Epidermolysis Bullosa Acquisita

What is Epidermolysis Bullosa Acquisita?

Epidermolysis bullosa acquisita (EBA) is a rare, long-lasting disease that causes blisters because our own immune system mistakenly attacks our bodies. This disease affects both the skin and the mucus-covered surfaces of our body like the mouth. This happens when certain proteins, called autoantibodies, attack a particular kind of collagen protein–type VII collagen. This type of collagen is essential in connecting the top layer of our skin (the epidermis) to the layer beneath it (the dermis).

However, when these autoantibodies mistakenly bind to the type VII collagen, they make the two skin layers detach from each other. This results in fragile skin that forms blisters, grazes, scars, small white bumps (called milia), and may even lead to loss of nails.

While EBA can appear differently in different people, the most common forms look like mechanobullous EBA and inflammatory EBA. The classic mechanobullous EBA looks a lot like dystrophic epidermolysis bullosa (EB). In this, blisters and grazes occur in areas where there has been an injury. But it’s important to understand that EBA mostly affects adults while EB is usually seen in children. They are different conditions even though they sound similar because they share some symptoms.

On the other hand, the inflammatory form of EBA has symptoms that are like other diseases where our own immune system mistakenly causes blisters. These include diseases like bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), IgA bullous dermatosis, and Brunsting-Perry pemphigoid.

Lastly, EBA has been linked to other body-wide diseases such as inflammatory bowel disease (a long-lasting problem that causes irritation and ulcers in the digestive tract), thyroiditis (inflammation of the thyroid gland), rheumatoid arthritis (a long-term disease causing stiffness, swelling and pain in the joints), hepatitis C infection, and diabetes.

What Causes Epidermolysis Bullosa Acquisita?

EBA, or Epidermolysis Bullosa Acquisita, is a condition that involves antibodies (proteins that are part the immune system) targeting a specific protein called type VII collagen. This protein is found in the basement membrane zone (a layer of skin), particularly within an area called the lamina densa and sublamina densa.

Type IV collagen, another important protein, is a major part of anchoring fibrils – structures which help to connect the top layer of skin to the lamina densa. These connections are crucial for keeping the integrity of the skin in place.

Specific antibodies in EBA target a part of type VII collagen found in the lamina densa. Studies carried out on mice and in labs have shown that antibodies that attack type VII collagen can lead to the skin separating, a symptom of EBA.

These antibodies might also directly interfere with the assembly of type VII collagen into anchoring fibrils, or prevent it from interacting with other proteins within the skin. This can result in the top layer of skin detaching, which leads to the skin becoming fragile and forming blisters, a symptom seen in people with EBA.

Certain versions of a gene that helps make a specific type of immune cell (HLA class II) are found more often in certain populations with EBA. For example, Korean patients more commonly have HLA-DRB1*13, while African-American patients more commonly have HLA-DRB1*15:03. This suggests that the presence of specific versions of this gene might increase someone’s likelihood of developing EBA. However, more research is needed since current data mainly comes from studies involving small groups of EBA patients.

Risk Factors and Frequency for Epidermolysis Bullosa Acquisita

EBA, or Epidermolysis Bullosa Acquisita, is seen as one of the least common skin conditions in Western Europe, with a rate of around 0.2 to 0.5 cases per million people a year. However, it is more common in Korean and African-American groups. EBA can develop in both kids and adults, but it’s usually seen in adults. Age, not gender, is a stronger influence on EBA occurrence. While it can start at any age, it usually begins between 40 to 50 years.

In an exhaustive review in 2018, which took into account 1159 cases of EBA, the middle age observed was 50. Interestingly, children made up about 4.6% of cases, and those 65 or older accounted for 11.3%. The age range of people with reported EBA cases spanned from 1 year to 94 years old.

Around 9.6% of people with EBA also had chronic inflammatory diseases.
The most common accompanying conditions were Irritable Bowel Disease (IBD), thyroiditis, and rheumatoid arthritis.
Though there is growing evidence linking EBA and IBD, more research is needed to confirm this relationship.

Signs and Symptoms of Epidermolysis Bullosa Acquisita

EBA, or Epidermolysis Bullosa Acquisita, is a condition with lots of different symptoms, typically showing as a skin disorder with fragile skin, hard blisters, sores, scars, milia or tiny cysts, and skin discoloration. These symptoms usually appear on areas like knees, elbows, back of hands and feet which are more exposed to trauma. Extreme cases can lead to deformities like fused fingers, finger malformations, and nail issues. Sometimes, it may affect the scalp causing sores and scarring alopecia, which is hair loss from scars.

Apart from these, EBA can also show up in different forms that may look like other autoimmune skin disorders, such as BP-like EBA, MMP-like EBA, LABD-like EBA, and Brunsting-Perry cicatricial pemphigoid–like EBA. BP-like EBA is identified by itching hard vesicles and blisters on a red base, usually affecting parts like the trunk, folds of the skin, and the limbs. Half of the cases might also involve the oral mucosa, leading to sores or whole vesicles inside the mouth. Unlike the usual EBA, lesions in BP-like EBA often heal without forming milia or scars.

MMP-like EBA primarily affects mucous membranes, where lesions and scars mainly appear in the mouth, the upper esophagus, conjunctivae, anus, and vagina. In rare situations, severe effects on eyes have also been reported, which could potentially cause blindness.

LABD-like EBA is characterized by hard vesicles, blisters, and a skin rash arranged in a ring or wave pattern. This version of EBA could also affect mucous membranes along with skin lesions.

Brunsting-Perry cicatricial pemphigoid–like EBA usually shows up as a vesicular or blistering eruption primarily on the head and neck region, with slight to no involvement of mucous membranes. If it does involve the scalp, it results in scarring alopecia.

Interestingly, EBA patients may exhibit a single or multiple subtypes at the same time. There have also been instances where patients’ symptoms shifted from one form to another throughout the disease’s progression.

Testing for Epidermolysis Bullosa Acquisita

Diagnosing EBA, a blistering disease of the skin, is often a challenge due to its similar appearance and features to other skin challenges.

A useful tool in helping to diagnose EBA is through examining a sample of skin from the affected area under the microscope (histological examination). In EBA, early signs of the disease can be seen as swelling in the lower layers of the skin and a kind of cellular breakdown along the DEJ (the boundary area where the outer and inner layers of the skin meet). In later stages of EBA, a blister beneath the skin layer becomes visible. The amount of inflammation seen can vary depending on the specific variant of EBA.

One common type of EBA shows very limited inflammation, with a small number of a certain type of white blood cell (neutrophils) in the lowermost skin layer. There is another type of EBA that is similar to Bullous Pemphigoid (BP), a blistering skin disease, which features a mix of different white blood cells that cause inflammation and tends to look very similar to BP.

If EBA is suspected, it’s advisable to perform a biopsy near the affected area to view under a microscope using a technique called Direct Immunofluorescence (DIF). This method often shows linear deposits of specific type of antibody (IgG) along the boundary area between outer and inner layers of the skin. Sometimes, other types of immune protein deposits might also be seen. However, the pattern of these deposits often helps distinguish EBA from other similar skin blistering disorders.

There is another technique involving salt-split skin which shows immune deposits on the inner side of the separated skin layers. This pattern is different from BP, where deposits are generally located on the outer side of the separation.

Indirect Immunofluorescence (IIF) is a test that might detect circulating autoantibodies against the boundary layer between the outer and inner layers of the skin in patients with EBA.

There’s also a specific technique using electron microscopy that reveals tiny separations in the boundary layer, reduction in the number of supporting fibers and the presence of a specific type of material beneath the layer in EBA skin. This material corresponds to the IgG deposits mentioned earlier.

Immunoelectron microscopy (IEM) is the traditionally approved gold standard in diagnosing EBA as it can show those immune deposits exactly where the supporting fibers within the important boundary layer of the skin are located.

There are other specific tests like Western Blot and ELISA, that can also detect autoantibodies, responsible for immune reactions, in serum.

Lastly, there have been criteria established to diagnose EBA which includes: having a blistering disorder matching the EBA type, no family history of blistering diseases, evidence of a blister below the skin from biopsy, IgG deposits along the boundary of skin layers seen in DIF test, and pinpointing IgG deposits in IEM. There are also alternative tests that can be used like IIF, salt-split skin technique, ELISA, and the Western Blotting method.

Treatment Options for Epidermolysis Bullosa Acquisita

EBA, or Epidermolysis Bullosa Acquisita, is a disease that can be tough to manage because every patient is different, and not everyone reacts positively to treatment. Thus, managing the symptoms of EBA can be as important as trying to treat the disease itself. This includes taking care of any wounds and ensuring a healthy diet, both of which are critical in keeping complications to a minimum.

People who have EBA need to be careful to prevent any further skin damage. This includes not using harsh soaps or hot water, avoiding vigorous scrubbing of the skin, and not overexposing the skin to sun. It’s also important for patients to know the signs of secondary skin infections. If they can spot these signs early, they can get medical attention and prevent the situation from getting worse.

Regular check-ups are crucial for monitoring the disease and spotting any new issues, such as mucosal lesions, which are often painful sores that can appear in the mouth and other areas of the body. Comprehensive reviews of the patient’s physical condition and medical history are necessary to notice any changes or progression in the disease. Because EBA is a rare disease, many of the treatments for it are based on case by case observations rather than large-scale studies. Nevertheless, there are some treatments that have shown promise.

For example, colchicine, a medication used to treat gout and other inflammatory conditions, has been effective in EBA patients when given in high doses. While it’s not entirely clear how this medication works, it’s thought to lower the production of antibodies, which are part of the immune system, and reduce their interaction with T cells, another type of immune cell.

If colchicine is not effective, systemic corticosteroids and other medications that prevent the immune system from causing harm to the body (immunosuppressives) may be useful. These include medications like azathioprine, cyclophosphamide, cyclosporine, methotrexate, and mycophenolate mofetil. For some EBA variants, Dapsone, another anti-inflammatory medication, might provide some benefits. For cases of EBA in children, a combination of Dapsone and prednisolone, a type of corticosteroid, has been suggested. Further, in severe EBA cases that do not respond to common immunosuppressive therapy, case reports have seen successful use of rituximab, a type of medication used to treat certain autoimmune diseases and cancers, and intravenous immunoglobulins, proteins that function as antibodies within the immune system.

The condition known as EBA (Epidermolysis Bullosa Acquisita) can be quite similar to other skin problems that cause blisters, making it a bit tricky to diagnose. These could include:

Dystrophic EB (a type of skin blistering disease)
Bullous pemphigoid (BP), an autoimmune skin disorder causing blisters
Mucous membrane pemphigoid (MMP), causing blistering on the skin and mucus membranes
Porphyria cutanea tarda (PCT), a type of porphyria affecting the skin
Pseudoporphyria, which mimics true porphyria conditions
IgA bullous dermatosis, a rare autoimmune skin condition
Brunsting-Perry pemphigoid, a rare autoimmune skin disorder
Bullous lupus erythematosus (LE), a form of lupus affecting the skin

Dystrophic EB might look a lot like a type of EBA that worsens with physical activity, but things like family history of bullous disorder, conditions present since birth, and certain tests can help differentiate them. BP and MMP might be mistaken for the inflammatory types of EBA, but again, specific tests including using salt-split skin substrate, ELISA, and so on, can rule out other autoimmune diseases.

It might be tough to tell EBA and PCT apart clinically, but specific tests can do the job. PCT would be associated with high levels of certain substances in urine and stool, which isn’t the case with EBA. Pseudoporphyria might also look like EBA, but these patients typically have a history of chronic kidney disease or have been on certain medications.

Bullous lupus can sometimes present as a type of EBA. However, closer examination of tissue from the bullous lupus reveals features typically associated with a skin condition called dermatitis herpetiformis. Also, bullous lupus would generally respond well when treated for lupus, unlike EBA.

What to expect with Epidermolysis Bullosa Acquisita

EBA, or Epidermolysis Bullosa Acquisita, is a long-term skin disease that causes blisters and has periods when symptoms can get worse or better, known as flare-ups and remissions. How severe the disease gets can depend a lot on how bad it was at the time of diagnosis and how effective the treatment is.

According to a study, on average, patients saw reduced symptoms or remission about 9 months after starting treatment with medications that suppress the immune system. After a year, about a third of the patients were symptom-free, and by six years, that number increased to near half. It’s important to note that typically, patients may need to continue treatment for a long time to keep the disease under control.

Death due to EBA is uncommon, and those who receive appropriate treatment and care can expect to live a normal lifespan. Also, the recovery and response to treatment may be more positive in children when compared to adults.

Possible Complications When Diagnosed with Epidermolysis Bullosa Acquisita

EBA, or Epidermolysis Bullosa Acquisita, is a tough medical condition to manage and can negatively impact the patient’s health. In severe cases, EBA may result in rapid scarring causing joint stiffness, webbed fingers or toes, and loss of nails. This condition also has the potential to impact the eyes, digestive tract, and lungs, significantly hindering their function.

Also, EBA can lead to complications such as being unable to move the tongue properly, gum disease, eyelid damage, formation of scar tissue inside the nose, narrow esophagus, and restrictive conditions of the upper airway. Often, the disease may not show any symptoms, resulting in delayed diagnosis and an increased risk for serious complications.

Treatments for EBA include medications that suppress the immune system such as systemic corticosteroids, dapsone, cyclosporine, or colchicine. These treatments can have serious side effects, especially if they have to be used for a long time.

Joint stiffness
Webbed fingers or toes
Loss of nails
Impact on eyes, digestive tract, and lungs
Unable to move the tongue properly
Gum disease
Eyelid damage
Formation of scar tissue inside the nose
Narrow esophagus
Restrictive conditions of the upper airway
Delayed diagnosis due to lack of symptoms
Increased risk of serious complications
Significant side effects from treatments

Preventing Epidermolysis Bullosa Acquisita

EBA, or Epidermolysis Bullosa Acquisita, makes the skin very delicate and prone to forming blisters, especially when injured. So it’s essential to take measures to avoid damaging the skin. For those with EBA, it is highly recommended to follow some simple steps to protect your skin.

Firstly, avoid rubbing your skin vigorously or washing it excessively. These actions can lead to the formation of blisters. It’s also important to stay away from using sticky bandages or tape on your skin, as they can cause extra damage.

You can lessen the friction and pressure on your skin by wearing loosely fitting clothes and comfortable shoes. It’s also a good idea to keep your skin cool and not spend too long in hot, humid environments to help reduce the risk of blisters forming.

Try to avoid taking hot showers as well. It’s best to keep the water temperature close to your body temperature because hot water can harm delicate skin.

Those with EBA need to know how to properly take care of blisters that have popped. Applying an antibacterial ointment can help reduce the chance of getting an infection from bacteria entering into skin erosions. When covering wounds, try to use dressings that don’t stick to the skin. Consider using gauze wraps for loose and gentle coverage, but make sure to avoid adhesives that can cause more damage to delicate skin.

Doctors should teach patients how to spot signs of secondary skin infection and when to seek medical help for wounds that do not get better or get worse. Doctors may also need to provide guidance on food and drink, as good nutrition helps wounds heal more quickly and keeping an eye out for any issues caused by not having enough of a certain nutrient in your diet.

Frequently asked questions

Epidermolysis Bullosa Acquisita (EBA) is a rare, long-lasting disease that causes blisters because our own immune system mistakenly attacks our bodies.

Epidermolysis Bullosa Acquisita is seen as one of the least common skin conditions in Western Europe, with a rate of around 0.2 to 0.5 cases per million people a year. However, it is more common in Korean and African-American groups.

The signs and symptoms of Epidermolysis Bullosa Acquisita (EBA) include: - Fragile skin: EBA is characterized by fragile skin that is prone to blistering and tearing. - Hard blisters: Hard vesicles and blisters may appear on the skin, often on areas that are more exposed to trauma such as the knees, elbows, back of hands, and feet. - Sores: EBA can cause sores on the skin, which may be painful and slow to heal. - Scars: Scarring is a common feature of EBA, and the skin may have permanent scars as a result of the condition. - Milia or tiny cysts: Milia are small, white cysts that can form on the skin affected by EBA. - Skin discoloration: The skin affected by EBA may have areas of discoloration, which can range from redness to darker pigmentation. - Deformities: In severe cases, EBA can lead to deformities such as fused fingers, finger malformations, and nail issues. - Scalp involvement: EBA can affect the scalp, causing sores and scarring alopecia, which is hair loss from scars. - Different forms: EBA can present in different forms, including BP-like EBA, MMP-like EBA, LABD-like EBA, and Brunsting-Perry cicatricial pemphigoid–like EBA. - Shifting symptoms: Some EBA patients may exhibit a single or multiple subtypes of the condition at the same time, and symptoms can shift from one form to another throughout the progression of the disease.

Epidermolysis Bullosa Acquisita (EBA) occurs when antibodies target a specific protein called type VII collagen, which is found in the basement membrane zone of the skin. These antibodies can cause the skin to separate and interfere with the assembly of type VII collagen into anchoring fibrils, leading to fragile skin and blister formation. Certain versions of a gene that helps make a specific type of immune cell (HLA class II) may increase the likelihood of developing EBA. However, more research is needed to fully understand the causes of EBA.

The doctor needs to rule out the following conditions when diagnosing Epidermolysis Bullosa Acquisita: 1. Dystrophic EB (a type of skin blistering disease) 2. Bullous pemphigoid (BP), an autoimmune skin disorder causing blisters 3. Mucous membrane pemphigoid (MMP), causing blistering on the skin and mucus membranes 4. Porphyria cutanea tarda (PCT), a type of porphyria affecting the skin 5. Pseudoporphyria, which mimics true porphyria conditions 6. IgA bullous dermatosis, a rare autoimmune skin condition 7. Brunsting-Perry pemphigoid, a rare autoimmune skin disorder 8. Bullous lupus erythematosus (LE), a form of lupus affecting the skin

The types of tests needed for Epidermolysis Bullosa Acquisita (EBA) include: 1. Histological examination: Examining a sample of skin from the affected area under a microscope to look for signs of EBA, such as swelling in the lower layers of the skin and cellular breakdown along the boundary area where the outer and inner layers of the skin meet. 2. Direct Immunofluorescence (DIF): Performing a biopsy near the affected area and using DIF to view the skin sample under a microscope. This method can show linear deposits of a specific type of antibody (IgG) along the boundary area between the outer and inner layers of the skin, helping to distinguish EBA from other similar skin blistering disorders. 3. Salt-split skin technique: This technique involves separating the layers of the skin and examining the immune deposits on the inner side of the separation. The pattern of these deposits can help differentiate EBA from other conditions like Bullous Pemphigoid. 4. Indirect Immunofluorescence (IIF): A test that can detect circulating autoantibodies against the boundary layer between the outer and inner layers of the skin in patients with EBA. 5. Electron microscopy: A technique that reveals tiny separations in the boundary layer, reduction in the number of supporting fibers, and the presence of a specific type of material beneath the layer in EBA skin. This material corresponds to the IgG deposits seen in DIF. 6. Immunoelectron microscopy (IEM): The gold standard test for diagnosing EBA, which can show immune deposits exactly where the supporting fibers within the boundary layer of the skin are located. 7. Western Blot and ELISA: These tests can detect autoantibodies responsible for immune reactions in the serum. In addition to these tests, there are also established criteria for diagnosing EBA, which include specific clinical features and findings from the above-mentioned tests.

Epidermolysis Bullosa Acquisita (EBA) can be treated with various medications depending on the individual case. One medication that has shown effectiveness is colchicine, which is typically used to treat gout and other inflammatory conditions. It is believed to reduce the production of antibodies and their interaction with T cells. If colchicine is not effective, other medications such as systemic corticosteroids and immunosuppressives like azathioprine, cyclophosphamide, cyclosporine, methotrexate, and mycophenolate mofetil may be used. Dapsone, an anti-inflammatory medication, may be beneficial for certain EBA variants, and a combination of Dapsone and prednisolone has been suggested for EBA in children. In severe cases that do not respond to common immunosuppressive therapy, rituximab and intravenous immunoglobulins have been used successfully.

The side effects when treating Epidermolysis Bullosa Acquisita can include: - Joint stiffness - Webbed fingers or toes - Loss of nails - Impact on eyes, digestive tract, and lungs - Unable to move the tongue properly - Gum disease - Eyelid damage - Formation of scar tissue inside the nose - Narrow esophagus - Restrictive conditions of the upper airway - Delayed diagnosis due to lack of symptoms - Increased risk of serious complications - Significant side effects from treatments

The prognosis for Epidermolysis Bullosa Acquisita (EBA) can vary depending on the severity of the disease at the time of diagnosis and the effectiveness of treatment. On average, patients may see reduced symptoms or remission about 9 months after starting treatment with immune system-suppressing medications. After a year, about a third of patients may be symptom-free, and by six years, that number may increase to nearly half. With appropriate treatment and care, death due to EBA is uncommon, and individuals can expect to live a normal lifespan.

Dermatologist.

Autoimmune Bullae Skin Problems And Treatments