CMS150 Clinical Medicine Week 4 PDF

CMS150 CLINICAL MEDICINE WEEK 4 JANUARY 2023 LEARNING OUTCOMES Understand terminology used to classify joint pain Follow a systematic approach to the diagnosis of joint pain Differentiate between inflammatory and non-inflammatory causes of joint pain Differentiate between monoarticular, oli...

CMS150 CLINICAL MEDICINE WEEK 4 JANUARY 2023 LEARNING OUTCOMES Understand terminology used to classify joint pain Follow a systematic approach to the diagnosis of joint pain Differentiate between inflammatory and non-inflammatory causes of joint pain Differentiate between monoarticular, oligoarticular and polyarticular causes of joint pain Differentiate between infectious and non-infectious causes of joint pain Differentiate between traumatic and non-traumatic causes of acute knee pain Differentiate between the epidemiological characteristics, risk factors, clinical features, diagnostic features, and threshold for management of septic arthritis, gout and other crystal-induced arthritis, rheumatoid arthritis, and osteoarthritis Apply the threshold model of medical decision-making to a case of acute joint pain WEEK 4: THE CASE OF ZAIN MARA 46-year-old CC: bilateral knee stiffness, pain and swelling Mild low-grade fever Fatigue Terms Definitions Arthritis Joint pain with inflammation Arthralgia Joint pain Articular pain Pain from the joint Periarticular pain Pain from soft tissue surrounding joint Pain from proximal or distal structures to the joint or Referred pain neurogenic Monoarticular Involving a single joint Oligoarticular Involving 2-4 joints Polyarticular Involving ≥ 5 joints Combination of redness, swelling, warmth, and/or Inflammatory arthritis tenderness Septic joint Generally refers to bacterial infection of the joint Symmetrical arthritis Affecting both sides of the body Asymmetrical arthritis Spotty distribution of affected joints Development of new joint symptoms with Migratory arthritis improvement of previously affected joints https://www.dynamed.com/approach-to/polyarticular-arthritis-approach-to-the-patient General Joint Pain Classifications Inflammatory vs. non-inflammatory Monoarticular vs. oligoarticular vs. polyarticular Symmetrical vs. asymmetrical polyarthritis Types of joints involved Vertebral joints, sacroiliac joint Wrists, carpometacarpals, MCP, PIP, DIP Ankle, MTP Shoulders, elbows, hips, knees  Inflammatory Joint Pain Non-Inflammatory Joint Pain Classic symptoms of inflammation May or may not present with Redness swelling and tenderness, but other Swelling signs notably absent Warmth Typically worsens with activity Tenderness Causes: May worsen with inactivity Osteoarthritis Joint stiffness or "gelling" in the Trauma morning Causes: Infection Polymyalgia rheumatica Gout Sarcoidosis Calcium pyrophosphate Spondyloarthritides deposition disease Reactive arthritis Rheumatoid arthritis Psoriatic arthritis Juvenile RA Ankylosing spondylitis Systemic lupus erythmatosus Enteropathic arthritis  Commonly Mono or Commonly Polyarticular Oligoarticular Septic arthritis Rheumatoid arthritis Spondyloarthritides Systemic lupus erythematosus Reactive arthritis Vasculides Psoriatic arthritis Polymyalgia rheumatica Ankylosing spondylitis Polyarteritis nodosa Enteropathic arthritis Viral infections (e.g., parovirus Gout B19) Calcium pyrophosphate Disseminated gonococcal deposition disease infection Osteoarthritis Sjogren syndrome Trauma Acute rheumatic fever Hemochromatosis Sarcoidosis History Evaluate number and types of joints affected and symmetry if polyarthritis is present Onset (sudden vs. gradual) and duration of pain/restriction (constant vs. intermittent) History of overuse, repetitive stress, trauma Pain/stiffness in the morning (with rest) vs. after activity Previous medical history Previous gastrointestinal or sexually transmitted disease Obesity, hypertension, diabetes, kidney stones Immunocompromised Prior joint surgery, prosthetic joints Medications Thiazide diuretics, cyclosporine, procainamide, hydralazine Family history Social history Drug and alcohol use, travel, tick bites, risky sexual behaviour Physical Examination and Workup Joint examination with evaluation of range-of-motion and function Verify the pain is intraarticular and not periarticular Signs of true intraarticular disorder: Effusion, redness, swelling Restricted AROM and PROM Maximum pain at end range Pain with motion in multiple directions Periarticular problems may restrict only AROM Pain on RROM suggest tendonitis or bursitis Assess for extraarticular manifestations Examine skin, eyes, oral cavity, lungs, heart Tests to consider: Synovial fluid analysis, blood tests (WBC count, ESR, CRP, serum uric acid, blood cultures, serology, rheumatoid factor, anticitrullinated peptide antibodies, ANA), X-ray, ultrasonography, CT, MRI  Inflammatory Joint Non-Inflammatory Pain Joint Pain Red, warm, Physical appearance Normal or bony boggy/rubbery of joint swelling swelling Appearance of Yellow-white, Colourless, clear, synovial fluid opaque, watery viscous Synovial fluid > 2000 to 50,000 55 years old Increased risk with age, immunosuppression, lower socioeconomic status Onset: sudden Duration: until ~6 weeks after effective antimicrobial treatment Usually no morning pain or stiffness Fever (may or may not be present) LR+ 0.67 (95% [CI] 0.43-1.0); LR- 1.7 (95% [CI] 1.0-3.0) Joint pain and effusion, typically in large joint https://www.aafp.org/afp/2011/0915/p653.html Septic Arthritis – Risk Factors Skin infection, cutaneous ulcers, osteomyelitis, septic bursitis, abscess Due to contiguous spread from local infections Previous intraarticular injection, arthrocentesis, arthroscopy, prosthetic joint, recent joint surgery, trauma Due to direct inoculation Diabetes mellitus, HIV infection, immunosuppressive medications, IV drug abuse, other cause of sepsis, sexual activity (specifically for gonococcal arthritis) Due to hematogenous spread during bacteremia – most common route of entry into joint https://www.aafp.org/afp/2011/0915/p653.html Septic Arthritis – Clinical Features Acute joint swelling, pain, erythema, warmth, and joint immobility Usually monoarticular Knee most commonly affected, followed by hip, shoulder, ankle, elbow, wrist Sternoclavicular or sacroiliac joint infection more common in patients with history of IV drug abuse Constitutional symptoms such as fever, chills, rigors may be present https://www.aafp.org/afp/2011/0915/p653.html https://www.aafp.org/afp/2011/0915/p653.html Risk Factors Sensitivity (%) Specificity (%) LR+ (95% CI) LR- (95% CI) Age >80 years 19 95 3.5 (1.8-7.0) 0.86 (0.73-1.00) Diabetes mellitus 12 96 2.7 (1.0-6.9) 0.93 (0.83-1.00) Rheumatoid 68 73 2.5 (2.0-3.1) 0.45 (0.32-0.72) arthritis Recent joint 24 96 6.9 (3.8-12.0) 0.78 (0.64-0.94) surgery Hip or knee 35 89 3.1 (2.0-4.9) 0.73 (0.57-0.93) prosthesis Skin infection 32 88 2.8 (1.7-4.5) 0.76 (0.60-0.96) Hip or knee 24 98 15.0 (8.1-28.0) 0.77 (0.64-0.93) prosthesis and skin infection HIV-1 infection 79 50 1.7 (1.0-2.8) 0.47 (0.25-0.90) Margaretten, Mary E et al. “Does this adult patient have septic arthritis?” JAMA 297 13 (2007): 1478-88. Physical Exam Sensitivity (%) Specificity (%) LR+ (95% CI) LR- (95% CI) Fever 46 31 0.67 (0.43-1.00) 1.7 (1.0-3.0) Serum laboratory Sensitivity (%) Specificity (%) LR+ (95% CI) LR- (95% CI) values Abnormal 90 36 1.4 (1.1-1.8) 0.28 (0.07-1.10) peripheral WBC count (>10,000/µL) Elevated 95 29 1.3 (1.1-1.8) 0.17 (0.20-1.30) erythrocyte sedimentation rate (>30 mm/h) Elevated C-reactive 77 53 1.6 (1.1-2.5) 0.44 (0.24-0.82) protein (>100 mg/L) Margaretten, Mary E et al. “Does this adult patient have septic arthritis?” JAMA 297 13 (2007): 1478-88. Synovial Fluid Sensitivity (%) Specificity (%) LR+ (95% CI) LR- (95% CI) Studies WBCs >100,000/µL 29 99 28.0 (12.0- 0.71 (0.64- 66.0) 0.79) WBCs >50,000/µL 62 92 7.7 (5.7-11.0) 0.42 (0.34- 0.51) WBCs >25,000/µL 77 73 2.9 (2.5-3.4) 0.32 (0.23- 0.43) Polymorphonuclear 73 79 3.4 (2.8-4.2) 0.34 (0.25- cells ≥90% 0.47) Margaretten, Mary E et al. “Does this adult patient have septic arthritis?” JAMA 297 13 (2007): 1478-88. Septic Arthritis – Evaluation Complete blood count – elevated WBC count Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) Can be normal When elevated, these markers used to monitor therapeutic response Serum uric acid – should not be elevated; used to rule out gout Other: blood cultures (positive in 25-50% cases) Arthrocentesis for synovial fluid analysis WBC count: > 50,000 WBC/mm3 Synovial fluid WBC differential: >90% polymorphonuclear cells Gram stain, aerobic and anaerobic bacterial culture Borrelia burgdorferi cannot be cultured from synovial fluid – PCR testing if suspecting Lyme arthritis (positive in 85% of patients) Imaging may be considered: X-ray, ultrasonography, MRI https://www.aafp.org/afp/2021/1200/p589.html https://www.aafp.org/afp/2011/0915/p653.html https://img.tfd.com/medical/Davis/Tabers/a45.jpg Septic Arthritis – Management Medical emergency - Needs immediate diagnosis and urgent referral for treatment! Failure to initiate appropriate antibiotic therapy within 24-48 hours of onset → subchondral bone loss and permanent joint dysfunction https://www.aafp.org/afp/2011/0915/p653.html Gout Middle-aged men (prevalence increases with advancing age); Post-menopausal women Increasing prevalence in Western countries; analogous to obesity epidemic Prevalence 2.7-6.7% in countries with a Western lifestyle Onset: sudden Duration: acute attacks lasting 3-14 days Morning pain or stiffness usually present https://doi.org/10.1038/s41572-019-0115-y Gout – Risk Factors Demographic factors Indigenous Taiwanese, Pacific Islander, New Zealand Maori Living in high-income countries (North America and western Europe) Male sex (incidence 2-6x higher than in females) Dietary factors High alcohol intake Diet rich in meat and seafood High fructose consumption https://www.aafp.org/afp/2020/1101/p533.html Gout – Comorbid Conditions Hyperuricemia Conditions that have rapid cell turnover Metabolic syndrome (such as psoriasis, hemolytic anemia, or certain cancers) Type 2 diabetes mellitus Lesch-Nyhan syndrome Cardiovascular disease Rare hereditary condition of purine metabolism; X-lined recessive pattern – Hypertension males affected; mutation in HPRT1 gene Hyperlipidemia (elevated triglyceride leading to deficiency or complete absence of hypoxanthine-guanine and cholesterol levels) phosphoribosyltransferase (enzyme Obesity responsible for recycling purines) Chronic kidney disease Kelley-Seegmiller syndrome Rare hereditary condition of purine Diuretic use (loop and thiazide) metabolism; mild form of hypoxanthine- guanine phosphoriboxyltransferase (HPRT) Obstructive sleep apnea deficiency Menopause https://www.aafp.org/afp/2020/1101/p533.html Fig. 1: Disease progression in gout. From: Dalbeth, N., Choi, H.K., Joosten, L.A.B. et al. Gout. Nat Rev Dis Primers 5, 69 (2019). https://doi.org/10.1038/s41572-019-0115-y The transition from normouricaemia to clinically evident gout occurs in a number of steps. The first step is the development of hyperuricaemia, which can be caused by various factors, including genetic variants, chronic kidney disease, high body mass index (BMI), medications and dietary factors. In some individuals with hyperuricaemia, monosodium urate (MSU) crystal deposition occurs, and in some individuals with MSU crystal deposition, the clinical manifestations of gout (gout flares, chronic gouty arthritis and tophaceous gout) occur. Factors that contribute to the transition from hyperuricaemia to clinically evident gout are less well understood. SNP, single-nucleotide polymorphism. Gout – Clinical Features Acute, rapidly developing, self-limiting monoarthritis Commonly involving first metatarsophalangeal joint (The term podagra refers to a gout flare at the first MTP joint) Other affected joints of lower limb: midfoot, knee Flares usually self-resolve within 14 days and are interspersed between asymptomatic intercritical periods Over time, flares can become more frequent and severe, and can also affect upper limbs and multiple joints (polyarticular flares) Tophi located at the first MTP joint, other joints and tendons of foot and ankle (e.g. Achilles tendon), prepatella bursae, olecranon bursae, helix of ear https://doi.org/10.1038/s41572-019-0115-y  Tophaceous deposits on elbow Figure 1: First toe of the right foot and second toe of the left foot show tophi. and ear. https://www.medscape.com/answers/329958- Skin on dorsa shows mottled hypopigmentation 10267/what-is-the-typical-presentation-of-tophi- https://www.e-ijd.org/articles/2014/59/6/images/IndianJDermatol_2014_59_6_609_143538_f1.jpg in-gout The Lancet Diabetes & Endocrinology 2017 5DOI: (10.1016/S2213-8587(15)00420-9) https://doi.org/10.1038/s41572-019-0115-y Copyright © 2017 Elsevier Ltd https://www.aafp.org/afp/2020/1101/p533.html Gout - Evaluation Based on clinical diagnosis, classification criteria and microscopy-based diagnosis of synovial fluid 2015 ACR-EULAR Gout Classification Criteria Not meant for diagnosis of gout, but can help inform the clinician; intended for research purposes to identify subjects who may be eligible for entry into clinical studies Online calculator available here: https://goutclassificationcalculator.auckland.ac.nz/ Serum uric acid levels to identify hyperuricaemia Gold standard for diagnosis: joint aspiration and microscopy analysis showing presence of monosodium urate crystals (identified by needle- like appearance and strong negative birefringence) Other tests: ultrasonography, dual-energy CT a | Gout flare affecting the first metatarsophalangeal joint (podagra). b | Dual-energy CT image of the feet in a patient with tophaceous gout, showing monosodium urate crystal deposition (green), particularly at the right first metatarsophalangeal joint. Image in part a courtesy of J.G. Puig, Hospital Universitario Quironsauld Madrid, Spain. https://doi.org/10.1038/s41572-019-0115-y Calcium Pyrophosphate Dihydrate Crystal Deposition aka pseudogout Persons > 65 years old Onset: sudden Duration: flares lasting days to weeks Morning pain or stiffness usually present Calcium pyrophosphate dihydrate crystals are polymorphic, weakly positive under birefringent microscopy Other types of crystal-induced arthritis: calcium oxalate, hydroxyapatite  Rheumatoid Arthritis (RA) 0.5-1% worldwide prevalence Higher risk in women (2-3x higher than men), smokers, patients with family history of RA Genetic predisposition: HLA-DR1 and HLA-DR4 Systemic autoimmune inflammatory disease May have multisystem involvement Chronic/relapsing destructive synovitis (local inflammation, cartilage destruction, bone erosion) Cytokines (TNF-α, IL-1, IL-6) drive chronic synovial inflammation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661097/  RA – Clinical Features Symmetrical, polyarticular pain and stiffness – most often affecting wrists, PIP, MCP, MTP joints Morning stiffness > 1 hour Systemic symptoms: fatigue, weight loss, anemia Visible boggy swelling caused by synovitis Palpable synovial thickening Affected joint painful if pressure applied on palpation or with movement Advanced disease: ulnar deviation, MCP joint subluxation, swan neck deformity, Boutonniere deformity Extra-articular manifestations: accelerated atherosclerosis, pericarditis, keratoconjunctivits sicca, episcleritis/scleritis, interstitial lung disease, pulmonary nodules, rheumatoid nodules, pleural effusion, vasculitis https://www.aafp.org/afp/2018/0401/p455.html FIGURE 1. Boggy swelling in proximal interphalangeal and metacarpophalangeal joints (more prominent on patient's right hand) in a patient with new-onset rheumatoid arthritis. Note that the skin creases over the proximal interphalangeal joints become less apparent with swelling. Reprinted with permission from Wasserman AM. Diagnosis and management of rheumatoid arthritis. Am Fam Physician. 2011;84(11):1246. https://www.aafp.org/afp/2018/0401/p455.html RA - Evaluation Classification criteria ACR/EULAR 2010 criteria (see next slide) replaced the 1987 ARA criteria Lab findings: Radiography: periarticular erosions, osteopenia, joint space narrowing Inflammatory markers: ESR, CRP Serology markers: 75-85% will test positive for RF, ACPA or both – these patients are designated as seropositive RA Rheumatoid factor sensitivity 65-73%; specificity 82-88% LR+ 3.95-5.97; LR- 0.33-0.44 https://doi.org/10.7326/0003-4819-146-11-200706050-00008 Anti-citrullinated protein antibodies (ACPA, or anti-CCP antibodies) sensitivity 53-71%; specificity 95-96% LR+ 12.5-15.9; LR- 0.36-0.42 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984588/ American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 Diagnostic Criteria for RA At least 1 joint with definite clinical synovitis (swelling) not explained by another disease plus 1 of the following: Presence of long-standing disease previously satisfying classification criteria Presence of ≥ 2 typical periarticular erosions Score ≥ 6 on following criteria: Joint involvement (0-5) 1 large joint - 0 2-10 large joints - 1 1-3 small joints (with or without involvement of large joints) - 2 4-10 small joints (with or without involvement of large joints) - 3 > 10 joints (at least 1 small joint) - 5 Serology (0-3) negative rheumatoid factor (RF) and antibodies to anti-citrullinated protein antibodies (ACPA) - 0 low positive RF or low positive ACPA - 2 high positive RF or high positive ACPA - 3 acute phase reactants (0-2) normal C-reactive protein and normal erythrocyte sedimentation rate (ESR) - 0 abnormal C-reactive protein or abnormal ESR - 1 duration of symptoms (0-1) Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis < 6 weeks - 0 classification criteria: an American College of ≥ 6 weeks - 1 Rheumatology/European League Against Rheumatism collaborative initiative. Annals of the Rheumatic Diseases 2010;69:1580-1588. https://ard.bmj.com/content/69/9/1580 RA - Management Low threshold for referral to rheumatologist > 12-week delay in treatment associated with reduced chance of drug-free remission and increased risk for progressive joint damage https://doi.org/10.1136/bmj.c6942 Goals of treatment: Early diagnosis and early initiation of treatment to prevent irreversible joint damage Achieve long-term clinical remission Optimize quality of life Monitor for extra-articular complications RA - Management Complications of RA Osteopenia and osteoporosis → fracture Lung manifestations – pleuritis, bronchiolitis, interstitial fibrosis Accelerated atherosclerosis → coronary artery disease, peripheral vascular disease Increased insulin resistance, diabetes mellitus Vasculitis, thromboembolic disease Depression Anemia of chronic disease Felty syndrome (RA, splenomegaly, neutropenia) BACK TO THE CASE OF ZAIN MARA: 46-year-old CC: bilateral knee stiffness, pain and swelling Mild low-grade fever Fatigue Non-traumatic, chronic and progressive symmetric oligoarthritis of the knees with prolonged morning stiffness and other systemic symptoms increases our suspicion for RA ALTHOUGH INFLAMMATORY JOINT PAIN IS MOST LIKELY IN ZAIN MARA’S CASE, OSTEOARTHRITIS IS A VERY COMMON CAUSE OF KNEE PAIN. LET’S REVIEW IT… Osteoarthritis Prevalence increases with age 7.3% in ages 18-44; 30% in ages 45-64; 50% in ages 65 and older Women > men Other risk factors: overweight/obese, previous joint injury, family history, frequent bending/squatting, repetitive impact Degenerative disorder of articular cartilage associated with hypertrophic bone changes Onset: gradual Duration: lifelong with flares Usually no morning pain or stiffness (or short-lived) https://www.aafp.org/afp/2012/0101/p49.html Osteoarthritis – Clinical Features Asymmetric joint pain and stiffness – commonly affecting hands, knees, hips, feet, spine May also have joint locking or joint instability Joint pain worsened by movement/activity, especially following a period of rest Joint swelling and tenderness Bony enlargement in prolonged or severe OA Pain on range of motion and limitation of range of motion Crepitus (typically knee) may be felt and heard Bouchard nodes on proximal interphalangeal joint Heberden nodes on distal interphalangeal joints https://www.aafp.org/afp/2012/0101/p49.html Figure 1. Hand affected by osteoarthritis. (1) Heberden nodes. (2) Bouchard nodes. https://www.aafp.org/afp/2012/0101/p49.html https://www.aafp.org/afp/2012/0101/p49.html https://www.aafp.org/afp/2018/0415/p523.html Katz JN, Arant KR, Loeser RF. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA. 2021;325(6):568–578. doi:10.1001/jama.2020.22171 Osteoarthritis – Evaluation Primarily a clinical diagnosis based on history and PE Imaging not required in patients with risk factors and typical symptoms X-ray – can confirm diagnosis and rule out other conditions; helpful before referral for joint replacement May see joint space narrowing (due to loss of articular cartilage), osteophyte formation, subchondral sclerosis, joint destruction CT or MRI when diagnosis is in doubt or strong suspicion for other etiology (e.g., meniscal injury); growing use of ultrasonography Laboratory testing not usually required https://www.aafp.org/afp/2012/0101/p49.html REFERENCES Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Annals of the Rheumatic Diseases 2010;69:1580-1588. Bunt, Christopher W et al. “Knee Pain in Adults and Adolescents: The Initial Evaluation.” American family physician vol. 98,9 (2018): 576-585. Chauhan K, Jandu JS, Brent LH, et al. Rheumatoid Arthritis. [Updated 2022 Nov 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441999/ Dalbeth, N., Choi, H.K., Joosten, L.A.B. et al. Gout. Nat Rev Dis Primers 5, 69 (2019). https://doi.org/10.1038/s41572- 019-0115-y Ebell, Mark H. “Osteoarthritis: Rapid Evidence Review.” American family physician vol. 97,8 (2018): 523-526. Katz, Jeffrey N et al. “Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review.” JAMA vol. 325,6 (2021): 568- 578. doi:10.1001/jama.2020.22171 Kay, Jonathan, and Katherine S Upchurch. “ACR/EULAR 2010 rheumatoid arthritis classification criteria.” Rheumatology (Oxford, England) vol. 51 Suppl 6 (2012): vi5-9. doi:10.1093/rheumatology/kes279 Margaretten, Mary E et al. “Does this adult patient have septic arthritis?” JAMA 297 13 (2007): 1478-88. Mueller, Anna-Lena et al. “Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies.” Cells vol. 10,11 3017. 4 Nov. 2021, doi:10.3390/cells10113017 Romão, Vasco C, and João Eurico Fonseca. “Etiology and Risk Factors for Rheumatoid Arthritis: A State-of-the-Art Review.” Frontiers in medicine vol. 8 689698. 26 Nov. 2021, doi:10.3389/fmed.2021.689698 Seidman AJ, Limaiem F. Synovial Fluid Analysis. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537114/ Sinusas, Keith. “Osteoarthritis: diagnosis and treatment.” American family physician vol. 85,1 (2012): 49-56. Wasserman, Amy. “Rheumatoid Arthritis: Common Questions About Diagnosis and Management.” American family physician vol. 97,7 (2018): 455-462.