Diagnosis: Intrahepatic cholestasis of pregnancy
Intrahepatic cholestasis of pregnancy (ICP) is caused by maternal intrahepatic bile secretory dysfunction.1 The disorder, which is also referred to as obstetric cholestasis and pruritus gravidarum, has no primary skin lesions. Patients have generalized pruritus and secondary excoriations (FIGURE 3). In about 20% of cases, patients are also jaundiced.2
The sudden onset of generalized pruritus, which is the hallmark of ICP, starts during the late second (20%) or third (80%) trimester, followed by secondary skin lesions, namely linear excoriations and excoriated papules caused by scratching.3 These excoriations are typically localized on the extensor surfaces of the limbs, but may also be found on the abdomen and back. The itching may involve the palms and soles, as well. The severity of the skin lesions correlates with the duration and degree of pruritus.3
According to one study, ICP occurred in 0.5% of 3192 pregnancies. The disorder resolves after delivery, and recurs with subsequent pregnancies.4
ICP has been linked to fetal distress (20%–30%), stillbirths (1%–2%), and preterm delivery (20%–60%).3 Autopsies of the placenta have shown signs of acute anoxia. Fetal complications in ICP may be caused by decreased fetal elimination of toxic bile acids.3
Hormones, genes, and even the weather may play a role
Increased hormone production during pregnancy plays a role in ICP. Estrogen, which increases 100-fold during pregnancy, interferes with bile acid secretion across the basolateral and canalicular membrane of the hepatocyte. Particularly noteworthy is the fact that estriol-16 α-D-glucuronide, the estrogen metabolite that increases most during pregnancy, is cholestatic, according to animal studies.3 In addition, progesterone metabolites play an important part in the pathogenesis of ICP. Progesterone inhibits hepatic glucuronyl transferase, thereby reducing the clearance of estrogens and amplifying their effects.
Familial clustering and geographical variation indicate that there is a genetic predisposition for ICP. There is a high prevalence of ICP in Chile (14%), especially among Araucanian Indian women (24%), and in Bolivia.3 ICP patients may have a family history of cholelithiasis and a higher risk of gallstones. There is a family history of cholelithiasis in 50% of ICP cases.2