AUTOIMMUNE DISEASES

Autoimmune disease arise as a result of breakdown of self-tolerance where either the antibody or T cells mount an attack against self- antigen ( normal body tissues) and cause tissue damage.

Etiology:

The cause is multifactorial,

Genetic susceptibility especially to certain HLA class I & class II

alleles.

Environmental influences are also involved such as the role of

microorganisms especially at the early stages of disease.

:Mechanism

In normal conditions autoimmunity is prevented by self-tolerance.

Classification: .Disorders with organ specific autoantibodies:1

Example : pemphigus with intercellular desmosomes

of spinous cell layer act as antigen

organ specific autoantibodies:-. Disorders with non2

Example : sjogrens syndrome with antigens concerning

exocrine glands, thyroid ,kidney , and liver cells

:Typical features of autoimmune disease

1. Female frequently affected. 2. Hypergammaglobulinaemia. 3. Specific circulating auto antibodies against specific tissue or organ. 4. Immunoglobulins and complement deposits detected by IF. 5. Association with HLA- B8 and DR3 in some. 6. Response to immunosuppressive treatment in many cases. 7. Positive family history. 8. Remit and relapse 9. Progress slowly

:Diagnosis of immunologically mediated diseases

. Tests for screening of possible immunologically mediated diseases:1 a. Full blood picture:MCH, MCV, RBC, WBC and Platelets b. Serum protein levels.

. Specific tests for autoimmune diseases2 a. Auto antibody profile: RF, ANA, gastric parietal cells, gastric intrinsic

factor, anti Ro, anti La, .... b. Histopathological , immunopathological and immunofluorescent study. c. Serum complement levels. d. detection of circulating immune complexes

. HLA typing:3 positive family history and significant HLA association especiallynHLA-DR3 &

B8. are features of autoimmune disease

Examples of Autoimmune diseases of dental interest:

1. Lupus Erythematosus 2. Rheumatoid arthritis

3. Progressive systemic sclerosis 4. Dermatomyositis

Raynaud's disease & Raynaud's

phenomenon Both are characterized by:

1. change of color of fingers to white or blue.

2. Worst at tip caused by cold.

3. C/C discomfort, pain, numbness & stiffness during the attack.

4. On recovery: redness, tingling, slight edema of digits.

5. Slowly progressive

6. Ischemia may cause atrophy of fat pads or ulceration of tip of fingers or toes.

Etiology:

vasomotor instability. cooling or emotional upset precipitate vasoconstriction

Raynaud's phenomenon

Common features of C.T disease. Affect only few fingers of each hand

Raynaud's disease

Seen in normal person Spare only the thumb

Management a. To stay in warm,

b. wear warm clothing, c. protect the wrists & hands

Most of collagen disease share:

- Multiple autoantibodies & immune complex reactions.1

2. Raynaud's phenomenon & Sjogren syndrome develop in association

with any of them.

3. Cancer may be a late complications.

LUPUS ERYTHMATOSIS

LE is a connective tissue disease with auto immune manifestation, of unknown etiology and exist in many clinical forms:

1. Systemic LE (acute)

It is serious and aggressive multisystem disease

There is marked systemic manifestation.

There is marked and specific serological abnormalities (antinuclear antibodies "ANA" and an, cytoplasmic antibodies).

2. Discoid (Chronic) LE

It is mucocutaneousdisease.

Least aggressive form.

There is no serological abnormalities

It rarely progress to SLE

3. Subacute Cutaneous LE

Lies between SLE and DLE.

Mild to moderate skin lesions.

Mild systemic features.

There is some serological abnormalities (anticytoplasmic antibodies) and some ANA may be found).

It rarely progress to SLE.

1. DISCOID LUPUS

ERYTHMATOSIS

Site: It is relatively common disease

confined only to skin and oral mucosa

(mucocutaneous disease).

Age: predominantly in the third and fourth

decade.

Sex: more common in female than in male.

Skin manifestation: Site: a) Face: where they involve malar regions and cross the ridge of the nose,

which assume butterfly distribution.

(bb)The scalp, ears, chest, back and extremities. Character: a) The cutaneous lesions are slightly elevated red or purple macules

which is often covered with gray or yellow adherent scales. When the

latter is removed it reveals numerous "carpet tack" extensions which

has dipped into enlarged pilosebaceous canals. b) The lesion has sharp borders which slowly expand and increase in size

by peripheral growth. The periphery of the lesion appears pink or red. c) The center exhibits atrophic depigmented scarred appearance,

indicative to the chronicity of the lesion, with characteristic central

healing

Oral Manifestation:

Oral lesions has been reported in 25% to 50% of cases of DLE. The early lesions begins as irregular erythematous macules

which may be elevated or depressed and without keratosis.

Later, the atrophic red area may be surrounded by keratotic

margin or covered by white keratotic spots. Other may appear as keratotic lesion surrounded by red

(telangiectatic) halo. A classical lesion has been described as alternating red

(atrophic), white (keratotic) and red (telangiectatic) zones, provide characteristic

appearance. is usually associated with atrophy of tongue Tongue lesion:

coating. The lower lip may reveal atrophic plaques Lip lesion:

surrounded by keratotic border which may involve the entire

vermillion border and extend to circumoral skin. Malignant

transformation of lip lesion has been reported.

N.B. The margins of many of these keratotic lesion reveal a fine lacy

white network of stria (Wickham) so they simulate lichen planus. The

differentiation of both lesions can sometime be extremely difficult on

clinical examination alone. In the DLE however: 1. The lesions are less often symmetrically distributed 2. The pattern of striae is less well defined or conspicuous.

Prognosis:

DLE is a slowly progressive disease over a period of

many years. Occasionally spontaneous remission occurs or in rare instances it

develops into SLE Patients with oral DLE alone should be seen at least yearly in

order to: 1. Secure an early diagnosis of eventually developing sign of

cutaneous DLE. Early skin lesion responds better to local treatment

than older lesions. 2. The occurrence of oral ulceration is of clinical significance, it may indicate the presence of or signal of latter developments of

SLE.

Treatment:

Topical steroid are used for both oral and cutaneous lesion. In refractory skin lesions antimalarial drug or sulphones may be used.

2. SYSTEMIC LUPUS ERYTHMATOSIS

Definition: SLE is an auto immune disease of unknown etiology , characterized by a

variety of immunologic disorder which result in multisystem involvement with

varied clinical presentation. Any organ can be involved e.g. joints, kidneys,

hearts, lungs, etc. Etiology: The etiology is exactly unknown but it may be attributed to: 1) Immunologic factors: auto antibodies arise as a result of polyclonal

activation of B-lymphocytes in an environment where there is impaired

function of Ts.

Pathogenesis: the autoanibodies include: A) Antinuclear, antierythrocytes, antithrombocytes, antiphospholipids,

antilymphocyte antibodies (mainly T-lymphocytes) and anticytoplasmic

antibodies, circulating anticoagulant, Rheumatoid factor are found in the

patient's serum and tissue. B) The autoantibody may be: i. Directed against RBC, WBC, platelets and coagulation factors and is

responsible for hematological features i.e. anemia, leukopenia,

thrombocytopenia and clotting disorders.

ii. Autoantibodies may combine with

antigen(chiefly nucleic acid) and immune

complex is formed, which can activate the

complement and attract neutrophils and

macrophages. Failure to eliminate the

immune complex by phagocytic system,

particularly when sufficient amount is

accumulated in the circulation, vasculitis and

tissue damage are induced and can affect any

organ e.g.liver,Iung,kidney,heart,CNS, skin

etc....

2) Genetic factors: Relatives of SLE patient have demonstrated a high

incidence of autoantibody titre and immune deficiency (Ts and C2) and this is

greater among identical twins, Patients with HLA DR3 & DR4 gene are at risk of developing SLE

3) Hormonal factors: The high prevalence of SLE among women of

reproductive age suggest that female hormones may modify the immune

response. 4) Infection: Viral like particles have been detected in tissues of SLE

patients and it may initiate the abnormal immune response. 5) Drug induced: Many drugs have been listed in the etiology of lupus

like syndrome . The drug induced alteration of DNA nucleoprotein and

subsequently auto-antibody production.

Clinical Features:

SLE is predominantly a disease of young women, there is female predominance

of 10: 1 and has higher incidence among blacks. SLE is serious cutaneous systemic disorder which characteristically manifest

repeated emission and exacerbation.

Diagnostic Criteria: of SLE. This classification is based on 11 criteria and requires

that the patient exhibits four or more criteria either serially or

simultaneously, during any interval of observation in order to be

diagnosed positively. 1.The skin manifestations may be widely spread over the

body and appear as erythematous, edematous, macules. 2. Discoid scaly rash is less common. }Skin 3. Photosensitivity Associated skin lesions Alopecia may be patchy or diffuse. Ravnaud's phenomenon characterized by pallor or cyanosis

and tingling of toes and fingers on exposures to cold or emotion

due to paroxysmal vasospasm. Skin ulcer secondary to vasculitis 4.Oral ulcers. 5.Serositis:Pleuritis, pericarditis & periotonitis. 6.Renal disorders: a. Proteinuria more than 0.5 gm/ day. b. Nephritis. c. Cells in urine (erythrocytes -leukocytes)

7.Musculoskelatal: a. Arthralgia .

b. Polyarthritis

c. Myosits.

8.Cardiopulmonary :

a. Pericarditis, myocarditis, endocarditis often

associated with pleurisy

b. Localized myositis of the diaphragm result

in shrinking lung syndrome diminution of both lung

volume & normal gas transfer

c. Circulating immune complex damage

heart valve called libman sacks endocarditis . as

a result fibrin & platelets deposits at site of damage &

act as nidus for bacterial colonization during

bacteremia ( e.g. as result of extraction, scalling). This

patient need prophylactic antibiotic to guard against

infective endocarditis.

9.Neurologic:

a. Epileptic attacks.

b. Psychosis.

10. Immunologic a.(+) ve anti- ds DNA 99% b. (+) ve LE cell. 80% c. Circulating antibodies against R.B.C,

W.B.C., platelets. 11.Hematological feature: a. Normocytic normchrornic anemia . b. Leucopenia . c. Thrombocytopenia,

Oral Manifestation: 1) The oral manifestations of SLE may be similar to those described for DLE

but with little keratinization. Oral lesions of SLE may be confused with oral Lichen planus , and

can be differentiated by histopathological and direct immunoflourescent

findings. 2) Erythematous patches,superficial erosion, or ulceration (induced

by vasculitis secondary to immune complex formation and complement

activation.) 3) Pallor, petechea, secondary infection or bleeding,(to

autoantibodies against RBCs,platelets, WBCs & clotting factors.) 4) The gingival tissues may take the form of desquamative gingivitis.

5) 30% of the patients complain of salivary gland swelling , ocular dryness ,

xerostomia & soreness as a part of Sjogren's syndrome.

Immunofluorescent Testing for diagnosis of skin and mucosal

lesions: Direct immunofluorescent technique is performed by incubating a

biopsy specimen of the lesion with a fluorescein - conjugated

antiglobulin and the slide examined under the ultraviolet microscope, 1. Immunoglobulin antisera :

Positive reaction which appear as granular linear deposits at the

level of basement membrane zone, 100% positive for SLE and 70%

positive for DLE.

Lupus band test: biopsies from uninvolved skin when subjected to

immunofluorescent testing reveal positive reaction (90%) in SLE and negative

reaction in DLE. 2. Antifibrinogen and anticomplement (CJ) antisera: Positive reaction i.e. granular, linear deposits along the basement membrane

zone.

Histopathologic Findings: 1. Hyperorthokeratosis or hyperparakeratosis with areas of atrophic

epithelium. 2. Acanthosis. 3. Hydropic degeneration of the basal cell layer 4. Vascular dilation with edema of the upper dermis or submucosa. 5. Diffuse infiltration of lymphocytes with small number of plasma

cells and occasional polymorphonuclear leukocytes in the superficial

and deep connective tissue. There is perivascular collection

oflymphocytes. 6. Degeneration of collagen and elastic fibers. In SLE the degenerative features and collagen disturbance are

more prominent and inflammatory features are less sever than DLE.

SLE exhibit histopathologic changes in the oral lesion which is

identical with DLE but with lack of keratinization.

Laboratory diagnosis of SLE: Detection of ANA in the serum:[ANA can be detected in 99% of

cases]

Complement Level: The serum complement is frequently reduced in the presence of

active disease because of increased utilization due to immune

complex formation, reduced synthesis or combination of both

factors. C3 and C4 decreased during the disease activity. N.B.: Complement C2 deficiency predispose to SLE,

Treatment: Systemic coricosteroids are probably the most useful

therapy to control early acute manifestation and

together with immunosuppressive agents such as

azathioprine , for the potentially lethal lesions such as

renal involvement. Otherwise most of the patient appear to do well in the

long term with non-steroidal anti-inflammatory agents or if these agents are

ineffective, a very low doses of corticosteroids taken

on alternate days. Anti-malarials such as chloroquine also appear to be

effective especially for skin and joint lesions. Topical steroids , local analgesic and antifungal drugs

are used for treatment of oral lesions

Dental Implication of S.L.E.: 1. There is excessive bleeding tendency ,so complete blood count

should be done in order to evaluate a. thrombocytopenia b. hemolytic anemia

c. leukopenia. *Bleeding time, PT and PTT should be available

2. Prophylactic antibiotic cover is necessary in S.L.E. because: a. bacteremia in these patients is dangerous and the patients are

liable to develop infective endocarditis. b. there is marked leukopenia induced by the disease or by the

immunosuppressive therapy. 3. Avoid drugs that may cause lupus flare eg penicillin and

sulfonamide and non steroid ant-inflammatory drugs as possible,

Avoid tetracyclines, it may cause photosensitivity rashes. 4. Avoid any dental surgery as possible since it may cause

exacerbation of the condition particularly if the patient has past

surgical. Flare. 5. Since these patients are on long term corticosteroid therapy,

atrophy of the adrenal gland may occur and adrenal crisis may

develop. These patients are liable to severe infection due to the

immunosuppressive therapy. 6. Among other problems of the dental management include;

anemia, heart failure , and renal disease.

Rheumatoid arthritis

the usual manifestations of RA ( +) splenomegaly and leukopenia,( mainly neutropenia)

Rheumatoid arthritis characterized by inflammation of the synovial membranes.

Subtypes:

1-Felty's syndrome:

2-Juvenile RA (Still's disease):

systemic extra-articular symptoms are prominent, including fever, lymphadenopathy, hepatosplenomegaly, carditis, rash, ...

Laboratory findings Anemia : normocytic normochromic .

Mild lymphocytosis. Mild thrombocytopenia.

Hypergammaglobulinemia Positive rheumatoid factor (60%-70% of cases) ANA: found in low titre (20%-60% patients)

Diagnostic criteria Diagnosis of RA is made with 4 or more of the following criteria: Morning stiffness of more than 6 weeks. Arthritis of 3 or more joint areas. Arthritis of hand joints. Symmetrical arthritis. Rheumatoid nodules. Positive rheumatoid factor. Radiological changes.

Clinical features: Onset: insidious Symptoms: fatigue, loss of weight, numbness and tingling of the

extremities with increased stiffness of the hands or feet in the morning Age: 30-40 years. The small joints are first involved followed by larger joints - The joints are involved bilaterally showing the signs of acute

inflammation, e.g. pain and swelling. The affected joints have fusiform appearance. The skin covering the joints become atrophic, smooth and glossy in

texture. The acute joint symptoms disappear gradually followed by

painful disabling contractures, muscular weakness and atrophy Extra capsular features Subcutaneous nodules in pressure points. Enlargement of lymph nodes and spleen. Chronic skin ulcers from diffuse arteritis. Pleural effusion. Pulmonary fibrosis

Treatment: l. Rest in acute stage. 2.NSAIDs. 3. Gold, penicillamine, methotrexate, cyclosporine, corticosteroids. 4.Iron therapy. 5.Physiotherapy & psychological care

Oral signs attribute to:

The long-term drug admistraion: methotrexate, cyclosporine may

cause gingival overgrowth & increased incidence of periodontal

disease

Sjogren's syndrome is a common complication

RA may affect the temporomandibular joint

Features of anemia

Dental management 1. The most common complication relates to the toxicity of the drugs treatment. a. The most common adverse effects ofNSAIDs involve GIT and the kidneys. b. Aspirin at dosages approaching 5 g/day affect platelet function c. Gold salts can cause stomatitis, blood dyscrasias, and nephrotic syndrome. d. penicillamine cause bone marrow suppression and renal toxicity, heptotoxicity,

or drug-induced pemphigus. e. Corticosteroids and immunosuppressive. 2. Patients with prosthetic joints may require prophylactic antibiotic. 3. Patients with Sjogren's syndrome may require additional instruction in personal

oral care. 4. Felty's syndrome affects bone marrow.

Dermatomyositis

It is degenerative inflammatory condition of :

a. the skin,

b. the skeletal muscles and

c. occasionally the blood vessels.

The disease is characterized by progressive muscular weakness with skin

rash

Laboratory investigations a) Elevated serum enzyme levels derived from muscle destruction :

creatin Kinase, creatinurea b) EMG evidence of muscle disease

c) Muscle biopsy d) MRI

Clinical features Course: the disease is acute, sub acute or chronic Sex : more women Age: 40 to 50 years. 1. Diffuse bilateral, and symmetric proximal muscle weakness and wasting

of limbs, neck and trunk 2. The weakness is progressive and spreads to muscles of the face, larynx

and heart. 3. Skin: a. purplish red - erythema on the face and edema of the eyelids that

become pinkish and violet and may be tender to touch. b. periungual erytherna with telangectasia. c. Flat topped violaceous papules on the dorsum of the interphalangeal

joints. 4. Risk of malignancy

Management: Corticosteroids Azathioprine Methotrexate Cyclosporin

Cyclophosphamide

Oral features and dental implication: 1. Weakness of pharyngeal and palatal muscles causes dysphagia and dystonia.

2. Involvement of muscles of mastication causes difficulty in chewing. 3. Calcinosis of soft tissue rarely seen in children.

4. Rare cases have pulp stones. 5. Side effects of high doses of cortiosteroids, antimetabolites and other

immunosupressive drugs. 6. It may be associated with internal malignancy in adults

Scleroderma

Scleroderma is multisystem C.T. disease of unknown etiology characterized by:

1. Fibrosis -hardening of skin & mucosa.

2. Smooth muscle atrophy.

3. Fibrosis of internal visceral organs:

- GIT - Lung

- Kidney - Heart

Secondary changes due to pressure may occur in the underlying osseous structure.

Age: 30-50y

Sex: Female three times as male

Etiology:

Unclear, it may be attributed to abnormal activation of immune system

and microvascular injury.

Pathogenesis:

Vascular wall fibrosis of small and medium-size arterioles is a

prominent alteration in PSS and plays a crucial role in the pathogenesis

of pulmonary hypertension, renal crisis, myocardial dysfunction, and

digital gangrene.

Excessive collagen deposition in affected tissues is responsible for

most of the clinical manifestations of this disease

Types: A) Progressive Systemic Sclerosis (PSS):

1) Diffuse cutaneous scleroderma Initial wide spread skin involvement.

Early visceral involvement. Major morbidity& mortality.

2) Limited cutaneous scleroderma, CREST syndrome Minimum skin involvement confined to fingers & face.

Visceral involvement occurs late. Fairly benign course.

CREST syndrome: Calcinosis cutis, Raynauds phenomenon,

Oesophageal dysfunction, .Sclerodactyl and Telangiectasia.

B) Localized Scleroderma: Scleroderma primary involve skin. Minimum if any systemic involvement. No visceral diseases. Rarely progress to PSS.

Clinical features: 1. Raynaud 's phenomenon 2. Cutaneous Manifestations: Skin: become indurated, smooth, atrophic with telangiectesia. Face: expressionless, mask like. Fingers: fibrosis, lead to stiffness & atrophy of the skin over the digits,

ischemia & ulceration of finger tips. Perioral skin: rigidity Salivary gland: fibrosis, xerostomia. 3. Musculoskeletal Manifestations 4. Gastrointestinal Manifestations 5. Cardiac Manifestations 6. Pulmonary Manifestations 7. Renal Manifestations

Oral findings & dental implications: Chicken tongue - fish mouth. Oral telangectasia The oral mucosa becomes thin, pale, tender, and rigid with poor reparatiye

properties. Calcinosis of soft tissues around the jaws. Pseudoankylosis. The lips become rigid and thin. The periodontal membrane space is markedly widened in 10% of cases

in the posterior teeth. Mandibular angle: resorbtion. Sjogren's syndrome: xerostomia.

Side effects of drug treatment A-Calcium channel blocking agents: gingival enlargement

B-Penicillamine: blood dyscrasia, lichenoid reaction. +

Atrophy of the alveolar process with premature loss of teeth. Difficulties in chewing and poor reparative capacity , anaemic and

undernourished patients. Facial hemiatrophy, pseudo ankylosis and alteration in speech psychic

disturbances.

Dental treatment complicated by: Narrowing of the mouth opening and rigidity of the tongue? Treatment: a- Stretching exercise b- Bilateral commissurotomy PSS : heart , lung , kidney involvement Mandibular fracture may occur during dental extraction ? (bone resorption at the angle of the jaw) Dysphagia.