Mucocutaneous Diseases

Terms used to describe skin / oral lesions

Lichen Planus
Aetiology: not clear yet
Viral aetiology (HPV-6, 11, 16, 18; HHV 6)
Autoimmune disease
Autocytotoxic CD8+ T cells trigger the apoptosis of oral epithelial cells
Sites affected in the body:
Skin
Scalp
Mucosa
Nails
Associated Diseases: ……may be coincidental
Hepatitis C virus
HPV and HHV
Primary biliary cirrhosis
Autoimmune chronic active hepatitis
Exacerbation have been linked to psychological stress and anxiety
Myasthenia gravis
Ulcerative colitis

Skin lesions:
Pink papules overlaid by fine white striations (Wickham’s striations).
Itchy and bilateral
Last for 9-12 months, but subjected to recurrency
Mainly on
front surfaces of wrists,
genitalia
abdomen
lumbar region

Kobner phenomenon

Bilateral, itchy papules with scaly surface

Nail lesions:
Vertical grooving and destruction of the nails (nails dystrophy).

Scalp lesions (lichen planopilaris)
Patches of alopecia in few patients, usually in females

Oral Lichen Planus
Non-erosive
Papular
Linear
Reticular
Annular
Plaque type
Erosive
Atrophic
Bullous
Ulcerative

Non-erosive LP.
Notice the bilateral Wickham’s striations
Asymptomatic but rough mucosa

Erosive LP.
White striations on erythematous or ulcerative base
Painful, specially with hot drink or spicy food.

Non-erosive LP.
Plaque type

Desquamative gingivitis on attached gingiva
Is a clinical rather than a pathological entity

Ulcers

Oral Lichen Planus
Diagnosis:
Clinical picture
Incisional biopsy
DIF & IIF to exclude other diseases
Prognosis:
Oral lesions are more reluctant than skin lesions
Malignant transformation rate (?) is < 1%, hence repeated biopsy may be needed.
Fibrinogen at BMZ (non-specific)

Histopathology of LP.
Epithelial hyperplasia or atrophy
Saw teeth appearance of rete ridges
Liquifaction degeneration of the basement membrane
Dense band of lyphocytic infiltration in the lamina propria
Hyaline (Civatte) bodies

Treatment of OLP
Aims of treatment
Resolution of oral painful symptoms
Resolution of oral mucosal lesions
Reducing the risk of oral cancer
Maintenance of good oral hygiene
Prolongation of symptom-free intervals
Concerns
No treatment is curative
Local and systemic adverse effects of therapy
Recurrence after treatment withdrawal

Treatment of OLP.
Skin lesions
Steroid cream
Systemic steroids
Oral lesions: Minor erosive type
Remove trauma
Antiseptic mouth wash
Local steroids
Betamethasone valerate aerosol,
Beclomethasone dipropionate,
0.1% triamcinolone acetonide in adhesoive paste,
Beclometasone dipropionate
0.05% Flucinonide ointment in an orabase paste
0.025% clobetasol propionate
Meconazole oral gel or chlorhexidine mouth wash

Treatment of OLP.
Oral lesions: Major erosive type
High concentration steroid mouth wash
Triamcinolone intra-lesional injections (0.2 to 0.4 ml of 10 mg/mL)
Topical tacrolimus
Systemic steroids: 40-80 mg/day prednisolone for <2 weeks
Azathioprine (50 to 100 mg/day)
Levamisole (150 mg/day)

?Potentially malignant condition
0.4%-2% per five years observation

OLP – Patient’s follow up
Follow up:
Every month till resolution of symptoms
Every 6-12 month afterward
The risk of oral cancer in patients with OLP may be reduced by means of the following:
Elimination of smoking and alcohol consumption
Effective treatment of atrophic, erosive, and plaque oral lichen planus lesions
Consumption of a nutritious diet including fresh fruit and vegetables
Elimination of C albicans super-infection
Regular clinical examination and repeat biopsy as required. Oral brush biopsy can be used to limit the number of scalpel biopsies

Lichenoid eruption
The expression or unmasking of the lichen planus antigen may be induced by:
Drugs (lichenoid drug reaction)
Contact allergens in dental restorative materials or toothpastes (contact hypersensitivity reaction)
Mechanical trauma (Koebner phenomenon)
Viral infection
Other unidentified agents

Lichenoid eruption
Precipitated by:
Non-steroidal anti-inflammatory
Antihypertensive drugs (beta-blockers, ACE inhibitors)
Oral hypoglycaemic agents (e.g. sulphonylurea)
Lithium
Gold injections
Antimalarial drugs
Some antibiotics
Chronic graft versus host disease
Amalgam
Coposite resine
Tooth paste (cinnamon flavored)
Management: remove the cause
Amalgam filling

Oral lichenoid lesions may be triggered by mechanical trauma (Koebner phenomenon) due to
Calculus deposits
Sharp teeth
Rough surfaces of dental restorations or prostheses
Cheek or tongue biting
Oral surgical procedures

Pemphigus
Auto-immune disease
The patients usually between 40-60 years old
Racial difference in incidence
Most of the patients have oral lesions which may be the initial presentation.
The prognosis used to be very poor.

Pemphigus – Clinical picture
Widespread fragile, clear fluid-filled, bullae affecting skin and mucosae
Large irregular ulcerations
Positive Nikolski sign.

Pemphigus
Oral lesions may be associated with other mucosal lesions
Bullae are more fragile
Spreading and enlarging ulcers
Clinical types
Pemphigus vulgaris
Pemphigus vegitans
Pemphigus erythematosus
Pemphigus foliaciois
Paraneoplastic pemphigus

Pemphigus - Diagnosis
Positive Nikolski sign on clinical examination
Incisional biopsy: intra-epithelial vesicle or bulla
Smear from bulla fluid to see Tzank cells

Pemphigus - Diagnosis
DIF: IgG auto-antibodies (also IgM and C3) on the intercellular substances (against the adhesion molecule desmoglein-3 and ? 1)
IIF (correlate with the severity of the disease): +ve IgG auto-antibodies in 90% of patients
ELISA: anti-desmoglien antibodies in serum

Direct & Indirect IF

Pemphigus - Treatment
Multidisplinary
Initial treatment with high doses of steroid (100mg prednisolone / day)
Patients are maintained on steroids and/or steroid sparing drugs (e.g. azathioprine)
High-concentration steroid mouth wash.
Antifungal therapy may be needed.
Dental considerations

Paraneoplastic pemphigus
http://emedicine.medscape.com/article/1064452-overview
Anhalt GJ, et al. Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med. Dec 20 1990;323(25):1729-35.
Autoimmune disease
Anti-plakin antibodies
90% mortality rate
Pemphigus + neoplasm commonly lymphoproliferative neoplasm (most commonly non-Hodgkin’s lymphoma)
No race or gender predilection
Age >60 yrs.
The only type affects epithelia other than squamous !!!

Mucosal lesions
Oral
Erosions and mucositis
Resembling SJS
Genital
Nasal: epistaxis
Skin lesions
Diffuse erythema
Vesiculobullous
Papules
Scaly plaques
Exfoliative erythroderma
Erosions
Ulcerations
Positive Nikolsky sign

Pemphigoid
Auto-immune disease
No racial predominance
Two basic clinical types:
Bullous (generalized) pemhigoid
Mucousal (cicatricial) pemhigoid

Generalized (bullous) pemphigoid
Patients > 60 yrs. Old
No racial or gender predominance
Skin:
Starts as skin rash
tense, blood-tenged, bullae mainly on limps
Oral:
In about 20% of patients
Bullae may remain intact for some time

Mucosal (cicatricial) pemphigoid
Patients age: 50-70 yrs.
M/F = ~ 1/4
Oral lesions
Almost always present, and mainly in the soft palate
Desquamative gingivitis is the most common lesion
Other mucosae may be affected
Conjunctiva
Nasal
Genital
Starts as bullae or erosions
Heals by scaring
Opacification and blindness

Mucosal pemphigoid - Diagnosis
Incisional biopsy: sub-epithelial bulla
DIF: on perilesional mucosa
+ve in 75% of patients.
Auto-antibodies (mainly IgG) in a linear distribution at the basement membrane zone. IgA and complement may be detected
IIF
Chemically separated normal human epithelium as substrate
Salt-split human skin
IgG in 20% of patients
Low titre

Pemphigoid – Treatment
This disorder is extremely difficult to treat. Even with optimum control, blisters may continue to develop in some patients
Generalized pemphigoid
Systemic steroids and / or steroid sparing immunosuppressive agents.
Topical steroid may be used for oral lesions.
Mucosal pemphigoid
Perforate the bullae if necessary
Topical steroids: e.g.
Beclamethasone spray
Triamcinolone in orabase
Antiseptic mouth wash.
Multidisplinary management e.g. ophthalmologist, dermatologist and internest opinion is mandatory
High-dose intravenous immune globulin in refractory cases

Oral Blood Blisters (angina bullosa haemorrhagica)
Unknown etiology
Sudden development of blood-filled blister on the oral mucosa
Possibility of airway obstruction
Blood clotting mechanism is normal
Platelets count is normal
Management:
Perforating the blister
No known preventive measures

Erythema multiforme
Precipitating factors: Type IV hypersensitivity reaction
Viral infections (e.g herpes simplex, mycoplasma)
Bacterial infections
Internal malignancy or its treatment with radiotherapy
Pregnancy
Drugs (e.g. sulphonamides, penicillins, phenylbutazone, barbiturates)
Excessive exposure to UV light
Unknown factors
More in males
More in young people

Erythema multiforme – Clinical features
Oral mucosal lesions:
Sudden development of widespread erosions
Crusting and bleeding lip lesions
Self-limiting
Recurrent
Skin lesions:
Target appearance
Symmetrical

EM
General features:
Cervical lymphadenitis
Pyrexia
Subside in 10 days
Subjected to recurrence
> in young patients

EM
Diagnosis and work-out
Clinical picture (lip lesions, target lesions and recurrence)
CBC: leukocytosis
Electrolytes
BUN
ESR: elevated
Liver function test: mildly elevated liver transaminase
Culture (sputum, erosion, blood) in severe cases
Biopsy: non-specific (to rule out differential diagnosis)
Sub-epidermal split
Lymphocytic infiltration
Hydropic changes in basal cells
Epithelial necrosis

EM
Treatment - Management
Remove the cause if possible
Treat infections
Fluid intake and soft diet; possibly IV line is needed
Oral antihistamines
Antiseptic mouth wash
Topical steroids
?? Systemic steroids
Acyclovir as a prophylaxis
Consultations:
Dermatologist
Ophthalmologist
Internal medicine specialist

Steven-Johnson Syndrome
Toxic epidermal necrosis
Mortality
5% SJS
40% TEN
Management
Fluid replacement
Sterile techniques
Wound care
Medical consultation
Systemic corticosteroid therapy is controversial
Cyclosporin therapy
Skin
Mucosae
Eyes

Lupus Erythematosus
Autoimmune disease
Two main clinical divisions:
Discoid lupus erythematosus (DLE)
Systemic lupus erythematosus (SLE)
M:F = 9:1 (18-65 years; peak 25-45 years)
DLE & SLE may represent different ends of the spectrum of the disease activity
SLE may be precipitated by some drugs e.g. Hydralazine (lupoid reaction).
Oral mucosal lesions in 25-75% of the cases

Lupus Erythematosus – Clinical Features
SLE:
Skin: erythematous itchy rash (butter fly appearance)
Systemic manifestations: arthritis, kidney, heart, lung, brain, depression, alopecia, Raynouds phenomena
Mucosa: superficial erosions and erythematous patches
SLE is similar to DLE
Oral symptoms:
Dryness
Soreness
Burning

DLE: mainly cutaneous lesions
Skin: resemble SLE, symmetrical, heals with scaring
Mucosa: superficial erosions and erythematous patches with peripheral white striations
DD: Oral lichen planus

Lupus Erythematosus
Diagnosis:
IMF: antinuclear antibodies (ANA) +ve in 90% of patients.
DMF
Biopsy and histopathological examination: resembles OLP

Prognosis
No cure
Renal disease is the main morbidity and mortality
Thrombocytopenia and hemolytic anemia in 85% of patients
Oral lesions are considered potentially malignant
Treatment: antifungal agents may be required for oral lesions
SLE:
High doses systemic steroids + steroid sparing drugs.
High concentration steroid mouth wash
DLE:
Topical steroids to reduce symptoms
Antimalarial drug (chloroquine) may be useful (? Retinopathy)
? Potentially malignant condition