Vesiculobullous Esions
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EPIDERMOLYSIS BULLOSA
Epidermolysis Bullosa is a group of rare, incurable genetic disorders caused by a mutation in at least one of 16 different genes. A defect in the attachment between the layers of the skin or mucosa leads to blistering and ulceration after relatively minor trauma or friction. The common clinical presentation includes:
- Blistering and ulceration of traumatized areas, usually seen on the hands and feet.
- Severity ranging from mild to debilitating.
- Lesions can lead to scarring, which may be associated with atrophy and leukoplakia.
- Variations include epidermolysis bullosa simplex, junctional epidermolysis bullosa, and dystrophic epidermolysis bullosa.
- Mucosal involvement is not present with all variants.
- Increased risk for squamous cell carcinoma development.
Diagnosis is based on the lesion history, clinical presentation, genetic testing and immunohistochemical and electron microscopy. Specific antibody markers are used to evaluate the basement membrane zone. The list of similar disorders is large due to the variability of this group of conditions. Your differential diagnosis should include:
- Bullous pemphigoid.
- Mucous membrane pemphigoid.
- Erosive lichen planus.
- Erythema multiforme.
There is no known cure and treatment is palliative only, often requiring a multidisciplinary team.
ERYTHEMA MULTIFORME
Erythema Multiforme is an cell-mediated auto-immune disorder, possibly caused by the deposition of immune complexes in the superficial layers of the skin and mucous membranes. It has been known to be associated with certain infections (herpes simplex virus, mycoplasma pneumoniae, cytomegalovirus, Epstein-Barr virus, influenza virus), a wide variety of medications (antibiotics, antiepileptics, non-steroidal anti-inflammatory drugs, statins, vaccines) and other medical conditions (inflammatory bowel disease, malignancy, menstruation). Erythema multiforme can be confused with the more serious Stevens-Johnson syndrome. The common clinical presentation includes:
- Target-like lesions (may be called iris lesions).
- Pink or red papules which can become plaques.
- Lesions on the hands, feet, arms and legs are common. Trunk less so.
- Early mucosal lesions are macular, erythematous, and occasionally bullous.
- Genital and ocular lesions may be present.
- Symptomatic, usually burning or itching. Itching can be very severe.
Diagnosis is usually based on the lesion history and clinical presentation only. If a biopsy is necessary, microscopic findings may include:
- Bulla formation visible in conventional and electron-microscopy.
- Edema in the papillary layer.
- Dermal inflammatory infiltrates consist of lymphocytes and histiocytes.
Your differential diagnosis should include:
- Acute herpetic gingivostomatitis.
- Pemphigus vulgaris.
- Major aphthous ulcers.
- Erosive lichen planus.
- Mucous membrane pemphigoid.
Treatment varies depending on the severity, but may include:
- Identification and elimination of predisposing factor(s).
- Mild form – palliative care only.
- Severe form – systemic corticosteroids and parenteral fluid replacement.
- In the case of a viral trigger, antiviral medications.
HAND FOOT and MOUTH
Hand-Foot-and-Mouth Disease is a very common childhood disease caused by an enterovirus (coxsackievirus A and B) infection. It is principally seen in children under 5 years of age. The common clinical presentation includes:
- Incubation period of 5 to 9 days, resolves in about a week.
- Oral mucosal lesions that are similar to those resulting from herpes simplex infection.
- Non-pruritic and painless maculo-papular eruption on the hands, feet, and mouth.
- Palmar, plantar, and digital lesions are vesicular and erythematous.
- Usually involves nonkeratinized mucosa (soft palate, floor of mouth, buccal mucosa).
- Symptoms are usually mild.
- Resolution occurs without scab formation and does not lead to scarring.
Diagnosis is usually based on the lesion history and clinical presentation only. Your differential diagnosis should include:
- Herpangina.
- Herpes simplex infection.
- Lymphonodular pharyngitis.
The disease is self-limiting and treatment is usually palliative only.
HERPANGINA
Herpangina is a highly contagious disease usually caused by a coxsackie (A and B) virus infection. Though primarily a pediatric disease it may present in newborns, adolescents, and young adult patients. The common clinical presentation includes
- Incubation period of 5 to 9 days, resolves within 2 weeks.
- Acute onset of symptoms that involves the posterior oral cavity.
- Macular erythematous areas precede short-lived vesicular eruption, followed by ulceration.
- Pharyngitis, dysphagia, fever, malaise, headache, and lymphadenitis.
Diagnosis is usually based on the lesion history and clinical presentation only. Your differential diagnosis should include:
- Hand-foot-and-mouth disease.
- Varicella (chicken pox).
- Acute herpetic gingivostomatitis.
The disease is self-limiting and treatment is usually palliative only.
HERPETIC GINGIVOSTOMATITIS
Herpetic gingivostomatitis describes inflammation of the gingiva and oral tissues caused by a herpes simplex virus infection. The majority of cases are caused by HSV1 (occasionally HSV2) and remain subclinical. Though primarily a pediatric disease it may present in adult patients. The initial reaction can be referred to as acute herpetic gingivostomatitis. Recurrent reactions are often termed secondary (recurrent) herpetic stomatitis. The common clinical presentation includes:
- Incubation period of up to 2 weeks, resolves within a week or two.
- Abrupt onset may include fever, lymphadenopathy, and headache.
- Coalescing small vesicles that ulcerate, appearing with a yellow fibrinous base and an erythematous halo.
- Affects keratinized and nonkeratinized mucosa.
- Gingival tissue with edema, erythema, and pain.
- Lips and perioral skin may be involved.
Diagnosis is usually based on the lesion history and clinical presentation only. Your differential diagnosis should include:
- Herpangina.
- Hand-foot-and-mouth disease.
- Varicella (chicken pox).
- Herpes zoster (shingles).
- Erythema multiforme (though typically doesn’t involve the gingiva).
The disease is self-limiting and treatment is usually palliative only.
MUCOUS MEMBRANE PEMPHIGOID
Mucous Membrane Pemphigoid is a rare auto-immune disorder caused by antibodies directed at the basement membrane zone that leads to subepidermal blister formation. The disease often first manifests with oral lesions, but systemic and serious multi-organ or ophthalmic involvement may be seen. The common clinical presentation includes:
- Nikolsky’s sign (slight rubbing of the skin results in exfoliation of the outermost layer).
- Short lived vesicles and bullae, followed by ulceration.
- Multiple intraoral sites including keratinized and non-keratinized tissue.
- Usually in older adults, twice as likely in females.
- Ocular lesions noted in one-third of cases.
- Scarring of ocular, laryngeal, nasopharyngeal, and oropharyngeal tissues possible.
Diagnosis is based on the lesion history, clinical presentation and microscopic findings, which may include:
- Subepithelial cleft formation.
- Linear deposition of IgG and complement (C3) along basement membrane zone.
- Direct immunofluorescence examination positive in 80% of cases.
- Indirect immunofluorescence examination is usually negative.
Your differential diagnosis should include:
- Pemphigus vulgaris.
- Erythema multiforme.
- Erosive lichen planus.
- Lupus erythematosus.
- Epidermolysis bullosa.
Treatment options include:
- Topical corticosteroids.
- Systemic corticosteroids (prednisone) or other immunosuppressive medications.
- Azathioprine or cyclophosphamide.
- Tetracycline/niacinamide.
- Dapsone (antibiotic).
Scarring of the oral tissue can be debilitating. Management can be difficult and usually requires a multidisciplinary approach.
PEMPHIGUS VULGARIS
Pemphigus Vulgaris is a rare auto-immune disorder (type II hypersensitivity reaction) caused by antibodies directed at the desmosome-related proteins desmoglein 3 or desmoglein 1. This leads to acantholysis (loss of intercellular cohesion) and subsequent subepidermal blister formation. The common clinical presentation includes:
- Nikolsky’s sign (slight rubbing of the skin results in exfoliation of the outermost layer).
- Painful, shallow irregular ulcers with friable adjacent mucosa.
- Multiple intraoral sites including keratinized and non-keratinized tissue.
- Can present with cutaneous blisters, as well as blistering on other mucosal surfaces (conjunctiva, nose, esophagus).
Diagnosis is based on the lesion history, clinical presentation and microscopic findings, which may include:
- Tzanck cells – large, rounded keratinocytes with a hypertrophic nucleus.
- Acantholysis between suprabasal and basal layer of epithelium.
- Vesicle forms at site of epithelial split.
- IgG and complement deposition in intercellular spaces.
- Direct immunofluorescence examination positive in all cases.
- Indirect immunofluorescence examination positive in most cases.
Your differential diagnosis should include:
- Mucous membrane pemphigoid.
- Erythema multiforme.
- Erosive lichen planus.
- Lichenoid drug reaction.
Treatment options include:
- Topical corticosteroids.
- Systemic corticosteroids (prednisone) or other immunosuppressive medications.
- Azathioprine or cyclophosphamide.
- Tetracycline/niacinamide.
- Dapsone (antibiotic).
STEVENS-JOHNSON SYNDROME
Stevens-Johnson syndrome is a rare but potentially life-threatening auto-immune disorder (type IV hypersensitivity reaction) that leads to blistering and skin-detachment. Drugs (lamotrigine, carbamazepine, allopurinol, sulfonamide antibiotics, nevirapine) and infection (mycoplasma pneumoniae, cytomegalovirus) are the most likely triggers. Stevens-Johnson syndrome is distinct from and can be confused with Erythema multiforme, but may sometimes be referred to as erythema multiforme major. The common clinical presentation includes:
- Cutaneous appearance of painful erythematous rashes, bullae, and erosions.
- May appear on the face and trunk and may spread to the extremities.
- Labial vermilion and anterior portion of oral cavity usually affected initially.
- Early macular phase followed by erosion, sloughing, and painful ulceration.
- Lip ulcers appear crusted and hemorrhagic.
- Target lesions (Iris lesions) on the skin.
- Several complications associated with the eyes, liver, kidneys, and respiratory tract.
Diagnosis is based on the lesion history, clinical presentation and microscopic findings, which may include:
- Epithelial and connective tissue edema.
- Separation with basal cell liquefaction.
- Intraepithelial neutrophils and perivascular lymphocytic infiltrate.
Your differential diagnosis should include:
- Pemphigus vulgaris.
- Mucous membrane pemphigoid.
- Bullous pemphigoid.
- Acute herpetic gingivostomatitis.
Treatment options include:
- Identification and elimination of predisposing factor(s).
- Topical corticosteroids.
- Systemic corticosteroids (prednisone) or other immunosuppressive medications.
- In the case of a viral trigger, antiviral medications.
VARICELLA-ZOSTER VIRUS
Varicella (chickenpox) and Herpes Zoster (shingles) are the primary and recurrent forms of varicella-zoster virus (VZV) infections respectively. Varicella is usually a pediatric infection but can be seen in adult patients. Secondary infections (shingles) most commonly affect the elderly or immunocompromised patients. The common clinical presentation includes:
Varicella (chickenpox):
- Incubation around 2 weeks.
- Fever, headache, malaise, and pharyngitis.
- Widespread vesicular eruption that rupture forming shallow, defined ulcers.
- Forms small, itchy blisters, which eventually scab over.
Herpes Zoster (shingles):
- Unilateral reactivation of latent virus causes grouped vesicular eruption of skin and/or oral mucosa associated with the dermatome (area of skin that is mainly supplied by a single spinal nerve) .
- Possible prodromal symptoms.
- Vesicles may coalesce prior to ulceration and crusting.
- Lesions can be extremely painful, and may cause paresthesia, burning, or tingling.
Diagnosis is based on the lesion history, clinical presentation and cytological findings, which may include:
- Cytologic smear with cytopathic multinucleated giant cells.
- Positive viral culture or PCR examination of blister fluid.
- Serologic evaluation of VZV antibody.
- Direct fluorescent examination using fluorescein-labeled VZV antibody.
Your differential diagnosis should include:
- Pemphigus vulgaris.
- Mucous membrane pemphigoid.
The disease is self-limiting and treatment is usually palliative only. Antiviral drugs (especially acyclovir) may be necessary for immunocompromised patients or may be of some benefit to immunocompetent patients during the prodromal phase. The prognosis is good, but recurrence is likely.
