Vesiculobullous Diseases




(1)
Department of Dermatology, University of Pennsylvania, Penn Presbyterian Medical Center Medical Arts Building, Philadelphia, PA, USA

 



4.1 Subcorneal Blisters/Superficial

4.2 Intraepidermal Blisters

4.3 Suprabasilar Blisters

4.4 Subepidermal Blisters

4.4.1 Neutrophilic

4.4.2 Lymphocytic

4.4.3 Eosinophilic and Mixed

4.4.4 Non-inflammatory/Cell-Poor

4.5 Other


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 diseases


Clinically 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

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May 14, 2016 | Posted by in Dermatology | Comments Off on Vesiculobullous Diseases

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