Examining the Evidence
6 skin disorders of pregnancy: A management guide
You can handle most of these dermatoses, but some require referral
IN THIS ARTICLE
The dermatoses of pregnancy are a poorly understood group of conditions. Their only common feature is a tendency to appear during pregnancy.
Only three of these conditions are considered unique to pregnancy, however; the others are probably exacerbations of preexisting conditions triggered by pregnancy. There isn’t even complete agreement on what to call them. To make management even more complex, two patients—mother and fetus—need to be considered in decisions about care.
Who manages these patients is another matter. These conditions fall into overlapping areas of health care, where family physicians, obstetricians, and dermatologists all might have some share in responsibility for diagnosis and treatment. You need to be sufficiently familiar with these conditions so that you can differentiate those that can be treated symptomatically and those that require referral to a specialist. This review and the handy TABLE, will help you toward that end.
Skin disorders of pregnancy: What you’ll see, how to treat
Diagnosis and sequelae
Erythematous papules that progress to vesicles and bullae, in a periumbilical distribution that spares the face, palms, and soles
Frequent; skips a pregnancy 8% of the time
Urticarial papules and plaques on the abdomen, legs, arms, buttocks, chest, and back
Topical corticosteroids and antihistamines
No primary lesions; secondary excoriations in any area that the patient can reach
Ursodeoxycholic acid, 450-1,200 mg/d
Grouped, crusted erythematous papules, patches, and plaques, most often on extensor surfaces of the arms and legs or on the abdomen
Symptomatic treatment with topical corticosteroids or antihistamines
Erythematous plaques and pustules that start on the inner thighs and groin and spread to the trunk and extremities
Management of associated hypocalcemia
Papules and pustules concentrated around hair follicles, often beginning on the abdomen and spreading to the extremities
DERMATOSES UNIQUE TO PREGNANCY
1. Pemphigoid gestationis
Years ago, this disorder was referred to as herpes gestationis, because the lesions are herpetiform. Pemphigoid gestationis (PG) has an incidence of approximately 1 in 10,000 pregnancies.1,2 Time of onset is usually about the 21st week of gestation, although, in about 20% of cases, the eruption appears immediately postpartum.3
Presentation. The disease usually begins with urticarial papules and plaques around the umbilicus and extremities. Bullous lesions tend to develop as the disease progresses, and are often not present on first presentation (FIGURE 1). Lesions of PG tend to spare the face, palms, and soles. Mucosal surfaces are involved in fewer than 20% of cases. In about 75% of cases, PG flares around the time of delivery, regressing spontaneously after the baby is born.4
FIGURE 1 Pemphigoid gestationis
As the disease progresses, bullous lesions tend to develop.
Pathophysiology. The pathophysiology of PG is nearly identical to that of bullous pemphigoid, a blistering skin disorder seen more often in elderly patients.5 Pemphigoid disorders are immune processes, involving an immunoglobulin G (IgG) immune response directed at a 180-kDa hemidesmosome transmembrane glycoprotein. This protein is the common target in several subepidermal blistering diseases.
Differential diagnosis. Disorders that may have some of the same features as PG include pruritic urticarial papules and plaques of pregnancy (PUPPP), erythema multiforme, intrahepatic cholestasis of pregnancy (ICP), contact dermatitis, and drug reactions.
Diagnosis. A biopsy is necessary for definitive diagnosis. Direct immunofluorescence (DIF) microscopy of a sample of perilesional skin can show tissue-bound immunoreactants. Linear deposition of the complement component protein C3 along the basement membrane zone is diagnostic for PG. IgG is also deposited about 40% of the time.3
Serum enzyme-linked immunosorbent assay (ELISA) studies are also helpful in diagnosis. They have excellent sensitivity and specificity, as well as the capacity to monitor levels of antibody, which correlate with the severity of disease.1
Treatment. Oral corticosteroids are the first-line treatment for PG, typically 20 to 60 mg/d of prednisone. Oral corticosteroids are generally most effective at ameliorating symptoms. Prednisone at a dosage of 40 to 80 mg/d for a short time has not been associated with congenital abnormalities.6 PG patients can also be treated successfully with intravenous immunoglobulin (IVIG) and cyclosporine in refractory cases.7
Pruritus associated with this condition can interfere with day-to-day activities and with the patient’s ability to sleep. Patients may also complain that the rash is painful, particularly if bullae rupture, leading to superficial ulcerations. Fortunately, the patient’s quality of life can be dramatically improved with systemic corticosteroids—with no significant risk to the fetus.
Sequelae. PG uniformly resolves within a few weeks, but the mother’s autoantibodies can be passively transferred to the fetus, causing vesicles and bullae in the newborn.8 An increased incidence of small-for-gestational age (SGA) infants has also been noted in PG, although no lasting morbidity or mortality in the offspring has been noted.5 The disease tends to recur in future pregnancies.
2. Pruritic urticarial papules and plaques of pregnancy
This condition is known by many names besides its acronym PUPPP: polymorphic eruption of pregnancy, toxemic erythema of pregnancy, and late prurigo of pregnancy.1 It is a pruritic, inflammatory skin disorder that has been variously estimated to occur in anywhere from 1 in 120 to 1 in 240 pregnancies.8 PUPPP is second only to eczema as the most common dermatosis of pregnancy.
Presentation. As the name suggests, the lesions of PUPPP are itchy, red papules that often coalesce into plaques (FIGURE 2). Lesions usually occur in primigravidas after the 34th week of gestation, although they may be seen at any time from the first trimester through the postpartum period.9
Lesions are classically found on the abdomen, sparing the umbilical area, and are found primarily in the striae. This distribution helps you to differentiate PUPPP from PG, in which lesions typically cluster around the umbilicus. Most PUPPP lesions (80% in one study) are dispersed on the abdomen, legs, arms, buttocks, chest, and back. Another 17% appear only on the abdomen and proximal thighs, and the remaining 3% on the limbs.10 Nearly 50% of the time, lesions also include discrete vesicles.11 There are no reported cases of mucosal involvement.
Patients with this condition are often very uncomfortable. The associated pruritus is severe enough to interfere with sleep. Despite the itching, however, lesions are seldom excoriated.
FIGURE 2 Pruritic urticarial papules and plaques of pregnancy
The itchy, red papules of PUPP often coalesce into plaques.
Pathophysiology. The disorder has been strongly associated with maternal weight gain and multiple gestations. One working hypothesis is that rapid abdominal distention observed in the third trimester leads to damage of the connective tissue, which then releases antigenic molecules, causing an inflammatory reaction.12 Another hypothesis is that increased levels of fetal DNA that have been detected in the skin of PUPPP patients may contribute to the pathology. One study detected male DNA in six of 10 PUPPP sufferers, but found none in any of 26 controls—pregnant women without PUPPP pathology.5 There is some evidence that patients with atopy may be predisposed to PUPPP, as well as patients who are hypertensive or obese.10,13
Differential diagnosis. Initially, PUPPP lesions can be difficult to differentiate from urticarial PG lesions. The distribution of the lesions is the best clue: PG lesions cluster around the umbilicus, whereas PUPPP lesions uniformly spare the umbilical area. Additional disorders in the PUPPP differential are atopic dermatitis, superficial urticarial allergic eruption, viral exanthema, and contact or irritant dermatitis.
Diagnosis. PUPPP can be diagnosed only by clinical observation. None of the available laboratory tests—immunofluorescence, histology, serology—yield findings specific for PUPPP, although histology and immunofluorescence can readily differentiate between this condition and PG.
Treatment. Because the disease holds no real danger for mother or fetus, treatment can be aimed solely at symptomatic relief. Mild-to-potent topical corticosteroids (consider triamcinolone or fluocinonide) should relieve pruritus within 48 to 72 hours.8 Antihistamines and, occasionally, low-dose systemic corticosteroids may also be used. Consider hydroxyzine, although diphenhydramine has the more proven safety profile in pregnancy.
Nonpharmaceutical treatments such as oil baths and emollients should also be considered. If the condition appears classic for PUPPP, it can be managed symptomatically. If there is any question about the diagnosis, however, referral to a dermatologist is prudent.
Sequelae. No increase in maternal or fetal morbidity or mortality is associated with PUPPP. Recurrence is fairly uncommon, as the disease primarily affects women during their first pregnancy.
This condition is also called recurrent or idiopathic jaundice of pregnancy, obstetric cholestasis, and pruritus gravidarum. Intrahepatic cholestasis of pregnancy (ICP) is caused by disruption of hepatic bile flow during pregnancy. It has been recorded at a rate of approximately 10 to 150 of every 10,000 pregnancies in Europe and 70 of every 10,000 in the United States.12 In 80% of patients, time of onset is after the 30th week.14
Although this disorder is not primarily a dermatosis of pregnancy, it is a pruritic condition that often presents with excoriations in pregnant women and is associated with fetal morbidity and mortality. It’s important to be able to identify this disease early to minimize sequelae.
Presentation. There are no primary lesions with ICP. The primary presenting symptom is a generalized pruritus affecting the palms and soles, and sometimes extending to the legs and abdomen (FIGURE 3). This itching is often so severe that it leads to chronic insomnia. You may see secondary skin lesions, such as erythema and excoriations. Observable jaundice occurs in 10% to 20% of patients.3 These patients do not develop the encephalopathy that is associated with cholestasis in the nonpregnant state, however.14
FIGURE 3 Intrahepatic cholestasis of pregnancy
ICP lacks primary lesions. Shown here are the secondary erythema and excoriations that results from scratching the intense pruritis.
Pathophysiology. The genesis of this condition is thought to be a combination of genetic and environmental factors. A family history of the disorder is present in one half of cases; cases with a familial component tend to be more severe.15 ICP may be an exaggerated response to increased estrogen levels in pregnancy, but the mechanism of this response is unknown.16
Differential diagnosis. Other conditions that must be considered in making the diagnosis are viral hepatitis, gallbladder disease, PG, PUPPP, drug hepatotoxicity, primary biliary cirrhosis, and uremia.
Diagnosis. Laboratory values are the definitive diagnostic tool in this condition. Increased levels of serum bile acids are the single most sensitive test. Average levels of serum bile acids in pregnancy are 6.6 µmol/L, with an upper limit of 11 µmol/L. The average value in women who have ICP is 47 µmol/L.17
Although serum bile acids remain the gold standard, a recent study showed that elevated urine bile acids have 100% sensitivity and 83% specificity for ICP.18 In 55% to 60% of cases, the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are mildly increased. Steatorrhea is often noted by the patient, and is followed by vitamin K deficiency.17