Autoimmune Blistering

Diseases
By
Dr. Dalia A Attallah, MD
Prof. of Dermatology, Venereology and Andrology
ILOs of Autoimmune Blistering Diseases

• Definition of autoimmune blistering diseases.

• Etiology of different diseases.

• Different clinical presentation of the diseases.

• Management of different autoimmune blistering diseases.

• Differential Diagnosis of different autoimmune blistering diseases.

• Definition
• Autoimmune blistering diseases are skin conditions characterized by the formation
of blisters, which are the result of the destruction of cellular or extracellular
adhesion molecules by antibodies.

• The two most significant autoimmune blistering diseases are bullous

pemphigoid, pemphigus vulgaris.
• The most common among these is bullous pemphigoid.
 Anatomy and physiology
• Desmosomes:
• Junctional complex
• Connect epidermal keratinocytes to
each other
• Hemidesmosomes:
• Similar to desmosomes

• Anchor the basal epidermal

keratinocyte layer to the underlying
basement membrane
• Form the dermal–epidermal junction
Bullous pemphigoid
• Definition
• A non–life-threatening, chronic autoimmune disease
• Characterized by subepithelial bullae
• Caused by loss of adhesion between the epidermis and dermis

• Etiology:
• Type II hypersensitivity reaction
• IgG autoantibodies attack hemidesmosomal proteins:
• Targeted proteins: Bullous pemphigoid antigens BP180 and BP230

• Desmosomes connecting keratinocytes to each other remain intact → overlying skin is

strong and taut
Clinical Presentation
• Prodromal phase (lasting weeks to months):
• Pruritus (moderate to severe)
• Skin lesions may appear:
• Papular
• Eczematous plaques
• Urticaria-like
• Subepidermal bullae develop:
• Tense (not easily ruptured), Large (1‒3 cm), Contain clear fluid, Numerous and widespread
• Appear on normal or erythematous skin
• Frequently affected locations:
• Lower abdomen Axillae Extremity flexures
• Inguinal folds
• Mucosal involvement (10%‒30% of patients)
Bullae rupture : Leave moist erosions and crusting
No scarring
Management

The goal of therapy for both bullous pemphigoid and pemphigus vulgaris is to decrease autoantibody
production while minimizing drug-induced side effects.

• Mainstay initial therapy:

• Corticosteroids (topical or systemic):

• Topical (localized disease): clobetasol propionate
• Systemic (widespread disease): prednisone, prednisolone
• Niacinamide

• Tetracyclines (for anti-inflammatory effect):

• Doxycycline Tetracycline Minocycline
• Advanced and refractory disease:
• Steroid-sparing immunomodulatory agents:
• Mycophenolate mofetil
• Azathioprine
• Dapsone
• Methotrexate
• Cyclophosphamide

• Biologic therapies:
• Monoclonal antibodies (e.g., rituximab)
• Intravenous immunoglobulin (IVIG)
• Prognosis:
• Chronic, relapsing course
• Long-term remission is possible (after months to years).
Pemphigus vulgaris
• Definition
• A life-threatening, chronic autoimmune disease
• Characterized by intraepithelial bullae
• Caused by loss of adhesion between keratinocytes (acantholysis)

• Aetiology
• Type II hypersensitivity reaction
• IgG autoantibodies attack desmosomal proteins:
• Targeted proteins: desmoglein (DSG) types 1 and 3

• Hemidesmosomes remain intact:

• Basal layer of keratinocytes remain anchored to the basement membrane → “row of
tombstones” appearance on histology
Clinical presentation
• Pemphigus vulgaris is characterized by bullae with the following properties:
• Superficial acantholytic blisters
• Flaccid
• Rupture very easily:
• Leads to erosions
• Bleed easily
• Painful
• Appear on normal or erythematous skin
• Can occur anywhere on the body, most commonly:
• Mucosa (almost always present):
• Oral (often 1st site) → odynophagia (painful swallowing) → malnutrition
• Esophagus
• Nasal mucosa → epistaxis
• Conjunctiva
• Vulva, vagina, and cervix
• Penis
• Anus
• Cutaneous:
• Face and scalp
• Trunk
• Groin and axilla
• Secondary infection is common:
• Purulent drainage
• Surrounding erythema and induration
Management
• Mainstay initial therapy:
• Systemic glucocorticoids: prednisone
• Steroid-sparing agents:
• Rituximab
• Azathioprine
• Mycophenolate mofetil
• Dapsone
• Methotrexate
• Refractory disease:
• IVIG
• Cyclophosphamide
• Complications:
• Secondary infection
• Effects of long-term steroid use
• Prognosis:
• Often fatal without treatment
• Sepsis is the leading cause of death.
Diagnosis
In addition to evaluating clinical appearance, specific tests are performed to confirm the diagnosis of a blistering disease.

• Nikolsky sign
Slight mechanical pressure (by rubbing) is exerted on the skin → upper epidermal layer
slips away from lower layer →separation of epidermis → blistering

• Test is positive on previously unaffected skin.

• Nikolsky sign is present in pemphigus vulgaris , toxic epidermal necrolysis,

staphylococcal scalded skin syndrome and Stevens-Johnson syndrome

Not present in bullous pemphigoid

• Tzanck test
• Microscopic examination of scrapings from the base of a lesion to
look for Tzanck cells
• Tzanck cells (multinucleated giant cells) are present in:
• Pemphigus vulgaris
• No detection of Tzanck cells in:
• Bullous pemphigoid
• Skin biopsy:
• the specimen is taken from the perilesional area and is analyzed with
• Histology
• Direct immunofluorescence (DIF):
• Autoantibodies directed against bullous pemphigoid antigen of
the epithelial basement membrane

• Autoantibodies directed against pemphigus antigen of the

desmosome
Immunofluorescence findings in bullous pemphigoid and pemphigus vulgaris:
A: In bullous pemphigoid, staining of complement and antibodies occurs at the dermal–
epidermal junction.
B: In pemphigus vulgaris, staining of antibodies occurs within the epidermis in a reticular
(net-like) pattern.
• Serology
• Bullous pemphigoid: anti-hemidesmosome antibodies: IgG antibodies against
hemidesmosomes (an epithelial cell junction that connects basal cells to
underlying basement membrane)

• Pemphigus vulgaris: anti-desmoglein antibodies: IgG antibodies against

desmoglein-1 and/or desmoglein-3 (desmogleins are components of
desmosomes, a cell-to-cell connection that mediates keratinocyte adherence in
stratum spinosum)

• Other tests
• Serum testing with indirect immunofluorescence (IDIF): Detection of
circulating autoantibodies
Differential Diagnosis
• Stevens–Johnson syndrome: an immune-complex–mediated hypersensitivity
reaction involving the skin and mucous membranes, commonly triggered by
medications
• Mucosal involvement is very common.
• Nikolsky’s sign is positive. Diagnosis is clinical, and management is supportive.
Withdrawal of the causative agent is required.
• Staphylococcal scalded skin syndrome (SSSS): a life-threatening toxin-
mediated disease, primarily of young children, caused by Staphylococcus aureus:
resulting in diffuse cutaneous erythema, tenderness, formation of bullae, and
superficial desquamation without mucosal involvement.
• Nikolsky’s sign is positive.
• Diagnosis is clinical and confirmed with culture data. Management is with
antibiotics and supportive care.