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Rheumatology Masumah & Tahmeena We will be covering… • Arthritis • Gout/Pseudogout • Vasculitis • Connective tissue diseases • Autoantibodies • Drug counsellingRheumatology history template PC - will usually be pain, swelling or stiffness of joint/s Pain: Stiffness: Swelling: - SOCRATES - When → morning? - Which joints? - S → single/multiple joints? - Duration? → significant = >30 - Associated sx → warmth, symmetrical/asymmetrical? mins redness, pain - O → acute (few hours) or - Exacerbating/relieving factors → - Unable to weight bear = RED chronic (>3 months)? rest? activity? FLAG - E → rest? Activity? - Diurnal variation? - Night time wakening? = RED REMEMBER: always ask about ICE + effect on life FLAG (especially important for rheum histories as conditions can severely impact QoL)Rheumatology history template Systems review: PMH + FH: ● General - fever, WL, fatigue 1. Arthritis → OA or RA ● Eyes - dry/gritty, red/inflamed, photophobia 2. HLA-b27 conditions → IBD, psoriasis, ● ENT - nose bleeds, crusting of the nose, mouth ulcers uveitis ● Chest - SoB, haemoptysis, chest pain ● GI - diarrhoea, blood in stools 3. Other autoimmune conditions → T1DM, thyroid disease, vitiligo, coeliac disease, ● GU - dysuria, discharge ● Skin - rashes pernicious anaemia, Addisons ● Hair - hair loss For completeness, you’d also do drug history and social history.Arthritis classification ARTHRITIS Inflammatory Non-inflammatory Other Vasculitis Septic Arthritis Crystal CTDs arthropathy Seropositive RA Gout OA Seronegative Pseudogout Ankylosing Spondylitis Psoriatic Arthritis Reactive Arthritis Enteropathic ArthritisArthritis classification ARTHRITIS Inflammatory Non-inflammatory Other Vasculitis Septic Arthritis Crystal CTDs arthropathy Seropositive RA Gout OA Seronegative Pseudogout Ankylosing Spondylitis Psoriatic Arthritis Reactive Arthritis Enteropathic ArthritisInflammatory v Non-inflammatory joint pain NON-INFLAMMATORY (e.g OA) INFLAMMATORY (e.g RA) Insidious onset (years) Acute onset Morning stiffness < 30 mins Morning stiffness > 30 mins Pain worse with movement Pain better with movement Mainly affects large, weight bearing joints Mainly affects smaller joints in hands/feet Affects DIP + PIP (spares MCP) à specific to OA Affects PIP + MCP (spares DIP) à specific to RA Not always symmetrical Usually symmetrical No constitutional symptoms Constitutional symptoms presentRheumatoid Arthritis Risk factors: RA = long-term autoimmune inflammatory arthritis - F>M - Age 40-60 Symptoms: (acute onset - days/weeks) 1. Painful/swollen/warm/red joints - PMH/FH of autoimmune disease } Worse with rest, better 2. Morning stiffness > 30 mins with activity - Smoking - Obesity 3. Systemic symptoms → fever, WL, lethargy 4. Extra-articular manifestations Commonly affected joints: - Small joints of the hands (PIP + MCP - DIP are spared in rheumatoid arthritis) - Small joints of the feet - Wrist (CMC joint) - Ankle b) Rheumatoid Arthritis O/E: • Bilateral symmetrical arthropathy of the small a) c) joints (usually PIP + MCP) • “Boggy” swelling • Pain/stiffness on movement e) • Deformities (only in established disease): - Z-thumb - Ulnar deviation d) - Swan neck deformity - Boutonniere’s f) - Guttering (muscle wasting) - Rheumatoid nodulesRheumatoid Arthritis Investigations: • Baseline bloods → FBC, U&E, LFTs, TFTs • Inflammatory markers → ESR/CRP • Antibodies → Rheumatoid Factor, Anti-CCP, ANA • Imaging: 1. X-ray hands + feet - soft tissue swelling, juxta- articular osteopenia, bony erosions, bony deformities 2. USS hands + feet - done if uncertainty about presence of synovitis O/E Diagnostic criteria = EULAR/ACR criteria - takes into account no. of joints affected, antibody status, ESR/CRP and duration of symptoms. - a score of >6/10 is needed for diagnosis.The presence of which antibody is diagnostic of Rheumatoid Arthritis? a) Anti-CCP b) Rheumatoid Factor c) ANA d) ANCA e) Anti-RoThe presence of which antibody is diagnostic of Rheumatoid Arthritis? a) Anti-CCP b) Rheumatoid Factor c) ANA NB: Rheumatoid factor is NOT diagnostic of RA. Not all patients with RA are rheumatoid factor d) ANCA positive. it can also be positive in other conditions e.g Sjogrens, malignancy, chronic infections e) Anti-RoRheumatoid Arthritis Stepwise escalation of DMARDs: 1. Conventional DMARD (methotrexate, leflunomide, sulfasalazine) + steroid Management: 2. 2x conventional DMARD • Analgesia e.g NSAIDs for pain relief 3. Methotrexate + anti-TNF • Referral to rheumatology: 4. Methotrexate + rituximab 1. Formal diagnosis 2. Start DMARDs 3. Start steroids Side effects of DMARDs: • physio/OT input - Methotrexate → pulmonary fibrosis - Leflunomide → HTN, peripheral neuropathy DMARDs + steroids → control disease - Sulfasalazine → male infertility activity, prevent joint damage, reduce CV - Hydroxychloroquine → vision loss, nightmares risk factors, provide symptomatic relief - Anti-TNF → reactivation of TB/Hep B - Rituximab → night sweats, thrombocytopeniaMethotrexate counselling ● Get a brief history → symptoms, ICE ● Ask them what they know about RA, then briefly explain what RA is - “your immune system is attacking your joints…” ● Ask them what they know about methotrexate, then explain: How it works “it dampens down your immune system so that it doesn’t attack your joints. This should help reduce the symptoms of joint pain/swelling/stiffness” Route oral Dose Gradually titrated up How to take 1x/week (usually for life) Must take folic acid as well but on a different day to methotrexate How long 6-8 weeks (steroids given for symptomatic relief to bridge the gap) before effects Side effects Common = Nausea, abdo pain, rash, mouth ulcers Rare but serious = unexplained bleeding, jaundice, SoB → get medical advice Monitoring Before: Hep B/C, TB ( mantoux ) → as these can reactivate with methotrexate After: WCC and LFTs every 2 weeks initially, less frequently thereafterMethotrexate counselling ● Get a brief history → symptoms, ICE ● Ask them what they know about RA, then briefly explain what RA is - “your immune system is attacking your joints…” ● Ask them what they know about methotrexate, then explain: How it works “it dampens down your immune system so that it doesn’t attack your joints. This should help reduce the symptoms of joint pain/swelling/stiffness” Route oral Dose Gradually titrated up How to take 1x/week (usually for life) Must take folic acid as well but on a different day to methotrexate How long 6-8 weeks (steroids given for symptomatic relief to bridge the gap) before effects Rare SE of Side effects Common = Nausea, abdo pain, rash, mouth ulcers methotrexate = Rare but serious = unexplained bleeding, jaundice, SoB → get medical advice pneumonitis + lung fibrosis Monitoring Before: Hep B/C, TB ( mantoux ) → as these can reactivate with methotrexate After: WCC and LFTs every 2 weeks initially, less frequently thereafter Methotrexate Counselling Methotrexate + Alcohol: - Can drink alcohol whilst on methotrexate, but be cautious as methotrexate can also affect liver - follow government guidance = no more than 14 units/week, with at least 2 alcohol free days Methotrexate + Pregnancy: - MUST safety net about methotrexate + pregnancy - do NOT miss!!! - If female of chilbearing age: ● Ask if she has children + any plans to have more ● Explain that Methotrexate is potentially harmful to the unborn baby ● Explain importance of taking measure to prevent pregnancy e.g OCP ● Explain that if she wishes to get pregnant, to contact the team to stop the Methotrexate and start an alternative drug e.g sulfasalazine or hydroxychloroquine ● MUST stop 6 months before conception - Males: take precautions not to conceive until 6 months after stopping Methotrexate as it can affect sperm quality and lead to birth defects. End by: summarising + questions, offering leaflets/websites and safety netting (offer number of rheumatology specialist nurse who they can ring if they have any questions/concerns)A 33-year-old female presents with pain and stiffness in her right knee, which she’s had for the last 3 months. On further questioning, she also has pain and stiffness in her left wrist and the distal interphalangeal joint of her right index finger. Her symptoms are worse in the morning and seem to improve throughout the day. She reports that her late mother also had joint problems; but does not know the diagnosis, although she recalls that her fingers were completely swollen before she started treatment. What is the most likely diagnosis? a) Psoriatic Arthritis b) Septic Arthritis c) Reactive Arthritis d) Rheumatoid Arthritis e) SLEA 33-year-old female presents with pain and stiffness in her right knee, which she’s had for the last 3 months. On further questioning, she also has pain and stiffness in her left wrist and the distal interphalangeal joint of her right index finger. Her symptoms are worse in the morning and seem toimprove throughout the day. She reports that her latemother also had joint problems; but does not know the diagnosis, although she recalls that her fingers were completely swollenbefore she started treatment. What is the most likely diagnosis? a) Psoriatic Arthritis b) Septic Arthritis c) Reactive Arthritis d) Rheumatoid Arthritis e) SLE Seronegative Spondyloarthropathies All are associated with the HLA b27 gene. 1. Ankylosing Spondylitis 2. Psoriatic Arthritis 3. Reactive Arthritis 4. Enteropathic ArthritisPsoriatic arthritis Symptoms: Extra-articular associations: 1. Joint pain/swelling/stiffness (synovitis) 1. Conjunctivitis 2. Tendon pain/swelling (enthesitis) 2. Uveitis - Achilles tendonitis - Plantar fasciitis 3. Aortitis NB: PsA can affect ALL the joints in the hands/feet (DIP, PIP and MCP) O/E: • Painful/swollen/stiff joints • Dactylitis (“sausage fingers”) • Enthesitis • Psoriatic skin plaques • Psoriatic nail changes → pitting, onycholysisPsoriatic Arthritis Investigations: - ESR/CRP - HLA b27 - X-ray of hand/foot: 1. Periostitis = inflammation of periosteum 2. Ankylosis = fusion of the bones 3. Osteolysis - destruction of the bone 4. Dactylitis = soft tissue swelling of entire digit 5. Pencil in cup appearance = due to central erosions of the bone at the articular surface NB: to support the diagnosis, look for a psoriatic skin plaque- sometimes these are found behind ears or on the scalpPsoriatic Arthritis Management: Complications: • NSAIDs - for pain relief Main complication = arthritis mutilans → severe • DMARDs (Methotrexate, Leflunomide, form of PsA that occurs in the phalanges of the Sulfasalazine) hand. • Biologics (anti-TNFs, infliximab, adalimumab) • There is osteolysis in the joints, which leads to shortening of the digits. • The skin folds as the digit shortens, resulting in a telescoping appearance. st Which DMARD is 1 line if there is tendon involvement? a) Methotrexate b) Leflunomide c) Sulfasalazine d) Etanercept e) Adalibumab st Which DMARD is 1 line if there is tendon involvement? a) Methotrexate b) Leflunomide c) Sulfasalazine d) Etanercept e) AdalibumabReactive arthritis Cause: GI or GU infection - reactive arthritis occurs ~2 weeks post-infection Presentation: Ddx: septic arthritis (key ddx • Acute onset monoarthritis (usually knee) that is to exclude), PsA, RA, gout warm/swollen/stiff • Extra-articular manifestations: Risk factors: 1. Conjunctivitis - Recent GI/GU infection 2. Uveitis - PMH/FH of HLA-b27 conditions 3. Balanitis “Can’t see, can’t pee, can’t climb a tree”Reactive arthritis Management: Investigations: Prognosis = should • Treat as septic arthritis until proven resolve within 6 - ESR/CRP otherwise!! months - HLA b27 - Sepsis 6 - WCC - Joint aspiration w/synovial - Joint aspiration + synovial fluid gram stain and MC&S fluid analysis • Once septic arthritis has been excluded: *to rule out septic arthritis - NSAIDs - Intra-articular steroid injectionsAn 18-year-old male presents with back pain. The pain has been present, intermittently, for around 6 months. It is particularly bad before his work in the morning and seems to ease off as the day goes on. He frequently wakes up in the middle of the night in significant pain. He is very active and finds that walking up hills relieves the pain as well. There is no past medical history and a spinal examination is unremarkable. a) Lumbar spinal stenosis b) Lumbar discitis c) Vertebral compression fracture d) Ankylosing Spondylitis e) Spinal malignancyAn 18-year-old male presents with back pain. The pain has been present, intermittently, for around 6 months. It is particularly bad before his work in themorning and seems to ease off as the day goes on. He frequently wakes up in the middle of the night in significant pain. He is very active and finds that walking up hills relieves the pain as well. There is no past medical history and a spinal examination is unremarkable. a) Lumbar spinal stenosis b) Lumbar discitis c) Vertebral compression fracture d) Ankylosing Spondylitis e) Spinal malignancy Ankylosing spondylitis Inflammation of spine and sacroiliac joints Symptoms Associations • Stiffness and pain in lower back ● Apical fibrosis ● Anterior uveitis • Worse at night and early O/E: morning ● Aortic regurgitation • Takes >30 mins to improve ● AV block • Reduced spinal movement ● Amyloidosis • Relieved by exercise (Modified Schober’s test) ● Achilles tendonitis • Weight loss ● And osteoporosis • Reduced chest expansion • Fatigue All As • Question mark posture • Night time wakening = red flag for Ank SpondWhat Modified Schober’s test measurement would be found in Ankylosing Spondylitis? a) Less than 15 cm b) Less than 20 cm c) Less than 25 cm d) More than 20 cm e) More than 10 cmWhat Modified Schober’s test measurement would be found in Ankylosing Spondylitis? a) Less than 15 cm b) Less than 20 cm c) Less than 25 cm d) More than 20 cm e) More than 10 cmAnkylosing spondylitis Investigations Management ● ESR, CRP (raised) 1) NSAIDs + physio ● HLA-B27 (?positive) 2) TNF alpha blockers ● FBC (?normocytic anaemia) (etanercept), steroid injections, Imaging bisphosphonates, treat complications ● X-ray of sacroiliac joint: 3) Surgery: joint syndesmophytes replacement ● CXR: bamboo spine (late sign); apical fibrosis ● MRI: marrow oedemaEnteropathic arthritis Enteropathic arthritis = seronegative spondyloarthropathy associated with IBD Risk factors: Prevalence: Occurs in 20-30% of IBD patients (usually during - PMH of IBD IBD flares) - PMH of HLA b27 conditions Joint involvement: Management: treat the underlying IBD - Large joints - Asymmetric distributionGout Most commonly affected joints: 1. MTP (base) of big toe = podagra Gout = deposition of monosodium urate crystals in the joints 2. MTP (base) of thumb Symptoms: - Acute onset severe joint pain (usually in 1 joint)v Risk factors: - M>F - swelling/erythema/warmth of joint - Obesity - Systemically well* - Excess alcohol *in septic arthritis = key ddx to rule out, - Diet high in purines (red meat, oily fish, patients will be systemically unwell. marmite) - FH of gout - Drugs – which drugs? O/E: ● red/hot/swollen joint ● Reduced ROM (due to pain) ● Gouty tophi → painless deposits of urate crystals in the SC tissue. Usually found on elbows, ears and near the small joints of the handsDrugs that cause Gout Thiazide diuretics Loop diuretics Pyrazinamide Tacrolimus Aspirin Gout NB: Gout is septic arthritis until proven otherwise!! Investigations 1. Bloods: - CRP/ESR → will be high in gout - WCC → to exclude septic arthritis - U&Es, LFTs → will influence choice of meds - Serum urate → not useful in acute attack, but should be repeated 2w after attack 2. Joint aspiration + synovial fluid analysis(GOLD STANDARD): Synovial fluid will be sent for gram stain, culture and polarising microscopy GOUT PSEUDOGOUT Monosodium urate crystals Calcium pyrophosphate crystals Needle shaped Rhomboid shaped Negatively birefringent to light Positively birefringent to lightGout Acute management: ● Rest, ice and elevate affected limb ● 1st line = NSAIDs (+ PPI cover) e.g Naproxen/Ibuprofen ● 2nd line = colchicine → if NSAIDs contraindicated e.g renal impairment ● 3rd line = steroids → if NSAIDs and colchicine are contraindicated/not tolerated. MUST make sure septic arthritis has been excluded before giving steroids. NSAIDs → Colchicine → SteroidsGout Prophylaxis: Lifestyle advice: - Reduce alcohol intake - Reduce purine intake (red meat, oily fish) - Stay hydrated - Eat foods high in vit C (vit C helps reduce serum urate) - Reduce CV risk factors Urate lowering therapy (ULT): - Started 2-4 weeks after acute attack - Works by lowering serum urate in order to prevent future attacks - 1st line = allopurinol - 2nd line = FebuxostatAllopurinol Counselling ● Lifelong medication ● Tablet form ● Taken once a day ● Works by lowering serum uric acid ● Serum uric acid must be monitored every 1-3 months initially, then every 6-12 months ● Can make things worse before they get better → allopurinol increases risk of gout attacks in the first 6-12 months. Patients should be started on NSAIDs/Colchicine 2 weeks prior to starting Allopurinol and continue for 6 months ● Side effects: N+V, diarrhoea, abdo pain, headache Allopurinol hypersensitivity syndrome: - Rare side effect of allopurinol (10%) - Drug induced rash e.g SJS - Most common in SE asian and Japanese - Mortality of 20-25% Management = symptomatic (symptoms Pseudogout usually resolve spontaneously over Pseudogout = deposition of calcium pyrophosphate crystals in the joint several weeks) Symptoms: red, hot, Risk factors: ● NSAIDs, colchicine, steroids (like 1. Older age swollen joint (similar to gout) gout) 2. Diabetes ● There is no role for ULTs as 3. Dehydration pseudogout isn't caused by high Investigations: urate 1. Joint aspiration + synovial fluid analysis: - Gram stain (? septic arthritis) - Culture (? septic arthritis) - polarising microscopy → rhomboid shaped calcium pyrophosphate crystals that are positively birefringent under polarised light 1. X-ray: will show the classific sign of chondrocalcinosis (thin white line in the middle of the joint space caused by calcium deposits)Rheumatology antibodies summary 3 main types: 1) ANAs - test for CTDs 2) ANCA - test for small vessel vasculitis 3) Anti-phospholipid antibodies - test for antiphospholipid syndrome Auto-Antibodies ANAs = test for CTDs ANCAs = for small vessel vasculitis Anti-dsDNA SLE • p-ANCA (+ MPO) = EGPA, microscopic polyangiitis Anti-smith SLE • c-ANCA (+ PR3) = GPA Anti-Ro/La SLE, Sjogren’s Anti-RNP SLE, MCTD Anti-Jo-1 Polymyositis, Dermatomyositis Anti-phospholipid Antibodies Anti-scl-70 Diffuse systemic sclerosis 1. Anti-cardiolipin Anti-centromere Limited cutaneous 2. Anti-b2 glycoprotein systemic sclerosis 3. Lupus anticoagulant (CREST) Anti-phospholipid Syndrome Lab criteria: (positive antibodies on 2+ occasions, at least 12 wks apart) 1. Anti-cardiolipin 2. Anti-b2 glycoprotein 3. Lupus anticoagulant PLUS Clinical criteria: - Increased risk of clots/DVT/PE/stroke/MI - Pregnancy complications (1 or more unexplained late miscarriage after 10/40 or 1 or more premature birth at or before 34/40) Diagnosis = lab criteria + clinical criteria SLE • Autoimmune disease causing widespread inflammation • Age 20-40 • More common in females, Afro-Caribbean/Asian Symptoms Signs ● Fatigue ● Malar rash ● Arthralgia ● Relapsing-remitting course ● Fever ● Splenomegaly ● SOB ● Livedo reticularis ● Mouth ulcers ● Hair loss ● Serositis: pleurisy, ● Raynaud’s phenomenon pericarditis ● Lymphadenopathy Complications: involves anywhere there’s connective tissue.SLE - Causes Unknown, genetic component Drug-induced Pathogens Hormonal changes • Hydralazine • EBV • Puberty • Isoniazid • CMV • Childbirth • Procainamide • HIV • Menopause • Parvovirus HIPSLE - Investigations Full examination of all systems ● Urinalysis + PCR (?proteinuria ?haematuria) ● FBC (?Normocytic anaemia) ● ESR (↑) ● CRP - usually normal ● Auto-antibodies ● Renal biopsyWhich autoantibody is is required for a diagnosis of lupus? a) pANCA b) Lupus DNA c) ANA d) Anti-dsDNA e) Anti-RoWhich autoantibody is is required for a diagnosis of lupus? a) pANCA b) Lupus DNA Other auto-antibodies may be positive as well, c) ANA but they're not as specific d) Anti-dsDNA Need to test for anti-phospholipid antibodies in e) Anti-Ro a woman of child bearing age as if these are positive, there’s increased risk of miscarriage Need to check for anti-Ro and anti-La antibodies - these can cross the placenta and cause neonatal lupusSLE - Management Lifestyle - Sun protection - Stop smoking Medications - NSAIDs for pain relief - 1 line = Hydroxychloroquine - Prednisolone used for internal organ involvementVasculitis Types VASCULITIS Large vessel Small Vessel Medium Vessel GPA EGPA HSP Takayasu’s Kawasaki Polyarteritis Microscopic Temporal nodosa polyarteritis arteritis/Giant CellTemporal Arteritis Symptoms Examination/Investigation ● >60 years ● Tender temporal arteries ● Temporal headache ● ESR raised >50 ● Jaw claudication ● LFTs (Raised alkaline phosphatase) ● Visual symptoms: ● Duplex Ultrasound of temporal artery (hypoechoic ○ Blurring halo sign) ○ Double vision ● Temporal artery biopsy (may appear normal due to ○ Amaurosis fugax (vision loss) skip lesions) ● Signs of an associated condition Management ● Start 40-60 mg prednisolone immediately on suspicion (40 if no visual/jaw symptoms) ● Urgent same day ophthalmology referral if visual symptoms ● Review in 48 hours after starting steroids Takayasu’s Arteritis • Mainly affects aorta and branches • <40 years • Affects Asian people more Symptoms: arm claudication, syncope, absent pulses Diagnosis: via CT/ MR AngiographyMedium Vessel Vasculitis Polyarteritis nodosa Kawasaki ● Can be associated with Hep B ● Children <5 infection ● More common in Japanese and Korean children ● Suspect with temp for >5 days ● Age 40-60 ● Dry cracked lips ● Myalgia + arthralgia ● Strawberry tongue ● Conjunctivitis ● Complications: ○ Coronary artery aneurysms ○ Thrombosis Management ● High dose aspirin ● IV immunoglobulinsAspirin is usually avoided in children due to the risk of: a) Reye’s syndrome b) Grey baby syndrome c) Haemolytic uraemic syndrome d) Gingival hypertrophy e) Discolouration of teethAspirin is usually avoided in children due to the risk of: a) Reye’s syndrome (swelling in brain + liver) b) Grey baby syndrome (reaction to chloramphenicol in infants) c) Haemolytic uraemic syndrome (caused by shiga toxin in E.coli) d) Gingival hypertrophy (side effect of some anti-epileptic meds) e) Discolouration of teeth (tetracycline use in children)Small Vessel Vasculitis General symptoms: GPA (Granulomatosis withEGPA (Eosinophilic Microscopic polyangiitis) granulomatosis with polyaPolyangiitis ● Joint pain ● Muscle pain ● Epistaxis ● Eosinophilia ● Renal failure ● GI problems ● Sinusitis ● Asthma ● SOB ● Fatigue ● Saddle-shaped ● Paranasal sinusitis ● Haemoptysis ● Fever nose ● Mononeuritis ● Rash ● Dyspnoea ● Hearing loss ● Skin problems ● Glomerulonephritis cANCA pANCASmall Vessel Vasculitis Management 1) Steroids - to induce immunosuppression 2) Once in remission: steroid sparing agent e.g. methotrexate, azathioprine What should be prescribed for patients on long-term steroids? a) Vitamin D + Calcium b) Bisphosphonate + Vitamin D c) PPI + Bisphosphonate d) Calcium + PPI e) Omeprazole What should be prescribed for patients on long-term steroids? a) Vitamin D + Calcium b) Bisphosphonate + Vitamin D c) PPI + Bisphosphonate d) Calcium + PPI e) OmeprazoleA 55-year-old woman presents to the Emergency Department after coughing up blood this morning. She is a non-smoker and reports that she has been feeling fatigued for the last three months and has lost 4 kg in weight. She has also experienced joint pains in her wrists and noticed blood in her urine on two separate occasions. Her past medical history includes sinusitis and recurrent epistaxis. Which is the most appropriate investigation to confirm the diagnosis? a) ANA b) cANCA c) pANCA d) Sputum fast stain e) Urine dipA 55-year-old woman presents to the Emergency Department after coughing up bloodthis morning. She is a non-smoker and reports that she has been feeling fatigued for the last three months and has lost 4 kg in weight. She has also experiencedjoint pains in her wrists and noticed blood in her urine on two separate occasions. Her past medical history includes sinusitis and recurrent epistaxis. Which is the most appropriate investigation to confirm the diagnosis? a) ANA b) cANCA c) pANCA d) Sputum fast stain e) Urine dipThank you Any questions?