ARTHRITIS  Inflammation of the Joint (over 100 specific diseases) Rheumatoid Arthritis Gout Degenerative Joint Diseases An...
ARTHRITIS:   Inflammation of the Joint Pain  Swelling Redness Warmth
IL-8  IL-6  GM-CSF IL-1  TNF-  FGF Fibroblast/ type B synovial cells Metalloproteinases  Prostaglandins  Complement IL-6 ...
IL-8  IL-6  GM-CSF IL-10 IL-1  TNF-  FGF Fibroblast/ type B synovial cells Metalloproteinases  Prostaglandins  Complement...
Points to Remember Cells involved in Inflammation: - macrophage, fibroblast, T-cells  Pro inflammatory cytokines: - IL-1, ...
Degenerative Joint Disease / Osteoarthritis <ul><li>A group of disorder in which the balance between degeneration and synt...
Osteoarthritis   <ul><li>Most common form of arthritis </li></ul><ul><li>10% of the worlds population </li></ul><ul><li>50...
Risk Factors for Osteoarthritis <ul><li>Age </li></ul><ul><li>Female sex </li></ul><ul><li>Race </li></ul><ul><li>Genetic ...
Clinical Features <ul><li>Deep ache, localized pain </li></ul><ul><li>Aggravated by activity, relieved by rest </li></ul><...
 
 
Biochemical markers in Osteoarthritis Major tissue of origin Biochemical markers Synovium Hyaluran, type 2 collagen propep...
Management of Degenerative Joint Disease <ul><li>Non-pharmacologic </li></ul><ul><li>Pharmacologic  </li></ul><ul><li>Surg...
Changes in lifestyle for patients with Osteoarthritis <ul><li>General measures </li></ul><ul><ul><li>- Maintain optimal we...
Pharmacologic  Agents <ul><li>1.  Analgesics </li></ul><ul><li>Simple Analgesics (acetaminophen) </li></ul><ul><li>Other A...
Pharmacologic  Agents <ul><li>1. Analgesics </li></ul><ul><li>2. NSAIDs </li></ul><ul><li>Anti inflammatory effects </li><...
Phospholipids Phospholipase A Arachidonic Acid ( PG, thromboxanes, prostacyclins) Lipooxygenase Cyclooxygenase (-) NSAID’s...
Mechanism of Action of NSAIDs – New hypothesis Arachidonic Acid Prostaglandins  Prostaglandins  Protection of  gastric muc...
COX-1 COX-2 -  produces PG from AA   - produces PG from AA -  constitutively expressed  - inducible -  governs PG producti...
Risks factors for UGI adverse events <ul><li>Age >65 y.o. </li></ul><ul><li>Co-morbid clinical conditions </li></ul><ul><l...
Pharmacologic  Agents <ul><li>Few joint involvement </li></ul><ul><li>NSAIDs,  capsaicin </li></ul>1. Analgesics 2. NSAIDs...
Pharmacologic  Agents <ul><li>(+) effusion </li></ul><ul><li>Relief lasts for a few weeks </li></ul>1. Analgesics 2. NSAID...
Pharmacologic  Agents 1. Analgesics 2. NSAIDs 3.Topical Agents 4. Intraarticular Steroid Injection 5. DMOAD’s <ul><li>Modi...
Pharmacologic  Agents 1. Analgesics 2. NSAIDs 3.Topical Agents 4. Intraarticular Steroid Injection 5. DMOAD’s 6. Other Age...
Surgical Treatment for Osteoarthritis <ul><li>History of joint locking  </li></ul><ul><li>- arthroscopy for removal of loo...
Points to Remember - Osteoarthritis <ul><li>Most common form of arthritis </li></ul><ul><li>Identify risk factors </li></u...
Rheumatoid Arthritis <ul><li>Chronic, inflammatory </li></ul><ul><li>Articular, extra-articular </li></ul><ul><li>Oligo, p...
Rheumatoid Arthritis <ul><li>Etiology is unknown </li></ul><ul><li>  - Genetics  </li></ul><ul><li>- HLA DR4 </li></ul><ul...
 
Extra-articular manifestation of RA <ul><li>rheumatoid nodules </li></ul><ul><li>vasculitis </li></ul><ul><li>pulmonary </...
Extraarticular Manifestations of RA
Immune Abnormalities <ul><li>Rheumatoid Factor </li></ul><ul><li>- anti - immunoglobulins </li></ul><ul><li>- anti IgG/IgM...
Other causes of (+) RF test: <ul><li>- other CTD  - leishmaniasis </li></ul><ul><li>- viral infections  - TB </li></ul><ul...
Revised criteria for RA diagnosis <ul><li>symmetrical joint involvement* </li></ul><ul><li>joint stiffness of at least1 ho...
Treatment of RA Experimental agents Cyclophosphamide, MTX, Azathioprine Gold salts, antimalarials, Penicillamine Salicylat...
DMARDs <ul><li>Non-analgesic </li></ul><ul><li>Slow onset of action – 10-20 weeks </li></ul><ul><li>More toxic than NSAIDs...
Disease Modifying Drugs (DMARD’s) <ul><li>Gold salts </li></ul><ul><li>Antimalarials </li></ul><ul><li>Sulfasalazine </li>...
Biologic Agents <ul><li>Anti TNF </li></ul><ul><li>- Etanercept </li></ul><ul><li>- Infliximab </li></ul><ul><li>- Adalimu...
Adverse effects of Biologic Agents <ul><li>Opportunistic infection </li></ul><ul><li>CHF </li></ul><ul><li>Demyelinating d...
Factors Associated with Poorer Prognosis <ul><li>Insidious polyarticular onset </li></ul><ul><li>Male patients </li></ul><...
Points to Remember <ul><li>Polyarticular, symmetrical </li></ul><ul><li>Joints stiffness more than 1 hour </li></ul><ul><l...
Gouty Arthritis <ul><li>King of diseases; disease of Kings </li></ul><ul><li>inflammatory arthritis due to urates </li></u...
Classification of Hyperuricemia and Gout <ul><li>Primary </li></ul><ul><ul><li>- Enzymatic Defect </li></ul></ul><ul><ul><...
Renal  Handling of Urates
Gouty Arthritis <ul><li>Statements </li></ul><ul><ul><li>- Hyperuricemia is not gout </li></ul></ul><ul><ul><li>- Gout is ...
 
 
<ul><li>The most important differential diagnosis for acute gouty attack is </li></ul><ul><li>infection </li></ul>
<ul><li>“  The most feared complication of Gouty Arthritis is  kidney involvement  “ </li></ul>
Risk Factors for the Development of Gout Alcohol <ul><li>Association of alcohol consumption and the risk of incident gout ...
Risk Factors for the Development of Gout  Diet <ul><li>High meat consumption </li></ul><ul><li>High seafood consumption </...
Risk Factors for the Development of Gout Drugs <ul><li>low dose steroids </li></ul><ul><li>aspirin </li></ul><ul><li>anti ...
Treatment <ul><li>Acute Attack </li></ul><ul><ul><li>- NSAIDS, Colchicine </li></ul></ul><ul><ul><li>- Analgesics </li></u...
PROPHYLACTIC COLCHICINE DOSES <ul><li>CClr > 60 </li></ul><ul><li>CClr  40-60 </li></ul><ul><li>CClr  30-40 </li></ul><ul>...
Points to Remember <ul><li>Acute, episodic; mono/oligoArthritis </li></ul><ul><li>Hyperuricemia – biochemical hallmark </l...
Spondyloarthropathies <ul><li>Ankylosing spondylitis </li></ul><ul><li>Psoriatic arthritis </li></ul><ul><li>Reiters disea...
General Features <ul><li>Familial aggregation – HLA-B27 </li></ul><ul><li>( - ) rheumatoid factor test </li></ul><ul><li>A...
Ankylosing Spondylitis <ul><li>Marie Strumpell disease, Bechterews disease </li></ul><ul><li>2 nd  – 3 rd  decade of life ...
Clinical Features <ul><li>Dull pain, insidious onset </li></ul><ul><li>Low back morning stiffness </li></ul><ul><li>- reli...
Radiographic Findings <ul><li>Syndesmophyte formation  </li></ul><ul><li>  - ossification of annulus fibrosus  </li></ul><...
 
Diagnosis <ul><li>Modified NY criteria (1984) </li></ul><ul><li>- Hx of inflammatory back pain </li></ul><ul><li>- LOM  sa...
AS vs other causes of LBP <ul><li>Age of onset before 40 </li></ul><ul><li>Insidious onset </li></ul><ul><li>Duration of s...
Treatment <ul><li>No definitive treatment </li></ul><ul><li>- appropriate exercise program </li></ul><ul><li>- NSAID’s </l...
Reactive Arthritis / Reiters Disease <ul><li>Asymmetric oligoarthritis </li></ul><ul><li>Urethritis </li></ul><ul><li>Conj...
 
Clinical Forms <ul><li>Post enteric infection </li></ul><ul><li>- shigella (flexneri), salmonella,  </li></ul><ul><li>yers...
Psoriatic Arthritis <ul><li>5 - 42 % of patients with psoriasis </li></ul><ul><li>Unknown cause </li></ul><ul><li>Indirect...
Major Types of Psoriatic Arthritis <ul><li>Asmmetric oligoA  </li></ul><ul><li>- most common </li></ul><ul><li>Symmetric p...
 
Treatment <ul><li>Patient education </li></ul><ul><li>Physical / occupational therapy </li></ul><ul><li>NSAID’s </li></ul>...
Enteropathic Arthritis ( IBD ) <ul><li>Ulcerative colitis / Crohn’s disease </li></ul><ul><li>Intestinal bypass surgery </...
Features <ul><li>oligoA, asymmetric </li></ul><ul><li>Spondylitis, sacroiliitis </li></ul><ul><li>Clubbing of fingers </li...
Points to Remember <ul><li>HLA - B27 association </li></ul><ul><li>(-) RA factor exam </li></ul><ul><li>Clinical features ...
Systemic Lupus Erythematosus <ul><li>chronic, inflammatory </li></ul><ul><li>multiorgan, multisystemic </li></ul><ul><li>u...
Theories <ul><li>Immunologic </li></ul><ul><ul><li>autoantibodies, immune complexes </li></ul></ul><ul><ul><li>   activit...
Clinical Manifestations <ul><li>Musculoskeletal </li></ul><ul><ul><li>- arthritis </li></ul></ul><ul><ul><ul><li>polyartic...
Clinical Manifestations <ul><li>Malar rash </li></ul><ul><ul><li>photosensitive, flat or raised </li></ul></ul><ul><ul><li...
Clinical Manifestations <ul><li>Discoid rash </li></ul><ul><ul><li>20 % </li></ul></ul><ul><ul><li>circular, raised border...
Clinical Manifestations <ul><li>Oral ulcers </li></ul><ul><ul><li>painless, shallow </li></ul></ul><ul><ul><li>buccal muco...
<ul><li>Lupus band test </li></ul><ul><ul><li>- deposition of IgG at dermal-epidermal junction </li></ul></ul>
<ul><li>Renal  </li></ul><ul><ul><li>- pyuria, hematuria, proteinuria, casts (UA) </li></ul></ul><ul><ul><li>- subendothel...
Clinical Manifestations <ul><li>Nervous system </li></ul><ul><ul><li>- overdiagnosed </li></ul></ul><ul><ul><li>- CNS, PNS...
Clinical Manifestations <ul><li>Hematologic </li></ul><ul><ul><li>- anemia    NN, hemolytic </li></ul></ul><ul><ul><li>- ...
Clinical Manifestations <ul><li>Cardiopulmonary </li></ul><ul><ul><li>carditis </li></ul></ul><ul><ul><ul><li>pericarditis...
Laboratories <ul><li>ANA </li></ul><ul><ul><li>- best screening test (WIL-2 or Hep-2 cells) </li></ul></ul><ul><ul><li>- (...
Laboratories <ul><li>Autoantibodies in SLE </li></ul><ul><ul><li>- anti-dsDNA </li></ul></ul><ul><ul><ul><li>nephritis, ac...
<ul><ul><li>- anti-La (SS-B) </li></ul></ul><ul><ul><ul><li>always associated with Ro </li></ul></ul></ul><ul><ul><ul><li>...
<ul><ul><li>- antierythrocyte </li></ul></ul><ul><ul><ul><li>hemolysis </li></ul></ul></ul><ul><ul><li>- antineuronal </li...
Revised Criteria for SLE <ul><li>Malar rash </li></ul><ul><li>Discoid rash </li></ul><ul><li>Photosensitivity </li></ul><u...
Revised Criteria for SLE <ul><li>Renal </li></ul><ul><ul><li>+++ protein (U/A), >500mg/24hrs </li></ul></ul><ul><li>Hemato...
Revised Criteria for SLE <ul><li>4/11 criteria </li></ul><ul><li>97 % sensitivity; 98 % specificity </li></ul><ul><li>SOAP...
Treatment <ul><li>no cure, rare complete sustained remission </li></ul><ul><li>non-pharmacologic </li></ul><ul><ul><li>- d...
Pharmacologic Therapy <ul><li>NSAIDs, analgesics   </li></ul><ul><ul><li>MS Sx </li></ul></ul><ul><li>antimalarials   </li...
<ul><li>Others </li></ul><ul><ul><li>plasmapheresis   </li></ul></ul><ul><ul><li>cyclosporins </li></ul></ul><ul><ul><li>i...
Prognosis <ul><li>Factors assoc’d w/ poor prognosis </li></ul><ul><ul><li>-    creatinine levels </li></ul></ul><ul><ul><...
Cause of Death <ul><li>1 st  decade </li></ul><ul><ul><li>- infection, active disease </li></ul></ul><ul><li>2 nd  decade ...
Osteoporosis <ul><li>Silent disease </li></ul><ul><li>Systemic skeletal disease 1 </li></ul><ul><ul><li>Low bone mineral d...
 
 
 
Wasnich RD: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 4th edition, 1999, p 257 Incidence ...
<ul><li>Non-Modifiable </li></ul><ul><li>Age </li></ul><ul><li>Female sex </li></ul><ul><li>Maternal family history of hip...
Unitary model for postmenopausal  bone loss: role of oestrogen deficiency Indirect effects Directly increases  osteoclast ...
 
Glucocorticoid dose Dependent Effect on Fracture Risk  0.99 1.77 5.18 1.55 2.59 2.27 0 1 2 3 4 5 6 Hip Vertebral Type of F...
Most rapid bone loss occurs in the first 6-12 months of Steroid therapy
WHO definition of osteoporosis <ul><li>The T-score </li></ul><ul><ul><li>the number of SDs from the mean (average) value o...
How should patients be evaluated to determine if they have osteoporosis? <ul><li>AACE recommend that evaluation include </...
Diagnosis and assessment <ul><li>X-rays </li></ul><ul><li>BMD </li></ul><ul><li>Ultrasound </li></ul><ul><li>Bone markers ...
<ul><li>Indications for Bone Density Measurements </li></ul><ul><li>estrogen deficient women  </li></ul><ul><ul><li>- peri...
Biochemical markers of bone turnover in osteoporosis *CrossLaps TM
Candidates for therapy:  the AACE guidelines <ul><li>The AACE guidelines indicate that the following women may benefit fro...
Therapeutic options for osteoporosis <ul><li>Stimulators of bone formation </li></ul><ul><li>- Fluoride </li></ul><ul><li>...
Osteoporosis prevention T-score >–2.5 Osteopenia  treatment with or without  previous fracture Osteoporosis treatment  wit...
Optimal Daily Calcium Requirements 1300 mg 1000 mg 1200 mg Recommended Calcium Intake (Daily) Age 1997 Recommended Dietary...
Recommendations for Vitamin D Intake <ul><li>Europe </li></ul><ul><li>The Scientific Committee for Food of the Commission ...
Widespread Prevalence of Vitamin D Inadequacy*  Regardless of Geographic Location *Vitamin D inadequacy was defined as ser...
Probable Reasons for High Prevalence of Vitamin D Inadequacy in Postmenopausal Women  <ul><li>Lack of sunlight exposure </...
Vitamin D Inadequacy* Has Important Consequences Appropriate neuromuscular function *Vitamin D inadequacy is defined as se...
Bisphosphonate mechanism of action Adapted from: Bone H, et al. Clin Ther 2000;22:15–25  RESTING RESORPTION Osteoclast FOR...
PTH - Mechanism of Action PTH binds to cell surface  G protein-coupled receptor Stimulates differentiation of bone lining ...
Osteoporosis has been thought of as a silent epidemic….this is not true anymore. At present, there is much noise in the fi...
One of the Many Faces of Osteoporosis “ You could have floored me when they told me.  It’s very frightening, very frighten...
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Rheumatology

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Rheumatology

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  • Rheumatology

    1. 1. ARTHRITIS Inflammation of the Joint (over 100 specific diseases) Rheumatoid Arthritis Gout Degenerative Joint Diseases Ankylosing spondylitis JRA Psoriatic Arthritis Bacterial Arthritis Systemic Lupus Erythematosus Scleroderma
    2. 2. ARTHRITIS: Inflammation of the Joint Pain Swelling Redness Warmth
    3. 3. IL-8 IL-6 GM-CSF IL-1 TNF-  FGF Fibroblast/ type B synovial cells Metalloproteinases Prostaglandins Complement IL-6 IL-1 IL-6 IL-8 GM-CSF M-CSF Macrophage/ type A synovial cells IL-1 TNF-  Adhesion molecule expression on blood vessels HLA-DR Complement metalloptoteinases CYTOKINE NETWORKS IN SYNOVITIS + FEEDBACK
    4. 4. IL-8 IL-6 GM-CSF IL-10 IL-1 TNF-  FGF Fibroblast/ type B synovial cells Metalloproteinases Prostaglandins Complement IL-6 TGF-  IL-4 IL-1 IL-6 IL-8 GM-CSF M-CSF Macrophage/ type A synovial cells IL-1 TNF-  Adhesion molecule expression on blood vessels HLA-DR Complement metalloptoteinases CYTOKINE NETWORKS IN SYNOVITIS + FEEDBACK - FEEDBACK
    5. 5. Points to Remember Cells involved in Inflammation: - macrophage, fibroblast, T-cells Pro inflammatory cytokines: - IL-1, TNF alpha, IL-6 - IL-8, FGF, GM-CSF Anti inflammatory cytokine: - IL-10, TGF-B, IL-4
    6. 6. Degenerative Joint Disease / Osteoarthritis <ul><li>A group of disorder in which the balance between degeneration and synthesis within the cartilage and subchondral bone is disturbed resulting to cartilage and subchondral bone destruction </li></ul>Dippe, Paul
    7. 7. Osteoarthritis <ul><li>Most common form of arthritis </li></ul><ul><li>10% of the worlds population </li></ul><ul><li>50% of people over the age of 60 years </li></ul><ul><li>At age 75, more than 80% of people have symptoms of the disease </li></ul><ul><li>More common in women than in men </li></ul>
    8. 8. Risk Factors for Osteoarthritis <ul><li>Age </li></ul><ul><li>Female sex </li></ul><ul><li>Race </li></ul><ul><li>Genetic factors </li></ul><ul><li>Repetitive stress </li></ul><ul><li>Obesity </li></ul><ul><li>Congenital / Developmental defects </li></ul><ul><li>Prior inflammatory joint dse. </li></ul><ul><li>Metabolic / Endocrine disorders </li></ul>
    9. 9. Clinical Features <ul><li>Deep ache, localized pain </li></ul><ul><li>Aggravated by activity, relieved by rest </li></ul><ul><li>Transient joint stiffness </li></ul><ul><li>Bony swelling, crepitus </li></ul><ul><li>Progressive cartilage loss </li></ul>
    10. 12. Biochemical markers in Osteoarthritis Major tissue of origin Biochemical markers Synovium Hyaluran, type 2 collagen propeptide, proteases Subchondral bone Type 1 collagen crosslinks, osteocalcin, alk. phosphatase, Cart. oligomeric protein (COMP)
    11. 13. Management of Degenerative Joint Disease <ul><li>Non-pharmacologic </li></ul><ul><li>Pharmacologic </li></ul><ul><li>Surgery </li></ul>
    12. 14. Changes in lifestyle for patients with Osteoarthritis <ul><li>General measures </li></ul><ul><ul><li>- Maintain optimal weight </li></ul></ul><ul><ul><li>- Encourage activity and regular general exercise </li></ul></ul><ul><ul><li>- Maintain positive approach </li></ul></ul><ul><li>Specific measures </li></ul><ul><ul><li>- Strengthening of local muscles </li></ul></ul><ul><ul><li>- Use of appropriate footwear and walking aids </li></ul></ul><ul><ul><li>- Pay attention to specific problems caused by disability (such as shopping, housework, and job) </li></ul></ul>
    13. 15. Pharmacologic Agents <ul><li>1. Analgesics </li></ul><ul><li>Simple Analgesics (acetaminophen) </li></ul><ul><li>Other Analgesics (opioids, tramadol) </li></ul><ul><li>or combination </li></ul>Acetaminophen is the first line agent for OA ACR recommendation
    14. 16. Pharmacologic Agents <ul><li>1. Analgesics </li></ul><ul><li>2. NSAIDs </li></ul><ul><li>Anti inflammatory effects </li></ul><ul><li>Safety concern </li></ul><ul><li>- renal, GI, platelet function </li></ul><ul><li>- CV risk </li></ul>
    15. 17. Phospholipids Phospholipase A Arachidonic Acid ( PG, thromboxanes, prostacyclins) Lipooxygenase Cyclooxygenase (-) NSAID’s (leukotrienes, bradykinin)
    16. 18. Mechanism of Action of NSAIDs – New hypothesis Arachidonic Acid Prostaglandins Prostaglandins Protection of gastric mucosa Homeostasis Mediates pain Inflammation and fever Conventional NSAIDs COX-1 COX-2 Coxibs
    17. 19. COX-1 COX-2 - produces PG from AA - produces PG from AA - constitutively expressed - inducible - governs PG production - governs PG production that mediate hemostatic that mediate inflammation function - essentially important in: gastric, bowel mucosa kidney, platelets
    18. 20. Risks factors for UGI adverse events <ul><li>Age >65 y.o. </li></ul><ul><li>Co-morbid clinical conditions </li></ul><ul><li>Oral glucocorticoids </li></ul><ul><li>History of PUD; UGIB </li></ul><ul><li>Anticoagulants </li></ul>
    19. 21. Pharmacologic Agents <ul><li>Few joint involvement </li></ul><ul><li>NSAIDs, capsaicin </li></ul>1. Analgesics 2. NSAIDs 3.Topical Agents
    20. 22. Pharmacologic Agents <ul><li>(+) effusion </li></ul><ul><li>Relief lasts for a few weeks </li></ul>1. Analgesics 2. NSAIDs 3.Topical Agents 4. Intraarticular Steroid Injection
    21. 23. Pharmacologic Agents 1. Analgesics 2. NSAIDs 3.Topical Agents 4. Intraarticular Steroid Injection 5. DMOAD’s <ul><li>Modify morphologic changes in </li></ul><ul><li>the joints </li></ul><ul><li>- glucosamine / chondroitin </li></ul><ul><li>- viscosupplementation </li></ul><ul><li>- doxycycline </li></ul>
    22. 24. Pharmacologic Agents 1. Analgesics 2. NSAIDs 3.Topical Agents 4. Intraarticular Steroid Injection 5. DMOAD’s 6. Other Agents <ul><li>Antidepressants </li></ul><ul><li>Mild tranquilizers </li></ul>
    23. 25. Surgical Treatment for Osteoarthritis <ul><li>History of joint locking </li></ul><ul><li>- arthroscopy for removal of loose body </li></ul><ul><li>Persistent synovitis </li></ul><ul><li>- arthroscopic washout or radioisotope synovectomy </li></ul><ul><li>Joint replacement is highly effective for hip & knee </li></ul><ul><li>- consider early referral for opinion </li></ul>
    24. 26. Points to Remember - Osteoarthritis <ul><li>Most common form of arthritis </li></ul><ul><li>Identify risk factors </li></ul><ul><li>- age is the most powerful risk factor </li></ul><ul><li>Deep ache localized pain related to activity </li></ul><ul><li>Hand lesions </li></ul><ul><li>- heberdens, bouchards nodes </li></ul><ul><li>Progressive cartilage loss </li></ul><ul><li>Paracetamol – 1 st line agent </li></ul>
    25. 27. Rheumatoid Arthritis <ul><li>Chronic, inflammatory </li></ul><ul><li>Articular, extra-articular </li></ul><ul><li>Oligo, polyarticular </li></ul><ul><li>Young, female/male ratio (4:1) </li></ul><ul><li>Remission and relapse </li></ul><ul><li>Unknown etiology </li></ul><ul><li>- genetic predisposition (HLA-DR4) </li></ul>
    26. 28. Rheumatoid Arthritis <ul><li>Etiology is unknown </li></ul><ul><li> - Genetics </li></ul><ul><li>- HLA DR4 </li></ul><ul><li>- Infection </li></ul><ul><li>- mycoplasma, EBV, CMG, parvo, rubella virus </li></ul><ul><li>- “Superantigens” </li></ul><ul><li> - staph, strep, M. arthritidis </li></ul><ul><li>- Environmental </li></ul><ul><li>- cigarette smoking </li></ul>
    27. 30. Extra-articular manifestation of RA <ul><li>rheumatoid nodules </li></ul><ul><li>vasculitis </li></ul><ul><li>pulmonary </li></ul><ul><li>- pleural effusion, fibrosing alveolitis, nodules </li></ul><ul><li>cardiac </li></ul><ul><li>- pericarditis, mitral valve disease, conduction defects </li></ul><ul><li>skin </li></ul><ul><li>- palmar erythema, cutaneous vasculitis </li></ul><ul><li>Feltys syndrome </li></ul><ul><li>- sero (+) RA, splenomegaly, neutropenia </li></ul>
    28. 31. Extraarticular Manifestations of RA
    29. 32. Immune Abnormalities <ul><li>Rheumatoid Factor </li></ul><ul><li>- anti - immunoglobulins </li></ul><ul><li>- anti IgG/IgM - immunologic hallmark </li></ul><ul><li>- Rose-Waaler assay </li></ul><ul><li>- (+) 80% of RA pts. </li></ul><ul><li>- high titer associated </li></ul><ul><li>- extra-articular sx </li></ul><ul><li> - progressive disease </li></ul><ul><li> - poor prognosis </li></ul><ul><li>ANA </li></ul>
    30. 33. Other causes of (+) RF test: <ul><li>- other CTD - leishmaniasis </li></ul><ul><li>- viral infections - TB </li></ul><ul><li>- leprosy - liver diseases </li></ul><ul><li>- SBE - sarcoidosis </li></ul>
    31. 34. Revised criteria for RA diagnosis <ul><li>symmetrical joint involvement* </li></ul><ul><li>joint stiffness of at least1 hour duration* </li></ul><ul><li>Involvement of at least 3/14 joints of the body* </li></ul><ul><li>Hand joint involvement* </li></ul><ul><li>(+) subcutaneous nodules </li></ul><ul><li>(+) RA test </li></ul><ul><li>radiographic findings </li></ul><ul><ul><li>Juxtaarticular osteoporosis, cystic lesions, evosions </li></ul></ul><ul><ul><li>* At least 6 weeks duration </li></ul></ul><ul><ul><li>4/7 criteria </li></ul></ul>
    32. 35. Treatment of RA Experimental agents Cyclophosphamide, MTX, Azathioprine Gold salts, antimalarials, Penicillamine Salicylates, NSAIDS, analgesics Education, rest, exercise, social service Intraarticular Steroid injection Mechanical devices
    33. 36. DMARDs <ul><li>Non-analgesic </li></ul><ul><li>Slow onset of action – 10-20 weeks </li></ul><ul><li>More toxic than NSAIDs </li></ul><ul><li>Mechanism of action: </li></ul><ul><ul><li>Decrease leukotriene B4 synthesis in neutrophils </li></ul></ul><ul><ul><li>Decreases IL-1 concentration in SF </li></ul></ul>
    34. 37. Disease Modifying Drugs (DMARD’s) <ul><li>Gold salts </li></ul><ul><li>Antimalarials </li></ul><ul><li>Sulfasalazine </li></ul><ul><li>D- Penicillamine </li></ul><ul><li>Methotrexate </li></ul><ul><li>Cyclosporin-A </li></ul>
    35. 38. Biologic Agents <ul><li>Anti TNF </li></ul><ul><li>- Etanercept </li></ul><ul><li>- Infliximab </li></ul><ul><li>- Adalimumab </li></ul><ul><li>T cell inhibitor </li></ul><ul><li>- Abatacept </li></ul><ul><li>B cell inhibitor </li></ul><ul><li>- Rituximab </li></ul><ul><li>Interleukin 1 receptor antagonist </li></ul><ul><li>- Anakinra </li></ul>
    36. 39. Adverse effects of Biologic Agents <ul><li>Opportunistic infection </li></ul><ul><li>CHF </li></ul><ul><li>Demyelinating disease </li></ul><ul><li>Systemic lupus erythematosus </li></ul><ul><li>Injection site reaction </li></ul><ul><li>Neutropenia </li></ul>
    37. 40. Factors Associated with Poorer Prognosis <ul><li>Insidious polyarticular onset </li></ul><ul><li>Male patients </li></ul><ul><li>Extraarticular manifestations </li></ul><ul><li>Functional disability at one year after start of disease </li></ul><ul><li>Substantially raised concentration of RF </li></ul><ul><li>Presence of HLA-DR4 </li></ul><ul><li>X-ray evidence of erosion within three years of start of disease </li></ul>
    38. 41. Points to Remember <ul><li>Polyarticular, symmetrical </li></ul><ul><li>Joints stiffness more than 1 hour </li></ul><ul><li>Cartilage destruction, bone erosions </li></ul><ul><li>Asso. with deformities, extra articular features </li></ul><ul><li>ACR revised criteria for diagnosis </li></ul><ul><li>Disease modifying, biologic agents </li></ul>
    39. 42. Gouty Arthritis <ul><li>King of diseases; disease of Kings </li></ul><ul><li>inflammatory arthritis due to urates </li></ul><ul><li>acute, episodic </li></ul><ul><li>monoarthritis  polyarticular </li></ul><ul><li>Hyperuricemia </li></ul><ul><li>- biochemical hallmark </li></ul>
    40. 43. Classification of Hyperuricemia and Gout <ul><li>Primary </li></ul><ul><ul><li>- Enzymatic Defect </li></ul></ul><ul><ul><ul><li>HGPRT deficiency </li></ul></ul></ul><ul><ul><ul><li>PRPP overactivity </li></ul></ul></ul><ul><li>Secondary </li></ul><ul><ul><li>- Endogenous </li></ul></ul><ul><ul><ul><li>Family history </li></ul></ul></ul><ul><ul><ul><li>Body build </li></ul></ul></ul><ul><ul><ul><li>Kidney function, HPN </li></ul></ul></ul><ul><ul><ul><li>Inc. cell breakdown </li></ul></ul></ul><ul><ul><li>- Exogenous </li></ul></ul><ul><ul><ul><li>diet, drugs </li></ul></ul></ul><ul><ul><ul><li>alcohol, stress </li></ul></ul></ul><ul><ul><ul><li>starvation </li></ul></ul></ul>
    41. 44. Renal Handling of Urates
    42. 45. Gouty Arthritis <ul><li>Statements </li></ul><ul><ul><li>- Hyperuricemia is not gout </li></ul></ul><ul><ul><li>- Gout is a result from hyperuricemia </li></ul></ul><ul><ul><li>- Extremely painful episodes of arthritis </li></ul></ul><ul><ul><li>- Tendency to abuse NSAIDS, steroids </li></ul></ul><ul><ul><li>- Treatable / Preventable </li></ul></ul>
    43. 48. <ul><li>The most important differential diagnosis for acute gouty attack is </li></ul><ul><li>infection </li></ul>
    44. 49. <ul><li>“ The most feared complication of Gouty Arthritis is kidney involvement “ </li></ul>
    45. 50. Risk Factors for the Development of Gout Alcohol <ul><li>Association of alcohol consumption and the risk of incident gout </li></ul><ul><li>- 12 year cohort study </li></ul><ul><li>- Biennial questionnaires </li></ul><ul><li>- 47,150 male health professionals with no gout at baseline </li></ul><ul><li>Alcohol intake strongly associated with an increased risk of gout </li></ul><ul><li>- Highest risk with beer consumption </li></ul><ul><li>- Moderate risk with liquor consumption </li></ul><ul><li>- Lower risk with wine consumption </li></ul><ul><li>Choi et al. Lancet, 2004;363:1277-1281 </li></ul>
    46. 51. Risk Factors for the Development of Gout Diet <ul><li>High meat consumption </li></ul><ul><li>High seafood consumption </li></ul><ul><li>High dairy consumption </li></ul><ul><li>High consumption of </li></ul><ul><li>purine-rich vegetable </li></ul>risk gout risk gout risk of gout no association Choi et al. NEJM, 2004;350(11):1093-1103
    47. 52. Risk Factors for the Development of Gout Drugs <ul><li>low dose steroids </li></ul><ul><li>aspirin </li></ul><ul><li>anti TB drugs - pyrazinamide </li></ul><ul><li>diuretics </li></ul>
    48. 53. Treatment <ul><li>Acute Attack </li></ul><ul><ul><li>- NSAIDS, Colchicine </li></ul></ul><ul><ul><li>- Analgesics </li></ul></ul><ul><ul><li>- IV/IM corticosteroids </li></ul></ul><ul><ul><li>- Non pharmacologic measures </li></ul></ul><ul><li>Hyperuricemia </li></ul><ul><ul><li>- Allopurinol </li></ul></ul><ul><ul><li>- Uricosuric drugs </li></ul></ul>
    49. 54. PROPHYLACTIC COLCHICINE DOSES <ul><li>CClr > 60 </li></ul><ul><li>CClr 40-60 </li></ul><ul><li>CClr 30-40 </li></ul><ul><li>CClr < 30 </li></ul>0.6 mg BID 0.6 mg QD 0.6 mg Q2 Days 0.6 mg Q3 Days - COLCHICINE NOT EXTRACTED BY DIALYSIS - DO NOT USE IN DIALYSIS PATIENTS - REDUCE COLCHICINE BY 50% FOR AGE >= 70 - CAUTION WITH DRUG INTERACTIONS: e.g., CSA, Statins, Macrolides, Gemfibrozil
    50. 55. Points to Remember <ul><li>Acute, episodic; mono/oligoArthritis </li></ul><ul><li>Hyperuricemia – biochemical hallmark </li></ul><ul><li>(+) uric acid crystal on SF, tophi – definitive Dx </li></ul><ul><li>Young male, post menopausal women </li></ul><ul><li>Provocative factors: </li></ul><ul><li>- inc. purine foods </li></ul><ul><li>- trauma, surgery </li></ul><ul><li>- alcohol ingestion </li></ul><ul><li>- ACTH, glucocorticoid withdrawal </li></ul><ul><li>- hypouricemic therapy </li></ul><ul><li>- medical illness – stroke, MI </li></ul><ul><li>- drugs – diuretics, PZA, low dose aspirin </li></ul>
    51. 56. Spondyloarthropathies <ul><li>Ankylosing spondylitis </li></ul><ul><li>Psoriatic arthritis </li></ul><ul><li>Reiters disease / Reactive arthritis </li></ul><ul><li>Enteropathic arthritis (IBD) </li></ul>
    52. 57. General Features <ul><li>Familial aggregation – HLA-B27 </li></ul><ul><li>( - ) rheumatoid factor test </li></ul><ul><li>Asymmetric peripheral oligoarthritis </li></ul><ul><li>Axial skeleton involvement </li></ul><ul><li>Sacroiliitis – low back pain </li></ul><ul><li>Enthesopathic </li></ul>
    53. 58. Ankylosing Spondylitis <ul><li>Marie Strumpell disease, Bechterews disease </li></ul><ul><li>2 nd – 3 rd decade of life </li></ul><ul><li>Male preponderance – 3:1 ratio </li></ul><ul><li>Syndesmophyte formation ( bamboo spine ) </li></ul><ul><li>Enthesitis, sacroiliitis </li></ul>
    54. 59. Clinical Features <ul><li>Dull pain, insidious onset </li></ul><ul><li>Low back morning stiffness </li></ul><ul><li>- relieved by activity, aggravated by rest </li></ul><ul><li>Peripheral asymmetric oligoarthritis </li></ul><ul><li>Acute anterior uveitis </li></ul><ul><li> - most common extra articular Mx </li></ul><ul><li>Aortic insufficiency </li></ul><ul><li>( + ) Schobers test </li></ul>
    55. 60. Radiographic Findings <ul><li>Syndesmophyte formation </li></ul><ul><li> - ossification of annulus fibrosus </li></ul><ul><li>Vertebral body disk margin erosion </li></ul><ul><li>“ Squaring” of vertebral bodies </li></ul><ul><li>Sclerosis of SI joint, sacroiliitis </li></ul>
    56. 62. Diagnosis <ul><li>Modified NY criteria (1984) </li></ul><ul><li>- Hx of inflammatory back pain </li></ul><ul><li>- LOM sagittal, frontal planes of LS </li></ul><ul><li>- limited chest expansion </li></ul><ul><li>- definite radiographic sacroiliitis </li></ul><ul><li>Definite AS: </li></ul><ul><li>- evidence of sacroiliitis + any of the other 3 criteria </li></ul>
    57. 63. AS vs other causes of LBP <ul><li>Age of onset before 40 </li></ul><ul><li>Insidious onset </li></ul><ul><li>Duration of sx > than 3 months before medical attention is sought </li></ul><ul><li>Prolonged morning stiffness </li></ul><ul><li>Improvement with exercise </li></ul>
    58. 64. Treatment <ul><li>No definitive treatment </li></ul><ul><li>- appropriate exercise program </li></ul><ul><li>- NSAID’s </li></ul><ul><li>- sulfasalazine </li></ul><ul><li>- methotrexate </li></ul><ul><li>- intralesional cortisone injection </li></ul><ul><li>- biologic agents </li></ul>
    59. 65. Reactive Arthritis / Reiters Disease <ul><li>Asymmetric oligoarthritis </li></ul><ul><li>Urethritis </li></ul><ul><li>Conjunctivitis </li></ul><ul><li>Mucocutaneous lesion </li></ul><ul><li>- balanitis </li></ul><ul><li>- keratoderma blenorrhagica </li></ul>
    60. 67. Clinical Forms <ul><li>Post enteric infection </li></ul><ul><li>- shigella (flexneri), salmonella, </li></ul><ul><li>yersinia, campylobacter </li></ul><ul><li>Post genital infection </li></ul><ul><li>- chlamydia trachomatis </li></ul>
    61. 68. Psoriatic Arthritis <ul><li>5 - 42 % of patients with psoriasis </li></ul><ul><li>Unknown cause </li></ul><ul><li>Indirect evidence: </li></ul><ul><li>- infection </li></ul><ul><li>- trauma </li></ul><ul><li>- inc. humoral / cellular immunity </li></ul><ul><li>- cytokine driven </li></ul><ul><li>- abn. fibroblast, dendritic cell, PMN function </li></ul>
    62. 69. Major Types of Psoriatic Arthritis <ul><li>Asmmetric oligoA </li></ul><ul><li>- most common </li></ul><ul><li>Symmetric polyA </li></ul><ul><li>- RA like features </li></ul><ul><li>DIP involvement </li></ul><ul><li>- nail lesion </li></ul><ul><li>Arthritis mutilans </li></ul><ul><ul><li> - deformities, young patients </li></ul></ul><ul><li>Psoriatic spondylitis </li></ul>
    63. 71. Treatment <ul><li>Patient education </li></ul><ul><li>Physical / occupational therapy </li></ul><ul><li>NSAID’s </li></ul><ul><li>Methotrexate + folic acid </li></ul><ul><li>Sulfasalazine </li></ul><ul><li>Gold salts </li></ul><ul><li>Antimalarials </li></ul>
    64. 72. Enteropathic Arthritis ( IBD ) <ul><li>Ulcerative colitis / Crohn’s disease </li></ul><ul><li>Intestinal bypass surgery </li></ul><ul><li>Whipples disease (intestinal lipodystrophy) </li></ul>
    65. 73. Features <ul><li>oligoA, asymmetric </li></ul><ul><li>Spondylitis, sacroiliitis </li></ul><ul><li>Clubbing of fingers </li></ul><ul><li>Development of amyloid – crohn’s </li></ul><ul><li>Osteoporosis – inactivity malabsorption, steroids </li></ul>
    66. 74. Points to Remember <ul><li>HLA - B27 association </li></ul><ul><li>(-) RA factor exam </li></ul><ul><li>Clinical features </li></ul><ul><li>- Musculoskeletal </li></ul><ul><li>- peripheral oligoA </li></ul><ul><li>- enthesitis </li></ul><ul><li>- sacroiliitis, spondylitis </li></ul><ul><li>- Systemic </li></ul><ul><li>- psoriasis </li></ul><ul><li>- IBD </li></ul><ul><li>- conjunctivitis, iritis </li></ul><ul><li>- genito urinary inflammation </li></ul><ul><li>- carditis </li></ul>
    67. 75. Systemic Lupus Erythematosus <ul><li>chronic, inflammatory </li></ul><ul><li>multiorgan, multisystemic </li></ul><ul><li>unknown etiology </li></ul><ul><ul><li>autoantibodies </li></ul></ul><ul><ul><li>immune complexes </li></ul></ul>
    68. 76. Theories <ul><li>Immunologic </li></ul><ul><ul><li>autoantibodies, immune complexes </li></ul></ul><ul><ul><li> activity of polyclonal T;B cells </li></ul></ul><ul><li>Genetics </li></ul><ul><ul><li> concordance in monozygotic than dizygotic twins (24 – 58%: 0 – 6%) </li></ul></ul><ul><ul><li>complement deficiencies – C1q, C2, C3, C4 </li></ul></ul><ul><li>Genetics </li></ul><ul><ul><li>HLA-DR2 – DR3 tissue types </li></ul></ul><ul><ul><li>Defective C4AQO allele </li></ul></ul><ul><ul><ul><li>marker for ethnic groups </li></ul></ul></ul><ul><li>Environment </li></ul><ul><ul><li>UV-B, UV-A rays </li></ul></ul><ul><ul><li>alfalfa, chemicals (hydrazine) </li></ul></ul><ul><ul><li>virus, type-C oncorna </li></ul></ul><ul><li>Hormonal </li></ul><ul><ul><li>woman, reproductive life </li></ul></ul><ul><ul><li>NZ mice </li></ul></ul><ul><ul><ul><li>estrogen  activates disease </li></ul></ul></ul><ul><ul><ul><li>androgens  protective </li></ul></ul></ul>
    69. 77. Clinical Manifestations <ul><li>Musculoskeletal </li></ul><ul><ul><li>- arthritis </li></ul></ul><ul><ul><ul><li>polyarticular, rheumatoid like </li></ul></ul></ul><ul><ul><ul><li>joint deformities </li></ul></ul></ul><ul><ul><ul><li>non-erosive </li></ul></ul></ul><ul><ul><li>- myopathy </li></ul></ul><ul><ul><ul><li>active disease </li></ul></ul></ul><ul><ul><ul><li>drug-induced (hypoK, steroids, antimalarials) </li></ul></ul></ul>
    70. 78. Clinical Manifestations <ul><li>Malar rash </li></ul><ul><ul><li>photosensitive, flat or raised </li></ul></ul><ul><ul><li>non-scarring </li></ul></ul>Cutaneous
    71. 79. Clinical Manifestations <ul><li>Discoid rash </li></ul><ul><ul><li>20 % </li></ul></ul><ul><ul><li>circular, raised borders </li></ul></ul><ul><ul><li>central, atrophic, hypopigmented area </li></ul></ul><ul><ul><li>scarring </li></ul></ul><ul><ul><li>photosensitive </li></ul></ul>Cutaneous
    72. 80. Clinical Manifestations <ul><li>Oral ulcers </li></ul><ul><ul><li>painless, shallow </li></ul></ul><ul><ul><li>buccal mucosa </li></ul></ul><ul><ul><li>disease activity </li></ul></ul>
    73. 81. <ul><li>Lupus band test </li></ul><ul><ul><li>- deposition of IgG at dermal-epidermal junction </li></ul></ul>
    74. 82. <ul><li>Renal </li></ul><ul><ul><li>- pyuria, hematuria, proteinuria, casts (UA) </li></ul></ul><ul><ul><li>- subendothelial, subepithelial mesangial deposits (E/M) </li></ul></ul><ul><ul><li>- renal biopsy  best guide to nephritis severity </li></ul></ul><ul><ul><li>- focal, mesangial, membranous, diffuse proliferative </li></ul></ul>
    75. 83. Clinical Manifestations <ul><li>Nervous system </li></ul><ul><ul><li>- overdiagnosed </li></ul></ul><ul><ul><li>- CNS, PNS </li></ul></ul><ul><ul><li>- cognitive dysfunction  most frequent </li></ul></ul><ul><ul><li>- seizures, psychosis </li></ul></ul><ul><ul><li>- neuropathy, autonomic dysfunction </li></ul></ul><ul><ul><li>- MRI (contrast)  acute, chronic </li></ul></ul><ul><ul><li>- lumbar tap  active disease, infection </li></ul></ul>
    76. 84. Clinical Manifestations <ul><li>Hematologic </li></ul><ul><ul><li>- anemia  NN, hemolytic </li></ul></ul><ul><ul><li>- leukopenia, lymphopenia </li></ul></ul><ul><ul><li>- thrombocytopenia </li></ul></ul><ul><ul><li>- arterial, venous thrombosis </li></ul></ul><ul><ul><li>- lupus anticoagulant, anticardiolipin </li></ul></ul><ul><ul><ul><li>prolong PTT (APS) </li></ul></ul></ul>
    77. 85. Clinical Manifestations <ul><li>Cardiopulmonary </li></ul><ul><ul><li>carditis </li></ul></ul><ul><ul><ul><li>pericarditis  most common </li></ul></ul></ul><ul><ul><ul><li>myocarditis  arrhythmias </li></ul></ul></ul><ul><ul><ul><li>endocarditis  valvular insufficiency  transesophageal echocardiogram </li></ul></ul></ul><ul><ul><ul><ul><li>Libmann-Sacks </li></ul></ul></ul></ul>
    78. 86. Laboratories <ul><li>ANA </li></ul><ul><ul><li>- best screening test (WIL-2 or Hep-2 cells) </li></ul></ul><ul><ul><li>- (+) test nonspecific; supports diagnosis </li></ul></ul><ul><ul><li>- other conditions: </li></ul></ul><ul><ul><ul><li>Elderly </li></ul></ul></ul><ul><ul><ul><li>chronic inflammatory conditions </li></ul></ul></ul><ul><ul><ul><li>other CTDs </li></ul></ul></ul><ul><ul><ul><li>viral infections </li></ul></ul></ul>
    79. 87. Laboratories <ul><li>Autoantibodies in SLE </li></ul><ul><ul><li>- anti-dsDNA </li></ul></ul><ul><ul><ul><li>nephritis, activity </li></ul></ul></ul><ul><ul><ul><li>relatively disease specific </li></ul></ul></ul><ul><ul><li>- anti-Sm </li></ul></ul><ul><ul><ul><li>cutaneous, musculoskeletal </li></ul></ul></ul><ul><ul><li>- anti-Ro (SS-A) </li></ul></ul><ul><ul><ul><li>neonatal, elderly lupus </li></ul></ul></ul><ul><ul><ul><li>ANA negative lupus </li></ul></ul></ul><ul><ul><ul><li>may cause nephritis </li></ul></ul></ul>
    80. 88. <ul><ul><li>- anti-La (SS-B) </li></ul></ul><ul><ul><ul><li>always associated with Ro </li></ul></ul></ul><ul><ul><ul><li>Sjogrens syndrome, low risk for nephritis </li></ul></ul></ul><ul><ul><li>- anti-histones </li></ul></ul><ul><ul><ul><li>drug-induced </li></ul></ul></ul><ul><ul><li>- anti-phospholipids </li></ul></ul><ul><ul><ul><li>3 types – LA, aCL, false VDRL test </li></ul></ul></ul><ul><ul><ul><li> LA, aCL  clotting abnormalities, fetal loss,  platelet antibodies for B 2 glycoprotein </li></ul></ul></ul>
    81. 89. <ul><ul><li>- antierythrocyte </li></ul></ul><ul><ul><ul><li>hemolysis </li></ul></ul></ul><ul><ul><li>- antineuronal </li></ul></ul><ul><ul><ul><li>diffuse CNS lupus </li></ul></ul></ul><ul><ul><li>- antiribosomal </li></ul></ul><ul><ul><ul><li>CNS lupus – </li></ul></ul></ul><ul><ul><ul><li>Psychosis </li></ul></ul></ul><ul><ul><li>- antiRNP </li></ul></ul><ul><ul><ul><li>MCTD </li></ul></ul></ul>
    82. 90. Revised Criteria for SLE <ul><li>Malar rash </li></ul><ul><li>Discoid rash </li></ul><ul><li>Photosensitivity </li></ul><ul><li>Oral ulcers </li></ul><ul><li>Arthritis, non-erosive, polyarticular </li></ul><ul><li>Serositis  carditis, pleuritis, effusion </li></ul>
    83. 91. Revised Criteria for SLE <ul><li>Renal </li></ul><ul><ul><li>+++ protein (U/A), >500mg/24hrs </li></ul></ul><ul><li>Hematologic </li></ul><ul><ul><li>blood “-penias” </li></ul></ul><ul><li>Neurologic </li></ul><ul><ul><li>seizures, psychosis </li></ul></ul><ul><li>Immunologic </li></ul><ul><ul><li>dsDNA, Sm, antiphospholipid </li></ul></ul><ul><li>(+) ANA </li></ul>
    84. 92. Revised Criteria for SLE <ul><li>4/11 criteria </li></ul><ul><li>97 % sensitivity; 98 % specificity </li></ul><ul><li>SOAP, BRAIN, MD </li></ul>
    85. 93. Treatment <ul><li>no cure, rare complete sustained remission </li></ul><ul><li>non-pharmacologic </li></ul><ul><ul><li>- doctor-patient relationship </li></ul></ul><ul><ul><li>- education </li></ul></ul><ul><ul><li>- support group </li></ul></ul>
    86. 94. Pharmacologic Therapy <ul><li>NSAIDs, analgesics </li></ul><ul><ul><li>MS Sx </li></ul></ul><ul><li>antimalarials </li></ul><ul><ul><li>cutaneous vasculitis </li></ul></ul><ul><ul><li>opthalmologic consult </li></ul></ul><ul><li>Steroids </li></ul><ul><ul><li>major organ </li></ul></ul><ul><ul><li>monitor side effects </li></ul></ul><ul><ul><li>oral / pulse therapy </li></ul></ul><ul><li>Immunosuppressives </li></ul><ul><ul><li>azathioprine, cyclophosphamide, chlorambucil, MTX </li></ul></ul><ul><ul><li>oral / pulse therapy </li></ul></ul>
    87. 95. <ul><li>Others </li></ul><ul><ul><li>plasmapheresis </li></ul></ul><ul><ul><li>cyclosporins </li></ul></ul><ul><ul><li>immunoablation </li></ul></ul><ul><ul><ul><li>high dose CYP </li></ul></ul></ul><ul><ul><li>antibodies to CD 4 </li></ul></ul><ul><ul><ul><li>suppress T/B cell </li></ul></ul></ul><ul><ul><li>IVIG </li></ul></ul><ul><ul><li>stem cell transplant </li></ul></ul>
    88. 96. Prognosis <ul><li>Factors assoc’d w/ poor prognosis </li></ul><ul><ul><li>-  creatinine levels </li></ul></ul><ul><ul><li>- hypertension </li></ul></ul><ul><ul><li>- nephrotic syndrome </li></ul></ul><ul><ul><li>- anemia,  albumin, low C 3 /C 4 at diagnosis </li></ul></ul><ul><ul><li>- low socioeconomic status </li></ul></ul>
    89. 97. Cause of Death <ul><li>1 st decade </li></ul><ul><ul><li>- infection, active disease </li></ul></ul><ul><li>2 nd decade </li></ul><ul><ul><li>- thromboembolic events </li></ul></ul>
    90. 98. Osteoporosis <ul><li>Silent disease </li></ul><ul><li>Systemic skeletal disease 1 </li></ul><ul><ul><li>Low bone mineral density (BMD) </li></ul></ul><ul><ul><ul><li>BMD  2.5 standard deviations below the mean BMD of young adults </li></ul></ul></ul><ul><ul><li>Microarchitectural deterioration of bone tissue </li></ul></ul><ul><ul><li>Bone fragility </li></ul></ul><ul><ul><li>Increased risk for fracture </li></ul></ul><ul><ul><li>1 Consensus Development Conference. Am J Med. 1991. </li></ul></ul>
    91. 102. Wasnich RD: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 4th edition, 1999, p 257 Incidence Rates for Vertebral, Wrist and Hip Fractures in Women After Age 50 40 30 20 10 Slide Modified: Review: Reviewer Memo: Source: Memo: 50 60 70 80 Vertebrae Hip Wrist Age (Years) Annual incidence per 1000 women
    92. 103. <ul><li>Non-Modifiable </li></ul><ul><li>Age </li></ul><ul><li>Female sex </li></ul><ul><li>Maternal family history of hip fracture </li></ul><ul><li>Low birth weight </li></ul><ul><li>Disease predisposing to osteoporosis </li></ul>Risk factors taken from Jordan & Cooper Best Practice and Res Clin Rheumatol, 2002 Categorized by Eli Lilly & Co. <ul><li>Potentially Modifiable </li></ul><ul><li>History of falls </li></ul><ul><li>Body mass index </li></ul><ul><li>Drug therapy (e.g. corticosteroid use, use of anti-convulsants) </li></ul><ul><li>Primary or secondary amenorrhea </li></ul><ul><li>Early menopause </li></ul><ul><li>Smoking </li></ul><ul><li>Excessive alcohol consumption </li></ul><ul><li>Dietary calcium and vitamin D deficiency </li></ul>Risk Factors for Osteoporosis and Fracture Slide Modified: Review: Reviewer Memo: Source: Memo:
    93. 104. Unitary model for postmenopausal bone loss: role of oestrogen deficiency Indirect effects Directly increases osteoclast number and longevity Dietary calcium (decreased absorption) Secondary hyperparathyroidism Increased bone resorption Bone loss Decreased bone formation Remodelling imbalance ? Adapted from: Riggs BL, et al. J Bone Miner Res 1998;13:763–73 Oestrogen deficiency
    94. 106. Glucocorticoid dose Dependent Effect on Fracture Risk 0.99 1.77 5.18 1.55 2.59 2.27 0 1 2 3 4 5 6 Hip Vertebral Type of Fracture Relative Risk of Fracture <2.5 mg 2.5 mg-7.5 mg >7.5 mg Dose* Van Staa TP, et al. J Bone Miner Res. 2000. *Prednisolone equivalent N = 488 470
    95. 107. Most rapid bone loss occurs in the first 6-12 months of Steroid therapy
    96. 108. WHO definition of osteoporosis <ul><li>The T-score </li></ul><ul><ul><li>the number of SDs from the mean (average) value of BMD at peak bone mass </li></ul></ul>WHO Study Group. WHO Technical Report Series 843, Geneva Switzerland: WHO;1994:1–129
    97. 109. How should patients be evaluated to determine if they have osteoporosis? <ul><li>AACE recommend that evaluation include </li></ul><ul><ul><li>a comprehensive medical examination </li></ul></ul><ul><ul><li>X-rays in patients with suspected vertebral fractures </li></ul></ul><ul><ul><li>BMD measurements </li></ul></ul><ul><ul><li>assessment of risk factors for fractures </li></ul></ul><ul><li>NOF guidelines are generally similar, but with greater emphasis on BMD testing </li></ul><ul><li>Neither guidelines take into account bone markers for diagnosing osteoporosis </li></ul>AACE Osteoporosis Task Force. Endocr Pract 2003;9:545–64 http://www.nof.org/professionals/clinical.htm
    98. 110. Diagnosis and assessment <ul><li>X-rays </li></ul><ul><li>BMD </li></ul><ul><li>Ultrasound </li></ul><ul><li>Bone markers </li></ul><ul><li>Bone biopsy and histomorphometry </li></ul>
    99. 111. <ul><li>Indications for Bone Density Measurements </li></ul><ul><li>estrogen deficient women </li></ul><ul><ul><li>- perimenopause </li></ul></ul><ul><ul><li>- early menopause </li></ul></ul><ul><ul><li>- premenopause </li></ul></ul><ul><li>radiologic osteoporosis </li></ul><ul><li>previous low-trauma fracture </li></ul><ul><li>corticosteroid therapy </li></ul><ul><ul><li>>7.5mg/day x 3 months </li></ul></ul><ul><li>diseases causing secondary osteoporosis </li></ul><ul><li>monitor treatment response </li></ul>
    100. 112. Biochemical markers of bone turnover in osteoporosis *CrossLaps TM
    101. 113. Candidates for therapy: the AACE guidelines <ul><li>The AACE guidelines indicate that the following women may benefit from pharmacologic therapy </li></ul><ul><ul><li>women with a prior vertebral or hip fracture </li></ul></ul><ul><ul><li>women with BMD T-score  –2.5 without risk factors </li></ul></ul><ul><ul><li>women with borderline-low BMD if risk factors are present </li></ul></ul><ul><ul><li>women in whom nonpharmacologic preventive measures are ineffective </li></ul></ul>AACE Osteoporosis Task Force. Endocr Pract 2003;9:545–64
    102. 114. Therapeutic options for osteoporosis <ul><li>Stimulators of bone formation </li></ul><ul><li>- Fluoride </li></ul><ul><li>- Parathyroid hormone </li></ul><ul><li>Mixed mechanism of action </li></ul><ul><li>- Vitamin D and metabolites </li></ul><ul><li>- Strontium ranelate </li></ul><ul><li>Recommended for all women at risk for osteoporosis </li></ul><ul><li>- Calcium and vitamin D </li></ul><ul><li>Inhibitors of bone resorption </li></ul><ul><li>Bisphosphonates </li></ul><ul><ul><li>- Alendronate </li></ul></ul><ul><ul><li>- Etidronate </li></ul></ul><ul><ul><li>- Risedronate </li></ul></ul><ul><li>Calcitonin </li></ul><ul><li>Estrogen ± progestin </li></ul><ul><li>Selective estrogen receptor modulators ( SERMs ) </li></ul><ul><ul><li>- Raloxifene </li></ul></ul>
    103. 115. Osteoporosis prevention T-score >–2.5 Osteopenia treatment with or without previous fracture Osteoporosis treatment with multiple fractures and at risk for hip fracture 50 55 60 65 70 75 80 85 Raloxifine Age (years) HRT Therapeutic Management of Postmenopausal Osteoporosis Teriparatide Bisphosphonates Adapted from Seeman & Eisman, MJA Vol 180 15 March 2004, p298-303
    104. 116. Optimal Daily Calcium Requirements 1300 mg 1000 mg 1200 mg Recommended Calcium Intake (Daily) Age 1997 Recommended Dietary Intakes 9-18 years 19-50 years 51 years or older National Academy Press. Available at: http://books.nap.edu/catalog/5776.html. 1999.
    105. 117. Recommendations for Vitamin D Intake <ul><li>Europe </li></ul><ul><li>The Scientific Committee for Food of the Commission of the European </li></ul><ul><li>Communities recommends </li></ul><ul><li>400 IU of vitamin D daily for the elderly (age  65) </li></ul><ul><li>United States </li></ul><ul><li>The Institute of Medicine has defined adequate daily intake of vitamin D </li></ul><ul><li>according to age </li></ul><ul><li>Adults up to age 50 200 IU </li></ul><ul><li>Adults 51–70 400 IU </li></ul><ul><li>Adults >70 600 IU </li></ul><ul><li>No toxic effects reported in 61 healthy adults given 4000 IU/day in a clinical </li></ul><ul><li>study to assess the efficacy and tolerability profile of high vitamin D intake </li></ul>Adapted from European Commission. Report on osteoporosis in the European community: Action on prevention. Luxembourg: Office for Official Publications of the European Communities, 1998; Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride . Washington, DC: Institute of Medicine, National Academy Press, 1997 ; Vieth R et al Am J Clin Nutr 2001;73:288–294.
    106. 118. Widespread Prevalence of Vitamin D Inadequacy* Regardless of Geographic Location *Vitamin D inadequacy was defined as serum 25(OH)D <30 ng/ml; **Interim results of ongoing study Study Design: Observational, cross-sectional study of 1285 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D distribution. Adapted from Lim S-K et al. Poster presented at ISCD, February 16–19, 2005, New Orleans, Louisiana,USA; Heaney RP Osteoporos Int 2000;11:553–555. Prevalence (%) 0 10 30 40 60 80 90 Latin America 51% 63% Asia All 59% Australia 59% Europe 52% Regions N=1285 81% Middle East 50 70 20 In a cross-sectional observational international study in 1285 postmenopausal women with osteoporosis**
    107. 119. Probable Reasons for High Prevalence of Vitamin D Inadequacy in Postmenopausal Women <ul><li>Lack of sunlight exposure </li></ul><ul><li>Vitamin D is not common in the diet </li></ul><ul><li>The ability to synthesize vitamin D in the skin decreases with age </li></ul><ul><li>Lack of compliance taking daily supplements </li></ul>Adapted from Marcus R Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill Medical Publishing Division, 2001:1715–1743; Bringhurst FR Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill Medical Publishing, 2005:2238–2249; Matsuoka LY J Clin Endocrinol Metab 1987;64:1165–1168; Parfitt AM Am J Clin Nutr 1982;36:1014–1031; Lawson RM Clin Nutr 2000;19:171–175.
    108. 120. Vitamin D Inadequacy* Has Important Consequences Appropriate neuromuscular function *Vitamin D inadequacy is defined as serum 25(OH)D <30 ng/ml. Adapted from Parfitt AM et al Am J Clin Nutr 1982;36:1014–1031; Allain TJ, Dhesi J Gerontology 2003;49:273–278; Holick MF Osteoporos Int 1998;8(suppl 2):S24–S29; DeLuca HF Metabolism 1990;39(suppl 1):3–9; Pfeifer M et al Trends Endocrinol Metab 1999;10:417 – 420; Lips P. In: Draper HH, ed. Advances in Nutritional Research . New York, Plenum Press, 1994:151–165. Bone mineral density Parathyroid hormone Calcium absorption Risk of fracture Artistic rendition
    109. 121. Bisphosphonate mechanism of action Adapted from: Bone H, et al. Clin Ther 2000;22:15–25 RESTING RESORPTION Osteoclast FORMATION Osteoblasts BISPHOSPHONATES INHIBIT OSTEOCLAST -MEDIATED BONE RESORPTION
    110. 122. PTH - Mechanism of Action PTH binds to cell surface G protein-coupled receptor Stimulates differentiation of bone lining cells and preosteoblasts to osteoblasts Decreases apoptosis of osteoblasts Net increase in number and action of bone forming osteoblasts
    111. 123. Osteoporosis has been thought of as a silent epidemic….this is not true anymore. At present, there is much noise in the field of research for its prevention, diagnosis and treatment. Ego Seeman ARCOS meeting, Feb 2002
    112. 124. One of the Many Faces of Osteoporosis “ You could have floored me when they told me. It’s very frightening, very frightening… I don’t want to end up in a nursing home incapacitated.”
    113. 125. Thank You ! Please visit: http://crisbertcualteros.page.tl
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