Pemphigus Vulgaris

What happens in pemphigus vulgaris

The outer skin (epidermis) is made of cells held together by connecting structures called desmosomes. In pemphigus vulgaris, the immune system makes antibodies against desmoglein 3 (mainly in mucous membranes) and often desmoglein 1 (mainly in skin). The cells lose their connections (acantholysis), and a split forms within the epidermis. Because the blister roof is thin, blisters break easily and leave painful erosions.

Symptoms

Mouth and mucous membranes

• painful sores and erosions on the gums, inside the cheeks, palate and tongue, often the first sign, sometimes months before skin involvement
• difficulty eating, drinking and brushing teeth
• sores in the throat, nose, eyes, genitals and anus in some people
• hoarseness if the larynx is involved

Skin

• soft, fragile (flaccid) blisters on normal-looking skin
• blisters that break quickly, leaving raw, painful, sometimes bleeding areas that crust
• common on the scalp, face, chest, back, armpits and groin
• Nikolsky sign: gentle rubbing of normal-looking skin causes the top layer to slide off

Pemphigus vs bullous pemphigoid

Causes and triggers

The cause is autoimmune. Contributing factors:

• genetics: certain HLA types, explaining higher rates in some populations
• medicines: rarely, drugs such as penicillamine, captopril and some antibiotics trigger pemphigus
• other triggers: possibly infections, stress, sun exposure and some foods, though evidence is limited

It is not contagious.

Diagnosis

• skin or mucosal biopsy from the edge of a fresh blister: shows the split within the epidermis
• direct immunofluorescence of a sample of skin next to a blister: shows antibodies deposited around skin cells in a "fishnet" pattern; this is the key test
• blood tests: ELISA for anti-desmoglein 1 and 3 antibodies, which also help monitor disease activity
• evaluation of other mucous membranes by eye, ear-nose-throat and gynecology specialists when needed

Other causes of chronic mouth sores, such as herpes simplex, oral lichen planus and recurrent mouth ulcers, are ruled out.

Treatment

First-line

• Rituximab: a monoclonal antibody that depletes the B cells producing harmful antibodies. Combined with short-term steroids, it leads to remission in most people and is FDA-approved for moderate to severe pemphigus vulgaris.
• Corticosteroids: oral prednisone at high doses initially, then tapered.

Other options

• steroid-sparing immunosuppressants: mycophenolate, azathioprine
• IV immunoglobulin (IVIG) and plasma exchange for severe or resistant cases
• topical and injected steroids for localized lesions

Supportive care

• gentle wound care with non-stick dressings and petroleum jelly
• treating secondary infections promptly
• mouth care: soft toothbrush, mild toothpaste, steroid mouth rinses or gels, numbing mouthwashes before meals, avoiding spicy, acidic or crunchy foods
• nutrition and hydration support
• bone protection, blood sugar monitoring and infection prevention during long-term steroids

Outlook

Before steroids, pemphigus vulgaris was often fatal. Today, most people can control it, and many achieve complete remission off treatment, particularly after rituximab. Relapses can occur and are treated with further courses. Side effects of long-term immunosuppression are an important consideration, so regular follow-up with a dermatologist is essential.

Frequently asked questions

What is pemphigus vulgaris?

Pemphigus vulgaris is a rare autoimmune disease in which antibodies attack proteins that hold skin cells together. It causes painful mouth sores and fragile skin blisters that break easily, leaving raw areas.

What are the first signs of pemphigus vulgaris?

The first sign is usually painful mouth sores or erosions that do not heal, often on the gums or inside the cheeks. Skin blisters may follow weeks to months later, usually on the scalp, face, chest or back.

Is pemphigus vulgaris curable?

There is no permanent cure, but treatment with rituximab and steroids leads to remission in most people, and many can eventually stop treatment. Relapses can occur and are treated again.

What is the difference between pemphigus and pemphigoid?

Pemphigus vulgaris causes fragile, easily broken blisters and nearly always affects the mouth, usually in middle age. Bullous pemphigoid causes tense, intact, often itchy blisters, rarely affects the mouth, and mainly occurs in older adults.