SEMINAR PRESENTATION
Clinical approach to a case of Blistering disorder
MODERATOR: Dr. Amit Malhotra
Introduction
• A blister is a fluid filled cavity formed within or beneath the epidermis.
• Can be categorized as vesicles or bullae.• Vesicle- < 0.5 cm in diameter• Bulla- > 0.5 cm in diameter• Blisters are an obvious sign of disease that always draw
attention of patient and physician.
Common causes of blistering
• Infection– Herpes simplex– Herpes zoster– Varicella– Bullous impetigo– SSSS
• Genetic– Epidermolysis bullosa– Hailey-Hailey disease– Incontinentia pigmenti
• Immunobullous– Pemphigus group of diseases– Paraneoplastic pemphigus– Bullous pemphigoid– Mucous membrane pemphigoid– Linear IgA disease– Dermatitis herpetiformis– Epidermolysis bullosa acquisita
• Mechanical– Friction blister
• Dermatitis– Allergic contact dermatitis– Irritant dermatitis
• Drugs– Bullous FDE– Erythema multiforme– SJS/ TEN
• Metabolic– Diabetic bullae– Porphyria
• Disorders, in which blistering is the primary event are traditionally termed as blistering disorders or vesiculobullous disorders.
• This group includes hereditary blistering disorders and immunobullous diseases.
Approach
• History
• Clinical examination
Age of onset
Pemphigus vulgaris Middle age (40-60 yrs)
Pemphigus foliaceus Middle age
Paraneoplastic pemphigus Adult, children
Bullous pemphigoid Elderly (60-75 yrs)
Mucous membrane pemphigoid Old age (60-80 yrs)
Pemphigoid gestationis Pregnant women
Dermatitis herpetiformis Adult
Linear IgA disease Before 5 & after 60 yrs
EBA Adults & childrenHailey- hailey disease Adults
Epidermolysis bullosa At birth or during infancy
Initial site
Pemphigus vulgaris Oral mucosa
Pemphigus foliaceus Scalp, chest
Bullous pemphigoid extremities
Mucous membrane pemphigoid Oral or other mucosa
Pemphigoid gestationis Periumblical, extremities
Dermatitis herpetiformis Trunk, scalp
Linear IgA disease Genital in children; no predilection in adults
EBA Mucosa, extremitiesHailey- hailey disease Friction sites
Mucosal involvement
Pemphigus vulgaris Almost all
Pemphigus foliaceus None
Intercelluar IgA dermatosis Uncommon
Paraneoplastic pemphigus Severe mucositis
Bullous pemphigoid 10 – 40%, transient, mild
Mucous membrane pemphigoid Almost all
Pemphigoid gestationis Rare
Dermatitis herpetiformis Rare
Linear IgA disease 80%
EBA 50%Hailey- hailey disease Uncommon
Distribution of lesions
Pemphigus vulgaris Scalp, face, flexures, trunk
Pemphigus foliaceus Seborrhoeic distribution
Intercelluar IgA dermatosis Axillae, groins, face, scalp, proximal limbs
Paraneoplastic pemphigus Upper body, palmoplantar
Bullous pemphigoid Trunk, limbs, flexures
Mucous membrane pemphigoid Infrequent; head, neck, upper trunk
Pemphigoid gestationis Abdomen, extremities
Dermatitis herpetiformis Symmetrical over extensors of trunk including buttocks, elbows, knees.
Linear IgA disease Perineum, face, trunk, limbs
EBA Generalized, variable
Epidermolysis bullosa Sites of trauma
Hailey- Hailey disease Sides of neck, axillae, groins, perineum
Morphology of lesions
Characteristics of bullae based on level of split
Lesions characteristics
Pemphigus vulgaris Flaccid blisters, erosions, flexural vegetations
Pemphigus vegetans Vesicles, pustules, erosions, vegetating Plaques
Pemphigus foliaceus Scaly papules, crusted erosions,Erythroderma
Intercelluar IgA dermatosis Flaccid pustules annular or circinate configuration
Paraneoplastic pemphigus Polymorphous, bullae, erosions, ‘target lesions’
Bullous pemphigoid Urticated plaques, tense blisters, (milia)
Mucous membrane pemphigoid Erosions, blisters, gingivitis, milia, Scarring
Pemphigoid gestationis Urticated plaques, tense blisters
Dermatitis herpetiformis Papulovesicles
Linear IgA disease Urticated plaques, annular lesions, tense blisters
EBA Urticated plaques, tense blisters, milia ,Scarring
Hailey- Hailey disease Flaccid vesicopustules, crusted erosions or expanding circinate plaques appear in areas exposed to friction
Pemphigus vulgaris A: flaccid blisters on normal skin.
B: superficial blisters and erosions which take long to heal.
Pemphigus vegetans: heaped up vegetatingplaques in flexures
Pemphigus foliaceus: extensive areas of scaling and crusting and no blisters. removal of scale-crust reveals a minimally moist area.
Bullous pemphigoid:
urticarial lesions.large hemorrhagic blisters some on normal skin
Pemphigoid gestationis
Early pruritic erythematous stageBullae arising on urticated erythematous skin onthe thigh.
Chronic bullous disease of childhood: string ofpearl appearance is typical
Dermatitis herpetiformis: grouped vesicles develop either on normal or erythematous skin. Since the lesions are extremely itchy, they are rapidly excoriated
Differentiating features of Epidermolysis bullosa
Type Time of presentation
inheriatnce
Clinical features MM/Nail/Teeth
Associated features
Prognosis
Weber-Cockyne EBS
Childhood
AD Localised to palms, soles, waist or neck, no scarring, more in summers
Normal Hyperhydrosis of palms, soles
good
Koebner EBS
At birth or infancy
AD On occiput, back or legs in infancy, Hands or feet in childhood, no scarring
Normal Aggravated by warm weather, Hyperhydrosis of palms, soles
May improve after puberty
Epidermolysis bullosa
Type Time of presentation
inheritance
Clinical features MM/Nail/Teeth
Associated features
Prognosis
Dowling-meara EBS
At birth or infancy
AD Herpitiform blisters on trunk, limbs, neck, No scarring
MM, nails involved
Milia, hyperpigmentation seen
Severe in infancy, better with age
EBS with muscular dystrophy
At birth or early infancy
AD Blisters on hands and feet then generalized
Nail deformities, MM involvement, alopecia
Muscle weakness early or late onset,milia
Poor
Epidermolysis bullosa
Type Time of presentation
inheritance
Clinical features MM/Nail/Teeth
Associated features
Prognosis
Autosomal recessive lethal EBS
At birth
AR Generalised more on distal limbs
Normal, oral mucosa mildly affected
No scarring or milia seen
Poor
EBS with mottled pigmentation
At birth or infancy
AD Reticulate pattern of macular pigmentation over trunk, limbs
Nails involved, MM, teeth normal
Punctate keratoses on palms and soles
Improves with age
Epidermolysis bullosa
Type Time of presentation
inheritance
Clinical features MM/Nail/Teeth
Associated features
Prognosis
Herlitz JEB At birth or soon after birth
AR Severe generalised blistering, skin fragility, difficult to handle child, erosions slow to heal
Mm, nails teeth involved, larynx may be involved
Sepsis or multiorgan failure may occur
Poor, child may die in early infancy due to infection
Non- Herlitz JEB
At birth AR Generalised blistetrs, scalp involvement causes alopecia
Involved Pigmentation and nevi seen
Improves with age
Epidermolysis bullosa
Type Time of presentation
inheritance
Clinical features MM/Nail/Teeth
Associated features
Prognosis
JEB with pyloric atresia
At birth
AR Generalised skin and mucosal blisters
Nail, teeth involved
Non- bilious vomiting in newborn
Very poor
Progressive JEB
5-8 years
AR Hands, feet, knees, elbows (sites of friction)
Nail, teeth involved
Finger contractures, deafness
good
Epidermolysis bullosaType Time of
presentation
inheritance
Clinical features MM/Nail/Teeth
Associated features
Prognosis
Dominant dystrophic EB
At birth or early infancy
AD Hands, feet, knees, elbows (sites of friction)
Nail dystrophy, MM, teeth normal
White papules on trunk, pasini variant
Good
Hallopeau- siemens EB
At birth or early infancy
AR Large, flaccid bullae at sites friction, healing slow, scarring
Dystrophic nails, scarring alopecia, carious teeth
Flexural contractures, esophagial strictures, inability to protude tongue
Poor- death by 3-4 decade
Non Hallopeau- siemens EB
At birth AR Skin and mucosae are fragile
Changes are localised
Few complications
good
Configuration
• Grouping of blisters: dermatitis herpetiformis.
• String of pearls sign- annular, polycyclic lesions often with blistering around the edge in CBDC
NIKOLSKIY SIGN• A positive Nikolskiy sign indicates intraepidermal cleavage and
differentiates intraepidermal blisters from subepidermal blisters.
• It is pathognomonic of pemphigus and staphylococcal scalded skin syndrome
• The sign is best elicited by applying lateral pressure with the thumb or fingerpad on skin over a bony prominence.
• This results in a shearing force that dislodges the upper layers of epidermis from the lower epidermis producing an erosion.
• Specifically, elicitation of the sign can help distinguish pemphigus vulgaris, which is strongly associated with the sign, from bullous pemphigoid, in which the sign is usually absent.
• other diseases associated with a positive Nikolsky’s sign -toxic epidermal necrolysis, bullous impetigo, and
epidermolysis bullosa
(a) Eliciting Nikolsky's sign on perilesional skin. Note the tangential pressure, (b) Eliciting Nikolsky's sign, peeling of skin revealing moist erosion
BULLA SPREAD SIGN• In the traditional "bulla spread" sign or Lutz sign, the margin
of an intact bulla is first marked by a pen.• Slow, careful and unidirectional pressure applied by a finger to
the bulla causes peripheral extension of the bulla beyond the marked margin.
• The bulla thus extended has an irregular angulated border in pemphigus vulgaris, while a regular rounded border is observed in bullous pemphigoid or other subepidermal blistering disorders.
• This sign is positive in all varieties of pemphigus and many cases of subepidermal blisters, including bullous pemphigoid, DH , EBA, cicatricial pemphigoid, dystrophic epidermolysis bullosa, SJS, TEN.
• Due to fragility of the roof of the blister it is usually negative in Hailey-Hailey disease and staphylococcal scalded skin syndrome.
Tzanck Smear• Is a quick bedside test.• A fresh blister is ruptured, the roof detached and the floor
scraped using a scalpel blade.• If blister not present, then taken from erosion, after removing
the crust.• The material so obtained is spread on a glass slide and stained
with Giemsa stain.
Tzanck smear findings in bullous disorders
PEMPHIGUS VULGARIS• It reveals multiple acantholytic
cells (Tzanck cells).
• A typical Tzanck cell – Large round keratinocyte – Hypertrophic nucleus, – Hazy or absent nucleoli, and – Abundant basophilic cytoplasm.
• The basophilic staining is deeper peripherally on the cell leading to a perinuclear halo.
Other differentials
Differential History Examination
Herpes simplex primary or recurrent outbreak of herpes simplex virus (HSV) vesicles associated with tenderness, burning, or tingling; HSV-1 is spread primarily through direct contact with infected saliva or other infected secretions, HSV-2 is spread primarily through sexual contact, symptoms typically start within 1 week after exposure
grouped vesicles on an erythematous base, may evolve to pustules or erosions, lesions resolve within 2 to 6 weeks
Herpes zoster (shingles)
prior history of varicella infection, presents with prodrome of pain, itching, hyperesthesia followed by vesicular eruption
painful, grouped vesicles on an erythematous base in a sensory dermatomal distribution, rarely crosses midline
Differential History Examination
Varicella, acute(chickenpox)
initial viremia between days 4 and 6; appearance of characteristic vesicular eruption on erythematous base, often referred to as "dewdrops on rose petals," low-grade fever, malaise, and headache
successive crops of lesions appear over several days on trunk, face, and oral mucosa; typically lesions are in different stages of evolution from vesicles to crust and do not scar
Impetigo typically occurs in children, very contagious, risk factors include increased humidity, poor hygiene, malnutrition and overcrowding, concomitant skin disease
bullae are ≥2 cm in diameter and initially clear, subsequently becoming turbid; buccal mucosa may be involved, classic facial yellowish to golden crusting, streptococcal form tends to have thicker and darker crusts
Differential History Examination
Staphylococcal scalded skin syndrome
typically child or adult with renal insufficiency
prodromal fever, tender skin evolve to generalized erythema with flexural accentuation and then flaccid bullae formation; Nikolsky sign present, desquamation follows starting in flexural areas; in contrast to toxic epidermal necrolysis, does not affect oral mucosa and may be a helpful clue to diagnosis
Congenital syphilis
40% of infected newborns have skin findings, neonate develops lesions within first 2 weeks of life through transplacental transmission, mother with history of secondary or tertiary syphilis
primarily acrally located vesicles and bullae, may be hemorrhagic
Differential History Examination
Eczematous dermatitis (contact, nummular, and pompholytic)
personal or family history of atopy, recent exposure to chemicals, personal hygiene products, fabrics, or plant allergens (e.g., poison ivy, poison oak)
predominantly localized distribution of vesicles and papules with surrounding erythematous base, later lesions may be covered by scale or crusting
Friction blister recent activity involving affected area (new shoes, gloves, or products)
tense bullae in area of pressure or friction
Miliaria exposure to hot or humid climates, febrile illness in bedridden patient, layered clothing preventing dissipation of heat or moisture
pruritic or asymptomatic papules or vesicles
Differential History Examination
Coma bullae coma from trauma, illness, or an overdose of a narcotic drug
erythema with vesicles or bullae at sites subjected to pressure (hands, wrists, scapulae, sacrum, knees, heels)
Bullous arthropod bite reaction
recent arthropod exposure in a sensitized patient, typically present as grouped pruritic or asymptomatic blisters in patients who are otherwise well
grouped pruritic or asymptomatic blisters, distribution and location of the lesions usually localized to a specific area of body (depending on causative arthropod)
Differential History Examination
Nutritional deficiencies (zinc, biotin, niacin, essential fatty acids)
inherited or acquired deficiency, breastfed newborns, history of parenteral nutrition, characteristic cutaneous finding is a photosensitive eruption (preferentially involving the face, neck, upper chest, dorsal hands, and extensor forearms), which worsens in spring and summer
dermatitis is bullous or pustular, periorificial and acral locations, associated erythematous eroded, crusted patches; with repeated sun exposure, the involved areas become thickened, scaly, and hyperpigmented
Diabetic bullae (bullosis diabeticorum)
longstanding history of diabetes, spontaneously healing blisters within 4 to 5 weeks of onset
painless noninflammatory blisters typically on acral locations, including amputation sites
Differential History Examination
Porphyria cutanea tarda
photosensitivity, fragility of sun-exposed skin that results in blistering and erosions of the dorsal hands, forearms, ears, feet, and face; ingestion of alcohol, estrogens, and polychlorinated cyclic hydrocarbons exacerbates condition
tense blisters on sun-exposed skin, heal with scarring, dyspigmentation, and milia; hypertrichosis, sclerodermatous thickenings, and scarring alopecia
Pseudoporphyria cutanea tarda
hemodialysis, drug exposures (NSAIDs, furosemide, nalidixic acid, tetracycline), skin fragility, photosensitivity, absence of hypertrichosis, and skin sclerosis
bullae on sun-exposed body areas (face, ears, dorsal hands, forearms)
Differential History Examination
Incontinentia pigmenti
X-linked dominant, female infant 4 to 6 weeks old with vesicles in a patterned distribution (Blaschko lines), cutaneous features evolve through 4 stages from infancy to adolescence
noninflammatory vesicles in a patterned distribution (Blaschko lines), abnormalities of teeth, eyes, hair
Bullous ichthyosiform erythroderma (epidermolytic hyperkeratosis)
presents at birth, or shortly after, with erythema, blistering, or peeling; may be confused with staphylococcal scalded skin syndrome or epidermolysis bullosa
widespread erythema, blistering and peeling infant with or without palmar-plantar involvement
Differential History Examination
Mastocytosis acquired solitary or widespread cutaneous eruption, lesion periodically urticates and blisters then returns to original form
5 mm to 15 mm papules, yellow-brown to yellow-red in color; edema, urtication, and vesicle and bullae formation, urticaria surrounding erythematous flare when rubbed (Darier sign)
Bullous lupus erythematosus
occurs in patients with a diagnosis of systemic lupus, sun-exposed skin is preferentially involved
lesions are not pruritic or symmetric, do not have a predilection for extensor surfaces of arms, elbows, knees, or scalp; vesicles and bullae typically photo-distributed or widespread, asymptomatic
Differential History Examination
Erythema multiforme
ingestion of new medications in the days or weeks before onset, implicated medications include antibiotics (trimethoprim-sulfamethoxazole), anticonvulsants (lamotrigine), NSAIDs, and allopurinol
characterized by atypical targetoid lesions, macules, vesicles, bullae on palms and soles; may be generalized
Stevens-Johnson syndrome
more fulminant form of erythema multiforme with systemic and mucosal involvement of <10% of body surface area, severe mucocutaneous reaction with prodrome of fever, malaise, chills, 1 day to 2 weeks before onset
palms, soles, and extensor surfaces with macules, may evolve to papules, vesicles, bullae, urticarial plaques, or confluent erythema; center of lesions purpuric, vesicular, or necrotic imparting targetoid appearance, secondary infection follows
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