Pemphigus

Pemphigus is a group of rare autoimmune diseases that cause painful blisters and sores to form on the skin and inside the mouth. While there is no cure, treatments can help control symptoms and allow many people to manage this lifelong condition.

Table of contents

• What is Pemphigus?
• Types of Pemphigus
• Who is Affected?
• What Causes Pemphigus?
• Symptoms and Signs
• Possible Complications
• How is Pemphigus Diagnosed?
• Treatment Options
• Living with Pemphigus
• Outlook and Prognosis

What is Pemphigus?

Pemphigus is a group of rare autoimmune skin conditions that cause sores, blisters or fluid-filled bumps to form on your skin and mucous membranes (the soft, moist linings of your eyes, nose, mouth, throat and genitals)^[1].

In an autoimmune disease, your body’s immune system mistakenly attacks healthy cells instead of protecting them. With pemphigus, the immune system attacks cells in the skin and mucous membranes^[2]. This causes the skin cells to separate from each other, which leads to the formation of blisters.

The blisters that form with pemphigus are soft and break open easily to form painful sores. Without treatment, they can spread over large areas of your body and carry a risk of infection^[1]. These blisters are often painful and heal slowly.

Pemphigus is not contagious and cannot spread from person to person^[2]. It is a lifelong condition that can be managed with ongoing medical treatment.

Types of Pemphigus

There are several types of pemphigus based on where and why the blisters develop^[1].

Pemphigus vulgaris is the most common type in the United States. Blisters always affect the mouth in this type. Some people may also have blisters on their skin and in other mucous membranes. These blisters develop in the deeper layers of the skin, can be painful, and heal slowly^[1]. In fact, most patients first present with sores inside the mouth and throat, which can make swallowing painful^[2]. Many people also get blisters on their skin, usually appearing a few months after the mouth is affected^[2].

Pemphigus vegetans is similar to pemphigus vulgaris but causes thicker lesions. These usually form in areas with skin folds such as the groin and armpit^[1].

Pemphigus foliaceus causes blisters to develop on the scalp, face, neck and back. Blisters rarely appear in the mouth with this type. It affects only the outermost skin layer. Small blisters may break open easily to form crusty lesions that can spread to cover large areas of skin^[1].

Pemphigus erythematosus (also called Senear-Usher syndrome) is an overlap syndrome with lupus that causes blisters to develop on the upper back, chest, cheeks and scalp. When lesions form, they are usually red and scaly^[1].

Drug-induced pemphigus can be caused by certain medications, including antibiotics and blood pressure medication. Blisters can develop months after taking the medicine^[1]. Some drugs that commonly cause this condition include penicillamine, certain antibiotics, and medicines used to control blood pressure^[5].

Endemic pemphigus (also called fogo selvagem) is a form of pemphigus foliaceus that occurs more often in South and Central America, particularly Brazil^[1].

Paraneoplastic pemphigus is the rarest type that develops in people diagnosed with cancer. Severe blisters form in the mouth. If a healthcare provider diagnoses paraneoplastic pemphigus, they will look for signs of cancer somewhere in the body^[1].

Who is Affected?

Pemphigus can affect anyone, but it is most common among people between the ages of 40 and 60^[1]. For pemphigus vulgaris specifically, onset typically occurs between ages 40 and 60, affecting both men and women equally^[3].

Certain groups of people have higher rates of pemphigus. It is more common in people of Jewish, Indian, Southeast European, or Middle Eastern ancestry^[4]. Specific geographical regions of the world have a higher number of cases, including Southeast Europe, India, the Middle East, Tunisia, and Brazil^[1].

Pemphigus is not common overall. An estimated 1 to 5 out of every 1 million people receive a pemphigus diagnosis throughout the world each year^[1].

What Causes Pemphigus?

Pemphigus is caused by a problem with the immune system, which is the body’s defense against infection. Instead of attacking germs, something goes wrong and the immune system attacks the skin by mistake^[2].

The precise cause of pemphigus is not fully understood. Multiple studies have found that it involves autoantibodies (harmful proteins made by the immune system) that target specific proteins called cadherins, particularly desmoglein 3 and desmoglein 1^[3]. These proteins normally act like glue to hold skin cells together. When antibodies attack these proteins, skin cells separate from each other and fluid fills the space, creating blisters^[5].

Some people may have a genetic predisposition for pemphigus. Several studies have linked it with certain genes involved in immune function^[3]. However, it is not clear why the condition develops, and it is not passed on in families in a predictable way^[2].

Several trigger and predisposing factors have been reported. These may include drug intake (especially medications containing certain chemical groups), vaccines, infections, pregnancy, radiation, emotional stress, and exposure to pesticides^[8]. Environmental factors such as diet, stress, viral infections, medications, ultraviolet radiation, ionizing radiation therapy, and allergens may all cause immune problems leading to a flare of pemphigus^[3].

Symptoms and Signs

Pemphigus causes blisters on the skin and mucous membranes. The blisters break easily, leaving open sores that may become infected and ooze^[9].

The most common area affected is inside the mouth and throat. Blisters burst easily and leave very sore patches^[2]. These blisters are often painful but typically do not itch. Oral blisters can make it hard to talk, drink and eat^[9]. In pemphigus vulgaris, oral lesions occur in 50 to 70 percent of patients and involve widespread areas within the mouth, creating painful, slow-to-heal ulcers^[5].

Many people also get blisters on their skin. In pemphigus vulgaris, these usually appear a few months after the mouth is affected^[2]. Skin lesions appear as thin-walled soft blisters filled with clear fluid that easily rupture, causing itchy and painful areas where skin has broken down^[5]. They most often arise on the upper chest, back, scalp, and face.

The blisters and sore areas can cover a large area of the body. Sometimes they can also affect the eyes, genitals or anus^[2]. Involvement of the throat can cause pain when swallowing and a hoarse voice. Nasal involvement causes congestion and bleeding^[5].

In people with darker skin tones, the presentation may differ. Diagnostic features may include blisters that lack redness, or darkened patches with shallow breakdown of skin and crusting with dried blood. At later stages, there may be patches with a pink base and surrounding darkened skin^[5].

Possible Complications

Pemphigus can lead to several serious complications if not properly managed^[2].

The most serious complication is infection of the blisters and sore patches. This can cause life-threatening problems such as sepsis (a dangerous condition where infection spreads throughout the bloodstream)^[2]. Infection of the skin is a significant risk^[9].

Other possible complications include weight loss and malnutrition because of pain when eating and drinking, especially when the mouth and throat are affected^[2]. Tooth decay and gum disease can occur because it can be painful to look after teeth and gums properly^[2]. If the genitals or anus are affected, there may be pain during sex and pain when urinating or having bowel movements^[2].

Scarring and changes in skin color can occur after the affected skin heals. This is called postinflammatory hyperpigmentation when the skin darkens and postinflammatory hypopigmentation when the skin loses color. People with brown or Black skin have a higher risk of long-term skin color changes^[9].

Side effects from the medicines used to treat pemphigus can also cause problems. Examples include high blood pressure and increased risk of infection^[9]. In rare cases, if certain types of pemphigus are left untreated, death can occur^[9].

How is Pemphigus Diagnosed?

A healthcare professional will start by talking with you about your medical history and symptoms and examining the affected area^[9]. They may refer you to a specialist in skin conditions called a dermatologist for tests and treatment^[2].

Pemphigus is diagnosed by the characteristic clinical appearance, along with specific tests^[3]. You may have the following tests:

A biopsy is a procedure to remove a small sample of tissue for testing in a laboratory. To test for pemphigus, a piece of the blister is removed and examined^[9]. This is typically done by taking a skin biopsy from the affected area or from the mucous membrane of the mouth^[3].

Blood tests are used to detect and identify antibodies in your blood that are known to be present with pemphigus^[9]. Antibody testing using special techniques is a useful tool to confirm the diagnosis^[3].

Treatment Options

There is no cure for pemphigus, but treatment can help control symptoms. The main goals of treatment are to stop new blisters from forming, to promote healing of existing blisters and sores, and to find the lowest dose of medication necessary to control the disease^[15].

Treatment typically occurs in three phases. The control phase involves intense therapy given to suppress disease activity until no new lesions appear. The consolidation phase maintains drugs and doses until complete clearance of lesions. The maintenance phase gradually reduces medications, aiming for the lowest dose that prevents new lesions^[13].

If your symptoms were caused by use of certain medicines, stopping that medicine may be enough to clear up your symptoms^[7]. Some people may need a hospital stay to receive fluids, nutrition or other treatments^[7].

Corticosteroids

Corticosteroids (also called steroids) remain the most established therapy for managing pemphigus. These medicines mimic the effect of hormones your body naturally produces and work by suppressing the immune system and limiting inflammation in the body^[13].

For people with mild disease, corticosteroid cream or injections may be enough to control it. For others, the main treatment is a corticosteroid medicine taken by mouth, such as prednisone pills^[7]. In most cases, when used in high doses, steroids can rapidly control the disease^[13].

Topical steroids can be used for treatment of pemphigus. To address mouth sores, steroid mouthwash, paste, ointment or spray can be used^[13]. If the gums are involved, topical therapy should be applied with flexible dental trays^[13].

It usually takes a few weeks for the blisters to heal. Blisters caused by pemphigus usually come and go over time^[2]. Once symptoms are under control, the steroid dose is gradually reduced to minimize side effects^[13].

Using corticosteroids for a long time or in high doses may cause severe side effects. These include diabetes, bone loss, an increased risk of infection, stomach ulcers, weight gain, mood swings, high blood pressure, easily bruised and thinned skin, increased appetite, and acne^[7][23]. To avoid these side effects, steroids are used only for short periods or gradually reduced to lower doses^[7].

Immunosuppressants

Immunosuppressants are medicines that suppress the immune system. They are used after initial treatment to manage pemphigus and can help reduce the amount of steroids needed^[13].

Azathioprine and mycophenolate mofetil are considered the first line of steroid-sparing treatment^[12]. These medications are usually added once symptoms are under control with steroids^[13].

Other immunosuppressants that may be used include cyclophosphamide and cyclosporine. These should be reserved for patients who do not respond to other immunosuppressive medicines^[13].

These medications may increase the risk of infection, which is why certain precautions should be taken, such as avoiding close contact with people who have infections^[23].

Rituximab

Rituximab is a newer treatment that targets specific immune cells. It is extremely effective in difficult-to-treat pemphigus when other treatments fail to control the disease^[12]. In June 2018, the United States Food and Drug Administration approved rituximab for the treatment of adults with moderate to severe pemphigus vulgaris^[13].

Rituximab is being used as first-line therapy by many doctors and appears to yield better outcomes when given as a first-line treatment^[15]. It is commonly given in combination with corticosteroids^[15].

Additional Treatments

Other treatments that may be used include antibiotics and antifungal treatment for infections or to prevent them, pain medications for severe pain, numbing mouthwashes or lozenges to control mouth pain, and intravenous nutrition if mouth ulcers are too severe to allow adequate feeding^[15][23].

You will probably need treatment for several years to help stop the blisters coming back. It may be possible to stop treatment eventually, but if the blisters come back, you may need to repeat treatment^[2].

Living with Pemphigus

Living with pemphigus presents unique challenges, but with the right strategies and a positive mindset, you can manage the condition effectively.

Oral and Dental Care

If you have pemphigus, there are important steps for caring for your mouth. Clean your teeth using a soft toothbrush and mint-free toothpaste. Use antiseptic or painkilling mouthwash, but try to avoid mouthwashes that contain alcohol. Have regular dental check-ups^[2].

Some people find it helpful to receive dental cleanings every four months instead of the typical six months^[22]. If you have blisters in your mouth, avoid eating spicy, acidic or hard foods^[2]. Foods to avoid include hot sauces, curry, nuts, chips, crisp raw vegetables, tomatoes, orange juice and citrus, as well as very hot foods or beverages^[21].

Skin Care

Keep any sore patches clean to reduce the risk of infection^[2]. If you have blisters on your skin, avoid activities that could damage your skin, such as contact sports^[2].

Protect your skin by using gentle skincare products, avoiding excessive sun exposure, and keeping your skin hydrated^[4]. Avoid the sun and heat. Dress in soft, breathable clothing. When bathing, avoid scrubbing your skin, use a gentle cleanser, and lightly pat dry with a towel leaving the skin damp^[21].

If you are dealing with blisters or wounds, practice good wound care. Ask your healthcare provider to show you how to dress a wound, how to keep it clean, and whether you should use antibiotic ointments. It is important that you know what to look for if there are signs of infection and when to call your healthcare provider^[21].

Daily Life Strategies

Build a support system. Surround yourself with a supportive network of family, friends, and healthcare professionals who understand your condition^[27]. Support groups and online communities can provide connection and shared experiences^[2].

Educate yourself about pemphigus, its triggers, and potential complications. This will help you make informed decisions about your care^[27]. Maintain open and honest communication with your medical team^[27].

Prioritize self-care. Get enough rest, eat a balanced diet, and engage in activities that reduce stress^[4]. Learning to manage stress can help, as stress can worsen pemphigus. Regular physical exercise can help with stress, but avoid physical contact sports. Make time for hobbies and passions. Consider practicing mindful exercises such as meditation or deep breathing^[21].

Plan your daily activities carefully to conserve energy and reduce the risk of injury. Do not hesitate to ask for help with tasks that may be too difficult^[4]. Choose clothing made from soft, breathable fabrics that will not irritate your skin. Loose-fitting clothes can also help prevent friction and blistering^[4].

When to Seek Urgent Care

Ask for an urgent appointment or get help immediately if your blisters or sore patches are very painful or feel hot, or if there is yellow or green pus coming from them. These are signs of an infection, which needs to be treated quickly^[2].

Outlook and Prognosis

Pemphigus is a lifelong condition that can be managed with ongoing medical treatment^[1]. There is no cure, but treatment can help control symptoms^[2].

With proper treatment, many people can achieve control of their disease and maintain a good quality of life. The main objective of treatment is initially to control the disease and heal the blisters and sores, and then to prevent relapses in the long run while avoiding side effects from medications^[12].

Treatment with corticosteroids has led to improved overall survival, though significant challenges remain related to managing the condition and side effects of therapy^[15]. The rapid reduction of steroids once control of the disease has been achieved and the introduction of newer immunosuppressants with fewer long-term side effects have decreased both illness and death rates in pemphigus patients in recent decades^[12].

You will have regular check-ups to look for complications and may be referred to other specialists if needed^[2]. Many individuals with pemphigus continue to work. It is important to communicate with your employer about any necessary accommodations^[4].

Living with pemphigus can be very difficult, but as well as support from your care team, it may help to get information and support from patient groups and organizations dedicated to pemphigus and related conditions^[2].

Pemphigus vulgaris, Pemphigus foliaceus, Pemphigus vegetans, Pemphigus erythematosus

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