Intrahepatic cholestasis of pregnancy
Intrahepatic cholestasis of pregnancy, also known as obstetric cholestasis, cholestasis of pregnancy, jaundice of pregnancy, and prurigo gravidarum, is a medical condition in which cholestasis occurs during pregnancy. It typically presents with troublesome itching and can lead to complications for both mother and fetus. Pruritis has long been considered to be a common symptom of pregnancy. The vast majority of times, itching is a minor annoyance caused by changes to the skin, especially that of the abdomen. However, there are instances when itching is a symptom of ICP. This is usually most intense on the palms of the hands, and the soles of the feet, but can be widespread. ICP occurs most commonly in the third trimester, but can begin at any time during the pregnancy.
Signs and symptoms Most women with this condition present in third trimester with itching without a rash. Typically, the itching is localized to the palms of the hands and soles of the feet but can be anywhere on the body. Hallmarks of ICP include the following symptoms: Most common: Itching, in particular but not limited to that of the palms of the hands and soles of the feet, without presence of a rash Itching that increases in the evening Itching that does not respond favorably to anti-histamines or other anti-itch remedies Often, elevated LFT results as well as serum bile acid counts Less common: Darker urine Lighter stools Increased clotting time Fatigue Increased nausea Decrease in appetite Jaundice Upper right quadrant pain It is important to note that not all ICP sufferers have all of the above symptoms. For example, Jaundice only occurs in relatively small subset of cases, and in some cases abnormal lab results were not seen until 15 weeks or more after the onset of symptoms. Mechanism The causes of intrahepatic cholestasis of pregnancy are still not fully understood. Hormones and genetic factors are likely to be important in the pathogenesis of the disease. A number of features of the disease suggest a link to hormones: ICP occurs in the third trimester at the time when hormone levels are at their highest.
Twin and triplet pregnancies, which are associated with higher hormone levels, show a higher incidence of ICP. ICP resolves quickly after delivery, when placental hormone production ceases. Older high-dose estrogen oral contraceptive pills could cause features of ICP.
= Estrogens = Estrogens, and particularly glucuronides such as estradiol-17β-D-glucuronide, have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes. = Progesterone = Treatment with progesterone in the third trimester of pregnancy has been shown to be associated with the development of ICP, and levels of metabolites of progesterone, particularly sulfated progesterone, are higher in patients with ICP than unaffected women, suggesting that progesterone also has a role in ICP. = Genetic factors = Clustering of cases of ICP in families, geographic variation in rates of ICP, and recurrence of ICP in 45-70% of subsequent pregnancies all suggest a genetic component to the disease. Genetic mutations in the hepatocellular transport protein ABCB4, which controls secretion of phosphatidylcholine into bile, have been found in 15% of cases of ICP. Genetic mutations affecting hepatic bile salt transport molecules have also been found in patients with progressive familial intrahepatic cholestasis. It has been found that mothers of patients with PFIC have a higher incidence of ICP, suggesting that heterozygote carriers of these mutations are also predisposed to ICP.
In addition to genetic changes to bile salt transport molecules, high levels of estrogen glucuronides have been shown to inhibit the bile salt export pump ABCB11, and high levels of progesterone to inhibit the ABCB4 phospholipid transporter. Consequently, both genetic mutations in hepatocyte proteins involved in bile secretion together with inhibition of those proteins by high levels of hormone metabolites in pregnancy may have roles in the pathogenesis of ICP. = Environmental factors = A number of features of ICP suggest that environmental factors also have a role in the disease: It has been reported that the incidence of ICP is higher in winter than summer.
The incidence of ICP in Chile has dropped from 14% of pregnancies before 1975 to less than 2% in 1997. ICP recurs in between 45% and 70% of subsequent pregnancies. Low serum selenium levels have been linked to ICP, although the role of selenium in bile secretion is not known. Diagnosis While most pregnant women experience some itch from time to time, itching on the palms and soles without a visible rash, or persisting severe or extensive itch symptoms should be reported to the midwife or obstetrican. To obtain a diagnosis of ICP, there are two LFT and Serum bile acid test. The liver function tests is a simple blood test, the results of which should be available by the next day. If the ALT level is elevated, this, plus pruritus of palms and soles, could be considered as potentially diagnostic of ICP but only with elevated bile acid levels.
The serum bile acid blood test for ICP is a quantitative measurement of bile salts. The results of this test often take longer to return, but the test is more specific for ICP. Other problems with the liver that occur in pregnancy should be considered by the treating clinician. These include preeclampsia, the HELLP syndrome, and acute fatty liver of pregnancy. Furthermore, other causes of hepatitis, like hepatitis viruses, cancer and certain medications, should also be considered. Treatment Upon diagnosis, many providers will prescribe Ursodeoxycholic Acid.
While there is no cure for ICP, and no way to guarantee a successful outcome, studies have shown a slightly better fetal and maternal outcome from administration of Ursodeoxycholic Acid, whereas Cholestyramine appears to only relieve itching. If additional blood tests to check clotting function identify a problem, giving Vitamin K may help avoid the risk of hemorrhage at delivery. Delivery by 35-37 completed weeks may be important to fetal outcome as a recent study demonstrated that in severe ICP the risk of stillbirth was 1.5% compared to 0.5% of uncomplicated pregnancies. This risk rose further if bile acids doubled, Risks if untreated Maternal consequences include the following: Itching, which can become intense and debilitating Premature labor Deranged clotting, which requires Vitamin K Fetal consequences include: Fetal distress Meconium ingestion Meconium aspiration syndrome Stillbirth Delivery has been recommended in the 38th week when lung maturity has been established. See also Pruritic Urticarial Papules and Plaques of Pregnancy an itchy condition of pregnancy that is associated with a rash.
Cholestasis Cholestatic pruritus List of cutaneous conditions References External links ICP Care Website ICP Care / Itchymoms Website ICP Support Website E A Fagan "Intrahepatic cholestasis of pregnancy".
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