This document provides an overview of clinical approaches to patients with arthritis. It discusses the importance of taking a thorough history and conducting a physical exam. Common rheumatologic diseases like rheumatoid arthritis and crystal-induced arthritides such as gout and calcium pyrophosphate deposition disease are reviewed. Diagnostic approaches and treatment options for acute and chronic arthritis are summarized. Management involves treating acute flares, initiating long-term disease-modifying drugs, addressing risk factors, and monitoring patients.

1. Topic Review :
How to Approach Arthritis
Ext.สรวิศ / พ.อภิญญา
8 พฤษภาคม 2555

2. What’s Heading in Topic
Clinical Approach to patients with Arthritis ?
Common Disease in Rheumatology
• Rheumatoid Arthritis
• Crystal induced arthritis (Gout and CPPD)
Case study

3. CLINICAL APPROACH
TO PATIENT WITH ARTHRITIS ?

4. Importance of History
Duration of Complaints
Number of Joints Involved
Distribution of Joints Involved
Pattern of Involvement
Duration of Early Morning Stiffness

5. Importance of History
History of Joint Swelling
Extra-articular Complaints
Associated Medical Illness
Significant Past History
Family History of Rheumatic Disease

6. Importance of Physical Examination
Presence of Swelling of Joint
Local Warmth
Redness
Range of Motion
Any Deformity

7. Diagnostic Approach to
Musculoskeletal Pain

8. Diagnostic Approach to
Patient with Arthritis
Arthritis
Acute Chronic
Mono / Mono /
Polyarthritis Polyarthritis
Oligoarthritis Oligoarthritis

9. Differential Diagnosis
Acute Acute Chronic Chronic
Monoarthritis Polyarthritis Monoarthritis Polyarthritis
Pyogenic Acute rheumatic fever Chronic infection (TB, Rheumatoid
Gout Pyogenic (2-3 ข้อ) pyogenic, fungus) Gout
Pseudogout esp. GC, salmonella Osteoarthritis Pseudogout
Acute rheumatic fever SLE Gout Osteoarthritis
Traumatic arthritis Serum sickness Pseudogout Psoraitic
Reiter’s disease Reiter’s disease Avascular necrosis Ankylosing spodylitis
Psoriasis Psoriatic arthritis Tumor SLE
Rheumatoid arthritis Ankylosing spondylitis Neuropathic Other connective
Hemophilic arthritis Viral tissue diseases
Leukemia Hypertrophic
Hemophilic osteoarthropathy
Neuopathic

10. Examination of Synovial Fluid
Normal Noninflammatory Inflammatory Septic
Clarity Transparent Transparent Cloudy Cloudy
Color Clear Yellow Yellow Yellow
WBC*/microliter <200 <200–2000 200–50,000 >25,000
PMNs (%)* <25 <25 >50 >90
Culture Negative Negative Negative >50% positive
None
Crystals None None Multiple or none
Gout, pseudogout,
Osteoarthritis, Nongonococcal or
Associated spondyloarthropat
- trauma, rheumatic gonococcal septic
conditions hy, rheumatoid
fever arthritis
arthritis, SLE

11. COMMON DISEASE
IN RHEUMATOLOGY

12. RHEUMATOID ARTHRITIS

13. Rheumatoid Arthritis
• The most common form, autoimmune
inflammatory arthritis
• Characterized by symmetric arthritis of
the small joints of the hands and feet
• Chronic erosive arthritis need early and
aggressive management
• Prevalence 0.5 – 1 %

14. Pathogenesis
• Characterized by
– synovial inflammation and hyperplasia
(“swelling”),
– autoantibody production (rheumatoid factor
and anti–citrullinated protein antibody
[ACPA]),
– cartilage and bone destruction
(“deformity”),
– systemic features, including
• cardiovascular, pulmonary, psychological, and
skeletal disorders.

15. Pathophysiology

16. Criteria Diagnosis
• At least 4 of these 7 criteria
– criteria 1 to 4 must have been present for ≥6 weeks
Morning stiffness
Arthritis of 3 or more joint areas
Arthritis of hands
Symmetric arthritis
Rheumatoid nodules
Serum rheumatoid factor
Radiographic changes
Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987
revised criteria for the classification of rheumatoid arthritis.
Arthritis Rheum. 1988;31:315-324.

17. Criteria Diagnosis

18. Criteria Diagnosis

19. Criteria Diagnosis

20. Criteria Diagnosis

21. Criteria Diagnosis

22. American College of Rheumatology (ACR)/European League
Against Rheumatism (EULAR) collaborative initiative 2010
rheumatoid arthritis classification criteria
Score
Joint involvement 1 large joint (shoulder, elbow, hip, knee, ankle) 0
2–10 large joints 1
1–3 small joints (MCP, PIP, Thumb IP, MTP, wrists) 2
4–10 small joints 3
>10 joints (at least 1 small joint) 5
Serology Negative RF and negative ACPA 0
Low-positive RF or low-positive anti-CCP antibodies 2
(3 times ULN)
High-positive RF or high-positive anti-CCP antibodies 3
(>3 times ULN)
Acute-phase Normal CRP and normal ESR 0
reactants Abnormal CRP or abnormal ESR 1
Duration of <6 weeks 0
symptoms 6 weeks 1

23. Extraarticular manifestations of
rheumatoid arthritis

24. Management

25. Management
For Primary care Physicians
Establish Diagnosis of Rheumatoid Arthritis Early
Document Baseline Disease Activity and Damage
Estimate Prognosis
Start Treatment
Patient Education
Start DMARD(s) within 3 months
Consider NSAIDs
Consider Local / Low-dose Steroid
Physical / Occupational Therapy
Periodically Assess Disease Activity

26. Baseline Evaluation
• Subjective
– Degree of joint pain
– Duration of morning stiffness
– Duration of fatigue
– Limitation of function
• Physical examination
– Actively inflamed joints (tender and swollen joint
counts)
– Mechanical joint problems: loss of motion, crepitus,
instability,
– malalignment, and/or deformity
– Extraarticular manifestations

27. Baseline Evaluation
• Laboratory
– Erythrocyte sedimentation rate/C-reactive protein level
– Rheumatoid factor
– Complete blood cell count
– Electrolyte levels and Creatinine level
– Hepatic enzyme levels (AST, ALT, and albumin)
– Urinalysis
– Synovial fluid analysis
– Stool guaiac
• Radiography
– Radiographs of selected involved joints
• Other
– Functional status or quality of life assessments using
standardized

28. DMARDs Used for the Treatment of
Rheumatoid Arthritis
Other Common
Drug Dosage Serious Toxicities Monitoring
Side Effects
Hydroxy 200–400 mg/d Irreversible retinal Nausea Funduscopic
chloroquine orally damage Diarrhea and visual
( 6.5 mg/kg) Cardiotoxicity Headache field testing
Blood dyscrasia Rash every 12
months
Sulfasalazine Initial: Granulocytopenia Nausea CBC every 2–4
500 mg orally Hemolytic anemia Diarrhea weeks for first
twice daily (with G6PD deficiency) Headache 3 months, then
Maintenance: every 3
1–1.5 g twice daily months

29. DMARDs Used for the Treatment of
Rheumatoid Arthritis
Other Common
Drug Dosage Serious Toxicities Monitoring
Side Effects
Methotrexate 10–25 mg/week Hepatotoxicity Nausea CBC,
orally Myelosuppression Diarrhea creatinine,
or SQ Infection Stomatitis/mouth LFTs every 2–
Folic acid : Interstitial pneumonitis ulcers 3 months
1 mg/d to reduce Pregnancy category X Alopecia
toxicities Fatigue
Leflunomide 10–20 mg/d Hepatotoxicity Alopecia CBC,
Myelosuppression Diarrhea creatinine,
Infection LFTs every 2–
Pregnancy category X 3 months

30. approximate time to benefit of disease-
modifying antirheumatic drugs used in the
treatment of rheumatoid arthritis

31. Physical Therapy

32. Management
by Rheumatologist

33. CRYSTAL - INDUCED ARTHRITIS

34. Type of Crystal Disease
Monosodium urate (MSU) Gout, tophaceous gout
Calcium pyrophosphate dihydrate (CPPD) Pseudogout, pyrophosphate arthropathy,
calcium pyrophosphate dihydrate deposition
disease, tophaceous pseudogout
Basic calcium phosphate; calcium carbonate Acute periarthritis, acute arthritis,
(CC), hydroxy apatite (HA), octacalcium destructive
phosphate (OCP), tricalcium phosphate (TCP) arthropathy, Milwaukee shoulder/knee
syndrome
Calcium oxalate Acute and subacute arthritis
Cholesterol Asymptomatic, chronic effusion
Lipid liquid Acute arthritis
Cryoglobulin Acute arthritis
Charcot-Leyden Acute arthritis, eosinophilic synovitis
Corticosteroid extrinsic crystal Post intra-articular injection
synovitis

35. GOUT

36. Gout
• Gout is a type of inflammatory arthritis
induced by the deposition of monosodium
urate crystals in synovial fluid and other
tissues.
• It is associated with hyperuricemia, which
is defined as a serum urate level of 6.8
mg per deciliter or more.
• In Population, 0.5% prevalence of gout
overall

37. Risk Factor
• Hyperuricemia
– thiazide diuretics, cyclosporine, and low-dose
aspirin (<1 g per day)
• Triggers for recurrent flares include
– recent diuretic use, alcohol intake,
hospitalization, and surgery.
• Urate-lowering therapy
– which reduces the risk of gout attacks in the
long term, can trigger attacks in the early
period after its initiation

38. Pathophysiology

39. Classification of Gout
Clinical category Cause Metabolic defect
Primary gout (90% of cases) Enzyme defects unknown (85%-90% - Overproduction of uric acid
of primary gout) - Normal excretion (majority)
- Increased excretion (minority)
- Normal production of uric acid
- Under-excretion
Known enzyme defects, e.g. partial - Overproduction of uric acid
HGPRT deficiency
Secondary gout (10% of cases) Associated with increased nucleic - Over production of uric acid with
acid turnover, e.g. leukemia increased urinary excretion
Chronic renal failure - Reduced excretion of uric acid
with normal production
Inborn errors of metabolism, e.g. - Overproduction of uric acid with
complete HGPRT deficiency (Lesh- increased urinary excretion
Nyhan syndrome)

40. Clinical Phase
Asymptomatic hyperuricemia
Acute gouty arthritis
Intercritical gout
Chronic tophaceous gout

41. Chronic tophaceous gout
Adapted from BMJ Case Reports 2009 [doi:10.1136/bcr.03.2009.1668]
Copyright © 2009 by the BMJ Publishing Group Ltd

42. Diagnosis
(Definite Dx)
• synovial fluid or tophus aspiration
with identification of
• light microscopy ; needle shape crystal
• compensated polarized light microscopy
; positive birefringence with negative
elongation

44. Diagnosis
(Presumptive Dx)
• Medical Treatment with Colchicine improve within 12 - 24 hr
• Criteria Diagnosis from American college of Rheumatology (6 in
12)
– More than one attack of acute arthritis
– Maximum inflammation developed within 1 day
– Monoarthritis attack, redness observed over joints
– First metatarsophalangeal joint painful or swollen
– Unilateral first metatarsophalangeal joint attack
– Unilateral tarsal joint attack
– Tophus (confirmed or suspected)
– Hyperuricaemia
– Asymmetric swelling within a joint on x-ray film
– Subcortical cyst without erosions on x-ray film
– Joint culture negative for organism during attack.

45. Complication
• Acute uric acid nephropathy
– most commonly in patients treated with
cytotoxic agents, especially for
lymphoproliferative disorders and large tumour
burdens
• Chronic urate or gouty nephropathy
– Accumulated in medullary interstitium induced
inflammation process
• Uric acid stone
– Uric acid calculi constitute 10% of the renal
stones

46. Management
Acute gout attack
• Aim of therapy for acute gout
– rapid relief of pain and disability caused by
intense inflammation.
• Drug used
– nonsteroidal antiinflammatory drugs (NSAIDs),
colchicine, glucocorticoids, and possibly
corticotropin.
• Adjunctive treatment include
– applying ice to and resting the affected joint.
• NSAIDs and colchicine are first-line agents
for acute attacks

48. What if treatment fails
in acute gout ?
• If there is no improvement in symptoms
after 2–3 days:
– Review the diagnosis, check compliance with
medication, and encourage self-care
strategies.
– Increase the dose of medication to maximum
and add paracetamol, with or without codeine.
• If there is still no improvement in symptoms,
try an alternative drug or consider
combining treatment, or seek specialist
advice.

49. What follow up is recommended
after an acute attack of gout?
• Follow up the person 4–6 weeks after an acute
attack of gout has resolved, and:
– Check the serum uric acid level.
– Measure their blood pressure and take blood for
fasting glucose, renal function, and lipid profile.
– Identify underlying conditions such as hypertension,
diabetes, or renal impairment, and assess the person's
overall cardiovascular risk.
– Assess and provide advice on risk factors such as
obesity, diet, excessive alcohol consumption, and
exercise.
– Consider the need to start prophylactic medication if
the person is having two or more attacks of gout in a
year.

50. Management
Patient with Hyperuricemia

51. Management
Patient with Hyperuricemia
• The purpose of lowering serum urate levels
– To prevent acute flares and development of tophi
• When treatment
– Severity and frequency of flares, the presence of
coexisting illnesses (including nephrolithiasis), and
patient preference are additional considerations
• Urate-lowering therapy
– should not be initiated during acute attacks
– started 2 to 4 weeks after flare resolution
• The dose should be adjusted as necessary
– maintain a serum urate level below 6 mg per
deciliter which is associated with a reduced risk of
recurrent attacks and tophi.

52. Management
Patient with Hyperuricemia
• How long for used Urate – lowering
therapy
– Suggest patient can keep uric acid level
below 6.0 mg/dl and no attack at least 4-5
years
– In Chronic tophaceous stage should stop
when tophaceous gout resolve and continue
for 4-5 years after resolution

53. Management
Patient with Hyperuricemia
• Flare Prophylaxis during Initiation
of Urate-Lowering Therapy
– general recommendation for flare
prophylaxis is to use colchicine at a dose of
0.6 mg once or twice daily, with dose
adjustments as needed for renal impairment
– Diarrhea was common, resulting in a once-
daily regimen of colchicine for many
patients

54. CALCIUM PYROPHOSPHATE DEPOSITION DISEASE
(CPPD)

55. Calcium pyrophosphate deposition
disease (CPPD)
• metabolic arthropathy caused by the
deposition of calcium pyrophosphate
dihydrate in and around joints,
– especially in articular cartilage and
fibrocartilage.
• Although CPDD is often asymptomatic, with
only radiographic changes seen
– (ie, chondrocalcinosis)
• various clinical manifestations may occur,
including
– acute (pseudogout) and chronic arthritis

56. Risk Factor
• Age is most important risk factor
• Osteoarthritis (OA) - threefold increased risk
if CPPD present
• Previous joint trauma/injury
• Joint surgery/lavage promotes crystal
shedding4
• Metabolic disease
– Hemochromatosis, 1˚Hyperparathroidism,
Hypomagnesemia, Malabsorption syndromes
– Consider in age <50-60 yo, especially if
polyarticular chondrocalcinosis (CC)
• Familial predisposition to CPPD

57. Clinical Presentation
• Associated with both acute and chronic arthritis
• Acute CPP crystal arthritis
– inflammatory arthritis of one or more joints. Knees,
wrists, shoulders, ankles, elbows, or hands can be
affected.
• chronic form of CPP arthritis
– mimics osteoarthritis or rheumatoid arthritis and is
associated with variable degrees of inflammation.
• Typically occurs in older patients but can occur in
younger patients with associated metabolic
conditions, such as hyperparathyroidism and
haemochromatosis.

58. Most common presentations
of CPDD
Type A. Pseudogout
Type B. Pseudorheumatoid arthritis
Type C and D. Pseudoosteoarthritis
Type E. Lanthenic or asymptomatic
Type F. Pseudoneuropathic joint
Other :
• ankylosing spondylytis or diffuse idiopathic skeletal
hyperostosis (DISH)
• pseudotophaceous disease

59. Diagnostic Criteria
(Definite & Probable)
• I. Demonstration of CPP crystals in tissues
or synovial fluid
– IIA. Identification of CPP crystals by
morphological analysis using compensated
polarising light microscopy.
– IIB. Typical calcifications on x-rays
(cartilage calcification); heavy punctuate or
linear calcifications in fibro-cartilage,
articular (hyaline) cartilage, or joint
capsules.

60. Chrondocalcinosis

61. Chrondocalcinosis

62. Diagnostic Criteria
(Possible)
• IIIA. Acute arthritis, especially of the knee or other large
joints.
• IIIB. Chronic arthritis of the knee, hip, wrist, elbow, shoulder,
or MCPs, particularly if accompanied by acute
exacerbations, and if characterised by:
– Involvement of uncommon sites for primary osteoarthritis
– Radiographical appearance, including severe patellofemoral
involvement
– Subchondral cyst formation
– Severe progressive joint degeneration with bony collapse
– Variable and inconsistent osteophyte formation
– Tendon calcifications, particularly of the Achilles, triceps, and
obturator tendons
– Axial skeletal involvement with subchondral cysts, disc
calcification, and vacuum disc phenomena, as well as
sacroiliac joint involvement.

63. Management
(Acute attack)
Ice and Rest
Joint aspiration
Oral Non steroidal Anti-inflammatory Drugs
Colchicine
Intraarticular glucocorticosteroids (GCS)
IV/IM/PO corticosteroid

64. Management
(Long term / Chronic)
• Prophylaxis against frequent recurrent acute
attacks
– Colchicine 0.6 mg twice daily
– Low dose oral NSAIDs
• Chronic CPP crystal inflammatory arthritis
– Correct metabolic disease
– Oral NSAIDs with gastro-protective treatment
– Colchicine 0.5-1.0 mg daily
– Daily low dose corticosteroids
– Magnesium –a cofactor for enzymes that break
down pyrophosphate
– MTX / Hydroxychloroquine

65. CASE STUDY

66. Case #1
• A 72-year-old woman presents with polyarticular
joint pain.
• She has long-standing mild joint pain, but over the
last 10 years notes increasing discomfort in her
wrists, shoulders, knees, and ankles. She has had
several recent episodes of severe pain in 1 or 2
joints, with swelling and warmth of the affected
areas. These episodes often last 3 to 4 weeks.
• Her examination shows severe bony changes
consistent with osteoarthritis in many joints, and
slight swelling, warmth, and tenderness without
erythema in the second and third MCP joints, left
shoulder, and the right wrist.

67. Case #2
• A 52-year-old woman presents with a 2-month
history of bilateral hand and wrist pain, and
swelling in her fingers.
• She has also recently noted similar pain in the
balls of her feet. She finds it hard to get going in
the morning and feels stiff for hours after waking
up. She also complains of increasing fatigue and
is unable to turn on and off taps or use a
keyboard at work without a significant amount of
pain in her hands.
• She denies any infections before or since her
symptoms started.

68. Case #3
• A 54-year-old man complains of severe pain and
swelling in his right first toe that developed
overnight. He is limping because of the pain and
states that this is the most severe pain he has
ever had ('even covering my foot with the bed
sheet hurts'). He has had no previous episodes.
His only medication is hydrochlorothiazide for
hypertension. He drinks 2 to 3 beers a day. On
examination, he is obese. There is swelling,
erythema, warmth, and tenderness of the right
first toe. There is also tenderness and warmth
with mild swelling over the mid foot.

69. REFERENCE

70. Reference
• American College of Rheumatoogy Ad Iloe Committee
on Clinical Guidelines. Guidelines for the initial
evaluation of the adult patient with musculoskeletal
symptoms, /Irth,.itis Rheum 1996; 39: 1-8.
• Ellrodt AG. Cho M. Cush J el. af. An evidence-based
medicine approach to the diagnosis and management
of musculoskeletal complaints. lIm J Med 1997:
103(45 ): 3-6.
• Ashok Kumar. ; Clinical Guide : Approach to Arthritis.
Vol. 4 No.1, January-March 2002; p.51-54
• William P. Arend AND George V. Lawry; Chapter 264
Approach to the Patient with Rheumatic Disease in
Goldman’s Cecil medicine. Rev. ed. of: Cecil
medicine. 23rd ed. c2008. p.1648-1651

71. Reference
• Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL,
Loscalzo J: Chapter 321. Rheumatoid Arthritis in Harrison's
Principles of Internal Medicine, 18th edition: McGraw-Hill
Companies,2012.
• Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL,
Loscalzo J: Chapter 331. Approach to Articular and
Musculoskeletal Disorders in Harrison's Principles of Internal
Medicine, 18th edition: McGraw-Hill Companies,2012.
• Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL,
Loscalzo J: Chapter 333. Gout and Other Crystal-Associated
Arthropathies in Harrison's Principles of Internal Medicine,
18th edition: McGraw-Hill Companies,2012.
• Tintinalli JE, Stapczynski JS, Ma OJ, Cline DM, Cydulka RK,
Meckler GD: Chapter 281. Acute Disorders of the Joints and
Bursae in Tintinalli's Emergency Medicine : A Comprehensive
Study Guide, 7th Edition. McGraw-Hill. 2010

72. Reference
• Arnett FC, Edworthy SM, Block DA, et al. The ARA
1987 revised criteria for the classification of
rheumatoid arthritis. Arthritis Rheum 1988, 31: 315-
24
• American College of Rheumatology Subcommittee on
Rheumatoid Arthritis Guidelines. Guidelines for the
management of rheumatoid arthritis 2002 update.
Arthritis Rheum 2002;46:328-46
• Aletaha D, Neogi T, Silman AJ, et al. 2010
Rheumatoid arthritis classification criteria: an
American College of Rheumatology/European League
Against Rheumatism collaborative initiative. Arthritis
Rheum. 2010;62:2569-2581
• แนวทางเวชปฏิบัติโรคข้ออักเสบรูมาตอยด์ (rheumatoid
arthritis) โดยสมาคมรูมาติสซั่มแห่งประเทศไทย. วารสาร
โรคข้อและรูมาติสซั่ม, 2545;13:25-31

73. Reference
• Iain B. McInnes, F.R.C.P., Ph.D., and Georg Schett,
M.D. The Pathogenesis of Rheumatoid Arthritis. N
Engl J Med 2011; 365:2205-2219
• Tuhina Neogi, M.D., Ph.D. ;Clinical Practice : Gout. N
Engl J Med 2011; 364:443-452February 3, 2011
• Emilio B. Gonzalez ; An update on the pathology and
clinical management of gouty arthritis.Clin Rheumatol
(2012) 31:13–21
• Newsome G. ;Guidelines for the management of
rheumatoid arthritis: 2002 update.J Am Acad Nurse
Pract. 2002 Oct;14(10):432-7.
• C. Ferrone, R. Andracco, M.A. Cimmino ; Calcium
pyrophosphate deposition disease: clinical
manifestations.Reumatismo, 2011; 63 (4): 246-252

74. Reference
• Iain B. McInnes, F.R.C.P., Ph.D., and Georg
Schett, M.D. The Pathogenesis of
Rheumatoid Arthritis. N Engl J Med 2011;
365:2205-2219
• Tuhina Neogi, M.D., Ph.D. ;Clinical Practice :
Gout. N Engl J Med 2011; 364:443-
452February 3, 2011
• Emilio B. Gonzalez ; An update on the
pathology and clinical management of gouty
arthritis.Clin Rheumatol (2012) 31:13–21
• Choi HK, Mount DB, Reginato AM.
Pathogenesis of gout. Ann Intern Med.
2005;143:499-516.

75. Reference
• Zhang W, Doherty M, Bardin T, et al. European League
Against Rheumatism recommendations for calcium
pyrophosphate deposition. Part I: terminology and
diagnosis. Ann Rheum Dis 2011; 70: 563-70.
• Zhang W, Doherty M, Pascual E, et al. EULAR
recommendations for calcium pyrophosphate deposition.
Part II: management. Ann Rheum Dis 2011; 70: 571-75.
• Rosenthal A, Ryan LM. Calcium pyrophosphate crystal
deposition diseases, pseudogout, and articular
chondrocalcinosis. In: Koopman WJ, Moreland LW, eds.
Arthritis and allied conditions. 15th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2004:2373-2396.
• McCarty DJ. Crystal identification in human synovial
fluids. Methods and interpretation. Rheum Dis Clin North
Am 1988;14:253-67.

76. Thank you for your kind attention