Rheumatology For Sports Physicians PDF

**[­Rheumatology For Sports physicians]** **[Investigations]** [ANA] - Order when high pre-test probability of rheumatic disease - Clinical: arthritis, photosensitivity, discoid rash, alopecia, xerophtalmia (dry eyes), xerostomia (dry mouth), mouth ulcers, sclerodadcyly, reynauds -...

**[­Rheumatology For Sports physicians]** **[Investigations]** [ANA] - Order when high pre-test probability of rheumatic disease - Clinical: arthritis, photosensitivity, discoid rash, alopecia, xerophtalmia (dry eyes), xerostomia (dry mouth), mouth ulcers, sclerodadcyly, reynauds - Lab findings that prompt an ANA: haemolytic anaemia, thrombocytopenia, lymphoma, hypergamaglobulinaemia, haematuria or proteinuria. - Not associated with disease activity. - 40% population have low titres and 5% of the healthy population have moderate titres ANA - Rate slightly higher in women and the elderly. - A negative result does not exclude rheumatic disease thus it is SENsitive NOT specific. - If positive speckled ANA do extractable nuclear antibodies (ENA) - Anti-SM -- SLE specific but only found in less then 1 thrid of SLE) - Anti SSA or SSB (know as Ro and La) -- Sjogrens and cutaneous lupus, and associated with congenital heart block - IF homeogeneous ANA - Anti dsDNA -- for SLE and may fluctuate with disease - If positive these should be combined with anti-CCP for RA, FBE looking for cytopenieas seen in SLE, urinanalysis for proteinuria's for renal manifestation of autoimmune disease. Serum complement which is decreased due to consumption in immune complex mediated disease like SLE, and serum immunoglobulins which are raised in sjrogens **[Viral Arthritis]** Amount of arthritis Very high rates: Ross River High: Parovirus B19, Rubella Moderate: Hep B, Hep C All viral arthritis present as polyarthritis except HIV and (oligoarthritis) and HCV (20% oligoarthritis, 80% polyarthritis) [**Ross River:**] Notifiable disease Group A arbovirus Incubation 3-21 days, Most infections are asymptomatic or mild Peripheral joints most frequently involved - Symmetrical joint involvement: Most common is ankle, knee, wrist and hand Sx - Joint pain:95% - Duration \>1 month 90% - Fatigue 90% - Arthralgia 80% - Myalgia 60% - Rash 50% - Fever 50% Mx - Non-specific - Rest in the acute stage - Gentle physical therapy - Simple analgesia + NSAIDS - Slap cheek in children - Adults: Non-specific flu-type symptoms - Rash is very common (70%) - Symmetrical arthropathy (up to 60% adults) - Hands, feet and knees - Pain and morning stiffness rather than swelling - Joint symptoms may last for years but is non-destructive - Commonly can be mislead as Ab formation, RF, ANA and anti-DNA and anti-ENA can be +ve - Symptomatic - Maculopapula rash on the hands, face and feet preserving the soles - Significant head and neck lymphadenopathy - Arthritis occurs in 30-50% females and 6% males - May be associated with vaccine - Most commonly small joints of the hands, wrist and knees and arthralia is more common than arthritis - Inflammatory - Post bacterial, urogenital or GIT - Asymetric arthritis usually lower limbs - Associated with urethritis, conjunctivitis - Age 20-30 - 80-90% Shigella - 79-80% Yersinia - 40-55% Chlamydia Clinical - Duration usually 4-5/12, can be up to 12 - Enthesitis - Conjunctivitis [Causative organisms] - Chlamydia - Enterobacters: Yersina, shigella, campylobacter - Less common: C.diff, mycoplasma, TB   Triad of - Urethritis - Conjunctivitis - Arthritis Mx - Treat the STD - Educate - Chronic autoimmune inflammatory joint disease - 1/1000-2000 - ?viral trigger - Most common rheumatological disease in children and adolescents - Defined as persistent arthritis of unknown aetiology that begins before 16 years old and persists for at least 6 weeks. If greater than 16, Still's disease. - Diagnosis of exclusion - Suspected cause could be from a viral infection / environmental factors - Synovitis can lead to joint destruction. Infiltration of plasma cells, B Lymphocytes, and T Lymphocytes. Hyperplasia of joint capsule and growth of fibrovascular connective tissue. Types (can't really differentiate for 6 months) 1. Oligoarticular F\>M (rare under 10, common in 2-3 year olds) - Affects 4 or fewer joints (MEDIUM + LARGE JTs, Asymmetric, rarely hips. Nondestructive) - 40-50% of cases - Knees, ankles, elbows and wrists. 20% Uveitis if ANA+) 2. Polyarticular (RhF negative) POLYARTICULAR- age 2-5 AND 10-14 (RARELY HIPS, DESTRUCTIVE, less frequent Uveitis) - 5+ joints - 20-25% cases - Symetrical, large and small joints 3. Polyarticular (RhF positive) - 5+ joints - 5% cases - Symetrical large and small joints - Errosive joint disease - May behave similar to rheumatoid arthritis of adults 4. Systemic - Chronic arthritis associated with systemic features; high fever, transient episodic rash (salmon), lymphadenopathy and hepatosplenomegaly - Systemic features can often precede arthritis - 5-10% cases.Destructive. - 50-60% severe destructive. 1/3 early total hip replacement. - Bony ankylosis in spine, carpal and tarsal bones. - Amyloidosis a complication too 5. Enthesitis related/associated - Previously known as juvenile spondyloarthropathy (M\>F) - Chronic arthritis associated with enthesitis with lower axial envolvement - HLA B27 is present of there is a family history of a first degree relative with a HLA B27 related disease - A significant proportion of patients will develop sacroilitis as an adult - Back and SIJ is uncommon during childhood - Associated with IBD. Uveitis will be symptomatic. 6. Psoriatic - Chronic arthritis usually with asymmetrical involvement of small and large joints - Associated with either the development of psoriasis or other evidence of a psoriatic diathesis (2 of the following, FHx in a 1^st^ degree relative, nail pits or oncycholysis or dactylitis) 7. Undifferentiated: 10 % Consider the mimickers of JIA - Septic arthritis / post-infective - ALL (acute lymphocytic leukemia) - SLE (systemic lupus erythematosus) - Trauma or non-accidental injury - Osteomyelitis - Bone tumours - IBD - HSP (Henoch0Schonlein purpura) and other vasculitis - Rheumatic fever - Hypermobility [Complications of JIA] - Uveitis-highest risk- poly or oligo, under 7 and positive ANA most at risk.- SLIT LAMP EXAM OF THESE KIDS every 3-4 months - Occurs in 30% of the oligoarticular varient, often asymptomatic and requires opthalmological surveillance. Can lead to blindness. - Presents as symptomatic acute uveitis in 7% of Enthesitis RA - Linear growth abnormality - Associated with active disease - Most common in polyarticular or systemic JIA - Osteopaenia and osteoporosis - Associated with chronic active arthritis, poor sunlight exposure, decreased physical activity and exposure to corticosteroids [Initial investigations] - ESR and CRP - FBE - ANA and RF - Antistreptolysin O titre if the patient has been recently febrile (to exclude rheumatic fever) - Plain xray if the condition has been present for \> 6months [Management (Anti- TNF agents have lead to a dramatic improvement in non systemic JIA)] - Rheumatologt referral - NSAIDS + paracetamol to start with - Rheumatologist may use - Methotrexate - Sulphasalazine - Leflunomide - Oral or intraarticular CSI - TNF alpha inhibitors **[Rheumatoid arthritis]** - 1% prevalence - Twice as common in women - Unknown aetiology - Genetic link with HLA-DR4 (this is present in 20-30% normal population) - Tobacco smoking is the best found environmental link, Obesity, Silica - Peak incidence 60-70 years - Infection trigger- Parvo/EBV **[Classification criteria for RA:]** - - Morning stiffness in / around joints ≥1/24 before maximal improvement.\* - Soft tissue swelling ≥3 or more joint areas\* - Swelling of PIP, MCP or wrist joints\* - Symmetric arthritis\* - Subcutaneous nodules - RF +ve (up to 85% cases) - ↑ titre aggressive disease / extra-articular features - XR erosions / periarticular osteopenia in hand or wrist joints. Clinical features - Typically a symmetrical arthritis affecting the wrists, metacarpophalangeal and proximal interphalangeal joints of the hand - Involvement of the MTPJ and PIPJ of the feet is not infrequent - Almost any joint can be affected - Inflammation of the synovial sheaths - Number of swollen or tender joint at baseline is an indicator of progressive disease and future radiographic progression - Morning stiffness which can last up to an hour is a cardinal feature - Systemic features may be present; flu-like symptoms, fatigue, malaise, weight loss - C-spine involvement common in 30-50% of cases Tell tail signs - Swann neck deformity - MCPJ dorsally: Synovial hypertrophy and cysts - Hyperextenion of IPJ ; Z deformity - Ulnar deviation, Boutonniere deformity, Swan neck deformity - Claw toe & hammer toe of the foot - C-spine involvement esp. C1-2 risk odontoid subluxation SC compression Variant presentations - Palindromic inflammatory arthritis - recurrent episodes of joint pain, swelling and stiffness that tend to be self limiting over several weeks. This may precede the onset of RA - Polymyalgic onset of RA -- sometimes seen in patients over the age of 65. Presents with limb girdle pain rather than peripheral arthritis and is associated with prominent stiffness - Infective - Reactive arthritis - Psoriatic arthritis - Crystal arthritis - Connective tissue diseases [Ix] - ESR and CRP - Usually elevated, correlate with disease activity - RF - +ve indicates a seropositive - It is an autoantibody against the Fc portion of IgG - Positive in 60-70% of RA patients - Less frequent in the early stages; 50% - Presents indicated an increased likelihood of extra-articular feature - Is positive in 5-10% of controls - Overall sensitivity of 65-73% and specificity of 82-88% - FALL +- NORMAL 5% OF POP, BACTERIA- ENDOCARDITIS/LEPROSY/LYME/SYPHYLIS/PERIODONTAL DISEASE VIRAL- HCV (A AND B), PARVO, CMV/EBV/HIV/PARASITE - Anti-CCP Ab - Always tested. Locally produced in inflammmed joints - More specific for RA (94-97%) and similar sensitivity (62-72%) - Strong predictor of more severe disease (erosive) - No association with Hep C unlike RF - FBE and LFT: Baseline re. medications - Plain x-rays - Limited early - Early: soft tissue swelling and periarticular osteopaenia - Later changes: cortical irregularity, erosions, loss of joint space, joint misalignment - XRAY FEET EVEN IF ASYMPTOMATIC - MRI: Early bone oedema and erosions (OCCASIONALLY NEED 40% DAMAGE TO SEE JOINT CHANGES ON XRAY) PERIDONTAL DISEASE IS A RF FOR RA. ARE BACTWERIA DRIVING AN IMMUNE RESPONSE  [Complications and extra-articular features]  - MSK - Muscle wasting - Tendon rupture - Atlanto-axial instability - Nodules - Occur in 30% - Occur on extensor tendon surfaces, lungs and heart (infection / tendon rupture) - Associated with extra-articular manifestations and poorer prognosis - Pulmonary - Most common site (40%) - Pleurisy, pleural effusion, nodules, pulmonary fibrosis, obstructive airway disease - Cardiac - CAD, pericarditis - Haematological - Anaemia (chronic disease), thrombocytosis, leucopaenia, lymphadenopathy - Neurological - Mononeuritis multiplex, sensory neuropathy, nerve impingement, cervical cord compression Pyodermic gangrenosum - Usually associated with vasculitis - Approx 25% have arthritis, usually seropositive RA - Can occur in 30% patients with IBD - Up to double overall mortality - Main causes are CV, infective and respoiritoy - Increased risk: Age of onset \ - Adaluminab, etanercept, infliximab, rituximab, abatacept - TNF alpha inhibitors - Used when mainstream DMARDS have failed - Rapid acting - Generally well tolerated but expensive - Immunosuppressive - Requires TB screening pre-use - Cancer risk is NOT increased The **diagnosis of rheumatoid arthritis (RA)** is based on a combination of **clinical signs**, **symptoms**, and **laboratory tests**. There are no definitive diagnostic criteria that can *absolutely confirm* RA in every case, but several **classification criteria** have been developed to help healthcare providers diagnose RA. One of the most widely used sets of diagnostic criteria is the **2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria for RA**. These criteria are primarily intended for classification, but they are also helpful in diagnosing RA early, which is important for effective treatment. The criteria are designed to assess **clinical features**, **serological tests**, and **radiologic findings** to determine the likelihood of RA. ### 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis: The criteria use a **point system**, with a total score of 6 or more points leading to a classification of **RA**. The criteria focus on four main components: #### 1. Joint Involvement (0--5 points) - **1 large joint** (shoulder, elbow, hip, knee, or ankle): **0 points** - **2--10 large joints**: **1 point** - **1--3 small joints** (e.g., metacarpophalangeal, proximal interphalangeal, or metatarsophalangeal joints): **2 points** - **4--10 small joints**: **3 points** - **\10 joints** (including at least one small joint): **5 points** - **Small joints** (especially the hands and feet) are more typical of RA and carry more weight in the classification. #### 2. Serology (Blood Tests) (0--3 points) - **Negative for both anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF)**: **0 points** - **Low positive for either ACPA or RF** (less than the upper limit of normal, but still elevated): **2 points** - **High positive for either ACPA or RF** (higher than the upper limit of normal): **3 points** - **ACPA** (Anti-Citrullinated Protein Antibodies): These are considered more specific for RA and are often present early in the disease. - **Rheumatoid Factor (RF)**: RF is an antibody that can be found in a variety of conditions, but it is also commonly elevated in RA. #### 3. Symptom Duration (0--1 point) - **Less than 6 weeks** of symptoms: **0 points** - **6 weeks or more** of symptoms: **1 point** - A duration of symptoms greater than 6 weeks is significant because RA is a chronic condition, and persistent symptoms are a hallmark of the disease. #### 4. Acute-Phase Reactants (0--1 point) - **Normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)**: **0 points** - **Abnormal CRP or ESR** (indicative of inflammation): **1 point** - **CRP** and **ESR** are markers of inflammation. Elevated levels can suggest active disease or inflammation, which is typical in RA. ### Scoring: - Total score ranges from **0 to 10 points**. - **A total of 6 or more points** is required for a diagnosis of **rheumatoid arthritis** according to the 2010 ACR/EULAR classification criteria. ### Additional Considerations: The ACR/EULAR criteria are designed to help classify RA and are especially useful for identifying **early RA**, but **clinical judgment** is still essential. This means that a rheumatologist or physician may make the diagnosis based on the overall clinical picture, even if the score falls slightly below the threshold. Other diagnostic tools may also be used, such as: - **X-rays**: Can reveal joint damage or erosions characteristic of RA, especially in advanced stages. - **Ultrasound or MRI**: Can detect inflammation, synovitis, or erosions in the joints earlier than X-rays. - **Other autoimmune tests**: In some cases, additional tests may be performed to rule out other causes of joint inflammation or to detect other underlying autoimmune conditions. ### Summary of Diagnostic Criteria: 1. **Joint Involvement**: Points based on the number and type of joints affected. 2. **Serology**: Points based on the presence of rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPA). 3. **Symptom Duration**: Points for symptoms lasting 6 weeks or longer. 4. **Acute-Phase Reactants**: Points for elevated CRP or ESR levels. **A total of 6 or more points** indicates the presence of RA according to these criteria. ### Other Important Diagnostic Elements: - **Early diagnosis** is crucial for improving outcomes, as treatment can slow progression and manage symptoms effectively. - **Exclusion of other conditions**: RA shares features with other inflammatory and autoimmune diseases, so differential diagnosis is important to rule out conditions like **psoriatic arthritis**, **systemic lupus erythematosus**, **gout**, and **reactive arthritis**. ### Conclusion: The 2010 ACR/EULAR criteria for rheumatoid arthritis use a point system based on joint involvement, serology, symptom duration, and inflammatory markers. While they are primarily used for classification, these criteria are an essential tool in diagnosing RA, especially in its early stages, and can guide treatment decisions. A healthcare provider will often rely on these criteria, along with clinical judgment, to diagnose RA and determine the most appropriate course of treatment.        **[SLE]** Chronic systemic autoimmune disease of unknown aetiology - 0.1% of the population - More severe and common for indigenous Australians and those of SE Asian descent + afro-caribeans - 9x more common in females - Often a significant delay between onset of Sx which may be non-specific - Course generally follows a relapsing-remitting pattern - Most frequent onset 15-50 years - 85% 10 year survival  AVASCULAR NECROSIS **[SLE : Classification Criteria:]** **[Malar "Butterfly" rash]:** fixed erythema - malar eminences, sparing nasolabial folds **[Discoid] [rash]:** erythema. raised patches w. adherent keratotic scaling & folicular plugs **[Photosensitivity]** exposure to UV light causes rash **[Oral] [ulcers]** including oral & nasopharyngeal ulcers **[Arthritis]:** ***[non-erosive, ≥2 peripheral joints] (\>90%),*** tender, swelling, effusion **[Serositis]:** pleuritis or pericarditis **[Renal]:** ***[persistent]*** ***[3+ proteinuria or cell. casts] (30-50%)...100% histol. abnormality*** **[Neurologic]**: seizures, ***psychosis (differential steroid psychosis)*** **[Hematologic]:** haemolytic anaemia / leukopenia / lymphopenia or TCP **[Immunologic]:** ***[Anti-dsDNA, Anti-Sm +/- Anti-phospholipid, ]*** **[ANA]** ***≥4 of the above 11 criteria either serially or simultaneously → SLE.*** ***(Spec. 95% / Sens. 75%)*** Clinical features - MSK - 95% have intermittent arthralgia - Generally symmetrical (hands, wrist, knees) - Frank synovitis is uncommon - Swelling less prominent than in RA and joint deformities are uncommon - Tenosynovitis is relatively common as is myalgia - AVN is a major cause of morbidity; hip, knee, ankle and wrist can be affected - Haematological - Anaemia of chronic inflammation; 70% - Autoimmune haemolytic anaemia - Leucopaenia and more frequently lymphoepaenia - Thrombocytopaenia - Cutaenous - Malar "butterfly" rash - Can be more generalised, photosensitive - NB: Discoid LE is slightly raised and scaly. This is a different rash - Face ad scalp and have the potential for scarring - Only 5% of those with DLE have SLE but in those with SLE 20% have DLE - Alopecia, oral ulceration, raynauds, urticaria, lichen planus, vasculitis, nail fold infarcts -- often present at times with increased disease activity - Renal - Lupus nephritis - 30-50% cases and may be silent - Needs regular surveillance with urina analyis, BP analysis and bloods - Key features = glomerular haematuria, proteinuria and casts - Serosal - Pleurisy /pleural effusions with pleuritic chest pain in 45-60\^ - Symptomatic pericarditis in 25% cases but often subclinical - CVD - Persistent disease activity is associated with accelerated atherosclerosis - Framingham offspring study: incidence of MI and carotid artery stenosis in female SLE patients aged 35-44 years was shown to be 50x more likely than the control group - Neuropsychiatric - 14-75% patients - Central: aeptic meningitis, CVD, demyelination, headache, movement disorders, myelopathy, seizures, acute confusional state, mood disorders, cognitive dysfunction, psychosis - Peripheral: Acute demyelinating polyneuropathy, autonomic disorders, mononeuropathy / multiplex, myasthenia gravis, cranial neuropathy, plexopathy, polyneuropathy Ix - ESR and CRP - CRP: Classically normal - ESR: Raised proportional to disease activity - FBE - ANA: 95% positive - Poor specificity - Titre of 320 or greater is clinically significant - ENA - DS-DNA and anti-smith antibodies - Anti dsDNA = some correlation with disease activity - C3 and C4 are usually reduced with active disease - Baseline LFT and UEC - Urinalysis Mx - Rheum referral - Avoidance of triggers -- ex// UV light - Mild disease: Control with NSAIDS or low dose prednisolone - Hydroxychloroquine is effective for arthritis and rash - Azathioprine and methotrexate are commonly used - Cyclophosphamide and mycophenolate are used in lupus nephritis - Anti-TNF is under Ix - CV risk reduction and protection of bone health is very important **[PMR]** Recent proposed criteria from ACR and EULAR -- debatable, mainly used for research Must Have -- Age \>50, bilateral shoulder aching and abnormal CRP or ESR plus - Morning stiffness \>45 minutes (2) - Hip pain or limited ROM (1) - Absence of RF or antiCCP antibodies (2) - Absence of other joint pain (1) - US: at least 1 abnormal shoulder, and 1 abnormal hip (GH synovitis or SA or SD bursitis, coxofemoral synovitis or trochanteric bursitis) (1) - US both shoulders abnormal. (1) Clinical - Inflammatory, characterised by aching and morning stiffness in shoulders, hip girdle and neck. - Associated with Giant Cell (Temporal) arteritis -- probably different manifestations of the same disease process - Often fatigue, anorexia, weightloss - Almost exclusively a disease of adults over 50 with increased prevalence with increased age with peak between 70-80 - W2-3:M1 - PMR 2-3 more common in GCA and occurs in 50% of patients with GCA - Associated with HLA-DR4 gene and HLA-DRB1 gene - IL-6 elevated - Histology -- muscle is normal Investigation Imaging - X-ray normal - USS and MRI -- typically Bilateral sub-acromial/deltoid bursitis is a Bloods - ESR can be normal, mildly elevated or sig elevated - CRP elevated - FBC -- normocytic anaemia - ANA, Rh Factor, CCP typically negative, however ANA and RhF typically increase with age - Typically LFT, ALP increased, however typically more in GCA - CK always normal Mx - Corticosteroids: If not 70% improvement in Sx then should be referred to rheumatologist for consideration of methotrexate ot TNF-alpha blocker. Prognosis - Usually good however may be the initial presentation to more sinister conditions (10% of patients) - This includes - Giant cell arteritis (38x increased risk) - RA, spondyloarthropathy, SLE, vasculitis, hyperparathyroidism, amyloidosis, multiple myeloma. PMR There is a lack of definitive evidence for steroid-sparing drugs in polymyalgia rheumatica. Methotrexate is typically used for relapsing disease. Leflunomide and tocilizumab are being investigated, but further research is needed. Polymyalgia rheumatica is the second most common autoimmune rheumatic disease after rheumatoid arthritis, with a lifetime risk of 2.4% for women, and 1.7% for men. It is the most common rheumatic disease in patients over 50 years old. The onset of polymyalgia rheumatica can be abrupt, often seemingly occurring overnight. There is bilateral shoulder girdle pain and prolonged early morning stiffness (typically \>45 minutes, but often lasting several hours). The hips are involved in the vast majority of patients, 2 with neck, back or buttock pain also commonly reported. Distal manifestations are less frequent and may include a peripheral arthritis of the wrists and knees which is typically more sensitive than rheumatoid arthritis to prednisolone. It is possible to confuse polymyalgia rheumatica with other conditions including rheumatoid arthritis, spondyloarthritis, mechanical tendinopathies and fibromyalgia. To further complicate matters, elderly-onset rheumatoid arthritis may have an initial 'polymyalgic' presentation before overt arthritis emerges. Diagnosis: The difficulty with diagnosis is accentuated by the absence of a gold standard investigation. Patients typically have a raised erythrocyte sedimentation rate or C-reactive protein, but infrequently the inflammatory markers are normal. Although interleukin-6 is typically elevated in untreated patients, no specific biomarker exists. Alternative diagnoses such as myositis, infection, malignancy and endocrinopathies should be excluded (Box).2,4 A rapid resolution of symptoms in response to prednisolone 15 mg daily was previously thought to represent a diagnostic surrogate for polymyalgia rheumatica. However, a small proportion of patients do not respond to three weeks of this therapy so it cannot be used to make the diagnosis. Classification criteria therefore combine clinical features and serology with the optional incorporation of ultrasound (Table 1).Ultrasound may show bursitis or tenosynovitis. In practice, the diagnosis is a clinical one and may require specialist involvement. Giant cell arteritis The most feared complication of polymyalgia rheumatica is giant cell arteritis. These conditions are closely related, and 16--21% of patients with polymyalgia rheumatica either have or will go on to develop giant cell arteritis. All patients with polymyalgia rheumatica should be educated about this complication and the need to seek urgent medical attention if they develop suggestive symptoms. Giant cell arteritis may present with headache, localised scalp tenderness, jaw claudication and, more concerningly, sudden visual loss or stroke. A small rise in erythrocyte sedimentation rate does not exclude giant cell arteritis. Giant cell arteritis requires high-dose corticosteroids, which should never be delayed while a diagnostic temporal artery biopsy is obtained. Extracranial giant cell arteritis is under-recognised and most commonly presents with constitutional features and persistently elevated inflammatory markers. Untreated it can eventually lead to formation of aortic aneurysms or stenoses of other large arteries. Imaging is being increasingly used to detect extracranial giant cell arteritis. CT angiography or magnetic resonance angiography may be useful. Nuclear medicine studies such as positron emission tomography (PET) with fluorodeoxyglucose (FDG) have been used. Although cost and radiation limit its use in routine practice, PET can identify important differential diagnoses such as infection and malignancy, and characteristic features of polymyalgia rheumatica may also be seen. Prednisolone 15 mg daily is highly effective in most patients, although a few may need up to 25 mg daily. Moderate-dose corticosteroids have been the first-line treatment for over 50 years, but were introduced before the widespread use of placebo controlled trials to confirm effectiveness. After several weeks of treatment, approximately one third of patients are able to gradually reduce their prednisolone over many months and can eventually stop.Different weaning protocols have been devised, although the ideal approach remains controversial and individual tailoring may be necessary. The British Society of Rheumatology has proposed a regimen which is globally accepted and reflected in local guidelines.This recommends prednisolone 15 mg daily for three weeks, then tapering to 12.5 mg daily for an additional three weeks, 10 mg daily for 4--6 weeks and then a reduction of 1 mg daily every 4--8 weeks thereafter. Disease relapse, defined by a recurrence of symptoms accompanied by a rise in inflammatory markers, warrants an escalation of prednisolone to the last effective dose before recommencing the weaning schedule from that dose. The British weaning schedule is more rapid than most others, but involves at least 46 weeks of prednisolone therapy. This is a much longer period of exposure compared to most other inflammatory diseases. In practice the majority of patients will need corticosteroids for at least two years and a large proportion will require ongoing low-dose prednisolone to control their symptoms.There are currently few data to help predict which patients will require ongoing therapy. Extended exposure to prednisolone is inevitable for these patients. Steroid-sparing drugs There is great impetus to develop treatment alternatives to corticosteroids. However, there is currently no alternative drug in polymyalgia rheumatica which is supported by good evidence and is affordable. Steroid-sparing drugs, such as methotrexate, are therefore not currently recommended to be started soon after diagnosis, as is the case in rheumatoid arthritis. The decision to commence a steroid-sparing drug is a personalised one based on perceived ongoing need for prednisolone. It is not possible to predict who will benefit. One approach is to consider a steroid- sparing drug in patients who flare at least twice while following the British weaning schedule or who develop overt inflammatory arthritis. Methotrexate is currently recommended by both international and local guidelines as the first-line steroid-sparing drug to consider in polymyalgia rheumatica. These recommendations acknowledge that the evidence to support this advice is of poor quality. Leflunomide might have promise, and it is currently the subject of a trial in Europe, but there may be problems with individualising the dosing. Both of these drugs are used in rheumatoid arthritis, but there is no role for most other antirheumatic drugs in polymyalgia rheumatica. This emphasises the fact that polymyalgia rheumatica is not merely an extension of rheumatoid arthritis. The use of either leflunomide or methotrexate in polymyalgia rheumatica is off label so specialist oversight is recommended Tocilizumab, an interleukin-6 receptor antagonist, has become of increasing interest as interleukin-6 is elevated in polymyalgia rheumatica.25 The drug has also had recent success in treating giant cell arteritis, but there are important immunological differences between the two diseases so the results are not necessarily transferrable. Dedicated studies in polymyalgia rheumatica are therefore required. Two phase II trials have supported the use of tocilizumab and a phase III trial is currently underway. Even if this trial is successful, the cost of tocilizumab is likely to be prohibitive for routine use, and there is a risk of serious infection, and dyslipidaemia, myelosuppression, hypertension.  **[Gout]** Purine metabolism disorder Monosodium urate crystal deposition Most common inflammatory arthritis in males. 8M:1F Associated with risk of CVD. Strong association with metabolic syndrome Uric acid = end product of purine metabolism and is excreted through kidneys (70%) ad gut (30%) 2/3 Urate load is from endogenous purine, the remainder from the diet. [Clinical ] - Acute arthropathy: Sudden onset pain, swellin and redness - Usually monoarticular (80% first attacks) - 1^st^ MTPJ : 60-75% - Followed by kneem elbow, elbow, wrist and small joints of hands and feet - Fever may occur - Lasts from days to weeks [Risk factors] - Hyperuricemia (\>,42M / \>0.36F) - Seafood, alcohol - Myeloproliferative disease - Decreased excretion - Renal abnormaility / imparement - Volume depletion - Acidosis (diabetic, lactic) - Obesity - HTN / High lipis - Genetic - Drugs - Impair excretion: Cyclosporine, thiazide, frusemide, ethambutol, low dose aspirin - Enhance excretion: Probenecid, high dose aspirin - Ethanol: Increases uric acid synthesis and decreases excretion - Beer \> wine \> spirits - Increase Uric acid excretion as contains purines - Reduces Kidneys ability to excrete - dehydration - Enhanced crystal formation: O.A [Pathogenesis of hyperuricemia ] *[Decreased Excretion Uric Acid (90%):]* - *Genetic* - *Renal insufficiency (including DM / HT / [Pb poisoning])* - *Drugs:* *- Diuretics (↑'s uric acid reabsorption)* *- Low dose aspirin (75mg/day- ↑'s uric acid concentration).* *- Cyclosporine (transplant patients)* - *Competitive anions that inhibit tubular urate secretion* *- Ketoacidosis* *- Starvation* *- Alcohol intoxication* *- Lactic acidosis.* *[Increased Production Uric Acid (10%):]* *Primary:* - *- PRPP superactivity* *- HGPRT deficiency* *Secondary:* - *- Myeloma* *- Haemolytic anemia / MPD* *- Pagets* *- Psoriasis.* - *- Gycogen Storage Diseases* *- Alcohol abuse* *[- Severe muscle exertion]* - *- Beer/alcohol* *- Shellfish* *- Offal* Stages 1. Asymptomatic hyperuricemia - Common biochemical abnormality 2. Acute gouty arthritis - Monoarthritis (85%) - MTPJ \> 90% times, then other lower limb - Can last a few hours, up to 2 weeks - Usually 11 months b/w episode 1+2 before increasing in frequency and number of joints 3. Intercritial gout - Asymptomatic b/w attacks 4. Chronic tophaceous gout - Usually after 10 yrs of intermittent gout - No pain-free periods - Periarticular tophi + polyarticular arthritis - May involve kidneys, heart valves + sclera [Risks] - Alcohol: Beer \> spirits \> wine - Increased production due to high purine content / liver ATP breakdown + decreased excretion from hyperlactate acidosis - Food: Red meat, seafood, fructose containing soft drinks - Renal disease - HTN + cholesterol - Autism [Protective] - Dairy and coffee [Ix] - Path - Joint aspirate: -ve bifreingent crystals - 20,000-100,000 leukocytes - Increased WCC + ESR - ? renal impairment - Xray: Needs years of disease before bony changes - Bony erosions - Overhanging edge to erosions - Diffuse, soft tissue calcifications [Mx] Short term: Never commence a drug that will alter serum urate levels - Simple - Education - Weight loss - Reduce alcohol intake and r/v purine intake - Maintain hydration - Medication review - Address risks - NSAIDS: indocid 100-200mg/day - Colchicine: 500mg orally 6-8 hourly. May dose is 6mg in 4 days: Inhibits phagocytosis of crystals - S/E Diarrhoea, Myopathy, NM disease, - NB: Colchicine works to inhibit neutrophil function and therefore does NOT decrease urate levels or prevent joint destruction - Colchicine is a medication commonly used to treat and prevent gout attacks. It works by reducing inflammation rather than lowering uric acid levels. Here's how it helps in gout: - - 1\. **Inhibiting Inflammatory Response**: Colchicine works by blocking the action of certain inflammatory cells called neutrophils. During a gout flare-up, neutrophils are attracted to uric acid crystals in the joints, where they release inflammatory chemicals. Colchicine prevents these cells from reaching the affected area and releasing those chemicals, reducing inflammation and pain. - 2\. **Interrupting Crystal-Driven Inflammation**: Colchicine interferes with the inflammatory process specifically triggered by uric acid crystals. By reducing the inflammation response, colchicine helps to alleviate the symptoms of a gout attack, including swelling, redness, and severe pain. - 3\. **Preventing Future Flare-Ups**: When taken in small doses over time, colchicine can help prevent future gout attacks by keeping inflammation at bay and reducing the frequency of painful episodes. - While colchicine helps manage the symptoms of gout, it doesn't reduce uric acid levels or address the root cause of gout. To prevent future attacks, lifestyle changes and medications to lower uric acid, such as allopurinol, are usually recommended. - Oral steroids - 30-35mg is as effective as NSAIDS - Intra-articular steroids: Likley to be effective however no RCT's to support this. Indications for urate lowering therapy - 2+ attacks in 1 year - Clinical or radiological evidence for gouty tophi - Tophaceous gout in soft tissue or subchondral bone - Gout with renal insufficiently - Recurrent nephrolithiasis - Urinary uric acid excretion \>1100mg.day Urate lowering therapy - Allopurinal - Do not start with acute attack - Commence 50-100mg orally for first month then increase by 50-100mg every 2-4 weeks - May need up to 900mg - Commence 2-4 weeks after attack - Monitor for hypersensitivity: rash, fever, hepatitis, eosinophilia, renal failure - Initiation of allopurinol may precipitate attack so consider covering with NSAIDS or colchicine - Febuxostat: Use in renal impairment - Febuxostat is a medication used to treat gout by lowering uric acid levels in the blood. It works by inhibiting an enzyme involved in uric acid production: - - 1\. **Inhibiting Xanthine Oxidase**: Febuxostat blocks the enzyme xanthine oxidase, which is crucial for converting purines (from food and cell breakdown) into uric acid. By inhibiting this enzyme, febuxostat reduces the amount of uric acid produced in the body. - 2\. **Reducing Uric Acid Levels**: With lower production of uric acid, febuxostat helps maintain blood uric acid levels below the threshold that causes crystals to form. Over time, this helps to dissolve existing uric acid crystals in the joints and reduces the likelihood of future gout attacks. - 3\. **Prevention of Gout Flares and Tophi**: By keeping uric acid levels low, febuxostat can help prevent the buildup of tophi (hard uric acid deposits under the skin) and reduce the frequency of gout flare-ups. - - Febuxostat is usually prescribed for people who cannot tolerate allopurinol or have not achieved adequate uric acid lowering with it. It is important to note that febuxostat may initially trigger gout flares as it mobilizes uric acid from the joints, so it is often started with an anti-inflammatory medication like colchicine for the first few months to prevent flare-ups. - Probenecis: Prevents uric acid reuptake [Chronic tophaceous gout] - Usually develop after 10 + years acute intermittent gout - Transition occurs at a time when inter-critical periods are no longer painfree - Clinically evident peri-articular and cartilaginous depostis (fingers, wrists, knees, olecranon bursa, Achilles tendon).  **[Crystal arthropathies]** CPPD / psuedogout (Calcium Pyrophosphate Deposition) - CPPD crystal deposition in fibrocartilage - Common in degenerative joints - Common in degenerative joints known as chondrocalcinosis - Pseudogout only occurs when crystals enter synovial fluid thus their presence on xray does not necessarily correlate with pain. [Epidemiology] - 15% of 65-74yrs - F\>M - Acute attacks 1.3/1,000 adults - Associated with metabolic disorders, surgery and trauma but more common idiopathic Associations - Hyperparathyroidism - Hypotheyroidism - Haemachromatosis - Hypophosphatasia - Hypomagnesaemia - Wilsons disease - Onchtonosis - Amyloidosis [Clinical] - Often seen in joints already affected by O.A - Acute onset, often not as severe as gout - Resolves in days -- weeks [Ix] - Weakly positive bifringent rhomboid shaped crystals [Mx] - NSAIDS for 1-2 weeks or pred 15-20mg. - Colchacine can be added in resistant cases - No preventative therapy **[CPPD (Calcium Pyrophosphate Dihydrate Deposition) ]** - May be incidental - Mimics gout but usually less painful - Usually only single joint - *\*\*\*\*\*Acute pseudogout: (commonest cause of acute monoarthritis in the elderly)* - Elderly may be unwell, confused and febrile - Large joints (esp knee, wrist, shoulder) affected more commonly than small - Like gout, abrupt onset and spontaneous resolution (quicker with NSAIDs). - Chronic pyrophosphate arthropathy signs as of OA, varying degree synovitis - Common in elderly / males 1.4:1 - Usually self limiting if untreated over a month or so - Patients frequently ASx between attacks. - May coexist with rheumatoid and osteoarthritis. - PMN cells engulf crystals release cytokines & other inflammatory mediators. - Rhomboic rectangular & weakly +ve birefringence crystals  [Tx] - NSAIDS - CSI to joint - Colchicine sometimes Clinical Associations: - Hyperparathyroidism - Hypothyrodiism - Hypomagnesaemia - Hypophosphatasia - *Haemochromatosis* - *Wilson's Disease* - Familial/hereditary forms - Post-traumatic including surgery (meniscectomy) and impact exercise. *Work-up for newly diagnosed CPPD deposition disease:* - Calcium (+/- PTH) \* Iron studies - Magnesium \* Phosphate - TSH \* Copper level - Alkaline phosphatase **Chondrocalcinosis** - - - Chondrocalcinosis and CPPD (calcium pyrophosphate deposition disease) are related but not exactly the same. Here's how they differ: **[Fibromyalgia]** - Fibromyalgia develops due to altered afferent sensory input known as central sensitisation and is triggered by long standing psychosocial stress or physical stress. - This results in the intensity of non-painful stimuli being amplified and experienced as painful. - Chronic musculoskeletal pain - Fatigue - Poor sleep - Cognitive disturbance - Headache/abdominal pain - Depression. - It is commonly accompanied by - Depression, anxiety, - Sensitivity to chemicals - Irritable bowel syndrome or restless legs. - Symptoms commonly start or worsen during a period of severe psychosocial or physical stress. Mx - Multidisciplinary - Exercise - Psychology - Social support **[Osteoarthritis]** - 10-12% of the population - Estimated to double between 2011 and 2020. - 2/3 patients are \