What is Bullous Pemphigoid?
Bullous pemphigoid, or BP, is a common skin condition where blisters form, making up about 80% of instances where this happens. This condition is most often seen in older adults aged between 60 and 80 years. The symptoms can vary quite a bit, but the telltale signs are tight blisters and severe itching all over the body. In less typical cases, there might not be any blisters, which means doctors have to be sharp in their observations. A biopsy – taking a small sample of skin to examine under a microscope – can help diagnose this condition. It shows a split underneath the skin filled with white blood cells called eosinophils, while a type of test called direct immunofluorescence can detect antibodies against the base layer of the skin. ELISA, another type of test, can also be useful for diagnosis. How it’s treated depends on how severe the disease is, but typically creams or medicines that weaken the immune system are used. How a patient fares over time can change case-by-case, and often they must be closely monitored for a long period.
What Causes Bullous Pemphigoid?
Most cases of bullous pemphigoid, a skin condition that causes blisters, often occur due to an immune response against proteins at where the skin layers meet. However, there are instances where this condition is caused by certain medications. This so-called ‘drug-induced’ bullous pemphigoid can happen up to three months after starting the medicine and is typically seen in younger patients.
Several drugs have been reported to trigger this blistering skin reaction. These include some water pills (like furosemide and spironolactone), pain relievers called NSAIDs, the antibiotic amoxicillin, medications that inhibit PD-1/PD-L1 (used in cancer treatment), gliptins (used for diabetes), and TNF-alpha inhibitors (used for certain autoimmune conditions).
Risk Factors and Frequency for Bullous Pemphigoid
Bullous pemphigoid (BP) typically affects individuals who are over 60 years old. On average, 6 to 13 new cases are reported per million people each year in the United States, and 12 to 13 per million people in Central Europe. It is interesting to note that BP affects both men and women equally and does not favour any particular race. Although the disease might show up in childhood, it’s quite unusual. Some specific genetic markers, known as HLA class II alleles, are found in patients with BP. For instance, DQB1*0301 is often seen in Caucasian patients, while DRB1*04, DRB1*1101, and DQB1*0302 are commonly found in Japanese patients.
Signs and Symptoms of Bullous Pemphigoid
Bullous pemphigoid is a skin condition that commonly starts with severe itching that may come with hives or small, raised bumps. Over time, typically spanning weeks to months, this can develop into blisters in areas like the armpits, the inner part of the forearms and thighs, the torso, and the belly. However, not all patients will show these blisters or sores at the initial stage. These symptoms generally get worse only if the disease is extensive and severe.
The blisters in the later stage of the disease unfortunately appear on normal or red skin. These blisters are tight, ranging from 1 to 4 centimeters in size, and may sometimes contain blood. Originally, these blisters are filled with a clear fluid and can last for several days before they turn into sores and crusts. Notably, the Nikolsky sign, a skin test, is negative in usual cases of bullous pemphigoid, unlike in another skin disorder, pemphigus vulgaris.
This condition is unusual in children. That said, there have been reported instances of baby bullous pemphigoid, showing up in the extremities during a baby’s first year. Other variants of this condition in children are found localized to the female genital region. However, these cases are uncommon and should be differentiated from other disorders due to their rarity. In some cases in children, they develop particular antibodies (IgA antibodies against the NC16A domain of BP180). It has also been reported that the infant version is not related to the transfer of autoantibodies from mother to baby.
There’s ongoing debate among scientists as to whether bullous pemphigoid is related to internal cancers. However, majority believe this association could be due to patients’ older age. A recent study found no increased risk for concurrent or later-developing cancers in patients with bullous pemphigoid.
Testing for Bullous Pemphigoid
To diagnose bullous pemphigoid, a skin condition that causes large blisters, doctors rely on both the symptoms a patient is experiencing and laboratory tests. These tests often include histology, which is a microscope examination of skin tissue, and immunofluorescence studies, a process which uses fluorescent dyes to identify certain molecules.
In a histology test for bullous pemphigoid, doctors look for a separation between the top and bottom layers of skin and numerous white blood cells called eosinophils. This same test can also help doctors identify early, or pre-bullous, stages of the condition where there is an unusually high number of these white blood cells but no separation in the skin layer yet.
Immunofluorescence studies are a critical part of accurately diagnosing this condition. These studies involve identifying any autoantibodies (cells that mistakenly attack your own body) within a skin tissue sample. This test is often considered the most reliable in diagnosing autoimmune skin conditions like bullous pemphigoid. To do this, doctors will take two small skin samples, one to stain and examine more closely, and another from an unaffected skin area for direct immunofluorescence. These tests will show if there are traces of a specific type of immune system protein present, which would indicate bullous pemphigoid.
Another more specialized test called the salt-split skin immunofluorescence study is also sometimes used. This test involves applying patient serum (a clear fluid from your blood) on skin that is split using salt. It helps to differentiate whether the condition is bullous pemphigoid or a similar skin disorder.
Additionally, an ELISA test can be used to detect the presence of antibodies to certain skin proteins. This test has a high level of both sensitivity (ability to correctly identify positive cases) and specificity (ability to correctly identify negative cases).
According to a study by the French Bullous Study Group, the likelihood of bullous pemphigoid can be strongly suggested if the patient is older than 70 years, has a blistering disorder with immune system proteins seen along the skin basement membrane, but there is no skin thinning (atrophy), nor any involvement of the mucous membrane or head and neck. They suggested that if three out of these four criteria are met, the diagnosis for bullous pemphigoid is highly probable.
Treatment Options for Bullous Pemphigoid
Bullous pemphigoid is primarily treated with systemic corticosteroids, but the treatment may also depend on the individual’s overall health and how widespread the disease is. If the disease affects less than 20% of the body’s surface and is detected in an older patient, highly potent topical steroids like clobetasol might be used. A combination of topical steroids with tetracycline, minocycline, or doxycycline and nicotinamide has been successful in a number of cases.
If the disease affects a larger part of the body, oral prednisone, which is a type of steroid, may be given. This treatment can keep the disease under control within about two weeks, and the dose can be slowly decreased over six to nine months, or even more. However, this approach may not suit everyone, especially older people or those with other health conditions, and it can also have side effects. Topical steroids might control the symptoms of widespread Bullous Pemphigoid with fewer side effects.
If the disease can’t be kept under control with steroids, or if someone can’t take systemic steroid treatments for certain reasons, treatments that suppress the immune system could be an alternative. These might include medications like azathioprine, methotrexate, mycophenolate mofetil, chlorambucil, or cyclophosphamide. When other treatment options fail to work, options such as intravenous immunoglobulin (IVIG), rituximab (anti-CD20), or omalizumab may be considered.
Studies have also discovered that the levels of certain antibodies (IgG autoantibodies) that react to BP180, a specific antigen involved in bullous pemphigoid, could be linked with how severe the disease is. A high BP180-NC16A ELISA score (a type of blood test) and the presence of specific antibodies identified by a procedure called direct immunofluorescence at the end of treatment might indicate a possibility of the disease returning.
What else can Bullous Pemphigoid be?
Bullae, or blisters, can appear on the skin due to a variety of health conditions and their presence often mirrors the pattern of different skin diseases. Potential causes include reaction to drugs, skin allergies or irritants, hives, bug bites, and a group of rare autoimmune disorders that cause blistering skin conditions like pemphigus vulgaris. Bullae can also occur because of severe skin reactions like Stevens-Johnson syndrome, types of eczema, pseudoporphyria, or porphyria cutanea tarda, a disease that affects the nervous system and skin.
If bullae appear during childhood, it is crucial to consider conditions like bullous impetigo (a bacterial skin infection), epidermolysis bullosa (a group of genetic conditions that cause the skin to be very fragile), and a type of mastocytosis, a disease caused by an excess of mast cells.
To confirm the cause of bullae, especially when bullous pemphigoid (a rare skin condition that causes large, fluid-filled blisters) is suspected, several tests might be required. These could include a skin biopsy for microscopic examination, special fluorescence tests to detect antibodies, tests identifying features of skin separation, and ELISA tests which measure antibodies in the blood.
What to expect with Bullous Pemphigoid
Bullous pemphigoid is a condition that usually improves on its own within a few months, but in some cases, it can last up to five years. The treatment methods mentioned previously can help ease symptoms like pain and itching.
Possible Complications When Diagnosed with Bullous Pemphigoid
Health problems and potential fatalities caused by bullous pemphigoid can include:
- Skin infections and blood poisoning caused by Staphylococcus and Streptococcus bacteria
- Viral infections, such as cold sores or chickenpox
- Negative side effects from treatment
Preventing Bullous Pemphigoid
This disease can make a person’s skin delicate and more likely to be invaded by tiny organisms like bacteria. It’s very important for these patients to avoid skin injuries. Keeping the skin clean plays a vital role in preventing further problems from developing. Patients should also learn to recognize any complications or harmful effects resulting from treatment so they can promptly report these to their doctor. It’s also crucial for patients to understand how serious their condition is.
