A 32-year-old serving soldier from Maharashtra presented with a 5-month history of non-healing mouth ulcers and fluid-filled skin lesions over the upper body. Examination revealed multiple raw areas over the scalp, face, neck, chest and back. Investigations including Tzanck smear, skin biopsy and immunofluorescence studies were consistent with a diagnosis of Pemphigus vulgaris.

1. Surg Capt J Sridhar
Sr Adv
Dr Krishan Mehra
PGT-I
Dept of Dermatology

2. Patient particulars
 32 years old serving solider
 National handball player
 Resident of Maharashtra
 Admitted in Jan 2016
221-Apr-16

3. Presenting complaints
 Mouth ulcers - 5 months
 Fluid filled lesions/erosions over upper
body including head, face, neck, upper
chest and back - 5months
321-Apr-16

4. History of present illness
 Five months ago the patient developed
raw areas in mouth, associated with
burning pain while eating food
 Oral lesions increased in number and
size with little tendency to heal
421-Apr-16

5. History of present illness ( Contd…)
 Patient developed multiple, painless clear fluid
filled lesions within three to four days of the
appearance of mouth lesions - over scalp, face,
neck, upper chest and upper back
 Blisters burst on their own to form raw areas
within two to three days with little tendency to
heal
 Gradual increase in number and size of blisters
21-Apr-16 5

6. History of present illness ( Contd…)
 No history of
 itching prior to the onset of skin lesions
 contact with topical drugs or chemicals
 lesions over other mucosae - eyes/ genitals
 drug intake
 palm and sole involvement
 loose stools, weight loss
 fever, malaise
 skin lesions over trauma prone areas
 photosensitivity/ joint pain
621-Apr-16

7. History of present illness ( Contd…)
 No history of
seasonal variation/ exacerbation on sun exposure
palpitations, breathlessness or chest pain
high risk behavior, IV drug abuse, blood transfusion
21-Apr-16 7

8. Relevance of the negative history?
821-Apr-16

9. Relevance of the negative history
9
History Disease
Itching prior to skin lesions Dermatitis herpetiformis, Bullous pemphigoid
Palm and sole involvement Erythema Multiforme
Lesions on trauma prone area Epidermolysis bullosa acquisita
Joint pain SLE
Drug intake SJS-TEN
Contact with topical drugs or
chemicals
Irritant contact dermatitis, Bullous
pemphigoid
Weight loss, anorexia Malignancies, Paraneoplastic Pemphigus
Photosensitivity / joint pain Bullous SLE, Porphyria cutanea tarda,
Pemphigus erythematosus, Hydroa
vacciniforme
High risk sexual behavior HIV with recurrent HSV
21-Apr-16

10. Past history
 No h/o diabetes mellitus, hypertension,
coronary artery disease, tuberculosis,
jaundice and epilepsy
 No h/o similar illness in the past
 No h/o any major surgical or medical
illness in the past
1021-Apr-16

11. Drugs implicated in vesiculobullous
disorders?
1121-Apr-16

12. Drugs implicated in Vesiculobullous
disorder
Offending drugs Eruption
Thiol groups - Penicillamine, Thiamazole, Captopril,
Lisnopril, Piroxicam, Phenylbutazone,
Non thiol group - Penicillin group, Rifampicin,
Propranolol, Phenytoin,
Pemphigus
Carbamazepine, Phenytoin, Valproic acid,
Barbiturates, Sulfonamides, NSAIDS, Penicillin,
Rifampicin, Isoniazid, Pyrazinamide
Erythema Multiforme
Psoralens, Thiazides, Furosemides, Doxycycline,
Fluroquinolone, Sulfonamides
Phototoxic drugs
eruptions
Allopurinol, Anticonvusants, Barbiturates,
Sulfonamides, Piroxicam, Phenylbutazone,
Nevirapine, Quinolones
SJS-TEN
Tetracycline, Furosemide, NSAIDS, Captopril,
Penicillamine, Penicillin group antibiotics
Bullous pemphigoid
1221-Apr-16

13. Personal history
 Graduate
 Married
 Vegetarian
 Teetotaller
 No h/o substance abuse
 Normal appetite, sleep
 Normal bowel and bladder habits
1321-Apr-16

14. Family history
 No h/o similar illness among family members
1421-Apr-16

15. Treatment history
 Under treatment from previous military
centre with monthly IV infusions and
daily oral tablets since four months
1521-Apr-16

16. Summary?
1621-Apr-16

17. Summary
 32 years serving soldier, hailing from
Maharashtra, married, with no
comorbidities with h/o non healing ulcers
in the mouth and painless fluid filled skin
lesions/ erosions over the upper part of
body with little tendency to heal for the
last five months
1721-Apr-16

18. Causes of blistering?
21-Apr-16 18

19. Causes of blistering (Adults)
S
No.
Causes Diseases
1 Infections Viral – Herpes simplex, Varicella, Hand foot mouth
disease, Dermatophytosis
2 Inflammations Pustular psoriasis, Subcorneal pustular
dermatosis, Bullous lichen planus
3 Genetic Hailey-Hailey disease, Darier’s disease
4 Antibody mediated Pemphigus,Llinear IgA bullous dermatoses,
Paraneoplastic pemphigus, Bullous pemphigoid,
Dermatitis herpetiformis, Epidermolysis bullosa
acquisita
5 Metabolic Porphyria cutanea tarda, Diabetic bullae
6 Allergic Atopic dermatitis
7 Mechanical Friction blisters
8 Drugs Bullous drugs reaction, SJS-TEN, Erythema
multiforme
9 Environmental Phototoxic reactions, Burns
21-Apr-16 19

20. Causes of blistering (Children)
S
No.
Casues Diseases
1 Infections Viral – Herpes simplex, Varicella, Hand foot mouth
disease,
Fungal – Candidiasis
Bacterial – Congenital syphilis, Bullous impetigo,
SSSS,
2 Inflammations Bullous mastocytosis, Miliaria, Erythema toxicarum
neonatorum, Suction blisters
3 Genodermatoses Epidermolysis bullosa, Incontinentia pigmenti,
Bullous congenital ichthyosiform erythroderma
4 Antibody
mediated
Pemphigus, IgA dermatoses, Paraneoplastic
pemphigus
5 Metabolic Acrodermatitis enteropathica
6 Allergic Atopic dermatitis
21-Apr-16 20

21. Possibilities on History
 Pemphigus Vulgaris
 Bullous Pemphigoid
 Linear IgA bullous disease
 Recurrent erythema multiforme
 Paraneoplastic Pemphigus
 Lupus erythematosus
2121-Apr-16

22. 2221-Apr-16

23. General physical examination
• General condition - fair
• Ht- 171 cm ; Wt – 75 kg
• BMI –25.65 Kg/m2
• Waist circumference – 88 cm
• Temp- 98.80 F
• Pulse- 94/min
• BP- 110/74 mmHg
• RR- 16/min
• No pedal edema
• No lymphadenopathy
• No pallor, icterus, cyanosis, clubbing
2321-Apr-16

24. Systemic examination
 CVS
 S1, S2 heard. No murmur
 Respiratory
 B/L equal air entry
 No adventitious sounds heard
2421-Apr-16

25. Systemic examination (contd…)
 Per abdomen
 Soft, non tender
 No hepatosplenomegaly
 CNS
 Higher mental functions normal
 No focal neurological deficit
2521-Apr-16

26. Dermatological examination
 Multiple erosions, covered with crusts
(corn flake like), on erythematous base,
B/L symmetrical, involving face, scalp,
neck, upper chest, upper back, sparing
the axillary area with a musty smell, of
various sizes (diameter of 1 to 3 cm)
with multiple hyperpigmented macules.
21-Apr-16 26

27. 21-Apr-16 27

28. 21-Apr-16 28

29. Dermatological examination (contd…)
 Nikolsky's sign – not elicitable
 Nails, Hair - Normal
 Palms, soles, flexures - Normal
 Genital & conjunctival mucosa – Normal
 External genitalia, perianal region –
Normal
 Joint- WNL
2921-Apr-16

30. Nikolsky's sign ?
3021-Apr-16

31. Nikolsky's sign ?
 Shearing or tangential force dislodges
the upper layer of epidermis from lower
epidermis
3121-Apr-16

32.  Nikolsky’s sign
 Bulla spread sign of Asboe-Hansen

33. video
21-Apr-16 33

34. Types of Nikolsky’s sign ?
21-Apr-16 34

35. Types of Nikolsky’s sign
 Direct Nikolsky’s sign-
 When sign is elicited in normal skin away from the
blister
 Indicates severe disease activity.
 Marginal Nikolsky’s sign-
 When sign is elicited in normal skin near blister.
 Pseudo Nikolsky’s sign-
 Shearing or tangential force cause peeling of skin
which is due to necrosis of the cells in contrast to
acantholysis in pemphigus. Seen in Stevens-
Johnson syndrome, Toxic epidermal necrolysis,
burns.
21-Apr-16 35

36. Types of Nikolsky’s sign cont…..
 Microscopic Nikolsky’s sign-
 Sign is elicited by rubbing normal appearing skin
with an eraser around the blister to cause a
microscopic blister.
 Useful for taking a biopsy for histopathology.
 False Nikolsky’s sign-
 This involves pulling of the peripheral remnants
of ruptured blister, thereby extending the erosion
on the surrounding skin. Sign is positive in sub
epidermal blistering disorders such bullous
pemphigoid, JEB, mucous membrane
pemphigoid.
21-Apr-16 36

37. Investigations
• Hb - 15.4 gm%
• TLC - 9600/cmm
• DLC -P68, L29 ,M01, E03
• Pl Count- 2,20,000/ mm3
• ESR - 08 mm 1st hr
• CRP - 0.15 mg/L
• Urine RE/ME -NAD
• S. bilirubin-0.7mg/dl
• SGOT- 24 IU/L
• SGPT- 28 IU/L
• Total protein - 7.0 gm/L
• Alb - 4.1 gm/L
• Glob - 2.9gm/L
• Blood urea- 29mg/dl
• S. creatinine- 0.9mg/dl
• Na - 140 meq/L
• K -4.2 meq/L
• S. Ca -9.6 mg/dl
• S. uric acid -5.5 mg/dl
• ANA -ve
• RA -ve
• Blood sugar : F - 72mg/dl
PP-120mg/dl
• Lipid profile-
• TC – 253 mg/dl
• TG – 173 mg/dl
• LDL -184 mg/dl
• HDL – 39 mg/dl
3721-Apr-16

38. Investigations
• ELISA for HIV - Neg
• VDRL - Neg
• HBV - Neg
• HCV - Neg
• ECG - WNL
• CXR PA view - NAD
• USG abdomen - NAD
• Mantoux - Neg
• Echocardigraphy - Normal
• Tzank smear - Acantholytic cells seen
• Skin Biopsy - Consistent with Pemphigus vulgaris
• Indirect Immunofluorescence –
Dsg-1 207.3 U/ml (<20 u/ml)
Dsg-3 92.7 U/ml (<20 U/ml)
21-Apr-16 38

39. Tzanck cells in pemphigus vulgaris (Giemsa stain, 40X )
 Rounded keratinocyte with:
 perinuclear halo
 Hypertrophic/ dysmorphic
nucleus
 hazy or absent nucleoli
 increased N:C ratio
 abundant eosinophilic to
basophilic cytoplasm
21-Apr-16 39

40. Tzanck Smear ?
21-Apr-16 40

41. Tzanck Smear
 It is a bedside procedure done in blistering
disorders
 The roof of the intact blister is opened
along one side and floor is gently scraped
with blunt edge of blade and material
obtained is smeared on a glass slide and
allowed to air dry.
 Stained with Giemsa stain
21-Apr-16 41

42. Tzanck smear in cytodiagnosis ?
21-Apr-16 42

43. Skin biopsy
 Epidermis :
 Suprabasal split with group of
acantholytic cells in the split.
 Basal layer shows loss of
adhesion with adjacent
keratinoctye but attached to
the basement membrane
giving appearance of “row of
tombstones”
 Dermis:
 Superficial dermis shows
scanty perivascular
lymphocytic infiltrate.
4321-Apr-16

44. Pemphigus vs Pemphigoid?
21-Apr-16 44

45. 21-Apr-16 45

46. Summary?
4621-Apr-16

47. Summary
 32 years serving solider , hailing from
Maharashtra, married with no co-
morbidities with h/o non healing ulcers in
mouth and fluid filled skin lesions/erosions
over upper body with little tendency to heal
for the last five months.
 Dermatological examination revealed
multiple raw area over scalp , face, neck,
chest and back.
 Tzanck smear, Skin biopsy, IF studies s/o
Pemphigus Vulgaris
4721-Apr-16

48. Diagnosis
 Pemphigus Vulgaris
4821-Apr-16

49. Pemphigus ?
21-Apr-16 49

50. Pemphigus
 Autoimmune blistering disease
characterized by blisters and erosions
on the skin or mucosal membranes or
both
 Characterized by intraepidermal split
21-Apr-16 50

51. Classification
 Pemphigus vulgaris
- Pemphigus vegetans
• Pemphigus vegetans of Neumann
• Pemphigus vegetans of Hallopeau
 Pemphigus foliaceus
- Pemphigus erythematosus
- Endemic pemphigus
 Paraneoplastic pemphigus
 Drug induced pemphigus
 IgA pemphigus
- Subcorneal pustular dermatosis
- Intraepidermal neutrophilic IgA dermatosis
21-Apr-16 51

52. Epidemiology
5221-Apr-16
 Prevalence 0.09% to 6.8% ( India 0.09 to 1.8 %)
 Both sex equally affected
 Average age fourth and fifth decades( third and
fourth in India)
 Pemphigus vulgaris is commonest type
 Most common in North India, Gujarat, Maharashtra
and Assam

53. Etiology
 Genetic Determinants
 Pemphigus vulgaris is linked to HLA DRB1 *0402, HLA
DQB1*0503.
 Environmental Factors
 Exposure to ultraviolet light
 Pesticides and foods (nuts, mangoes, bananas, tomatoes,
garlic, onion) having thiol, phenols, polyphenolic
compound, drugs
 Immunological Factors
 Autoimmune disease and autoantibodies against antigens
located in the epidermis
○ Desmogleins (Dsg-1, Dsg-3)
○ Acetylcholine receptors (AChR alfa 9)
○ Pemphexin
21-Apr-16 53

54. Pathogenesis
 Antibodies to epidermal Desmoglein
1&3 (cell-cell adhesion molecule)
 Immune complexes deposited b/w
keratinocytes - intraepidermal clefting
 Acantholytic cells
 ‘Row of tombstones’

 Fishnet pattern on DIF

55. Clinical features
 Oral ulcers- 50-70% patient present with oral
lesions only
 Painful
 Little tendency to heal
 Skin blisters-
 Flaccid on normal appearing skin
 Easily rupture its own
 Usually painless without itching
 Little tendency to heal
 Characteristic musty offensive odour
 Head, face, neck, upper trunk, axilla, groin and
pressure points are common area involved
21-Apr-16 55

56. Course and prognosis
 Average mortality without treatment is about 100% in severe
disease
 With the use of steroids mortality is about 23%
 With early diagnosis, use of steroids, immunosuppressants and
improved treatment of complications mortality is about 5 – 15%
 Most common cause of deaths
 Septicemia
 Pulmonary embolism
 Complication of steroids and immunosuppressants
21-Apr-16 56

57. Management
 Aim of treatment :
 Decrease blister formation
 Promote healing of blisters and erosions
 Determine minimal dose of medication
necessary to control the disease process
5721-Apr-16

58. Contd…..
 Therapy must be tailored for each patient, taking
into account severity, preexisting and coexisting
conditions
 Evaluation by Physician
 For any comorbidities
 Evaluation by Ophthalmologist
 Those patients requiring prolonged high-dose steroids for
ocular involvement i.e Intraocular pressure, cataract.
 Evaluation by a Rheumatologist
 Patients requiring long term systemic corticosteroids/ ‘mabs
21-Apr-16 58

59. Contd…
 Adequate nutrition
 Nursing care
 Control of secondary infections
 Fluid and electrolyte monitoring
21-Apr-16 59

60. Treatment
 Topical (mild cases)
 Topical potent steroid
 Topical tacrolimus
 Topical epidermal growth factor(EGF)
 Intralesional steroids (to hasten remission)
 Triamcinolone acetonide (5-10mg/ml for mucosal) (10-
20mg/ml for cutaneous lesions) every weekly
 Systemic steroids: Mainstay of treatment
 Daily dosing
 Pulse therapy
 Oral steroids + Immunosuppressants
 Cyclophosphamide, Azathioprine, Cyclosporine,
Mycophenolate mofetil, Methotrexate
 Dexamethasone cyclophosphamide pulse
21-Apr-16 60

61.  Biologics
 Rituximab with or without Immunosuppressants
 IVIG
 Plasmapheresis
 Immunoadsorption
 Extracorporeal photochemotherapy
21-Apr-16 61

62. Definitive Management – this patient
• Monthly Dexamethasone Cyclophosphamide Pulse
• Interval Prednisolone 15mg daily
• Interval oral Cyclophosphamide 50mg daily
Five cycles of DCP given with moderate control of blisters
6221-Apr-16

63. Management (contd)…..
 In view of:
 Moderate control of the disease
 Long course of DCP therapy
 Long term side effect of systemic steroids
 Sports career of the patient
 Family not complete
 Patient given Rituximab after thorough work up
 RA protocol- Two does o f 1gm 15 days apart, slow IV infusion.
 1st dose given and patient tolerated therapy well
 Oral Cyclophosphamide 50mg daily continuing
 In remission without daily steroids
21-Apr-16 63

64. THANK YOU
21-Apr-16 64