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Introduction to rheumatology: epidemiology, diagnostics

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Title: Introduction to rheumatology: epidemiology, diagnostics


1
Introduction to rheumatologyepidemiology,
diagnostics, therapy
  • Dr. Zoltán Szekanecz
  • DEOEC 3rd Dept. Medicine
  • Reumatology Division

2
Rheumatology is the internal medicine of the
locomotor system
3
Classification - brief
  • 1. Arthritides (inflammatory diseases)
  • 2. Degenerative diseases
  • 3. Soft tissue rheumatism
  • 4. Muscular disorders
  • 5. Bone disorders
  • 6. Other

4
Classification 1.
  • 1. Diffuse connective tissue (autoimmune)
    diseases
  • 2. Rheumatoid arthritis and related conditions
  • 3. Seronegative spondylarthropathies (SNSA)
  • 4. Osteoarthritis (OA), spondylosis
  • 5. Spine disorders (discopathy, scoliosis, etc.)
  • 6. Arthropathies (metabolic, neurogenic, etc.)

5
Classification 2.
  • 7. Knee - internal abnormalities
  • 8. Other joint diseases (palindrom, arthralgia)
  • 9. Skin disorders (vasculitis, ITP)
  • 10. Tendinitis, bursitis
  • 11. Synovium, tendon, bursa disorders (Bakers
  • cyst, De Quervain tendinitis)
  • 12. Soft tissue rheumatism (restless legs, TOS,
  • carpal tunnel, fibromyalgia, fasciitis, etc.)

6
Classification 3.
  • 13. Muscle, ligament, fascia (plantar fasciitis)
  • 14. Crystal arthropathies (gout, CPPD, HA)
  • 15. Plasma protein abnormalities
  • 16. Other inflammatory diseases (Lyme,
  • erythema nodosum-associated arthritis)
  • 17. Bone disorders
  • (Klippel JH, Dieppe PA Rheumatology, 1998)

7
Epidemiology - general
  • At a given time 15-20 of the population may have
  • a rheumatic condition
  • Every second person will have a rheumatic disease
  • during lifetime
  • In family prcatice, 15-20 of patients see the
    doctor
  • due to rheumatic conditions
  • 20 of patients with other complaints also have
  • rheumatic conditions

8
Epidemiology - detailed 1.
  • Degenerative diseases
  • OA clinical 10-30
  • X-ray (gt55 yr) 80
  • Bone disorders
  • Osteoporosis 9-20
  • Pagets disease (gt6o yr) 2-3
  • Sudeck atrophy (after fracture) 7-35
  • Soft tissue rheumatism
  • Fibromyalgia 2-3

9
Epidemiology - detailed 2.
  • Arthritides, autoimmune diseases
  • Rheumatoid arthritis 1-2
  • AS (Bechterews disease) 0.1-1
  • Psoriatic arthritis 0.1
  • Gout (30-60 yr) 1.6
  • SLE 0.03
  • Scleroderma (SSc) 0.02
  • Sjögrens syndrome 1
  • Antiphospholipid syndrome 1-14

10
Social and economical effectsOsteoarthritis (OA)
  • Epidemiology (US data) malefemale
  • clinical symptoms 10-30
  • radiology 80
  • hip (gt60 yr) 10 11
  • knee (gt60 yr) 20 14
  • Altogether 43 million OA patients in the US
  • 2020 59 million expected
  • 2 million patients in Hungary (estimated)
  • Cost 65 billion USD / yr
  • 2020 82 billion USD expected

11
Social and economical effects Osteoporosis
  • Epidemiology
  • worldwide 9-20
  • Hungary (estimated) 15-20
  • Fractures
  • Hip (US) 1.3 billion / yr
  • 65 yr age 1
  • 85 yr age 11
  • 90 yr age 22
  • Mortality fracture complications 3rd after CV
    and cancer
  • Costs
  • fractures, total 10 billion USD / yr
  • one hip fracture 10-15.000 USD

12
Social and economical effects Rheumatoid
arthritis
  • Epidemiology
  • worldwide 1-3
  • Hungary (estimated) 1-2
  • Mortality
  • life expectancy 10 yrs less
  • III-IV. ACR stage mortality equals to
  • 3-vessel coronary heart disease
  • stage 4 Hodgkins disease

13
Social and economical effectsNon-steroidal
antiinflammatory drugs (NSAID)
  • USA
  • 13 million current user
  • 70 million prescriptions / yr
  • 30 billion OTC tablets / yr
  • GI mortality 0.22
  • NSAID assoc. Hospital admittance 103.000 / yr
  • cost of one admittance 15-20.000 USD
  • total cost 2 billion USD / yr !!!
  • Hungary
  • NSAID overabuse (e.g. in OA treatment)
  • 18 products (2000)

14
Diagnostics
  • Dr. Zoltán Szekanecz
  • DEOEC 3rd Dept. Medicine
  • Reumatology Division

15
Diagnostics in rheumatology
  • 1. History taking
  • 2. Physical examination
  • 3. Radiology (imaging)
  • 4. Laboratory methods
  • 5. Histology (biopsy)
  • 6. Other tests
  • 7. Consultations

16
History taking 1.
  • 1. Complaints (duration)
  • 2. History of present symptoms
  • 3. Previous illnesses
  • 4. Social history
  • 5. Family history
  • 6. Summary of findings

17
History taking 2.
  • 1. Onset (acute - chronic)
  • 2. Distribution (symmetry, migration,
    mono-polyart.)
  • 3. Specific complaints
  • 4. Severity (impairment, hospitalization)
  • 5. Functional capacity (at home, at work)
  • 6. Previous and current treatments
  • 7. Understanding of the disease
  • 8. Psychosocial, economical considerations

18
History taking 3.
  • 1. Trauma
  • 2. Operation
  • 3. Special associated conditions
    dermatological (psoriasis) gastrointestinal
    (Crohns disease, colitis ulcerosa) eye
    (uveitis, iritis) metabolic (diabetes,
    hemochromatosis) endocrine (thyroid,
    parathyroid, acromegaly)
  • 4. Drug treatment (past and current)
    drug-induced SLE
  • Raynaud beta blockers

19
History taking 4.
  • 1. Professional causes toxins, chemicals
    (scleroderma) "overuse" syndrome (carpal
    tunnel)
  • 2. Sexual history
  • (STD, AIDS, Reiters)
  • 3. Quality of life overcrowded apartment
    (rheumatic fever) endemic diseases (Lyme)
  • 4. Emotional and physical stress
  • 5. Diseases of family members infectious
    diseases (rubella, hepatitis)
  • 6. Travelling Reiters, AIDS, reactove
    arthritis

20
History taking 5.Genetics
  • 1. Gout, urolithiasis
  • 2. Rheumatoid arthritis and other autoimmune
    diseases (HLA-DR)
  • 3. AS and other SNSA (HLA-B27)
  • 4. Osteoarthritis
  • 5. Real" connective tissue diseases (Marfan)

21
History taking 6.Summary (review of symptoms)
  • 1. General symptoms (fever, fatigue, weight
    loss)
  • 2. Eye (iritis, uveitis, sicca syndrome)
  • 3. Oral (aphtha, sicca, scleroderma)
  • 4. Gastrointestinal (pain, diarrhea)
  • 5. Urogenital (dysuria, haematuria,
    prostatitis, urethral discharge)
  • 6. Skin (rash, ulcer, Raynauds, psoriasis,
    photosensitivity, nodules, etc. )
  • 7. Neuropsychiatric (epilepsy, neuropathies,
    depression, headache, etc. )

22
Physical examination 1.Guidelines
  • Gait
  • Arms
  • Legs
  • Spine

23
Physical examination 2.Positions
  • 1. Standing gait posture position of lower
    limbs spine movement
  • 2. Sitting head and neck movement chest
    expansion dorso-lumbar spine,
    temporomandibular upper extremities
  • 3. Lying abdomen low back lower
    extremities neurological exam

24
Physical examination 3.Detailed 1.
  • Gait and posture
  • Position of limbs
  • Spine dorsal spine (anteflexion,
    lateralflexion) head and neck movement
    dorso-lumbar spine movement lumbar spine
    flexion Schober sign (gt 5 cm) neurological,
    Lasegue sign
  • Chest expansion (gt6-7 cm)
  • Sacroiliac (tenderness, Mennel sign)

25
Physical examination 4.Detailed 2.
  • Temporomandibular joints
  • Shoulders contours (atrophy, swelling)
    elevation, rotation (in-out)
  • Elbows flexion, extension olecranon bursitis,
    synovitis nodules, tophi
  • Wrists, hands wrist, MCP, PIP, DIP, CMC
    swqelling, motion, pain fist formation, grip

26
Physical examination 5.Deatiled 3.
  • Lower limb length
  • Hips abduction, adduction rotation (in-out)
    flexion, extension
  • Knees patella position, mobility flexion,
    extension swelling (patella ballot., click)
    popliteal region (synovial cysts) knee
    stability (drawer sign)
  • Ankles, feet (hallux, MTP, IP joints)
    swelling flexion, extension, subtalar motion

27
Physical examination 6.Detailed 4.
  • Muscles inspection weight loss, atrophy,
    hypertrophy palpation tenderness muscular
    function
  • Neurological examination tendon reflexes
    (Achilles, patella, radial, ulnar) nerve
    function (sensory, motoric) entrapment (carpal
    tunnel, TOS, ulnar, etc.)

28
Physical examination 7.Systematic review,
scales, questionnaires
  • Systematic review swelling pain, tenderness
    temperature, color crepitation deformities
  • Scales, questionnaires joint motion in 2-3 axes
    (in degrees) swelling and tenderness (1-3)
    heat and redness (1-3) Ritchie index complex
    scales (HAQ, WOMAC, DAS, etc.)

29
Radiological examination aims
  • Diagnostic value (RA, AS, OA)
  • Differential diagnostic value (metast.)
  • Progression, indicator of therapy (erosions)

30
Imaging
  • 1. X-ray (simple, comparative, tomography)
  • 2. Radioisotope scanning Tc-99m scan (bone,
    joint) - SPECT infection Ga-67, labelled
    leukocyte scan In-111, INFLAMON,
    anti-granulocyte antibody
  • 3. CT (hernia, tumor)
  • 4. MRI (hernia, soft tissue, early erosions)
    indication cartilage, tendon, meniscus, muscle
  • 5. Ultrasound (cysts, joints, fluid)
  • 6. Invasive techniques arthrography,
    myelography

31
Laboratory examination 1.General, immunological
  • 1. Acute phase reactants ESR, CRP
  • 2. Hematology RBC, leukocytes, platelets, Hgb,
    Htc blood smear
  • 3. Immunology rheumatoid factor (Latex,
    Rose-Waaler) ANF (immunofluorescence Hep-2
    cells) DNA, ENA, RNP, Sm, SS-A, SS-B
    autoantibodies complement (CH50, C3, C4)
    immunocomplexes cryoglobulin other

32
Laboratory examination 2.Synovial fluid
  • 1. General assessment color (yellow)
    clarity, opacity (clear-opalescens) viscosity
    (inflammation decreased)
  • 2. Cell count
  • 3. Crystal analysis (polarized light) urate
    yellow Ca-pyrophosphate blue
  • 4. Microbiology (smear, culture)
  • 5. Biochemistry glucose (infection, tb low)
    protein, complement, RF ??

33
Histology(Diagnostic value)
  • Rheumatoid arthritis (?)
  • Tuberculosis
  • Sarcoidosis
  • Gout
  • Hemochromatosis
  • Multicentric reticulohistiocytosis (RHS)
  • Pigmented villonodular synovitis

34
Important consultations
  • Dermatologist (AP, SLE, vasculitis, etc.)
  • Ophthalmologist (AS, RA - chloroquin, Behcet)
  • ENT (reactive arthritis, RA)
  • Dentist (Sjögrens, RA)
  • Neurologist (neuropathies, CNS involvement)
  • Psychiatrist (chr. pain, fibromyalgia, SLE)
  • Urologist (reactive arthritis - Reiter, STD)
  • Gynecologist (reactive arthritis, STD)

35
Other diagnostic techniques
  • Arthroscopy diagnostic and therapeiutic
  • Electromyography (EMG) myositis, myopathy
  • Electroneurography (ENG) neuropathies
  • Saliva, tear secretion Sjögrens syndrome

36
REUMATOLOGICAL THERAPY
  • Drug treatment
  • symptomatic (NSAID, corticosteroids)
  • disease-modifying (DMARD)
  • Physiotherapy
  • Ortopedic surgery
  • Psychotherapy, education, social therapy
  • (Alternative medicine)

37
NSAID therapy
  • Dr. Zoltán Szekanecz
  • DEOEC 3rd Dept. Medicine
  • Reumatology Division

38
NSAID mechanism of actionThe Vane theory
COOH
Arachidonic acid
COX
NSAID
Prostaglandins
Pain, inflammation,fever, GI defense
Cited from Vane JR Nature New Biol 1971231232
235
39
Role of cyclooxygenase (COX)
  • COX is involved in the transformation of
    arachidonic acid and oxygen into PGH2
    (prostanoid precursor)
  • COX inhibition results in decreased PG production

Cited from Robinson DR J Rheumatol 199724(suppl
47)32-39.
40
NSAID effects
  • 1. Anti-inflammatory (COX-2 PG) COX
    inhibition inhibition of free radical
    production lysosomal enzyme inhibition
  • capillary permeability inhibition leukocyte
    migration inhibition phagocytosis inhibition
  • 2. Analgetic (COX-2 PG)
  • 3. Anti-pyretic

41
NSAID classification
  • 1. Salicylates (aspirin)
  • 2. Pyrazolons (amidazophenum)
  • 3. Pyrazolidines (butazons) phenylbutazon,
    azapropazon
  • 4. Indols indomethacin, tolmetin, sulindac
  • 5. Phenylacetates diclofenac, paracetamol,
    phenacetin, aceclofenac
  • 6. Antranilic acid nifluminic acid
  • 7. Propionates ibuprofen, tiaprofenate,
    naproxen
  • 8. Oxicams piroxicam, tenoxicam
  • 9. Non-acidic NSAIDs proquazon, nabumeton,
    COX-2 selective

42
NSAID in inflammatory rheumatic diseases
  • 1. Initial (powerful, short-term, more side
    effects) salicylates - maximum 7-10 days
    phenylbutazon max. 1-2 weeks indomethacinum
    (3x25-50 mg) naproxen (2x250-500mg) piroxicam
    (20-40mg) diclofenac (3x25-50mg, SR)
  • 2. Prolonged (weaker, less side effects,
    longer) nabumeton (1g) azapropazon
    (3x300mg) niflumic acid (3x250mg) ibuprofen (
    3x400mg) proquazon (3x200mg) sulindac,
    tolmetin (?indomethacinum)
  • 3. Selective COX-2 inhibitors anytime ?

43
Gastrointestinal risk
  • Nabumeton
  • Etodolac
  • Ibuprofen
  • Aspirin
  • Diclofenac
  • Naproxen
  • Indomethacin
  • Ketoprofen
  • Piroxicam
  • Flurbiprofen
  • Ketorolac

Increased risk
44
New hypothesis by Vane
COOH
Arachidonic acid
NSAID
COX-1 constitutive
COX-2 inducible
Prostaglandins
Prostaglandins
Defense of gatric mucosa
Mediators of pain, fever and inflammation
Hemostasis Kidneys
Cited Paulus HE, Bulpitt KJ. In Klippel JH,
szerk. Primer on the Rheumatic Diseases. 11th ed.
Atlanta Arthritis Foundation, 1997442-426
Robinson DR J Rheumatol 199724(suppl 47)32-39,
Vane JR, Botting RM Inflamm Res 1995441-10.
45
Terminology
  • Specific COX-2 inhibitor
  • Selective COX-2 inhibitor
  • More selective COX-2 inhibitor
  • Preferential COX-2 inhibitor
  • Coxibs vs others

46
COX-1/COX-2 ratios in whole blood assay
100
80
60
COX-1/COX-2 IC80 ()
40
20
0
DFP
aspirin
NS-398
tolmetin
diflunisal
suprofen
L-745,337
rofecoxib
etodolac
ibuprofen
naproxen
ketorolac
nimesulide
celecoxib
piroxicam
tomoxiprol
fenoprofen
zomepirac
ampyrone
ketoprofen
flurbiprofen
diclofenac
meloxicam
niflumic acid
indomethacin
sulindac sulphide
meclofenamate
sodium salicylate
Warner et al. PNAS 1999 967563-7568
47
Corticosteroid therapy
  • Dr. Zoltán Szekanecz
  • DEOEC 3rd Dept. Medicine
  • Reumatology Division

48
Corticosteroids
  • basis cortisone, cortisol
  • 80 bound to transcortin, 10 to albumin, 10
    bioactive
  • 95 kD corticosteroid receptor in plasma
  • complex transfers to nucleus
  • effect lipocortin stimulation - phospholipase A2
    inhib. - prostanoid metabolism inhibition -
    proinflammatory cytokine inhib. (IL-1, IL-2, TNF)
    - enzyme inhibition

49
Corticosteroids in practice
50
Practical guidelines
  • Disease and its severity
  • Planned duration of treatment
  • Optimal dose
  • Optimal product
  • Optimal route of administration (PO, IV)
  • Associated diseases
  • Chances for steroid sparing
  • Alternating dosage

51
Side effects I.
  • Gastrointestinal
  • ulcer, gastropathy, pancreatitis
  • Endocrine
  • Cushings syndrome
  • acne, hirsutismus, virilismus, impotency
  • growth retardation
  • hyperglycemia, diabetes, hyperlipidemia
  • potassium loss, sodium and fluid retention, edema
  • secondary hypadrenia

52
Side effects 2.
  • Cardiovascular
  • hypertension
  • edema, CHF
  • atherosclerosis
  • Locomotor
  • myopathy
  • osteoporosis, fractures
  • aseptic bone necrosis (femoral, humerus, etc.)

53
Side effects 3.
  • Neuropsychiatric
  • convulsions
  • psychosis
  • characteropathies
  • Ocular
  • posterior cataract
  • glaucoma

54
Side effects 4.
  • Skin
  • facial erythema
  • thin, fragile skin, petechiae, striae
  • retardation of wound healing
  • Immunological, infectious
  • neutrophilia, monocytopenia, lymphocytopenia
  • increased susceptibility to infections

55
Ulcer - gastropathy
  • Only anecdotic reports
  • not significant at low doses
  • not proven in large, controlled studies
  • usually ulcer is due to concomittant NSAID
    treatment

56
Infections
  • bacterial Staphylococci, Gram negative,
    tuberculosis, Listeria
  • viral, fungal rare
  • few large studies
  • tuberculosis was not more common
  • importance of other diseases, other therapies

57
General guidelines to dosage
  • Always choose the optimal dose, product and
    duration for the specific disease
  • in children, even 7.5 mg prednisone equivalent
    may cause growth retardation
  • high dose short term, slowly decrease
  • very short pulse therapy faster decrease
  • steroid sparing methotrexate, azathioprine,
    cyclophosphamide

58
Dosages
  • Low dose (lt 15 mg/d)
  • arthritis, inactive SLE, polymyalgia
  • High dose (20-60 mg/d)
  • active SLE, vasculitis
  • Very high dose (pulse 250-1000 mg)
  • acut nephritic crisis, vasculitic crisis

59
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