INTRODUCTION TO RHEUMATOLOGY

Definition Rheumatology (Greek ρεύμα, rheuma, river) is a sub-specialty in internal medicine and pediatrics, devoted to diagnosis and therapyof rheumatic diseases. Clinicians who specialize in rheumatology are called rheumatologists. Rheumatologists deal mainly with clinical problems involving joints, soft tissues, autoimmune diseases, vasculitis, and heritable connective tissue disorders. Many of these diseases are now known to be disorders of the immune system, and rheumatology is increasingly the study of immunology.

Introduction Immune system - protects the body against Bacteria Viruses Fungi Toxins Parasites Cancer

Defenses Against Disease Nonspecific Defenses Species Resistance Mechanical Barriers Chemical Barriers Fever Inflammation Phagocytosis Nonspecific defenses - mechanisms to protect us against pathogens in general

Specific Defenses Against Disease Specific defenses are called immunities and protect the body against very specific pathogens Lymphocytes (T&B) and macrophages are the major white blood cells involved in specific defenses. Antibodies and complement are the major proteins involved in specific defenses

Immunity Can Be Divided Into 2 Main Components: Innate immunity Rapid acting, nonspecific Specific or adaptive immunity Slower onset of action Targets pathogens that escape the innate immune system Activated by the innate immune system

Physical barrier Complement Innate NK cells Phagocytic cells - neutrophils - macrophages IMMUNITY Eosinophils Mast Cells Humoral ( B cells) Specific CMI ( T cells)

Two major types of lymphocytes B Cells & T Cells Two major types of lymphocytes B Cells and T Cells Recognize antigens in the body B cells Respond to antigens by becoming plasma cell - make antibodies against the specific antigen T Cells Cell-mediated bind to antigens on cells and attack them directly

T Cells Helper T cells increase antibody formation, memory cell formation, B cell formation, and phagocytosis Memory T cells memory cells “remember” the pathogen that activated the original T cell person is later exposed to the same pathogen, memory cells trigger an immune response that is more effective than the first immune response

Antibodies IgG - recognizes bacteria, viruses, and toxins. It can also activate complement. IgA - found in secretions of the body such as breast milk, sweat, tears, saliva, and mucus-prevents pathogens from entering the body. IgM - very large - primarily binds to antigens on food, bacteria, or incompatible blood cells- activates complement. IgE - found wherever IgA is located- involved in triggering allergic reactions.

Causes: Signs: Inflammation Redness Heat Swelling Pain Injured or infected with a pathogen, inflammation can result Signs: Redness Heat Swelling Pain Arthritis & Musculoskletal Disorders

Major Immune System Disorders Diseases and disorders that challenge the immune system: (the following are the most significant) HIV/AIDS Infections Autoimmune disease Cancer Allergies

Why even care? 3500 rheumatologists 2002 CDC reported arthritis as the leading cause of disability in the US. 55.4 million have chronic joint symptoms lasting for more than 3 months 21.5 million have not seen a physician 2 million have activity limitations 25% will be unable to work within 7 years of disease onset Direct and indirect costs are estimated at 1% of the US gross domestic product = $86.2 billion Center for Disease Control and Prevention. MMWR 2004;53:383-6. Center for Disease Control and Prevention. MMWR 2004;53:388.

Musculoskeletal Complaint Joint Pain Joint Swelling Diffuse/Systemic Initial Rheumatic History and Physical Exam to Determine: 1. Is it articular 2. Is it acute or chronic? 3. Is inflammation present? 4. How many/which joints are involved? 5. Are there RED FLAGS?

Goals of Assessment Identify “Red Flag” conditions Conditions with sufficient morbidity/mortality to warrant an expedited diagnosis Make a timely diagnosis Common conditions occur commonly Many MSk conditions are self-limiting Some conditions require serial evaluation over time to make a Dx Provide relief, reassurance and plan for evaluation and treatment

RED FLAG CONDITIONS FRACTURE INFECTION ORGAN INVOLVEMENT

Articular vs. Periarticular Finding ARTICULAR PERIARTICULAR Pain Diffuse, deep "point" tenderness ROM Pain Active+passive Active motion in all planes in few planes Swelling Common Uncommon

Peri-/Non-articular Pain Fibromyalgia Fracture Bursitis, Tendinitis, Enthesitis, Periostitis Carpal tunnel syndrome Polymyalgia rheumatica Sickle Cell Crisis Raynaud’s phenomenon Reflex sympathetic dystrophy Myxedema

Formulating a Differential Dx Condition Articular Nonarticular Inflammatory Septic Gout Rheumatoid arthritis Psoriatic arthritis Bursitis Enthesitis PMR Polymyositis Noninflammatory Osteoarthritis Charcot Joint Fracture Fibromyalgia Carpal tunnel RSD

Mono/Oligo vs Polyarticular Less than 4 joints Osteoarthritis Fracture Osteonecrosis Gout or Pseudogout Septic arthritis Lyme disease Reactive arthrtis Tuberculous/Fungal arthritis Sarcoidosis 4 or more joints Osteoarthritis Rheumatoid arthritis Psoriatic arthritis Viral arthritis Serum Sickness Juvenile arthritis SLE/PSS/MCTD

History: Clues to Diagnosis Age Young: JRA, SLE, Reiter's, GC arthritis Middle: Fibromyalgia, tendinitis, bursitis, LBP RA Elderly: OA, crystals, PMR, septic, osteoporosis Sex Males: Gout, AS, Reiter's syndrome Females: Fibrositis, RA, SLE, osteoarthritis Race White: PMR, GCA and Wegener's Black: SLE, sarcoidosis Asian: RA, SLE, Takayasu's arteritis, Behcet's

Rheumatic Review of Systems Constitutional: fever, wt loss, fatigue Ocular: blurred vision, diplopia, conjunctivitis, dry eyes Oral: dental caries, ulcers, dysphagia, dry mouth GI: hx ulcers, Abd pain, change in BM, melena, jaundice Pulm: dyspnea, cough, hemoptysis, wheezing CVS: angina/CP, arrhythmia, HTN, Raynauds Skin: photosensitivity, alopecia, nails, rash CNS: Head Ache, Sizure, weakness, paraesthesias Reproductive: sexual dysfunction, promiscuity, genital lesions, miscarriages, impotence SkM: joint pain/swelling, stiffness, ROM/function, nodules

Rheumatic Review of Systems Fever/Constitutional: septic arthritis, vasculitis, Still’s disease Ocular: Reiters, Behcets, Sjogrens, Cataracts (steroids) Oral: Sjogrens, Lupus, GC, myositis, drugs GI: Reactive arthritis, IBD, hepatitis, Polyarteritis, Scleroderma Pulm: SLE, RA lung, Churg-Strauss, Wegeners, Scleroderma CVS: Vasculitis, PSS, Raynauds, antiphospholipid syndrome Skin: SLE, psoriatic, vasculitis, Kawasaki syndrome CNS: lupus carpal tunnel, antiphospholipid, vasculitis GYN/GU: antiphospholipid, SLE, Reiters, Behcets, CTX Musculoskeletal: Gout, RA, OA, fibromyalgia, fracture

Onset & Chronology Acute: Fracture, septic arthritis, gout, rheumatic fever, Reiter's syndrome Chronic: OA, RA, SLE, psoriatic arthritis, fibromyalgia Intermittent: gout, pseudogout, Lyme, palindromic rheumatism, Behcet's, Familial Mediterranean Fever Additive: OA, RA, Reiter's syndrome, psoriatic Migratory: Viral arthritis (hepatitis B), rheumatic fever, GC arthritis, SLE

Location

Osteoarthritis Rheumatoid Arthritis Musculoskeletal Complaint Initial Rheumatic History and Physical Exam to Determine: 1. Is it articular 2. Is it acute or chronic? 3. Is inflammation present? 4. How many/which joints are involved? Nonarticular Condition Trauma/Fracture Fibromyalgia Polymyalgia Rheumatica Bursitis Tendinitis Is it Articular? No Yes Is Complaint > 6 wks Duration? No Yes Is Inflammation Present? 1. Is there prolonged AM stiffness? 2. Is there soft tissue swelling? 3. Are there systemic symptoms? 4. Is the ESR or CRP elevated? Acute Arthritis Infectious Arthritis Gout Pseudogout Reiter’s Syndrome Initial Presentation of Chronic Arthritis Acute Chronic No Yes Chronic Inflammatory Arthritis Chronic Inflammatory Mono/oligoarthritis Consider: Indolent infection Psoriatic Arthritis Reiter’s Syndrome Pauciarticular JA Chronic Noninflammatory Arthritis <4 How Many Joints Involved? Are DIP, CMC, Hip or Knee Involved? 4+ Chronic Inflammatory Polyarthritis No Yes No Consider: Psoriatic Arthritis Reiter’s Syndrome Is it Symmetric? Unlikely to be Osteoarthritis Consider: Osteonecrosis Charcot Arthritis Osteoarthritis Yes Consider: SLE Scleroderma Polymyositis Rheumatoid Arthritis Are PIP, MCP or MTP Joints Involved? No Yes Adapted from J. Cush, MD

Know It When You See It Osteoarthritis Hard bony enlargements Heberden’s nodes at the DIP joints Bouchard’s nodes at the PIP joints Often have “squared” first CMC joint due to osteophytes at that joint Osteoarthritis 3

Know It When You See It Rheumatoid arthritis Soft synovial swelling Synovitis and volar subluxation at the MCP joints Synovitis of the wrists Synovitis of the PIP joints with early swan neck deformities Rheumatoid arthritis 4

Rheumatoid Arthritis: Late Stages Associated deformities: Zeta thumb, swan neck, buttonierres, subluxation, ulnar deviation Deformities Nodules Tendon Rupture 5

Know It When You See It Jaccoud’s Deformity of SLE Associated deformities: Zeta thumb, swan neck, buttonierres, subluxation, ulnar deviation Jaccoud’s Deformity of SLE 5

Know It When You See It Seronegative asymmetric arthritis Often associated with: Inflammatory eye disease Balanitis, oral ulceration, or keratoderma Enthesopathy Sacroiliitis Seronegative asymmetric arthritis 10

Know It When You See It Psoriatic arthritis Inflammation of the DIP joints Sausage fingers Joint involvement shows radial pattern Nail changes Psoriatic patches Arthritis may start before the skin Psoriatic arthritis 7

Know It When You See It May look like psoriasis or syphilis Can occur in patches or as sterile pustules Keratoderma blennorrhagica in Reiter’s syndrome 9

Know It When You See It Systemic lupus erythematosus “Butterfly”/Malar rash Involves cheeks, spares nasolabial fold Systemic lupus erythematosus 12

Know It When You See It Dermatomyositis Interarticular dermatitis of SLE Both have periungual erythema 13

Know It When You See It Periungual changes Seen in lupus erythematosus, dermatomyositis, and scleroderma Thickening of capillary loops Dropout of capillary loops Hemorrhage in the nail fold may also be present 15

Know It When You See It “Mantle” aka “Shawl” Sign of Dermatomyositis 17

Know It When You See It Not usually associated with systemic disease Linear scleroderma 18

Know It When You See It Appears in a broad- based interrupted pattern in systemic vasculitis, including SLE May occur as a fine, connected, lacy pattern in normals Livedo reticularis 19

Know It When You See It Can be 1o or 2o Stress/cold can trigger Keep extremities and body warm Raynaud’s phenomenon 19

Know It When You See It Palpable purpura Characteristic of dermal vasculitis Palpable purpura 20

Know It When You See It Saddle nose deformity Relapsing polychondritis May also occur in Wegener’s granulomatosis and syphilis Saddle nose deformity 21

Relapsing polychondritis Know It When You See It Relapsing polychondritis Left: Ear changes with inflammation in the cartilage and swelling Right: Loss of ear cartilage in late stages Relapsing Polychondritis 22

Know It When You See It Gout Tophi appear rather late in gout Prick the tophus with a needle. Put the drop of material on a slide Gout 24

Know It When You See It Usually a few lesions Usually found on the extremities Skin pustule with disseminated gonorrhea 27

Know It When You See It Infection Tap if joint/bursa infection suspected Do not tap through cellulitis Infection 28

Know It When You See It Ehlers-Danlos syndrome A true connective-tissue disease Left: Hypermobility of joints. Can touch thumb to volar surface of forearm Right: Hyperelasticity of skin Associated with vascular abnormalities Ehlers-Danlos syndrome 33

Know It When You See It Acropachy Right: Soft tissue swelling between joints Left: Periosteal new bone formation Hyperthyroidism 32

Know It When You See It Amyloidosis Shoulder pad sign The worst case you are likely to see Patient also has macroglossia and purpura Amyloidosis 31

Rheumatologic Assessments LABS DO NOT MAKE A DIAGNOSIS. DOES! How can labs lead you astray? ESR/CRP: Origins and associations Serologies (RF, ANA, CCP, APL, ANCA): when to do & in what OTHER diseases are they positive? Arthrocentesis for diagnosis

Further Investigations Many conditions are self-limiting Consider when: Systemic manifestations (fever, wt.loss, rash, etc) Trauma (do exam or imaging for Fracture, ligament tear) Neurologic manifestations Lack of response to observation & symptomatic Rx (<6wks) Chronicity ( > 6 weeks)

Acute Phase Reactants Erythrocyte Sedimentation Rate (nonspecific) C-Reactive Protein (CRP) Fibrinogen Serum Amyloid A (SAA) Ceruloplasmin Complement (C3, C4) Haptoglobin Ferritin Other indicators: leukocytosis, thrombocytosis, hypoalbuminemia, anemia of chronic disease

Erythrocyte Sedimentation Rate ESR : Introduced by Fahraeus 1918 Mechanisms: Rouleaux formation Characteristics of RBCs Shear forces and viscosity of plasma Bridging forces of macromolecules. High MW fibrinogen tends to lessen the negative charge between RBCs and promotes aggregation. Methods: Westergren method Low ESR: Polycythemia, Sickle cell, hemolytic anemia, hemeglobinopathy, spherocytosis, delay, hypofibrinogen, hyperviscosity (Waldenstroms) High ESR: Anemia, hypercholesterolemia, female, pregnancy, inflammation, malignancy,nephrotic syndrome

ESR & Age M=Age/2 F=(Age+10)/2

ACP Recommendations for Diagnostic Use of Erythrocyte Sedimentation Rate The ESR should not be used to screen asymptomatic persons for disease The ESR should be used selectively and interpreted with caution....Extreme elevation of the ESR seldom occurs in patients with no evidence of serious disease If there is no immediate explanation for an increased ESR, the physician should repeat the test in several months rather than search for occult disease The ESR is indicated for the diagnosis and monitoring of temporal arteritis and polymyalgia rheumatica In diagnosing and monitoring patients with rheumatoid arthritis, the ESR should be used prinicipally to resolve conflicting clinical evidence The ESR may be helpful in monitoring patients with treated Hodgkin’s disease

IRAN Epidemiology of Rheumatic Diseases

Musculoskeletal complaints during the past 7 days. (Tehran COPCORD) Men % Women % Total Pain 33.7 49.8 41.5 Swelling 8.2 19 13.5 Stiffness 19.5 32.9 26 Overall 34.1 50.4 The Journal of Rheumatology 2008; 35:7

Osteoarthritis . (Tehran COPCORD) Men % Women All Knee 11 19.9 15.3 Hand 1.4 4.5 2.9 Hip 0.35 0.28 0.32 Neck 1.1 2.4 1.7 The Journal of Rheumatology 2008; 35:7

Inflammatory disorders (Tehran COPCORD) Men % Women All Rheumatoid arthritis 0.09 0.58 0.33 Seronegative spondyloarthropathis 0.27 0.20 0.23 Ankylosing spondylitis 0.17 0.07 0.12 Systemic lupus erythematosus ------ 0.08 0.04 Behcet’s disease The Journal of Rheumatology 2008; 35:7

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