New assay helps physicians distinquish dermatoses unique to pregnancy

Key Points

"Until recently, controversial, confusing and disputable information has swirled around skin conditions occurring during pregnancy either as pre-existing conditions exacerbated by pregnancy or those that are strictly unique to pregnancy," says Xuan Hong Nguyen, M.D., chief of dermatology, Maricopa Integrated Health System, Phoenix. "But now, three dermatoses unique to pregnancy have been classified."

The advent of direct immunofluorescence in the early 1970s paved the way for more definitive ways of distinguishing between two unique dermatoses of pregnancy.

Three to know

The three dermatoses identified exclusively in pregnant women are: pemphigoid gestationis (PG), previously called herpes gestationis; pruritic urticarial papules and plaques of pregnancy (PUPPP), sometimes referred to as pruritic eruptions of pregnancy (PEP); and intrahepatic cholestasis of pregnancy (ICP).

"Of the three dermatoses mentioned above, PG and ICP are especially rare," Dr. Nguyen says. "However, it is important that dermatologists make the distinction between these skin eruptions, because the treatments are different and the fetal compromises can range from premature birth to gestational growth retardation, and even fetal demise, as previously reported in PG and ICP."

Clinical presentation of pemphigoid gestationis, which includes blisters and urticarial papules, presents with a mean onset at 21 weeks and postpartum in 20 percent of cases. The lesions circumvent the umbilicus and involve the umbilicus, and usually spare the face, palms and soles. Although PG is rare, about 10 percent of babies whose mothers have the condition can contract pemphigoid gestationis because of the maternal IgG antibodies that cross the placenta.

"PG has serious fetal risks associated with it," Dr. Nguyen says. "Once the woman is diagnosed with PG, treatment with oral prednisone has been found to be safe in pregnancy, and sometimes treatment includes delivery of the fetus. The new ELISA of the NC16a of the BP180 protein is about 96 percent sensitive and specific for pemphigoid gestationis."

Another condition - and one more commonly seen than pemphigoid gestationis - is PUPPP or PEP. This condition typically shows up late in pregnancy, and presents with itchy papules and plaques, usually presenting within the abdominal striae and sparing the umbilicus.

Distinguishing PUPPP, PG

"Patients might not follow the textbook examples of PG versus PUPPP," Dr. Nguyen says.

"If dermatologists can't clinically make the distinction between pemphigoid gestationis and PUPPP, they should definitely follow up with biopsies, direct immunofluorescence and even ELISA," she says. "While PUPPP or PEP dermatoses will just result in discomfort to the woman, pemphigoid gestationis can result in far worse outcomes involving the health of the unborn fetus.

"Direct immunofluorescence with C3 complements binding to the epidermal part in salt-split skin is seen in PG," she added.

Once PUPPP or PEP has been diagnosed, patients can be managed with topical steroids for comfort.

The third condition - intrahepatic cholestasis of pregnancy (ICP) - while extremely rare, is nonetheless very important to know and distinguish, because it, too, can cause fetal prematurity, among other problems.

"A medication called ursodeoxycholic acid (UDCA) can be given to lower the bile salts in women with ICP because of the risk of premature birth," Dr. Nguyen says. "This is very effective and should be given to the patient in collaboration with the gastroenterologist."

Diagnosis

Theories about the causes of these skin eruptions vary. Pemphigoid gestationis has been associated with HLA-DR3 and HLA-DR4, making pregnant women slightly more susceptible to having the dermatoses. PUPPP or PEP has been associated with rapid weight gain - which causes abdominal striae - and primigravida and multiple gestational pregnancies.

With intrahepatic cholestasis of pregnancy, the culprit may be a secondary response to increased estrogen that may lead to an increase in retention of bile salts, causing the patient to experience intense pruritus without any primary skin lesions.

The advent of molecular biology and improving technologies are ensuring a brighter future for pregnancy dermatoses and dermatoses exacerbated by pregnancy, according to Dr. Nguyen.

"There are a lot of treatment options out there and a wide range of knowledge," she says. "Even the patients are better equipped today with knowledge, and they come with good and sometimes tough questions for the clinicians.

"As dermatologists, we should be knowledgeable of the three dermatoses unique to pregnancy," Dr. Nguyen says, "and the skin conditions that are exacerbated by pregnancy such as atopic dermatitis and psoriasis. Also, it's important to be cautious of the safety of medication in treatment of pregnant women. After all, we are treating two people: the mother and the unborn fetus."