Patients with chronic multiple oral lesions, continuously present, for weeks to months are frequently misdiagnosed since their lesions are often confused with recurring oral mucosal disorders such as RAS and recrudescent HSV. The clinician can avoid misdiagnosis by carefully questioning the patient on the initial visit regarding the natural history of the lesions.

1. In the name of God
pemphigus/pemphigoid
student name: Maryam Adham Haghighipour
Guilan university of medical sciences
(Iran)

2. THE PATIENT WITH CHRONIC
MULTIPLE ULCERS:
Patients with chronic multiple oral lesions, continuously present, for
weeks to months are frequently misdiagnosed since their lesions are
often confused with recurring oral mucosal disorders such as RAS and
recrudescent HSV. The clinician can avoid misdiagnosis by carefully
questioning the patient on the initial visit regarding the natural history of
the lesions. In recurring disorders such as severe RAS, the patient may
experience continual new episodes of ulceration of the oral mucosa, but
individual lesions heal and new ones form. In the category of disease
described in this section, the same lesions are present for weeks to
months often expanding in size The major diseases in this group are PV,
pemphigus vegetans, BP (bullous pemphigoid), MMP, linear IgA disease
(LAD), and erosive lichen planus.

3. pemphigus:
 Pemphigus includes a group of autoimmune, potentially life-threatening diseases
that cause blisters and erosions of the skin and mucous membranes
 Desmoglein1 and Desmoglein3
 reactive B and T cells
 a loss of cell-to-cell adhesion
 The major variants of pemphigus:
1)PV: Pemphigus vegetans
• 2)pemphigus foliaceus: pemphigus erythematosus
• 3)PNPP
• 4)IgA pemphigus:subcorneal pustular dermatosis and intraepithelial neutrophilic
dermatosis
 “fogo selvagem”
 D-penicillamine and captopril

4. Different type of it:
• Pemphigus Vulgaris
• Pemphigus Foliaceous
• Pemphigus Eryhematousus
• Pemphigus vegetan
• Neonatal pemphigus
• Drug-induced pemphigus
• Paraneoplastic Pemphigus
• IgA pemphigus
• Pemphigus Herpetiformis
• Endemic Pemphigus Foliaceous

5. Pemphigus Vulgaris:
• Etiology and
Pathogenesis:
- the most common form
- HLA DRB*0402 and
HLADQB*0503
- Thymoma,Other
autoimmune disorders,
neoplasms such as
lymphoma.
- Death occurs most
frequently in elderly
patients and in patients
requiring high doses of
corticosteroids
Clinical
Manifestations:
-The classic lesion of
PV
-the Nikolsky sign
-Some patients with
pemphigus develop
acute fulminating
disease,but, in most
cases, the disease
develops more slowly.
Oral Finding:
-shallow irregular
erosions and ulcers
because the bullae
rapidly break
-the lesions start on the
buccal mucosa,palatal
mucosa and gingiva
-oral lesions for months
before the skin lesions
appear.
-misdiagnosed as HSV
infection or candidiasis
-patients whose disease
remains confined to the
oral mucosa.

6. • Differential Diagnosis:
- acute viral infections or EM
- RAS
- desquamative gingivitis.
Management:
- early diagnosis
- high doses of systemic corticosteroids, 1–2
mg/kg/d.
- adjuvant therapy :immunosuppressive drugs
such as mycophenolate mofetil, azathioprine,
cyclophosphamide,cyclophosphamide pulse
therapy.
- Prednisone
- the clinician should weigh the potential benefits
of adding adjuvant therapy against the risks
oflong-term immunosuppression, such as blood
dyscrasias and an increased risk of malignancy.
- Recalcitrant cases:rituximab and intravenous
immunoglobulins.
- Dapson

7. Paraneoplastic pemphigus(PNPP)
- with an underlying neoplasm, most
frequently non-Hodgkin lymphoma,
chronic lymphocytic leukemia, or
thymoma.
- Castleman disease and Waldenström
Macroglobulinemi
- the variable skin findings, namely,
pemphigus, pemphigoid, EM-like, graft-
vs-host disease-like and lichen planus-
like

8. • Clinical Findings:
- severe blistering and erosions
- oral and conjunctival lesions
are both common
- In severe cases, the lesions
may mimic TEN
- continue to progress over
weeks to months.
- Progressive pulmonary
involvement occurs in up to
40% of patients
Oral Manifestations:
- Oral ulcers and erythema
- The lesions are frequently
inflamed and necrotic,
with large erosions covering the
lips, tongue, and soft
Palate.
- Hemorrhagic crusts on the lips

9. • Management:
PNPP secondary to localized tumors such as
• Castleman:surgical removal of the
• tumor.
 PNPP resulting from lymphoma:
have a poor prognosis and usually die within two
yearscombination of prednisone, immunosuppressive
• drug therapy
 Rituximab and intravenous immunoglobulins
 High-potency topical steroid therapy, topical tacrolimus,
and intralesional Steroid injection

10. Pemphigus Vegetans:
- 1%–2% of pemphigus
- Two forms of pemphigus vegetans are recognized:
1) Neumann
2) Hallopeau
• Oral Findings:
• Oral lesions are common in both forms of
pemphigus vegetans and may be the initial sign of
disease. Gingival lesions may be lace-like ulcers
with a purulent surface on a red base or have a
granular or cobblestone appearance. Oral lesions
that are associated with inflammatory bowel
disease and resemble pemphigus vegetans
clinically are referred to as pyostomatitis
vegetans.
• Management:
• the same as that for PV.

11. Pemphigoid:
• Subepithelial Bullous Dermatoses
Bullous Pemphigoid(BP)
Mucous Membrane Pemphigoid(MMP)
LAD and Chronic Bullous Disease of Childhood
Epidermolysis Bullosa Acquista(EBA)

12. 1.Bullous Pemphigoid(BP):
Etiology and Pathogenesis:
• Is the most common of the subepithelial blistering diseases
• Age : 60<
• Self-limited
• BP has occasionally been reported in conjunction with oder
diseases:multiple sclerosis,malignancy,drug therapy(diuretics)
• BP is an autoimmune disease
• Binding of antibody to antigen→activates leukocytes
and complement→localized damage to the basement
membrane→vesicle formation in the subepithelial region

13. Clinical Mnifestations:
• Tense blister on an inflamed base
accompanied by urticarial plaques
• Chiefly involve the
scalp,abdomen,extremities,axilla and
groin
• Pruritus
• Experience one episode or recurrent
bouts of lesions
• Unlike pemphigus,BP is rarely life
threatening
• Death from sepsis or cardiovascular
disease secondary to long-term steroid
use has been reported to brhigh in group
of sick elderly atients

14. Oral Finding:
• In10-20% of patients
• The oral lesions of BP are
smaller,form more slowly, and are
less painful than those seen in PV
is not present
• Desquamative gingivitis
• Generalized areas of
edema,inflammation,desquamati
on with localized areas of discrete
vesicle formation
• The oral lesions are
indistinguishable from oral
lesions of MMP(early remission
of BP)
Differential Diagnosis:
-Erosive form of lichen planus→white
wickham striae
-Pemphigus Vulgaris(PV)→has more
extensive erosion of mucosa as well
as skin involvment
-Other subepiithelial bullous
dermatoses→similar to MMP
Laboratory Findings:
DIF study
IIF study
Salt split skin
ELISA

15. Management:
• Localized oral lesions→high-potency topical
steroids(clobetasol,betamethasone)
• More extensive disease→systemic corticosteroids alone
or combined with immunosuppressive
drugs(azathioprine,cyclophosphamide,mycpphenolate,
rituximab)
• Moderate levels of disease →minimize the use of
systemic steroids by the use of dapsone or
tetracycline,doxycycline,or minocycline,which may be
combined with niacinamide

16. 2.Mucous Membrane Pemphigoid
(MMP,Cicatricial Pemphigoid)
Etiology and Pathogenesis:
• Chronic autoimmune subepithelial disease
• Age: 50<
• Mucosal blistering,ulceration,subsequent scarring in some
organs
• Occurs twice as frequently in women
• Clinicians should consider a referral to rule out a possible
underlying malignancy in newly diagnosed MMP patients
• Drugs such a clonidine,D-penicillamine,L-DOPA have been
reported as triggers for MMP

17. Clinical Manifestation:
• Oral mucosa is involved in more than80% of cases
• Conjunctiva: second most common site of involvement→
Scarring and adhesions developing between the bulbar and palpebral
conjunctiva(symblepharon)
• Corneal damage→progressive scarring→blindness(15%)
• Genital mucosa
• Laryngeal involvment→pain,hoarseness,difficulty in
breathing→death due to asphyxiation
• Esophageal involvment→dysphagia→debilitation and death
• Skin lesions→head and neck(20-30%)
• Increased of HLA DQB0301in widespread lesions

18. Oral Findings:
• Oral lesions in90% of patients
• Desquamative gingivitis: the most common
manifestation of the disease→bright red
• Desquamative gingivitis resemble the lesions of
erosive lichen planus and PV →biopsy , DIF
• Lesions may present as intact vesicles of the
gingival or other mucosal surfaces(nonspecific-
appearing erythema and erosions)
• Unlike ocular pemphigoid,ora MMPrarely results
in scarring
Laboratory Finding:
Biopsy for routine studies
Biopsy for DIF+
IIF+( 10%)

19. Management:
Lesions are confined to the oral mucosa→use of
systemic corticosteroids should only be considered
for short periods for severe outbreaks until steroid-
sparing therapy can be instituted
Mild oral disease →topical and intralesional steroids
Desquamative gingivitis → topical steroids in a soft
dental splint
(closely monitor the patient for side effects such as
candidiasis and effects of systemic absorption)
Tetracycline,doxycycline,minocycline
Severe oral lesions,conjunctival or laryngeal
involvment →dapson is the next choice before
considering long-term systemic
steroids,immunosuppressive drug therapy or
retuximab
(dapson hypersensitivity syndrome)
→fever,lymphadenopathy,skineruptions,oc
casional liver involvement)
Resistant to dapson →combination of
systemic corticosteroids and
immunosuppressive
drugs(cyclophosphamide)
High-dose intravenous immunoglobulin
therapy and retuximab →adjuvant therapy

20. 3.LAD and Chronic Bullous Disease of Childhood:
Etiology and Pathogenesis:
• LAD : in children below the age of 10(CBDC)
in adult older than60
• Clinical manifestation may resemble either dermatits
herpetiformis ore pemphigoid
• Cause : unknown,drug-induced(vancomycin,amiodarone,NSAIDs)
, associated with systemic diseases(hematologic
malignancies,ulcerative colitis,connective tissue diseases such as
dermatomyositis)

21. Clinical Mnifestations:
• Annular pruritic papules and blisters,giving a cluster of jewels
• In children: skin of the lower abdomen,genitalia,perineum
• In adults: trunk,limbs
• Ocular finding in adults and children
Oral Findings:
In 70% of patients
Are clinically indistinguishable from
the oral lesions of MMP,with
blisters,erosions and ulcers of
mucosa frequently accompanied by
desquamative gingivitis
Laboratory Findings:
Routin histology
DIF
IIF
Neutrophils are a prominent feature within the
blister

22. Management:
• Dapson and sulfapyridine are often effective when topical
steroids alone are insufficient
• More severe cases; combination of systemic corticosterroids
and immunosuppressivecdrug therapy such as mycophenolate
mofetil and some antibiotics such as
trimethoprim/sulfamethoxazole are effective when used in
combination with prednisone
• Some cases of LAD and CBDC exhibit spontaneous remission

23. 4.Epidermolysis Bullosa Acquista(EBA)
There are two forms of EBA:
1-classic form: lesion of the basement membrane with little
inflammation
2-inflammatory form: significant infiltration of neutrophils
Clinical Manifestations:
• Resemble BP ore MMP with widespread skin lesion or
primary involvmen of the oral mucosa,genital
mucosa,conjunctiva,and larynx
• Oral lesions: erythema,erosion,ulcers and desquamative
gingivitis

24. Management:
• Classic form tends to be resistant to treatment
• Inflammatory form responds well to dapson
• Some patients with an inadequate response to dapsone have
obtained remiission by combining it with colchicine
• Control the lesions in severe widespread EBA: systemic
corticosteroids,immunosuppressive drugs,rituximab,intravenous
immunoglobulin

25. Thank you
