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1. Rheumatoid Arthritis (RA)

2. INTRODUCTION
• A chronic inflammatory disease of unknown etiology marked
by a symmetric, peripheral polyarthritis
• Most common form of chronic inflammatory arthritis
• RA often results in articular cartilage and bone destruction
and functional disability, it is vital to diagnose and treat this
disease early and aggressively before damage ensues

3. Epidemiology
• RA affects about 1% of the population
• Women are affected 2 to 3 times more often than men
• Onset may be at any age, most often between 25 yr and 55 yr

4. Etiology
• Although RA involves autoimmune reactions
• The precise cause is unknown;
• many factors may contribute:
A genetic predisposition has been identified
Unknown environmental factors (eg, viral infections) are thought
to play a role.

5. Pathogenesis

7. CLINICAL FEATURES
• Incidence : between 25-55 years of age.
• The presenting symptoms result from inflammation of the
joints, tendons, and bursae.
• Early morning joint stiffness lasting more than 1 h that eases
with physical activity

8. CLINICAL FEATURES
• Earliest involved joints - small joints of the hands & feet.
• May be monoarticular, oligoarticular (≤4 joints), or
polyarticular (>5 joints).
• RA have a higher number of tender and swollen joints,
test positive for serum rheumatoid factor (RF) or anti-CCP
antibodies, and have higher scores for physical disability

9. CLINICAL FEATURES
• Wrists, MCP & PIP joints stand  most
frequently involved joints
• DIP joint- rarely involved & denotes
coexistent osteoarthritis
• Flexor tendon tenosynovitis  a
hallmark of RA

10. CLINICAL FEATURES
• Large joints involved  knees and shoulders
• Spine usually spaired except cervical spine, which may
cause compressive myelopathy & neurologic dysfunction.
• temporomandibular joint occur commonly in patients with
RA, but they are generally not associated with significant
symptoms or functional impairment

11. Extraarticular Manifestations
• Extraarticular manifestations may develop during the clinical
course of RA in up to 40% of patients, even prior to the onset
of arthritis
• Risk Factors:-
1. History of smoking,
2. Early onset disability
3. Test positive RF or anti-CCP antibodies

12. Extraarticular Manifestations
Most common:
• Subcutaneous nodules
• Secondary Sjögren’s syndrome
• Pulmonary Nodules
• Anemia

13. CONSTITUTIONAL
• weight loss
• fever >38.3°C (101°F)
• fatigue
• Malaise
• Depression
• cachexia
reflect a high degree of inflammation

14. NODULES
• 30–40%
• Firm; non tender
• Develop in areas of repeated trauma
• E.g. : forearm, sacral prominences, Achilles
tendon
• Also in lungs, pleura, pericardium &
peritoneum

15. SJOGREN’SSYNDROME
• defined by the presence of either keratoconjunctivitis sicca
(dry eyes) or xerostomia (dry mouth) in association with
another connective tissue disease, such as RA.

16. PULMONARY
• Pleuritis - most common pulmonary manifestation of RA.
• Pleural effusions
• Interstitial lung disease (ILD)
• Caplan’s syndrome characterized by nodules &
pneumoconiosis following silica exposure
• bronchiolitis and bronchiectasis

17. CARDIAC
• The most frequent site is pericardium
• Cardiomyopathy, result from necrotizing or granulomatous
myocarditis
• Mitral regurgitation is most common valvular abnormality
in RA

18. HEMATOLOGIC
• A normochromic, normocytic anemia
• Degree of anemia denotes degree of inflammation,
correlating with CRP & ESR levels
• Platelet elevated in RA as acute-phase reactant.

19. Extraarticular Manifestations

20. DIAGNOSIS
• signs and symptoms of chronic inflammatory arthritis
• with laboratory & radiographic results
• American College of Rheumatology (ACR) classification criteria for RA,a score of
0–10, with a score of ≥ 6 fulfil the requirements for definite RA.(1987)
• In 2010, a collaborative effort between the American College of Rheumatology
(ACR) and the European League Against Rheumatism (EULAR) revised the 1987
ACR classification criteria for RA in an effort to improve early diagnosis with the
goal of identifying patients who would benefit from early introduction of
disease-modifying therapy

22. LABORATORY FEATURES
• 1. Elevated nonspecific inflammatory markers E.g. ESR, CRP
• 2. Detection of serum RF and anti-CCP antibodies
• Serum IgM RF found in 75–80% of patients
• Anti-CCP antibody : specificity 95%, so a positive test , with early inflammatory
arthritis, helps distinguishing RA from other arthritis.
• some patients with RA are positive for RF but negative for anti-CCP and vice versa.
The presence of RF or anti-CCP antibodies also has prognostic significance, with
anti-CCP antibodies showing the most value for predicting worse outcomes.

23. SYNOVIAL FLUID ANALYSIS
• Reflects an inflammatory State
• white blood cell (WBC) counts can vary widely, but generally range
between 5000 and 50,000 WBC/μL compared to <2000 WBC/μL for a
noninflammatory condition such as osteoarthritis

24. JOINT IMAGING
• For diagnosing RA
• For tracking progression of joint damage
1. Plain x-ray (M/C)-
• – Peri-articular osteopenia, soft tissue swelling, symmetric joint space loss, subchondral erosions.
• – signs of severe destruction :- joint subluxation and collapse
(X-rays are done symmetrically on both hand)
2. MRI
3. Ultrasound techniques
• Detect changes in soft tissues
• E.g. synovitis, tenosynovitis, effusions & bony abnormalities

25. X-ray progression of erosions PIP joint

26. Marginal erosions at metatarsal heads

28. Ulnar deviation of the fingers

29. Treatment
• Primary Objectives
• - Target is low disease activity or remission
• – Reduction of inflammation and pain
• – Preservation of function
• – Prevention of deformity
• DRUGS USED
– NSAIDs
– CORTICOSTEROIDS
– DMARDs
• SYNTETIC
• BIOLOGICAL

30. NSAIDs
• Symptomatic relief in RA
• Do not prevent erosions/alter disease progression.
• Not appropriate for monotherapy
• Used in combination with DMARDs

31. Corticosteroids
• Prompt anti-inflammatory effect in RA & slow rate of erosion.
• Multiple side effects limit their long term use
• low to moderate doses corticosteroids – as a bridge to reduce disease activity until
the slower acting DMARDs take effect
• Use : as Adjunctive therapy for active disease that persists despite treatment with
DMARDs.
• 10 mg of prednisone or equivalent per day is appropriate for articular disease.

32. Corticosteroids
• Higher doses use : to manage extra-articular
manifestations
– eg: pericarditis, necrotizing scleritis.
• Intra-articular corticosteroids
– if one or two joints are highly inflamed.
– Not more than four times a year.

33. Synthetic DMARDs
The conventional DMARDs include hydroxychloroquine, sulfasalazine,
methotrexate, and leflunomide
Methotrexate is the initial synthetic DMARD of choice.
• Effect in 2–6 weeks.
• The usual initial dose is 7.5 mg of methotrexate orally once weekly.
• Daily folate supplementation

34. Biological DMARDs

35. Other Treatments
Surgery
• Synovectomy of wrist or finger tendon sheaths for pain relief or to prevent tendon rupture
when medical interventions have failed.
• Osteotomy
• Arthrodesis
• Athroplasty
PHYSICAL THERAPY AND ASSISTIVE DEVICES
• all patients with RA should receive a prescription for exercise and physical activity. Dynamic
strength training, community-based comprehensive physical therapy, and physical-activity
• Foot orthotics for painful valgus deformity decrease foot pain and may reduce disability
and functional
• Judicious use of wrist splints can also decrease pain

36. Pregnancy
• 1. Prednisone
• 2. Hydroxychloroquine
• 3. Sulfasalazine
• are the safest DMARDs
• Methotrexate & leflunomide are contraindicated

37. Systemic Lupus Erythematosus (SLE)

38. Definition and Prevalence
• SLE is an chronic inflammatory multisystem autoimmune disease that
can affect the skin, joints, kidneys, lungs, nervous system, serous
membranes, and/or other organs of the body
• Immunologic abnormalities, especially the production of a number of
antinuclear antibodies, are prominent feature of the disease.
• The clinical course of SLE is variable and may be characterized by
periods of remissions and of chronic or acute relapses.
• Mostly affects (90%) childbearing age group females.

39. Pathogenesis

40. CLINICAL MANIFESTATIONS
Prevalence%
1. Systemic: fatigue ,malaise , fever, wt. Loss ,anorexia 95
2. Musculoskeletal 95
• Arthralgia/myalgia 95
• Nonerosive polyarthritis 60
• Myopathy/myositis 25/5
3. Hematological 85
• Anemia 70
• Leucopenia(<4000) 65
• Lymphopenia(<1500) 50
• Thrombocytopenia(<100000) 15

41. CLINICAL MANIFESTATIONS
Prevalence %
4. Cutaneous 80
• Photosensitivity 70
• Malar rash 50
• Oral ulcers 40
• Alopecia 40
• Discoid rash 20
5. Neurological 60
• Cognitive disorders, Seizures, Psychosis
• 6. Cardiopulmonary 60
• Pleurisy, pericarditis, effusion
• Myocarditis, endocarditis, CAD
• 7. Renal 30-50
• Proteinuria , Cellular casts, Nephrotic syndrome, ESRD

42. CLINICAL MANIFESTATIONS
Prevalence %
8. Gastrointestinal 40
Nonspecific(nausea, mild pain, diarrhea)
Abnormal liver enzymes
vasculitis
9. Thrombosis 15
• Venous, Arterial
10. Ocular 15
• Sicca syndrome, Conjuctivitis, Episcleritis, Vasculitis

43. LABORATORY TESTS IN SLE
ANA - Best screening test
Anti dsDNA - Specific for SLE; Correlate with disease severity
Anti-Sm- Specific for SLE
Complement C3 and C4 - Specific for SLE; Correlate with disease severity
 Complete blood count
 Urinalysis

44. ANA
• Most important autoantibody- test is positive in 95% of patients
• Present in 4-5% of healthy population
• Its sensitivity is high for SLE (98%) but specificity is low
• Diseases associated : SLE, MCTD, Systemic sclerosis, Drug induced SLE,
Inflammatory myopathies, RA,Sjogrens , Thyroid ds, AI hepatitis, PBC, Hep C

45. dsDNA and Sm antibodies
• There are two commonly obtained autoantibodies that are highly
specific for SLE: anti-double-stranded DNA (dsDNA) antibodies and
anti-Sm antibodies .
• Sensitivity — 66-95 percent
• Specificity — 75-100 percent
• Predictive value — 89-100 percent

47. SYSTEMIC LUPUS INTERNATIONAL COLLABORATING
CLINIC (SLICC) CRITERIA FOR CLASSIFICATION OF SLE
A.Clinical Manifestations
1. Acute cutaneous Lupus
2. Chronic cutaneous Lupus
3. Oral or nasal ulcers
4. Non scarring alopecia
5. Arthritis
6. Serositis
7. Renal
8. Neurological
9. Hemolytic anemia
10. Leucopenia
11. Thrombocytopenia

48. SYSTEMIC LUPUS INTERNATIONAL COLLABORATING
CLINIC (SLICC) CRITERIA FOR CLASSIFICATION OF SLE
• B. Immunological manifestations
1. ANA
2. Anti- dsDNA
3. Anti Sm
4. Antiphospholipid Ab
5. Low serum complement (C3,C4,CH50)
6. Positive direct coombs test
• Requirements: >= 4 criteria (atleast 1 in each category) OR
Biopsy proven Lupus Nephritis in presence of ANA or Anti ds DNA

49. Malar rash Discoid rash Oral Ulcer

50.  Biopsy — Biopsy of an involved organ (eg, skin or kidney) is necessary
in some cases.
 In the absence of renal abnormalities, renal biopsy has nothing to
offer and should not be performed.
 Renal involvement occurs in 40–70% of all SLE patients and is a major cause of morbidity and hospital
admissions. Immune complex formation/deposition in the kidney results in intra-glomerular inflammation
 Proteinuria of various levels is the dominant feature of lupus nephritis (LN) and is usually accompanied by
glomerular hematuria.
 Urinalysis is the most important and effective method to detect and monitor disease renal activity.

51. TREATMENT
• Goals of treatment:
- prevent flares
- treat flares when they occur
- minimize organ damage and complications
• Treatment plans are based on patient age, sex, health, symptoms and disease severity
– Fever, skin, musculoskeletal and serositis - milder disease
– CNS and renal involvement - Life threatening

52. TREATMENT - NON LIFE THREATENING SLE
• NSAIDS
• Antimalarials – Hydroxychloroquine
• Resistent cases – Low dose steroids (prednisolone 0.07 to 0.3mg/kg)
- systemic immunosuppressants
• Dermatitis: Topical sunscreens, steroids, antimalarials or Tacrolimus.

53. TREATMENT - LIFE THREATENING SLE
• Glucocorticoids :
- Prednisolone - 0.5-1mg/kg orally or
- Methylprednisolone 1g/d for 3 days followed by 0.5-1mg/kg daily prednisolone
- Maintenance dose 5-10 mg/day
• Cytotoxic therapy :
- Induction therapy :
Cyclophosphamide - 500-750 mg/mt2 monthly for 6 months
Mycophenolate mofetil(MMF) 2-3 gm/day
- Maintanence therapy :
Azathioprine(2mg/kg/d) or MMF(1.5-3 gm/d)
• Cyclophosphamide and mycophenolate responses begin 3–16 weeks after treatment is
initiated, whereas glucocorticoid responses may begin within 24 h.

54. TREATMENT
Other drugs
Chlorumbucil, Methotrexate, Leflunamide
Cyclosporine & tacrolimus
Biological agents : used in resistent cases
• Rituximab (Anti CD20 Ab)
• Belimumab (Anti BLyS)

57. Prognosis
• The overall 5-year survival of SLE is over 95%.
• The overall 10-year survival of SLE is over 90%.
• The overall 20-year survival of SLE is over 78%.
• The leading causes of death in the first decade of disease are systemic disease activity, renal
failure, and infections; subsequently, thromboembolic events become increasingly frequent
causes of mortality.

58. Drugs induce lupus
• This is a syndrome of positive ANA associated with symptoms such as fever, malaise, arthritis or intense
arthralgias/myalgias, serositis, and/ or rash
• appears during therapy with certain medications and biologic agents, is predominant in whites, has less
female predilection than SLE, rarely involves kidneys or brain, is rarely associated with anti-dsDNA, is
commonly associated with antibodies to histones, and usually resolves over several weeks after
discontinuation of the offending medication
• list of dugs: antiarrhythmics - procainamide, disopyramide, and propafenone; the anti-hypertensive -
hydralazine; several angiotensin-converting enzyme inhibitors and beta blockers; antithyroid
propylthiouracil; the antipsychotics- chlorpromazine and lithium; the anticonvulsants- carbamazepine and
phenytoin; the antibiotics - isoniazid, minocycline, and nitrofurantoin the antirheumatic sulfasalazine; the
diuretic hydrochlorothiazide; the antihyperlipidemic lovastatin and simvastatin and Biologics - include
inhibitors of IFNs and TNF.
• Treatment is focused on stopping the medication. NSAID and antimalarials can be temporarily used if
constitutional and musculoskeletal symptoms do not clear rapidly

59. Spontanous LUPUS Drug induced LUPUS
Usual age 20-40 50
F:M 9:1 1:1
Onset Gradual Abrupt
Constitutional symptoms ++ +
Arthalgia/ serositis/ hepatomegaly ++ ++
Rash ++ +
Renal ++ +
CNS ++ -
Hematologic Common Unusual
Immunologic abnormalities
ANA
LE CELLS
ANTI RNP
ANTI HISTONE
ANTI SM
ANTI DSDNA
COMPLEMENTS
IMMUNE COMPLEX
++
++
++
+
++
++
Reduced
Elevated
++
++
+
++
-
-
Normal
Normal

60. Antiphospholipid Syndrome (APS)
• APS is an autoantibody-mediated acquired thrombophilia characterized by
recurrent arterial or venous thrombosis and/or pregnancy morbidity.
• It affects primarily females
APS may occur: Primary
Secondary
• CAPS (Catastrophic APS): is a life-threatening rapidly progressive
thromboembolic disease involving simultaneously three or more organs.

61. Antiphospholipid antibodies (aPL) are directed against protein
which binds to phospholipids
• Beta2-glycoprotein
• Protein C
• Annexin V
• Prothrombin

62. Clinical manifestations and risk group
RISK GROUPS :
• Women
• SLE
• White than black

63. Diagnosis
Clinical Criteria:
• vascular thrombosis defined as one or more clinical episodes of arterial, venous,
or small vessel thrombosis in any tissue or organ
• pregnancy morbidity
Laboratory criteria:
• Anticardiolipin test
• Lupus Anticoagulant test
• Anti Beta2- glycoprotein 1 test
For confirmation of APS, test result should be positive on at least 2 occasion >= 12
weeks apart.

64. Treatment
• Warfarin used for life
• LMW heparin + Warfarin - aim to keep INR between 2.0 – 3.0
• Warfarin + Aspirin
• Aspirin reduces risk of thrombosis in aPL positive individuals
Pregnancy:
Heparin + Aspirin
IV immunoglobulin (IVlg) 400 mg/ kg every day for 5 days may
also prevent abortions

65. Treatment
Heparin-induced thrombocytopenia and thrombosis
syndrome: inhibitors of phospholipid-bound activated
factor X (Fxa)-fondaparinux 7.5 mg SC daily or
rivaroxaban 10 mg PO daily

66. Thank You