Rheumatology Flashcards
1
Q
Osteoarthritis note:
A
Osteoarthritis is not an inflammatory condition like RA. It occurs in the synovial joints and is a result of a combination of genetic factors, overuse and injury.
2
Q
RF’s for osetoarthritis ?
A
- Obesity
- Age
- Occupation
- Trauma
- Being female
- Family history
3
Q
It is thought that osteoarthritis is the result of an imbalance between the cartilage being worn down and the chondrocytes repairing it, leading to structural issues in the joint. These abnormalities can be seen on an xray, what are they ?
A
Four key Xray changes (LOSS):
- L - Loss of joint space
- O - Osteophytes
- S - Subarticular sclerosis (increased density of the bone along the joint line)
- S - Subchondral cysts (fluid filled holes in the bone)
Note: Xray changes do no necessarily correlate with symptoms. Significant xray changes might be found incidentally in someone without symptoms. Equally, someone with severe symptoms of osteoarthritis may have only mild changes on an xray.
4
Q
Presentation of osteoarthritis ?
A
It presents with joint pain and stiffness. This pain and stiffness tends to be worsened by activity in contrast to inflammatory arthritis where activity improves symptoms. It also leads to deformity, instability and reduced function in the joint.
5
Q
What joints are commonly affected in osteoarthritis ?
A
- Hips
- Kness
- Sacro-iliac joints
- Distal interphalangeal joints (DIPs)
- The MCP joint at the base of the thumb
- Wrist
- Cervical spine
6
Q
Signs of osteoarthritis in the hands ?
A
- Heberdens nodes (in the DIP joints)
- Bouchards nodes (in the PIP joints)
- Squaring at the base of the thumb at the carpo-metacarpal joint
- Weak grip
- Reduced range of motion
Note: The carpo-metacarpal joint at the base of the thumb is a saddle joint with the metacarpal bone of the thumb sat on the trapezius bone, using it like a saddle. It gets a lot of use from everyday activities. This makes it prone to wear when used for complex movements.
7
Q
Diagnosis of osteoarthritis ?
A
NICE (2014) suggest that a diagnosis can be made without any investigations if the pt is over 45, has typical activity related pain and has no morning stiffness or stiffness lasting less than 30 minutes.
8
Q
Management of osteoarthritis ?
A
Start with patient education about the condition and advise on lifestyle changes such as weight loss if overweight to reduce the load on the joint, physiotherapy to improve strength to support the joint and occupational therapy and orthotics to support activities and function.
Stepwise use of analgesia to control the symptoms:
- Oral paracetamol and topical NSAIDs or topical capsaicin (chilli pepper extract)
- Add oral NSAIDs and consider also prescribing a PPI to protect their stomach such as omeprazole. They are better used intermittently rather than continuously.
- Consider opiates such as codeine and morphine. These should be used cautiously as they can have significant side effects and pts can develop dependence and withdrawal. They also don’t work for chronic pain and result in pts becoming dependent without benefitting from pain relief
Intra-articular steroid injections provide a temporary reduction in inflammation and improve symptoms.
Joint replacement can be used in severe cases. The hip and knee are the most commonly replaced joints.
9
Q
What is rheumatoid arthritis ?
A
It is an autoimmune condition that causes chronic inflammation of the synovial lining (synovitis) of the joints, tendon sheaths and bursa. It is a symmetrical polyarthritis. Inflammation of the tendons increases the risk of tendon rupture.
10
Q
Is RA more common in men or women, at what age does it usually present and is family history relevant ?
A
It is three times more common in women than men.
It most often develops in middle age but can present at any age. Family history is relevant and increases the risk of RA.
11
Q
Genetic associations of RA ?
A
HLA DR4 (a gene often present in RF positive pts) HLA DR1 (a gene occasionally present in RA pts)
12
Q
What is rheumatoid factor, what does it target,what does this lead to and what class of immunoglobulin is RF normally ?
A
It is an autoantibody presenting in around 70% of RA pts. It targets the Fc portion of the IgG antibody. This causes activation of the immune system against the pts own IgG resulting in systemic inflammation. RF is most often IgM, however they can be any class of immunoglobulin.
13
Q
What are anti-citrullinated cyclic antibodies (anti-CCP antibodies) ?
A
Autoantibodies that are more sensitive and specific to RA than RF. Anti-CCP antibodies often pre-date the development of the RA and give an indication that a pt will go on to develop RA at some point.
14
Q
Presentation of RA ?
A
It typically presents with a symmetrical distal polyarthropathy. The key symptoms are joint:
- Pain
- Swelling
- Stiffness
Pts usually attend complaining of pain and stiffness in the small joints of the hands and feet, typically the wrist, ankle, MCP and PIP joints in the hands. They can also present with larger joints affected such as the knees, shoulders and elbows. The onset can be very rapid (i.e. overnight) or over months to years.
There are also associated systemic symptoms:
- Fatigue
- Weight loss
- Flu like illness
- Muscle aches and weakness
15
Q
TOM TIP:
A
Pain from an inflammatory arthritis is worse after rest but improves with activity. Pain from a mechanical problem such as osteoarthritis is worse with activity and improves with rest.
16
Q
What is palindromic rheumatism, how long does it last and what may indicate that it will progress to full RA ?
A
This involves self limiting short episodes of inflammatory arthritis with joint pain, stiffness and swelling typically affecting only a few joints. The episodes typically only last 1-2 days and then completely resolve. Having positive antibodies (RF and anti-CCP) may indicate that it will progress to full RA.
17
Q
Common joints affected by RA ?
A
- PIP joints
- MCP joints
- Wrist and ankle
- MTP joints
- Cervical spine
- Large joints can also be affected such as the knee, hips and shoulders
18
Q
TOM TIP
A
The DIP joints are almost never affected by RA. If you come across enlarged painful DIP joints this is most likely to be Heberden’s nodes due to osteoarthritis.
19
Q
What is atlantoaxial subluxation ?
A
It occurs in the cervical spine of RA pts. The axis (C2) and the odontoid peg shift within the atlas (C1). This is caused by local synovitis and damage to the ligaments and bursa around the odontoid peg of the axis. Subluxation can cause spinal cord compression and is an emergency. This is particularly important if the pt is having a general anaesthetic and requiring intubation. MRI scans can visualise changes in these areas as part of pre-operative assessment.
20
Q
Signs in the hands of RA ?
A
- Z shaped deformity to the thumb
- Swan neck deformity (hyperextended PIP with flexed DIP)
- Boutonnieres deformity (hyperextended DIP with flexed PIP)
- Ulnar deviation of the fingers from the MCP joints
21
Q
Extra-articular manifestations of RA ?
A
- Pulmonary fibrosis with pulmonary nodules (Caplan’s syndrome)
- Bronchiolitis obliterans (inflammation causing small airway destruction)
- Felty’s syndrome (RA, neutropenia and splenomegaly)
- Secondary Sjogren’s Syndrome (AKA sicca syndrome)
- Anaemia of chronic disease
- CVD
- Eye manifestations
- Rheumatoid nodules
- Lymphadenopathy
- Carpal tunnel syndrome
- Amyloidosis
22
Q
Name some eye related complications of RA ?
A
- Scleritis
- Episcleritis
- Keratitis
- Keratoconjunctivitis sicca
- Cataracts (secondary to steroids)
- Retinopathy (secondary to chloroquine)
23
Q
The diagnosis of RA is clinical in pts with features of RA (i.e. symmetrical polyarthropathy affecting small joints). Which extra investigations are required at diagnosis ?
A
- Check RF
- If RF negative, check anti-CCP antibodies
- Inflammatory markers such as CRP and ESR
- X-ray of hands and feet
US scan of the joints can be used to evaluate and confirm synovitis. It is particularly useful where the findings of the clinical examination are unclear.
24
Q
Xray changes seen in RA (4) ?
A
- Joint destruction and deformity
- Soft tissue swelling
- Periarticular osteopenia
- Bony erosions
25
When do NICE recommend a referral of suspected RA and when would it be urgent ?
Any adult with persistent synovitis, even if they have negative RF, anti-CCP antibodies and inflammatory markers.
The referral should be urgent if it involves the small joints of the hands or feet, multiple joints or symptoms have been present for more than 3 months.
26
Diagnosis of RA note:
Diagnostic criteria come from the American College of Rheumatology (ACR) / European League Against Rheumatism (ELAR) from 2010. Pts are scored based on:
- The joints that are involved (more and smaller joints score higher)
- Serology (RF and anti-CCP)
- Inflammatory markers (ESR and CRP)
- Duration of symptoms (more or less than 6 weeks)
Scores are added up and a score greater than or equal to 6 indicates a diagnosis of RA.
27
What is the DAS28 score + what is it used for ?
It is the disease activity score. It is based on the assessment of 28 joints and points are given for:
- Swollen joints
- Tender joints
- ESR / CRP result
It is useful in monitoring disease activity and response to treatment in RA.
28
What is the health assessment questionnaire (HAQ) ?
The questionnaire measures functional ability. NICE recommend using this at diagnosis of RA to check the response to treatment.
29
Prognosis of RA ?
Prognosis varies between pts from mild and remitting to severe and progressive. There is a worse prognosis with:
- Younger onset
- Male
- More joints and organs affected
- Presence of RF and anti-CCP antibodies
- Erosions seen on xray.
30
Management of RA ?
Starting treatment early is associated with better outcomes. It is important to have fully involvement of MDT including specialist nurses, physiotheraphy, OT, psychology and podiatry.
A short term of steroids can be used at first presentation and during flare ups to quickly settle the disease. NSAIDs are often effective but risk upper GI bleeding so are often avoided or co-prescribed with PPIs.
The aim is to induce remission or get as close to remission as possible. CRP and DAS28 is used to monitor the success of treatment. Aim to reduce the dose to the "minimal effective dose" that controls the disease.
NICE guidelines for DMARDS:
- First line is monotherapy with methotrexate, leflunomide or sulfasalazine. Hydroxychloroquine can be considered in mild disease and is considered the "mildest" anti rheumatic drug.
- Second line is 2 of these used in combination
- Third line is methotrexate plus a biological therapy, usually a TNF inhibitor.
- Fourth line is methotrexate plus rituximab.
Note: Pregnant women tend to have an improvement in symptoms during pregnancy, probably due to the higher natural production of steroid hormones. Sulfasalazine and hydroxychloroquine are considered as DMARDs in pregnancy.
31
Biology therapies used in RA treatment with examples:
Anti - TNF (adalimumab, infliximab, etanercept)
Anti - CD20 (rituximab)
Anti - IL6 (sarilumab)
Anti - IL6 receptor (tocilizumab)
JAK inhibitors (tofacitinib and baricitinib)
32
TOM TIP:
The most important biologics to remember are the TNF inhibitors adalimumab, infliximab and etanercept and it is also worth remembering rituximab. The others are very unlikely to come up in your exams but are worth being aware of. Just remember they all lead to immunosuppression so pts are prone to serious infections. They can also lead to reactivation of dormant infections such as TB and hepatitis B.
33
Note:
Orthopaedic surgery used to be an important part of managing RA where joint deformities caused significant problems with function, however the DMARDs and biologics mean that now pts are less likely to progress to that stage.
34
Discuss how methotrexate is used in the management of RA (include notable side effects) ?
It works by interfering with the metabolism of folate and suppressing certain components of the immune system. It is taken by injection or tablet once a week. Folic acid 5mg is also prescribed once a week to be taken on a different day to the methotrexate.
Notable side effects:
- Mouth ulcers and mucositis
- Liver toxicity
- Pulmonary fibrosis
- Bone marrow suppression and leukopenia (low white blood cells)
- It is teratogenic so needs to be avoided prior to conception in mothers and fathers.
35
What is leflunomide and how is it used in the management of RA (include notable side effects) ?
It is an immunosuppressant medication that works by interfering with the production of pyrimidine. Pyrimidine is an important component of RNA and DNA.
Notable side effects:
- Mouth ulcers and mucositis
- Increased blood pressure
- Rashes
- Peripheral neuropathy
- Liver toxicity
- Bone marrow suppression and leukopenia (low white blood cells)
- It is teratogenic so needs to be avoided prior to conception in mothers and fathers.
36
What is sulfasalazine (include notable side effects) ?
It works as an immunosuppressive and anti-inflammatory medication. It appears to be safe in pregnancy however women need adequate folic acid supplementation.
Notable side effects:
- Temporary male infertility (reduced sperm count)
- Bone marrow suppression
37
What is hydroxychloroquine and how is it used in the management of RA (include notable side effects) ?
It is traditionally an anti-malarial medication. It acts as an immunosuppressive medication by interfering with Toll-like receptors, disrupting antigen presentation and increasing the pH in the lysosomes of immune cells. It is thought to be safe in pregnancy.
Notable side effects:
- Nightmares
- Reduced visual acuity (macular toxicity)
- Liver toxicity
- Skin pigmentation
38
How do anti-TNF drugs work and name some examples (include side effects)?
Tumour necrosis factor is a cytokine involved in stimulating inflammation. Blocking TNF reduces inflammation. Some examples of anti-TNF drugs are:
- Adalimumab
- Infliximab
- Golimumab
- Certolizumab pegol
- Entanercept
Notable side efects:
- Vulnerability to severe infections and sepsis
- Reactivation of TB and hep B
Note: Adalimumab, infliximab, golimumab and certolizumab pegol are monoclonal antibodies to TNF. Entanercept is a protein that binds TNF to the Fc portion of IgG and thereby reduces its activity.
39
What is rituximab, what is it used for and name some notable side effects ?
It's a monoclonal antibody that targets the CD20 protein on the surface of B cells. This causes destruction of B cells. It is used for immunosuppression in autoimmune conditions such as RA and cancers relating to B cells.
Notable side effects:
- Vulnerability to severe infections and sepsis
- Night sweats
- Thrombocytopenia
- Peripheral neuropathy
- Liver and lung toxicity
40
(RA management ) TOM TIP: There are a lot of side effects to remember for your exams. Many of them are shared between medications. Try to remember the unique ones as these are more likely to be tested
Methotrexate: pulmonary fibrosis
Leflunomide: HTN and peripheral neuropathy
Sulfasalazine: Male infertility (reduces sperm count)
Hydroxychloroquine: Nightmares and reduced visual acuity
Anti-TNF medications: Reactivation of TB or hep B
Rituximab: Night sweats and thrombocytopenia
41
What is psoriatic arthritis ?
An inflammatory arthritis associated with psoriasis.
42
Psoriatic arthritis can vary in severity. Pts may have a mild stiffening and soreness in the joint or the joint can be completely destroyed in a condition called what ?
Arthritis mutilans
43
How common is psoriatic arthritis in pts that have psoriais, when does it usually occur / at what age ?
It occurs in 10-20% of pts with psoriasis and usually occurs within 10 years of developing the skin changes. It typically affects people in middle age but can occur at any age.
44
Psoriatic arthritis is part of what group of conditions ?
The seronegative arthropathies
45
Patterns of presentation of psoriatic arthritis ?
The condition does not have a single pattern of affected joints in the same way as osteoarthritis or rheumatoid. There are several recognised patterns:
Symmetrical polyarthritis - presents similarly to RA and is more common in women. The hands, wrists, ankles and DIP joints are affected. The MCP joints are less commonly affected (unlike rheumatoid).
Asymmetrical pauciarthritis - affecting mainly the digits and feet. Pauciarthritis describes when the arthritis only affects a few joints.
Spondylitic pattern - is more common in men. It presents with:
- Back stiffness
- Sacroiliitis
- Atlanto-axial joint involvement
Other areas can be affected:
- Spine
- Achilles tendon
- Plantar fascia
46
Signs of psoriatic arthritis ?
- Plaques of psoriasis on the skin
- Nail pitting
- Onycholysis (separation of the nail from the nail bed)
- Dactylitis (inflammation of the full finger)
- Enthesitis (inflammation of the entheses, which are the points of insertion of tendons into bone)
47
Other associations of psoriatic arthritis ?
- Eye disease (conjunctivitis and anterior uveitis)
- Aortitis
- Amyloidosis
48
Screening tool for pts with psoriasis to screen for psoriatic arthritis + what would a high score trigger ?
Psoriasis epidemiological screening tool (PEST)
A high score triggers a referral to a rheumatologist
49
Xray changes seen in psoriatic arthritis ?
- Periostitis - causes a thickened and irregular outline of bone
- Ankylosis - is where bones join together causing joint stiffening
- Osteolysis - is destruction
- Dactylitis
- Pencil in cup appearance
Note: The classic xray change to the digits is the "pencil-in cup appearance". This is where there are central erosions of the bone beside the joint. This causes the appearance of one bone in the joint being hollow and looking like a cup whilst the other is narrow and sits in the cup.
50
What is arthritis mutilans, where does it occurs and what happens ?
The most severe form of psoriatic arthritis. It occurs in the phalanxes. There is osteolysis of the bones around the joints in the digits. This leads to progressive shortening of the digit. The skin then folds as the digit shortens giving an appearance that is often called a "telescopic finger"
51
Management of psoriatic arthritis ?
Similar to the management of RA. There is a crossover between the systemic treatments of psoriasis and treatment of psoriatic arthritis. Treatment is often coordinated between dermatologists and rheumatologists.
Depending on the severity the pt might require:
- NSAIDs for pain
- DMARDS (methotrexate, leflunomide or sulfasalazine)
- Anti-TNF medications (etanercept, infliximab or adalimumab)
- Ustekinumab is last line (after anti-TNF medications) and is a monoclonal antibody that targets interleukin 12 and 23
52
What is reactive arthritis ?
Where synovitis occurs in the joints as a reaction to a recent infective trigger.
It used to be known as Reiter syndrome
53
Presentation of reactive arthritis ?
It typically causes an acute monoarthritis, affecting a single joint in the lower limb (most often the knee) presenting with a warm, swollen and painful joint.
54
Obvious differential diagnosis to reactive arthritis + difference between the two ?
Septic arthritis (infection in the joint). In reactive arthritis there is no joint infection.
55
Common infections that trigger reactive arthritis ?
Gastroenteritis and sexually transmitted infections. Chlamydia is the most common sexually transmittted cause of reactive arthritis.
56
Reactive arthritis is part of what group of conditions + what gene is it linked with ?
The seronegative spondyloarthopathies.
The HLA B27 gene
57
Associations of reactive arthritis ?
- Bilateral conjunctivitis (non-infective)
- Anterior uveitis
- Circinate balanitis - is dermatitis of the head of the penis
58
TOM TIP:
These features of reactive arthritis (eye problems, balanitis and arthritis) lead to the saying "cant see, pee or climb a tree".
59
Management of reactive arthritis ?
Pts presenting with an acute warm, swollen, painful joint need to be treated according to the local "hot joint" policy. This will involve giving antibiotics until the possibility of septic arthritis is excluded. Aspirate the joint and send a sample for gram staining, culture and sensitivity testing to exclude septic arthritis.
Aspirated fluid can also be sent for crystal examination to look for gout and pseudogout.
Management of reactive arthritis when septic arthritis is exclude:
- NSAIDs
- Steroid injections into the affected joints
- Systemic steroids may be required, particularly where multiple joints are affected.
Most cases resolve within 6 months and don't recur. Recurrent cases may require DMARDs or anti-TNF medications.
60
What is ankylosing spondylitis ?
An inflammatory condition mainly affecting the spine that causes progressive stiffness and pain
61
AS is part of which group of conditions + is linked to what gene
The seronegative spondyloarthropathies
The HLA B27 gene
62
Key joints affected by AS ?
The sacroiliac joints and the joints of the vertebral column.
63
AS can progress and cause what of the spine and sacroiliac column ?
Fusion
64
Fusion of the spinal bodies gives what classical xray finding ?
"Bamboo spine"
65
Presentation of AS ?
Typically a young male in their late teens or 20s. It affects males three times more often than females. Symptoms gradually develop over more than 3 months.
The main presenting features are lower back pain and stiffness and sacroiliac pain in the buttock region. The pain and stiffness is worse with rest and improves with movement. The pain is worse at night and in the morning and may wake them from sleep. It takes at least 30 minutes for the stiffness to improve in the morning and it gets progressively better with activity through the day.
Symptoms can fluctuate with flares of worsening symptoms and other periods where symptoms improve.
Vertebral fractures are a key complication of AS.
66
Associations of AS
- Systemic symptoms - such as weight loss and fatigue
- Chest pain - related to costovertebral and costosternal joints
- Enthesitis - inflammation of the entheses. This is where tendons or ligaments insert in to bone. This can cause problems such as plantar fasciitis and achilles tendonitis.
- Dactylitis - inflammation in a finger or toe
- Anaemia
- Anterior uveitis
- Aortitis
- Heart block - can be caused by fibrosis of the heart's conduction system
- Restrictive lung disease - can be caused by restricted chest wall movement
- Pulmonary fibrosis
- IBD
67
What is schober's test and what disease is it used in supporting a diagnosis ?
A test used as part of a general examination of the spine.
Have the pt stand straight. Find the L5 vertebrae. Mark a point 10cm above and 5cm below this point. Then ask the pt to bend forward as far as they can and measure the distance between the points. If the distance with them bending forwards is less than 20cm, this indicates a restriction in lumbar movement and will help support a diagnosis of spondylitis.
68
Investigations for AS ?
- Inflammatory markers (CRP and ESR) may rise with disease activity
- HLA B27 genetic test
- Xray of the spine and sacrum
- MRI of the spine can show bone marrow oedema early in the disease before there are any xray changes
69
Xray changes seen in AS ?
"Bamboo spine" is the typical exam description of the xray appearance of the spine in the later stages of AS.
Xray images in AS can show:
- Squaring of the vertebral bodies
- Subchondral sclerosis and erosions
- Syndesmophytes - are areas of bone growth where the ligaments insert into the bone. They occur related to the liagments supporting the intervertebral joints.
- Ossification of the ligaments, discs and joints
- Fusion of the facet, sacroiliac and costovertebral joints
70
Management of ankylosing spondylitis ?
Medication:
- NSAIDs - can be used to help with pain. If the improvement is not adequate after 2 to 4 weeks of a maximum dose consider switching to another NSAID
- Steroids - can be used during flares to control symptoms. This could be oral, intramuscular slow release injections or joint injections.
- Anti-TNF medications such as etanercept or a monoclonal antibody against TNF such as infliximab, adalimumab or certolizumab pegol.
- Secukinumab is a monoclonal antibody against IL-17. It is recommended by NICE if the response to NSAIDs and TNF inhibitors is inadequate
71
Additional management for AS ?
- Physiotherapy
- Exercise and mobilisation
- Avoid smoking
- Biphosphonates to treat osteoporosis
- Treatment of complications
- Surgery is occasionally required for deformities to the spine or other joints.
72
What is systemic lupus erythematosus ?
An autoimmune inflammatory connective tissue disorder. It is "systemic" because it affects multiple organs and systems, and "erythematosus" refers to the typical red malar rash that occurs across the face.
73
What course does SLE usually take ?
A relapsing-remitting course, with flares and periods where symptoms are improved
74
The result of chronic inflammation means that pts with lupus often have a shortened life expectancy. What are the leading causes of death ?
CVD and infection
75
Pathophysiology of lupus ?
SLE is characterised by anti-nuclear antibodies. These are antibodies to proteins within the persons own cell nucleus. This causes the immune system to target these proteins. When the immune system is activated by these antibodies targeting proteins in the cell nucleus it generates an inflammatory response. Inflammation in the body leads to the symptoms of the condition. Usually inflammation is a helpful response when fighting off an infection, however it creates numerous problems when it occurs chronically and against the tissues of the body.
76
Presentation of SLE ?
SLE presents with non-specific symptoms:
- Fatigue
- Weight loss
- Arthralgia and non-erosive arthritis
- Myalgia
- Fever
- Photosensitive malar rash - This is a butterfly shaped rash across the nose and checck bones that gets worse with sunlight
- Lymphadenopathy and splenomegaly
- Shortness of breath
- Pleuritic chest pain
- Mouth ulcers
- Hair loss
- Raynaud's phenomenon
77
Investigations for SLE ? (7 bullet points)
- Autoantibodies (see more on different flashcard)
- FBC (normocytic anaemia of chronic disease)
- C3 and C4 levels (decreased in active disease)
- CRP and ESR
- Immunoglobulins (raised due to activation of B cells with inflammation)
- Urinalysis and urine protein: creatinine ratio for proteinuria found in lupus nephritis
- Renal biopsy can be used to investigate for lupus nephritis
78
Autoantibodies associated with SLE ?
- Anti-nuclear antibodies (ANA) - performing an ANA blood test is the initial step in testing for SLE in someone with symptoms of the condition. They can be positive in healthy pts and those with other autoimmune conditions thus a positive result needs to be interpreted in the context of their symptoms.
- Anti-double stranded DNA (anti-dsDNA) is specific to SLE. The levels vary with disease activity so they are useful in monitoring the disease activity and response to treatment.
- If you send a test for antibodies to extractable nuclear antigens (anti-ENA antibodies) the lab will check for antibodies to specific proteins in the cell nucleus. These are all types of antinuclear antibody:
- Anti-Smith (highly specific to SLE but not very sensitive)
- Anti-centromere antibodies (most associated with limited cutaneous systemic sclerosis)
- Anti-Ro and anti-La (most associated with Sjogren's sndyrome)
- Anti-Scl-70 (most associated with systemic sclerosis)
- Anti-Jo-1 (most associated with dermatomyositis)
Antiphospholipid antibodies and antiphospholipid syndrome can occur secondary to SLE. They can occur in up to 40% of pts with SLE and are associated with an increased risk of VTE.
79
Diagnosis of lupus note:
You can use the SLICC criteria or the ACR criteria for establishing a diagnosis. This involves confirming the presence of antinuclear antibodies and establishing a certain number of clinical features suggestive of SLE.
80
Complications of SLE ?
- CVD - is a leading cause of death. Chronic inflammation in blood vessels leads to HTN and coronary artery disease
- INFECTION - is more common in pts with SLE as part of the disease process and secondary to immunosuppressants
- ANAEMIA OF CHRONIC DISEASE -is common in SLE. It affects the bone marrow causing a chronic normocytic anaemia. Pts can also get leucopenia, neutropenia and thrombocytopenia
- PERICARDITIS
- PLEURITIS
- ILD - caused by inflammation in the lung tissue. This leads to pulmonary fibrosis
- LUPUS NEPHRITIS - occurs due to inflammation in the kidney. It can progress to end stage renal failure. It is assessed with a urine protein:creatinine ratio and renal biopsy. The renal biopsy is often repeated to assess response to treatment.
- NEUROPSYCHIATRIC SLE - is caused by inflammation in the CNS. It can present with optic neuritis, transverse myelitis (inflam of the spinal cord) or psychosis.
- RECURRENT MISCARRIAGE - SLE is associated with other pregnancy complications such as IUGR, pre-eclampsia and pre-term labour
- VTE - is particularly associated with antiphospholipid syndrome occurring secondary to SLE.
81
Treatment of SLE ?
Anti-inflammatory medication and immunosuppression is the mainstay of treatment. There is no cure and the aim is to reduce symptoms and complications. Treatment is usually titrated upwards to find the minimal medication with the least side effects required to control the symptoms
First line treatments are:
- NSAIDs
- Steroids (prednisolone)
- Hydroxychloroquine (first line for mild SLE)
- Suncream and sun avoidance for the photosensitive malar rash
Other commonly used immunosuppressants in resistant or more severe lupus:
- Methotrexate
- Mycophenolate mofetil
- Azathioprine
- Tacrolimus
- Leflunomide
- Ciclosporin
Biological therapies are considered for pts with severe disease or where pts have not responded to other treatments. The main options in SLE:
- Rituximab is a monoclonal antibody that targets the CD20 protein on the surface of B cells
- Belimumab is a monoclonal antibody that targets B-cell activating factor.
82
What is discoid lupus erythematosus + who is it more common in/ when does it tend to present ?
A non-cancerous chronic skin condition.
It is more common in women and usually presents in young adulthood between ages 20 and 40. It is also more common in darker skinned pts and smokers.
83
What is discoid lupus erythematosus associated with ?
An increased risk of developing SLE, however this risk is still below 5%. Rarely the lesions can progress to SCC of the skin.
84
Presentation of discoid lupus erythematosus ?
Lesions typically occurr on the face, ears and scalp. they are photosensitive. They are associated with scarring alopecia (hair loss in affected areas that does not grow back) and hyper or hypo pigmented scars.
The appearance of the lesions are:
- Inflamed
- Dry
- Erythematous
- Patchy
- Crusty and scaling
85
Management of discoid lupus erythematosus (include diagnosis) ?
Skin biopsy can be used to confirm the diagnosis.
Treatment is with:
- Sun protection
- Topical steroids
- Intralesional steroids
- Hydroxychloroquine
86
Note:
The terms systemic sclerosis and scleroderma are often used interchangeably. Most pts with scleroderma have systemic sclerosis, however there is a localised version that only affects the skin. Scleroderma translates directly to hardening of the skin
87
What is systemic sclerosis ?
An autoimmune inflammatory and fibrotic connective tissue disease.
Note: The cause of the condition is unclear. It most notably affects the skin in all areas but it also affects the internal organs
88
Two main patterns of disease in systemic sclerosis ?
- Limited cutaneous systemic sclerosis
| - Diffuse cutaneous systemic sclerosis
89
What is limited cutaneous systemic sclerosis ?
The more limited version of systemic sclerosis. It used to be called CREST sydnrome. this forms a helpful mnemonic for remembering the features of limited cutaneous systemic sclerosis:
- C - Calcinosis
- R - Raynaud's phenomenon
- E - oEsophageal dysmotility
- S - Sclerodactyly
- T - Telangiectasia
90
Diffuse cutaneous systemic sclerosis ?
Includes the features of CREST syndrome plus is affects internal organs causing:
- Cardiovascular problems, particularly HTN and coronary artery disease
- Lung problems, particularly pulmonary HTN and pulmonary fibrosis
- Kidney problems particularly glomerulonephritis and scleroderma renal crisis.
91
What is scleroderma, what appearance does it give and where are these changes most noticeable ?
Hardening of the skin. This gives the appearance of shiny, tight skin without the normal folds in the skin. These changes are most notable on the hands and the face.
92
What is sclerodactyly ?
Describes the skin changes that occur in the hands as a result of systemic sclerosis. As the skin tightens around the joints it restricts the range of motion in the joint and reduces the function. As the skin hardens and tightens further the fat pads on the fingers are lost. The skin can break and ulcerate
93
What are telangiectasia ?
Dilated small blood vessels in the skin. They are tiny veins that have dilated. They have a fine, thready appearance.
94
What is calcinosis ?
Where calcium deposits build up under the skin. This is most commonly found on the fingertips
95
What is Raynaud's phenomenon + what causes it ?
It is where the fingertips go completely white and then blue in response to even mild cold. It is caused by vasoconstriction of the vessels supplying the fingers.
Note: This commonly occurs without any associated systemic disease, it is a classical feature of systemic sclerosis
96
What is oesophageal dysmotility commonly associated with ?
Swallowing difficulties, acid reflux and oesophagitis
97
What is a scleroderma renal crisis ?
An acute condition where there is a combination of severe HTN and renal failure.
98
Most important autoantibodies commonly found in systemic sclerosis pts ?
- Antinuclear antibodies (ANA)
- Anti-centromere antibodies - most associated with limited cutaneous systemic sclerosis
- Anti-Scl-70 antibodies - are most associated with diffuse cutaneous systemic sclerosis. They are associated with more severe disease.
99
What is nailfold capillaroscopy, what does it allow you to examine and which disease is it used in ?
A technique to magnify and examine the area where the skin meets the base of the fingernail (the nailfold). This allows the observer to examine the health of the peripheral capillaries. It is used to investigate for systemic sclerosis
100
Name 3 things that could indicate systemic sclerosis during nailfold capillaroscopy ?
Abnormal capillaries, avascular areas and micro-haemorrhages.
101
Note:
Nailfold capillaroscopy is useful to support a diagnosis of systemic sclerosis and to investigate pts with Raynaud's phenomenon to exclude SS. Pts with primary Raynaud's without SS will have normal nailfold capillaries.
102
Diagnosis of systemic sclerosis ?
Based on classification rom the ACR and EULAR published in 2013. This involves a number of criteria for clinical features, antibodies and nailfold capillaroscopy..
103
Pts with systemic sclerosis should be managed and followed up by ?
A specialist MDT
104
Systemic sclerosis note:
Steroids and immunosuppressants are usually started with diffuse disease and complications such as pulmonary fibrosis. There is no standardised and proven treatment for SS. There is ongoing research trying to find effective ways of treating the condition.
105
Non-medical management of systemic sclerosis (6 bullet points) ?
- Avoid smoking
- Gentle skin stretching to maintain the range of motion
- Regular emollients
- Avoid cold triggers for Raynaud's
- Physio to maintain healthy joints
- Occupational therapy for adaptations to daily living to cope with limitations
106
Medical management of systemic sclerosis ?
Focuses on treating symptoms and complications:
- Nifedipine can be used to treat symptoms of Raynaud's phenomenon
- Anti acid medications (e.g. PPIs) and pro-motility medications (e.g. metoclopramide) for GI symptoms
- Analgesia for joint pain
- Antibiotics for skin infections
- Antihypertensives can be used for HTN (usually ACEi)
- Treatment of pulmonary artery HTN
- Supportive management of pulmonary fibrosis
107
What is polymyalgia rheumatica ?
An inflammatory condition that causes pain and stiffness in the shoulders, pelvic girdle and neck.
108
There is a strong association between polymyalgia rheumatica and which disease ?
Giant cell arteritis
Note: The two conditions often occur together
109
Demographic of polymyalgia rheumatica (3 bullet points) ?
- It usually affects old adults (above 50 years)
- More common in women
- More common in caucasians
110
5 core features of polymyalgia rheumatica + how long should they be present for ?
These should be present for at least 2 weeks:
- Bilateral shoulder pain that may radiate to the elbow
- Bilateral pelvic girdle pain
- Worse with movement
- Interferes with sleep
- Stiffness for at least 45 minutes in the morning
111
Name 4 other features of polymyalgia rheumatica ?
- Systemic symptoms such as weight loss, fatigue, low grade fever and low mood
- Upper arm tenderness
- Carpel tunnel syndrome
- Pitting oedema
112
One of the key challenges with diagnosing polymyalgia rheumatica is to exclude other conditions that can cause and similar symptoms thus not missing other diagnoses. Name 9 of these potential differentials ?
- Osteoarthritis
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Myositis (due to conditions like polymyositis or medications like statins)
- Cervical spondylosis
- Adhesive capsulitis of both shoulders
- Hyper or hypothyroidism
- Osteomalacia
- Fibromyalgia
113
Diagnosis of polymyalgia rheumatica ?
Based upon the clinical presentation and the response to steroids. Other conditions need to be excluded in order to make a diagnosis of PMR.
Note: Inflammatory markers are usually raised however normal inflammatory markers do not exclude PMR.
114
In polymyalgia rheumatica NICE clinical knowledge summaries advise a number of investigations prior to starting steroids to exclude other conditions. Name these ?
- FBC
- U&Es
- LFTs
- Calcium - can be raised in hyperPTH or cancer or low in osteomalacia
- Serum protein electrophoresis for myeloma and other protein disorders
- TSH for thyroid function
- Creatine kinase for myositis
- Rheumatoid factor for RA
- Urine dipstick
115
Additional investigations to consider for polymyalgia rheumatica (4 bullet points) ?
- Anti-nuclear antibodies (ANA) for systemic lupus erythematosus
- Anti-cyclic citrullinated peptide (anti-CCP) for RA
- Urine Bence Jones protein for myeloma
- CXR for lung and mediastinal abnormalities
116
Note:
The treatment of polymyalgia rheumatica is with steroids. The NICE CKS have clear guidelines on the steroid regime to follow. This is a summary:
Initially pts are started on 15mg of prednisolone per day.
Assess 1 week after starting steroids. If there is a poor response in symptoms it is probably not PMR and an alternative diagnosis needs to be considered. Stop the steroids.
Assess 3-4 weeks after starting steroids. You would expect a 70% improvement in symptoms and inflammatory markers to return to a normal to make a working diagnosis of PMR.
If 3-4 weeks of treatment with steroids has given a good response then start a reducing regime with the aim of getting the pt off steroids.
If symptoms reoccur whilst on the reducing regime they may ned to increase the dose or stay on the dose longer before reducing again. It can take 1 to 2 years to fully wean off. If there is doubt about the diagnosis, difficulty controlling symptoms, difficulty weaning steroids or steroids are required for more than 2 years refer to a rheumatologist.
117
Additional measures for pts on long term steroids ?
Don't STOP !!
- DON'T-Make them aware that they will become steroid dependant after 3 weeks of treatment and should not stop taking the steroids due to the risk of adrenal crisis if steroids are abruptly withdrawn
- S - Sick day rules: Discuss increasing the steroid dose if they become unwell
- T - Treatment card: Provide a steroid treatment card to alert others that they are steroid dependant in case they become unresponsive
- O - Osteoporosis prevention: Consider giving giving osteoporosis prophylaxis with biphosphonates and calcium and vit D supplements
- P - PPI: Consider gastric protection with a PPI
118
What is giant cell arteritis ?
A systemic vaculitis of the medium and large arteries.
119
GCA typically presents with symptoms affecting which artery ?
Temporal arteries.
This is why GCA is also known as temporal arteritis.
120
There is a strong link between GCA and ?
Polymyalgia rheumatica
121
Key complication of GCA + is it reversible + how is this managed ?
Vision loss. This is often irreversible. High dose steroids are used immediately once a diagnosis is suspected to prevent the development or progression of vision loss.
122
Symptoms of GCA ? (include main presenting feature + associated systemic symptoms)
The main presenting feature is a headache:
- Severe unilateral headache typically around temple and forehead
- Scalp tenderness may be noticed when brushing hair
- Jaw claudication
- Blurred or double vison
- Irreversible painless complete sight loss can occur rapidly
There may be associated systemic symptoms such as:
- Fever
- Muscle aches
- Fatigue
- Loss of appetite and weight loss
- Peripheral oedema
123
Definitive diagnosis of GCA ?
- Clinical diagnosis
- Raised ESR: usually 50mm/hour or more
- Temporal artery biopsy findings
TOM TIP: Multinucleated giant cells are found on the temporal artery biopsy.
124
Additional investigations for GCA + what would they show? (4 bullet points)
- FBC shows a normocytic anaemia and thrombocytosis
- LFTs can show a raised ALP
- CRP is usually raised
- Duplex US of the temporal artery shows the hypoechoic halo sign
125
Initial management of GCA ?
STEROIDS:
-Start steroids immediately before confirming the diagnosis to reduce the risk of permanent sight loss. Start 40-60mg prednisolone per day. 60mg is given depending where there are jaw claudication or visual symptoms. Review that response to steroids within 48 hours. There is usually a rapid and significant response to treatment.
OTHER MEDICATIONS:
- Aspirin 75mg daily decreases vision loss and strokes
- PPIs for gastric protection while on steroids
REFERALLS:
- Vascular surgeons for temporal artery biopsy in all pts with suspected GCA
- Rheumatology or specialist diagnosis and management
- Opthalmology review as an emergency same day appointment if they develop visual symptoms
126
Ongoing management of GCA ?
Once the diagnosis is confirmed they will need to continue high dose steroids (40-60mg) until the symptoms have resolved. They then need to slowly wean off the steroids. This can take several years. This is a similar process to managing polymyalgia rheumatica.
Don't STOP measures also need to be taken for pts on long term steroids.
127
Complications of GCA ? (early + late)
Early neuro-opthalmic complications:
- Vision loss
- Cerebrovascular accident
Late:
- Relapses of the condition are common
- Steroid related side effects and complications
- Cerebrovascular accident
- Aortitis leading to aortic aneurysm and aortic dissection
128
What are polymyositis and dermatomyositis ?
They are both autoimmune disorders. Polymyositis is a condition of chronic inflammation of muscles. Dermatomyositis is a connective tissue disorder where there is chronic inflammation of the skin and muscles.
129
Key investigation for diagnosing polymyositis and dermatomyositis ?
Creatine kinase blood test.
130
Note:
Creatine kinase is an enzyme found inside muscle cells. Myositis leads to the release of CK. CK is usually less than 300 U/L. In polymyositis and dermatomyositis the result is over 1000, often in the multiples of thousands.
131
Name 5 causes of a raised CK other than polymyositis and dermatomyositis ?
- Rhabdomyolysis
- AKI
- MI
- Statins
- Strenuous exercise
132
Polymyositis or dermatomyositis can be caused by an underlying malignancy. This makes them paraneoplastic syndromes. The most common associated cancers are ?
- Lung
- Breast
- Ovarian
- Gastric
133
Presentation of polymyositis and dermatomyositis ?
- Muscle pain, fatigue and weakness
- Occurs bilaterally and typically affects the proximal muscles
- Mostly affects the shoulder and pelvic girdle
- Develops over weeks
Note: Polymyositis occurs without any skin features whereas dermatomyositis is associated with involvement of the skin.
134
Dermatomyositis skin features ? (5 bullet points)
- Gottron lesions (scaly erythematous patches) on the knuckles, elbows and knees
- Photosensitive erythematous rash on the back, shoulders and neck
- Purple rash on the face and eyelids
- Periorbital oedema (swelling around the eyes)
- Subcutaneous calcinosis (calcium deposits in the subcutaneous tissue)
135
Autoantibodies associated with polymyositis and dermatomyositis + state which condition there are more commonly associated with ? (3 bullet points)
- Anti-Jo-1 antibodies: polymyositis (but often present in dermatomyositis)
- Anti-Mi-2 antibodies: dermatomyositis
- Anti-nuclear antibodies: dermatomyositis
136
Diagnosis of polymyositis and dermatomyositis ?
Diagnosis is based on:
- Clinical presentation
- Elevated creatine kinase
- Autoantibodies
- Electromyography (EMG)
Muscle biopsy can be used to establish a definitive diagnosis
137
Management of polymyositis and dermatomyositis ?
Management is guided by a rheumatologist. New cases should be assessed for possible underlying cancer. They may require physiotherapy and occupational therapy to help with muscle strength and function.
Corticosteroids are the first line treatment of both conditions.
Other medical options where the response to steroids is inadequate:
- Immunosuppressants (such as azathioprine)
- IV immunoglobulins
- Biological therapy (such as infliximab or etanercept)
138
What is antiphospholipid syndrome ?
An autoimmune hypercoagulable state caused by antiphospholipid antibodies.
Note: The main associations are with thrombosis and complications in pregnancy, particularly recurrent miscarriage.
139
Antiphospholipid syndrome can occur on its own or secondary to an autoimmune condition, particularly what ?
SLE
140
Antiphospholipid syndrome is associated with which antibodies ?
- Lupus anticoagulant
- Anticardiolipin antibodies
- Anti-beta-2 glycoprotein I antibodies
Note: These antibodies interfere with coagulation and create a hypercoagulable state where the blood is more prone to clotting.
141
Complications of antiphospholipid syndrome ?
VTE:
- DVT
- Pulmonary embolism
Arterial thrombosis:
- Stroke
- MI
- Renal thrombosis
Pregnancy complications:
- Recurrent miscarriage
- Stillbirth
- Preeclampsia
- Livedo reticularis is a purple lace like rash that gives a mottled appearance to the skin.
- Libmann-Sacks endocarditis - is a type of non-bacterial endocarditis where there are vegetations on the valves of the heart. The mitral valve is the most commonly affected. It is also associated with SLE.
- Thrombocytopenia is common in antiphospholipid syndrome
142
Diagnosis of antiphospholipid syndrome ?
When there is a history of thrombosis or pregnancy complications plus persistent antibodies:
- Lupus anticoagulant
- Anticardiolipin antibodies
- Anti-beta-2 glycoprotein I antibodies
143
Management of antiphospholipid syndrome ?
Pts are usually managed jointly between rheumatology, haematology and obstetrics (if pregnant).
Long term warfarin with an INR range 2 to 3 is used to prevent thrombosis.
Pregnant women are started on low molecular weight heparin (e.g. enoxaparin) plus aspirin to reduce the risk of pregnancy complications. Warfarin is contraindicated in pregnancy
144
What is Sjogren's syndrome + what symptoms does it lead to?
This is an autoimmune condition that affects the exocrine glands. It leads to symptoms of dry mucous membranes, such as dry mouth, dry eyes and dry vagina.
145
What the difference between primary and secondary Sjogren's disease ?
Primary Sjogren's is where the condition occurs in isolation.
Secondary Sjogren's is where it occurs related to SLE or RA.
146
Sjogren's syndrome is associated with which two antibodies ?
anti-Ro and anti-La antibodies.
147
What is the schirmer test + which disease is it used as test for ?
It involves inserting a folded piece of filter paper under the lower eyelid with a strip hanging out over the eyelid. This is left in for 5 minutes and the distance along the strip that becomes moist is measured. The tears should travel 15mm in a healthy young adult. A result of less than 10mm is significant.
It is used to test for Sjogren's disease.
148
Management of Sjogren's disease ? (4 bullet points)
- Artificial tears
- Artificial saliva
- Vaginal lubricants
- Hydroxychloroquine is used to halt the progression of the disease
149
Complications of Sjogren's disease ?
- Eye problems such as conjunctivitis and corneal ulcers
- Oral problems such as dental cavities and candida infections
- Vaginal problems such as candidiasis and sexual dysfunction
150
Note:
Sjogren's can rarely affect other organs causing complications such as:
- Pneumonia and bronchiectasis
- NHL
- Peripheral neuropathy
- Vasculitis
- Renal impairment
151
What is vasculitis ?
The inflammation of the blood vessels
152
Types of vasculitis affecting the small vessels ?
- Henoch-Schonlein purpura
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
- Microscopic polyangiitis
- Granulomatosis with polyangiitis (Wegener's granulomatosis)
153
Types of vasculitis affecting the medium sized vessels ?
- Polyarteritis nodosa
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
- Kawasaki disease
154
Types of vasculitis affecting the large vessels ?
- GCA
| - Takayasu's arteritis
155
General symptoms of vasculitis ? (7 bullet points)
- Purpura - purple coloured non-blanching spots caused by blood leaking from the vessels under the skin.
- Joint and muscle pain
- Peripheral neuropathy
- Renal impairment
- GI disturbance (diarrhoea, abdominal pain and bleeding)
- Anterior uveitis and scleritis
- HTN
156
Vasculitic conditions are also associated with systemic manifestations of what ?
- Fatigue
- Fever
- Weight loss
- Anorexia (loss of appetite)
- Anaemia
157
Inflammatory markers are usually raised in vasculitis. What is the blood test to remember for vasculitis ?
Anti neutrophil cytoplasmic antibodies (ANCA).
158
What are the two types of ANCA blood tests ?
p-ANCA and c-ANCA
Note:
p-ANCA is a.k.a anti PR3 antibodies
c-ANCA is a.k.a anti-MPO antibodies
159
Note:
The management of vasculitis depends on the type. Suspected cases should be referred to a specialist, usually a rheumatologist, to guide diagnosis and management. Treatment usually involves a combination of steroids and immunosuppressants.
Steroids can be administered to target the affected area:
- Oral (i.e. prednisolone)
- Intravenous (i.e. hydrocortisone)
- Nasal sprays for nasal symptoms
- Inhaled for lung involvement (e.g. Churg-Strauss syndrome)
Immunosuppressants that are used include:
- Cyclophosphamide
- Methotrexate
- Azathioprine
- Rituximab and other monoclonal antibodies
The management of HSP and Kawasaki disease (the types mainly affecting children) is different.
160
Henoch-Schonlein purpura (HSP) is an Ig... vasculitis that commonly presents with a purpuric rash affecting what in whom ?
IgA vasculitis
Affecting the lower limbs and buttocks in children
161
In HSP inflammation occurs due to IgA deposits in the blood vessels of affected organs such as what ? (name 3)
Skin, kidneys and GI tract.
162
HSP is often triggered by what ?
An upper airway infection (e.g. tonsillitis) or gastroenteritis.
163
HSP is most common in children under the age of ?
10
164
In HSP the rash is caused by ?
Inflammation and leaking of blood from small blood vessels under the skin, forming purpura
165
The four classic features of HSP are ?
Pupura (100%), joint pain (75%), abdominal (50%) and renal involvement (50%).
166
HSP affects the kidneys in about 50% of pts causing an ?
IgA nephritis
167
Management of HSP ?
Supportive with simple analgesia, rest and proper hydration
168
Note:
In HSP the abdominal pain usually settles within a few days. Pts without kidney involvement can expect to fully recover within 4 to 6 weeks. A third of patients have a recurrence of the disease within 6 months. 1% of pts will go on to develop end stage renal failure
169
Eosinophilic granulomatosis with polyangiitis used to be called Churg-Strauss sydnrome. Which type of vasculitis does it cause, what is it most associated with, how does it often present and what is the characteristic finding ?
- Small and medium vessel vasculitis
- Lung and skin problems, but can affect other organs such as the kidneys
- It often presents with severe asthma in late teenage years or adulthood
- A characteristic finding is elevated eosinophil levels on the FBC
170
Microscopic polyangiitis is a small smell vasculitis. The main feature is what + what can it also affect / cause ?
The main feature is renal failure. It can also affect the lungs causing SOB and haemoptysis
171
Granulomatosis with polyangiitis (Wegener's granulomatosis) is a small vessel vasculiitis that affects ?(two points)
The respiratory tract and kidneys
172
Wegener's granulomatosis: Name some common symptoms (excluding lung symptoms) + what is a classic sign in exams ?
It commonly affects the nose causing epistaxis and crusty nasal secretions, ears causing hearing loss and sinuses causing sinusitis.
A classic sign in exams is the saddle shaped nose due to a perforated nasal septum. This causes a dip halfway down the nose.
173
How does Wegener's granulomatosis affect the lungs, what may a CXR show + what can this lead to and how does it affect the kidneys ?
It causes a cough, wheeze and haemoptysis. A CXR may show consolidation and it can be misdiagnosed as pneumonia. In the kidneys it can cause a rapidly progressive glomerulonephritis.
174
Polyarteritis nodosa is a what sized vessel vasculitis ?
Medium vessel vasculitis
175
Polyarteritis nodosa is most associated with ...... but can also occur without .............. or with ..... and .......
It is most associated with hep B but can also occur without a clear cause or with hep C and HIV
176
Polyarteritis nodosa affects the medium sized vessels in locations such as ....., ......., ..... and ....... This can cause ...., .... and ......
Polyarteritis nodosa affects the medium sized vessels in locations such as the skin, GI tract, kidneys and heart This can cause renal impairment, strokes and MIs.
177
Polyarteritis nodsa is associated with a rash called what
| + what does this look like ?
Livedo reticularis. This is a mottled, purplish lace rash.
178
Kawasaki disease is a medium vessel vasculitis. It affects young children, typically under 5 years of age/. There is no clear cause. How is it diagnosed ?
-A high temperature (fever) of 38C or above for longer than 5 days + 4 out of 5 key symptoms:
- Bilateral conjunctivitis
- Erythematous rash
- Erythema and desquamation of palms and soles
- "Strawberry tongue"
- Cervical lymphadenopathy
179
Key complication of Kawasaki disease + treatment
A key complication is coronary artery aneurysms.
Treatment is with aspirin and IV immunoglobulins.
180
Takayasu's arteritis is a form of .................. It mainly affects the ....... and its branches. It also affects the ................... These large vessels and their branches can swell and form .................. or become narrowed and .............. This leads to its other name of "..................".
It usually presents before the age of ............... with non-specific symptoms, such as ..........., .......... and ..............., or with more specific symptoms of ................... or ............ It is diagnosed using ............ or ..............
............. of the carotids can be useful in detecting carotid disease.
Takayasu's arteritis is a form of LARGE VESSEL VASCULITIS. It mainly affects the AORTA and its BRANCHES. It also affects the PULMONARY ARTERITIS. These large vessels and their branches can swell and form ANEURYSMS or become narrowed and BLOCKED. This leads to its other name of "PULSELESS DISEASE".
It usually presents before the age of 40 YEARS with non-specific symptoms, such as FEVER, MALAISE and MUSCLE ACHES, or with more specific symptoms of ARM CLAUDICATION or SYNCOPE. It is diagnosed using CT or MRI ANGIOGRAPHY.
DOPPLER ULTRASOUND of the carotids can be useful in detecting carotid disease.
181
Note:
Behcet's disease is a complex inflammatory condition. It characteristically presents with recurrent oral and genital ulcers. It can also cause inflammation in a number of other areas such as the skin, GI tract, lungs, blood vessels, musculoskeletal system and central nervous system. The presentation can vary a lot between patients, with some patients mildly affected and others affected dramatically.
182
There is a link between Behcet's disease and which gene ?
HLA B51 gene.
Note: This is a prognostic indicator of severe disease.
183
Mouth ulcers are very common in Behcet's disease. Name 7 differentials for mouth ulcers ?
- Simple aphthous ulcers
- Squamous cell carcinoma
- Herpes simplex ulcers
- Hand, foot and mouth disease (coxsackie A virus)
- Inflammatory bowel disease (particularly Crohn's disease)
- Inflammatory conditions such as rheumatoid arthritis
- Folate deficiency
184
Features of Behcet's disease ?
MOUTH ULCERS - Pts with Behcet's are expected to get at least 3 episodes of oral ulcers per year. They are painful, sharply circumscribed erosions with a red halo. They can occur on the oral mucosa and heal over 2 to 4 weeks.
GENITAL ULCERS - Similar in appearance to the oral ulcers. "Kissing ulcers are where an ulcer develops on two opposing surfaces so that they are facing each other
```
SKIN
The skin is very easily inflamed in Behcet's. Particular skin findings are:
-Erythema nodusum
-Papules and pustules (similar to acne)
-Vasculitic type rashes
```
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EYES
Eye manifestations need emergency review by ophthalmology as they can be sight threatening.
-Anterior or posterior uveitis
-Retinal vasculitis
-Retinal haemorrhage
```
MUSCULOSKELETAL SYSTEM
- Morning stiffness
- Arthralgia
- Oligoarthritis often affecting the knee or ankle. This causes swelling without join destruction
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GI SYSTEM
Inflammation and ulceration can occur in the GI tract. This tends to affect the:
-Ileum
-Caecum
-Ascending colon
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CENTRAL NERVOUS SYSTEM
- Memory impairment
- Headaches and migraines
- Aseptic meningitis
- Meningoencephalitis
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VEINS
In Behcet's disease the veins can become inflamed and this can lead to vein thrombosis. These thrombosis tend to stay in place and don't embolism as they are related to inflammation in the vessel. Examples:
-Budd Chiari syndrome
-Deep vein thrombosis
-Thrombus in pulmonary veins
-Cerebral venous sinus thrombosis
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LUNGS
Pulmonary artery aneurysms can develop. If they rupture they can be fatal.
185
Diagnosis of Behcet's disease, name one key investigation + what it is ?
Behcet's disease is a clinical diagnosis based on the features of the condition. One key investigation is the pathergy test.
The pathergy test involves using a sterile needle to create a subcutaneous abrasion on the forearm. This is then reviewed 24 to 48 hours later to look for a weal 5mm or more in size. It tests for non-specific hypersensitivity in the skin.
Note: It is positive in Behcet's disease, Sweet's syndrome and pyoderma gangrenosum.
186
Management of Behcet's disease ?
Management is coordinated by a specialist, usually rheumatomologist. Other specialities may be involved depending on the affected areas.
Management involves a combination of:
- Topical steroids to mouth ulcers (e.g. soluble betamethasone tablets)
- Systemic steroids (i.e. predisolone)
- Colchicine is usually effective in treating symptoms (As an anti-inflammatory)
- Topical anaesthetics for genital ulcers (e.g. lidocaine ointment)
- Immunosuppressants such as azathioprine
- Biologics therapy such as infliximab.
187
Note:
Behcet's disease is a relapsing remitting condition. Pts generally have a normal life expectancy and the condition may go into complete remission. There is an increased mortality with haemoptysis, neurological involvement and other major complications
188
What is gout ?
A type of crystal arthropathy associated with chronically high blood uric acid levels. Urate crystals are deposited in the joint causing it to become hot, swollen and painful.
Note: Gouty tophi are subcutaneous deposits of uric acid, typically affect the small joints and connective tissues of the hands, elbows and ear. The DIP joints are the most affected joints in the hands.
189
How does gout typically present + what is the obvious and extremely important DD ?
It typically presents with a single acute hot, swollen and painful joint. The obvious and extremely important differential diagnosis is septic arthritis.
190
RF's for gout (7 bullet points) ?
- Male
- Obesity
- High purine diet (e.g. meat seafood)
- Alcohol
- Diuretics
- Existing CVD or kidney disease
- Family history
191
Typical joints affected by gout ? (4 points)
- Base of the big toe (metatarso-phalangeal joint)
- Wrists
- DIP joints
- Base of the thumb (carpometacarpal joint)
Note: Gout can also affect big joints like the knees and ankles.
192
Diagnosis of gout ?
Gout is diagnosed clinically or by aspiration of fluid from the joint. An xray of an affected joint may also be done. Excluding septic arthritis is essential as this is a potentially joint and life threatening diagnosis.
193
What would aspirated fluid show in a pt with gout ?
- No bacterial growth
- Needle shaped crystals
- Negative birefringent of polarised light
- Monosodium urate crystals
194
What would a joint xray show in a joint affected by gout ?
- Typically the joint space is maintained
- Lytic lesions in the bone
- Punched out erosions
- Erosions can have sclerotic boarders with overhanding edges.
195
Management of gout ?
During the acute flare:
- NSAIDs are first line
- Colchicine is second line
- Steroids can be considered third line
Colchicine is used in pts that are inappropriate for NSAIDs, such as those with renal impairment or significant heart disease.
196
Prophylaxis of gout ?
Allopurinol is a xanthine oxidate inhibitor - it reduces uric acid levels
Lifestyle changes can reduce the risk of developing gout. This involves losing weight, staying hydrated and minimising the consumption of alcohol and purine-based food.
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TOM TIP:
Do not initiate allopurinol prophylaxis until after the acute attack is settled. Once treatment of allopurinol has been started then it can be continued during an acute attack
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What is pseudogout ?
A crystal arthropathy caused by calcium pyrophosphate crystals being deposited in the joints causing joint problems
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What is pseudogout also known as ?
Chondrocalcinosis
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How does pseudogout present + which joints does it typically affect?
With a hot, swollen, still painful joint(s). It typically affects the knees, shoulders, wrists and hips.
Note: It can be a chronic condition and affect multiple joints. It can also be asymptomatic and picked up incidentally on an xray of the joint.
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Diagnosis of pseudogout ?
Note: In any patient presenting with a hot, painful and swollen joint, septic arthritis needs to be excluded as it is a medical emergency that is joint and life threatening. It tends to be milder in presentation compared with gout and septic arthritis.
To establish a definitive diagnosis the joint needs to be aspirated for synovial fluid. Aspirated fluid will show:
- No bacterial growth
- Calcium pyrophosphate crystals
- Rhomboid shaped crystals
- Positive birefringent of polarised light
Chondrocalcinosis is the classic xray change. It appears as a thin white line in the middle of the joint space caused by the deposition of calcium. This is pathognomonic (diagnostic) of pseudogout.
Other joint xray changes are similar to osteoarthritis. LOSS:
- L - Loss of joint space
- O - Osteophytes
- S - Subarticular sclerosis
- S - Subchondral cysts
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Management of pseudogout ?
Chronic asymptomatic changes found on an xray do not require any action.
Symptoms usually resolve spontaneously over several weeks. Symptomatic management involves:
- NSAIDs
- Colchicine
- Joint aspiration
- Steroid injections
- Oral steroids
Joint washout (arthrocentesis) is an option in severe cases.
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What is osteoporosis + osteopenia and why are they problematic ?
Osteoporosis is a condition where there is a reduction in the density of the bones. Osteopenia refers to a less severe reduction in bone density than osteoporosis.
A reduced bone density makes bone more prone to fractures.
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Risk factors for osteoporosis ? (8 bullet points)
- Older age
- Female
- Reduced mobility and activity
- Low BMI (under 18.5 kg/m2)
- Rheumatoid arthritis
- Alchohol and smoking
- Long term corticosteroids
- Other medications such as SSRIs, PPIs, anti-epileptics and anti-oestrogens
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Note:
Post-menopausal women are a key group where osteoporosis should be considered. Oestrogen is protective against osteoporosis. Unless they are on HRT, post-menopausal women have less oestrogen. They also tend to be older and often have other risk factors for osteoporosis.
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What does the FRAX tool predict ?
The risk of a fragility fracture over the next 10 years.
Note: This is usually the first step in assessing someones risk of osteoporosis.
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Note:
The FRAX tool involves inputting information such as the pts age, BMI, co-morbidities, smoking, alcohol and family history. You can enter a result for bone mineral density (from a DEXA scan) for a more accurate result but it can also be performed without the bone mineral density.
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How does the FRAX TOOL give results ?
It gives results as a percentage 10 year probability of a:
- Major osteoporotic fracture
- Hip fracture
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How is bone mineral density measured ?
Using a DEXA scan
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What does DEXA stand for?
Dual-energy xray absorption
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What are DEXA scans ?
Brief xray scans that measure how much radiation is absorbed by the bones, indicating how dense the bone is.
Note: BMD can be measured at any location on the skeleton, but the reading at the hip is key for classification and management.
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Bone density can be represented by which two scores+ what do they both mean ?
As a Z score or a T score.
Z scores represent the number of SDs the pts bone density falls below the mean for their age.
T scores represent the number of SDs below the mean for a healthy young adult their bone density is.
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The WHO classification of osteoporosis uses which measurement + produce a table of this classification
T SCORE AT THE HIP (BMD):
More than -1 = Normal
-1 to -2.5 = Osteopenia
Less than -2.5 = Osteoporosis
Less than -2.5 plus a fracture = Severe osteoporosis
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How do you assess for osteoporosis ?
Perform a FRAX assessment on pts at risk of osteoporosis:
- Women over 65
- Men over 75
- Younger pts with RF's such as a previous fragility fracture, history of falls, low BMI, long term steroids, endocrine disorders and rheumatoid arthritis.
FRAX outcome without a BMD result will suggest one of three outcomes:
- Low risk - reassure
- Medium risk - offer DEXA scan and recalculate the risk with the results
- High risk - offer treatment
FRAX outcome with a BMD result will suggest one of two outcomes:
- Treat
- Lifestyle advice and reassure
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Management of osteoporosis ? (2 simple headings)
Lifestyle changes + biphosphonates
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Lifestyle changes for pts at risk of osteoporosis ? (7 bullet points)
- Activity and exercise
- Maintain a healthy weight
- Adequate calcium intake
- Adequate vitamin D
- Avoiding falls
- Stop smoking
- Reduce alcohol consumption
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Note:
NICE recommend calcim supplementation with vit D in pts at risk of fragility fractures with an adequate intake of calcium. An example of this would be Calcichew-D3 (colecalciferol)
Pts with an adequate calcium intake but lacking sun exposure should have vitamin D supplementation.
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Biphosphonates are the first line treatment for osteoporosis. How do they work + name four side effects ?
They work by interfering with osteoclasts and reducing their activity, preventing the reabsorption of bone.
Side effects:
- Reflux and oesophageal erosions - oral biphosphonates are taken on an empty stomach sitting upright for 30 minutes before moving or eating to prevent this.
- Atypical fractures
- Osteonecrosis of the jaw
- Osteonecrosis of the external auditory canal
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Examples of biphosphonates are:
Alendronate 70mg once weekly (oral)
Risedronate 35mg once weekly (oral)
Zolendronic acid 5mg once yearly (IV)
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Other medical options to biphosphonates if they are contraindicated, not tolerated or not effective:
- Denosumab - a monoclonal antibody that works by blocking the activity of osteoclasts
- Strontium ranelate - is a similar element to calcium that stimulates osteoblasts and blocks osteoclasts but increases the risk of DVT, PE and MI
- Raloxifene - is used as secondary prevention only. It is a selective oestrogen receptor modular that stimulates oestrogen receptors on bone but blocks them in the breasts and uterus
- Hormone replacement therapy - should be considered in women that go through the menopause
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Follow up for pts at risk of osteoporosis ?
Low risk pts not on treatment should be given lifestyle advice and followed up within 5 years for a repeat assessment.
Pts on biphosphonates should have a repeat FRAX and DEXA scan after 3 to 5 years. A treatment holiday should be considered if their BMD has improved and they have not suffered any fragility fractures. This involves a break from treatment of 18 months to 3 years before repeating the assessment.
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What is osteomalacia ?
A condition where there is defective bone mineralisation causing "soft" bones.
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What does osteomalacia result from ?
Vit D deficiency
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When osteomalacia occurs in children prior to their growth plates closing what does it lead to ?
Rickets
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Simplified pathophysiology of osteomalacia ?
Vit D is a hormone created from cholesterol by the skin in response to UV radiation. Pts with darker skin require a longer period of sun exposure to generate the same quantity of vit D. A standard diet contains inadequate levels of vit D to compensate for a lack of sun exposure. Reduced sun exposure without vit D supplementation leads to vit D deficiency.
Pts with malabsorption disorders (such as IBD) are more likely to have vit D deficiency. The kidneys are essential in metabolising vit D to its active form, therefore vit D deficiency is common in CKD.
Vit D is essential in calcium and phosphate absorption from the intestines and kidneys. Vit D is also responsible for regulating bone turnover and promoting bone reabsorption to boost the serum calcium level.
Inadequate vit D leads to a lack of calcium and phosphate in the blood. Since calcium and phosphate are required for the construction of bone, low levels result in defective bone mineralisation. Low calcium causes a secondary hyperparathyroidism as the parathyroid gland tries to raise the calcium level by secreting parathyroid hormone. PTH stimulates increased reabsorption from the bones. This causes further problems with bone mineralisation.
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Presentation of osteomalacia ?
Pts with vit D deficiency and osteomalacia may not have any symptoms. Potential symptoms are:
- Fatigue
- Bone pain
- Muscle weakness
- Muscle aches
- Pathological or abnormal fractures
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TOM TIP:
Think about the risk factors for vit D deficiency in your exams and clinical practice. Pts with osteomalacia are likely to have risk factors such as darker skin, low exposure to sunlight, live in colder climates and spend the majority of their time indoors.
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Investigations for osteomalacia + what results are likely to show if someone has the condition?
Serum 25-hydroxyvitamin D is the laboratory investigation for vit D. The interpretation of the results is as follows:
- Less than 25 nmol/L - vit D deficiency
- 25 to 50 nmol/L - vit D insufficiency
- 75 nmol/L or above is optimal
Other investigation results include:
- Serum calcium is low
- Serum phosphate is low
- Serum ALP may be high
- PTH may be high (secondary hyprparathyroidism)
- Xrays may show osteopenia (more radiolucent bones)
- DEXA scan shows low BMD
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Treatment of osteomalacia ?
Supplementary vit D (colecalciferol).
Note: Theare are various regimes suggested by the NICE CKS on vit D deficiency. They involve correcting the initial vit D deficiency with on one of the following:
- 50,000 IU once weekly for 6 weeks
- 20,000 IU twice weekly for 7 weeks
- 4000 IU daily for 10 weeks
A maintenance supplementary dose of 800 IU or more per day should be continued for life after the initial treatment.
Pts with vit D insufficiency can be started on the maintenance dose without the initial treatment regime.
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What is Paget's disease of bone, what happens in it and what does this result in ?
A disorder of bone turnover.
There is excessive bone turnover (formation and reabsorption) due to excessive osteoblast and osteoclast activity. This excessive turnover is not coordinated, leading to patchy areas of high density (sclerosis) and low density (lysis).
This results in enlarged and misshapen bones with structural problems that increase the risk of pathological fractures. It particularly affects the axial skeleton (the bones of the head and spine)
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Presentation of Paget's disease of bone ?
It typically affects older adults. It presents with:
- Bone pain
- Bone deformity
- Fractures
- Hearing loss can occur if it affects the bones of the ear
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Key investigations for Paget-s disease of the bone + findings ?
Xray findings:
- Bone enlargement and deformity
- Osteoporosis circumscripta - describes well defined osteolytic lesions that appear less dense compared with normal bone
- Cotton wool appearance of the skull - describes poorly defined patchy areas of increased density (sclerosis) and decreased density (lysis)
- V-shaped defects in the long bones - osteolytic bone lesions surrounded by healthy bone
Biochemistry:
- Raised ALP (other LFTs are normal)
- Normal calcium
- Normal phosphate
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Management of Paget's disease of the bone (include how you monitor)?
Biphosphonates are the main treatment. They are generally very effective. They interfere with osteoclast activity and seem to restore normal bone metabolism. They improve symptoms and prevent further abnormal bone change.
Other measures include:
- NSAIDs for bone pain
- Calcium and vit D supplementation, particularly whilst on biphosphonates
- Surgery is rarely required to treat fractures, severe deformity and arthritis.
Monitoring involves checking the serum ALP and reviewing symptoms. Effective treatment should normalise the ALP and eliminate symptoms.
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Two key complications of Paget's disease of the bone ?
- Osteosarcoma
| - Spinal stenosis
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Note:
Osteosarcoma is a type of bone cancer with a very poor prognosis. It presents with increased focal bone pain, bone swelling or pathological fractures. The risk is increased in Paget's disease and pts need to be followed up to detect it early. They can usually be seen on a plain xray.
Spinal stenosis may occur where deformity in the spine leads to spinal canal narrowing. If this presses on the spinal nerves it causes neurological signs and symptoms. This is diagnosed with an MRI scan and is often treated effectively with biphosphonates. Surgical intervention may be considered.
