Musculoskeletal Flashcards
What is the definition and epidemiology of Amyloidosis?
Amyloidosis is a group of diseases in which abnormal protein, known as amyloid fibrils, build up in tissue. There are about 30 different type of amyloidosis, each due to a specific protein mis-folding. Deposits of amyloid may be localised in tissue or part of a systemic process. It is quite rare, with 60 new cases a year. Median age is 64 years at diagnosis, but patients can present at any age.
What is the aetiology of Amyloidosis?
Primary amyloidosis is also known as immunoglobulin light chain amyloidosis. It is similar to multiple myeloma in the sense that it involves clonal plasma cells releasing light chains. However there is a distinction in the percentage of plasma cells in the bone marrow. Less than 0.5% of amyloid patients go on to develop multiple myeloma during the course of their disease.
Secondary amyloidosis can be divided into familial and non-familial:
Non-familial:
○ Inflammatory polyarthropathies account for 60% of cases. Conditions include rheumatoid arthritis, juvenile arthritis, psoriatic arthritis and ankylosing spondylitis.
○ Chronic infections such as bronchiectasis, subcutaneous injection of illicit drugs, decubitus ulcers, chronic UTIs and osteomyelitis.
○ Inflammatory bowel disease specifically Crohn’s disease can result in secondary amyloidosis.
○ Castleman’s disease is a lymphoproliferative disorder where the plasma cell variant can cause secondary amyloidosis.
Familial is caused by familial mediterranean fever, TNF receptor-associated periodic fever syndromes, Muckle-Wells syndrome, Hyper-IgD syndrome.
What are the clinical features of Amyloidosis?
Presentation is broad and depends on the site of amyloid accumulation. The kidneys and heart are the most common organs involved.
Amyloid deposition in the kidneys can cause Nephrotic Syndrome. This presents as lower extremity oedema (due to Hypoalbuminaemia).
Amyloid deposition in the heart causes restrictive cardiomyopathy. This produces a raised JVP, as well as symptoms of heart failure such as fatigue, dyspnoea on exertion.
People with amyloidosis do not get CNS involvement but can develop sensory and autonomic neuropathies. These develop in a symmetrical pattern an progresses in a distal to proximal manner. Autonomic neuropathy can present as orthostatic hypotension, but manifest more gradually with nonspecific gastrointestinal symptoms like constipation, nausea, or early satiety.
Other key diagnostic features include periorbital purpura - present in 15% of patients - eyelid petechial are common, and macroglossia which may cause sleep apnoea.
How can Amyloidosis be investigated?
Serum immunofixation and urine immunofixation can confirm the presence of monoclonal protein.
Immunoglobulin free light chain assay will show an abnormal kappa:lambda ratio. This test is relatively new but has a extremely high sensitivity.
Bone marrow biopsy is a good source of tissue, and shows clonal plasma cells.
Tissue biopsy can show the presence of amyloids. Seen as a positive green birefringence when stained with Congo red.
What is the definition and epidemiology of Ankylosing Spondylitis?
Ankylosing Spondylitis is a chronic progressive inflammatory arthropathy commonly affecting the spine and sacroiliac joints. It is the most common of the seronegative spondyloarthropaties affecting 150 per 100 000. Affects men more than women 3:1, and peaks at ages 17-35.
What is the aetiology of Ankylosing Spondylitis?
Caused by both genetic and environmental factors. Strongly genetic with heritability of 97%. HLA-B27 is the most common predisposing gene.
What are the symptoms of Ankylosing Spondylitis?
As sacroiliac joint is usually affected first, patient present with dull back pain (radiating to the hips and buttocks) and stiffness for >6 months. The symptoms are worse at night and in the early morning and relieved by exercise and worsened by rest.
Soon after, there is also involvement of the spine (intervertebral disks, zygapophysial, costovertebral and costotransverse joints). This manifests as reduced motion in the lumbar spine and cervical spine movements can be globally reduced.
30% of patients complain of peripheral synovitis - typically asymmetrical oligoarthritis, most commonly affecting the hip and knee.
Patients also present with extra-articular features of AS. Most commonly (40%) present with iritis. Can also have apical lung fibrosis, aortic incopetence, AV node block, achilles tendinitis, and rarely amyloidosis.
What are the examination features of Ankylosing Spondylitis?
- Note loss of lumbar lordosis and increased thoracic kyphosis and neck hyperextension (question mark posture).
- Reduced chest expansion due to progressive loss of spinal movements.
How can Ankylosing Spondylitis be investigated?
Pelvic X-ray should be requested in all patients with inflammatory back pain. Sacroiliitis can be unilateral or bilateral, and graded from 1 to 4 on severity. The presence of sacroiliitis is a requirement for the diagnosis of AS (based on the modified New York classification criteria).
Bloods: • FBC is normal • ↑ESR and CRP in active disease • RF and ANA negative • HLA-B27 is positive in up to 95% of white patients with AS, but has little role in diagnosis, but may indicate a predisposition (as only 6.5% of patients with HLA-B27 will develop AS).
MRI spine may show early sacroiliitis and early inflammatory changes in the spine.
Thoracic, cervical and lumbar X-Ray (lateral) should be performed on all AS patients to give a baseline and monitor disease progression with. Late disease may show bamboo spine.
What is the definition of Antiphospholipid syndrome?
Antiphospholipid syndrome is an autoimmune hypercoagulable state caused by antiphospholipid antibodies. APS provokes thrombosis in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery and severe preeclampsia.
What is the aetiology of Antiphospholipid syndrome?
APS can occur in patients without an underlying autoimmune disease (primary APS) . Secondary APS occurs with another autoimmune disease, most notably Systemic Lupus Erythromatosus but also Sjogren’s syndrome, rheumatoid arthritis, systemic sclerosis, etc. The actual incidence of APS is unknown, and the disorder is probably underdiagnosed.
What are the clinical features of Antiphospholipid Syndrome?
Patients have a history of vascular thrombosis such as stroke, coronary artery thrombus, peripheral arterial disease, and renal thrombotic microangiopathy.
Female patients have a history of pregnancy loss, defined as three or more consecutive pregnancy losses <10 weeks’ gestation and/or unexplained foetal death >10 weeks’ gestation.
There may also be a history of pregnancy-associated morbidity such as premature delivery due to pre-eclampsia, placental abruption, growth restriction.
Patients also commonly present with features of thrombocytopaenia such as petechial rash or mucosal bleeding.
How is Antiphospholipid syndrome investigated?
The antiphospholipid antibodies must be detected and elevated on 2 occasions, 12 weeks apart:
• Lupud anticoagulant
• Anticardiolipin antibodies
• Anti-beta2-glycoprotein I antibodies
ANA, dsDNA antibdoes are positive in SLE
FBC may show thrombocytopaenia.
What is the definition and epidemiology of Behçet’s disease?
Behçet’s disease is a systemic vasculitis most commonly seen in Turkey, Israel, the Mediterranean basin, and eastern Asia. It can cause skin and mucsoal lesions, uveitis, major arterial and venous disease, and GI and neurological manifestations.
What are the clinical features of Behçet’s disease?
As the vasculitis affects any organ, there are a wide variety of symptoms.
This commonly includes recurrent oral ulcers (related to apthous ulcers but are larger, more painful and take weeks to heal) as well as painful genital ulcers in the anus, vulva or scrotum.
Patients also complain of uveitis which may be painful presenting as a redness of conjunctiva and a decrease in vision. Posterior uveitis can present as a painless decrease in vision with visual field floaters.
Folliculitis and Erythema Nodosum are also common in the lower extremities.
There may also be bowel, lung, musculoskeletal (athralgia) and neurological involvement.
How is Behçet’s disease investigated?
Importantly, the patient is RF, ANA and ANCA negative.
A skin pathergy test is performed where a subcutaneous skin prick is performed on a patient. Up to 60% of patients form a pustule within 48 hours.
What is the definition and epidemiology of Carpal Tunnel Syndrome?
CTS is a collection of symptoms and signs caused by the compression of the medial nerve in the carpal tunnel. Quite common affecting 3.7% of the population.
What are the risk factors for Carpal Tunnel Syndrome?
Risk factors include: • Age over 30 • High BMI • Female sex • Alterations in carpal tunnel space • Fractured wrist/carpal bones • Square wrist • Rheumatoid arthritis • Diabetes • Dialysis • Pregnancy
