Rheumatology Flashcards
What is OA?
osteoarthiritis
DEGENERATIVE JOINT DISEASE
Patho of OA?
Wear and Tear leads to destroying the T2 collagen and proteoglycans
Chondrocytes will try and rescue by producing T2 collagen and proteoglycans
But after a while it does not work, and instead they start producing type 1 collagen.
T1 collagen and proteoglycans don’t interact and hence the joint loses elasticity
After a while, the chondrocytes cant keep up and undergo apoptosis causing cartilage to flake off and float in the synovial cavity
These flaky segments invite macrophages and pro-inflammatory cytokines to join the party – and they bring their cleaning booze with them
This leads to synovitis and fibrillation aka cracks – these cracks continue to erode – until just bone is remaining.
This bone on bone movement is called eburnation, and makes the bones look like polished ivory. Later this leads to bone stretching laterally producing osteophytes
Classification of OA
Primary where aetilogy is unknown and Secondary where aetilogy is known
In primary the joint has worn out Naturally, age related, normal wear and tear (Genetic, biochemical, Mechanical, Age-related)
Most people after 60 will have some percentage of OA
Secondary: Trauma, Neuropathic Joint disease, Other inflammatory joint disease, previous repeated steroid injections.
WHat is the grading for OA?
WHat are the four radiological signs seen in OA
What are OA changes in the joints
What are the signs you look for in hands for OA
Herberdens node
Bouchards node
What are the risk factors for OA?
- AGE is THE BIGGEST RF
- Inflammation increases the progression of OA (some of the factors cause proteolysis and some factors block formation of new cart) : which is usually caused after JOINT INJURY
- Mechanical stress and OBESITY
- Genetics
- Meds
- Neuro Disorders
- Ocuupation
- Female
What are the Important Features seen in OA
Usually bilateral: Usually one joint at a time is affected over a period of several years. The carpometacarpal joints, distal interphalangeal joints are affected more than the proximal interphalangeal joints.
Episodic joint pain: An intermittent ache. Provoked by movement and relieved by resting the joint.
Stiffness: Worse after long periods of inactivity e.g. waking up in the morning. Stiffness lasts only a few minutes compared to the morning joint stiffness seen in rheumatoid arthritis.
Painless nodes (bony swellings): Heberden’s nodes at the DIPJs, Bouchard’s Nodes at the PIPJs. These nodes are the result of osteophyte formation
Squaring of the thumbs: Deformity of the carpometacarpal joint of the thumb resulting in fixed adduction of the thumb.
What is this seen in?
OA
How is osteoarthritis different to inflammatory arthritis?
Osteoarthritis 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.
Treatment for OA
patient education: weightloss, physio, OT
Medical / Conservative
- Oral paracetamol and topical NSAIDs or topical capsaicin (chilli pepper extract).
- Add oral NSAIDs and consider also prescribing a proton pump inhibitor (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 patients can develop dependence and withdrawal. They also don’t work for chronic pain and result in patients becoming depending without benefitting from pain relief.
Surgical
- Intra-articular steroid injections provide a temporary reduction in inflammation and improve symptoms.
- Replacement
What is Gout
Inflammatory disease in which monosodium urate crystals deposit into a joint making it red, hot, tender and swollen within hours
Crystals usually develop in areas of fast blood flow like the joints and liver
TRUE OR FALSE
FALSE
Crystals usually develop in areas of slow blood flow like the joints and kidney tubules.
What is uric acid present in?
Uric acid is present in Purines, Foods - shellfish, anchovies, red and organ meat.
WHat joint is affected in gout usually?
1st metatarsal joint is usually affected, its called podagra. person will wake up from sleep, and will feel as if their big toe is on fire.
- Base of the big toe (metatarsophalangeal joint)
- Wrists
- Base of thumb (carpometacarpal joints)
In gout you might find the presence of _____: White, Chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in soft tissues and joints aka permanent deposits of uric acid crystals.
In gout you might find the presence of Tophi: White, Chalky aggregates of uric acid crystals with fibrosis and giant cell reaction in soft tissues and joints aka permanent deposits of uric acid crystals.
Risk factors for gout
Male
Obesity
High purine diet (e.g. meat and seafood)
Alcohol
Diuretics
Existing cardiovascular or kidney disease
Family history
Prophylaxis of Gout
Allopurinol is a xanthine oxidase inhibitor used for the prophylaxis of gout. It reduces the uric acid level.
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 (such as meat and seafood).
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.
Radiological features for gout?
- Joint effusion is an early sign
- Well defined punched out erosions
- Relative presentation of joint space until late disease
- Eccentric (well defined) erosions
- No particular osteopenia (in contrast with RA)
- Soft tissue tophi many be seen
Compare and contrast gout and pseudogout?
crystal composition
crystal shape
birefringent
Most common joint affect
Radiography
First line treatment
What Can lead to GOUT?
Decreased Uric Acid Excretion
- drugs: diuretics
- chronic kidney disease
- lead toxicity
Increased production of uric acid
- myeloproliferative/lymphoproliferative disorder
- cytotoxic drugs
- severe psoriasis
How do you diagnose Gout?
History and Exam
Serum Urate - may be normal during an attack
Joint aspiration - synovial fluid will show negatively bi-fringent needle shaped crystals under polarized light
Management of Gout
During the acute flare:
- NSAIDs (e.g. ibuprofen) are first-line
- Colchicine second-line
- Steroids can be considered third-line
Colchicine is used in patients that are inappropriate for NSAIDs, such as those with renal impairment or significant heart disease. A notable side effect is gastrointestinal upset. Diarrhoea is a very common side effect. This is dose-dependent meaning lower doses cause less upset than higher doses.
Pathogenesis of SLE
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 theses 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.
What can increases your chances of getting an acute gout attack?
- Rise or sudden fall in urate level
- Binge drinking
- High protein intake?
- Trauma/ surgery, rapid cell destruction (releases purines)
- Weight loss( increased cell apoptosis)
- Reduced urate clearance - dehydration, renal disease
Management of SLE
First line treatments are:
- NSAIDs
- Steroids (prednisolone)
- Hydroxychloroquine (first line for mild SLE)
- Suncream and sun avoidance for the photosensitive the malar rash
Other commonly used immunosuppressants in resistant or more severe lupus:
- Methotrexate
- Mycophenolate mofetil
- Azathioprine
- Tacrolimus
- Leflunomide
- Ciclosporin
Biological therapies
- 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
Epidemiology
of SLE
1 in 1000 white females
More common in females than males (>8:1) in childbearing years
More common in black and Hispanic, Asian populations
What is SLE
Systemic lupus erythematosus (SLE) (lupus)
- Autoimmune condition
- Pathogenesis- inflammation gone wrong, Anti nuclear antbodies
- Skin biopsy; lupus band test= immunofluorescent staining of IgG and complement deposits in dermo-epidermal junction
Diagnosis for SLE?
- Skin biposy
- Lupus band test= immunofluorescent staining of IgG and complement deposits in demo epidemal junction
- Positive ANA (anti-nuclear antibodies)
- Full blood count (normocytic anaemia of chronic disease)
- C3 and C4 levels (decreased in active disease)
- CRP and ESR (raised with active inflammation)
- Immunoglobulins (raised due to activation of B cells with inflammation)
- Urinalysis and urine protein:creatinine ratio for proteinuria in lupus nephritis
- Renal biopsy can be used to investigate for lupus nephritis
Clinical Features
of SLE
(multi-systemic)
- Fatigue
- Weight loss
- Arthralgia (joint pain) and non-erosive arthritis
- Myalgia (muscle pain)
- Fever
- Photosensitive malar rash. This is a “butterfly” shaped rash across the nose and cheek bones that gets worse with sunlight.
- Lymphadenopathy and splenomegaly
- Shortness of breath
- Pleuritic chest pain
- Mouth ulcers
- Hair loss
- Raynaud’s phenomeno
CREST syndrome- type of limited cutaneous systemic
sclerosis
what does CREST stand for?
What is Scleroderma
Scleroderma is an uncommon condition that results in hard, thickened areas of skin and sometimes problems with internal organs and blood vessels.
Multi-systemic disease, unknown cause
• Vascular damage
• Overproduction of collagen
• Immunological features
Scleroderma,
epidemiology
mainly in females
what is Raynaud’s phenomenon
Common affects 3-5% of the UK population;
episodic colour changes in response to cold or
emotion
Raynaud’s phenomenon is a problem that causes decreased blood flow to the fingers. In some cases, it also causes less blood flow to the ears, toes, nipples, knees, or nose. This happens due to spasms of blood vessels in those areas. The spasms happen in response to cold, stress, or emotional upset.
Patho of raynauds phenomenon
Pathology: increased vasoconstriction,
smooth muscle more reactive, damage to
endothelial cells, fibrosis
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 syndrome)
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
What is primary and secondary raynauds phenomenon
Primary RP- no underlying cause
• Secondary RP- associated with connective
tissue disease ie systemic sclerosis, vasculitis,
malignancy or peripheral vascular disease
Diagnosis for RP
Diagnosis made clinically- digits turn white (pallor) then blue with deoxygenation and or red with reperfusion
Patho of RA
Rheumatoid Factor (RF) is an autoantibody presenting in around 70% of RA patients. It is an autoantibody that targets the Fc portion of the IgG antibody. This causes activation of the immune system against the patients own IgG causing systemic inflammation. Rheumatoid factor is most often IgM however they can be any class of immunoglobulin.
Cyclic citrullinated peptide antibodies (anti-CCP antibodies) are autoantibodies that are more sensitive and specific to rheumatoid arthritis than rheumatoid factor. Anti-CCP antibodies often pre-date the development of rheumatoid arthritis and give an indication that a patient will go on to develop rheumatoid arthritis at some point.
WHat is Systemic Sclerosis
Name the two types
Systemic sclerosis is an autoimmune inflammatory and fibrotic connective tissue disease. The cause of the condition is unclear. It most notably affects the skin in all areas but it also affects the internal organs.
There are two main patterns of disease in systemic sclerosis:
- Limited cutaneous systemic sclerosis (CREST)
- Diffuse cutaneous systemic sclerosis
What is Polymyositis and dermatomyositis
Polymyositis and dermatomyositis are autoimmune disorders where there is inflammation in the muscles (myositis). 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.
Antibodies associated with Polymuosititis and Dermatomyositis
- Anti-Jo-1 antibodies: polymyositis (but often present in dermatomyositis)
- Anti-Mi-2 antibodies: dermatomyositis.
- Anti-nuclear antibodies: dermatomyositis.
WHat is a marker for Polymyositis and Dermatomyositis
Creatine Kinase
The key investigation for diagnosing myositis is a creatine kinase blood test. Creatine kinase is an enzyme found inside muscle cells. Inflammation in the muscle cells (myositis) leads to the release of creatine kinase. Creatine kinase is usually less than 300 U/L. In polymyositis and dermatomyositis, the result is usually over 1000, often in the multiples of thousands.
Other causes of a raised creatine kinase include:
- Rhabdomyolysis
- Acute kidney injury
- Myocardial infarction
- Statins
- Strenuous exercise
Dermatomyositis Skin Features
- 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)
What is this seen in?
RA
What does seronegative mean?
giving a negative result in a test of blood serum, e.g. for the presence of a virus.
More inflammaory than autoimmune
Examples of inflammatory arthiritis (seronegative)
Spondyloarthropathies:
- Psoriatic arthritis
- Ankylosing spondylitis
- Reactive arthritis
- Seronegative RA
- Juvenile idiopathic arthritis
Management for RA
DMARD
NICE guidelines for Disease Modifying Anti-Rheumatic Drugs (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
- Sulfasalazine and hydroxychloroquine are considered as DMARDs in pregnancy.
Examples of inflammatory arthritis (autimmune)
Rheumatoid arthritis
Triggeres for RA?
- Smoking
- Infection
- Susceptible genes (PTPN22 gene) (HLA_DR1, HLA-DR4)
- Women: Pregnancy, oral contraceptives, HRT, sex hormones
What is the genetic trigger for RA
Epigenetic changes & post-translational modifications in collagen => conversion of amino acid arginine to citrulline
HLA DR4 (a gene often present in RF positive patients)
HLA DR1 (a gene occasionally present in RA patients)
What are the three stages for RA
- Trigger
- Misrecognition & Immunity Activation
- Local inflammatory response
- symptoms of RA
What is Palindromic Rheumatism
This involves self limiting short episodes of inflammatory arthritis with joint pain, stiffness and swelling typically affecting only a few joints. The episodes only last 1-2 days and then completely resolve. Having positive antibodies (RF and anti-CCP) may indicate that it will progress to full rheumatoid arthritis.
Common joints affected in RA
Which joint is usually never affected
- Proximal Interphalangeal Joints (PIP) joints
- Metacarpophalangeal (MCP) joints
- Wrist and ankle
- Metatarsophalangeal joints
- Cervical spine
- Large joints can also be affected such as the knee, hips and shoulders
TOM TIP: The distal interphalangeal joints are almost never affected by rheumatoid arthritis. If you come across enlarged painful distal interphalangeal joints this is most likely to be Heberden’s nodes due to osteoarthritis.
CF for RA
- Females > males
- Morning stiffness > 1 hour => improves with activity (as the day passes)
•Symmetric distribution of symptoms
•Pain and swelling initially in SMALL joints => PIP, MCP, MTP
- Extra-articular manifestations (more in RA than spondyloarthropathies!)
- Fatigue, weight loss
Extra articular maifesations of RA
- 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
- Cardiovascular disease
- Episcleritis and scleritis
- Rheumatoid nodules
- Lymphadenopathy
- Carpel tunnel syndrome
- Amyloidosis
Ix for RA
BLOODS:
- FBC, CRP, ESR, U&Es, LFTs
- ANA (present in 40% patients)
- Anti-CCP (more specific)
- Rheumatoid factor (more sensitive; only present in 50% of RA patients)
- Usually clinical diagnosis!
IMAGING:
- X-ray findings:
- Loss of Joint Space
- Periarticular osteoporosis
- Soft tissue swelling
- Ill-defined marginal/ bony erosions
Ultrasound 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.
SPONDYLOARTHROPATHIES (Arthritis in joints & entheses) can be classified into two
what are these?
Axial
Peripheral
Examples of axial SPONDYLOARTHROPATHIES
- Psoriatic arthritis
- Ankylosing spondylitis
- Non radiographic axial SpA
- Juvenile idiopathic arthritis
Examples of peripheral SPONDYLOARTHROPATHIES
- Psoriatic arthritis
- Reactive arthritis
- Seronegative RA
Patho of Spondylarthritis
1) Genetic predisposition: Misfolding of HLA-B27 gene (chromosome 6) => unfolded proteins in macrophages => inflammation & production of cytokines
2) Infection
What does Enthesitis mean?
Enthesitis is when they get inflamed and become painful because of injury, overuse, or disease. Enthesitis is common in some forms of arthritis, including psoriatic arthritis and ankylosing spondyliti
CF for SpA
- Insidious onset; intermittent flares
- Fever, weight loss, fatigue
- Morning stiffness
- Sleep disturbance
- Exercise makes it better
- Asymmetrical Peripheral SpA
- Extra-articular: anterior uveitis, aortic regurgitation, pulmonary fibrosis, amyloidosis, Coronary Heart Disease
CF axial SpA specifically
•Axial skeleton > peripheral joints and entheses
CF specifically for Peripheral SpA
Peripheral joints and entheses > Axial skeleton
Feet (Achilles tendonitis, plantar fasciitis) and elbows (epicondyles)
CF for Ankylosing Spondylitis
- Males > Females
- Stiffness + Kyphosis (stooping)
- Pain radiates to buttocks (sacroiliitis)
- Positive Schober’s test
- Associated with extra-articular manifestations.
Non radiographic axial SpA
- Male = Female
- Sacroiliac joint damage => NOT seen on X-Ray
What is Psoriatic arthritis?
•Axial/Peripheral SpA + Psoriasis
Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.
Presentation for Psoriatic arthritis
- Pattern of presentation: Symmetrical polyarthritis, Asymmetrical oligoarthritis,Spondylitic pattern (back stiffness, sacroilitis, atlanto-axial joint involvement )
- Hands: Silvery plaques on extensors
- Fingers: Arthritis mutilans (“telescoping fingers”)
- Nails: dystrophy, pitting, onycholysis
- Often associated with uveitis, sacroiliitis, DIP joint disease > MCP, PIP joints.
- 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)
What is reactive arthritis?
- Onset of Arthritis: 4 weeks after diarrhoea (GI)/genitourinary infection (trigger).
- Organism remains in the joint causing symptoms for 4-6 months.
- Triad: Conjuctivitis, Urethritis, Joint inflammation (Pain, Swelling, Enthesopathy).
Ix for Reactive Arthritis
Laboratory:
- FBC, CRP, ESR, U&Es
- Stool culture
- Genital swab
Imaging:
- Ankylosing spondylitis
- X-Ray Spine: Squaring of vertebrae, bamboo spine, syndesmophytes, bone ankylosis/fusion
- X-Ray Pelvis: Sacroiliitis (ankylosing spondylitis)
- MRI: Sacroiliac joint damage (ankylosing spondylitis) + bone marrow oedema + fatty changes
•
Psoriatic Arthritis
X-Ray Hand:
Pencil-in-cup deformities at DIP joints
Management for Reactive Arthritis
- NSAIDs + intra-articular steroid injections + biologics
- Surgery
What are the commonly affected joints in OA?
Hips
Knees
Sacro-iliac joints
Distal-interphalangeal joints in the hands (DIPs)
The CMC joint at the base of the thumb
Wrist
Cervical spine
What type of joint is a the carpo-metacarpal joint
saddle joint
Diagnosis for OA
NICE (2014) suggest that a diagnosis can be made without any investigations if the patient is over 45, has typical activity related pain and has no morning stiffness or stiffness lasting less than 30 minutes
TRUE OR FALSE
Pain from an mechanical problem such as osteoarthritis is worse after rest but improves with activity
FALSE
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.
Atlantoaxial Subluxation occurs in which cervical spine
he axis (C2) and the odontoid peg shift within the atlas (C1)
When is referral for RA neccessary?
NICE recommend referral for any adult with persistent synovitis, even if they have negative rheumatoid factor, 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.
Criterias used in RA
American College of Rheumatology (ACR) / European League Against Rheumatism (ELAR) from 2010:
DAS28 Score
Management for RA
Biological Therapies
- Anti-TNF (adalimumab, infliximab, etanercept, golimumab and certolizumab pegol)
- Anti-CD20 (rituximab)
- Anti-IL6 (sarilumab)
- Anti-IL6 receptor (tocilizumab)
- JAK inhibitors (tofacitinib and baricitinib)
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 patients are prone to serious infections. They can also lead to reactivation of dormant infections such as TB and hepatitis B.
Methotrexate S/E
Why is that ?
- Mouth ulcers and mucositis
- Liver toxicity
- Pulmonary fibrosis
- Bone marrow suppression and leukopenia (low white blood cells)
- It is teratogenic (harmful to pregnancy) and needs to be avoided prior to conception in mothers and fathers
Methotrexate 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.
Common sides effects of DMARD and Biolgics
Methotrexate: pulmonary fibrosis
Leflunomide: Hypertension and peripheral neuropathy
Sulfasalazine: Male infertility (reduces sperm count)
Hydroxychloroquine: Nightmares and reduced visual acuity
Anti-TNF medications: Reactivation of TB or hepatitis B
Rituximab: Night sweats and thrombocytopenia
Ix for Psoriatic Arthritis
Other Associations
- Eye disease (conjunctivitis and anterior uveitis)
- Aortitis (inflammation of the aorta)
- Amyloidosis
Psoriasis Epidemiological Screening Tool (PEST)
This involves several questions asking about joint pain, swelling, a history of arthritis and nail pitting. A high score triggers a referral to a rheumatologist.
Xray Changes
- Periostitis is inflammation of the periosteum causing a thickened and irregular outline of the bone
- Ankylosis is where bones joining together causing joint stiffening
- Osteolysis is destruction of bone
- Dactylitis is inflammation of the whole digit and appears on the xray as soft tissue swelling
- Pencil-in-cup appearance
WHat is Arthritis Mutilans
This is the most severe form of psoriatic arthritis. This occurs in the phalanxes. There is osteolysis (destruction) 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”.
Mx for Psoriatic Arthritis
Treatment is often coordinated between dermatologists and rheumatologists.
Depending on the severity the patient 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
Differential for reactive arthritis?
What are common infectoins that trigger reactive arthritis?
septic arthritis (infection in the joint)- r in reactive arthritis there is no infection in the joint.
gastroenteritis or sexually transmitted infection. Chlamydia is the most common sexually transmitted cause of reactive arthritis. Gonorrhoea commonly causes a gonococcal septic arthritis.
link with the HLA B27 gene.
Associations with Reactive Arthritis?
- Bilateral conjunctivitis (non-infective)
- Anterior uveitis
- Circinate balanitis is dermatitis of the head of the penis
TOM TIP: These features of reactive arthritis (eye problems, balanitis and arthritis) lead to the saying “can’t see, pee or climb a tree”.
Management of reactive arthritis when septic arthritis is excluded:
- NSAIDs
- Steroid injections into the affected joints
- Systemic steroids may be required, particularly where multiple joints are affected
What is Ankylosing spondylitis
is an inflammatory condition mainly affecting the spine that causes progressive stiffness and pain. It is part of the seronegative spondyloarthropathy group of conditions relating to the HLA B27 gene. Other conditions in this group are reactive arthritis and psoriatic arthritis.
What is Schober’s Test
Have the patient stand straight. Find the L5 vertebrae. Mark a point 10cm above and 5cm below this point (15cm apart from each other). Then ask the patient 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 ankylosing spondylitis.
Investigations for Ankylosing Spondylitis
- 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
- Schobers test
Xray Changes
- Squaring of the vertebral bodies
- Bamboo spine
- Subchondral sclerosis and erosions
- Syndesmophytes are areas of bone growth where the ligaments insert into the bone. They occur related to the ligaments supporting the intervertebral joints.
- Ossification of the ligaments, discs and joints. This is where these structures turn to bone.
- Fusion of the facet, sacroiliac and costovertebral joints
Mx for Ankylosing Spondylitis
Medication:
- NSAIDs can be used to help with for pain. If the improvement is not adequate after 2-4 weeks of a maximum dose then consider switching to another NSAID.
- Steroids can be use during flares to control symptoms. This could 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 are known to be effective in treating the disease activity in AS.
- Secukinumab is a monoclonal antibody against interleukin-17. It is recommended by NICE if the response to NSAIDS and TNF inhibitors is inadequate.
Additional management:
- Physiotherapy
- Exercise and mobilisation
- Avoid smoking
- Bisphosphonates to treat osteoporosis
- Treatment of complications
- Surgery is occasionally required for deformities to the spine or other joints
What is Diffuse Cutaneous Systemic Sclerosis
Diffuse cutaneous systemic sclerosis includes the features of CREST syndrome plus many internal organs causing:
- Cardiovascular problems, particularly hypertension and coronary artery disease.
- Lung problems, particularly pulmonary hypertension and pulmonary fibrosis.
- Kidney problems, particularly glomerulonephritis and a condition called scleroderma renal crisis.
Features of systemic sclerosis
Scleroderma
Sclerodactyly
Telangiectasia
Calcinosis
Raynaud’s phenomenon
Oesophageal dysmotility
Systemic and pulmonary hypertension
Pulmonary fibrosis
Scleroderma renal crisis
classification criteria for systemic sclerosis is called?
American College of Rheumatology (ACR)
European League Against Rheumatism (EULAR)
Medical management for systemic sclerosis?
- 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 gastrointestinal symptoms
- Analgesia for joint pain
- Antibiotics for skin infections
- Antihypertensives can be used to treat hypertension (usually ACE inhibitors)
- Treatment of pulmonary artery hypertension
- Supportive management of pulmonary fibrosis
What is Discoid lupus erythematosus
Discoid lupus erythematosus is a non-cancerous chronic skin condition. It is more common in women and usually presents in young adults between ages 20 to 40. It is more common in darker-skinned patients and smokers.
It is associated with an increased risk of developing systemic lupus erythematosus, however this risk is still below 5%. Rarely the lesions can progress to squamous cell carcinoma (SCC) of the skin.
presentation of Discoid Lupus Erythematosus
The lesions typically occur on the face, ears and scalp. They are photosensitive, meaning that they are made worse by exposure to sunlight. They are associated with scarring alopecia (hair loss in affected areas that does not grow back) and hyper-pigmented or hypo-pigmented scars.
The appearance of the lesions are:
- Inflamed
- Dry
- Erythematous
- Patchy
- Crusty and scaling
Mx for Discoid Lupus Erythematosus
Skin biopsy can be used to confirm the diagnosis.
Treatment is with
- Sun protection
- Topical steroids
- Intralesional steroid injections
- Hydroxychloroquine
WHat is Giant cell Arteritis?
Giant cell arteritis is a systemic vasculitis of the medium and large arteries. It typically presents with symptoms affecting the temporal arteries and is also known as temporal arteritis.
Giant cell artheritis has a strong link to which disease?
polymyalgia rheumatica
he patients at higher risk are white females over 50.
Complication of Giant cell artheritis
Early neuro-ophthalmic complications:
- Vision loss
- Cerebrovascular accident (stroke)
Late:
- Relapses of the condition are common
- Steroid related side effects and complications
- Cerebrovascular accident (stroke)
- Aortitis leading to aortic aneurysm and aortic dissection
Symptoms of Giant cell artheritis
The main presenting feature is a headache:
- Severe unilateral headache typically around temple and forehead
- Scalp tenderness my be noticed when brushing hair
- Jaw claudication
- Blurred or double vision
- Irreversible painless complete sight loss can occur rapidly
There may be associated systemic symptoms such as:
- Fever
- Muscle aches
- Fatigue
- Weight loss
- Loss of appetite
- Peripheral oedema
*
Diagnosis of Giant Cell Arthritis
A definitive diagnosis is based on:
- Clinical presentation
- Raised ESR: usually 50 mm/hour or more
- Temporal artery biopsy findings
TOM TIP: Multinucleated giant cells are found on the temporal artery biopsy. This is what gives rise to the giant cell arteritis name. This is worth remembering for your exams as it is a popular question.
- Full blood count may show a normocytic anaemia and thrombocytosis (raised platelets)
- Liver function tests can show a raised alkaline phosphatase
- C reactive protein is usually raised
- Duplex ultrasound of the temporal artery shows the hypoechoic halo sign
Management for Giant Cell Arthritis?
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 the response to steroids within 48 hours. There is usually a rapid and significant response to treatment.
Other medications:
- Aspirin 75mg daily decreases visual loss and strokes
- Proton pump inhibitor (e.g. omeprazole) for gastric prevention while on steroids
Referrals:
- Vascular surgeons for a temporal artery biopsy in all patients with suspected GCA
- Rheumatology for specialist diagnosis and management
- Ophthalmology review as an emergency same day appointment if they develop visual symptoms
Giant Cell Arthritis
There are additional measures for patients on steroids that can be remembered by the mnemonic “Don’t STOP”:
What is it
- DON’T – Don’t stop taking steroids abruptly. There is a risk of adrenal crisis.
- S – Sick Day Rules.
- T – Treatment Card.
- O – Osteoporosis prevention with bisphosphonates and supplemental calcium and vitamin D.
- P – Proton pump inhibitor for gastric protection
Polymyositis or dermatomyositis can be caused by an underlying malignancy. This makes them ___________ ________. The most common associated cancers are:
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
Mx for Polymyositis and Dermatomyositis
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 etanerce
What is Sjogren’s Syndrome
This is an autoimmune condition that affects the exocrine glands. It leads to the symptoms of dry mucous membranes, such as dry mouth, dry eyes and dry vagina.
What antibodies are sjorgren’s syndrome associated with?
It is associated with anti-Ro and anti-La antibodies.
WHat is the schirmer Test?
The Schirmer test 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 hanging out that becomes moist is measured. The tears should travel 15mm in a healthy young adult. A result of less than 10mm is significant.
Mx for Sjogren’s Syndrome
Artificial tears
Artificial saliva
Vaginal lubricants
Hydroxychloroquine is used to halt the progression of the disease.
Complications of sjogren’s syndrome?
- Eye infections such as conjunctivitis and corneal ulcers
- Oral problems such as dental cavities and candida infections
- Vaginal problems such as candidiasis and sexual dysfunction
Sjogrens can rarely affect other organs causing complications such as:
- Pneumonia and bronciectasis
- Non-Hodgkins lymphoma
- Peripheral neuropathy
- Vasculitis
- Renal impairment
What is Vasculitis?
Vasculitis is the name for inflammation of the blood vessels. There are many different types of vasculitis that affect different sizes of blood vessel. They are categorised based on whether they affect small vessels, medium sized vessels or large vessels. They each have some unique features that will help you spot them in exams.
Name 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
Name Types of Vasculitis Affecting The Medium Vessels
- Polyarteritis nodosa
- Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome)
- Kawasaki Disease
Name Types of Vasculitis Affecting The Large Vessels
- Giant cell arteritis
- Takayasu’s arteritis
Presentation of Vasculitis
- Purpura. These are purple-coloured non-blanching spots caused by blood leaking from the vessels under the skin.
- Joint and muscle pain
- Peripheral neuropathy
- Renal impairment
- Gastrointestinal disturbance (diarrhoea, abdominal pain and bleeding)
- Anterior uveitis and scleritis
- Hypertension
There are two type of ANCA blood tests: p-ANCA and c-ANCA.
What is the difference?
P-ANCA are also called anti-MPO antibodies. C-ANCA are also called anti-PR3 antibodies. These different ANCA tests are associated with different types of vasculitis:
- p-ANCA (MPO antibodies): Microscopic polyangiitis and Churg-Strauss syndrome
- c-ANCA (PR3 antibodies): Wegener’s granulomatosis
Vasculitis management?
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 involves (e.g. Churg-Strauss syndrome)
Immunosuppressants that are used include:
- Cyclophosphamide
- Methotrexate
- Azathioprine
- Rituximab and other monoclonal antibodies
management of HSP and Kawasaki disease (the types mainly affecting children) is different.
What is Behçet’s Disease
Behçet’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, gastrointestinal 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.
There is a link with the HLA B51 gene. This is a prognostic indicator of severe disease.
Differentials for Behçet’s Disease
Mouth ulcers are very common. There is a long list of differentials to mouth ulcers:
- Simple aphthous ulcers are very common
- Inflammatory bowel disease (particularly Crohn’s disease)
- Coeliac disease
- Vitamin deficiency (B12, folate or iron)
- Herpes simplex ulcers
- Hand, foot and mouth disease (coxsackie A virus)
- Squamous cell carcinoma
Ix Behçet’s disease
Behçet’s disease is a clinical diagnosis based on the features of the condition. The only particular investigation to be aware of 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 – 48 hours later to look for a weal 5mm or more in size. It tests for non-specific hypersensitive in the skin. It is positive in Behçet’s disease, Sweet’s syndrome and pyoderma gangrenosum.
Behçet’s disease Management?
- Topical steroids to mouth ulcers (e.g. soluble betamethasone tablets)
- Systemic steroids (i.e. oral prednisolone)
- Colchicine is usually effective as an anti-inflammatory to treat symptoms
- Topical anaesthetics for genital ulcers (e.g. lidocaine ointment)
- Immunosuppressants such as azathioprine
- Biologic therapy such as infliximab
Behçet’s Disease Features
Mouth Ulcers
Patients with Behçet’s disease are expected to get at least 3 episodes of oral ulcers per year. They are painful, sharply circumscribed erosions with a red halo. They occur on the oral mucosa and heals over 2-4 weeks.
Genital Ulcers
Genital ulcers are 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 Behçet’s disease. Particular skin findings in Behçet’s disease are:
- Erythema nodosum
- Papules and pustules (similar to acne)
- Vasculitic type rashes
Eyes
Eye manifestations need emergency review by ophthalmology as they can be sight treating.
- Anterior or posterior uveitis
- Retinal vasculitis
- Retinal haemorrhage
Musculoskeletal System
- Morning stiffness
- Arthralgia
- Oligoarthritis often affecting the knee or ankle. This causes swelling without joint destruction.
Gastrointestinal System
Inflammation and ulceration can occur through the gastrointestinal tract. This tends to affect the:
- Ileum
- Caecum
- Ascending colon
Central Nervous System
- Memory impairment
- Headaches and migraines
- Aseptic meningitis
- Meningoencephalitis
Veins
In Behçet’s disease the veins can become inflamed and this can lead to vein thrombosis. Examples of this are:
- Budd Chiari syndrome
- Deep vein thrombosis
- Thrombus in pulmonary veins
- Cerebral venous sinus thrombosis
These thrombosis tend to stay in place and don’t embolism as they are related to inflammation in the vessel wall.
Lungs
Pulmonary artery aneurysms can develop. If they rupture this can be fatal.
Commonly affected joints in OA
- Hips
- Knees
- Sacro-iliac joints
- Distal-interphalangeal joints in the hands (DIPs)
- The CMC joint at the base of the thumb
- Wrist
- Cervical spine
Bone and soft tissue tumours
Hx
O/E
Hx
- Bone pain
- Night pain
- Previous history of Cancer
- Red flags: worsening pain, weight loss, night sweats
O/E
- Lump/ soft tissue mass
- Skin may be stuck to mass
- Lymph nodes
- nothing
Bone and soft tissue tumours
Ix
- Bloods: FBC, U&E, CRP, ESR
- Bone profile: Ca, Phosphate, albumin, ALP
- LFTs, LDH (lactate dehydrogenases)
Markers of bone tumours: LDH, ALP
-X-ray (rule of 2)
Whole bone, 2 views, 2 joints (above and below)
Bone and soft tissue tumours
Diagnosis?
Bone and soft tissue tumours
Benign more common in children
TRUE OR FALSE
TRUE
Compare and contrast well defined, ill defines and sclerotic bone and soft tissue tumours
What is the malignant bone and soft tissue tumour in children
Ewing’s sarcoma most common
Examples of benign tumours
Osteoma
Osteochondroma
Giant cell tumours
Bone cysts
endochrondromas
What is Osteoma?
- benign overgrowth of bone most typically occurring on the skull
- more common in children
- resolve by itself in about 18 months
- night pain relieved by NSAIDs
- associated with Gardner’s syndrome (a variant of familial adenomatous polyposis, FAP)
What is Osteochondroma?
exotosis
most common benign bone tumour
more in males, usually diagnosed in patients ages <20 years
cartilage-capped bony porkection on the external surface of a bone
WHat is a giant cell tumour?
- tumour of multinucleated giant cells within a fibrous stroma
- peak incidence 20-40 years
- occus most frequently in th epiphyses of long bones
- X-ray shows a “double bubble” or “soap bubble” appearance
Examples on malignant bone tumours
- Metastasis
- Multiple myelomas
Primary
- Osteosarcoma
- Chondrosarcoma
- fibrosarcoma
Haematological
- Leukaemia
- Lymphoma
Features of malignant bone tumours
More common in older (>40yr)
Hypercalcemia
Fractures
Cauda equina
Multiple myelomas are neoplastic plasma cells
TRUE OR FALSE
TRUE
Features of Osteosarcoma?
Features of Ewing’s sarcoma
Features of Fibrosarcoma
Which one is Sun burst appearance and which one is Codman’s triangle
Muscle and ligamentous injuries
How do you grade in muscle injuries
What is grading for ligamentous injuries like?
How do you identify multiple myelomas
- Bence-jones proteins in urine
- Presentation: CRAB
HyperCalcaemia
Renal failure
Anaemia
Punced out Bony lesions
Pathological fractures
- Histology: round plasma cells, eccentric nucleus, clock face chromatin
Examples of primary bone tumours (malignant)
Osteosarcoma
Ewing’s sarcoma
Fibrosarcoma
What is the healing potential for Ligaments
Depends upon grade of injury and ligament injured.
3 phases - same as bone.
- Inflammation.
- Repair - Type III collagen
- Remodelling - Type I collagen
What is the healing potential for Tendon
- Depend upon Grade of injury.
- Repairs weakest at 7 - 10 days.
- Regain most of original strength at 21 - 28 days.
- Maximum strength at 6 months
What is the importance of physio?
- Promote early function.
- Increase ROM.
- Encourage weight bearing.
- Improve muscular strength/endurance and control.
Bone structure
- Outer= inner=
- ECM=
- Bone is layer down in lamellae
- Osteon-=
- Volkmann’s cannal=
- Woven bone=
- Outer= cortex, inner=trabecular
- ECM= osteoclasts, osteoblasts and osteocytes
- Bone is layer down in lamellae
- Osteon-= concentric lamellae with central haversian canal
- Volkmann’s cannal= in between osteons
- Woven bone= immature bone
Normal function of bone
- Support
- Movement
- Protects organs
- Hematopoiesis
- Mineral homeostasis
Bone remodelling
RANKL-RANK-OPG:
RANK binds to osteoclast precursor
RANKL binds to RANK->stimulates NFkB-> activates osteoclast formation
OPG inhibits RANK/RANKL binding-> inhibiting osteoclast formation
WHat is Reverse RANK-RANKL signaling
RANK binds to extracellular vesicle-> attaches to RANKL on osteoblast-> stimulates RUNX2-> osteogenesis
Sclerostin inhibits Wnt-> inhibiting osteogenesis
Bone mineralisation is associated with?
calcium and phosphate
Ca2+ regulated by ____ cells of the Parathyroid gland
Ca2+ regulated by chief cells of the Parathyroid gland
What happens if there is a decrease in calcium?
If decrease in Ca2+-> PTH-> decrease PO4 & increase Ca2+
What happens next after increase in calcium and decrease in phosphate
binds to osteoblasts-> promotes osteoclastogenesis via RANKL upregulation-> excess Ca2+ ( CKD -> 2dary hyperparathyroidism)
stimulates production of calcitriol-> promotes synthesis of calbindin in intestinal epithelial cells-> increased absoprtion of Ca2+ in GI tract
promotes Ca2+ reabsorption in kidneys
What does oestrogen inhibit
sclerostin
inhibition of sclerostin allows?
osteoblastogenesis
+ inhibits RANKL-> no osteoclastogenesis
What happens when there is oestrogen deficiency?
Oestrogen deficiency-> osteoclastogenesis, no inhibition of sclerostin-> inhibited osteoblastogenesis
Perimenopause/Childbearing-> estrogen-> osteoblastogenesis
Postmenopausal-> problems start – osteoporosis/ osteopenia
What is osteoporosis?
- Porous bones- reduced trabecular bone à increased risk of fracture (50 y/o female = 50% lifetime risk of fragility fractures)
- resorption>formation
- Most common metabolic bone disease
Osteoporosis RF
- Affects women more after menopause à less oestrogen àosteoclastogeneis + uninhibited sclerostin à deceased osteoblastogenesis
- Affects old people more (senile osteoporosis) à impaired osteoblast function à more resorption
- Older age
- Female
- Reduced mobility and activity
- Low BMI (<18.5 kg/m2)
- Rheumatoid arthritis
- Alcohol and smoking
- Long term corticosteroids. NICE suggest the risk increases significantly with the equivalent of more than 7.5mg of prednisolone per day for more than 3 months)
- Other medications such as SSRIs, PPIs, anti-epileptics and anti-oestrogens
What is the determinant of osteoporosis
•Determinants of peak bone mass: genetics, body weight, sex hormones, diet, exercise
Determinants of bone loss: sex hormone deficiency, genetics, diet, immobility, diseases, drugs (corticosteroids, aromatase inhibitors, glitazones
What can you see radiologically with rickets
CF of osteoporosis
- height loss
- thoracic kyphosis or lumbar lordosis
- protuberant abdomen
- decreased lung capacity
- early satiety, weight loss, oesophageal reflux
Ix for osteoperosis?
-DEXA scan
- Compares pts bone density to that of a normal adult
- Produces a T-score = 2.5 è osteoporosis
- X ray
- PTH, TFTs, vit D, urinary calcium (24hr), bone turnover markers- CTX & P1NP
Treatments for osteoporosis
Antiresorptive:
- Bisphosphonates eg alendronic acid
- Anti-RANKL ab eg Denosumab
Anabolic:
- recombinant PTH eg teriparatide
- Anti-sclerostin Ab eg Romosozumab
What is pagets disease
- Disorder of bone remodelling – focally increased and disorganised bone turnover
- driven by abnormal osteoclasts à increased and haphazard osteoblast activity à formation of poor quality woven bone
Paget’s disease of bone refers to a disorder of bone turnover. There is excessive bone turnover (formation and reabsorption) due to excessive activity of both osteoblasts and osteoclasts. 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).
Causes for pagets disease
Genetics
- Fx
- Mutations- SQSTM1 most common
- Ethnicity
Environmental
- Involvement of paramyxovirus
- Mechanical loading of affected bone
- Poor nutrition in childhood
Ix for osteomalacia?
CF of pagets disease
- Early – asymptomatic
- Bone Pain= bone impinges on nerves
- Overgrowth of bone
- Facial deformity- leontiasis
- Hearing loss- impingement on auditory nerve
- Vision loss – impingement on optic nerve
- Osteosarcoma à pagets sarcoma
- Kyphosis
- Lower limb muscle weakness
- Pelvic asymmetry
- Bow legs
- Arthritis
- Fractures
- Bone deformity
- Fractures
- Hearing loss can occur if it affects the bones of the ear
Ix for pagets disease
- Elevated ALP (isolated)
- Elevated bone turnover markers à P1NP and CTX
- X ray- osteolysis, osteosclerosis, chaotic bone architecture, bone expansion and deformity
- Radionucleotide bone scan- increase in tracer uptake in affects bones
Pagets disease treatment
•Bisphosphonates eg Zoledronate and risedronate – they cause osteoclast dysfunction/death
Other measures include:
- NSAIDs for bone pain
- Calcium and vitamin D supplementation, particularly whilst on bisphosphonates
- Surgery is rarely required for fractures, severe deformity or arthritis
What does DEXA SCAN show
WHO Classification
Bone mineral density (BMD
What is rickets
- decreased serum calcium/phosphate à widening and delay of mineralisation of growth plates in bones
- Associated with osteomalacia
Causes for Rickets
•Causes bowing deformity of bones, rachitic rosary, Harrison sulcus, widened wrist
Rickets
other features
- Widening gair/ delay in walking
- Bone pain, fatigue
- Fractures
- Short stature
- Tetany/ seizures
- Cardiomyopathy
What other types of rickets
Vitamin d dependent rickets
Hypophosphatemic rickets
Vitamin d dependent rickets
Causes?
Types?
Caused by
- Deficiency in 1 alpha hydroxylase
- Inactivating mutations in the vit D receptor
VDDR type I:
- Deficiency in 1-alpha hydroxylase ( converts into calcitriol)
- 25(OH) will be normal/high but 1,25(OH) will be low
VDDR type II:
- Inactivating mutations in Vit D receptor- VDR
- Both 25(OH), 1,25(OH) will be normal or high
Hypophosphatemic rickets
WHat is it
subtypes?
- Excessive renal phosphate losses
- Low serum phosphate for normal bone mineralisation
- Excess in FGF23 expressed by osteocytes
- PHEX, DMP1 normally inhibit FGF23-> mutations increase FGF23
- Subtypes:
- XLH: X-linked, PHEX- more common
- ADHR:AD, FGF23
- ARHR:AR, DMP1
What is osteomalacia?
causes
- Softening of bones dues to defective mineralisation of newly formed bones
- Mainly caused by vit D deficiency, Hypophosphatemia, inhibitors of mineralisation
CF for osteomalacia
Fatigue
Bone pain
Muscle weakness
Muscle aches
Pathological or abnormal fractures
Looser zones are fragility fractures that go partially through the bone.
Treatment for Rickets and osteomalacia
Treatment is with supplementary vitamin D (colecalciferol). There are various regimes suggested by the NICE CKS on vitamin D deficiency. They involve correcting the initial vitamin D deficiency with 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 for of 800 IU or more per day should be continued for life after the initial treatment.
Patients with vitamin D insufficiency can be started on the maintenance dose without the initial treatment regime.
Investigations for osteomalacia
Serum 25-hydroxyvitamin D is the laboratory investigation for vitamin D. The interpretation of the results is as follows:
<25 nmol/L – vitamin D deficiency
25 – 50 nmol/L – vitamin D insufficiency
75 nmol/L or above is optimal
Other investigation results include:
- Serum calcium is low
- Serum phosphate is low
- Serum alkaline phosphatase may be high
- Parathyroid hormone may be high (secondary hyperparathyroidism)
- Xrays may show osteopenia (more radiolucent bones)
- DEXA scan shows low bone mineral density
What is FRAX Tool
The FRAX tool gives a prediction of the risk of a fragility fracture over the next 10 years. This is usually the first step in assessing someone’s risk of osteoporosis.
It involves inputting information such as their 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.
It gives results as a percentage 10-year probability of a:
- Major osteoporotic fracture
- Hip fracture
What is FRAX assessment
Assessing For Osteoporosis
The first step is to perform a FRAX assessment on patients at risk of osteoporosis:
- Women aged > 65
- Men > 75
- Younger patients with risk factors 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:
FRAX outcome with a BMD result will suggest one of two outcomes:
FRAX outcome without a BMD result will suggest one of three outcomes:
- Low risk – reassure
- Intermediate 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
Management for osteoporosis
Lifestyle Changes:
Vitamin D and Calcium:Calcichew-D3, which contains 1000mg of calcium and 800 units of vitamin D (colecalciferol).
Bisphosphonates are the first-line treatment for osteoporosis.
- Alendronate 70mg once weekly (oral)
- Risedronate 35 mg once weekly (oral)
- Zoledronic acid 5 mg once yearly (intravenous)
Simplified Pathophysiology Osteomalacia
Patients with darker skin require a longer period of sun exposure to generate the same quantity of vitamin D. A standard diet contains inadequately levels of vitamin D to compensate for a lack of sun exposure. Reduced sun exposure without vitamin D supplementation leads to deficiency. Patients with malabsorption disorders (such as inflammatory bowel disease) are more likely to have vitamin D deficiency. The kidneys are essential in metabolising vitamin D to its active form, therefore vitamin D deficiency is common in chronic kidney disease.
Vitamin D is essential in calcium and phosphate absorption from the intestines and kidneys. Vitamin D is also responsible for regulating bone turnover and promoting bone reabsorption to boost the serum calcium level.
Inadequate vitamin 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. Parathyroid hormone stimulates increased reabsorption from the bones. This causes further problems with bone mineralisation.
Patients 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.
TRUE OR FALSE
TRUE
Investigations Osteomalacia
Serum 25-hydroxyvitamin D is the laboratory investigation for vitamin D. The interpretation of the results is as follows:
- <25 nmol/L – vitamin D deficiency
- 25 – 50 nmol/L – vitamin D insufficiency
- 75 nmol/L or above is optimal
Other investigation results include:
- Serum calcium is low
- Serum phosphate is low
- Serum alkaline phosphatase may be high
- Parathyroid hormone may be high (secondary hyperparathyroidism)
- Xrays may show osteopenia (more radiolucent bones)
- DEXA scan shows low bone mineral densit
Ix Pagets disease
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 are V shaped osteolytic bone lesions within the healthy bone
Biochemistry
- Raised alkaline phosphatase (and other LFTs are normal)
- Normal calcium
- Normal phosphate
Complications Paget’s Disease
- Osteogenic sarcoma (osteosarcoma)
- Spinal stenosis and spinal cord compression
What is Polymyalgia rheumatica
Polymyalgia rheumatica is an inflammatory condition that causes pain and stiffness in the shoulders, pelvic girdle and neck.
There is a strong association to giant cell arteritis and the two conditions often occur together. Both conditions respond well to treatment with steroids.
Demographics of polymyalgia rheumatica
It usually affects old adults (above 50 years)
More common in women
More common in caucasians
polymyalgia rheumatica Features
The NICE Clinical Knowledge Summary gives some core features that can be used to determine which patients may have PMR. 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
Other features
- Systemic symptoms such as weight loss, fatigue, low grade fever and low mood
- Upper arm tenderness
- Carpel tunnel syndrome
- Pitting oedema
polymyalgia rheumatica differentials
One of the key challenges is to exclude other conditions that can cause similar symptoms and not miss other diagnoses. The list of differentials is very long however some examples are:
- Osteoarthritis
- Rheumatoid arhtirits
- Systemic lupus erythematosus
- Myositis (from conditions like polymyositis or medications like statins)
- Cervical spondylosis
- Adhesive capsulitis of both shoulders
- Hyper or hypothyroidism
- Osteomalacia
- Fibromyalgia
Ix of polymyalgia rheumatica
Diagnosis is mainly based on the clinical presentation and the response to steroids. Other conditions need to be excluded in order to make a diagnosis of PMR.
Inflammatory markers (ESR, plasma viscosity and CRP) are usually raised however normal inflammatory markers do not exclude PMR.
The NICE clinical knowledge summaries advise a number of investigations prior to starting steroids to exclude other conditions:
- Full blood count
- Urea and electrolytes
- Liver function tests
- Calcium can be raised in hyperparathyroidism or cancer or low in osteomalacia
- Serum protein electrophoresis for myeloma and other protein disorders
- Thyroid stimulating hormone for thyroid function
- Creatine kinase for myositis
- Rheumatoid factor for rheumatoid arthritis
- Urine dipstick
Additional investigations to consider:
- Anti-nuclear antibodies (ANA) for systemic lupus erythematosus
- Anti-cyclic citrullinated peptide (anti-CCP) for rheumatoid arthritis
- Urine Bence Jones protein for myeloma
- Chest xray for lung and mediastinal abnormalities
Treatment for polymyalgia rheumatica
Initially patients are started on 15mg of prednisolone per day.
If 3-4 weeks of steroids has given a good response then start a reducing regime with the aim of getting the patient off steroids:
Additional measures for patients on long term steroids. You can use the mnemonic “Don’t STOP”:
- DON’T – Make them aware that they will become steroid dependent 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 (“sick day rules”)
- T – Treatment Card: Provide a steroid treatment card to alert others that they are steroid dependent in case they become unresponsive
- O – Osteoporosis prevention: Consider osteoporosis prophylaxis whilst on steroids with bisphosphonates and calcium and vitamin D supplements
- P – Proton pump inhibitor: Consider gastric protection with a proton pump inhibitor (e.g. omeprazole)
What is Antiphospholipid Syndrome
Antiphospholipid syndrome is a disorder associated with antiphospholipid antibodies where the blood becomes prone to clotting. The patient is in a hyper-coagulable state.
The main association with Antiphosolipid Syndrome are with ________ and complications in ________ particularly recurrent miscarriage.
The main associations are with thrombosis and complications in pregnancy, particularly recurrent miscarriage.
Antiphospholipid syndrome can occur on its own or secondary to an autoimmune condition, particularly _______ _______ ________
Antiphospholipid syndrome can occur on its own or secondary to an autoimmune condition, particularly systemic lupus erythematosus.
What are the antiobodies associated with antiphosolipid syndrome
- Lupus anticoagulant
- Anticardiolipin antibodies
- Anti-beta-2 glycoprotein I antibodies
These antibodies interfere with coagulation and create a hypercoagulable state where the blood is more prone to clotting.
Associations woth Antiphosolipid syndrome
Venous thromboembolism
- Deep vein thrombosis
- Pulmonary embolism
Arterial thrombosis
- Stroke
- Myocardial infarction
- 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 growths (vegetations) on the valves of the heart. The mitral valve is most commonly affected. It is associated with SLE and antiphospholipid syndrome.
Thrombocytopenia (low platelets) is common in antiphospholipid syndrome.
Diagnosis for antiphosolipid syndrome
Diagnosis is made when there is a history of thrombosis or pregnancy complication plus persistent antibodies:
- Lupus anticoagulant
- Anticardiolipin antibodies
- Anti-beta-2 glycoprotein I antibodies
What is the management for antiphosolipid syndrome
Patients are usually managed jointly between rheumatology, haematology and obstetrics (if pregnant).
Long term **warfarin **with an INR range of 2-3 is used to prevent thrombosis (3-4 may be used with recurrent 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.
