Internal Medicine Al Azhar university Faculty of Oral and Dental Medicine Lama El Banna connective tissue diseases

1. Dr. Suhail S. KishawiDr. Suhail S. Kishawi
Consultant in Endocrinology and DiabetesConsultant in Endocrinology and Diabetes
Consultant in internal MedicineConsultant in internal Medicine

2. Connective Tissue Diseases
Perivascular collagen deposition=Collagen
Vascular Diseases
Autoimmune diseases-not the primary cause
Exact cause remains obscure
Different diseases associated with specific
autoantibodies

3. Connective Tissue Diseases
Histopathology: Connective tissue and blood
vessel inflammation and abundant fibrinoid
deposits
Varying tissue distribution and pattern of
organ involvement
Symptoms nonspecific and overlapping
Difficult to diagnose

4. Connective Tissue Diseases
Disease Autoantibody
 Systemic Lupus Erythematosus Anti-dsDNA, Anti-SM
 Rheumatoid Arthritis RF, Anti-RA33
 Sjögren's Syndrome Anti-Ro(SS-A),Anti-La(SS-
B)
 Systemic Sclerosis Anti-Scl-70, Anti-
centromere
 Polymyositis/ Dermatomyositis Anti-Jo-1
 Mixed Connective Tissue Disease Anti-U1-RNP
 Wegener’s Granulomatosus c-ANCA

5. Systemic Lupus Erythematosus
 Inflammatory autoimmune
disorder affecting multiple
organ systems characterized
by the production of
autoantibodies directed
against cell nuclei.
 The name by which this
disease is known alludes to
the wolf -lupus in Latin-
because of the destructive
injuries that can bring to
mind the bites of this animal.

6. Systemic Lupus Erythematosus
General
Autoimmune multisystem disease
Prevalence 1 in 2,000
10 to 1: female to male (1 in 700)
Peak age 15-25
Black > white (1:250 vs. 1:1000)
HLA DR3 association, family history
Immune complex deposition
Photosensitive skin eruptions, serositis,
pneumonitis, myocarditis, nephritis, CNS
involvement
Severity is equal in male and female

7. Systemic Lupus Erythematosus
Specific native(Double stranded) DNA, SM
antigen
Lupus like reaction by drugs
(procainamide, hydralazine, ect)
LE cells

8. LE Cell
The LE cell is a neutrophil
that has engulfed the
antibody-coated nucleus
of another neutrophil.
LE cells may appear in
rosettes where there are
several neutrophils
varying for an individual
complement covered
protein.

9. PATHOPHYSIOLOGY

10. CLINICAL FEATURES:
Mucocutaneous
Malar Rash (butterfly
erythema)
Discoid rash
Photosensitive rash
Subacute cutaneous LE
Livedo reticularis
Alopecia
Raynaud’s
 Vasculitic ulceration
 Oral ulceration
 Nasal septal perforation
 Nailfold capillary changes

11. MALAR RASH
Fixed erythema, flat or raised, over the malar
eminences
Tending to spare the nasolabial folds

12. DISCOID RASH
Erythematous raised
patches with adherent
keratotic scaling and
follicular plugging;
Atrophic scarring may
occur in older lesions

13. Subacute cutaneous LE

14. Alopecia

16. ORAL ULCERS
Oral or nasopharyngeal ulceration
Usually painless, observed by a physician

17. SLE - VASCULOPATHY
 Small vessel vasculitis
 Raynaud's phenomenon is
excessively reduced blood flow in
response to cold or emotional
stress, causing discoloration of the
fingers, toes, and occasionally other
areas.
This condition may also cause nails
to become brittle with longitudinal
ridges, the phenomenon is believed
to be the result of vasospasms that
decrease blood supply to the
respective regions.
 Antiphospholipid antibody
syndrome

18. CLINICAL FEATURES:
Musculoskeletal
Arthritis is NONEROSIVE, transient, symmetrical,
affecting small joints, seldom deforming, less severe
than RA
Most common presenting feature of SLE

19. CLINICAL FEATURES:
Musculoskeletal
Synovitis-90% patients, often the earliest sign
Osteoporosis
 From SLE itself and therapy (usually steroids)
Osteonecrosis (avascular necrosis)
 Can occur with & without history of steroid
therapy

20. Osteonecrosis (Avascular Necrosis)

21. CLINICAL FEATURES: Ocular
Conjunctivitis
Photophobia
Monocular blindness-transient or permanent
Blurred vision
Cotton-Wool spots on retina-degeneration nerves
fibers due to occlusion retinal blood vessels

22. CLINICAL FEATURES:
PLEUROPULMONARY
Pleuritis/Pleural effusion
Infiltrates/ Discoid Atelectasis
Acute lupus pneumonitis
Pulmonary hemorrhage
“Shrinking lung” - diaphragm dysfunction
Restrictive lung disease

23. CLINICAL FEATURES: Cardiac
Pericarditis –in majority of patients
Libman Sacks endocarditis
Cardiac failure
Cardiac Arrythmias-common
Valvular heart disease
Coronary Artery Disease

24. Lupus - Endocarditis
Noninfective thrombotic endocarditis involving mitral valve in SLE.
Note nodular vegetations along line of closure and extending onto
chordae tendineae.

25. CLINICAL FEATURES:
HEMATOLOGICDISORDER
A) Hemolytic anemia - with reticulocytosis
OR
B) Leukopenia - less than 4,000/mm3
total on 2 or
more occasions
OR
C) Lymphopenia - less than 1,500/mm3
on 2 or more
occasions
OR
D) Thrombocytopenia - less than 100,000/mm3
in the
absence of offending drugs

26. CLINICAL FEATURES: Neurologic
Behavior/Personality changes, depression
Cognitive dysfunction
Psychosis
 May be difficult to distinguish from steroid psychosis or primary
psychiatric disease
Seizures
Stroke
Chorea
Pseudotumor cerebri
Transverse myelitis
Peripheral neuropathy

27. CLINICAL FEATURES: Renal (Lupus
Nephritis)
Develops in up to 50% of patients
10% SLE patients go to dialysis or transplant
Hallmark clinical finding is proteinuria
Advancing renal failure complicates assessment
of SLE disease activity
Nephritis remains the most frequent cause of
disease-related death.

28. CLINICAL FEATURES: Renal (Lupus
Nephritis)
Usually asymptomatic
 Gross hematuria
 Nephrotic syndrome
 Acute renal failure
 Hypertension
 End stage renal failure (ESRD)

29. CLINICAL FEATURES: Gastrointestinal &
Hepatic
Uncommon SLE manifestation
Severe abdominal pain syndromes in SLE often
indicate mesenteric vasculitis, resembling medium
vessel vasculitis (PAN)
Diverticulitis may be masked by steroids
Hepatic abnormalities more often due to therapy
than to SLE itself

30. Laboratory Findings
Complete blood count
Anemia
Leukopenia
Lymphopenia
Thrombocytopenia
Urine Analysis
 Hematuria
 Proteinuria
Granular casts

31. Monitoring Test: Erythrocyte Sedimentation Rate

32. Immunological findings
 ANA - 95-100%-sensitive but not specific for SLE
 Anti -ds DNA-specific(60%)-specific for SLE, but positive to other non
lupus conditions
 4 RNA associated antibodies
 Anti-Sm (Smith)
 Anti Ro/SSA-antibody
 Anti La/SSB-antibody
 Anti-RNP
 Antiphospholipid antibody
 Biologic false + RPR
 Lupus anticoagulant-antibodies coagulation factors, risk factor for venous
and arterial thrombosis and miscarriage.
 Anti-cardiolipin
 Depressed serum complement

33. Homogeneous ANA

34. Speckled ANA

35. DIFFERENTIAL DIAGNOSIS
 Almost too broad to consider given number of clinical
manifestations
 Rheumatic: RA, Sjogren’s syndrome, systemic sclerosis,
dermatomyositis
 Nonrheumatic: HIV, endocarditis, viral infections, hematologic
malignancies, vasculitis, ITP, other causes of nephritis
 “Overlap Syndrome” (MCTD)*
*MCTD ( Mixed Connective Tissue Disease)

36. CLASSIFICATION
1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
7. Renal disease.
> 0.5 g/d proteinuria
≥ 3+ dipstick proteinuria
Cellular casts
8. Neurologic disease.
Seizures
Psychosis (without other cause)
9. Hematologic disorders.
Hemolytic anemia
Leukopenia (< 4000/uL)
Lymphopenia (< 1500/uL)
Thrombocytopenia
(< 100,000/uL)
10. Immunologic abnormalities.
Positive LE cell
Anti-ds- DNA
Anti- Sm
Any antiphospholipid
11. Positive ANA ( 95-100% )
THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

37. Systemic Lupus Erythematosus: Diagnostic Criteria

38. CLASSIFICATION CRITERIA
Must have 4 of 11 for Classification
Like RA, diagnosis is ultimately clinical
Not all “Lupus” is SLE
 Discoid Lupus
 Overlap syndrome
 Drug induced lupus
 Subacute Cutaneous Lupus

39. LUPUS RELATED SYNDROMES
Drug Induced Lupus
Classically associated with hydralazine, isoniazid,
procainamide
Male: Female ratio is equal
Nephritis and CNS abnormalities rare
Normal complement and no anti-DNA antibodies
Symptoms usually resolve with stopping drug

40. LUPUS RELATED SYNDROMES
 Antiphospholipid Syndrome (APS)
 Hypercoagulability with recurrent thrombosis of either venous or arterial
circulation
 Thrombocytopenia-common
 Pregnancy complication-miscarriage in first trimester
 Lifelong anticoagulation warfarin is currently recommended for patients with
serious complications due to common recurrence of thrombosis
 Antiphospholipid Antibodies
 Primary when present without other SLE feature.
 Secondary when usual SLE features present

41. LUPUS RELATED SYNDROMES
Raynaud’s Syndrome:
 Not part of the diagnostic criteria for SLE
 Does NOT warrant ANA if no other clinical evidence to
suggest autoimmune disease

42. SLE – treatment
 Mild cases (mild skin or joint involvement): NSAID, local treatment,
hydroxy-chloroquin
 Cases of intermediate severity (serositis, cytopenia, marked skin or
joint involvement): corticosteroid (12-64 mg methylprednisolon),
azathioprin, methotrexat
 Severe, life-threatening organ involvements (carditis, nephritis,
systemic vasculitis, cerebral manifestations): high-dose intravenous
corticosteroid + iv. cyclophosphamide + in some cases:
plasmapheresis or iv. immunoglobulin, or, instead of
cyclophosphamide: mycophenolate mofetil
 Some cases of nephritis (especially membranous), myositis,
thrombocytopenia: cyclosporine

43. PROGNOSIS
Unpredictable course
10 year survival rates exceed 85%
Most SLE patients die from infection, probably
related to therapy which suppresses immune system
and renal failure
Recommend smoking cessation, yearly flu shots,
pneumovax q5years, and preventive cancer
screening recommendations

45. Rheumatoid Arthritis
1% of the population
Women affected 2-3 X more than men
Age of onset is 40-50
Juvenile form

46. Rheumatoid Arthritis
Inflammation of the synovial tissue (lymphocytic)
with synovial proliferation
Symmetric involvement of peripheral joints, hands,
feet and wrists
Occasional systemic effects: vasculitis, visceral
nodules, Sjogren syndrome, pulmonary fibrosis
Anti-RA-33 autoantibodies
RA associated nuclear antigen (RANA)

47. Rheumatoid Arthritis: Diagnostic Criteria
1. Morning stiffness (>1h)
2. Swelling of three or more joints
3. Swelling of hand joints (proximal interphalangeal, metacarpophalyngeal,
or wrist)
4. Symmetric joint swelling
5. Subcutaneous nodules
6. Serum Rheumatoid Factor
7. Radiographic evidence of erosions or periarticular osteopenia in hand or
wrists
Criteria 1-4 must have been present continuously for 6 weeks or longer and must be observed
by a physician. A diagnosis of rheumatoid arthritis requires that 4 of the 7 criteria are
fulfilled.

48. Rheumatoid Arthritis
General
Nonarticular muscular structures
 Tendon, ligament, fascia
Systemic disease occas.
 Vasculitis, pulmonary fibrosis
Pathogenosis
 Inflammatory cell infiltrates
 Synovial proliferation
HLA Dw4

49. Rheumatoid Arthritis
General
Prevalence
 1% of population
 2-3 times F>M
 4th and 5th decade
Signs and symptoms
 Morning stiffness
lasting greater than 30
min
 Subcutaneous
rheumatoid nodules
 Synovial fluid
inflammation

50. Rheumatoid Arthritis
General
Synovial tissue
involvement
Symmetric peripheral
joints (hands, feet,
wrists)

51. Rheumatoid Arthritis
General
Diagnosis based on clinical grounds
Labs
RF pos. in 12 months 90%
RA associated nuclear antigen
anti-RA-33

52. Rheumatoid Arthritis
Head and Neck
Manifestations
 TM joint
 55% symptomatic
 70% incidence on X-ray
 Juvenile RA –
micrognathia : is a
condition where the jaw is
undersized. It is also
sometimes called
"Mandibular hypoplasia"

53. Rheumatoid Arthritis
Head and Neck Manifestations
Cricoarytenoid joint
 Most common cause of arthritis
 30% patients hoarse
 86% pathologic involvement
 Exertional dyspnea, ear pain, globus
Hoarseness
 Rheumatoid nodules, recurrent nerve involvement
Stridor
 Local/systemic steroids
 Possible Tracheotomy

54. Rheumatoid Arthritis
Treatment
 Physical therapy, daily exercise, splinting, joint protection
 Salicylates, NSAID’s, gold salts, penicillamine,
hydroxychloroquine, immunosuppressive agents
 Systemic steroids should be avoided
 Prognosis
 10-15 yrs of disease
 50% fully employed
 10% incapacitated
 10-20% remission

55. Sjögren's Syndrome
 Chronic disorder characterized by immune-mediated destruction of
exocrine glands
 Primary vs Secondary: Primary” Sjögren's syndrome occurs in
people with no other rheumatologic disease. “Secondary”
Sjögren's occurs in people who have another rheumatologic
disease, most often systemic lupus erythematosus and rheumatoid
arthritis.
 Primary is diagnosis of exclusion
 Secondary refers to the sicca complex accompanying any of the
connective tissue diseases (xerophthalmia, keratoconjuntivitis,
xerostomia with/without salivary gland enlargement)

56. Sjögren's Syndrome
1% of the population and in 10-15% of RA patients
9:1 female:male preponderance
Age of onset 40-60 years
Associated with a 30-40 times increased risk of
lymphoma.

57. Sjögren's Syndrome
May affect the skin, external genitalia, GI tract,
kidneys, and lungs
Minor salivary gland biopsy demonstrates
lymphocytic infiltration.
Parotid biopsy more sensitive and specific

58. Sjögren's Syndrome : Diagnostic Criteria
1. Dry eyes (>3mos), sensation of sand or gravel in eyes, or use of tear
substitutes>3x per day
2. Dry mouth (>3mos), recurrent or persistent swollen salivary glands, or
frequent drinking of liquids to aid in swallowing dry foods.
3. Schirmer-I test (<5mm in 5 min) or Rose Bengal score >4.
4. >50 mononuclear cells/4mm2
glandular tissue
5. Abnormal salivary scintigraphy or parotid sialography or unstimulated
salivary flow <1.5ml in 15 min
6. Presence of anti-Ro/SS-A, anti-La/SS-b, antinuclear antibodies, or
rheumatoid factor.

59. Sjögren's Syndrome
80% experience xerostomia
Difficulty chewing, dysphagia, taste changes,
fissures of tongue and lips, increased dental caries
and oral candidiasis
Salivary gland enlargement
Sicca syndrome

60. Sjogren’s Syndrome
General
Clinical manifestations
 Xerophthalmia, keratoconjunctivitis
 Xerostomia
 Other areas
 Skin, vagina, genitalia, chronic bronchitis, GI tract, renal
tubules
Diagnosis
 Minor salivary gland biopsy
 Labs
 RF and ANA
 SS-A/ro 60%
 SS-B/La 30%

61. Sjögren's Syndrome

62. Sjögren's Syndrome
Head and neck
manifestations
80% c/o xerostomia, most
prominent symptom
Difficulty chewing,
dysphagia, taste changes,
fissures of tongue and
lips, increased dental
caries, oral candidiasis

63. Sjögren's Syndrome
Head and Neck
Manifestations
Salivary quantification-
salivary scintigraphy
Salivary gland enlargement

64. Sjögren's Syndrome
Eye complaints
 Dryness, burning, itching, foreign body sensation
Keratoconjunctivitis sicca
 Corneal abrasions - rose bengal staining

65. Sjögren's Syndrome: Treatment
 Symptomatic: saliva substitutes, artificial tears, increased oral
fluid intake
 Avoid decongestants, antihistamines, anticholinergics,
diuretics
 Pilocarpine, antifungals, close dental follow-up, surveillance for
malignancy

66. Sjögren's Syndrome
Treatment
Symptomatic
 Oral fluid intake
 Saliva substitutes
 Artificial tears
Avoid
 Decongestants
 Antihistamines
 Diuretics
 Anticholinergic

67. POINTS TO
REMEMBER
•To reduce risk for
cavities and other
dental problems,
patients must pay
close attention to
proper oral
hygiene and
regular dental
care.

68. POINTS TO REMEMBER
 Sjögren's syndrome is an autoimmune condition that can occur at any
age, but is most common in older women. Many patients develop
Sjögren's syndrome as a complication of another autoimmune disease,
such as rheumatoid arthritis or lupus.
 Most of the treatment for Sjögren's syndrome is aimed at relieving
symptoms of dry eyes and mouth and preventing and treating long-
term complications such as infection and dental disease. Treatments
often do not completely eliminate the symptoms of dryness.
 Most patients with Sjögren's syndrome remain healthy, but some rare
complications have been described, including an increased risk for
cancer of the lymph glands (lymphoma). Thus, regular medical care
and follow up is important for all patients.

69. Scleroderma(Progressive Sclerosis)
General
Increased depostion collagen in interstitium of
small arteries and connective tissue
Sclerotic skin changes, often multisystem disease
Prevalence
 4-12/million/year
 3-4 to 1 F>M
 30-50 yrs
 Prognosis
 Black worse than white
 Men worse than women

70. Scleroderma
General
Presentation
 Raynaud’s phenomenon
 Edema fingers and hands
 Skin thickening
Visceral manifestations
 GI tract, lung, hear, kidneys, thyroid
Arthralgias and muscle weakness often

71. Scleroderma
General
Four categories
1. Diffuse cutaneous
 Worse prognosis
1. Limited cutaneous (CREST)
 More benign, less renal
1. Systemic sclerosis sine scleroderma
 Visceral manifestations without skin changes
1. Systemic sclerosis in overlap
 Concomitant with SLE, polymyositis, RA

72. Scleroderma

73. Scleroderma -CREST
Calcinosis
Raynaud’s
Esophageal
Dysmotility
Sclerodactily
Telangactasia

74. Scleroderma
Head and neck manifestations
 80 % have, 30% present with
 Tight skin, thin lips, vertical perioral
furrows
 Dermal and subcutaneous
inflammatory process
 Edema precedes epidermal atrophy,
loss of appendages

75. Scleroderma
Head and neck manifestations
Dysphagia
 Most common initial complaint
 80% distal 2/3 pathology on BS
 Decrease/absent paristalsis, dilation, hiatal
hernia

76. Scleroderma
Head and neck manifestations
 Decreased mouth opening
 Initial complaint 19%

77. Scleroderma
Treatment
Symptomatic
 Calcium channel blockers in raynaud’s
 H2 blockers for reflux
 NSAID’s and steroids for arthralgias and
myalgias
 Hand rehab
 Intra-arterial reserpine- decreases
vasoconstriction>healing

78. Mixed Connective Tissue Disease
Head and neck manifestations
Combination of features of other CTD
 Mucocutaneous rash, malar rash, discoid lupus,
sclerodermatous changes, nasal septal perforation,
esophageal dysfunction
Treatment
Steroid therapy for symptomatic relief
Immunosuppressives for complications of vital
organs

79. Vasculitides
Inflammation and necrosis of blood vessels
Immunologic mechanism
Any blood vessel involved
Diverse symptoms and overlap
Difficult classification

80. Vasculitides
Pathogenesis
Unclear
Deposition of antibody-antigen-complement in
vessel walls
Antigen deposition triggering lymphcytic reaction

81. Classification of Systemic Vasculitides

82. Behcet’s
Disease
Vasculitis with triad
 Oral, genital ulcers,
uveitis or iritis
 Oral
 Aphthous-like
 Painful, clusters on
lips, gingiva, buccal,
tongue
 Less often palate,
oropharynx

83. Behcet’s
Disease
Genital
 Similar in
appearance

84. Behcet’s
Disease
 Occular
 Uveitis, iritis
 Hypopyon
 Healing in
days to weeks
some scarring
 Symptoms
simultaneousl
y, months
apart

85. Behcet’s Disease
Other findings
 Progressive SNHL ( sensorineural hearing loss), tinnitus,
vertigo
 Nasal, laryngeal, tracheal mucosal ulceration
 CNS involvement, bowel dysfunction, large vessel arteritis
Treatment
 Azothioprine, methotrexate possibly, not documented

86. THANK YOUTHANK YOU