What is Pemphigus Vulgaris?
Pemphigus vulgaris (PV) is a type of disease where the immune system mistakenly attacks the body, resulting in blisters on the skin and the inner linings of the body. A key characteristic of this condition is a process called ‘acantholysis,’ which is a loss of connections between skin cells.
The term ‘Pemphigus’ comes from the Greek word ‘pemphix,’ which means blister. The disease was first identified by a man named Stephen Dickson in 1788 when he noted a patient with a blister on her tongue.
While it was originally believed that the disease could be passed from person to person, it has since been determined that this is not the case. However, it’s been identified that certain triggers could cause Pemphigus Vulgaris in people who already have other autoimmune disorders, which are conditions where the body’s immune system mistakenly attacks its own cells.
What Causes Pemphigus Vulgaris?
The exact cause of pemphigus vulgaris, a skin condition, isn’t known. However, research suggests it’s associated with our body’s own defenses (autoantibodies) mistakenly attacking proteins (cadherins) that hold skin cells together. This can lead to disconnection and breakdown of skin cells.
Some people might have genes that make them more likely to develop pemphigus vulgaris. It’s suggested that certain types of human leukocyte antigens (HLA) – proteins in our cells that help our immune system identify what’s part of our body and what’s not – are linked to this condition. For instance, HLA-DRB1 0402 is connected with pemphigus vulgaris in Ashkenazi Jews, while DRB1 1401/04 and DQB1 0503 HLA are connected with this condition in non-Jewish patients of European or Asian descent.
Environmental aspects such as diet, stress, viral infections, medications, sunlight exposure, radiation therapy, pesticides, or allergens might all cause immune system disruption, leading to an outbreak of pemphigus vulgaris.
Medications like penicillamine and captopril may trigger pemphigus vulgaris as well. This could be due to their effect on molecules involved in cell binding, enzyme action that affects skin cell clustering, and the creation of new antigens (foreign bodies that trigger immune response). Besides these, nonsteroidal anti-inflammatory drugs, penicillin, and cephalosporins are also linked to drug-induced pemphigus vulgaris. However, there are differing opinions on whether certain foods, like red wine, garlic, leek, and peppers, can lead to pemphigus vulgaris as the robust evidence to support this is missing.
Risk Factors and Frequency for Pemphigus Vulgaris
PV, or Pemphigus Vulgaris, is a condition that affects people all over the world. However, its occurrence can often be related to a person’s ethnicity and where they live. On average, there are between 0.1 and 0.5 new cases of PV for every 100,000 people each year. Certain ethnicities, such as Ashkenazi Jews, have higher rates of PV and it’s most usually seen in people between the ages of 40 and 60. People living in India, Southeast Europe, and the Middle East are more likely at risk of developing PV. Men and women are both equally affected by this condition, but in Tunisia, women are more prone to PV than men, with a ratio of 4:1.
There is also evidence to suggest that genetics can play a part in PV, even though cases of PV appearing in families are rare. People with PV are known to have a higher chance of having non-symptomatic first-degree relatives with certain PV antibodies in their blood, when compared to healthy individuals. These relatives are also more likely to have autoimmune diseases. Specific gene variants have been associated with PV, which also serve to protect against rheumatoid arthritis. Finally, there have been links established between PV and other conditions like myasthenia gravis and ulcerative colitis.
Signs and Symptoms of Pemphigus Vulgaris
Pemphigus Vulgaris (PV) is a skin condition where blisters form on the body. In most cases, it starts with blisters in the mouth, leading to painful sores when they burst. These sores can make eating difficult and potentially cause inadequate nutrition. Skin lesions typically appear after the mouth blisters. These can be blisters, sores, or pouches filled with fluid on red or ordinary-looking skin. The condition also can make skin prone to blistering with minor pressure or trauma. This symptom is known as the Nikolsky sign.
Oral sores can cause considerable discomfort and potentially impact a person’s nutritional intake. Apart from the mouth, blisters can appear in the eyes, inside the nose, voice box, throat, esophagus, genitals, and anus. When PV occurs in the cervix, it can confuse the results of a Pap smear. Skin lesions usually appear on the face, trunk, groin, head, and underarm areas but it rarely affects the palms and soles. The blisters typically heal without leaving scars, but there can be changes in skin color. If the condition affects the scalp, it could lead to hair loss. In severe cases, fingernails and toenails can be involved.
In rare cases, PV can cause a condition called pemphigus herpetiformis. This presents as itchy, hivelike patches and blisters organized in a ring-like or clusters similar to shingles.
Testing for Pemphigus Vulgaris
Pemphigus Vulgaris (PV) is a condition that affects your skin and can be diagnosed using a combination of examination, lab tests, and skin biopsy. In the biopsy, a small bit of your skin is taken for a detailed examination known as histopathology, using a stain known as a Hematoxylin and Eosin (H&E) stain. This biopsy will show what is happening in your skin at a microscopic level and is a key part of diagnosing PV.
Another important diagnostic test for PV is something called direct immunofluorescence. This sophisticated test helps to visualize a network-like or chicken wire-like pattern of antibodies called IgG in the outer layer of your skin, the epidermis.
An enzyme-linked immunosorbent assay (ELISA) is another kind of test that can check if you have antibodies against certain proteins in your skin cells known as Dsg 1 and Dsg 3. These antibodies are found in the blood of most people who have PV.
Another simple and quick testing mechanism called a Tzanck smear can be performed, which shows a condition in skin cells called acantholysis, which is seen in PV. Then, more complex tests like indirect immunofluorescence and ELISA are performed to detect more antibodies that are attacking cells on the surface of your skin and mucous membranes in PV.
In patients that present with positive direct immunofluorescence results, an ELISA test can confirm the presence of antibodies called IgG against Dsg 1, Dsg 3, or both.
The doctor will also need to perform other health checks like checking your vital signs, full blood count, and kidney function. Women in certain age groups might have to undergo a pregnancy test. For those who are at the risk of osteoporosis, perhaps due to long-term use of certain medications like corticosteroids, a bone density scan might be needed. The doctor might also assess your overall well-being and will note how active your disease is to keep track of your progress during your treatment.
To scientifically measure the severity of PV, scoring systems like the Pemphigus Disease Area Index (PDAI) and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) can be utilized. These scoring systems are user-friendly and don’t take more than a few minutes to complete.
Treatment Options for Pemphigus Vulgaris
For the treatment of the skin condition called Pemphigus Vulgaris (PV), systemic corticosteroids are usually the first line of defense. These are powerful anti-inflammatory drugs that can help reduce the symptoms. However, it may take a few weeks to start seeing an improvement. The dosage of these drugs is reduced when symptoms get better but should be increased if the condition worsens with the appearance of more skin lesions.
Anti-CD20 monoclonal antibodies, like rituximab and ofatumumab, are often used along with corticosteroids for moderate-to-severe cases of PV. These medications work by halting certain immune cells (B lymphocytes) from turning into cells that produce harmful antibodies. Rituximab is administered through the veins, and effects can usually be seen within three months. Some common side effects include reactions such as nausea, vomiting, headache, and fever. However, a rare but serious side effect of rituximab includes a brain infection called progressive multifocal leukoencephalopathy (PML).
If the first line of treatment isn’t effective enough, additional treatments may be combined with corticosteroids. These “second-line” treatments may include immunosuppressive drugs like azathioprine or mycophenolate mofetil (MMF). Azathioprine inhibits the synthesis of purine, a substance needed for DNA replication in cells. Before using azathioprine, it’s important to test an enzyme called “thiopurine methyltransferase (TPMT)” to ensure your body can metabolise the drug properly. Lack of this enzyme can lead to side effects such as reduced blood cell count and weakened immunity. MMF works similarly to azathioprine and is usually effective within two months of starting the treatment. Side effects may include nausea, vomiting, diarrhea, and stomach discomfort. When given intravenously, it might cause superficial vein inflammation and clots.
If the second line treatment still doesn’t work, third-line treatments for PV might be necessary. These can include intravenous immunoglobulin (IVIG), cyclophosphamide, dapsone, immunoadsorption, and methotrexate. In some cases, additional treatments or medications for pain relief may be necessary.
There are also some promising new therapies being explored for the treatment of PV. Most of these are monoclonal antibodies, similar to rituximab but with other targets, such as obinutuzumab, ofatumumab, and veltuzumab. Other therapies are hoping to target specific molecules and proteins involved in PV, like B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), CD19, Bruton Kinase (BTK), and interleukin (IL-4). However, cost is a significant factor in carrying out large trials for these potential new treatments.
What else can Pemphigus Vulgaris be?
When doctors are considering diagnoses for Pemphigus Vulgaris (PV), they look at various conditions with similar symptoms. These includes:
- IgA Pemphigus: This condition also results in painful blisters like PV. However, it doesn’t cause blisters in the mouth. Tests known as DIF and IIF can help differentiate between PV and IgA pemphigus.
- Pemphigus Foliaceus: This is another autoimmune disease that causes blistering. But like IgA pemphigus, it doesn’t affect the mouth since its majorly due to something called Dsg 1 autoantibodies, also it’s less common than PV.
- Paraneoplastic Pemphigus: People with this condition get blisters and sores on their skin and mucous membranes, very similar to PV. But this can also be differentiated from PV using Immunofluorescence (IIF) and immunoblot tests.
By considering these other conditions and running appropriate tests, physicians can diagnose PV more accurately.
What to expect with Pemphigus Vulgaris
It’s very important for patients with Pemphigus Vulgaris (PV) to closely monitor the progression of the disease and their response to the treatment. PV is a dynamic or ever-changing condition that often requires adjustments in medication dosage and sometimes even a change in the medication itself, depending on the individual’s response to treatment.
It’s important to note that Sepsis, a life-threatening condition caused by the body’s response to an infection, is the leading cause of death in PV patients. A study conducted in Israel showed that those with PV typically have lower survival rates compared to the general population. The study also found that patients diagnosed with PV at an older age have a lower survival rate. On average, from the time of diagnosis, patients lived for 10.1 years, though this ranged from 0.2 to 29.8 years. Interestingly, there was no significant difference in survival rates between men and women.
Possible Complications When Diagnosed with Pemphigus Vulgaris
Systemic corticosteroids, which are often used as a treatment for Pemphigus Vulgaris (PV), are known for causing various side effects. These side effects can include osteoporosis and further complications. In fact, they can cause fractures in 30% to 50% and osteonecrosis in 9% to 40% of patients who undergo long-term treatment. The Fracture Risk Assessment (FRAX) is a tool that doctors use to calculate the potential risk for osteoporotic fractures. There are also other side effects such as high blood sugar levels, sleeplessness, increased appetite, high blood pressure, swelling, adrenal suppression, cataracts, and delayed wound healing.
In a case study by Namazi and his team, they looked at the frequency of P-wave dispersion or PWD (an irregular heart rhythm indicator) in patients with PV. By excluding patients with obesity, high cholesterol, high blood pressure, diabetes, and heart or lung disease, they hypothesized that atrial fibrillation (irregular heartbeats) might be more common in PV patients. Regardless of the smaller sample size of 90 patients and the higher use of corticosteroids, they found that the incidence of PWD was indeed higher in the PV group compared to the control group.
Other issues PV patients may experience could include other autoimmune diseases and malignancy. Moreover, secondary infections might also be reasonably common. Therefore, it’s crucial that the proper care regimen be put in place, including practicing good oral hygiene and avoiding triggers that may cause blistering.
Below are the common side effects of corticosteroid treatment, and other possible complications:
- Osteoporosis
- Fractures
- Osteonecrosis
- High blood sugar levels
- Sleeplessness
- Increased appetite
- High blood pressure
- Swelling
- Adrenal suppression
- Cataracts
- Delayed wound healing
- Irregular heart rhythm (PWD)
- Other autoimmune diseases
- Malignancies
- Secondary infections
- Oral complications
Patients should monitor infections carefully, as serious blood infections are the most common cause of death in patients with PV. For those with severe oral symptoms, they may need to adjust their diets to prevent further complications.
Preventing Pemphigus Vulgaris
It’s important for patients to understand that regular check-ups with their health care provider and specialists play a crucial role in managing their Polycythemia Vera (PV). Taking prescribed medication as directed is critical, and this adherence to the prescribed regimen can be encouraged and supported by the patient’s pharmacist. Patients should also be informed about available support groups as well as resources to help with behavioral changes, such as adjusting their diet. These measures can help prevent their condition from getting worse.
