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VESICOBULLOUS DISORDER
Surg Capt J SridharSr Adv
Dr Krishan MehraPGT-I
Dept of Dermatology
May 1, 2023 2
Patient particulars
32 years old serving solider
National handball player
Resident of Maharashtra
Admitted in Jan 2016
May 1, 2023 3
Presenting complaints
Mouth ulcers - 5 months
Fluid filled lesions/erosions over upper body including head, face, neck, upper chest and back - 5months
May 1, 2023 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
May 1, 2023 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
May 1, 2023 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
May 1, 2023 7
History of present illness ( Contd…)
No history ofseasonal variation/ exacerbation on sun exposurepalpitations, breathlessness or chest painhigh risk behavior, IV drug abuse, blood transfusion
May 1, 2023 8
Relevance of the negative history?
May 1, 2023 9
Relevance of the negative history
History DiseaseItching prior to skin lesions Dermatitis herpetiformis, Bullous
pemphigoidPalm and sole involvement Erythema MultiformeLesions on trauma prone area Epidermolysis bullosa acquisitaJoint pain SLEDrug intake SJS-TEN
Contact with topical drugs or chemicals
Irritant contact dermatitis, Bullous pemphigoid
Weight loss, anorexia Malignancies, Paraneoplastic PemphigusPhotosensitivity / joint pain Bullous SLE, Porphyria cutanea tarda,
Pemphigus erythematosus, Hydroa vacciniforme
High risk sexual behavior HIV with recurrent HSV
May 1, 2023 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
May 1, 2023 11
Drugs implicated in vesiculobullous disorders?
May 1, 2023 12
Drugs implicated in Vesiculobullous disorder
Offending drugs EruptionThiol 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
May 1, 2023 13
Personal history
Graduate Married Vegetarian Teetotaller No h/o substance abuse Normal appetite, sleep Normal bowel and bladder habits
May 1, 2023 14
Family history
No h/o similar illness among family members
May 1, 2023 15
Treatment history
Under treatment from previous military centre with monthly IV infusions and daily oral tablets since four months
May 1, 2023 16
Summary?
May 1, 2023 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
May 1, 2023 18
Causes of blistering?
May 1, 2023 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
May 1, 2023 20
Causes of blistering (Children) S No.
Casues Diseases
1 Infections Viral – Herpes simplex, Varicella, Hand foot mouth disease,Fungal – CandidiasisBacterial – 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
May 1, 2023 21
Possibilities on History
Pemphigus Vulgaris Bullous Pemphigoid Linear IgA bullous disease Recurrent erythema multiforme Paraneoplastic Pemphigus Lupus erythematosus
May 1, 2023 22
EXAMINATION
May 1, 2023 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
May 1, 2023 24
Systemic examination
CVS
S1, S2 heard. No murmur
Respiratory
B/L equal air entry No adventitious sounds heard
May 1, 2023 25
Systemic examination (contd…)
Per abdomen
Soft, non tender No hepatosplenomegaly
CNS
Higher mental functions normal No focal neurological deficit
May 1, 2023 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.
May 1, 2023 27
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May 1, 2023 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
May 1, 2023 30
Nikolsky's sign ?
May 1, 2023 31
Nikolsky's sign ?
Shearing or tangential force dislodges the upper layer of epidermis from lower epidermis
Nikolsky’s signBulla spread sign of Asboe-Hansen
May 1, 2023 33
video
May 1, 2023 34
Types of Nikolsky’s sign ?
May 1, 2023 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.
May 1, 2023 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.
May 1, 2023 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
May 1, 2023 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)
May 1, 2023 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
May 1, 2023 40
Tzanck Smear ?
May 1, 2023 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
May 1, 2023 42
Tzanck smear in cytodiagnosis ?
May 1, 2023 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.
May 1, 2023 44
Pemphigus vs Pemphigoid?
May 1, 2023 45
May 1, 2023 46
Summary?
May 1, 2023 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
May 1, 2023 48
Diagnosis
Pemphigus Vulgaris
May 1, 2023 49
Pemphigus ?
May 1, 2023 50
Pemphigus
Autoimmune blistering disease characterized by blisters and erosions on the skin or mucosal membranes or both
Characterized by intraepidermal split
May 1, 2023 51
Classification Pemphigus vulgaris
- Pemphigus vegetans • Pemphigus vegetans of Neumann • Pemphigus vegetans of Hallopeau
Pemphigus foliaceus - Pemphigus erythematosus - Endemic pemphigus
Paraneoplastic pemphigus Drug induced pemphigusIgA pemphigus
- Subcorneal pustular dermatosis - Intraepidermal neutrophilic IgA dermatosis
May 1, 2023 52
Epidemiology 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
May 1, 2023 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
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
May 1, 2023 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
May 1, 2023 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
May 1, 2023 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
May 1, 2023 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
May 1, 2023 59
Contd…
Adequate nutrition Nursing care Control of secondary infections Fluid and electrolyte monitoring
May 1, 2023 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
May 1, 2023 61
BiologicsRituximab with or without Immunosuppressants
IVIG
Plasmapheresis
Immunoadsorption
Extracorporeal photochemotherapy
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
62May 1, 2023
May 1, 2023 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
May 1, 2023 64
THANK YOU
