Module 3: Oral Manifestations of Collagen Vascular Disease

collagen vascular disease

-group of acquired disease that have common diffuse inflammation of small blood vessels and connective tissue, but various etiologies

Sjorgen syndrome pathophysiology

*Chronic, systemic autoimmune disease

*Unknown cause

*Lymphocytic infiltration of exocrine glands that produce tears (lacrimal glands) and saliva (salivary gland) → chronic impairment

1. Plasmacytoid dendritic cells release interferon (protein released in response to pathogens)

2. IFN stimulates salivary acinar and duct cells to produce autoantigens: Ro (SSA) & La (SSB)

3. Post-transcriptional modification of Ro/La increases autoantigenicity

4. Acinar and ductal epithelial cells present Ro/La to Th-cells

5. Th Cells activate cytotoxic T Cells and B/Plasma Cells

6. Autoreactive T Cells and autoantibody producing B Cells → necrosis of salivary gland epithelium

7. Upon necrosis, more Ro/La released which is taken up by APC 

8. APC releases more interferon (cycle beings again)

Sjorgen syndrome epidemiology

*0.5% population

*Middle-aged adults

*Female 9:1

Sjorgen syndrome clinical features

*Enlargement of Major Salivary Gland

  - 30-50%

  - diffuse, firm enlargement of major salivary glands

  - usually bilateral, nonpainful or slightly tender, intermittent or persistent

  - risk of retrograde bacterial sialadenitis
  - acini destroyed in chronic inflammation & dilation of salivary ducts 

  - punctate sialectasia (fruit-laden branchless tree) on sialogram

*Xerostomia (dry mouth)

  - fissured tongue and atrophy of papillae

  - saliva may appear frothy

  - difficulty swallowing, altered taste, or difficulty in wearing dentures

  - secondary candidiasis

  - dental decay, especially cervical caries

*Xerophthalmia (dry eyes) – Keratoconjunctivitis sicca

  - reduced tear production by the lacrimal glands → decreased watery layer of tear film but normal mucin production → mucoid discharge, resulting in scratchy, gritty sensation, perceived presence of foreign body

  - defects of the ocular surface epithelium – blurred vision +/- aching pain

  - ocular dryness worsens as day progresses

→Xerostomia + Xerophthalmia = Sicca Syndrome (extremely red conjunctiva)

1. Primary Sjogren Syndrome = Sicca Syndrome for > 3mo

2. Secondary Sjogren Syndrome = Sicca Syndrome + Another CT Disorder

- RA (15%), SLE (30%), Scleroderma, PBC

                 - may develop years after onset of above disease

*40x increased risk for lymphomas (MALT lymphomas)

Sjorgen syndrome diagnosis- Keratoconjunctivitis sicca

- Schirmer Test: confirms decreased tear production - filter paper placed over margin of lower eyelid; diagnostic if length of wetting <5mm after 5 min

- Rose Bengal Dye: stains damaged conjunctival and corneal cells

Sjorgen syndrome diagnosis- histopathology

- harvest minor salivary glands from incision on lower labial mucosa

- 1+ foci of chronic inflammatory cells (50+ lymphocytes & plasma cells) adjacent to normal=appearing acini per 4mm2

Sjorgen syndrome diagnosis- autoantibodies

 - Specific for SS: presence of SSA and/or SSB antigens

 - Non-specific: Rheumatoid Factor (60% of cases +, auto-Ab against Fc portion of IgG); ANA (75-85% of cases +, auto-Ab against various proteins in nucleus)

*High rbc sedimentation rate (non-specific measure of inflammation)

*Elevated serum IgG levels (indicative of immune status)

Sjorgen syndrome diagnosis- exclusion criteria

- Past head and neck radiation treatment

  - Hepatitis C Infection

  - AIDS

  - Preexisting Lymphoma

  - Sarcoidosis

  - Graft-Versus-Host Disease (GVHD)

  - Use of Anticholinergic Drugs

Sjorgen syndrome treatment

*Supportive Care:

  - dry eyes → artificial tears

  - dry mouth → artificial saliva, sugarless gum or candy, sialagogue modifications (pilocarpine, cevimeline)

  - dental caries → daily fluoride application

  - secondary candidiasis → antifungal therapy

systemic lupus erythematosus (SLE) pathophysiology

*Chronic disease of variable severity with waxing and waning course

*Significant morbidity, can be fatal

*Preclinical Phase: autoantibodies common to other autoimmune diseases

*More Disease: organ specific clinically overt autoimmune phase

*Late Damage: infection, atherosclerosis, malignancies – related to complications of longstanding disease and immunosuppressive therapy

*Apoptosis related release of endogenous nucleic acid antigens stimulate IFN production which in turn activate B and T cells

SLE epidemiology

*Average age at diagnosis = 31 years

*Women 8-10x

SLE clinical features

*Fever, weight loss, arthritis, fatigue, general malaise

SYSTEMIC:

*Malar Rash

  - 40-50%

  - butterfly pattern over malar area and nose

  - sunlight makes lesions worse

*Cardiac Involvement:

  - 30-50% - pericarditis with chest pain

  - 50% - Libman-Sacks Endocarditis 

(warty vegetations → mitral valve regurgitation)

SLE oral manifestations

*Oral lesions in 5-25% 

  - palate, buccal mucosa, gingiva

  - variable appearance – lichenoid areas, nonspecific ulcer, granulomatous lesion

*Lupus Cheilitis: vermillion of lower lip with varying degrees of ulceration, pain, erythema, hyperkeratosis

SLE diagnosis

*Direct immunofluorescence:

  - Normal tissue (+ 26-60%) → Positive Lupus Band Test

  - Lesional tissue (+95%)

  - Deposition of immunoreactants (IgM, IgG, C3) in a shaggy or granular band at the basement membrane zone

  - RA, Sjogren Syndrome, Systemic Sclerosis may have similar findings

*Serum Antibody Detection:

  - ANA (antinuclear antibodies): 95%, non-specific (also in SS)

  - Antibodies vs dsDNA: 70-80% (specific for SLE)

  - Anti-SM (very specific for SLE)

SLE treatment

*Avoid excessive exposure to sunlight (UV may precipitate disease activity)

*Mild active disease: NSAIDS + antimalarials

*Severe acute episodes that involve arthritis, pericarditis, thrombocytopenia, nephritis: systemic corticosteroids +/- other immunosuppressive agents

SLE prognosis

*82-90% 5 year survival rate

*63-75% 20 year survival rate

*Depends on which organs are affected and how frequently disease reactivated

*Renal failure is most common cause of death

*Long-term immunosuppression medication → increased mortality due to infection and malignancy

*Worse prognosis for men than women

systemic sclerosis (Scleroderma) pathophysiology

*Relatively rare

*Immune-mediated condition

*Deposition of dense collagen in tissues and organs in extraordinary amounts → obliteration of blood vessels

*Most dramatic effects seen in skin

*Major organ-based complications involving lungs, heart, kidneys, GI determine morbidity and mortality

*Unknown etiology

systemic sclerosis epidemiology

*Relatively rare

*19/1,000,000 each year

*Female 5x

*Adults

systemic sclerosis clinical features

*Raynaud Phenomenon:

  - often 1^st sign

  - vasoconstriction in fingers, toes, ears, nose triggered by emotional distress or exposure to cold

  - skin becomes white → blue and numb → red and throbbing

  - can occur in healthy people 

*Acro-osteolysis:

  - resorption of terminal phalanges and flexion contractures (shortening of muscle tissue) → shorted fingers

  - due to microvascular occlusion

*Sclerodactyly:

  - due to abnormal collagen deposition → fingers become stiff, skin becomes tense/shiny

  - fingers undergo permanent flexure → claw-like fingers

*Ulceration of fingertips – due to vascular damage

*Skin:

  - diffuse, hard texture with smooth surface

  - Mask-Like Facies: subcutaneous collagen deposition in facial skin → smooth, taut face

  - Mouse Facies: Atrophy of the nasal alae due to tightening of the skin → pinched nose

*Fibrosis of lungs, heart, kidneys, GI tract → organ failure

  - Pulmonary Fibrosis → pulmonary hypertension and heart failure, primary cause of death (image: yellow-ish area is collagen, brown is normal parenchyma)

systemic sclerosis oral manifestations

*Microstomia: limitation of mouth opening due to collagen deposition in perioral skin (70%)

*Purse String-Like Mouth: furrows radiating from mouth

*Loss of attached gingival mucosa and multiple gingival recession

  - decreased vascularity and tissue ischemia resulting in increased periodontal disease and tooth mobility

*Dysphagia: collagen deposition in lingual and esophageal mucosa produces firm, hypomobile tongue and inelastic esophagus → hinders swallowing

*Xerostomia: collagen deposition in salivary gland tissues (secondary Sjogren Syndrome a possibility)
*Diffuse widening of the periodontal ligament space 

(increased collagen synthesis in PDL)1
*Resorption of posterior ramus of the mandible, coronoid process, chin, condyle (+individual tooth resorption): due to increases pressure from collagen production

systemic sclerosis diagnosis

*Clinical signs: stiffened skin texture + Raynaud Phenomenon

*Skin biopsy: abundant collagen deposition

*Anti-topoisomerase I (anti-Scl70): systemic sclerosis – autoantibodies vs enzymes that regulate over/underwinding of DNA

systemic sclerosis treatment

*No medication for complete treatment

*Directed at controlling symptoms

  - esophageal dilation for dysphagia

  - Ca Channel blockers to increase blood flow

  - ACEI for controlling HTN related to renal dysfunction

*Dental Management:

  - Collapsible dental appliances with special hinges to facilitate insertion and removal of dentures for patients with microstomia

  - Surgical correction of open bite associated with condylar resorption

systemic sclerosis prognosis

*Poor

*Especially poor if heart affected (most die of pulmonary involvement)

*Better in patients with limited cutaneous involvement: 80-90% 10 year survival

*Worse in patients with diffuse systemic sclerosis: 60-75% 10 year survival

1 scleroderma

*Mild variant of systemic sclerosis

*Affects only a solitary patch of skin

*”En Coup de Sabre” – Strike of the Sword: resembles scars

*Only a cosmetic concern, rarely life threatening

CREST syndrome (limited scleroderma)

*Mild variant of systemic sclerosis

*Adults: 50-70 years

*Female

*Signs may not appear synchronously but develop sequentially over months to years

    Calcinosis cutis – calcium deposits in skin

    Raynaud Phenomenon – spasm of vlood vessels to cold or stress

    Esophageal Dysfunction – acid reflux and decrease in motility of esophagus

    Sclerodactyly – thickening and tightening of skin on fingers and hands

    Telangiectasia – dilations of capillaries causing red marks on skin surface

*Diagnosis: Anti-centromere antibodies (part of chromosome that links sister chromatids)