Rheumatoid A PBL

• Pathogenesis of RA:

  • enviro and genetic factors -> citrullination of arginine -> APC activated -> adaptive immune response -> T cells, B cells and macrophages are activated -> overproduction of TNF alpha (which encourages the overproduction of IL-6 , pro - inflammatory cytokines and chemoattractant ) -> recruit more inflammatory cells -> synovitis and tissue destruction

  
• pathogenesis of RA:

  • TGF-beta and interleukins produced by macrophages and dendritic cells supresses T reg function
  • Th17 secrete pro-inflammatory cytokines like IL-17, 21 , 22 and TNF-alpha
  • synovial cells - type A and B both produce pro - inflammatory cytokines
  • macrophages through RANKL activate osteoblasts which is needed to activate osteoclasts -> causing bone destruction / erosion , cartilage is also destroyed

  
• pathogenesis of RA:

  synovial fibroblasts:

  • VCAM-1 -> promote B cell proliferation and survival
  • DAF -> prevents complement mediated cell lysis
  • cadherin II -> mediate cell-to-cell interactions

  allows for the development of ectopic lymphoid tissue in the synovium

  
• Pathogenesis of RA:

  • synovial B cells: cytokine-activated macrophages and T cells -> activate B cells -> release IgM and IgA RF antibodies -> RFs bind to Fc of IgG -> self-aggregation and immune complex formation in synovium -> can trigger macrophages via IgG Fc receptors to produce even more cytokines IL-1, IL-8, TNF-α , and fibroblasts to produce IL-6.

  
• clinical presentation of RA:

  • pain and stiffness in joints
  • MCPs, PIPs, MTPs mainly
  • can also be wrists, elbow, shoulder, knees, ankle
  • reduced range of movment
  • morning stiffness >1hr
  • heat, swelling and tenderness of the joint
  • sx may present as polymyalgia rheumatica in older patients
• complications of untreated RA -> amyloidosis and septic arthritis
• describe the signs see

  • fixed flexion deformity - boutonniere deformity
  • hyperextension deformity - swan-neck deformity
  • ulnar deviation - due to ulnar drift and palmar subluxation of joints
  • swelling and tenosynovitis

  
• the soft tissue padding may slip foreward, exposure of the metatarsal heads to pressure of feet -> hammer-foot deformities -> ulcers and callus under the metatarsal heads

  -> ankles may assume a valgus position

  
• knees

  • swelling -> increases risk of a popliteal cyst
  • synovitis
  • erosion of bone and cartilage
  • may have a varus or valgus deformity
  • knee replacement may be needed to restore pain or mobility
• subcutaneous (rheumatic) nodules

  firm nodules over pressure points like the wrist, ankle and Achilles tendon -> can be removed surgically but may reoccur
• pathology

  • synovitis of the tendon sheaths, joints and bursae -> hyperplasic synovium and increased vascular proliferation -> increased permeability of the synovium and vasculature -> effusion of lymphocytes and dying polymorphs
  • hyperplasia causes pannus formation -> prevents cartilage from getting its nutrients -> degenerates -> exposes the underlying bone -> combined with cytokines -> juxta-articular osteroporosis
  • fibroblasts grow along the blood vessels and cause bone erosion

  
• diagnosing RA:

  • physical exam - look for the clinical presentations
  • blood count - normochromatic, normocytic anaemia
  • ESR and CRP - elevated as inflammation happening, useful to monitor treatment
  • serology - ACPA positive, RF present
  • X-rays show tissue swelling
  • US and MRI - show synovitis and early erosions
  • aspirate the joint is fluid present -> will be cloudy due to the presence of WBCs
  • musculoskeletal ultrasounds - see synovitis and whether DMARDs would be effective
• Anti-cyclic citrullinated peptide (anti-CPP) ​

  Sensitivity: 60-70%   Specificity: 97% ​

  • Predicts progression of RA: positive more likely to get erosions and joint deformity – worse prognosis. 
  • Rheumatoid Factor ​

  Anti-immunoglobulin antibody – usually IgM antibodies against Fc portion of IgG which forms immune complexes (deposited in joint)​

  Sensitivity: 80%   Specificity: 75%  for RA ​

  • Can be elevated in serum in e.g. SLE, TB. Can be negative in others e.g. reactive arthritis, ankylosing spondylitis.​

  ​
• X-ray imaging

  • Used to assess affected joints and severity / progression of RA​
  • Hands and feet imaging primarily ​
  • Identify joint erosion, misalignment and changes in joint spacing, but can show some soft tissue swelling. ​
  • Early changes:  periarticular osteopenia especially in hands and feet ​
  • Later changes: pannus formation, deformity, erosions, subluxations, collapse 
• Periarticular osteopenia is the earliest radiographic sign of rheumatoid arthritis (RA). Recent studies using dual-energy X-ray absorptiometry (DXA) have indicated that the loss of periarticular BMD can be quantified by whole-hand bone mineral density (BMD) measurements.
• why order a Chest X-ray ​

  • Extra-articular respiratory manifestations of RA: Pulmonary fibrosis, pulmonary nodules, pleuritis, pleural effusions.​
  • Rule out pre-existing chest infections or significant conditions prior to starting Methotrexate. Methotrexate is reported to cause severe pneumonitis (inflammation of alveolar walls) ​
• why is the use of joint ultrasound important?

  • Used to assess extent of soft tissue damage and inflammation ​
  • Can show blood flow to affected area (good indicator of progression) using doppler​
  • Can be used to check for tenosynovitis​
  • More sensitive to the presence of erosions and early inflammatory damage signs than X ray ​
  • Used more increasingly especially in monitoring disease progression ​
• functional assessments

  1. DAS23 - disease activity score in 2 joints. Clinical assessment of tender and swollen joints, global pain and an inflammatory biomarker (ESR or CRP)
  2. HAQ - health assessment questionnaire, is the disability index for functional ability
• GALS is part of investigations - see the hand and feet symptoms hopefully
• T2T or treat to target - a strategy that defines a treatment target (such as remission or low disease activity) and applies tight control (for example, monthly visits and respective treatment adjustment) to reach this target.
• A DAS28 score of greater than 5.1 implies active disease, less than 3.2 low disease activity and less than 2.6 remission.
• treatment:

  • NSAIDs - pain relief and morning stiffness
  • corticosteroids - shown to slow down progression (not in early RA): intraarticular, intra-muscular or oral
  • DMARDs - conventional synthetic DMARDs and Biological therapy DMARDs
  • physiotherapy, hydrotherapy, occupational therapy, podiatry
  • surgery - joint implants, arthroplasty -> reduce pain and improve function
• Early intervention csDMARDs within 3months of onset improves the outcome. Combinations of up to four drugs (steroids, sulfasalazine, methotrexate and hydroxychloroquine) may be used; the number of agents then reduced once remission has been achieved. Several DMARDs are contraindicated in pregnancy
• Biological therapies

  • more expensive than csDMARDs.
  • however, are being reduced by the introduction of biosimilar medicines

  TNF-α blockers

  • used after at least two csDMARDs (usually sulfasalazine and methotrexate) have failed.
  • given in combination with methotrexate to reduce loss of efficacy due to anti-drug antibody formation
• Comparison:

  • Mechanism: DMARDs broadly target immune pathways, biologics more specific in targeting particular molecules.
  • Source: DMARDs chemically synthesized, biologics derived from living organisms or produced through biotechnological processes.
  • Administration: DMARDs taken orally, biologics via injection or infusion.
  • Onset of Action: Biologics have a faster onset of action
  • Monitoring: Both require regular monitoring for side effects and disease progression.
  • biological DMARDs are more expensive
• CAM

  1. Acupuncture: This involves inserting thin needles into specific points on the body to alleviate pain, promote relaxation, and restore balance according to traditional Chinese medicine principles.
  2. Herbal Medicine: Herbal remedies involve using plants or plant extracts for medicinal purposes. Examples include echinacea for immune support or chamomile for relaxation
• CAM

  Homeopathy: This system uses highly diluted substances to trigger the body's natural healing processes. It operates on the principle of "like cures like," where a substance that causes symptoms in a healthy person is used in a highly diluted form to treat similar symptoms in an unwell individual.

  Mind-Body Practices: These include techniques like meditation, yoga, tai chi, and mindfulness, which aim to enhance mental well-being, reduce stress, and improve overall health through the connection between the mind and body.
• CAM

  Aromatherapy: Essential oils derived from plants are used for their aromatic and therapeutic effects, often through inhalation or topical application for relaxation, mood enhancement, or addressing certain health issues.

  Traditional Chinese Medicine (TCM): TCM includes practices like herbal medicine, acupuncture, cupping therapy, and qigong, focusing on restoring balance and energy flow in the body.
• CAM

  Ayurveda: Originating in India, Ayurvedic medicine involves a holistic approach to health using herbal remedies, dietary changes, yoga, and meditation to balance the body's energies (doshas).
• what are the differences between RA, OA, Acute gout and fibromyalgia?

  here