This document discusses pemphigus, a group of immunologically-mediated mucocutaneous blistering disorders. Pemphigus vulgaris is the most common variant seen in oral medicine, characterized by intra-epithelial blister formation and anti-desmoglein antibodies. Clinical presentation includes widespread ulceration/blistering, rapid progression, and positive Nikolsky's sign. Histology shows intra-epithelial blisters and Tzank cells. Treatment involves systemic corticosteroids and immunosuppressants to control symptoms and progression. The role of dentists is in early diagnosis and monitoring of pemphigus patients.

1. D R . Z A I N A K R A M B . D . S .
D E M O N S T R A T O R , O R A L M E D I C I N E D E P A R T M E N T
F M H C O L L E G E O F D E N T I S T R Y
Mucocutaneous Blistering
Disorders

2. Pemphigus
Pemphigus is defined as an immunologically mediated
blistering mucocutaneous disorder characterised by
INTRA-EPITHELIAL bulla formation and circulation of
anti-DSG antibodies
 Pemphigus vulgaris is the most common variant in oral
medicine (70%) .
 Occasionally Vegetans or Paraneoplastic variant
 Pemphigus Foliaceus does not affect the oral mucosa
 Drug induced variant (eg. ACE inhibitors such as
captopril)

3. Clinical presentation of Pemphigus on oral
mucosa and skin

4. Histology of oral mucosa in Pemphigus

5. Pemphigus variants and associated desmosmal
antigens
Pemphigus
Variant
Desmosomal antigen Serum antibodies Oral lesions
Pemphigus vulgaris
(mucosal only)
Desmoglein 3 IgG Common
Pemphigus vulgaris
(mucosal+skin)
Desmoglein 1 and 3 IgG Common
Pemphigus Foliaceus Desmoglein 1 igG Uncommon
Drug induced
pemphigus
Desmoglein 3 igG Common
Paraneoplastic
pemphigus
Desmoplakin 1 and 2 IgG or IgA Common
IgA Pemphigus Desmocolin 1 and 2
Desmoglein 3
IgA Common

6. 1 . W I D E S P R E A D U L C E R A T I O N / B L I S T E R I N G
2 . R A P I D P R O G R E S S I O N
3 . V E R Y R A R E L Y F L U I D - F I L L E D B L I S T E R S
C A N B E S E E N I N T A C T
4 . P O S I T I V E N I K O L S K Y S I G N
5 . D E S Q U A M A T I V E G I N G I V I T I S
Oral manifestations of
Pemphigus vulgaris

7. Oral manifestations of pemphigus

8. Nikolsky sign
 Stroking the skin or mucosa with a finger may induce
vesicle formation in an apparently unaffected area or
cause a bulla to extend .

9. Desquamative gingivitis
 It is the term given to clinical description of chronically red and
occasionally sore gingivae . It is an extremely painful condition .
 Previously known as ‘RED BAND GINGIVITIS’ because it is known to
spare interdental papillae.
 Interdental papillae may become involved because patients are unable
to maintain oral hygiene because of the pain

10. Causes of desquamative gingivitis
 Lichen Planus
 Pemphigoid
 Chronic ulcerative stomatitis
 Dermatitis herpetiformis
 Linear IgA disease
 Pemphigus
 Erythema multiforme
 Pyostomatitis vegetans

11. Clinical features of pemphigus Vulgaris
 Affects middle to late aged females
 Common in Ashkenazi Jews
 Produces blisters(intraepithelial) on skin and mucosa
 Oral cavity is almost always involved in 50% of the cases in initial
lesion
 Blisters are fragile and tend to rupture readily giving rise to crusting
and weeping area of denudation on skin and ragged mucosal
ulceration
 Sites most commonly affected include:
I. Buccal mucosa
II. Soft palate
III. Gingiva
 Bullae formed by the process of acantholysis
 Histopathology shows intraepithelial bullae and TZANK cells

12. Death in Pemphigus
 Pemphigus is fatal because of
1. Infection(due to disease or pharmacological
immunosuppressants)
2. Loss of electrolytes and proteins > Cardiac /Renal
Failure

13. Investigations of pemphigus Vulgaris
1. Medical history (drug induced? Rapid progression)
2. Biopsy (H&E staining) histology (fluid filled
intraepithelial bullae)
3. Direct immunofluorescence (net-like appearance)
4. Indirect immunofluorescence ( Pemphigus
antibodies) IgG and C3.
5. ELISA (anti DSG 1 and /or anti DSG 3)
6. Tzank cells –detached epithelial cells,round in
shape as a result of contraction of cytoplasm(not
specific)

14. Immunofluorescence -Pemphigus vulgaris
Fish-net appearance

15. Pemphigus vulgaris-Therapy
Systemic corticosteroids remain the
maintstream therapy for Pemphigus .their
use has transformed what was almost
invariably a fatal illness into one whose
mortality rate is now below 10 %.
 Even with 100-150 mg daily azathioprine ,40-80 mg daily
of prednisolone may be required.

16. Therapy –Pemphigus Vulgaris
 Systemic corticosteroids
 Azathioprine
 Methotrexate
 Cyclophosphamide
 Cyclosporin
 Chlorambucil
•Mycophenolate mofetil
•Plasmapheresis
•Levamisole
•Immunogloins
•Photophoresis
•High dose IV Ig
•Anti-TNF (Infliximab)
•Anti-CD20 (Rituximab)

17. Pemphigus Vulgaris-Treatment monitoring
 Weight
 Blood pressure
 Blood glucose
 CBC
 LFTs
 Renal function
 Osteoporosis
 Cataract

18. Pemphigus Vulgaris-Role of Dentist
 DIAGNOSIS(early stage)
 MONITORING

19. MMP IS A GROUP OF SUB-EPITHELIAL
IMMUNE BLISTERING DISEASES WITH
AUTOANTIBODIES DIRECTED TO
DIFFERENT EPITHELIAL BASEMENT
MEMBRANE PROTEINS
•COMMON VARIANT OF MMP HAS
ANTIBODIES AGAINST BULLOUS
PEMPHIGOID ANTIGEN 2 (BP2)
•TYPES AFFECTING THE MOUTH HAVE
ANTIBODIES AGAINST INTEGRIN OR
EPILIGRIN
Mucous Membrane Pemphigoid

20. Mucous Membrane Pemphigoid-Oral
manifestations
 Less widespread than pemphigus.Predominantly
affects females 50 to 70 years old.
 Sites involved:
1. Buccal mucosa
2. Gingivae
3. Soft palate
 Progression is very slow
 Blood filled blisters/irregular superficial ulcers
 Oral scarring is rare but may cause limited mouth
opening and loss of vestibular depth
 Desquamative gingivitis

21. Mucous Membrane pemphigoid
Eye lesion
Oral lesion

22. High risk sites - MMP
 Conjuctiva
 Larynx
 Ano-genital area
*In the eyes MMP results in the adhesion between bulbar and palpebral
conjunctiva called symblepharon*

23. High risk sites-MMP
Conjunctiva
Larynx

24. Investigations -MMP
 History(drug induced)
 Biopsy(histopath reveals sub epithelial bullae)
 Direct immunofluorescence (Linear band of IgG at
the basement membrane zone)
 Indirect immunofluorescence-Pemphigoid
antibodies
1. Anti Integrin antibodies-against oral mucosa
2. Anti Epiligrin antibodies –against eyes (conjunctiva)
3. Others such as laminin 5 etc.

25. Immunofluorescence-MMP
Linear band of IgG at basement membrane

26. Treatment –MMP
 Topical corticosteroids similar to lichen planus
 Systemic corticosteroids (prednisolone,deflazacort)
 Azathioprine
 Dapsone
 High dose IV Ig
 Consider appropriate referral eg. Eyes ,larynx ,skin,
genitalia

27. Drugs -Pemphigoid

29. Erythema Multiforme
Erythema multiforme (EM) is an acute, self-limited,
and sometimes recurring mucocutaneous sub-
epithelial blistering condition that is considered to
be a type IV hypersensitivity reaction associated with
certain infections, medications, and other various
triggers.
 Usually affects young males
 Rarely chronic
 Precipitating factors include
1. Drugs(sulfonamides,barbiturates etc.
2. Infection (HSV, Mycoplasma)

30. Classification- Erythema Multiforme
1. Erythema Multiforme Minor
2. Erythema Multiforme Major
3. Stevens Johnson Syndrome (SJS) and Toxic
Epidermal Necrolysis are extreme variants .

31. Classification
 Erythema Multiforme Minor (Emm)
 Skin target lesions on < 10 % of body surface + 1 mucosal site(usually the mouth)
 Oral mucosa only
 Erythema Multiforme Major (EMM)
 Skin target lesions on < 10 % of body surface but more severe than Emm + atleast
2 mucosal sites affected (usually mouth+ genitals)
 SJS(Stevens Johnson Syndrome)
 Target /atypical skin lesions on <10 % body surface but more severe than EMM +
multiple mucosal sites + systemic features (fever , muscle/joint pain, pneumonia
etc.)
 SJS/TENS overlap
 Target/atypical skin lesions on 10-30 % body surface +mucosal sites+systemic
features +scarring
 TENS(Toxic epidermal necrolysis)
 Target /atypical lesions on >30 % body surface +mucosal sites+ systemic features
+scarring

33. Oral Manifestations -EM
 Very rapid onset(few hours)
 Widespread irregular erosions/ulcers and erythema in
the mouth
 Swollen blood-encrusted lips
 Very painful
 Duration 10-15 days
 Sometimes erythema and desquamation and sloughing
only.
 Target lesions / iris lesions may occur
o Target lesions are usually red macules 1 or greater than 1 cm in
diameter with a bluish cyanotic center

34. Erythema multiforme

35. Blood Crusted Lips

36. Erythema Multiforme (Cutaneous lesions)

37. Intraoral Erythema Multiforme

38. Erythema Multiforme
 Variable oral ulceration
 Often areas of ragged erythema ,blistering and
ulceration seen
 Diagnosis and management can be difficult.

39. Investigations-EM
 Biopsy and routine histopathology
 Direct immunofluorescence is not helpful
 Diagnosis is usually clinical (medical History-
triggers-rapid onset)
Histopathology of erythema multiforme

40. Management -EM
 Identify and correct any precipitant (drug or
infection)
 Topical corticosteroids +short course of systemic
corticosteroids
 For chronic/recurrent EM
 Acyclovir(reduced dosage daily for 6-12 months).
 Immunosuppressants (azathioprine/cyclosporine
etc)

41. Dermatitis herpetiformis
 Blistering muco-cutaneous disease
 Usually affects young and middle aged adult males
 Uncommon
 Not caused by herpes

42. Dermatitis herpetiformis
 Skin rashes-typically affecting extensor surfaces of
elbows and knees .Vesicobullous with ragged
ulcerations(herpes-like)
 85 % patients present with Celiac disease(GSE)
 Oral blood filled bullae, ulceration and desquamative
gingivitis-similar to MMP

43. Dermatitis herpetiformis-Associations

44. Skin rash on extensor surface of elbow
In dermatitis herpetiformis

45. Oral lesions –Dermatitis herpetiformis affecting the lips
and portion of the palate

46. Investigations-Dermatitis herpetiformis
 Medical history-Coeliac disease in 85% patients
 Biopsy –Routine H&E . Histology (Fluid filled sub epithelial bullae.
 Serology for Coeliac disease
1. Anti-reticulin
2. Anti-endomycium
3. Anti-gliadin
4. Anti-transglutaminase
 CBC and heamatinics(nutrient malabsorption leading to
decreased iron ,vit. B12 ,folate)
 LFT may be abnormal (increased AST,ALT,ALP)

47. Immunofluorescence –Dermatitis Herpetiformis

48. Treatment-Dermatitis herpetiformis
 Gluten free diet
 Topical corticosteroids as with lichen planus
 Dapsone
 Sulfapyridine
 Referral regarding possible coeliac disease

50. Linear IgA disease
 Uncommon, affects adults
 Children may have a similar presentation 9Chronic
bullous disease of childhood)
 Skin rashes –vesicobullous with annular pattern-
similar to bullous pemphigoid
 15 % patients will have Coeliac disease(GSE)
 Oral blood-filled bulae and desquamative gingivitis
similar to MMP

51. Investigation –Linear IgA disease
 Medical history(Coeliac disease?)
 Biopsy-routine H&E .Histology (fluid filled sub-
epithelial bullae)
 Direct immunofluorescence –linear deposits of IgA
at basement membrane zone
 Serology for coeliac disease + CBC and heamatinics.

52. Immunofluorescence of Linear IgA disease
Linear deposit of IgA at basement membrane zone

53. Treatment-Linear IgA disease
 Gluten-free diet
 Topical corticosteroids as with lichen planus
 Dapsone
 Sulphapyridine
 Referral regarding possible coeliac disease

54. Diseases characterised by linear IgA deposits at
Basement Membrane Zone
 Dermatitis herpetiformis
 Linear IgA disease
 Chronic Bullous disease of Childhood

55. Lupus Erythematosus
 an inflammatory autoimmune disease causing scaly
red patches on the skin, especially on the face, and
sometimes affecting connective tissue in the internal
organs.
 There are two types
1. SLE-systemic lupus erythematosus
2. DLE-Discoid lupus erythematosus
(mucocutaneous)

56. Chronic discoid lupus erythematosus
 Erythematous skin rashes
 Mucocutaneous white/red patches with ulceration or
erythema
 ORAL MANIFESTATIONS
 Radiating(sun-ray) red/white patches with central area
of erythema and ulceration(reticular/plaque/erosive
features)
 Often unilateral .May affect palate (rare in lichen planus)
 Desquamative ginigivitis maybe found

57. Oral manifestations-systemic lupus
erythematosus
 More widespread than DLE
 Generally similar to OLP but maybe unilateral
 Other oral manifestations:
Oral manifestations of Sjogren’s syndrome
Oral features of neutropenia,anemia,thrombocytopenia
Oral features of therapy(lichenoid reactions –
Hydroxychloroquinone therapy)
Lichen-Lupus overlap

59. SLE –Butterfly shaped rash

60. Investigations-Lupus erythematosus
 Medical history
 Biopsy (H&E).Histology (non specific ulcers /lichenoid
type features)
 Direct immunofluorescence-linear deposits of IgG,IgM
and C3 at basement membrane zone(lupus band)
 Serology for systemic disease
I. Anti-nuclear antibodies(ANAs)
II. Extractable nuclear antigens (ENAs)
 CBC and haematinics
 Investigate xerostomia if present

61. Biopsy taken from vesicular lesion revealed a subepidermal split,
containing numerous red blood cells. A marked neutrophilic infiltrate is seen
suggesting autoimmune disease.

62. Management-lupus erythematosus
 Topical agents as with lichen planus
 Systemic therapies as with pemphigus
 Hydroxychloroquinone
 Treatment of secondary Sjogren’s syndrome
 Consider referral to rheumatology or dermatology
*CDLE may have a malignant potential(controversial)*