Cholestasis

WASHINGTON -- Women who had either pemphigoid gestationis or cholestasis of pregnancy should be counseled that later oral contraceptive use may trigger a flare-up of dermatoses, Dr. Thelda M. Kestenbaum said at the annual meeting of the American Academy of Dermatology.

Itchy rashes, blisters, and other symptoms associated with these two dermatoses of pregnancy also may recur when menstruation resumes, or in subsequent pregnancies, she added.

Dermatoses of pregnancy "has been a particularly murky and confusing area" for a number of reasons, observed Dr. Kestenbaum of the University of Kansas, Kansas City. "Many diseases that were thought to be exclusive for pregnancy were not particularly," she said, citing atopic eczema/dermatitis as an example. "When it appears in a pregnant woman, it doesn't need to be called a special name," she added.

A second reason is that many names were given to the same disorder--"a primary example is PUPPP [pruritic urticarial papules and plaques of pregnancy]," Dr. Kestenbaum said. PUPPP has probably been called polymorphic eruption of pregnancy, toxic erythema, late onset prurigo, and toxemic rash of pregnancy.

An estimated 1 in 160 pregnant women will develop PUPPP, usually during the first pregnancy. The symptoms begin with itching in stretch marks, followed by erythematous papules and plaques and stretch marks that spread to the breasts, thighs and arms. Women with PUPPP also may have vesicles (up to 40%) and erythema multiforme-like lesions (up to 20%). PUPPP tends to spare the face, palms, soles, and mucous membranes. Symptoms typically begin at 36-39 weeks' gestation, but also can occur postpartum. Dr. Kestenbaum cited one study that suggests fetal cells in maternal circulation may play a role in PUPPP (Lancet 351[9102]:559-62, 1998).

According to Dr. Kestenbaum, pemphigoid gestationis (formerly called herpes gestationis) and cholestasis of pregnancy (also called interhepatic cholestasis of pregnancy) are the two dermatoses of pregnancy that are associated with increased risks and thus deserve a special classification.

Pemphigoid gestationis is considered a rare disorder, with an incidence rate of 1 in 50,000 pregnant women. The onset is typically in the second trimester, usually at 21 weeks' gestation; but it also may occur from 9 weeks' gestation to 1 week postpartum. In subsequent pregnancies, pemphigoid gestationis tends to occur earlier and more severely, Dr. Kestenbaum said.

Clinically, these women have malaise, fever, nausea, headache, alternating hot and cold sensations, and burning and itching that might precede the skin eruption, she said. They have extremely itchy urticarial papules, target lesions, and annular wheals--and these may persist for at least a month before actual blisters occur. The blisters may be annular, may have prominent pustules, and may have circinate plaques. These women tend to have recurrent crops of blisters.

Usually, pemphigoid gestationis begins on the abdomen, with a predilection for the periumbilical region, and becomes widespread. Sometimes, there are no blisters. If blisters do occur, they usually resolve within a couple of months postpartum. The urticarial-like lesions may resolve within a year postpartum.

"Often, there's decrease in the severity in the last few weeks of the pregnancy, but then a flare immediately postpartum," Dr. Kestenbaum continued. "Some cases have persisted up to 10 years and more. In subsequent pregnancies, it tends to start earlier and it lasts longer ... although there are sometimes skipped pregnancies that are unaccounted for, even with the same consort."

Up to 11% of women with pemphigoid gestationis may have other autoimmune disorders--particularly Graves' disease, she noted.

Further, up to 10% of infants born to mothers with pemphigoid gestationis have transient skin eruption. One study also suggested an increase in small-for-date babies, possibly because of slight impairment of placental function (Br. J. Dermatol. 110[1]:67-72, 1984). But pemphigoid gestationis does not appear to be linked with an increase in spontaneous abortions or stillbirths, according to Dr. Kestenbaum, based on a study of 126 patients (J. Am. Acad. Dermatol. 26[4]:563-66, 1992).

If pemphigoid gestationis is mild, "topical steroids would be the way to go," Dr. Kestenbaum said. "But typically, women may require systemic steroids--prednisone at 0.50-1 mg/kg per day (40-60 mg)." She added, however, that some women respond to a low dose of 5-10 mg prednisone daily.

Breast-feeding may help, but there are conflicting reports on this, Dr. Kestenbaum said. Other treatments for pemphigoid gestationis may include ritodrine, a drug used to prevent premature labor. Chemical oophorectomy would be a lastresort treatment only, she said.

Cholestasis of pregnancy occurs in 0.1%-0.2% of pregnant women in the United States. The incidence rate is up to 10% in Chile, and 1%-2% in Scandinavia. Low rates are seen among blacks and Asians, Dr. Kestenbaum reported.

The symptoms tend to occur in the third trimester in 70% of cases, but may appear as early as 8 weeks.

"These women have severe itching that's worse at night," Dr. Kestenbaum said. "There's jaundice in 20%-60% of patients that begins 1-4 weeks after itching. There's a positive family history in up to 50% of cases, and in some cases, it's perhaps autosomal dominant." The itching usually disappears 24-48 hours postpartum. But if the woman has jaundice, the itching may take 1-2 weeks to resolve.

Cholestasis of pregnancy is linked with a fivefold increase in stillbirth, fetal distress, and preterm labor, Dr. Kestenbaum said.

"Probably your first-line treatment would be ursodeoxycholic acid--1 g/day total dose, given in three divided doses--and a second-line treatment would be cholestyramine," Dr. Kestenbaum said.

One study suggests that the use of oral guar gum may increase elimination of bile acids and help pruritus, she said (Acta Obstet. Gynecol. Scand. 79[4]:260-64, 2000).

BY ELIZABETH LOHR

Associate Editor

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