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.