Pemphigoid gestationis (PG) is a rare autoimmune skin condition that usually develops during pregnancy, typically in the second trimester, but it can also appear after childbirth. Despite being formerly called herpes gestationis, PG is not related to the herpes virus. This condition occurs when the body’s immune system mistakenly attacks proteins in the skin that are important for the structure of the skin layers. PG primarily affects women, especially those with a history of autoimmune diseases like Graves’ disease. It affects about 1 in 50,000 pregnancies in the United States. Although PG often goes away after delivery, it can be uncomfortable and may come back in future pregnancies.

Pathophysiology

Pemphigoid gestationis (PG) occurs when the body’s immune system produces antibodies that target specific proteins called hemidesmosomes, such as BP180 (collagen XVII), which are essential for holding the skin layers together. These antibodies build up at the area where the epidermis and dermis meet, triggering inflammation. This leads to fluid accumulating under the skin’s surface, forming blisters. The inflammation also causes redness, swelling, and separation of the skin layers. While the exact cause of this autoimmune reaction is not completely understood, hormonal changes are believed to play a major role, as PG is commonly seen during pregnancy and may return in future pregnancies, menstrual cycles, or with contraceptive use.

Clinical Features

PG often begins as an itchy, red rash that forms raised patches and bumps, usually starting around the belly button. The rash can spread to other areas such as the arms, legs, chest, back, buttocks, palms, and soles, but typically does not affect the face or mucous membranes. Over time, the rash may develop into blisters, often forming in a circular pattern. Some lesions may appear as target-shaped. The condition is very itchy, and symptoms can range in severity, with some cases leading to larger blisters. Ruptured blisters usually heal without scarring, but scratching or secondary infections may cause scarring.

PG typically resolves within 3 months after delivery, though flare-ups can happen after birth. In rare instances, the condition may persist. In less than 5% of cases, maternal antibodies may cross the placenta and cause temporary rashes or blisters in the newborn. Most neonatal cases are mild and need little treatment, though in some cases, more severe symptoms such as skin lesions or imbalances in fluids and electrolytes can occur.

Diagnosis

Pemphigoid gestationis (PG) is diagnosed through a clinical evaluation, which is supported by additional tests. A skin biopsy is often performed, where the tissue is examined under a microscope to check for subepidermal blistering, a key feature of PG. However, the biopsy results alone may not clearly differentiate PG from other pregnancy-related skin conditions, such as pruritic urticarial papules and plaques of pregnancy (PUPPP), which can have similar symptoms. To confirm the diagnosis, direct immunofluorescence (DIF) testing is used to detect antibodies at the dermal-epidermal junction. Indirect immunofluorescence (IIF) can also be performed to find circulating autoantibodies in the mother’s blood. In some cases, thyroid function tests may be done because PG is more commonly seen in women with autoimmune thyroid conditions, like Graves’ disease.

Differential Diagnosis

It’s important to correctly diagnose pemphigoid gestationis (PG) because it shares symptoms with other skin conditions. Some conditions that may be confused with PG include:

• Pruritic urticarial papules and plaques of pregnancy (PUPPP): This common rash in pregnancy usually affects the abdomen and typically doesn’t form blisters like PG.
• Epidermolysis bullosa acquisita: A blistering disorder that looks similar to PG but is caused by antibodies against a different skin protein, collagen VII.
• Bullous scabies: This condition causes severe itching and blistering, and is linked to scabies, which can be diagnosed through a skin scraping.
• Allergic contact dermatitis, drug eruptions, and erythema multiforme: These can cause blisters or bumps but don’t have the same specific immune system markers as PG.

Management and Treatment

The treatment for pemphigoid gestationis (PG) depends on the severity of the condition:

• Mild Cases: Topical corticosteroids are usually the first treatment and can effectively control symptoms.
• Moderate to severe cases: Oral corticosteroids are prescribed, starting with higher doses that are gradually reduced once blisters stop forming. These are often taken on alternate days to minimize side effects. Antihistamines like diphenhydramine can help relieve itching.
• Severe or persistent cases (especially after childbirth): More aggressive treatments may be needed, such as:
  • Intravenous immunoglobulin (IVIG): Used for severe or persistent cases.
  • Plasmapheresis: A procedure to remove the harmful antibodies from the blood.
  • Rituximab: A medication that targets and depletes B cells, which produce the autoantibodies.
  • Dapsone:  An immunosuppressive drug with antibacterial and anti-inflammatory properties.
  • Cyclophosphamide and methotrexate:  Chemotherapy drugs sometimes used in difficult cases.
  • Tetracyclines with nicotinamide: A treatment that can help manage inflammation in some cases.

Complications and Prognosis

The outlook for pemphigoid gestationis (PG) is usually positive, with most cases resolving within 3 months after delivery. However, PG can lead to some complications, such as secondary bacterial infections, fluid loss, and electrolyte imbalances due to blister formation. PG is also linked to a small increased risk of premature birth, but it does not significantly affect the chances of fetal death. Babies born to mothers with PG may be smaller than expected for their gestational age, but they generally recover well with minimal treatment.

Conclusion

Pemphigoid gestationis is a rare autoimmune skin condition that happens during pregnancy, causing itchy rashes and blisters. While the condition usually goes away on its own after delivery, it can come back in future pregnancies and may cause complications for both the mother and baby. Early diagnosis and treatment with corticosteroids and other medications are important to manage the condition effectively. With proper care, both the mother and baby typically have a good outcome.

References

1. Nguyen, S. P., et al. (2019). Pemphigoid gestationis: A review of clinical features, pathophysiology, and management. Journal of the American Academy of Dermatology, 81(3), 623-631. https://doi.org/10.1016/j.jaad.2019.03.044
2. Nguyen, V., et al. (2020). A comprehensive review of pemphigoid gestationis: Pathophysiology, diagnosis, and treatment. American Journal of Obstetrics and Gynecology, 222(6), 523-529. https://doi.org/10.1016/j.ajog.2019.11.106
3. Sjögren, H., et al. (2020). Immunologic aspects of pemphigoid gestationis. Clinical Reviews in Allergy and Immunology, 58(1), 78-87. https://doi.org/10.1007/s12016-019-08790-6
4. Weber, J. M., et al. (2021). Epidemiology and pathophysiology of pemphigoid gestationis. International Journal of Dermatology, 60(3), 258-264. https://doi.org/10.1111/ijd.15108