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• Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE). Around 30% of patients with SLE have positive antiphospholipid antibodies.
• Antiphospholipid syndrome causes a paradoxical rise in the APTT. This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade.
• Antiphospholipid syndrome Investigations

  • antibodies
  • anticardiolipin antibodies
  • anti-beta2 glycoprotein I (anti-beta2GPI) antibodies
  • lupus anticoagulant
  • thrombocytopenia
  • prolonged APTT
• Antiphospholipid syndrome Management - based on EULAR guidelines

  • primary thromboprophylaxis
  • low-dose aspirin
  • secondary thromboprophylaxis
  • initial venous thromboembolic events: lifelong warfarin with a target INR of 2-3
  • recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin then consider adding low-dose aspirin, increase target INR to 3-4
  • arterial thrombosis should be treated with lifelong warfarin with target INR 2-3
• Methotrexate in 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
• Methotrexate toxicity

  • the treatment of choice is folinic acid
• Persistent fatigue, oral ulcers, and mild macrocytic anaemia are suggestive of folic acid deficiency, a common side effect of methotrexate therapy. Methotrexate inhibits dihydrofolate reductase, which is necessary for the synthesis of tetrahydrofolate - a coenzyme involved in the synthesis of purines and pyrimidines. This can lead to reduced production of red blood cells resulting in megaloblastic anaemia characterised by macrocytosis.
• Prescribing methotrexate

  • methotrexate is taken weekly, rather than daily
  • FBC, U&E and LFTs need to be regularly monitored (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)
• Adjusted calcium, PTH, ALP and PO4 levels are usually normal in osteogenesis imperfecta. This is also known as brittle bone disease. It is a group of disorders of collagen metabolism, resulting in bone frailty and fractures. The most common and mild form is type 1. Presenting features include fractures following minor trauma, blue sclera, deafness secondary to otosclerosis and dental imperfection. It is usually diagnosed in childhood.
• A raised adjusted calcium raised PTH, normal ALP and low PO4 may be seen in primary hyperparathyroidism. ALP may be normal or raised here.Low adjusted calcium, low PTH, normal ALP and raised PO4 may be seen in hypoparathyroidism. Low adjusted calcium, high PTH, normal ALP and low PO4 can be seen in secondary hyperparathyroidism. PO4 levels can be variable here. Raised adjusted calcium, low PTH, raised ALP and raised PO4 may be seen when there is a malignant PTH related protein. This can occur in certain cancers including squamous cell lung cancer. ALP may be normal here also.
• Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy. It typically presents in males (sex ratio 3:1) aged 20-30 years old.
• Plain x-ray of the sacroiliac joints is the most useful investigation in establishing a diagnosis of ankylosing spondylitis. Radiographs may be normal early in disease, later changes include:

  • sacroiliitis: subchondral erosions, sclerosis
  • squaring of lumbar vertebrae
  • 'bamboo spine' (late & uncommon)
  • syndesmophytes: due to ossification of outer fibers of annulus fibrosus
  • chest x-ray: apical fibrosis

  If negative, the next step in the evaluation should be obtaining an MRI. Signs of early inflammation involving sacroiliac joints (bone marrow oedema) confirm the diagnosis
• Spirometry in ankylosing spondylitis may show a restrictive defect due to a combination of pulmonary fibrosis, kyphosis and ankylosis of the costovertebral joints.
• Proximal muscle stiffness that is worse in the morning and improves throughout the day is highly suggestive of polymyalgia rheumatica (PMR), and bilateral headaches and vision loss are suggestive of giant cell arteritis (GCA). PMR is linked with GCA in ~25% of cases.
• GCA can lead to vision loss and this is a result of anterior ischaemic optic neuropathy due to the immune system damaging arteries supplying the optic nerve, leading to thrombus formation and occlusion, leading to the death of nerve fibres at the anterior aspect of the optic nerve. The ischaemia in the optic nerve leads to optic disc pallor.
• Temporal arteritis (also known as giant cell arteritis: GCA) is a vasculitis of unknown cause that affects medium and large-sized vessels arteries. It occurs in those over 50 years old, with a peak incidence in patients who are in their 70s. It requires early recognition and treatment to minimize the risk of complications such as permanent loss of vision. Hence, when temporal arteritis is suspected, treatment must be started promptly with high-dose prednisolone as well as urgent referral for assessment by a specialist.
• GCA Investigations

  • raised inflammatory markers
  • ESR > 50 mm/hr (note ESR < 30 in 10% of patients)
  • CRP may also be elevated
  • temporal artery biopsy
  • skip lesions may be present
  • note creatine kinase and EMG normal
• GCA Treatment

  • urgent high-dose glucocorticoids should be given as soon as the diagnosis is suspected and before the temporal artery biopsy
  • if there is no visual loss then high-dose prednisolone is used
  • if there is evolving visual loss IV methylprednisolone is usually given prior to starting high-dose prednisolone
  • there should be a dramatic response, if not the diagnosis should be reconsidered
  • urgent ophthalmology review
  • other treatments - bone protection with bisphosphonates is required as long, tapering course of steroids is required
• In contrast to other DMARDs, sulfasalazine is considered safe to use in both pregnancy and breastfeeding.
• Corticosteroids impair bone remodelling by diminishing osteoblast numbers and augmenting osteoclast activity, leading to increased bone resorption and subsequent bone loss.The BNF recommends alendronic acid—or risedronate sodium—as the first-line treatment for the prevention of glucocorticoid-induced osteoporosis. This inhibits osteoclast-mediated bone resorption.A daily dietary supplement containing calcium and colecalciferol—a form of vitamin D— alone does not constitute sufficient bone protection for patients commencing long-term corticosteroid therapy.
• A ruptured baker's cyst would typically present with a painful swelling behind the knee, and without erythema
• • Subscapularis - positioned anteriorly on your chest, helps with internal rotation of shoulder
  • Supraspinatus - positioned on top of your shoulder and runs parallel to your deltoid. Needed for the first 20° of shoulder abduction, then the rest of abduction is done by the deltoid
  • Infraspinatus - positioned posteriorly on the superior aspect of your back, helps with external rotation of shoulder
  • Teres minor - positioned posteriorly on the superior aspect of your back, helps with external rotation of shoulder
• Osteoarthritis - Pain exacerbated by exercise and relieved by restReduction in internal rotation is often the first signAge, obesity and previous joint problems are risk factors
• Inflammatory arthritis - Pain in the morningSystemic featuresRaised inflammatory markers
• Referred lumbar spine pain - Femoral nerve compression may cause referred pain in the hipFemoral 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
• Greater trochanteric pain syndrome (Trochanteric bursitis) - Due to repeated movement of the fibroelastic iliotibial bandPain and tenderness over the lateral side of thighMost common in women aged 50-70 years
• Meralgia paraesthetica - Caused by compression of lateral cutaneous nerve of thighTypically burning sensation over antero-lateral aspect of thigh
• Avascular necrosis - Symptoms may be of gradual or sudden onsetMay follow high dose steroid therapy or previous hip fracture or dislocation
• Pubic symphysis dysfunction - Common in pregnancyLigament laxity increases in response to hormonal changes of pregnancyPain over the pubic symphysis with radiation to the groins and the medial aspects of the thighs. A waddling gait may be seen
• Transient idiopathic osteoporosis - An uncommon condition sometimes seen in the third trimester of pregnancyGroin pain associated with a limited range of movement in the hipPatients may be unable to weight bearESR may be elevated
• Hypermobility, tall stature, long fingers are all features of Marfan's disease, especially given the family history of aortic dissection.

  A high-arched palate is associated with Marfan's, not a cleft palatePes planus (flat foot) is associated with Marfan's, not talipes equinovarus (clubfoot) or hallux valgusA positive Schober's test is associated with ankylosing spondylitis and has nothing to do with Marfan's
• Marfan's syndrome is an autosomal dominant connective tissue disorder. It is caused by a defect in the FBN1 gene on chromosome 15 that codes for the protein fibrillin-1.
• Patients who are allergic to aspirin may also react to sulfasalazine
• asymmetrical polyarthritis that worsens in the morning is a classical feature of psoriatic arthritis. soft tissue manifestations are evident through dactylitis
• Psoriatic arthropathy is an inflammatory arthritis associated with psoriasis and is classed as one of the seronegative spondyloarthropathies. It correlates poorly with cutaneous psoriasis and often precedes the development of skin lesions.

  • psoriatic skin lesions
  • periarticular disease - tenosynovitis and soft tissue inflammation resulting in:
  • enthesitis
  • tenosynovitis
  • dactylitis
  • nail changes
  • pitting
  • onycholysis
• Psoriatic arthritis X-ray

  • often have the unusual combination of coexistence of erosive changes and new bone formation
  • periostitis
  • 'pencil-in-cup' appearance
• Bisphosphonates have a range of side effects, most notably oesophageal problems such as oesophagitis and ulceration, acute phase response characterised by fever, myalgia and arthralgia, and hypocalcaemia. This
• Amlodipine is a calcium channel blocker used in angina and hypertension. While it can cause dyspepsia, it does not cause gastrointestinal ulceration. Furthermore, some studies have shown that amlodipine may be protective. Common side effects of amlodipine include constipation, lower limb oedema, and headache.
• De Quervain's tenosynovitis tends to present with wrist pain but pains can radiate up the forearm. Exacerbation is typically seen with hand gripping or thumb extension.
• Cervical radiculopathy is caused by spinal nerve impingement as they exit the spinal cord. This typically presents with neck pain but will also be associated with other neurological symptoms like decreased sensation, muscular weakness not limited by pain and a ' pins and needles' sensation.