Blistering skin diseases

This article provides an overview of blistering skin diseases, including bullous impetigo, staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), epidermolysis bullosa acquisita, bullous pemphigoid, pemphigus vulgaris, and dermatitis herpetiformis.

For more information on each specific condition, see the respective articles.

Overview of blistering diseases
	Median age	Etiology	Clinical features		Treatment
Bullous impetigo	2–6 years of age	Staphylococcus aureus: Exfoliative toxin A and B cleave desmoglein-1 → disruption of keratinocyte attachments	Vesicles that grow to form large, flaccid bullae, which go on to rupture and form thin, brown crusts Affects the trunk and upper extremities Severe cases: systemic signs (e.g., fever, malaise, weakness) Negative Nikolsky sign		Wound cleansing with antibacterial washes First-line First-generation cephalosporins (e.g., cephalexin) Dicloxacilin Alternative Amoxicilin-clavulanate Macrolides MRSA infection Clindamycin Trimethoprim-sulfamethoxazole Doxycycline
Staphylococcal scalded skin syndrome (SSSS)	6 months–5 years of age		Initially: fever and diffuse or localized erythema that begins periorally After 24–48 hours Flaccid, easily ruptured blisters that break to reveal moist, red skin beneath (resembles scalding) No mucosal involvement Positive Nikolsky sign		Hospitalization IV antibiotics Nafcillin, oxacillin Vancomycin (in settings with high MRSA prevalence) NSAIDs Supportive case (esp. fluid resuscitation) Emollients Dressing of areas where skin has sloughed off
Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)	All ages	Adverse drug reaction (most common) Sulfasalazine Oxicam NSAIDs Antiepileptics (e.g., phenytoin, phenobarbital) Antibiotics: sulfonamides (e.g., TMP/SMX), aminopenicillins Infections: mycoplasma pneumonia	Prodromal phase (1–3 weeks after trigger exposure/infection) High fever, malaise, sore throat, myalgia, and/or arthralgia Mucocutaneous lesions (1–3 days after prodromal phase) Cutaneous Painful, erythematous/purpuric macules May have a targetoid appearance Bullae and/or vesicles Mucosal Oropharyngeal: stomatitis, mucositis, pharyngeal involvement Ocular: severe conjunctivitis, corneal ulcers, anterior uveitis Urogenital: urethritis, ulcerative vaginitis, vulvar bullae Positive Nikolsky sign		Discontinue causative drug Supportive therapy and wound management Antibiotic therapy (in infection/sepsis) Regular dermatological, ophthalmological, and urological/gynecological evaluation
Epidermolysis bullosa acquisita	40–60 years of age	Autoantibodies against type VII collagen	Subepidermal blistering Noninflammatory form (most common) Tense vesicles and blisters on extensor surfaces (e.g., hands, knees, knuckles) Inflammatory form Tense vesicles and bullae on areas such as the trunk and skin folds) Negative Nikolsky sign		Systemic steroids Immunosuppressants Avoid skin trauma
Bullous pemphigoid	> 60 years of age	Type II hypersensitivity reaction Antihemidesmosome antibodies (IgG)	Prodromal stage: urticarial lesions Large, tense, subepidermal blisters on normal, erythematous, or erosive skin weeks to months after prodromal stage Intensely pruritic, possibly hemorrhagic, lesions, heal without scar formation Distributed on palms, soles, lower legs, groin, and axillae Oral involvement is rare Negative Nikolsky sign		First-line: high-dose topical steroids (e.g., clobetasol, betamethasone) Second-line: systemic glucocorticoids and immunosuppressants (e.g., methotrexate, azathioprine)
Pemphigus vulgaris	40–60 years of age	Type II hypersensitivity reaction IgG antibodies against desmoglein 3 and desmoglein 1	Initially affects the oral mucosa before extending to parts of the body exposed to pressure Progression in stages First, spontaneous onset of painful flaccid, intraepidermal blisters Then, rupture and confluence of lesions → development of erosions and crusts → reepithelialization with hyperpigmentation but without scarring Pruritus is typically absent Positive Nikolsky sign		First-line: Rituximab and systemic glucocorticoids (e.g., prednisone) Systemic glucocorticoids plus immunosuppressive therapy (e.g., azathioprine) Topical treatment
Dermatitis herpetiformis	15–40 years of age	Most likely genetic predisposition to autoimmune reaction Associated with celiac disease and sensitivity to potassium iodide (e.g., contrast medium)	Tense, grouped subepidermal vesicles, papules, and/or bullae (herpetiform appearance) Intensely pruritic Bilateral, symmetrical distribution (e.g., elbows, knees, buttocks, shoulders, scalp) No mucosal involvement Negative Nikolsky sign		First-line: dapsone Gluten-free diet Topical steroids to control severe pruritus Low-iodine diet

• Also see:
  • Differential diagnosis of autoimmune blistering diseases
  • Differential diagnoses of severe exfoliative skin conditions

Nikolsky sign is positive in intraepidermal blisters and is therefore present in pemphigus vulgaris and severe exfoliative skin conditions (SSSS, SJS, TEN).