Rheumatic Disease

Paul V. Santos Estrella, M.D.

ACRFP

RHEUMATIC DISEASES

COMMONLY SEEN IN PRIMARY

• Soft tissue rheumatism• Osteoarthritis• Rheumatoid arthritis• Gout• Systemic lupus erythematosus• Septic arthritis• Juvenile rheumatoid arthritis• Ankylosing spondylitis• Psoriatic arthritis• Scleroderma• Henoch-Schonlein purpura

ACRFP

KEY QUESTIONS

•Do you have pain or stiffness in your joints or spine?

•Do you have difficulties with walking, climbing stairs or getting up from bed?

•Do you have difficulties with dressing? ACRFP

Autoimmunity: Rheumatoid Arthritis

Autoimmunity: Multiple Sclerosis

Normal islet of Langerhan

Insulitis - Pre type1 diabetes

Alpha cells(Glucagon)

Beta dells(Insulin)

Normal Thyroid Grave’s disease(anti-TSHR Abs)

Hashimoto’s thyroiditisAnti-thyroid T cells

Autoimmunity: Diabetes and Thyroiditis

Normal stomach

Autoimmune gastritis(anti-parietal cell Ab)

Autoimmunity

Myositis

Pemphigus vulgaris

Intercellular IgGstaining

Immunological damage in the kidney

Normal glomerulus Goodpasture’s syndrome(linear staining)

IgA nephropathy(mesangial area staining)

Post streptococcal GN(lumpy bumpy staining)

Autoimmunity

Normal salivary gland Sjogren’s Syndrome salivary gland

Sjogren’s Syndrome

Systemic Lupus Erythematosus

Systemic Lupus Erythematosus

an autoimmune disease

18

19

Sn = TP / (TP + FN)

ACR classification criteria for systemic lupus erythematosus and their operating characteristics

Sp = TN / (TN + FP)

LR+ = Sensitivity / (1 - Specificity) LR- = (1 - Sensitivity) / (Specificity

Criterion Sn, % Sp, % Likelihood ratio

Finding Present

Finding Absent

Malar rash 57 96 14 0.45

Discoid rash 18 99 18 0.83

Photosensitiviy 43 96 11 0.59

Oral ulcers 27 96 6.8 0.76

Arthritis 86 37 1.4 0.38

Serositis 56 86 4.0 0.51

Renal disorder 51 94 8.5 0.52

Neurologic disorder 20 98 10 0.82

Hematologic disorder 59 89 5.4 0.46

Operating characteristics of systemic lupus erythematosus (SLE) based on increasing number

of manifestations (assuming that each manifestation carries an equal weight)

Diagnostic strategies for common medical conditions, 1999

Number of manifestations

Sensitivity, % Specificity, %Probability of

SLE, %

0 100 0 0

1 100 52 2

2 99 81 5

3 90 94 13

4 80 98 29

5 63 99 39

6 45 100 100

Operating characteristics of laboratory test in the diagnosis of systemic lupus erythematosus

Diagnostic strategies for common medical problems, 1999

Diagnostic testDefinition of

(+) resultSn, % Sp, % Likelihood ratio

Positive result

Negative result

ANA by fluorescencePositive

undiluted99 80 5.0 0.013

LE cell preparation Two cells 73 97 25 0.25

Anti-dsDNA antibody by Farr test

(radioimmunoassay)! 40% binding 73 (50-91) 98 (96-100) 37 0.28

Anti-dsDNA antibody by Crithidia lucillae assay (immunofluorescence)

(+) at 1:10 dilution

52 (42-69 98 (98-100) 26 0.49

Sequential evaluation of the probability of systemic lupus erythematosus based on clinical and laboratory

data

Diagnostic strategies for common medical problems, 1999

Number clinical

criteria met

Step 1Pretest probability of

SLE, %

Step 2 Post-test probability,

%

Step 3 Post-test probability, %

(+) ANA (-) ANA(+) ANA and

(+) anti-dsDNA

(+) ANA and (-) anti-dsDNA results

1 2 10 <1 80 3

2 5 20 <1 90 6

3 13 42 <1 96 17

4 29 67 1 98 45

5 39 78 2 99 47

Disease Course

0

100

Complemen factorsDisease activity

Infection

Cardiopulmonary failure Renal failure

WHO Classification of SLE Nephritis

II Pure mesangial alterations mesangiopathy)

III-a Focal segmental glomerulonephritis

III-b Focal proliferative glomerulonephritis

IV Diffuse glomerulonephritis V Diffuse membranous

glomerulonephropathyVI advanced sclerosis

Goals:

1) to control acute, severe flares

2) to develop maintenance strategies in which symptoms are suppressed to acceptable levels

Treatment of SLE

Treatment

Neuropsychiatric

manifestations

Pregnancy in lupus Antiphospholipid

syndrome

Lupus nephritisHematologic

manifestations

Musculoskeletal

manifestation

Dermatologic

manifestationCardiac Pulmonary

•Non-Pharmacologic Therapies

"

Patient education and psychosocial interventions

# - psychological support group (e.g. Lupus Club)

"

Lifestyle changes

# - avoid intense sun exposure

Pharmacologic Therapies

Corticosteroids - both anti-inflammatory properties and cause profound and varied metabolic effects

! Modify the body's immune response to diverse stimuli.

! High-dose glucocorticoids used for severe SLE complications, such as hematologic or CNS disease, serositis, vasculitis, or glomerulonephritis

4. NSAIDs

5. Antimalarials (e.g. Hydroxychloroquine)

6. Cytotoxic agents

7. Biologic agents

Factors associated with poor prognosis:

• high serum creatinine #

• hypertension

• nephrotic syndrome# #

• anemia

• hypocomplementemia##

Years after diagnosis Survival rates

1 95-97%

5 85-91%

10 72-80%

15 63-64%

Survival rates in systemic lupus erythematosus

Rheumatoid ArthritisNew Treatment of RA:

TNF-alpha has multiple roles in leading to damage:

1. hyperplastic hypertrophic synovial lining found

2. stimulates production of metalloproteinases by synovial cells as well as by chondrocytes.

3. Partly in response to TNF-alpha, chondrocytes also decrease synthesis of matrix elements.

Etanercept is essentially two TNF receptors held together by the Fc portion of an immunoglobulin. Thus etanercept acts like the soluble cytokine receptors to bind and inactivate TNF. Infliximab is a monoclonal antibody to TNF-alpha and blocks the actions of TNF-alpha in a similar way to etanercept.

Note the juxta-

articular osteopenia,

joint space

narrowing, and

erosions at the joint

margins of several

joints

Note juxta-articular

osteopenia and a large

effusion. An air-fluid level

can be seen in the

prepatellar bursa.

Typical features are seen in this

photo: swollen MCP 2 and 3

without redness, extension

deformities of fingers and

involvement of the PIPs and 2

and 5 DIPs as well

Right knee

effusion