(1)
Department of Dermatology, University of Pennsylvania, Penn Presbyterian Medical Center Medical Arts Building, Philadelphia, PA, USA
Abstract
Vesiculobullous diseases are characterized by the presence of blisters and erosions on mucous membranes and/or skin. Blisters are caused by splits in either the epidermis or dermis. They can be classified by the level of this split and type of associated inflammation.
Keywords
Vesiculobullous diseasesVesicobullous diseaseBlistering diseasesClinically it can be difficult to distinguish the level of a blister. However, one can infer the level of the split based on certain findings:
If mostly flaccid bullae are seen, it is more likely to be intraepidermal
If most blisters are tense and intact, and if there are associated milia and scarring, it is more likely to be subepidermal.
Yet for blisters on hands and feet, keep in mind that all blisters tend to remain tense given the thickened stratum corneum.
With time, tense blisters can become flaccid, but flaccid blisters cannot become tense.
Hemorrhagic blisters presumably are subepidermal, since vessels are in the dermis.
Blisters caused by infection or inflammation should start on an erythematous base
When performing biopsies to diagnose blistering diseases: for H&E, perform a biopsy of lesional skin; for direct immunofluorescence (DIF), most recommend biopsy of perilesional skin; the rationale for perilesional in this case is that normal structures will be intact without blister, and for a DIF, intact anatomy is important for identifying the targeted antigen.
Three primary causes of blisters in the epidermis:
Acantholysis (loss of keratinocyte cohesion)
Spongiosis (intercellular edema)
Ballooning degeneration (viral)
Clinical signs suggestive of suprabasilar split or full thickness epidermal necrosis:
Nikolsky’s sign = slight tangential pressure of skin causes denudation; seen in TEN and pemphigus; implies epidermal separation
Asboe-Hansen sign = aka pseudo-Nikolsky’s sign, an extension of blister with pressure applied on top
4.1 Subcorneal Blisters/Superficial
1.
Pustular psoriasis and palmoplantar pustulosis
These are two separate entities; psoriasis should have physical findings beyond palmoplantar pustules
With palmoplantar pustulosis, consider SAPHO syndrome
Path = subcorneal neutrophilic pustules, ddx AGEP, candidiasis
See also Papulosquamous: Psoriasiform
2.
Acute generalized exanthematous pustulosis (AGEP)
Non-follicular, sterile pustules on erythematous background, may start on face/axilla/inguinal folds, then generalize; ddx pustular psoriasis, candidiasis
Caused most commonly by beta-lactams, macrolides, terbinafine
<4 days after exposure, non-antibiotics have longer latency period
Can be associated with neutrophilia/elevated WBC (18–25), fever
Patch testing positive in 80 %
May cause upregulated IL-8 (neutrophil chemoattractant)
See also Vascular: Toxic Erythema: Drug Eruptions
3.
Infections (except viral)
(a)
Bacterial infections
I.
Bullous impetigo (S. aureus)
Can be considered a localized form of SSSS
Increased incidence in atopic dermatitis
See also Infectious Diseases: Bacterial
II.
Staphylococcal scalded skin syndrome (SSSS)
Aka Ritter’s disease
See primarily in children <5
Can see in adults in context of renal failure (unable to clear toxin) or immunosuppression
Can present with erythroderma, scarlatiniform eruption
Caused by Staph exfoliative toxin A, from Staph (group 2, phage 71) against Dsg1
Path: granular layer split (unlike apoptotic keratinocytes in TEN, in entire epidermis)
See also Infectious Diseases: Bacterial and Vascular: Toxic Erythema: Drug Eruptions: Scarlatiniform
(b)
Superficial fungal infections
I.
Bullous tinea
Bullous tinea pedis usually T. mentagrophytes
Bullous tinea corporis usually T. rubrum
See also Infectious Diseases: Fungal
II.
Bullous candida/ candidiasis
See also Infectious Diseases: Fungal
(c)
Bullous syphilis
See also Infectious Diseases: Treponemes and Spirochetes
4.
Pemphigus foliaceus
Can be subcorneal or intraepidermal
Antigen = desmoglein-1 = 160kD
Clinically scale/crust can resemble “cornflakes”
Path: may see cling-on keratinocytes attached to the roof of the blister (aka “the dingleberry”)
DIF = intercellular IgG and complement
IIF done on guinea pig esophagus
Antibodies can cross placenta in pregnancy, but do not cause neonatal skin disease since Dsg3 more present in neonate skin (mucosa-like skin)
(a)
Pemphigus erythematosus (Senear-Usher syndrome)
A controversial entity that was formulated to describe an overlap syndrome of pemphigus foliaceus and SLE; however, more accepted now as just a localized variant of pemphigus foliaceus
Scaly, crusted lesions in malar, scalp, chest, back (seborrheic distribution)
Only rare patient has features of both pemphigus and SLE; but classical description includes positive ANA, DIF with DEJ and intraepidermal involvement
(b)
Fogo selvagem (endemic pemphigus foliaceus in Brazil)
Associated with the black fly (Simulium)
Fogo selvagem means “wild fire” in Portuguese
May be autoimmune? No clear infectious etiology yet identified
5.
Subcorneal pustular dermatosis (Sneddon-Wilkinson disease)
Annular or polycyclic plaques and subcorneal pustules in flexures (especially axillae)
May have associated IgA paraproteinemia
Responds to dapsone (unlike pustular psoriasis)
Immunofluorescence should be negative
6.
IgA pemphigus
(a)
Subcorneal pustular dermatosis type
Might include Sneddon-Wilkinson, which is clinically and histologically indistinguishable, plus can have IgA? This remains controversial.
Antigen target = desmocollin-1 (110 kD)
DIF shows intercellular IgA deposition
(b)
Intraepidermal neutrophilic type
Sunflower-like configuration
May have IgA Ab against Dsg1 or 3
7.
Infantile blisters/pustules
(a)
Erythema toxicum neonatorum (ETN)
Extremely common (50 % of full term neonates)
Presents with papules, vesicles, macules
Clinically can do a Wright stain to check for eosinophils to confirm diagnosis
(b)
Infantile acropustulosis
Typically more acral distribution
Ddx scabies, Gianotti-Crosti
May be induced post-scabetic
(c)
Transient neonatal pustular melanosis (TNPM)
Presents at birth, ddx ETN (may be a variant?)
Vs. ETN, has neutrophils, and leaves hyperpigmentation behind for months
(d)
Miliaria crystallina
See also Vesiculobullous: Other: Miliaria
4.2 Intraepidermal Blisters
1.
Herpes
Infects keratinocyte nuclei causing “ballooning degeneration”: keratinocyte necrosis leads to formation of multi-nucleated giant cells with chromatin margination, molding of nuclei (3Ms)
Clinically, herpes may show umbilicated vesicles (like poxviruses)
(a)
Herpes simplex virus (HSV)
(b)
Varicella zoster virus (VZV)
See also Infectious Diseases: Viral
2.
Acute eczematous dermatitis
Classic example = allergic contact dermatitis to poison ivy
Blisters caused by spongiosis
On path, ddx arthropod assault, drug (“drug or bug”)
See also Eczematous
3.
Friction/trauma blisters
Path: intraepidermal blister on acral skin, minimal inflammation
4.
Epidermolysis bullosa simplex (Weber-Cockayne type)
5.
Incontinentia pigmenti
Four stages: 1. Vesicular, 2. Verrucous, 3. Hyperpigmentation, 4. Hypopigmentation
Aka Bloch-Sulzberger syndrome
First three stages usually in infancy, in lines of Blaschko; fourth stage (hypopigmented, atrophic streaks) may persist indefinitely
X-linked dominant disease, lethal in males
Can have dental (conical or peg teeth), eye (coloboma, strabismus), neurologic, musculoskeletal abnormalities
Defect in NEMO, NF-κΒ essential modulator; thus lose regulation of apoptosis
Path (vesicular stage) = eosinophilic spongiosis, necrotic keratinocytes, dyskeratosis, dermal eosinophilic infiltrateRelated posts:
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