1. Musculoskeletal disorders
Systemic Connective Tissue Disorders
Inflammatory Joint diseases
Osteoarthritis
Fibromyalgia
Diseases of bone

2. Systemic Connective Tissue Disorders

3. Systemic Connective Tissue Disorders
SLE
Scleroderma
Mixed CTD
Sjoren’s syndrome
Polymyositis and dermatomyositis
Systemic vasculitis

4. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

5. SLE is a chronic autoimmune multisystem connective tissue disease.
In autoimmune diseases, the immune system attacks the body’s cells and tissue, resulting in inflammation and tissue damage.
SLE most often affects the heart, joints, skin, lungs, blood vessels, liver, kidney, and nervous system.
The course of the disease is unpredictable, with periods of illness (called flares) alternating with remissions.
Peak age: 2nd-3rd decade
Female : male ratio =9:1

6. Etiology: Exact cause of SLE is unknown. The predisposing factors are:
Genetic predisposition
Genes are located in the HLA region on chromosome 6
Mutations may occur randomly (de novo) or it may be inherited
When triggered by environmental factors
Environmental factors like :
UV rays(sunlight)
Drugs: Hydralazine , procainamide , Isoniazid , methyldopa and chlorpromazipine, Penicillamine, sulfasalazine, lithium and lovastin
Extreme stress
Viral infection
Pregnancy and puerperium
Etiology:

7. This is Multifactorial disorder in which there is profound disturbance of immune regulation
Defect of suppressor T lymphocytes is associated with uncontrolled production of auto antibodies and immune complexes
Inflammatory process in SLE may occur by the two mechanisms:
Auto antibodies react with cell nuclei therefore antigen-antibody reaction results in inflammation.
Deposition of immune complexes in the tissues causing vasculitis.
Pathogenesis:

9. Clinical features: May involve one organ system at the onset
Multisystem involvement
Severity varies from mild and intermittent to persistent and fluminant
Exacerbations with intermittent remissions
True remission with no symptoms and requiring no therapy occur up to 20% cases

10. 1. Systemic features:
Fatigue, fever, anorexia and weight loss
Musculoskeletal manifestations:
Arthralgia and non deforming Arthritis, Myalgia
Small joints of hands ,wrist and knee are involved in symmetrical fashion
Joint deformities are unusual and erosions are rare

11. Skin lesion:
Erythema on the cheeks of the face and across the bridge of the nose Malar rash/Butterfly rash is the characteristic of SLE. It is present in 50% of cases and is photosensitive.
Photosensitivity
Loss of scalp hair
Discoid lupus erythematous: Occurs in 20%,presents as circular erythematous lesions with scaliness and telengectasia, scarring causing disfiguring. Found in scalp, ears, face and sunexposed areas of arms, back and chest

12. Butterfly rash

13. Malar rash

14. Vasculitic skin lesions are purpura, subcutaneous nodules, nail folds infarcts, ulcer, urticaria and gangrene of digits
Painful ulcers occurring in mouth and in nose
Raynaud’s phenomenon: May be sever enough to result in digital gangrene

15. Raynaud’s phenomenon:

16. Photosensitivity:

17. Discoid rash

18. Kidneys:
Renal involvement ranges from insignificant proteinuria to nephrotic syndrome and renal failure
Urinalysis may show hematuria and proteinuria>0.5g/day, Renal biopsy show types of glomerulonephritis responding to steroids or not
HTN may occur due to either nephrotic syndrome or renal failure

19. CNS manifestations:
Mild cognitive dysfunction, headache, depression, psychosis, Focal infarcts, seizures, aseptic meningitis
Abnormal EEG and CSF shows elevated protein
Vascular changes:
Thrombosis to vessel of any size
Pregnancy:
Spontaneous abortion/stillbirth

20. 8. Hematologic changes:
Hemolytic anemia: Coomb’s positive
Leucopenia
Lymphopenia
Thrombocytopenia
9. Cardiovascular manifestations:
Pericarditis, Pericardial effusion, pericardial tamponade, Myocarditis
Valvular insufficiency
SLE induced endocarditis called “Libman-sacks syndrome”
10. Respiratory changes:
Pleurisy, Pleural effusion, Lupus pneumonia

21. 11.Gastrointestinal manifestations:
Anorexia, nausea, diarrhea and vague discomfort are common
Vasculitis of intestine manifest as acute crampy abdominal pain, vomiting and diarrhea, Intestinal perforation can occur
12.Eye changes:
Episcleritis
Retinal vasculitis is serious manifestation, blindness can develop over a few days.

22. DIAGNOSTIC CRITERIA FOR SLE
REVISED AMERICAN RHEUMATISM ASSOCIATION
Malar rash:
Fixed erythema, flat or raised over the Malar eminence
2. Discoid rash:
Erythematous raised patches with adherent keratotic scaling and follicular plugging, atrophic scarring may occur
3. Photosensitivity:
Skin rash due to unusual reaction to light
Oral ulcer:
Oral and nasopharyngeal ulceration

23. Arthritis:
Non erosive arthritis involving 2 or >2 peripheral joints
characterized by tenderness, swelling and effusion
Serositis:
Pleuritis or Pericarditis
Renal disorder:
Proteinuria>0.5g/day or
cellular cast(RBC/WBC/Granular)
Neurological disorder:
Seizures/psychosis in the absence of offending drug/metabolic derangement

24. 9. Hematologic disorder:
Hemolytic anemia or
leucopenia<4000/mm or
Lymphopenia<1500/mm or
Thrombocytopenia <100,000/mm in the absence of offending drugs
Immunologic disorder:
Anti-DNA antibodies in abnormal titer or
Anti-Sm antibodies or
Positive phospholipid antibodies
11. Antinuclear antibodies:
An abnormal titer of ANA by immunofluorescence in absence of drugs

25. Diagnosis: Presence of 4 criteria at anytime during course of disease.
Specificity:98%
Sensitivity:97%

26. LUPUS VARIANTS 1.CHRONIC DISCOID LUPUS ERYTHEMATOSUS(DLE):
Benign variant of SLE in which skin involvement is often the only feature although systemic abnormalities may occur with time.
The rash appears on face as well defined erythematous plaque that progress to scarring and pigmentation.
2. DRUG INDUCED SLE:
Characterized by Arthralgia and mild systemic features, rashes and Pericarditis, but often without involvement of kidneys and CNS.
Often disappears after withdrawal of responsible drug.
Hydralazine and procainamide are the common cause, others are Isoniazid, methyldopa, Chlorpromazine, Alpha interferon and Penicillamine
All patients have ANA but Anti-dsDNA and hypocomplementaemia are rare.

27. 3. SLE AND PREGNANCY:
SLE patients in remission are not likely to have exacerbations during pregnancy, however women with active SLE, especially those with renal disease, have increased frequency of exacerbations of their disease.
Pre-eclampsia is a frequent complication of pregnancy
Fertility rates are normal but spontaneous abortion occur in 10-30% of women .
Disease flares in a small proportion, especially during the first weeks of postpartum

28. Prognosis: Disease pursues a relapsing and remitting course.
10 year survival rates are >85%
In some patients there is severe impairment of vital organs such as lungs,heart,brain or kidneys
Infection specially with opportunistic organisms have become the number one cause of death followed by active SLE, mainly due to renal and CNS disease.

29. Poor prognostic factors:
Hypertension
High serum creatinine
Anemia
Hypoalbuminemia
Hypocomplementaemia at the time of diagnosis
Thrombocytopenia
Severe CNS involvement
Presence of antibodies against Phospholipids
20% patients achieve remissions-transient
Likelihood of remission increase with each decade after diagnosis
Increase morbidity
Death due to: Renal failure and Thrombo-embolism

30. Investigations: 1. Blood: Normochromic Normocytic Anemia Leucopenia
Thrombocytopenia
Lymphopenia
2. ESR and C-reactive protein
ESR is raised and co-relates with disease activity
C-reactive protein is normal
3. Immunological findings:
Antinuclear antibodies (ANA) =95%
Anti-Double stranded DNA (Anti-dsDNA)=60%
Anti-Sm antibodies=30%
Anti Phospholipid antibodies
RA factor
LE cells
Anti histone antibodies=>95%
Serum complement level=Low
4.VDRL
5.Urinalysis
6. Serum creatinine

31. Treatment: There is no cure of SLE therefore management plan is:
To control exacerbation
To suppress symptoms to an acceptable level
Treatment option depends upon severity of disease.

32. NSAIDS:
Mild disease with Arthralgia, arthritis, fever and mild Serositis
2. Glucocorticoids:
Systemic Glucocorticoids are reserved for patients with life threating manifestations of SLE such as CNS or Renal involvement, myocarditis, Pericarditis or significant thrombocytopenia
In active SLE with fever and pleurisy start Prednisolone 1-2 mg/kg orally in 2-3 divided doses
After the controlling of disease only one morning dose is given
Thereafter the daily dose should be tapered .
With remission of disease withdraw steroids after few weeks or kept to maintenance level of around 10-15mg daily or alternate day regimen

33. In life threating, severely disabling patients including those with proliferative glomerulonephritis can be started with 3-5 days of 1g IV “Pulses” of Methylprednisolone followed by maintenance dose of daily or alternate day Prednisolone.

34. Steroid pulse therapy:
Prednisolone 40-60mg/day
Methylprednisolone g/day
Cyclophosphamide pulse therapy:
mg/m2 monthly and
Monthly for every 6 months
3 monthly for 6 months then
Every 6 months once for 2 years
ADR: Hemorrhagic cystitis, Bone marrow suppression, Hepatotoxicity

35. 3. Chloroquine:
Useful in management of troublesome skin lesions or Arthralgia that cannot be controlled with NSAIDS
Dose of Hydroxychloroquine is 400mg daily
4. Immunosuppressive drugs:
Drugs such as Azathioprine, Cyclophosphamide and Chlorambucil are used in:
Patients with severe focal or diffuse proliferative Glomerulonephritis not responding adequately to corticosteroids.
Patients in whom maintenance dose of steroid is so high as to cause severe side effects
Steroid resistant patients.
5. Immunomodulators:
Mycophenolate mofetil
Tacrolimus

36. Monitoring: Complete blood count:TLC,DLC,Hb,Platelet
Urine:Proteinuria,cast
ANA level
Anti-dS-DNA

38. SCLERODERMA

39. This is a generalized connective tissue disorder characterized by fibrosis and degenerative changes in the skin , Blood vessels and Visceral organs.
Etiology and incidence:
Unknown , May be immunologically mediated
Environmental risk factors : Silica dust, Vinyl chloride, Resins
F:M ratio=4:1
Peak age of onset:30-50 years

40. Types of Scleroderma:
Scleroderma is classified according to degree and extent of skin thickening
1.Systemic scleroderma:
Diffuse Cutaneous scleroderma
Limited Cutaneous scleroderma
2.Localized scleroderma:
Morphea
Linear scleroderma
3.In combination of other connective tissue disease:
Overlap syndrome
Mixed connective tissue disease.

41. 1.Systemic Scleroderma:
Diffuse cutaneous scleroderma:
It is characterized by the rapid development of symmetric skin thickening or tightening of proximal and distal extremity,face,and trunk.
These patients are at greater risk for developing kidney and other visceral involvement early in the course of disease.
Limited cutaneous scleroderma:
It is characterized by symmetric skin thickening limited to the distal extremities and face.
It is also called as CREST syndrome. [Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, and Telengectasia]
Prognosis is better than diffuse variety because of much lower frequency of internal organ involvement.

42. 2.Localized scleroderma:
It is limited to skin, subcutaneous tissue and muscle without systemic involvement.
1.Morphea:
Occurs as a single or multiple plaques of skin indurations and skin discoloration which evolve in sclerotic lesions
2.Linear scleroderma:
It appears as a linear streaks or bands most commonly on extremities and less frequently on forehead, trunk or fronto-parietal scalp.

43. Clinical features: 1.Raynaud’s phenomenon:
Severe Raynaud’s phenomenon is usually the presenting complaint .
It presents with three color changing, initially pallor, then blue due to peripheral cyanosis and then red due to reactive hyperemia along with tingling sensation.
2. Cutaneous changes:
a. Hand:
Non pitting edema and indurations with restriction of movement
Later skin becomes shiny with atrophy and ulcerations of the finger tips
b. Face:
In advanced cases the face may become taut and difficulty in opening the mouth.
Thinning and furrowing of the lips
Clinical features:

44. 3. Musculoskeletal: Arthralgia Mild non-erosive inflammatory arthritis
Morning stiffness
Muscle weakness and wasting due to tissue atrophy and low grade Myositis
Restricted hand movement.
4. GI:
Reflux oesophagitis
Esophageal dysmotility
Dysphasia and heart burn
Small bowel can be involved, producing Malabsorption from bacterial overgrowth due to dilatation and atony.

45. 5. Respiratory:
Pulmonary hypertension
Lower lobe fibrosis leads to cyst formation and honeycombing in advance disease.
6.Cardiovascular:
Diffuse myocardial fibrosis with development of arrhythmias
Pericarditis , cardiomyopathy , heart block and aortic valve lesion may occur.
7. Renal:
Renal failure and malignant hypertension

46. Investigations: Autoantibodies: Antinuclear antibody(ANA)
Anticentromere antibody(ACA) is most commonly seen in limited scleroderma
Antibodies to Topoisomerase 1(Scl 70) called Anti-Scl 70 –
--30% with diffuse scleroderma, and
--60% with limited scleroderma
2. Radiography:
X-ray chest
X-ray hands
Barium swallow
3. Blood: Normocytic Normochromic anemia
4. Urea and electrolytes
5. Urinalysis
Investigations:

47. Management: General management:
Regular monitoring to detect complications with measurement of BP,Blood counts,Urinaylysis and renal and pulmonary function test
Regular exercise to maintain flexibility of extremities
Avoidance of cold exposure,frequent use of detergent and soap as they can cause dryness of skin.
Massaging of skin may be helpful

48. Specific management:
Patients with Myositis and Alveolitis and arthritis:
Corticosteroids : 40-60mg/day
Immunomodulators like: Mycophenolate mofetil and Tacrolimus
Penicillamine: Reduce skin thickening and prevent development of significant organ involvement. Start with 250mg/day and increases at 1-3 month interval up to 1.5g/d
For Raynaud’s phenomenon: Nifidipine and Prostacycline infusion
ACE inhibitors are drug of choice in patients with Renal crisis and Accelerated Hypertension.

49. POLYMYOSITIS AND DERMATOMYOSITIS

50. Polymyositis:
Disorder of the muscle in which the pathological features are necrosis of muscle fibers together with evidence of regeneration and inflammation.
It presents with proximal muscle weakness and wasting
When Polymyositis is accompanied by skin rash, it is called dermatomyositis.

51. DERMATOMYOSITIS Autoimmune disease Cutaneous: Gottron’s papule
Heliotrope rash
Abnormal nail fold capillaries
2. Musculoskeletal:
Arthralgia
Myositis: Proximal muscle weakness, pain
3. Systemic
Fever, loss of weight
Investigations:
Creatinine kinase
EMG
Muscle biopsy

52. Gottron's papules, seen in dermatomyositis (an inflammatory disease of the muscles and skin). Violet colored inflammation (violaceous color) over the knuckles

53. This photograph demonstrates the sign "heliotrope eyelids" in which the eyelids develop a brown (violaceous - rather than red) color.

54. Management: 1. Steroid: Prednisolone 2.Immunosuppresive therapy:
Azathioprine
Methotrexate
3. Intravenous immunoglobulins

55. SJOGREN’S SYNDROME

56. SJOGREN’S SYNDROME Autoimmune disorder of unknown etiology
Occurs as a result of chronic dysfunction of exocrine glands and is characterized by:
Dryness of mouth,eyes, and other areas covered by mucus membranes
Onset:40-50 years
F:M=9:1

57. Clinical features:
Salivary gland and lacrimal glands are mainly affected
1. Salavary gland enlargement
Decrease salivary secretion—Dryness of mouth i.e Xerostomia leading to difficulty in speaking and swallowing, and to severe dental caries.There may be loss of taste and smell
2.Ocular:
Decrease tear production
Keratoconjunctivitis sicca– Results from inadequate tear production caused by lymphocyte and plasma cell infitration of lacrimal glands
3.Pancreatitis,Pleuritis,neuropsychiatric dysfunction and vasculitis may be present.
4.Renal tubular acidosis and chronic interestitial nephritis may also occur.

58. Investigations: 1. Autoantibodies: ANA Rheumatoid Factor
Anti-Ro, Anti-La
2. Schirmer’s test
To determine/demonstrate decrease tear production
3. Raised ESR
4. Salivary gland biopsy

59. Management: 1.General Artificial tear drop
Oral gel for shooting effect
2.Steroid :
Prednisolone
3. Immunosuppressive:
Azathioprine
Methotrexate.

60. MIXED CONNECTIVE TISSUE DISORDER

61. Mixed connective tissue disease(MCTD)
The condition is characterized by overlapping clinical features suggesting :
SLE
Scleroderma
Rheumatoid arthritis
Myositis
These conditions should be associated with very high titers of circulating autoantibodies to nuclear RNP,(Anti-nRNP)
With time in many patients, the manifestations evolve to one of the predominant disease such as scleroderma or SLE

62. Clinical features: Age:3rd-4th decade, F:M=4:1
Raynaud’s phenomenon, Puffy hands, Arthralgia and myalgia are common presenting features
High grade fever, Polymyositis, Arthritis
Sclerodermal changes are usually limited to distal extremities
Some present with Butterfly rash and other features of SLE
Deformities of hands similar to RA may present without erosions
Esophageal dysmotility is present causing dysphagia:70%
Lung involvement: Pleurisy, Diffuse interstitial Pulmonary fibrosis and Pulmonary Hypertension
ESR and Muscle enzymes are moderately raised
Clinical features:

63. Investigation:
Anemia, Coomb’s test positive>60%
Leucopenia, Thrombocytopenia
Hypergammaglobinemia
RA factor positive in >50%
Management:
Depends upon predominant cause.