Connective tissue disorders and xerostomia symposium Flashcards
Types of connective tissue disorders (5)
Rheumatoid arthritis
Systemic and discoid lupus erythematosus
Systemic sclerosis
Sjogren’s syndrome
Rheumatoid arthritis epidemiology (6)
Affects 1-2% of UK population F > M (3:1) Peak incidence 30-40 Often familial Significant risk of mortality 50% of individuals unable to work 10 years post onset -anti-CCP is highly specific
What is rheumatoid arthritis? (4)
Autoimmune
HLA-DR4 (70%)
Multisystem inflammatory disease of synovium & adjacent
tissues
Rheumatoid arthritis-associated autoantibodies
- IgM class antibodies (Rheumatoid Factor) to the Fc protein of IgG are not
disease specific
-anti-CCP is highly specific
Clinical features of rheumatoid arthritis (11)
Insidious onset Pain and stiffness of small joints Fatigue and malaise Anaemia Weight loss Muscle weakness and wasting Neurological effects – carpal tunnel syndrome Lymphadenopathy Lung problems - pleural effusion, pleural nodules 15% cases have Sjögren’s syndrome TMJ damage in juvenile RA
Rheumatoid arthritis - joints most commonly affected (10)
Metacarpophalangeal/proximal interphalangeal 90% Metatarsophalangeal 90% Wrist 80% Ankle 80% Knee 80% Shoulder 60% Elbow 50% Hip 50% Cervical spine 40% TMJ 30%
Extra-articular manifestations of rheumatoid arthritis (8)
Weight loss Malaise Fever Lymphadenopathy Rheumatoid nodules Felty’s syndrome Amyloidosis Sjögren’s syndrome
Toothbrush for rheumatoid pts (2)
Electric with small head
-don’t need to move it as much so easier to use
Diagnosis of rheumatoid arthritis (7)
Clinical
Radiographic changes
Anaemia
Raised ESR, CRP
-C-reactive protein is accurate indicator for inflammation (goes up within hours, falls quickly too)
-erythrocyte sedimentation rate goes up slowly but lingers
Anti-CCP positive (80%+)
{Rheumatoid factor positive (80%)}
{ANA positive (30%)} - anti-nucleic antibodies
Management of rheumatoid arthritis - general measures (5)
Education: Empower – self management programmes Exercise: Maintenance of general fitness & maintain muscle bulk Physio/OT: Individual needs identified Surgery: For progressive deformity etc -synovectomy, tenosynovectomy, reconstructive surgery Dietary advice: Weight reduction (3 omega fatty acids)
Management of rheumatoid arthritis: pharmacotherapy (4)
DMARDs (Disease Modifying AntiRheumatic Drugs)
Corticosteroids – IA/IM/PO
Biological agents
– Anti-TNFα “biological agents”
– E.g. etanercept & infliximab
{Symptomatic relief – NSAIDs, COX-2 inhibitors}
NSAIDs side effects (3)
Stomatitis Erythema multiforme -target lesions Gastrointestinal bleeding – Depapillated tongue – Burning tongue – Candidosis
DMARDs and their oral effects (5)
Methotrexate (makes you folate deficient) -oral ulceration Gold (rarely used) -lichenoid reactions Penicillamine (rarely used) -loss of taste perception -lichenoid reactions -severe oral ulcerations Hydroxychloroquine -lichenoid reactions Cyclosporin -gingival hyperplasia
Biologic drugs and oral relevance (4)
Adalimumab (“Humira”)
-TB, oral candidosis, erythema multiforme
Etanercept (“Enbrel”)
-oral candidosis, sarcoid nodules to face, erythema multiforme
Infliximab (“Remicade”)
-histoplasmosis infection, OLP, mandibular osteomyelitis, parotid swelling, ulceration, erythema mutiforme
Rituximab (can be used for severe stubborn pemphigus)
-candidosis, ulceration
Orofacial aspects of rheumatoid arthritis (6)
Access
– Individual with RA less likely to visit dentist
Atlanto-axial joint dislocation
– Physical support – pillows, short appointments
Impaired manual dexterity
– Electric toothbrush more effective than manual
TMJ
– commonly affected but one of last joints
involved
– may lead to open bite
Secondary Sjögrens syndrome
Felty’s syndrome
– RA & splenomegaly and lymphadenopathy
– increased risk of infection (chronic sinusitis)
– oral ulceration
– angular cheilitis
What is lupus erythematosus and what are the forms? (3)
Immunologically mediated condition
2 forms
-DLE
-SLE
Aetiology of lupus erythematosus (4)
Genetic predisposition (more in black people, more in females)
Environmental trigger
T cell dysregulation of B cell activity
Possible defect in clearance of apoptotic cells?
Discoid lupus erythematosus (5)
- where does it affect
- epidemiology
- diagnosis
Affects skin & oral mucosa F>M peak incidence 40 years Oral lesions similar to lichen planus in appearance -but lichen planus usually bilateral Diagnosis based on clinical/biopsy/immunology
Discoid lupus erythematosus - skin features (4)
Scaly, erythematous patches
Atrophic, hypopigmented areas
Occur on exposed surfaces
May be premalignant
DLE - diagnosis (3)
Clinical appearance
Biopsy
Circulating autoantibodies – ANA, dsDNA
may be positive
DLE - management (1)
Treat as for lichen planus
Systemic lupus erythematosus - epidemiology (2)
Age of onset ~ 30 yrs
F:M 8:1
Systemic features of SLE (6)
Malar rash Polyarthritis Photosensitivity Oral lesions Renal/cardiac/haematological/neurological Up to 40% with oral lesions
SLE - oral features (4)
Up to 40% have oral lesions Unilateral or bilateral white patches with central area of erythema or ulceration May involve the palate May be extensive
Diagnosis of SLE (5)
Clinical Immunological: - hypergammaglobulinaemia - hypocomplimentaemia - ANA (DNA + ENA) 90% - RF 30%
Pharmacological management of SLE (5)
NSAIDs Hydroxychloroquine Corticosteroids Cytotoxic drugs – Cyclophosphamide – Azathioprine – (methotrexate) – (mycophenolate mofetil) – (ciclosporin) (Dapsone) (Thalidomide) (Tacrolimus)
Survival rate of SLE (1)
85% 10 years
Prognosis of SLE (3)
Depends on extent of disorder
Death due to renal involvement
Males > females
Lupus-like drug reactions (5)
Carbamazepine Hydralazine Methyldopa Penicillamine Procainamide
What is systemic sclerosis? (4)
Autoimmune disorder Affects mainly females 20 - 50yrs Dense collagen is deposited in the tissues of the body Clinical features include Raynaud’s phenomenon
Types of systemic sclerosis (3)
Localised cutaneous
- limited to the skin on the face, hands and feet
- 10-year survival of 75%
- <10% develop pulmonary arterial hypertension after 10-20yrs
Diffuse cutaneous
- more extensive skin involvement
- may progress to the visceral organs
- 10-year survival of 55%
- death most often from pulmonary, heart & kidney involvement
CREST syndrome
- collection of symptoms seen in limited cutaneous
CREST syndrome (5)
C – Calcinosis R – Raynaud’s phenomenon E – oEsophageal dysfunction S - Sclerodactyly T - Telangiectasia
Orofacial manifestations of systemic sclerosis (12)
Facial skin rigidity Sharp nose Thinning of lips Loss of facial wrinkles Microstomia – Poor access for oral hygiene – ↑ incidence of dental caries – ↑ incidence periodontal disease (abnormal immunoregulation & obliterative microvasculopathy) Hypomobile tongue Dysphagia and xerostomia Periodontal ligament widened on XR Pseudoankylosis of TMJ Speech Eating Deteriorating quality of life
Diagnosis of systemic sclerosis (5)
Difficult Essentially clinical Skin biopsy Scl-70 autoantibodies Periodontal widening on radiograph (30%)
Management of systemic sclerosis (4)
Difficult
Nifedipine
D-penicillamine
Iloprost infusions
Microstomia (5)
Exercise programme – Mouth stretching and oral augmentation Iontophoresis & ultrasound Sectional dentures Implants Surgical commissurotomy - High incidence of wound dehiscence
Sjogrens syndrome epidemiology (4)
Incidence 0.5-2%
Females mainly
15% RA patients have secondary SS
30% SLE patients have secondary SS
Sjogrens syndrome - what is it (3)
Autoimmune exocrinopathy
Primary & Secondary (with another systemic autoimmune condition such as RA/SLE)
Focal lymphocytic infiltration of salivary & lacrimal glands
Aetiology of Sjogrens syndrome (2)
Genetic predisposition -HLA-B8 -HLA-DR3 Viral agents -Herpes viruses (EBV, CMV, HHV-6) -Hepatitis C virus (HCV) -Retroviruses (HRV-5, HTLV-1)
Sjogrens syndrome - pathogenesis (4)
Lymphocytic infiltration of exocrine glands Hypertrophy of ductal epithelium; formation of epimyoepithelial islands Acinar atrophy and fibrosis Probable hyperactivity of B-cells
Subjective symptoms of xerostomia in pts with Sjogren’s syndrome (lots)
Difficulty swallowing / chewing dry food Sensitivity to spicy food Altered salty bitter metallic taste Burning mucosa Lack or diminished taste Salivary gland swelling / pain Cough Voice disturbance Nocturnal discomfort
Sjogren’s syndrome - oral signs (5)
Initially often little change
Oral mucosa - dry, atrophic, wrinkled, ulcerated, increased debris
Tongue - dry, red, lobulated,
loss of papilla
Teeth - increased caries
Salivary glands- firm on palpation - if swollen
Summary of Classification of signs and symptoms of Sjogren’s Syndrome: European Diagnostic Criteria (6)
I Ocular symptoms II Oral symptoms III Ocular signs IV Histopathology V Salivary gland involvement VI Autoantibodies (anti-RO [positive in 70%] and anti-LA [positive in 30%])
European Diagnostic Criteria: rules for classification of primary SS (2)
Presence of any 4 of the 6 items as long
as either item IV or VI positive
Presence of any 3 of III, IV, V, or VI
European Diagnostic Criteria: rules for classification of secondary SS (1)
Well-defined CT disease & presence of item I or II plus any 2 from III, IV and V
Sjogren’s syndrome - non Hodgkin’s lymphoma (3)
- type
- risk
Type - predominantly B-cell (80% marginal zone of MALT type) Risk - 44x normal population - worse in patients with: vasculitis, peripheral neuropathy, anaemia and lymphopenia and chronic glandular swelling
Management of Sjogren’s Syndrome (5)
Palliative - increase lubrication - maintain oral/dental health - review candida status Therapeutic - pilocarpine - immunomodulating agents
What is mixed connective tissue disease? (5)
Clinical signs of a number of A-I diseases Oral lichenoid lesions Trigeminal neuropathy Presence of - ANA (speckled) - RNP autoantibody
Xerostomia versus hyposalivation (3)
Xerostomia is a symptom of oral dryness
May exist with or without hyposalivation
Hyposalivation is an actual decrease in
saliva flow rate
Salivary glands - anatomy
3 major • Parotid -account for 60% of total salivary tissue • Submandibular (30%) • Sublingual (5%) •> 600 minor salivary glands (5%) • Within lips/cheeks & palate
What are acini? (3)
Saliva producing cells Serous - watery secretion Mucous - viscous saliva Parotid glands mainly serous cells Other glands mainly mucous
Salivary duct system (4)
Initial fluid secreted into ductal system Intercalated/striated & secretory ducts Protein & ion content modified within duct Ion exchange in striated ducts
Amount of water in saliva (1)
99.4% water
Organic solids in saliva (a lot)
Protein Gamma globulin Amylase Lysozyme Lactoferrin Glucose Lipids Amino acids
Inorganic solids in saliva (a lot)
Sodium Potassium Calcium Magnesium Chloride Phosphate Iodide Fluoride
Formation of saliva (4)
Salivary gland secretion mainly under autonomic nervous control
Various hormones may modify salivary composition
Increased salivary flow mainly a result of parasympathetic activity
Vasodilation in blood vessels within glands
2 components of saliva (5)
Fluid component includes ions produced by
parasympathetic stimulation
Protein component arising from secretory vesicles in
acini - released in response to sympathetic stimulation
Effects of parasympathetic stimulation stronger & longer
lasting
Parasympathetic stimulation –> copious saliva of low
protein concentration
Sympathetic stimulation –> little saliva but with high
protein concentration
Saliva flow rate (lots)
500mls saliva in 24 hour period
Unstimulated/resting flow rate 0.3ml/minute
Flow rate during sleep –> 0.1 ml/minute
During eating or chewing –> 4.0-5.0 ml/minute
Unstimulated conditions –> 60-65% saliva from
submandibular glands, 20-25% from parotids &
2-5% from sublingual glands
During eating –> parotid contributes 50% saliva
Smell/taste –> increased salivary flow
Anxiety –> increased salivary flow
Saliva flow rate: unstimulated whole saliva (2)
Measured by spitting into gradated container for
15 minutes
<1.5 mls in 15 minutes suggests decreased function
Saliva flow rate: stimulated flow rate (3)
Carlsson-Crittenden cups placed over parotid
orifice
Saliva stimulated by placing 1ml 10% citric acid
on tongue dorsum
<5ml in 5 minutes implies decreased function
Functions of saliva (8)
Lubricant effect
Physical cleanser
Caries control – high HCO3
- buffers acid
Saliva saturation with Ca++ & PO4 prevents
demineralisation
Pellicle formation – salivary proteins form barrier
Antimicrobial – Igs/lysozyme/proteins/lactoferrin
Taste – substances in solution for sense of taste
Digestion of carbohydrates begin (amylase)
Effects of long-standing xerostomia (lots)
Difficulties in oral function & wear of dentures
Increased Frequency of caries (particularly cervical caries)
Acute gingivitis
Dysarthria
Dysphagia
Taste disturbances
Increased susceptibility to oral candidosis
Burning tongue/depapillation of tongue
Dry, sore cracked lips
Salivary gland
enlargement
Factors associated with hyposalivation and/ or xerostomia (6)
Age ~ 30% aged > 65 yrs Anxiety/depression states Dehydration Drugs Radiotherapy/ chemotherapy Diabetes
Drug-related xerostomia - common (lots)
Tricyclics SSRIs Antihistamines Diuretics Sympathomimetics Anticholinergics Antipsychotics Antiparkinsonian Sedatives
Drug-induced xerostomia - must consider other confounding factors: (6)
Age Gender Smoking Psychological factors Other diseases causing hyposalivation Drug-related xerostomia reversible with cessation of drug
Radiation-induced salivary dysfunction (5)
Therapeutic doses of radiation for head & neck
cancer –> permanent reduction in salivary gland
function
Degree of damage dependent on no & volume
of salivary glands exposed
26Gy = threshold below which recovery of 25%
stimulated saliva flow rate can occur
Acute inflammatory reaction –> eventual fibrosis
–> decreased blood flow –> loss of acinar cells
Scant/sticky saliva –> increased caries risk/oral
candidosis/ taste disturbance/ dysphagia etc
Chemotherapy-induced salivary dysfunction (2)
Chemotherapy may also adversely affect
salivary function but the extent & underlying mechanism requires further
clarification
Effect appears reversible over the following year
Factors associated with hyposalivation and/ or xerostomia (9)
Autoimmune/immune-based -Sjogren’s syndrome 1. & 2. -primary biliary cirrhosis -autoimmune thyroiditis -chronic graft versus host disease -sarcoidosis Infections -HIV -hepatisis C -CMV -Epstein Barr virus
Rare factors associated with hyposalivation and/ or xerostomia (4)
Amyloidosis
Haemochromatosis
Wegener’s disease
Salivary gland agenesis
Xerostomia - history (13)
Does your mouth usually feel dry? Does your mouth feel dry when eating? Do you have difficulty swallowing food? Do you require liquids to sip to swallow foods? Do you take water to bed at night because your mouth feels dry at night? Have you noticed difficulty wearing your dentures? Any soreness of your mouth? Dry sore eyes/skin/genital area? Past medical history Anxiety/depression Drug history Social history – smoking/alcohol Family history – ? autoimmune diseases
Xerostomia - clinical examination (lots)
General appearance -access problems Extraoral features -stigmata of connective tissue diseases -salivary gland swellings Intraoral findings -lack of pooling of saliva in floor of mouth -dental mirror sticks to mucosa -food retention -gingival health -caries -candidosis -depapillation/lobulation of tongue
Clinical investigations for xerostomia (3)
Sialometry
Schirmer’s test
Rose Bengal staining
Radiological investigations for xerostomia (6)
USS Sialography Salivary scintigraphy PET scan PET scan MRI CT
Lab-based investigations for xerostomia (lots)
Immunology –ENA/ANA/Rh Factor Haematology –FBC/CRP/ESR SACE Liver function Thyroid function Cryoglobulins Other antibodies -anti-mitochondrial -anti-smooth muscle
Scintigraphy (2)
Technique that investigates glandular function rather than structure Measures the active uptake of a radiolabelled marker such as technetium-99m after IV infusion
Labial gland biopsy (2)
Examination of at least 5 lobules of minor glands ideally Histopathological features supportive of Sjogren’s syndrome -acinar loss -duct dilation -periductal fibrosis -focal lymphocytic infiltrate -focal aggregate of at least 50 lymphocytes --> > 1 focal aggregate per 4mm2 has high specificity
Treatment of xerostomia (9)
Treatment is directed at underlying cause
Prevention is key due to lack of efficacy of
saliva replacement therapy
Assess patients before radio & chemoTx
Manage xerostomia early
Prevent dental complications
Multidisciplinary approach often required
Stimulation of saliva production
Use of saliva substitutes
Oral healthcare to prevent & manage:
- Caries
- Gingivitis
- Candidosis
Management of SS - the multidisciplinary team (6)
Rheumatologist Ophthalmologist Oral Medicine specialist GDP GMP Psychologist
Dental caries prevention strategy - xerostomia (7)
Patient education Diet and nutrition counselling Hygiene control Fluoride Microbial control Rehydration therapy Dental treatment considerations
Diet and nutrition counselling - xerostomia (5)
Avoid soft sticky and liquid diets which promote dental plaque development
Eliminate salty spicy foods - irritant
Non cariogenic foods –suggest sugar substitutes
Limit caffeine – dehydration
Nutrient deficiencies have been described
Hygiene control - xerostomia (5)
Soft electric tooth brush – handle modification Accessories - interdental brush / floss Use disclosing tablets Children’s toothpaste – mint irritant Oranurse toothpaste - bland
Microbial control - xerostomia (5)
High levels lactobacilli reported Chlorhexidine rinse Chlorhexidine varnish Fluoride rinse has some antimicrobial activity Alcohol containing mouthwashes avoided
Dental treatment considerations - xerostomia (6)
3-4 monthly visits Remember fragility of oral tissues Consider fissure sealants Glass ionomer choice for provisional restorations Dentine of exposed roots – dentine bonding resin adhesive systems Amalgam more successful than bonded materials
Dental treatment considerations - prosthetics (5)
Some patients use dentures successfully
Tongue adheres to and dislodges denture
Mucosal irritation and ulceration common
Dentures with reservoirs for artificial saliva
Implants
– Increased comfort and function of prostheses
Management of dry mouth (6)
Oral moisturisers Gustatory and mechanical stimulation of salivation Special toothpastes and mouthwashes Saliva substitutes Lip creams and ointments Systemic therapy
Oral moisturisers (4)
Frequent sips of water Saline solutions Water plus sodium bicarbonate Overuse removes small amounts mucous saliva from oral tissues and increases dry mouth sensation
Gustatory and mechanical stimulants (3)
Acidic stimulation – uncomfortable & increase enamel demineralisation Sugarless chewing gum Lozenges –Salivix® pastilles –SST® tablets
Other stimulatory methods (2)
Acupuncture
– mainly stimulated salivary function affected
– result of neuropeptide release (VIP and calcitonin generelated peptide)
– In recent systematic review inconclusive evidence to confirm efficacy
Electrostimulation
About saliva substitutes (lots)
Carboxymethyl cellulose, mucin, polyacrylic acid Oils & glycerin Majority of patients prefer water Relief insignificant & short lived Unpalatable Impractical to handle Expensive Choice based on personal preference Mucin may have better patient acceptance
Systemic therapy for Sjogrens syndrome (2)
When residual secretory capacity in salivary glands
exists may use cholinergic agents:
Pilocarpine
– Parasympathomimetic with mild β-adrenergic stimulating
properties & non-specific
– RCT
– Increased salivary output is transient dose related and consistent
– No tolerance
– Animal studies show caries reduction
– Lack of correlation between improved salivary flow and QoL scores may be related to coexistence of comorbidities
– Approved for treatment of radiation-induced
xerostomia
– 5mg orally 3 times daily with titration up to 10mg
– From present evidence advisable to prescribe
pilocarpine after completion of radiotherapy for 3 month trial if no contraindications
Adverse effects / contraindications of pilocarpine (4)
• Adverse effects - flushing sweating urinary frequency • Contraindicated in -uncontrolled asthmatics -narrow angle glaucoma -acute iritis
Systemic therapy for Sjogrens syndrome: hydroxychloroquine (4)
– Flow rate increased in 82% patients
– Improved oral discomfort
– 40% decrease in number of oral infections
– Few adverse effects
Systemic therapy for Sjogren’s syndrome: corticosteroid irrigation parotid gland (3)
– Increased flow rate
– Relief of symptoms
– Risk of infection and pain
