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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