Management of Vesiculo-Bullous

Diseases

Dr. Tamar Kartin- Gabbay

Department of oral medicine
May 2009
 Vesiculoulcerative diseases
— Pemphigus •Immune mediated diseases
— Pemphigoid •Oral ulcerations w/wo skin
lesions
— Lichen planus •Oral discomfort
— Erythema multiforme •Limited nutrition and
hydration
•Limited Oral hygiene

Local control of the Systemic control of the

disease disease
Goals of treatment
1. Control of disease lesions
2. Patient nutrition and hydration
3. Relief oral discomfort
4. Oral hygiene
5. Prevention and treatment of secondary
infection
Corticosteroids
Play a central role in treatment of vesiculoerosive lesions.

Anti Inflammatory, Immunosupressive role.

Glucocorticoids receptors,
Glucocorticoid responsive genes,
Release of anti inflammatory molecules –
lipocortin -1. (inhibition of prostaglandins
formation).
Suppresion of antigen – driven T cell
proliferation.

Increase use of topical corticosteroids.

M.A.Gonzalez- Moles, C.Scully J Dent Res 84(4) 294-301, 2005.

Topical treatment for oral lesions
Table 1. Candidate Oral Erosive Lesions for Treatment with Topical
Corticosteroids

• Recurrent aphthous ulcers

• Oral manifestations of Behçet's disease, Reiter's syndrome, acute
vulvar ulcer, MAGIC syndrome. PFAPA syndrome, ulcerative colitis,
Crohn's disease, Melkersson-Rosenthal syndrome, Sweet's
syndrome, among others
• Drug-induced ulcerations mediated by an immune mechanism
• Lichen planus
• Cicatricial pemphigoid
• Mucous membrane pemphigoid
• Bullous pemphigoid a
• Erythema multiforme
• Linear IgA dermatosis
• Pemphigus vulgaris a

a Topical corticosteroids should be applied only in cases that onset

with exclusively oral lesions and low titers of circulating antibodies.
Weekly clinical follow-up and monthly measurement of circulating
antibody rate are mandatory.

M.A.Gonzalez- Moles, C.Scully J Dent Res 84(4) 294-301, 2005.

Pemphigus
 Treatment
Mortality rates before steroids use - 30%
Electrolyte loss and sepsis

Current mortality - 6% due to effects of immunosupresive

therapy

morbidity
Therapies for Pemphigus

Drug trial for Pemphigus are difficult.

There is great variability in severity and
response to treatment between patients.
 Therapies for Pemphigus

The aim of treatment is to induce a

complete remission with minimum side-
effects.
Main treatment of choice – Systemic steroids:
Prednisone 1.0-1.5 mg/kg (tapered to maximal
effect with minimal dosage).
Treatment is tailored to the needs of individual
patient.
 Assessment and management
before treatment
• E.N.T assessment.
• Ophthalmological assessment.
• Tuberculin test & chest X-ray.
• CBC + differential.
• Serum urea, Createnine, Electrolytes.
• Liver functions.
• Fasting glucose test .
• (Drug induced pemphigus must be excluded on every
new patient)
 Treatment phases

Control Disease activity must be brought

under control. Cessation of
phase
formation of new lesions.
Commencement of healing of
established lesions (weeks).
Consolidation
Intensity of treatment maintained,
phase until about 80% of established
lesions have been healed.

Therapy reduced to lower levels

Maintenance
need to prevent deterioration
phase
.
Lancet 2005; 366:61-73
 Control Phase
Corticosteroids are the main therapy
Great importance of treating the disease intensely.
Pemphigus responds rapidly to treatment if the right
dose of medication is used.

Start with topical steroids à systemic 20-40mg/d

à 70-90mg/d à >120 mg\d ( some cases
>240mg\d).
 Control phase:

Weight gain Risk of infections

Moon face Osteoporosis*
Side Insomnia
Depression
effects Cataract
Anxiety Swelling
Confusion Dry mouth
Peptic ulcers DM

•Adequate vit D and calcium supplements should

be taken. Bisphosphonate prophylaxis.
Clinical and laboratory follow up during
systemic steroid therapy
• Logarithmic reduction of dosage
• Low Na++ intake regimen
• Continuous monitoring of blood
pressure and vital signs
• Blood glucose
 Control phase, cont.

• Plasmapheresis 3/w –physically remove

pathogenic intercellular antibodies.
• Most effective if coupled with a cytotoxic drug.
• Azathyoprine or Cyclophosphamide
(prevent Ab rebound)

• IVIg –Intravenous Immunoglobulin

Catabolism of Immunoglobulin, particularly Pemphigus
Ab.

2g\Kg over 3-5 d à works within 1-2w repeat every

2-4w.
• Most effective if coupled with a cytotoxic drug.
 Consolidation phase:

• Maintained therapy until most (80%)

lesions have healed.
• Consider adjuvant therapy (in debate)
• Weeks
 Maintenance phase
• Begins once most lesions have healed.
• Doses of medication gradually tapered concentration
needed to suppress the disease.
• Final goal – discontinue all systemic drugs
(most patients)
(Herbst et al, J am Acad Dermatol. 2000)

• Dose reduction – too rapidly increases the chances of

flare up.
• One approach is to reduce prednisone dose a quarter
every one/two weeks
• Convert to alternate day schedule.
 Adjuvant therapies
With corticosteroids, Not instead

Immunosuppressive Anti-inflammatory
drugs:
drugs:
• Dapsone
• Cyclophosphamide • Anti malarias
• Cyclosporin Drugs
• Azathioprine Antibiotics:
• Methotrexate
• Tetracycline
• Mycophenolate
• Minocycline
mofetil
Not enough data, Expert opinion
 Pemphigus treatment in Pemphigus patient
present many clinical dilemmas.

• Systemic steroids - Efficacy Vs side effects

• Systemic steroids Vs Adjuvant therapies

• Systemic steroids Vs Topical steroids

• “regular” topical steroids Vs Intralesional Injections

(no protocol)

• Dental treatment à Dentures Vs Implants

Adjuvant therapy -Immunosuppressive

• Azathioprine (IMURAN) 1-3mg/kg/day

• Purine synthesis inhibitor
• Steroid sparing drug e.g. allows maintenance
with lower doses of steroids
• 12% of patients develop bone marrow
suppression, pancytopenia, aplastic anemia
 Future therapy - Rituximab
• Chimeric monoclonal Ab against CD20 B
cells.
• Deplete mature B cell
• Usually effective (even severe cases)
• Side effects – severe infections

(Salopek et al, J am Acad Dermatol, 2002)

• 11 refractory pemphigus
patients
• Combination treatment –
Rituximab (two cycles for
1/w*3)
and IVIg (1 on fourth week)
• 9 of 11 had almost full
remission for 31.1 months in
average

(Ahmed et al, N engl J med. 2006 ) –

 Topical treatment for oral lesions

Lack of evidence for the efficacy of TC, in oral medicine.

Information derived from Dermatology.
The medical history may warrants systemic corticosteroids.

Tc of appropiate potency should be used

Protocols for TC USE Lowest concentration and frequency
Right vehicle
 Topical treatment for oral lesions

Drug Vehicle - adherent vehicles , aqueous solutions most

widely used.
Orabase – adhesive paste widely used.
Cream - less scientific evidence for there use.
Ointments do not have adhesive properties.

Application of TCs – apply on small target after meal do not

eat/ drink at least 30 min.
M.A.Gonzalez- Moles, C.Scully J Dent Res 84(4) 294-301, 2005
Topical treatment for oral lesions
1. cream/ oint. clobetasole propionate 0.05% . (Dermovate®)
apply 1-2 times daily.
2. Triamcinolone (Oracort E®,Sterocort®) 0.1%-0.5%, -may be
used with mouth guard.
3. Mouth rinse with corticosteroids: Dexamethasone elixir 0.04%
(0.5 mg/ml), cyclosporine rinses 100 mg/ml.
4. Intra lesional injections (Triamcinolone acetonide)
most effective for topical treatment.
Side effects –Local and temporary atrophy of skin.
(Jean-Claude, Lancet. 2005)
 Topical treatment for oral lesions

Mild potency steroid

Moderate potency steroids –Triamcinolone acetonide
High potency steroids – Clobetasol propionate
Topical treatment for oral lesions
secondary infection and supportive
treatment
1. Secondary infection
• Fungal infection
• Long standing ulcers
Less common: bacterial infection
purulent lesions & acute lymphadenopathy make
antibiotic coverage necessary
2. Pain – analgesia (Lignocaine 2% mouth wash)
3. Nutrition and hydration
Pemphigoid
General
— Refer to ophthalmologist & dermatologist

— Avoid trauma (avoid hard foods & habits)

— Improve oral hygiene

— Add antimycotics- miconazole gel and/or CHX
Pemphigoid treatment
— Localized disease- topical steroids +systemic
anti –inflammatory.
— Severe cases systemic steroids +
immunosuppresive – if remission is achieved
Prednisone is tapered & disontinued.
— Rituximab

eMedicine Dermatology
Topical treatment for oral lesions
1. cream/ oint. clobetasole propionate 0.05% . (Dermovate®)
apply 1-2 times daily.
2. Triamcinolone (Oracort E®,Sterocort®) 0.1%-0.5%, -may be
used with mouth guard.
3. Mouth rinse with corticosteroids: Dexamethasone elixir 0.04%
(0.5 mg/ml), cyclosporine rinses 100 mg/ml.
4. Intra lesional injections (Triamcinolone acetonide)
most effective for topical treatment.
Side effects –Local and temporary atrophy of skin.
(Jean-Claude, Lancet. 2005)
 Adjuvant therapies
With corticosteroids, Not instead

Anti-inflammatory
Immunosuppressive
drugs:
drugs: • Corticosteroids
• Cyclophosphamide • Dapsone
• Cyclosporin
Antibiotics:
• Azathioprine
• Tetracycline
• Methotrexate
• Minocycline
• Mycophenolate
mofetil Not enough data, Expert opinion
Systemic treatment

• Tetracyclines, Nicotinamide
Anti-collagenase activity, suppression of leukocyte
chemotaxis, inhibition of lymphocyte blast
transformation.
Tetracyclines, Nicotinamide – 0.5-2 mg.
Systemic treatment – intravenous
immunoglobulin therapy

Indications:
üA failure of conventional therapy
üPrednisone 60 mg/d for 6 weeks didn’t produce
control of disease
üAdverse effect of conventional treatment
üRapid progressive disease

Dose: 2g/kg/ cycle

A cycle consists of total dose divided into 3 doses

Frequency: 1 cycle/3-4 weeks, then the intervals are

increased
Topical treatment

Night guard with topical treatment

Erythema multiforme
— A self limiting disease in 2-6 weeks, necessity of
treatment is controversial
— Supportive treatment:
— Hydration
— Nutrition supplements
— Analgesia (lignocaine 3%)
— Oral hygiene (chlorhexidine 0.05%)

— Elimination of trigger (if known)

— Systemic steroids: (topical in minor EM)
— Prednisolone 0.5-1 mg/kg/d tapered for 7-10 d
(controversial).
HAEM:

• acyclovir for 5 days from first lesion

• Prophylaxis : acyclovir 400mg x4/d for 6 m
Valcylovir 500 mgx2/d for 6 m

Helpful only before eruption of lesions.

Consultations
Dermatologist – For diagnosis and management.
Internal Medicine specialist – For evaluation of the
underlying cause.
Early consultation with an ophthalmologist – For
ocular involvement.

eMedicine Dermatology
Lichen planus
Management of Oral Lichen
Planus
Good Oral hygiene is essential (erythematous and

erosive gingival lesions).

Avoid mechanical trauma.

Stress, anxiety relief.

Lichenoid contact reactions: replacement of dental

materials in contact with lesions.

Lichenoid lesions drug associated, replace drug if

possible.
Topical treatment for oral lesions

— Asymptomatic reticular form – follow up.

— Symptomatic ulcerative:

— Topical steroids
— Second line: retinoids. (Vit. A derivates)
 Systemic treatment
• Systemic steroids:
Not more effective than topical Corticosteroids.
• Use when :
Unresponsive to topical treatment,
Widespread oral LP with skin, genital,
esophageal or scalp involvement
Topical treatment for oral
lesions
— Retinoids
— Tretinoin 0.05%- Retavit©, Retin A©, Airol© Oint -
Topical use.
— Clinical results show remission after a short time of
treatment.
— Systemic use is less common as primary treatment
due to side effects and short periods of remission.
— Retinoids treatment is an adjunctive treatment.
 Systemic treatment
• Systemic steroids:
It is not more effective than topical
Corticosteroids.
• Use when :
Unresponsive to topical treatment,
Widespread oral LP with skin, genital,
esophageal or scalp involvement
. Lodi G, Scully C, Carrozzo M et al. Current
controversies in oral lichen planus : Report of
an international consensus meeting. Part 2.
Clinical management and malignant
transformation. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2005; 100:164-
100:164-178.
Systemic treatment
• Daily dose of Prednisone in range of 40-80 mg usually sufficient
to achieve a response.
• Due to toxicity use when necessary at the lowest dose possible,
and for the shortest duration of time. (Or for brief periods of
time 5-7 days and stop abruptly, or reduce drug by 5-10 mg day
over 2-4 week period).
• If possible to tolerate by patient alternate day administration of
same total dose may minimize adverse effects.
• Start with Topical treatment.
— Immunomudalatory treatment – not common

(detailed before).
— Candida albicans is present in 37% of OLP

lesionsà antifungal treatment

Thank you