Pharmacology Rheumatoid Arthritis & SLE

Pharmacology of Rheumatoid Arthritis & Systemic Lupus Erythematosus

• Rheumatoid Arthritis (RA) Treatment Goals: Control disease activity, slow joint damage, minimize pain/stiffness/complications.

• RA Treatment General Guidelines:

  • High Disease Activity: Start with methotrexate, avoid steroids.
  • Low Disease Activity: Hydroxychloroquine (HCQ), Sulfasalazine (SSZ), Methotrexate (MTX). Vaccinate before treatment.
  • Symptomatic Control: Use NSAIDs or corticosteroids for flares, adjunct to DMARD therapy.

• Disease-Modifying Anti-Rheumatic Drugs (DMARDs):

  • Non-Biologic DMARDs:
    • Methotrexate: First-line, folic acid antagonist, blocks purine synthesis, weekly dosing. Adverse effects: stomatitis, nausea/diarrhea, alopecia, myelosuppression, hepatic/pulmonary fibrosis. Contraindications: liver/lung disease, alcohol abuse, pregnancy.
    • Hydroxychloroquine: Increases pH, inhibits immune cells, hepatic/renal excretion. Adverse effects: cardiomyopathy, ocular changes (retinal depigmentation, retinopathy, corneal deposits). Contraindications: long-term use in children.
    • Leflunomide: Inhibits pyrimidine synthesis (prodrug). Adverse effects: nausea, weight loss, alopecia, hepatotoxicity, thrombocytopenia. Contraindications: pregnancy.
    • Sulfasalazine: Mechanism uncertain, may be leukotriene/TNF inhibitor. Adverse effects: nausea, dyspepsia, headache, rash, fatal blood dyscrasias.
    • JAK Inhibitors (Tofacitinib, Baricitinib, Upadacitinib): Block immune signaling. Used as monotherapy or with other non-biologic DMARDs. Adverse effects: infection, hypertension, anemia, hepatic injury, latent TB reactivation.
  • Biologic DMARDs:
    • TNF Inhibitors: Used after DMARD failure. Adverse effects: headache, infection, rash, injection site reactions, allergic reactions, demyelinating disorders, heart failure, leukemias. Contraindications: demyelinating disorders, heart failure, recent malignancy, latent TB, avoid live vaccines.
    • Anti-B Cell (Rituximab): Used if TNF inhibitors fail. Adverse effects: infection, rare fatal reactions, GI perforation, interstitial pneumonitis.
    • T-Cell Co-Stimulation Inhibitors: Blocks T-cell activation. Adverse effects: headache, nausea, infection, hypertension, leukemia, malignancies. Contraindications: immunocompromised patients.
    • IL-6 Receptor Blockers: Reduces cytokine reactions. Adverse effects: headache, diarrhea, increased liver function tests (LFTs), LDL elevation. Contraindications: hypersensitivity, demyelinating polyneuropathies, infection, TB reactivation.

• Systemic Lupus Erythematosus (SLE) Treatment Goals: Remission with minimal adverse effects, prevention of comorbidities (e.g., osteoporosis).

• SLE Treatment General Guidelines:

  • Mild Disease: NSAIDs, low-potency immunosuppressants, HCQ.
  • Organ Involvement: Prolonged steroids, potent immunosuppression (cyclosporine, mycophenolate, azathioprine). High-dose glucocorticoids + cytotoxic agents (combo therapy).
  • Drug-Induced Lupus: Treat with NSAIDs, glucocorticoids (adjust dose based on affected areas).

• SLE Risk Factors: Radiation, chemotherapy, genetics (retinoblastoma, Li-Fraumeni syndrome), Paget's disease.

Pediatric Musculoskeletal Oncology

• Key Cancers: Ewing sarcoma, Langerhans cell histiocytosis, rhabdomyosarcoma, synovial sarcoma.
• Ewing Sarcoma: Second most common childhood bone cancer. Small round blue cell tumors, arise from neural crest, commonly in diaphysis. Associated with EWS-FLI 1 mutation. Radiographic features: mixed radiolucent/radiodense, permeative destructive pattern, "onion skinning."
• Langerhans Cell Histiocytosis: Proliferation of Langerhans cells. CD1a and S100 positive, Birbeck granules on electron microscopy. Lesions in skin, lymph nodes, spleen, marrow, lungs, brain.
• Rhabdomyosarcoma: Most common soft tissue sarcoma. Originates from skeletal muscle, often in head/neck/GU. Risk factors: Li-Fraumeni syndrome, radiation. Histology: sheets of small round blue cells. Subtypes: embryonal (MYOD1, desmin, actin positive) and alveolar (PAX3/FKHR or PAX7/FKHR fusion gene).
• Synovial Sarcoma: Spindle cell carcinoma of soft tissue, in deep extremities (knees, shoulder), slow-growing. Epithelial markers (keratins, EMA, S100) positive. Associated with SYT/SSX fusion gene.
• Risk Factors for Pediatric Musculoskeletal Sarcomas: Li-Fraumeni syndrome (p53 mutation), neurofibromatosis 1 (NF1), hereditary retinoblastoma, radiation exposure.

Physiatric Approach to Non-Rheumatologic MSK Care

• MSK Anatomy: Layered approach includes osteochondral, joint congruence (static stability), arthrokinematic movement, contractile (dynamic stability), neuromechanical (mechanical rhythm, neurovascular structures).
• MSK History: Onset, provocation/palliation, quality, radiation, severity, time. Duration, disability, desire, patient goals, training changes.
• MSK Physical Exam: Visual: skin, symmetry, posture. Palpation: pain reproduction, masses, step-offs. Range of motion (ROM): active, passive. Neuro: strength, sensation, reflexes, long track signs. Functional tests (squat, step-down, gait). Special tests (provocative).
• Treatment Options: Activity modification (posture, sleep), home exercises, medications (analgesics, NSAIDs, neuropathic), orthotics, surgical interventions.
• Athlete Care: Identify operative candidates (neurologic/vascular compromise, structural damage, minimal non-surgical improvement, intractable pain, malignancy/infection).

Management of the Patient with Pelvic Pain

• PM&R Physician Role: Focus on physical impairments, restore/enhance function, maximize quality of life, support patients/families, coordinate interdisciplinary care, improve access to rehab.
• PM&R Physician Background/Training: 1 year internship, 3 year residency. Subspecialties exist in brain injury, sport medicine, pediatric rehabilitation, spinal cord injury, hospice/palliative care, neuromuscular medicine, pain medicine, pelvic health.
• Physical Therapist Role: Movement expert, improve quality of life through hands-on care, education, prescribed movement/exercise. Doctor of Physical Therapy degree, state licensure, additional fellowships/residencies.
• MSK Assessment: Global screen (UE/LE joint motion, scapular motion, function squat, heel/toe walk), spinal movement screen, single-leg stance, strength tests, peripheral nerve screen, special tests, movement screens (lunge, squat, step-up, stairs), sport/work-specific screens, balance.
• Collaboration: PM&R physician and PT utilize each other's expertise, referrals are common, early PT involvement improves outcomes.

Synthesis

• Brachial Plexus: Formed by anterior rami of C5-T1, innervating the upper limb and shoulder.
• Erb-Duchenne Palsy: Upper brachial plexus injury (C5, C6). Arm adducted, medially rotated, and elbow extended.
• Klumpke Paralysis: Lower brachial plexus injury (C8, T1). Claw hand, forearm supinated, wrist extended, fingers flexed.
• Brachial Plexus Injury Prognosis: Spontaneous recovery possible in early stages (first 3 months). Complete recovery is more likely with early biceps contraction and normal contraction by month 2. EMG and myelography are imprecise monitoring tools. Surgery is indicated for non-recovering infants, especially those with complete palsy after birth. Early intervention is key for better outcomes.
• Ethical Disclosure: Clear, objective explanation of error/complication, sincere apology, avoidance of future incidents, minimized interruptions, family support, and presence of involved personnel.

Breaking Bad News

• Bad News Definition: Serious, life-altering news impacting patient and loved-ones.
• Respectful Setting/Tone: Focus on delivering news empathetically, not methodically. Establish trust for better outcomes.
• Communication Skills: Anticipate and imagine patient/family experiences; notice and recognize emotions (body language, paralanguage, emotional statements); acknowledge and respond effectively (empathic responses).
• SPIKES Model: S - Setting, P - Perception, I - Invitation, K - Knowledge, E - Emotion.
• NURSE Model: N - Name emotions, U - Understanding, R - Respect, S - Support, E - Explore Emotions.

Fibromyalgia & Myofascial Pain

• Fibromyalgia (FM) Pathophysiology: Widespread musculoskeletal pain/tenderness, genetic predisposition, central sensitization (reduced descending pain inhibition), potential peripheral pathology (reduced nerve fibers, AV shunt changes).
• Myofascial Pain Syndrome (MPS) Pathophysiology: Regional soft tissue pain, acute/repetitive microtrauma or chronic strain, calcium release -> sustained muscle contraction, ischemia/inflammation/nociceptor sensitization, increased pro-nociceptive mediators and sympathetic activity.
• Fibromyalgia Clinical Features: Widespread pain (3+months), diffuse/bilateral, tenderness/increased sensitivity (tender points), sleep disturbance/fatigue, anxiety/depression, cognitive complaints.
• Myofascial Pain Clinical Features: Localized/regional deep pain, one/two muscles, trigger points, less systemic symptoms.
• Fibromyalgia Diagnostic Workup: Symptoms 3+ months, rule out other disorders, WPI ≥ 7 & SS ≥ 5 (or WPI 3-6 & SS ≥ 9).
• Myofascial Pain Diagnostic Workup: Suspect based on regional pattern, trigger points, persistent pain.
• Fibromyalgia Treatment: Education, pain-independent behaviors, CBT, aerobic exercise, sleep hygiene. Medications (pregabalin, duloxetine, milnacipran).
• Myofascial Pain Treatment: PT (stretching, strengthening, trigger point release), heat/cold therapy, massage, trigger point injections, NSAIDs, muscle relaxants, SNRIs, TENS.

Osteoarthritis

• Osteoarthritis Pathophysiology: Chronic degenerative joint failure; loss/failure of joint protection, cartilage loss, bony sclerosis, weakness, pain, mild-moderate inflammation, dysfunction; post trauma OA, genetics, obesity (increases incidence/progression). Loss of joint protection, accelerated wear, loss of lubricant, stress/synovial inflammation (more catabolic factors than anabolic), bone collapse, joint capsule/ligament injury, muscle weakness, peripheral neuropathy.
• Osteoarthritis Diagnostic Workup: May be diagnosed without investigations, but imaging may be useful to guide treatment; synovial fluid analysis (non-inflammatory, mostly mononuclear cells), ESR/CRP typically normal, tests for rheumatoid arthritis (RA). Persistent usage-related joint pain (one or few joints), age > 45, morning stiffness.