds mostly affected (can be seen in children).
- Five fold increase in mortality compared to age-and-gender-matched controls (cardiovascular disease).
List the risk factors of SLE. (LO2)
- Female sex - associated with the effects of oestrogen.
- > 30 years of age.
- African descent in Europe and US.
- Alopecia, photosensitivity, oral ulcers, arthritis and malar rash may also be more common among female patients.
Describe the pathophysiology of SLE. (LO2)
- No clear picture.
Different factors:
- Genetic factors.
- Monozygotic twins.
- Polymorphic variants at the the HLA locus.
- Inherited mutations in complement components, C1q, C2 and C4, in the immunoglobulin receptor FcyRIIIb or in the DNA exonuclease TREX1.
- Polymorphisms of genes that predispose to SLE, most of which are involved in regulating immune cell function.
- Autoantibodies production usually directed against antigens present within the cell/nucleus.
Describe the systemic features of SLE. (LO2)
- Fatigue.
- Weight loss.
- Fever.
- Mild lymphadenopathy.
- Arthralgia.
Describe the joint involvement in SLE. (LO2)
- Arthralgia seen in 90% of patients with early morning stiffness.
- Tenosynovitis may result in tendon damage.
- Synovitis is rare.
- Jaccoud’s arthropathy is rare - lupus related to joint damage to chronic tenosynovitis rather than to joint erosive disease specifically.
Describe the dermatological presentations of SLE. (LO2)
- Malar (butterfly) rash.
- Photosensitive rash.
- Discoid rash.
- Atrophic scarring.
- Diffuse, non-scarring alopecia.
- Urticaria.
- Livedo reticularis.
- Vasculitis.
What is meant by malar rash? (LO2)
- Also known as butterfly rash.
- Classic facial rash (in up to 20% of SLE patients).
- Erythematous, raised and painful or itchy over the cheeks.
- Sparing of the nasolabial folds.
What is meant by photosensitive rash? (LO2)
- Occurs after sun exposure.
- Can be painful and pruritic.
- Usually lasts a few days, healing without scarring.
What is meant by discoid rash? (LO2)
- Erythematous raised patches.
- With adherent keratotic scaling (hyperkeratosis) and follicular plugging.
- Can lead to alopecia if involving scalp.
Describe the renal involvement in SLE. (LO2)
- Renal disease is a hallmark of severe SLE.
- Do a regular urinalysis and BP check.
- Proliferative glomerulonephritis.
Describe the presentations of proliferative glomerulonephritis as a result of SLE. (LO2)
- Presents with heavy haematuria.
- Proteinuria.
- Casts on urine microscopy.
Describe the cardiovascular involvement in SLE. (LO2)
- Heart: pericarditis, myocarditis, Libman-Sacks endocarditis (sterile vegetations; non-infection related, inflammation related).
- Arteries: atherosclerosis greatly increased, causing a higher risk of stroke and myocardial infarction. Atherosclerosis occurs due to inflammatory disease on the endothelium.
What is meant by antiphospholipid syndrome? (LO2)
- Antiphospholipid syndrome is where the antiphospholipid antibodies increase the risk of forming blood clots.
- The most serious complication of this, is that women with this syndrome have a higher risk of miscarriage.
Describe lung involvement in SLE. (LO2)
Common:
- Serositis (pleuritic pain) - inflamed lining of the chest wall and rubs against the lining of the lung.
- Pleural effusion - local inflammation of the lining of the pleura.
Less common:
- Pneumonitis.
- Atelectasis.
- Reduced lung volume.
- Pulmonary fibrosis that leads to breathlessness.
- Increased risk of thromboembolism (DVT, PE) is increased, especially if antiphospholiid antibodies are present.
Describe the neurological involvement in SLE. (LO2)
Common:
- Headache and poor concentration are common.
Less common:
- Visual hallucinations.
- Chorea.
- Organic psychosis .
- Transverse myelitis.
- Lymphocytic meningitis.
Describe the gastrointestinal involvement in SLE. (LO2)
Common:
- Mouth ulcers.
Uncommon:
- Peritoneal serositis - causes acute pain.
- Mesenteric vasculitis is serious (abdominal pain, bowel infarction/perforation).
Rare:
- Hepatitis.
Describe the haematological involvement in SLE. (LO2)
Antibody-mediated destruction of peripheral blood cells may cause:
- Neutropenia.
- Lymphopenia.
- Thrombocytopenia.
- Haemolytic anaemia.
- A degree of lymphopenia is an indicator of lupus activity.
Antiphospholipid syndrome (APLS):
- Vascular thrombosis.
- Pregnancy loss - early or late.
- Lab criteria: on two occasions, 3 months apart:
1. Lupus anticoagulant.
2. Anticardiolipin antibodies.
Describe pregnancy outcomes in patients with SLE. (LO2)
- Poor with or without APLS.
- Pregnancy loss - 13.1% total.
- Preterm birth.
How does neonatal lupus occur and how does it present? (LO2)
- Maternal antibodies crossing the placenta causing lupus in the unborn baby.
- Rash.
- Pericardial effusion.
- Conduction (heart beat) defects.
Describe the investigations for SLE. (LO2)
Autoantibody screen:
- Anti-dsDNA antibodies.
- Antinuclear antibodies (ANA).
- Antiphospholipid antibodies.
If autoantibodies are present, U+Es to assess effect on kidneys (creatinine and eGFR) and use EULAR criteria (don’t need to know the specifics of this). If absent, do not classify as SLE.
Describe the education aspect of management for SLE. (LO2)
- Control the symptoms and to prevent symptoms.
- To prevent organ damage and maintain normal function.
- Avoid sun exposure and use sun block (SPF 50).
- Vitamin D supplementation due to avoidance of sunlight.
Describe the drug therapy aspect of management for SLE. (LO2)
- Analgesics.
- NSAIDs.
- Hydroxychloroquine.
- Prednisolone.
- MMF (mycophenolate mofetil).
- MTX.
- Azathioprine.
- Belimumab (monoclonal antibody targets the β-cell growth factor BLyS).
Describe the drug therapy required during end-organ disease of SLE. (LO2)
- High dose glucocorticoids and immunosuppressants.
- IV methylprednisolone (10mg/kg IV).
- Renal: rituximab.
Describe the drug therapy required during end-organ disease of SLE. (LO2)
- High dose glucocorticoids and immunosuppressants.
- IV methylprednisolone (10mg/kg IV) + IV cyclophosphamide for 6 cycles. Side effects: infection, haemorrhagic cystitis, infertility.
- Renal: rituximab.
What is vasculitis? (LO3)
Vasculitis is an umbrella term for a group of diseases involving the inflammation of blood vessels. They are classified according to the size of blood vessel affected. (This can predict how the vasculitis will respond to treatment.)
Describe the epidemiology of vasculitis. (LO3)
- Incidence of 40-60 cases/million/year.
- Very rare.
- Increases with age.
List the the risk factors for vasculitis. (LO3)
- Dust exposure.
- Farming.
- Infection.
- Drugs.
- Season.
- Geography.
- Ethnicity.
Describe the pathophysiology of vasculitis. (LO3)
- Can be primary or secondary.
- Thought to be immune-mediated.
- Primary - no known cause.
- Secondary - could be a result of drugs, infection or rheumatological conditions such as rheumatoid arthritis or SLE.
List the vasculitidities included under the term vasculitis. (LO3)
- Giant cell arteritis.
- Takayasu arteritis.
- Polyarteritis Nodosa.
- Kawasaki disease.
- Wegener’s granulomatosis (WG).
- Microscopic polyangiitis (MPA).
- Churg-Strauss syndrome (CSS).
List the vasculitidities included under the term vasculitis. (LO3)
- Giant cell arteritis.
- Takayasu arteritis.
- Polyarteritis Nodosa (PAN).
- Kawasaki disease.
- Granulomatosis with polyangiitis (GPA), aka, Wegener’s granulomatosis (WG).
- Microscopic polyangiitis (MPA).
- Eosinophilic granulomatosis with polyangiitis (EGPA), aka, Churg-Strauss syndrome (CSS).
Describe the presentation of giant cell arteritis. (LO3)
- New headache.
- Temporal artery abnormality - biopsy might be diagnostic.
- Jaw claudication.
- Polymyalgic symptoms - pain and shoulder/pelvic girdle morning stiffness.
- Visual symptoms - medical emergency.
- > 50 years of age.
Describe the investigation findings for giant cell arteritis. (LO3)
- High inflammatory markers.
- Negative antibodies.
Describe the presentation of Takayasu arteritis. (LO3).
- <40 years of age.
- Generally unwell, fever.
- Weight loss.
- Myalgia, arthralgia.
- Claudication.
- Feeble or unequal pulse.
- Possible aortic murmur.
Describe the presentation of polyarteritis Nodosa (PAN). (LO3)
- Elderly.
- Weight loss.
- Neuropathy - peripheral nerve involvement.
- Gastrointestinal involvement - bowel ischaemia/infarction, pancreatitis.
- Testicular involvement.
- Skin involvement - leg ulcers/livedo reticularis.
- Renal involvement - hypertension.
- Rare, medium-sized vasculitis is associated with a Hep B infection.
Describe the investigation findings for polyarteritis Nodosa (PAN). (LO3)
- ANCA test is negative.
Describe the presentation Kawasaki disease. (LO3)
- Small, medium-sized vessels.
- Seen in childhood.
- 50% of cases are seen in children <2 years.
- Fever.
- Bilateral conjunctival congestion.
- Mucosal involvement - reddening of lips, lining of the mouth and/or strawberry
- Small, medium-sized vessels.
- Fever.
- Skin rash on the the trunk.
- Red palms and soles.
- Oedema of the hands and feet.
- Cervical lymphadenopathy.
- Seen in childhood.
- 50% of cases are seen in children <2 years.
Describe the investigation findings for Kawasaki disease. (LO3)
- ANCA test is negative.
Describe the presentation of granulomatosis with polyangiitis (GPA). (LO3)
- Also known as Wegener’s granulomatosis (WG) - changed cos he was evil (Nazi).
- Granulomata and vasculitis.
- ENT involvement - nasal, collapsed nose (saddle nose).
- Pulmonary-renal syndrome - histologically seen granuloma formation.
- Generalised form is fatal if untreated.
Describe the investigation findings for granulomatosis with polyangiitis (GPA). (LO3)
- Associated with proteinase 3 ANCA.
Describe the presentation of microscopic polyangiitis (MPA). (LO3)
- No granulomata.
- Predominantly kidney affected.
- Skin involvement.
- Peripheral nerves affected.
Describe the investigation findings for microscopic polyangiitis. (LO3)
- Myeloperoxidase ANCA.
Describe the presentation of eosinophilic granulomatosis with polyangiitis (EGPA). (LO3)
- Also known as Churg-Strauss syndrome (CSS) - changed cos he was also an evil Nazi.
- Resistant asthma.
- Neuropathy.
- Cardiac involvement.
- Other features of renal disease.
Describe the investigation findings for eosinophilic granulomatosis with polyangiitis (EGPA). (LO3)
- Can be associated with myeloperoxidase ANCA.
What is jaw claudication? (LO3)
Fatigue of the jaw muscles from chewing. Predictive of temporal arteritis.
List the differential diagnoses for vasculitis. (LO3)
- Bacterial endocarditis.
- Cancer (paraneoplastic).
- Systemic lupus erythematosus (SLE).
- Atrial myxoma (tumour originating in the heart).
- Cholesterol emboli.
- Calciphylaxis (calcium accumulation in the small blood vessels of fat and skin tissues).
List the different categories of investigations for vasculitis. (LO3)
- Blood test.
- ANCA.
- Urine - blood, protein, casts.
- Tissue.
- Imaging.
List the aspects of a blood test used for vasculitis investigations. (LO3)
- Haematology:
- FBC - neutrophilia, eosinophilia (EGPA).
- ESR - raised. - Biochemistry:
- Assesses organ involvement and the severity.
- CRP - raised. - Immunology.
- Complement levels.
- Rheumatoid factor.
- Protein electrophoresis.
- Serum immunoglobulins.
- Cryoglobulins.
- ANCA.
What is the ANCA test? (LO3)
There are two techniques.
- Indirect immunofluorescence technique:
- Cytoplasmic (C-ANCA) pattern found or,
- Perinuclear (P-ANCA) pattern found. - ELISA technique:
- Proteinase 3 (PR3) antibody or,
- Myeloperoxidase (MPO) antibody - associated with granulomatosis polyangiitis.
What is meant by casts? (LO3)
Casts are cells that can be detected in the urine in renal disease.
What is the definitive test for diagnosing vasculitidies? (LO3)
- Biopsy is highly recommended, although the yield is variable.
- Renal biopsy is best and almost always positive.
- Biopsy can be taken from any tissue.
- Arteries can be biopsied but only small vessels are easily biopsied.
List the different types of imaging used for investigation vasculitis. (LO3)
Artery-specific imaging for large and medium vessel disease:
- Angiography - dye is injected into an artery.
- Magnetic resonance imaging (MRI).
- Positron emission tomography (PET).
- Ultrasound.
Tissue-specific imaging for small vessel vasculitis.
Describe the management for large vessel vasculitis. (LO3)
- Glucocorticoids.
- Immunosuppressive agents.
Describe the management for polyarteritis Nodosa (PAN), microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA). (LO3)
Localised:
- Methotrexate.
- Steroids.
Generalised:
- Cyclophosphamide.
- Steroids.
Describe the management for resistant vasculitis (ANCA positive). (LO3)
- Rituximab.
List the reasons for needing to monitor vasculitis patients closely. (LO3)
- Comorbidities.
- Treatment side effects.
List the relevant comorbidities to be aware of when monitoring vasculitis patients. (LO3)
- Elderly - they may have other comorbidities that may be exacerbated by vasculitis.
- Cardiac comorbidity - vasculitis would exacerbate cardiac symptoms.
- Risk of relapse - vasculitis could become chronic.
Describe the treatment side effects to be aware of when monitoring vasculitis patients. (LO3)
- Steroids - bone health, prescribe bisphosphonates and dosage of steroids should be reduced where possible.
- Immunosuppressive agents, especially cyclophosphamide can cause bladder complications.
Describe the prognosis of vasculitis. (LO3)
- If left untreated, survival chances are low.
- With treatment, 60-75% of patients survive 10 years post-vasculitis.
List the prognostic factors for vasculitis. (LO3)
- Age.
- Target organ involvement.
- Damage caused.
List the secondary causes of death from vasculitis. (LO3)
- Infection.
- Target organ damage.
- Cancer.
Obviously, death could be directly due to the vasculitis itself.
What is meant by connective tissue disease? (LO4)
This describes conditions where the connective tissues of the body are targeted. Generally, these are multi-system inflammatory disorders associated with immunological abnormalities. They share many clinical features.
List some single-gene defect connective tissue diseases. (LO4)
- Ehlers-Danlos syndrome.
- Epidermolysis Bullosa.
- Marfan syndrome.
- Osteogenesis imperfecta.
List some autoimmune inflammatory connective tissue diseases. (LO4)
- Polymyositis.
- Dermatomyositis.
- Rheumatoid arthritis.
- Scleroderma.
- Sjogren’s syndrome.
- Systemic lupus erythematosus (SLE).
- Vasculitis.
What is Raynaud’s phenomenon? (LO4)
- Temporary spasm of blood vessels which block the flow of blood.
- Triphasic colour change: white, blue, red.
- Fingers, toes, ears, nose, lips or nipples affected.
- Usually triggered by cold temperatures, anxiety or stress.
Describe the triphasic colour change in Raynaud’s phenomenon. (LO4)
- White: immediate lack of blood.
- Blue: lasting lack of blood.
- Red: when blood flow is restored (rushes back in).
List the areas that can potentially be affected by Raynaud’s phenomenon. (LO4)
- Fingers.
- Toes.
- Ears.
- Nose.
- Lips.
- Nipples.
List the symptoms of Raynaud’s phenomenon. (LO4)
- Pain.
- Numbness.
- Pins and needles.
Describe the management of Raynaud’s phenomenon. (LO4)
- Keep warm.
- Stop smoking.
- Calcium-channel blockers.
- Iloprost.
- Sildenafil (usually used in erectile dysfunction).
Describe Raynaud’s phenomenon as part of SLE. (LO4)
- Common symptoms and may predate other symptoms.
- Consider secondary Raynaud’s.
Describe the signs of Raynaud’s phenomenon. (LO4)
- Capillary nail-fold loops (and vegatable oil placed on skin) can show loss of normal loop pattern.
- Chronic ischaemia may lead to colour change.
- Digital ulcers in severe diseases.
Describe the maintenance therapy for SLE. (LO4)
- Taper prednisolone, long-term, low-dose.
- Immunosuppressants: azathioprine. methotrexate, MMF.
- Assess cardiovascular risk factors (hypertension and hyperlipidaemia).
- Patients should be advised to stop smoking.
- Anticoagulation with warfarin if thrombosis and antiphospholipid syndrome.
- Assess risk of osteoporosis and hypovitaminosis D.
What is systemic sclerosis (SS)? (LO4)
- Causes fibrosis affecting: skin, internal organs and vasculature.
- Categorised by Raynaud’s phenomenon, sclerodactyly and cardiac, lung, gastrointestinal and renal disease.
- Subdivides into:
1. Diffuse cutaneous systemic sclerosis.
2. Limited cutaneous systemic sclerosis.
Describe the epidemiology of systemic sclerosis. (LO4)
- Onset in 40-50s.
- 10-20 cases per 100,000.
- More likely in women, 4:1.