Pemphigoid gestationis is a rare autoimmune blistering skin disease that occurs during pregnancy or shortly after delivery. Despite affecting roughly 1 in 20,000 to 50,000 pregnancies, it stands out among pregnancy-related skin conditions because it carries real risks for both the mother and the baby, and because it is frequently misdiagnosed early on as a more common rash.1Europe PMC. Pemphigoid gestationis: current perspectives The condition was previously called herpes gestationis, a name that has nothing to do with the herpes virus and that still causes confusion among patients and some clinicians today.
What the Rash Looks Like
The eruption usually begins around the belly button. In its earliest stage it looks like intensely itchy red bumps and ring-shaped welts, which can easily be mistaken for hives or an allergic reaction. Over days to weeks, small fluid-filled blisters appear, and these can progress into large, tense blisters sitting on red, inflamed skin. The rash often spreads from the abdomen to the trunk, arms, legs, and sometimes the palms and soles.2Clinical, Cosmetic and Investigational Dermatology. Pemphigoid Gestationis – Case Report and Review of Literature The face and mucous membranes are almost always spared.
The itch tends to be severe and relentless, often worse than the rash itself looks. Many patients describe it as the most debilitating part of the disease, interfering with sleep and daily functioning. Most cases begin in the second or third trimester, though onset in the first trimester or even the postpartum period is documented. Earlier onset has been linked to more severe disease overall.
A hallmark pattern of pemphigoid gestationis is a flare around the time of delivery. The rash and blistering can intensify dramatically during labor or in the first few days postpartum, only to begin resolving spontaneously in the weeks and months that follow.3PubMed Central. Gestational pemphigoid Some women experience persistent or relapsing disease for months after delivery, and a small number deal with ongoing symptoms for years.
Why the Immune System Attacks the Skin
Pemphigoid gestationis is driven by the mother’s immune system producing antibodies against a protein called collagen XVII (also known as BP180), which is found in both the skin and the placenta. The current understanding is that the process starts in the placenta, not in the skin. Placental tissue normally keeps a low immune profile so the mother’s body does not reject the developing fetus. In PG, placental cells abnormally display certain immune-signaling molecules on their surface, exposing collagen XVII to the maternal immune system in a way that triggers an antibody response.4PubMed. Pemphigoid gestationis: current insights into pathogenesis and treatment Because the same collagen XVII protein exists at the junction between the outer and inner layers of the skin, those antibodies then cross-react with the skin, causing inflammation, separation of the skin layers, and blistering.5American Journal of Obstetrics and Gynecology. Pemphigoid gestationis: A review
The antibodies involved are primarily of the IgG1 and IgG3 types, and they target specific segments of the collagen XVII protein that overlap with those attacked in bullous pemphigoid, a blistering disease that occurs mainly in elderly adults outside of pregnancy.6Journal of Investigative Dermatology. IgG1 and IgG3 are the Major Immunoglobulin Subclasses Target Distinct Epitopes within the BP180 NC16A Domain in Pemphigoid Gestationis This shared target explains why the two diseases look similar under the microscope, even though they affect very different populations.
Genetic Predisposition
Not every pregnant woman develops PG, and the reason lies partly in genetics. The condition is strongly associated with specific immune-system gene variants, particularly HLA-DR3 and HLA-DR4. Studies have found that nearly all women with PG carry one or both of these variants.7PubMed. Class II MHC typing in pemphigoid gestationis These gene variants influence how the immune system presents proteins to its own cells for inspection. When the placenta abnormally exposes collagen XVII, women carrying these particular variants are more likely to mount an immune response against it. This genetic link also helps explain why PG is associated with other autoimmune conditions, since DR3 and DR4 are well-known risk factors for autoimmune thyroid disease and other immune-mediated disorders.
A population-level study found that PG was more common among African-American women, those with lower incomes, those with pre-existing thyroid disease, smokers, and women with severe obesity.8PubMed. Maternal and Fetal Outcomes Among Pregnant Women Developing Pemphigoid Gestationis Whether some of these associations reflect true biological risk or are shaped by access-to-care differences is still being worked out.
How PG Is Diagnosed
Clinical appearance can be suggestive, but the diagnosis usually cannot be made on looks alone. The periumbilical start, the progression from welts to blisters, and the intense itch during pregnancy all raise suspicion. Confirmation typically requires a skin biopsy, and the key test is direct immunofluorescence. In this test, a small piece of skin near an active lesion is examined for the deposition of immune proteins along the basement membrane zone, the junction where the outer skin layer meets the deeper layers. In the large majority of PG patients, a linear band of complement C3 and IgG is found at this zone.9PubMed Central. Pemphigoid gestationis: clinical and laboratory evaluation This finding is the gold standard for diagnosis and is what separates PG from clinically similar rashes.
Blood tests measuring circulating anti-BP180 antibodies can support the diagnosis and are also used to track disease activity over time. Antibody levels measured by ELISA have been shown to correlate with disease severity and, as discussed below, with certain pregnancy outcomes.10Journal of the European Academy of Dermatology and Venereology. Anti-BP180 IgG antibody ELISA values correlate with adverse pregnancy outcomes in pemphigoid gestationis
Distinguishing PG from Other Pregnancy Rashes
The condition most commonly confused with pemphigoid gestationis is polymorphic eruption of pregnancy (PEP, also called PUPPP). PEP is far more common and also presents as an itchy rash during pregnancy, but it almost never produces true blisters, tends to start in stretch marks rather than around the belly button, and does not carry the fetal risks associated with PG. The timing, location, and character of the lesions help point toward one or the other, though definitive separation requires immunofluorescence and sometimes histopathology.11PubMed Central. Dermatoses of pregnancy – clues to diagnosis, fetal risk and therapy
Under the microscope, PG and PEP also differ. PG shows a much denser concentration of eosinophils (a type of immune cell involved in allergic and autoimmune inflammation) in the skin, along with eosinophils infiltrating the junction between the skin layers and, in a substantial percentage of cases, actual separation of the outer skin layer from the layers beneath. In a comparative study, that kind of subepithelial separation was found exclusively in PG and never in PEP.12PubMed. Histopathological features of pemphigoid gestationis and polymorphic eruption of pregnancy: A blinded retrospective comparative study of 31 cases These microscopic differences can help when the clinical picture is ambiguous and immunofluorescence results are borderline.
Other conditions that enter the differential include intrahepatic cholestasis of pregnancy (which causes itching but not a rash), atopic eruption of pregnancy, contact dermatitis, and drug reactions. The stakes of getting the diagnosis right are high: PEP and atopic eruption are uncomfortable but benign for the baby, whereas PG can affect fetal outcomes and requires closer monitoring.
Risks for the Baby
Pemphigoid gestationis is not just a maternal skin disease. Because the antibodies responsible for PG are IgG class, they cross the placenta and can affect the developing fetus. The primary concerns are preterm birth, low birth weight, and intrauterine growth restriction. A study examining outcomes found that women whose PG began in the first or second trimester, and those who developed blisters (as opposed to only welts and plaques), were significantly more likely to experience these adverse outcomes.13PubMed. Pemphigoid gestationis: early onset and blister formation are associated with adverse pregnancy outcomes
Antibody levels appear to add prognostic value. Research using ELISA measurements of anti-BP180 antibodies identified a threshold above which the risk of intrauterine growth restriction increased roughly fivefold. When high antibody levels were combined with the presence of blisters, the overall risk of adverse pregnancy outcomes climbed further still.14Journal of the European Academy of Dermatology and Venereology. Anti-BP180 IgG antibody ELISA values correlate with adverse pregnancy outcomes in pemphigoid gestationis This suggests that tracking antibody levels during pregnancy may help identify which patients need the most intensive fetal surveillance.
In rare cases, newborns can develop blisters of their own due to the transplacental passage of maternal antibodies. Neonatal pemphigoid gestationis is uncommon, and the blisters tend to resolve on their own as the maternal antibodies are cleared from the infant’s circulation over a few weeks.15PubMed Central. Neonatal pemphigoid gestationis: An atypical presentation of a rare disease Still, the possibility is worth knowing about, because blisters on a newborn can be alarming and may lead to unnecessary workups if the connection to maternal PG is not recognized.
Treatment During and After Pregnancy
Managing PG involves balancing symptom control against the safety constraints of pregnancy. For mild disease limited to welts and mild itching, potent topical corticosteroids and oral antihistamines are the first line. When blisters develop or the rash is widespread, oral corticosteroids become the mainstay. The goal is to use the lowest effective dose to control blistering and itch while minimizing steroid exposure for both mother and baby.
In cases that do not respond to standard corticosteroid therapy, or where the side effects of prolonged steroid use become a concern, intravenous immunoglobulin (IVIG) has been used as an alternative or add-on therapy with reported success.16PubMed Central. Pemphigoid gestationis and intravenous immunoglobulin therapy IVIG works by broadly modulating the immune response and can bring refractory disease under control when other options have failed.
After delivery, if the disease persists or flares, the treatment toolkit expands because medications that are off-limits during pregnancy become available. Azathioprine, an immunosuppressive drug, has been used in postpartum cases to taper off corticosteroids while maintaining disease control.17PubMed. Successful treatment of a severe persistent case of pemphigoid gestationis with antepartum and postpartum intravenous immunoglobulin followed by azathioprine Other immunosuppressants like dapsone, mycophenolate, and rituximab have been used in severe, persistent postpartum cases, though the evidence for these comes mostly from case reports and small series rather than controlled trials. Women who are breastfeeding need to discuss medication safety with their care team, since some of these drugs pass into breast milk.
Most patients see gradual resolution within weeks to months after delivery, particularly once hormone levels normalize. Some women experience minor flares with menstrual cycles or with the use of hormonal contraceptives, presumably because hormonal shifts can reactivate the immune response. This is worth discussing with a gynecologist when considering postpartum contraception.
Recurrence in Future Pregnancies
One of the most common questions women with PG ask is whether it will happen again. The answer, unfortunately, is that recurrence is the rule rather than the exception. The recurrence rate in subsequent pregnancies is estimated at around 50%, and when PG does return, it tends to come back earlier and with greater severity than the first episode.18Journal of Dermatology Research and Therapy. Pemphigoid Gestationis: A Third-Trimester Multigravida with a Severe Disease So-called “skipped” pregnancies, where a woman with a history of PG goes through a subsequent pregnancy without any flare, do occur but are uncommon. In one retrospective study of 87 patients, only about 8% reported a skipped pregnancy.19PubMed Central. Recurrent pemphigoid gestationis in the setting of first-trimester spontaneous abortions
The recurrence pattern has practical implications for family planning. Women considering another pregnancy after PG benefit from a conversation with both a dermatologist experienced in autoimmune blistering diseases and a maternal-fetal medicine specialist. Knowing that the disease often recurs earlier and more aggressively allows the care team to plan for closer monitoring and earlier intervention. There is currently no reliable way to prevent recurrence, though some clinicians begin low-dose corticosteroids or close surveillance early in a subsequent pregnancy for women with a known history.
PG has also been documented in pregnancies that end in early loss. Flares triggered by first-trimester miscarriages have been reported, reinforcing that even brief hormonal and immunological shifts of pregnancy can reactivate the disease in susceptible women.20PubMed Central. Recurrent pemphigoid gestationis in the setting of first-trimester spontaneous abortions
The Link to Thyroid Disease
An association between pemphigoid gestationis and autoimmune thyroid disease, particularly Graves’ disease, has been noted repeatedly in the literature. The connection makes biological sense: the same HLA gene variants that predispose women to PG also increase the risk of autoimmune thyroid conditions. Additionally, pregnancy itself is a time of immune system shifts that can unmask or worsen autoimmune tendencies. However, the strength of the association is debated. Some studies find it clearly, while others find the link weaker than expected.21PubMed Central. Do We Need to Monitor for Graves’ Disease After a Diagnosis of Pemphigoid Gestationis?
Despite the mixed evidence, it is reasonable for women diagnosed with PG to have thyroid function checked, both during pregnancy and in the postpartum period. Thyroid dysfunction during and after pregnancy is common even without PG, and women with one autoimmune condition are at higher baseline risk for developing another. Autoimmune thyroid disease can affect energy, mood, weight, and milk production, so catching it early matters for postpartum recovery.
The broader point is that PG does not exist in isolation. It sits within a web of autoimmune predisposition. For most women it remains a pregnancy-limited event that resolves and does not lead to other autoimmune diagnoses. But awareness of the overlap means that unusual symptoms after the skin has healed, like unexplained heart palpitations, significant weight changes, or persistent fatigue beyond what new parenthood explains, deserve a clinical evaluation rather than being written off as postpartum adjustment.
Why PG Is Often Diagnosed Late
Because pemphigoid gestationis is rare, many obstetricians and primary care providers have never seen a case. The early rash, before blisters develop, can look like hives, eczema, or a drug allergy, and it is not unusual for patients to be treated with topical antihistamines or mild steroids for weeks before the correct diagnosis is pursued. The periumbilical distribution and progression to blisters are the strongest clinical clues, but they are easy to miss if the clinician is not thinking about PG.
Diagnostic delay matters for several reasons. First, untreated or undertreated PG causes miserable itching and can spread widely, reducing quality of life during an already demanding time. Second, the fetal risks associated with earlier-onset and blister-forming disease mean that prompt diagnosis and treatment may allow for better pregnancy monitoring. Third, PG sometimes first appears in the postpartum period, which is especially tricky because the pregnancy is already over by the time the rash starts, and the connection to a pregnancy-specific disease may not be obvious. In postpartum presentations, the condition can be confused with postpartum drug reactions, postoperative wound complications (after cesarean delivery), or even bullous pemphigoid in a young adult, which is itself unusual and would prompt investigation.
For patients, the practical takeaway is this: if you develop an intensely itchy rash during pregnancy or soon after delivery that starts around the belly button and progresses to blisters, ask specifically about pemphigoid gestationis and request a referral to a dermatologist for biopsy and immunofluorescence. Many patients report that they were the ones who raised the diagnosis after reading about it online, and that it was confirmed once the appropriate testing was done. Early recognition leads to better symptom control and more proactive monitoring for the baby.