What is IgA Pemphigus?
Immunoglobulin A (IgA) pemphigus is a rare condition where the immune system, which usually defends the body against harmful invaders, mistakenly targets skin cells, causing painful and itchy blisters that resemble pimple-like eruptions. The cause of this condition is not yet clear, however, it has been found to occur in individuals with certain chronic illnesses and cancers.
IgA pemphigus has two main types: subcorneal pustular dermatosis and intraepidermal neutrophilic dermatosis. In the first type, the immune system produces IgA antibodies that attack a protein in the skin called desmocollin-1, causing blisters mainly in the outer layers of skin. In the second type, the immune system targets other proteins in the skin, mainly in the lower parts of the skin, causing similar symptoms.
Even though IgA pemphigus is generally not as severe as some similar conditions caused by different types of antibodies (like IgG), it’s still important to diagnose it accurately and treat it intensively with steroid medication and a drug called dapsone to stop the symptoms from coming back.
What Causes IgA Pemphigus?
IgA pemphigus is a skin condition caused by antibodies (which are part of your immune system) attacking your own skin cells. However, we don’t yet know what triggers this to happen. Researchers believe that a protein made by the immune system called interleukin 5 (IL-5) might be involved. It encourages the production of the type of antibodies that are found in IgA pemphigus. These antibodies have a unique ability to attach to specific receptors on certain cells, possibly leading to a build-up of a type of white blood cell called neutrophils in the outer layer of skin, which could cause the blisters associated with this condition.
IgA pemphigus is often found alongside a condition called monoclonal IgA gammopathy and a type of cancer known as multiple myeloma. The sequence of these conditions’ onset is still under debate, but usually, they’re present at the time of diagnosis. Additionally, IgA pemphigus has been observed in patients with various other conditions, including HIV, Sjögren syndrome, rheumatoid arthritis, lung cancer, ulcerative colitis, peripheral T-cell lymphoma, chronic myeloid leukemia, and diffuse large B-cell lymphoma. While it’s unclear how all of these illnesses relate to IgA pemphigus, it’s crucial for healthcare providers to evaluate patients with IgA pemphigus for signs of blood-related disorders, gut conditions, inflammatory joint conditions, and infections.
Risk Factors and Frequency for IgA Pemphigus
IgA pemphigus is a very rare type of autoimmune disease where blisters form on the skin. It can occur at any age, but it’s mostly seen in adults, typically between the ages of 40 and 60. It’s important to note that this condition doesn’t favor any particular gender.
Signs and Symptoms of IgA Pemphigus
When a doctor takes a patient’s medical history, they look out for signs of skin changes, as this can help identify different types of a skin disease called pemphigus. In one type of pemphigus, known as IgA pemphigus, the skin changes do not affect the mucous membranes (such as the mouth or nose).
The early symptoms of IgA pemphigus typically start with the sudden appearance of soft, fluid-filled blisters on skin that may look red. These blisters then change into small rashes that quickly burst, creating ring-shaped scabs. These skin changes often hurt and itch.
These skin changes are often spotted in areas where skin rubs against itself frequently, like underarms or groin. However, the trunk and limbs are where these changes are most commonly seen. People with this condition usually do not experience body-wide symptoms like fever, discomfort, headaches, or weight loss. They mostly deal with skin-related symptoms.
- Sudden appearance of soft, fluid-filled blisters on red-looking skin
- Blisters change into small, quickly bursting rashes, creating ring-shaped scabs
- Skin changes that hurt and cause itching
- Changes typically occurring in areas like the underarms, groin, trunk, or limbs
- General absence of body-wide symptoms like fever, discomfort, headaches, or weight loss
Testing for IgA Pemphigus
If your doctor suspects that you might have a skin condition called IgA pemphigus, the first step in the evaluation process is a skin biopsy. A skin biopsy involves taking a small sample of your skin to be examined in a lab. The doctor will pick skin from the edge of a new lesion or sore for this procedure. They will stain the skin sample with a dye called hematoxylin and eosin to look at it under a microscope. Another skin biopsy will also be taken from a section of skin that isn’t affected by the condition, but close to the lesion or sore (about 4mm away). This additional biopsy helps ensure that the presence or absence of the IgA autoantibodies— proteins that the immune system mistakenly makes against your own tissues—can be determined.
IgA pemphigus is characterized by immune cells called neutrophils infiltrating or gathering within the epidermis, the outermost layer of skin. Under a microscope, this infiltration along with other characteristic changes can be seen. However, a process called acantholysis, where the cells in the epidermis separate from each other, doesn’t happen much in IgA pemphigus. This is why a technique called direct immunofluorescence is used as an early diagnostic tool for patients with widespread pustular eruptions (small bumps on the skin filled with pus). This technique helps detect the IgA autoantibodies on the surface of the skin cells.
Another method called indirect immunofluorescence is used to detect the presence of IgA autoantibodies in the patient’s blood. Here, the patient’s blood serum (liquid part of the blood) is exposed to monkey esophagus or other epithelial substrates. This finds the circulating IgA autoantibodies, which are found in about half of the patients with IgA pemphigus.
There are also other tests known as immunoblotting and enzyme-linked immunosorbent assay (ELISA). Immunoblotting is used to identify the specific antigen (substance that triggers an immune response) in the skin that the IgA autoantibodies are reacting against. However, this test may show IgA reactivity to any antigen in about 40% of the cases. ELISA can detect specific antigens in the skin’s desmosomes (structures that connect skin cells) but it’s identified in only about 55% of the cases.
Treatment Options for IgA Pemphigus
IgA pemphigus is an inflammatory disease that usually requires treatment with oral and topical corticosteroids. However, these medications can have long-term side effects, including weak bones (osteoporosis), diabetes, eye conditions like cataracts, diminished adrenal gland function, and infection.
Interestingly, compared to other similar diseases, IgA pemphigus often does not respond well to steroid treatment alone. Research shows that a combination of corticosteroids with a medication called dapsone, which helps by reducing inflammation, tends to give better results. Still, it’s important to note that dapsone can have side effects, like breaking down red blood cells (hemolysis) and increasing a form of hemoglobin that can’t transport oxygen (methemoglobinemia).
There are other medications that have been found effective in treating IgA pemphigus. These include colchicine, retinoids, mycophenolate mofetil, and adalimumab. Most of these were initially used to successfully treat other skin conditions and are now being applied to the treatment of IgA pemphigus. For example, adalimumab works by blocking a particular molecule (tumor necrosis factor-α) that leads to inflammation. Rituximab, which targets a particular protein on cells, has also been used safely to treat IgA pemphigus.
Healthcare providers may also recommend medicines to prevent stomach ulcers and bone loss, and to suggest weight-bearing exercises and adequate intake of calcium and vitamin D. It’s important for patients to have a thorough physical examination and, when necessary, additional tests to check for other diseases. These might include cancer, inflammatory bowel disease, joint and musculoskeletal diseases, and infectious diseases.
What else can IgA Pemphigus be?
If a person develops conditions like IgA pemphigus, which is uncommon, doctors need to keep in mind other possible diagnoses. This is because the symptoms of these conditions are often very similar. To tell these conditions apart, doctors may need to investigate using procedures like tissue examination (histology) and tests to look for certain proteins (immunofluorescence).
Some conditions that could be mistaken for IgA pemphigus include:
- Bullous impetigo
- Pustular psoriasis
- Linear IgA bullous dermatosis
- Dermatitis herpetiformis
- Subcorneal pustular dermatosis or Sneddon-Wilkinson disease
- Pemphigus foliaceus
For example, Sneddon-Wilkinson disease also known as classic subcorneal pustular dermatosis, is a chronic skin condition. It has patterns of pustular lesions (a type of skin bump filled with puss) that burst and form crusty patches. The lesions in this condition and IgA pemphigus are often found in the same places, like the groin and trunk, and both avoid places that produce mucus. However, protein tests (immunofluorescence) show no findings of the IgA antibody in Sneddon-Wilkinson disease, unlike in IgA pemphigus.
Another condition is Pemphigus foliaceus, which shows soft, blister-like bumps typically on the trunk of the body that finally crust over, much like the lesions in IgA pemphigus. It’s generally not harmful and responds well to treatment with creams and oral steroids. The distinguishing factor between Pemphigus foliaceus and IgA pemphigus is the presence of a different antibody (IgG and IgA respectively), which can only be determined using immunofluorescence tests. Because of this, correct testing for histology and immunofluorescence is necessary to differentiate these conditions.
What to expect with IgA Pemphigus
Compared to classic pemphigus, a skin condition that causes blisters, IgA pemphigus is usually milder and affects a smaller part of the body. Typically, with the right treatment and regular check-ups, IgA pemphigus often gets better without leaving any scars.
However, studies have shown that if oral steroids, a common treatment for this condition, are suddenly stopped, the sores might come back. Therefore, healthcare providers should slowly lessen the dose over time.
Beyond this, if IgA pemphigus appears alongside other health issues like cancer, gastrointestinal diseases (illnesses affecting the digestive system), or monoclonal gammopathy (a condition where there is an abnormal increase of a specific type of protein in the blood), the overall prognosis or health outlook depends on how advanced these other conditions are.
Possible Complications When Diagnosed with IgA Pemphigus
IgA pemphigus, a skin disorder, can lead to various complications. These are primarily due to the long-lasting effects of the treatment itself. The main complications include infection of the skin lesions and scarring. However, medications used for treatment, such as corticosteroids and dapsone, may also have potential side effects.
The complications that can arise from the use of corticosteroids are:
- Osteoporosis or weakened bones
- Peptic ulcer disease or sores in the stomach lining
- Adrenal insufficiency or reduced adrenal gland function
- Infections
- Slowed growth in children
- Weight gain
- Anemia or low red blood cell count
- High blood pressure or hypertension
- Diabetes
If dapsone, another medication, is used, the following complications might occur:
- Methemoglobinemia or abnormal oxygen levels in the blood
- Hemolytic anemia or destruction of red blood cells
- Neutropenia or low white blood cell count
- Agranulocytosis or extremely low white blood cell count
- Liver failure
- Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, a severe drug reaction
