Pemphigus vulgaris in AdultSee also in: Anogenital,Oral Mucosal Lesion
Alerts and Notices
SynopsisPemphigus vulgaris (PV) is an acquired autoimmune bullous disease of the mucous membranes with or without skin involvement. It is typically characterized by the presence of circulating pathogenic autoantibodies (predominantly immunoglobulin [Ig]G4) against desmoglein, a cadherin-family, keratinocyte cell surface adhesion molecule of the desmosome, although other antibody subtypes and autoantibodies against other antigenic targets have been described. The target antigens in PV are desmoglein 3 (Dsg3) with or without desmoglein 1 (Dsg1). More than half of patients have both skin and mucosal involvement. In the mucosal-dominant type of PV, autoantibodies against Dsg3 (anti-Dsg3 Ig) are typically present, and in the mucocutaneous type, autoantibodies against Dsg1 and Dsg3 are typically present; however, variations in these patterns can be seen in the real-world setting.
The estimated incidence worldwide is 0.76-5 cases per million per year, although PV occurs in higher incidences in individuals of Jewish ancestry, as well as in certain geographic areas (Middle East, Southeastern Europe, and India). Variants of the ST18 gene have been found to confer increased risk of PV in some populations. PV is typically a disease of adults, with average onset between the ages of 40 and 60 years, but PV rarely can occur in childhood and young adulthood. There does not appear to be a consistent sex predilection.
Severe cases of PV can be life-threatening, and complications can be related to immunosuppression from drugs used to treat severe PV, secondary infections, loss of the skin barrier, and poor oral intake.
L10.0 – Pemphigus vulgaris
49420001 – Pemphigus vulgaris
Differential Diagnosis & Pitfalls
- Pemphigus foliaceus
- Drug-induced pemphigus (penicillamine, captopril, thiol-containing compounds)
- IgG/IgA pemphigus – A rarely reported condition. It is unclear whether it represents a separate entity or pemphigus vulgaris that it transitioning to IgA pemphigus. Clinical findings in a recently reported series resembled pemphigus vulgaris, pemphigus foliaceus, and IgA pemphigus. In IgG/IgA pemphigus, dapsone can be used as an ancillary treatment.
- Paraneoplastic pemphigus – Associated with underlying neoplasms (non-Hodgkin lymphoma, chronic lymphocytic leukemia, Castleman disease, thymomas, sarcomas, Waldenström macroglobulinemia).
- Erythema multiforme – This condition may appear clinically identical to paraneoplastic pemphigus. Patients may have a history of previous episodes that resolved within 2-4 weeks. The presence of classic targetoid lesions of the skin is more consistent with erythema multiforme.
- Bullous pemphigoid – Tense vesicles and bullae are the predominant feature of this condition, and only 20% of patients have oral involvement.
- Stevens-Johnson syndrome – Usually drug induced and accompanied by high fever, skin tenderness, mucosal erosions, and desquamation 1-3 weeks after starting the inciting medication.
- Reactive infectious mucocutaneous eruption (RIME) – Hemorrhagic crusting of lips is accompanied by a sparse macular, papular, or vesicular cutaneous eruption.
- Staphylococcal and streptococcal toxic shock syndrome and toxic shock-like syndrome – Look for sudden onset of exanthematous eruption.
- Epidermolysis bullosa acquisita
- Linear IgA dermatosis
- Acute graft-versus-host disease – Clinical history of bone marrow transplantation.
- Drug-induced hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [DRESS]) – Look for facial edema (hallmark of DRESS), eosinophilia, hepatitis, and other visceral involvement.
- Subcorneal pustular dermatosis (Sneddon-Wilkinson syndrome)
- Hailey-Hailey disease
- Dermatitis herpetiformis
- Drug-induced erythroderma
- Erythrodermic psoriasis
- Atopic dermatitis with erythroderma
- Contact dermatitis
- Sézary syndrome (see cutaneous T-cell lymphoma)
- Phototoxic reaction
- Photoallergic reaction
- Lichen planus – The erosive oral lesions of lichen planus are usually surrounded by characteristic radiating keratotic striae.
- Oral ulcers of systemic lupus erythematosus
- Mucous membrane pemphigoid – This condition mostly affects the mucosa, most commonly the gingiva and palatal mucosa, with only 20% of patients showing cutaneous lesions.
- Primary herpes gingivostomatitis – The oral ulcerations may be diffuse but are composed of smaller lesions (1-2 mm) that coalesce.
- Aphthous stomatitis
- Chemotherapy-induced mucositis
- Plasma cell gingivitis – This hypersensitivity reaction presents as marked erythema of the gingiva (desquamative gingivitis) without blister formation.
- Epidermolysis bullosa acquisita – This almost never presents intraorally without skin involvement.
- Linear IgA disease – This almost never presents intraorally without skin involvement.
- Chronic oral erythema multiforme – These ulcers remit completely and then recur and are associated with recurrent herpes simplex virus infection.
- Bullous pemphigoid – This autoimmune bullous dermatosis is less likely to have oral involvement (20% of cases) and can be distinguished by histological and immunofluorescence studies.
Drug Reaction DataBelow is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.
Patient Information for Pemphigus vulgaris in Adult
OverviewPemphigus vulgaris (PV) is an autoimmune disease of the skin and mouth (mucous membrane). Autoantibodies attack molecules that essentially hold the skin cells together, causing them to separate and resulting in blisters. Pemphigus vulgaris is characterized by multiple lesions or blisters that do not heal, or that recur and spread to larger portions of the body. As many as 80% of the cases first exhibit symptoms in the mouth, and the mouth is sometimes the only site of lesions.
Typically, those with pemphigus vulgaris will have multiple ulcers that persist for weeks to months. Blistering may be accompanied by severe pain, itching, burning, and stinging. If extensive, blistering can lead to life-threatening fluid loss, infection, and disfigurement. Fatalities from pemphigus vulgaris are extremely unlikely in the United States; however, timeliness of treatment is critical.
Pemphigus vulgaris is categorized as an ultra-rare disease, and, consequently, as many as 80% of cases are misdiagnosed for an average of 6 months. With treatment, lesions can heal normally without scarring. Most patients treated for pemphigus will enter a partial or full remission within 2-5 years.
Who’s At RiskPemphigus vulgaris affects men and women approximately equally. Although sometimes appearing in younger people, the average onset of symptoms is in those aged 50-60 years. Pemphigus vulgaris can occur in persons of any ethnicity, but the disorder tends to appear more often in persons of Mediterranean or Ashkenazi Jewish ancestry.
Pemphigus vulgaris is categorized as an ultra-orphan disease (meaning it is very rare), affecting approximately 10 000-30 000 people in the United States.
Signs & SymptomsEighty percent of the time, symptoms begin in the mouth, with soft (flaccid) blisters or erosions, and these symptoms are often mistaken for other conditions of the mouth.
Two-thirds of those affected with pemphigus vulgaris eventually experience lesions on both the skin and in the mouth.
If left untreated, the erosion/blisters gradually spread over an increasing surface area and can be complicated by severe infections, metabolic disturbances, or fluid loss.
Self-Care GuidelinesSelf-care measures for pemphigus vulgaris are as follows:
- Keep wounds clean – Be very gentle and do not use harsh cleansers.
- If bandaging is necessary, use bandages that provide moisture and protection, or keep the skin moist with sterile lotions. Silicone bandages, such as those used in burn centers, can be useful. Bandages should allow for airflow but protect against contaminants.
- Avoid touching ointment and bandages.
- Do not use bandages that are dry or stick to your skin.
- Avoid spicy foods (eg, garlic and onions) and nuts, which may help relieve symptoms.
- Antibiotic ointment or cream can help treat infection – An antibiotic that includes a local painkiller can bring some relief of pain associated with pemphigus vulgaris.
- Oral rinses and ointments can be used to reduce pain in the mouth.
When to Seek Medical CareIt is very important to get an accurate confirming diagnosis as soon as possible, so see your doctor if you display any of the signs or symptoms discussed here or suspect you might have pemphigus vulgaris. Early expert diagnosis is important, as pemphigus vulgaris – as with other autoimmune diseases – becomes more resistant to treatment if it is not promptly and appropriately controlled.
TreatmentsDiagnosis is confirmed through a biopsy of the skin or the inner lining of the mouth (oral mucosa). The tissue specimen is sent for a test called direct immunofluorescence. After a diagnosis is made, treatment begins with a period of intense therapy with corticosteroids (eg, prednisone) in an effort to gain control and suppress disease activity until no new lesions appear. The duration of this phase ranges from several weeks to months. Often, a second medication is added to allow lower doses of the corticosteroid and reduce associated side effects.
After all lesions heal, medications can gradually be tapered, aiming for the lowest dose that prevents new "flares" of lesions from appearing.
If pemphigus vulgaris fails to respond to corticosteroids, results in unacceptable side effects, or is extensive or progressing rapidly, your doctor may add an immunosuppressant, IVIG treatment, plasmapheresis, or biologic agents.
Pemphigus vulgaris in AdultSee also in: Anogenital,Oral Mucosal Lesion