Pemphigus Vegetans

What is Pemphigus Vegetans?

Pemphigus is a group of disorders where the immune system attacks the skin, leading to blisters. The most common type is pemphigus vulgaris, which creates sores on the skin and mucous membranes. Within pemphigus diseases, pemphigus vegetans is the rarest form. It differs from pemphigus vulgaris as it forms growths in moist areas of the body and inside the mouth.

Although people generally consider pemphigus vegetans to be a variant of pemphigus vulgaris, it only accounts for 1-2% of all pemphigus cases. It can be difficult to diagnose since its symptoms can vary and the growths can be misleading. There are two well-known types of pemphigus vegetans: the Hallopeau type and the Neumann type. The Hallopeau type progresses slowly and typically shows small, pus-filled sores that heal and turn into growths. The Neumann type, on the other hand, is more severe and more resistant to treatment. It often has growths that appear during a blister outbreak, usually involving the mouth.

The leading cause of pemphigus vegetans is when the immune system incorrectly attacks proteins called desmoglein 3 (DSG3) and desmoglein 1 (DSG1). These proteins play an essential role in helping skin cells stick together and maintain skin strength. The primary treatment for this disease is similar to that of pemphigus vulgaris, including systemic corticosteroids (medicine to reduce inflammation) and immunosuppressants (drugs that reduce the body’s immune response).

What Causes Pemphigus Vegetans?

Pemphigus vegetans is a condition that occurs when your immune system mistakenly produces substances called autoantibodies. These autoantibodies attack certain proteins in your skin cells. Specifically, these proteins are called transmembrane proteins and they are a key part of structures known as desmosomes. Desmosomes are like tiny little connectors that hold your skin cells together.

Most commonly, Pemphigus vegetans is caused by autoantibodies that target proteins called desmoglein 3 and sometimes desmoglein 1. When these proteins are attacked, it affects the way your skin cells stick together, leading to the symptoms of pemphigus vegetans.

It’s interesting to note that the type of pemphigus vegetans you might have depends on which proteins are being targeted by the autoantibodies. If desmoglein 3 is mainly targeted, it’s more likely that the disease will affect the mucosal surfaces like your mouth. When both desmoglein 3 and desmoglein 1 are targeted, the disease might affect both the mucosal surfaces and the skin.

In addition, some patients with pemphigus vegetans also produce other autoantibodies that target proteins called desmocollins. These are also present in desmosomes and help your skin cells stick together.

Risk Factors and Frequency for Pemphigus Vegetans

Pemphigus vegetans is a condition that hasn’t been extensively studied. It is reported to account for 1 to 2% of all pemphigus cases. Worldwide, there’s an occurrence of about 0.7 cases of pemphigus vulgaris for every 100,000 people. It’s believed that the number and distribution of pemphigus vegetans cases are similar to those of pemphigus vulgaris.

Pemphigus vulgaris is more common in women, with 1.3 to 2.3 females for every male.
In the United States and Europe, pemphigus vulgaris is usually diagnosed in people between 50 and 70 years old. In other countries, it’s typically diagnosed in people between 30 and 50 years old.
The condition appears to be more prevalent among Ashkenazi Jewish, Mediterranean, and Middle Eastern communities.

Signs and Symptoms of Pemphigus Vegetans

Most people with this condition first see their doctor due to mouth sores. A few weeks to months afterwards, skin blisters appear, usually on the trunk, arms, legs, and folds of the skin. There are different variations of the condition – the Hallopeau subtype, which starts with pustule skin lesions and tends to progress slowly, and the Neumann subtype, which is characterized by large, erosive skin blisters and tends to be more severe.

Over time, the skin blisters break open and develop into painful ulcers. These ulcers often turn into hard, crusty skin growths. These different types of skin lesions typically show up in skin folds including the groin, armpits, thighs, and flexible surfaces. Less frequently affected areas include the scalp, the bottoms of the feet, and places where a skin graft was done. There have also been cases where the nose, vagina, and eyes were affected. In the mouth, these hard growths often appear on the tongue in a brain-like pattern.

On top of the physical symptoms, it’s important for the doctor to understand the patient’s medical history. This should include any personal or family history of autoimmune diseases and skin issues. Other important information includes stress levels, whether the patient has been exposed to radiation, recent illnesses, changes in medication, and whether eating, swallowing, or sexual activity causes pain. It’s also useful to know if the symptoms get worse during menstruation.

Testing for Pemphigus Vegetans

To diagnose pemphigus vegetans, a type of skin condition, doctors often look at three things: physical symptoms, results from a tissue examination, and the detection of certain antibodies in your body. Antibodies are molecules that your immune system creates to fight off germs, but in pemphigus vegetans, your body mistakenly produces antibodies that attack your own skin cells.

The first step is typically a blood test, using methods like an immunoblot or ELISA analysis. Here, doctors are looking for a specific type of antibody called desmoglein 3. This antibody can be found in almost everyone with pemphigus, with a specificity and sensitivity of 98 to 100%. This means that the test is extremely accurate in identifying people who do have the disease.

Another way to diagnose this condition is to perform a Direct Immunofluorescence test (DIF), where a small skin sample is removed and examined under a microscope. In this case, doctors check for IgG and C3 antibodies within your skin cells. The outcome is often linked with a recognizable “fishnet” or “chicken wire” pattern. For best results, this test is performed on a skin patch that appears normal but is near the affected area.

Observations on the levels of IgG and IgA in your blood (kind of like a body’s disease meter) could also help doctors monitor the disease and see how you’re responding to treatments.

There are other less commonly used methods as well. For example, doctors might use Indirect Immunofluorescence (IIF), a method that helps identify antibodies in a semi-quantitative manner. They may also examine skin samples under an electron microscope, which may show a reduced number of filament structures in the skin cells and few desmosomes, which are structures that help cells stick together. Sometimes, the skin’s foundation layer might appear damaged due to inflammation.

Other evaluation methods include the ‘Nikolsky sign’ test, where doctors apply pressure to a blister to see if it will extend. While positive results are often seen in pemphigus vegetans, this test isn’t specific and could be indicative of several skin diseases. The ‘Tzanck’ test, which examines cells from the skin, is another method that may help rule out pemphigus. However, doctors usually rely on a combination of physical exams, skin tissue study, and antibody detection to confirm the diagnosis. The last test is a blood count test where doctors check for a high number of eosinophils, a type of white blood cell that could indicate inflammation or an allergic reaction, conditions typically seen in individuals with pemphigus vegetans.

Treatment Options for Pemphigus Vegetans

 If you’re suffering from vegetating lesions, there are a number of treatments you could consider. For immediate wound care, consider daily cleaning and dressing. Some people find that medicated gauzes and chemical cautery, which uses heat to treat the tissue, provide some relief.

Your doctor might recommend surgery to remove these lesions if they’re significantly impacting your quality of life. For oral lesions, a special mouthwash containing a medicine called dexamethasone, or an ointment called clobetasol, might be prescribed to reduce inflammation and provide relief.

You could also be given cream containing steroids or tacrolimus for facial lesions or if you can’t tolerate long-term steroid treatment. There’s also a topical treatment that contains minocycline and nicotinamide, which has been successful in some cases and doesn’t use steroids.

Another possibility is a local injection of a drug called triamcinolone into difficult-to-treat vegetative lesions.

In some cases, oral or injection medication may be necessary. The most common treatment is a type of medication called corticosteroids. These drugs are thought to encourage cells in the skin to produce a protein called desmoglein, leading to rapid relief. They’re often used in combination with other treatments like azathioprine, dapsone, mycophenolate mofetil, methotrexate, or cyclophosphamide. These drugs often work well, but do have side effects that your doctor will discuss with you. If the standard treatments aren’t effective, you might be given rituximab or high-dose corticosteroid treatment.

Once a successful treatment has been found, the recommendation is generally to continue for a year, then gradually reduce the treatment over the following year. This will be tailored to your individual needs and any other health issues you have.

Less commonly used treatments include filtering the blood to remove harmful substances (plasmapheresis), removing antibodies from the blood (immunoadsorption), or a type of stem cell transplant. Researchers are currently exploring new treatments with fewer side effects, including medications that target specific components of the immune system and signaling pathways within cells. This area of research is promising and could lead to new treatments in the future.

Here are some diseases that might show similar clinical and histological (examining tissues under a microscope) features:

Pyodermatitis pyostomatitis vegetans: This ailment often looks like pemphigus vegetans and usually occurs with inflammatory bowel disease. Testing would show no deposits of immunofluorescent substances.
Bullous pemphigoid: This disease typically displays tense blisters, rash-like patches, and itching. Although there is rarely mucosal (lining of the digestive system) involvement, examination under a microscope shows a split under the epidermal (outer layer of skin) cells. Certain proteins and autoantibodies (antibodies that attack the patient’s own cells) can be found in the patient’s system.
IgA pemphigus: This is a mild autoimmune disease that causes blisters to form within the skin’s surface and is linked with circulating IgA antibodies. These antibodies can be found within the skin cells.

Here’s information about some additional diseases:

Hailey-Hailey Disease: This is a genetic skin disease that often leads to recurring inflammatory patches in skin folds. This can lead to eroded, scabby areas with velvety splits. Microscope inspection of skin cells shows characteristics similar to a “dilapidated brick wall”.
Pyoderma vegetans: This rare disease causes blister-like lesions and vegitative patches, usually found in the underarm and groin folds. It mostly occurs in patients with weakened immune systems and is heavily linked with bacterial infections. Histological examination would show skin cell overgrowth with tiny abscesses in and under the skin.
Paraneoplastic pemphigus: The symptoms of this disease are similar to pemphigus vulgaris, often accompanied by serious mucosal involvement. It is necessarily connected with an underlying cancer, mostly a blood cancer like chronic lymphocytic leukemia or other B-cell lymphomas. An anti-periplakin substance can also be found in association with this ailment.
Epidermolysis bullosa acquisita (EBA): EBA is an autoimmune blistering disease with mucosal involvement, caused by the body producing self-targeting antibodies against type VII collagen, a protein essential for skin structure. This disease shows variable clinical characteristics, with deposits of specific proteins and antibodies at the skin-junction confirming the diagnosis.
Porphyria: Genetic diseases affecting the pathway responsible for producing heme (a part of hemoglobin in red blood cells). The most common type of porphyria shows skin symptoms like erosions, vesicles, and blisters in sun-exposed areas.
Pemphigus foliaceus: Similar to pemphigus vulgaris, but the antibodies target a specific protein and the disease doesn’t involve the mucosal membranes.
Disseminated Herpes infection: This causes blister-like rashes due to viral infection. Microscopic examination, viral studies, and culture help identify this condition.
Stevens-Johnson syndrome and toxic epidermal necrolysis: These are diseases characterized by initial respiratory symptoms followed by a rash that progresses to full or partial skin loss. This condition is often caused by medications or infections.
Desquamative gingivitis: It is related to diseases like herpes, oral lichen planus, erythema multiforme, and the conditions listed above, and is often seen in these diseases.

What to expect with Pemphigus Vegetans

Autoimmune conditions, such as pemphigus including pemphigus vegetans, can’t be completely cured. However, they can be managed with proper treatment. It’s important to treat these conditions, as they can be very dangerous if left untreated. Pemphigus and pemphigus vegetans can lead to death within 5 years due to severe blistering, consequent infections, and malnutrition. The rate of death per year from these conditions ranges from 5% to 15%. So it’s crucial to manage these conditions effectively with timely and relevant treatments.

Possible Complications When Diagnosed with Pemphigus Vegetans

Secondary infection of lesions: Skin sores can become secondarily infected by common bacteria or fungi. Some types of bacteria that usually infect are Staphylococcus aureus and MRSA. Herpes can also occur.

People may also be at a greater risk for whole-body infections, especially if they are on medicines that can weaken the immune system.

Eating and nutrition problems: Because of painful sores in the mouth, one might not eat enough and lose weight.

Pap smears: A pap smear is a test that checks for changes in the cells of the cervix. These cells might look different under a microscope (dysplastic) because of the presence of acantholytic cells. Acantholytic cells occur in the cervix and vagina lining when pemphigus vulgaris affects these areas.

Simplified Information:

Secondary infection of skin sores:

Commonly by Staphylococcus aureus and MRSA bacteria
Also possible with Herpes
Possible with fungal organisms

Increased risk for whole-body infection, especially when on immune-suppressing medicines
Eating and nutrition problems due to painful sores in the mouth, leading to decreased food intake and weight loss
Pap smears revealing different looking cells (dysplastic) due to presence of acantholytic cells in the cervix and vagina lining

Preventing Pemphigus Vegetans

Pemphigus vulgaris, a rare skin condition, has been linked to other health conditions like myasthenia gravis, a neurological disorder, and thymoma, a tumor in the thymus gland. People diagnosed with these conditions are more likely to develop pemphigus.

Certain medications can also increase the risk of developing pemphigus. People taking penicillamine or ACE inhibitors—which are mostly heart and blood pressure medications such as captopril and enalapril—have a higher risk. In fact, approximately 7% of people taking penicillamine have been reported to develop pemphigus.

Interestingly, there’s a connection between using heroin through the nose (intranasal use) and a specific type of pemphigus called pemphigus vegetans.

People with pemphigus need to be especially careful with their skin to avoid infections. It’s important not to pop the blisters that the condition causes. This means staying away from scrubbing and high-pressure water, which can break the blisters and increase the risk of infection.

Frequently asked questions

Pemphigus Vegetans is the rarest form of pemphigus diseases, accounting for 1-2% of all pemphigus cases. It differs from pemphigus vulgaris as it forms growths in moist areas of the body and inside the mouth.

Pemphigus vegetans accounts for 1 to 2% of all pemphigus cases.

The signs and symptoms of Pemphigus Vegetans include: - Mouth sores, which are often the initial symptom that leads patients to seek medical attention. - Skin blisters that appear a few weeks to months after the mouth sores. These blisters typically occur on the trunk, arms, legs, and folds of the skin. - Different variations of the condition, including the Hallopeau subtype, which starts with pustule skin lesions and progresses slowly, and the Neumann subtype, which is characterized by large, erosive skin blisters and tends to be more severe. - Skin blisters that break open over time and develop into painful ulcers. - Hard, crusty skin growths that often form from the ulcers. - Skin lesions that typically show up in skin folds such as the groin, armpits, thighs, and flexible surfaces. - Less frequently affected areas such as the scalp, the bottoms of the feet, and places where a skin graft was done. - Rare cases where the nose, vagina, and eyes are affected. - Hard growths in the mouth that often appear on the tongue in a brain-like pattern. In addition to these physical symptoms, it is important for the doctor to consider the patient's medical history, including any personal or family history of autoimmune diseases and skin issues. Other relevant information includes stress levels, exposure to radiation, recent illnesses, changes in medication, and whether eating, swallowing, or sexual activity causes pain. The doctor may also inquire about whether the symptoms worsen during menstruation.

Pemphigus Vegetans occurs when your immune system mistakenly produces autoantibodies that attack certain proteins in your skin cells.

The doctor needs to rule out the following conditions when diagnosing Pemphigus Vegetans: 1. Pyodermatitis pyostomatitis vegetans: This disease often resembles Pemphigus Vegetans and is usually associated with inflammatory bowel disease. Testing would show no deposits of immunofluorescent substances. 2. Bullous pemphigoid: This disease typically presents with tense blisters, rash-like patches, and itching. Although mucosal involvement is rare, examination under a microscope shows a split under the epidermal cells. Certain proteins and autoantibodies can be found in the patient's system. 3. IgA pemphigus: This is a mild autoimmune disease that causes blisters to form within the skin's surface and is associated with circulating IgA antibodies. These antibodies can be found within the skin cells. 4. Hailey-Hailey Disease: This is a genetic skin disease that leads to recurring inflammatory patches in skin folds. It can result in eroded, scabby areas with velvety splits. Microscope inspection of skin cells shows characteristics similar to a "dilapidated brick wall". 5. Pyoderma vegetans: This rare disease causes blister-like lesions and vegetative patches, primarily found in the underarm and groin folds. It is more common in patients with weakened immune systems and is strongly associated with bacterial infections. Histological examination would show skin cell overgrowth with tiny abscesses in and under the skin. 6. Paraneoplastic pemphigus: This disease has symptoms similar to Pemphigus Vulgaris and often involves serious mucosal involvement. It is always associated with an underlying cancer, typically a blood cancer like chronic lymphocytic leukemia or other B-cell lymphomas. An anti-periplakin substance can also be found in association with this condition. 7. Epidermolysis bullosa acquisita (EBA): EBA is an autoimmune blistering disease with mucosal involvement caused by the body producing self-targeting antibodies against type VII collagen, a protein essential for skin structure. This disease shows variable clinical characteristics, with deposits of specific proteins and antibodies at the skin-junction confirming the diagnosis. 8. Porphyria: Genetic diseases affecting the pathway responsible for producing heme, a part of hemoglobin in red blood cells. The most common type of porphyria shows skin symptoms like erosions, vesicles, and blisters in sun-exposed areas. 9. Pemphigus foliaceus: Similar to Pemphigus Vulgaris, but the antibodies target a specific protein and the disease does not involve the mucosal membranes. 10. Disseminated Herpes infection: This causes blister-like rashes due to viral infection. Microscopic examination, viral studies, and culture help identify this condition. 11. Stevens-Johnson syndrome and toxic epidermal necrolysis: These are diseases characterized by initial respiratory symptoms followed by a rash that progresses to full or partial skin loss. This condition is often caused by medications or infections. 12. Desquamative gingivitis: It is related to diseases like herpes, oral lichen planus, erythema multiforme, and the conditions listed above, and is often seen in these diseases.

The types of tests needed for Pemphigus Vegetans include: 1. Blood tests: - Immunoblot or ELISA analysis to detect desmoglein 3 antibodies. - Observations on the levels of IgG and IgA in the blood. 2. Direct Immunofluorescence test (DIF): - Skin sample examination under a microscope to check for IgG and C3 antibodies. 3. Indirect Immunofluorescence (IIF) test: - Helps identify antibodies in a semi-quantitative manner. 4. Skin sample examination under an electron microscope: - May show reduced number of filament structures in skin cells and few desmosomes. 5. Nikolsky sign test: - Applying pressure to a blister to see if it extends. 6. Tzanck test: - Examining cells from the skin to help rule out pemphigus. 7. Blood count test: - Checking for a high number of eosinophils, a type of white blood cell that could indicate inflammation or an allergic reaction. These tests, along with physical exams and skin tissue study, are used to confirm the diagnosis of Pemphigus Vegetans.

Pemphigus Vegetans can be treated through various methods. For immediate wound care, daily cleaning and dressing can be done. Medications such as medicated gauzes and chemical cautery can provide relief. Surgery may be recommended if the lesions significantly impact the quality of life. Special mouthwash or ointment can be prescribed for oral lesions. Creams containing steroids or tacrolimus can be used for facial lesions or if long-term steroid treatment is not tolerated. Topical treatment with minocycline and nicotinamide is also an option. Local injection of triamcinolone into difficult-to-treat lesions is another possibility. Oral or injection medication, such as corticosteroids, may be necessary. Other drugs like azathioprine, dapsone, mycophenolate mofetil, methotrexate, or cyclophosphamide can be used in combination with corticosteroids. If standard treatments are not effective, rituximab or high-dose corticosteroid treatment may be given. Once a successful treatment is found, it is generally recommended to continue for a year and then gradually reduce the treatment over the following year. Less commonly used treatments include plasmapheresis, immunoadsorption, and stem cell transplant. Researchers are also exploring new treatments with fewer side effects.

The prognosis for Pemphigus Vegetans can be serious if left untreated, as it can lead to death within 5 years due to severe blistering, consequent infections, and malnutrition. The rate of death per year from Pemphigus and Pemphigus Vegetans ranges from 5% to 15%. Therefore, it is crucial to manage these conditions effectively with timely and relevant treatments.

Dermatologist

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