Vesiculobullous Diseases
General Information
- group of conditions associated with blister formation
- Blister = fluid-filled raised area
Ø Vesicle = < 5 mm in diameter
Ø Bulla = > 5 mm in diameter
Ø Pustule = blister filled with pus
- Acantholysis = loss of the cohesion between the keratinocytes due to disruption of intercellular bridges
- Ballooning degeneration
- Dyskeratosis
- Spongiosis – intercellular edema within the epidermis, causing spaces between the keratinocytes
- Tzanck smear
Dermoepidermal Junction
- Hemidesmosomes attach the keratinocytes to the basal lamina
- Anchoring filaments extend from the plasma membrane of the basal layer of the keratinocytes to the lamina densa
- Anchoring fibrils tie the epidermis to the dermis.
Categories of Vesiculobullous Diseases
1) Primary
Ø Immune mediated
Ø Non-immune mediated
2) Secondary
Major Vesiculobullous Diseases
Pemphigus
- occurs mostly in middle-aged adults
- Two major types
1) Pemphigus vulgaris (PV)
Ø most common type
Ø skin and mucosal involvement (head, trunk, axilla, groin, pressure points)
Ø lesions begin as flaccid blisters that enlarge and rupture easily
Ø crust-covered shallow erosions
Ø Positive Nikolsky’s sign – applying pressure into the blister causes it to extend into adjacent skin
2) Pemphigus foliaceus (PF)
Ø primary skin involvement (head and trunk especially)
Ø blisters are more superficial than those of PV
Ø ss severe
Ø erythema and crusting
- HISTO
q PV-suprabasal cleft (single layer of basal keratinocytes remains attached to the dermis like a “row of tombstones”
q Acantholytic cells are present in the blister cavity
- PV and PF are both immune mediated disorders
§ PV – IgG against desmoglein 3 (component of interkeratinocytic desmosomes)
§ PF – IgG against desmoglein 1 (1o in desmosomes of the upper epidermis)
§ Both can be identified by immunoflourescence of the skin
Ø net-like intercellular pattern seen
Bullous Pemphigoid (BP)
- most common subepidermal bullous disease
- clinically: occurs in elderly
- urticaria and tense bullae, may become large but do not rupture easily
- skin & mucosal involvement
- HISTO
Ø subepidermal cleft
Ø eosinophils are usually present in the blister cavity and dermis
- Immune mediated disorder
Ø IgG’s against antigens in hemidesmosomes
- these IgG’s are named bullous pemphigoid antigens 1 and 2 (BPAg1 and BPAg2)
- linear pattern of immunofluorescence with IgG and C3
- Treatment: corticosteroids and steroid-sparing agents
Herpes Gestationis
- Not due to Herpes infection
- Occurs in women in the 2nd or 3rd trimester of pregnancy or postpartum period
- Starts as a pruitic papulovesicular eruption on the abdomen
- Becomes vesiculobullous and may spread to trunk and extremities
- Rarely, infant may have mild involvement
- HISTO: similar to BP
- Immune mediated disorder
Ø IgG against a placental antigen
Ø This Ab crossreacts with BPAg2.
Ø Associated with HLA-DR3 and HLA-DR4 haplotypes
Ø Immunofluorescence: linear C3 +/- IgG at the BMZ
- Prognosis: if untreated the lesions go away days to weeks after delivery; may recur with subsequent pregnancies or with hormonal stimulation
- Treatment – corticosteroids
- Also known as pemphigoid gestationis.
Dermatitis Herpetiformis
- NOT due to herpes virus infection
- Associated with gluten-sensitive enteropathy
- Usually occurs in young adults
- Pruitis and blisters on extensor surfaces (elbows, knees, buttocks, back)
- HISTO: subepidermal cleft; neutrophilic microabscesses form at the tips of the dermal papillae; vacuolization occurs over these abscesses and eventually the vacuoles coalesce and form blisters
- Immune Mediated Disorder
Ø IgG and IgA which react with gliadin and reticulin
Ø Immunofluorescence: granular deposits of IgA at the DEJ
Ø Associated with HLA-DRw3 and HLA-B8 haplotypes
- Treatment: gluten-free diet; dapsone
Epidermolysis Bullosa – Congenita or Acquired
Epidermolysis Bullosa Congenita
- manifest at birth
- blisters develop spontaneously or following minor trauma
- range from mild blistering to severe and life threatening
- can cause scarring, deformities, and extracutaneous involvement
- usually autosomal (dominant or recessive) inheritance
- HISTO: location of cleft varies with subgroups (subepidermal in most cases); usually little or no inflammation
- Immunofluorescence is negative
- Treatment: supportive
Epidermolysis Bullosa acquisita
- non-hereditary and usually presents in adulthood
- IMMUNE-MEDIATED: positive IF with linear IgG and C3 at the BMZ
- MICRO
Porphyria
- This clinical feature is from a group of inborn or acquired disorders of porphyrin metabolism
- Most common for of porphyria in Europe and North America – porphyria cutanea tarda
Ø due to reduced activity of uroporphyrinogen decarboxylase (Uro—gen to Copro—gen)
Ø lab results: increased uroporphyrins in urine and plasma; increased coproporphyrins in feces
- Lesions are exacerbated by sunlight; heal with scarring
- HISTO
Ø subepidermal cleft
Ø marked thinning of superficial dermal vessels
Ø dermal papillae project into the floor of the blister (called festooning)
Erythema Multiforme
- this group of vesiculobullous diseases is divided into categories
Erythema multiforme skin lesions w/ or w/o mucosal lesions
Stevens-Johnson syndrome skin & mucosal lesions; association with systemic symptoms & internal organ involvement
Toxic epidermal necrolysis > 30% of total body surface area involved by blistering skin lesions
- Cell mediated immune reaction to numerous different agents (drugs, infection)
- HISTO
Ø subepidermal cleft if present
Ø epidermal spongiosis and basal layer vacuolization
Ø in the less severe forms – individual dyskeratotic keratinocytes
Ø Lymphocytes at the DEJ and around the upper dermal vessels
Disease Microscopic Findings
Pemphigus vulgaris Intercellular (netlike) IgG
Pemphigus foliaceus Intercellular (netlike) IgG
Bullous pemphigoid Linear IgG + C3 at BMZ
Herpes Gestationis Linear C3 +/- IgG at BMZ
Dermatitis herpetiformis Granular IgA at tips of dermal papillae
Epidermolysis bullosa congenita NONE
Epidermolysis bullosa acquisita Linear IgG + C3 at BMZ
Tags: Acantholytic cells, Dermatitis Herpetiformis, Epidermolysis Bullosa acquisita, Epidermolysis Bullosa Congenita, Erythema Multiforme, hemidesmosomes, Herpes Gestationis, Pemphigus, Porphyria, subepidermal cleft, Vesiculobullous Diseases
