What is Pemphigoid Gestationis?
Pemphigoid gestationis (PG), previously known as herpes gestationis, is a rare skin condition that occurs during pregnancy. Different from its initial name, it actually has no connection to the herpes virus. Instead, it’s an autoimmune skin issue that causes blisters; its former name was due to the blisters that looked similar to those caused by herpes. This condition was first identified in 1872 by a scientist named Laws Milton.
Typically, PG shows up during the third trimester of pregnancy, but it can appear at any stage, even after childbirth. It leads to skin inflammation and severe itching. The skin changes usually start near the belly button and then spread outward to other body parts such as the abdomen and limbs. However, it generally doesn’t affect the face or the inner lining of body parts (mucous membranes). In later pregnancies, there is a 30% to 50% chance of PG occurring again, usually starting earlier and with more severity.
To diagnose PG, doctors usually rely on the specific signs on the patient’s skin and a special skin test (direct immunofluorescence). Additional tests may also be conducted to rule out other skin conditions. The primary goal of treatment is to manage symptoms and stop new skin lesions from appearing. Moderate to severe cases of PG are often treated with corticosteroids, a type of medication that reduces inflammation. In some instances, intravenous immunoglobulins, which are antibodies given through the vein, can also be effective.
PG usually gets better on its own in most patients. However, it has been linked with premature birth, babies that are smaller than usual for their gestational age, and also a thyroid condition called Graves’ disease in the mother. So, it’s crucial that doctors understand how to appropriately diagnose and treat PG and work closely with a team of health professionals to ensure the best possible health outcomes for both mother and baby.
What Causes Pemphigoid Gestationis?
In Pregnancy-associated Dermatitis (PG), skin issues are caused by the mother’s immune system mistaking certain proteins in the skin and placenta as foreign substances. These proteins, named bullous pemphigoid 180 (BP 180) and bullous pemphigoid 230 (BP 230), are found in a specific skin layer and in placental tissue.
Although we don’t fully understand why the mother’s body produces these harmful antibodies, it’s clear that PG is strongly associated with two types of human leukocyte antigens, HLA-DRB1*0301 (HLA-DR3) and HLA-DRB1*0401/040X (HLA-DR4). Antigens are substances that can trigger an immune response. These two types of antigens are parts of the major histocompatibility complex (MHC) class II – a group of genes that help the immune system distinguish the body’s own proteins from proteins made by foreign invaders like viruses and bacteria. PG is also strongly associated with human leukocyte antigens named PG3 and PG4.
Risk Factors and Frequency for Pemphigoid Gestationis
PG is a condition that happens during pregnancy, with its occurrence estimation ranging from 1 in every 2,000 to 60,000 pregnancies. The majority of PG cases happen during the second and third trimesters. It’s more common in women who have had more than one pregnancy compared to those who are pregnant for the first time. Often, if a woman has had PG in a previous pregnancy, it may happen again in future pregnancies, usually starting earlier and with more severe symptoms. It’s important to note that, although rare, PG has been linked with certain types of pregnancy complications like hydatidiform moles and choriocarcinomas.
- PG happens during pregnancy and occurs in between 1 in 2,000 to 60,000 pregnancies.
- The majority of cases are seen in the second and third trimesters.
- Women who have been pregnant more than once are more likely to experience PG than those pregnant for the first time.
- In women who have had PG before, it can happen again in future pregnancies, often starting earlier and having worse symptoms.
- Although uncommon, PG has been connected with hydatidiform moles and choriocarcinomas.
Signs and Symptoms of Pemphigoid Gestationis
Pemphigoid Gestationis (PG) is a rare skin condition that can occur during pregnancy. Clinicians can diagnose this condition by understanding its unique features and how they differ from other similar skin conditions. It’s important for doctors to gather a complete medical history, including past and current pregnancy details, because the symptom patterns of PG can change, often intensifying around childbirth and following delivery.
PG typically resolves itself within one to two months postpartum, although symptoms can persist or worsen due to increased antibodies following pregnancy. PG can recur in future pregnancies or with certain menstrual cycles and oral contraceptives. PG can also present risks to the fetus such as growth restriction, premature labor, and temporary skin lesions. Notably, there’s no observed increase in the risk of stillbirth or miscarriage.
- Intensifying symptoms around childbirth and postpartum
- Self-resolution within one to two months postpartum
- Possibility of symptoms persisting or worsening
- Recurrence in future pregnancies or with certain menstrual cycles and contraceptives
- Associated fetal risks such as delayed growth, premature labor, and temporary skin lesions
The main symptom of PG is itching, which can sometimes occur before any visible skin changes. As the skin lesions evolve, other features can appear such as red itchy bumps and patches, and in over 65% of cases, they develop into fluid-filled bladder-like appearances. These lesions can start around the belly button and spread to other parts of the body, including the thighs, palms, and soles of the feet. The face and the inside of the mouth are typically not affected.
In the early stage, the physical examination findings and the distribution of the lesions are not always clear cut, making it hard for doctors to tell PG apart from other itchy skin conditions of pregnancy such as the Polymorphic Urticarial Papules and Plaques of Pregnancy (PUPPP). Because of this difficulty, a test known as a direct immunofluorescence is typically used to confirm the diagnosis of PG.
Testing for Pemphigoid Gestationis
If someone’s doctor suspects that they may have a skin condition called Pemphigoid Gestationis (PG), often several tests will be needed since the symptoms alone may not be specific enough to make a diagnosis. Tests that can be used in these cases include histopathology (the study of changes in tissues caused by disease), direct immunofluorescence (a test that uses special markers to identify certain proteins in tissue), and enzyme-linked immunosorbent assay (ELISA – a test that can identify proteins in blood or other fluids).
However, the most effective test to confirm PG is the direct immunofluorescence (DIF) test conducted on a sample of skin. When skin affected by PG is examined under DIF, it often shows a specific pattern of certain proteins, named C3 and IgG, which can usually be seen lining the bottom layer of the skin. The presence of C3 deposits is a key indicator of PG, as it is usually seen in all patients with this condition. It is interesting to note that DIF can remain positive for up to 4 years after the symptoms of PG have resolved.
Apart from DIF, other tests can also be helpful. Histopathology can help in ruling out other skin diseases. The findings may vary depending on the stage and severity of the disease. In the early stages before blisters appear, it may show certain changes such as swelling and infiltration of the underlying skin layers. Immunochemistry studies might show another protein called C4d along the skin layers.
Indirect immunofluorescence microscopy can detect circulating IgG antibodies in the blood of approximately 30% to 100% of patients with PG. ELISA testing can help tell PG apart from other skin conditions that occur during pregnancy by identifying specific antibodies labeled as BP 180 IgG in blood samples. It has a very high success rate of approximately 95%, which could potentially make DIF, the current gold standard, unnecessary.
However, there are limitations to both DIF and indirect immunofluorescence, such as the need for special handling of tissue samples and having the necessary lab equipment, which can increase costs. This might be a challenge in developing countries.
Treatment Options for Pemphigoid Gestationis
The treatment for Pemphigoid gestationis (PG), a skin condition, depends on how severe the symptoms are and what stage the skin lesions are at. The goal of treatment is to provide relief from itching and prevent more blisters from forming. The first step in treatment usually involves high-strength topical corticosteroids and antihistamines, which are medicines applied directly to the skin. But if these aren’t effective, additional treatments may be considered. Recent treatment plans aim to reduce the use of high-dose steroids to avoid potential complications, especially during pregnancy.
Most of the current recommendations for treating PG, including the use of topical corticosteroids and oral antihistamines, come from case studies. These treatments are typically chosen when the disease is localized and has minimal blistering. However, patients who don’t respond to topical treatment, or who have a more severe form of the disease that covers more than 10% of the body, may need systemic corticosteroids. These are drugs that work throughout the entire body. Prednisone and prednisolone are typically chosen for this purpose because they cross the placenta in lower concentrations. If no new blisters form within two weeks, the treatment is deemed a success, and the dose of the corticosteroid can be gradually reduced.
For patients who don’t respond to these treatments, the disease can be controlled by using drugs that suppress the immune system, such as cyclosporine, dapsone, or azathioprine. However, these medicines can have adverse effects, such as suppressing bone marrow activity, causing premature birth, and damaging the liver.
IVIG, or intravenous immunoglobulins, have been used successfully alone or along with other treatments. These have a better safety profile than immunosuppressants. There are also biotherapies such as dupilumab, a drug that targets elements of the immune system, which have been used, especially in resistant cases or cases where steroid therapy isn’t recommended due to other health issues such as diabetes. Notably, use of this treatment has been associated with rapid symptom relief and less need for high-dose systemic steroids.
Another effective treatment is rituximab, particularly in preventing PG from recurring when given before conception. Patients are advised to avoid becoming pregnant for 12 months following the last infusion of this medicine.
What else can Pemphigoid Gestationis be?
When doctors are trying to figure out if a patient has Pyoderma Gangrenosum (PG), they also need to think about other disorders that can cause similar symptoms. These include:
- Urticaria (also known as hives)
- Allergic contact dermatitis (a skin reaction caused by contact with a certain substance)
- Bullous pemphigoid (a skin disease that causes large, fluid-filled blisters)
- Cicatricial pemphigoid (a rare skin disorder that causes blistering)
- Dermatitis herpetiformis (an itchy, blistering skin condition)
- Erythema multiforme (a skin disorder resulting from an allergic reaction or infection)
- Impetigo (a common skin infection)
- Intrahepatic cholestasis of pregnancy (a liver disorder that occurs in pregnant women)
- Linear IgA dermatosis (a rare skin disorder)
- Bullous drug eruption (skin reaction to certain medications)
- Atopic eruption of pregnancy (skin rash that can occur during pregnancy)
What to expect with Pemphigoid Gestationis
The general outlook for PG, or Pemphigoid gestationis, which is a rare skin condition that happens during pregnancy, is usually positive. However, women who have experienced PG during pregnancy are more likely to experience it again during subsequent pregnancies. Moreover, these women may also be at a higher risk of developing other immune system-related illnesses, such as Grave’s disease, later on.
In around 10% of pregnancies with PG, the disease can affect the newborn baby due to the mother’s antibodies transferring to the baby while in the womb. Fortunately, these conditions in newborns usually resolve on their own.
However, PG can increase the risks to the unborn baby, like premature birth and slow growth inside the womb. Reducing these risks rely heavily on early diagnosis of Pemphigoid gestationis via clinical and biopsy testing.
During pregnancy, it is crucial to monitor for slowed fetal growth and watch for any side effects of the high-dose steroid treatment used to manage PG. This vigilant monitoring helps to lessen potential complications for the mother and the baby.
Treating and managing PG effectively requires teamwork from different specialists, including infant specialists, pediatricians, obstetricians who care for pregnant women, and dermatologists. This team-based approach ensures the well-being of both the mother and her baby during and after pregnancy, and also during any future pregnancies.
Possible Complications When Diagnosed with Pemphigoid Gestationis
While the condition known as Pemphigoid Gestationis (PG) doesn’t generally cause many issues for the mother or baby, the itching it produces can be very upsetting. Long-term use of corticosteroids, a common treatment for PG, during pregnancy might lead to complications such as early birth, high blood pressure during pregnancy (preeclampsia), early rupture of the membranes surrounding the baby, blood clots in the veins, possible birth defects, kidney infections, and even potentially death of the baby before birth.
Although babies born smaller than usual are more common when corticosteroids have been used for a long time in pregnancy, we are not sure if the steroids are a direct cause, or if it’s the health problem that needs steroid treatment that causes it. Some animal studies suggest that using steroids might interfere with the healthy development of the placenta, which can limit the growth of the baby, but the exact process and link are still not entirely clear.
When considering treatment strategies that involve long-term use of steroids during pregnancy, we must weigh the risks against the benefits. More studies are needed to figure out whether using steroids during pregnancy has any long-term effects on children born to mothers who used these medications.
- Intense itching
- Possible risks from long-term steroid use:
- Preterm birth
- High blood pressure during pregnancy
- Premature rupture of protective membranes
- Blood clots in veins
- Potential birth defects
- Kidney infections
- Possibility of death of the baby before birth
- Small size at birth of the baby
- Possible interference with placenta development
