photo rounds

Barbara Orr, MD Pruritus in Loma Linda University Medical School Our patient had excoriations all over her body—but no Richard P. Usatine, MD University of Texas Health blistering. What do you suspect was causing her itching? Science Center at San Antonio

EDI t o R Richard P. Usatine, MD 32-year-old mother of 2 came into men, chest, arms, and legs (FIGURES 1 our facility during her 31st week and 2). She had no jaundice or scleral ic- Aof pregnancy and told us that she terus. The fundal height was 31 mm and couldn’t stop itching. She said that her the fetal heart tones were 150 bpm. whole body was itchy and it got worse at night. She was unable to get a good night’s sleep. Up until this point, her pregnancy had been uncomplicated and she had no z What is your diagnosis? past history of medical problems. An examination revealed excoria- z How would you manage tions—but no blistering—on her abdo- this condition?

figures 1 & 2 Excoriations on the abdomen and chest

A 32-year-old woman in her 31st week of pregnancy with excoriations on her abdomen and arm, as well as her chest.

www.jfponline.com vol 56, No 11 / November 2007 913 ds n rou z Diagnosis: Intrahepatic anoxia. Fetal complications in ICP may cholestasis of pregnancy be caused by decreased fetal elimination Intrahepatic cholestasis of pregnancy of toxic bile acids.3 photo (ICP) is caused by maternal intrahepatic bile secretory dysfunction.1 The disorder, which is also referred to as obstetric cho- Hormones, genes, and even lestasis and pruritus gravidarum, has no the weather may play a role primary skin lesions. Patients have gen- Increased hormone production during preg- eralized pruritus and secondary excoria- nancy plays a role in ICP. Estrogen, which tions (Figure 3). In about 20% of cases, increases 100-fold during pregnancy, inter- patients are also jaundiced.2 feres with bile acid secretion across the ba- The sudden onset of generalized pru- solateral and canalicular membrane of the ritus, which is the hallmark of ICP, starts hepatocyte. Particularly noteworthy is the during the late second (20%) or third fact that estriol-16 a-D-glucuronide, the (80%) trimester, followed by second- estrogen metabolite that increases most ary skin lesions, namely linear excoria- during pregnancy, is cholestatic, according tions and excoriated papules caused by to animal studies.3 In addition, progester- scratching.3 These excoriations are typi- one metabolites play an important part cally localized on the extensor surfaces in the pathogenesis of ICP. Progesterone of the limbs, but may also be found on inhibits hepatic glucuronyl transferase, the abdomen and back. The itching may thereby reducing the clearance of estro- involve the palms and soles, as well. The gens and amplifying their effects. severity of the skin lesions correlates with Familial clustering and geographical the duration and degree of pruritus.3 variation indicate that there is a genetic According to one study, ICP occurred predisposition for ICP. There is a high in 0.5% of 3192 . The dis- prevalence of ICP in Chile (14%), espe- order resolves after delivery, and recurs cially among Araucanian Indian women with subsequent pregnancies.4 (24%), and in Bolivia.3 ICP patients may fast track ICP has been linked to have a family history of cholelithiasis Intrahepatic (20%–30%), (1%–2%), and and a higher risk of gallstones. There is preterm delivery (20%–60%).3 Autopsies a family history of cholelithiasis in 50% cholestasis of of the placenta have shown signs of acute of ICP cases.2 pregnancy has been linked to figure 3 fetal distress, Excoriations down the legs stillbirths, and preterm delivery

Patients with intrahepatic cholestasis of pregnancy have generalized pruritus, as evidenced by the excoriations down the patient’s legs.

914 vol 56, No 11 / November 2007 The Journal of Family Practice Pruritus in pregnancy

Exogenous factors have been impli- will show mites, eggs, and mite feces. cated in the pathogenesis of ICP. There is a If you suspect ICP in a patient who higher incidence of ICP during the winter. is also jaundiced, you’ll also need to Low selenium levels have also been linked rule out several other conditions. These to ICP. This suggests that the environment include: and nutritional factors play a role.2 • acute liver disease of pregnancy • preeclampsia complicated by in- creased liver enzymes z The differential Dx • includes scabies • viral hepatitis Itching has been reported to occur in • drug reaction 17% of pregnancies,2 so it is important • obstructive biliary disease, such as to differentiate ICP from the conditions a gallstone lodged in the common listed below. bile duct. • Pruritic urticarial papules and plaques of pregnancy—also known as polymorphic eruption of pregnancy—is a dermatosis of z Order a blood chemistry pregnancy. Unlike the excoriations of ICP, or liver profile this condition involves papulovesicular If you suspect that your patient has ICP, or urticarial eruptions on the trunk and start by ordering a blood chemistry or extremities. It is particularly pronounced liver profile. If any of the liver tests are around the abdominal striae, and is more elevated, order a total bile acid level common in nulliparous women. (which is the most sensitive indicator of • Pemphigoid gestationis, also known ICP) and a hepatitis panel (or specific as herpes gestationis because of its ap- hepatitis tests based on the patient’s his- pearance, is a bullous or blistering dis- tory of exposures and vaccinations). If ease that is associated with pregnancy. It there is laboratory evidence of cholesta- is often periumbilical and can also have sis, a right upper quadrant ultrasound target lesions, which are absent in ICP. will help you to spot gallstones and evi- fast track • Atopic eruption of pregnancy is a dence of obstruction. A total bile new term used to include previous non- In ICP, there will be mild abnormali- specific diagnoses such as of ties of the liver function tests, including acid level is the pregnancy and pruritic folliculitis of transaminases, alkaline phosphatase, most sensitive pregnancy. Prurigo of pregnancy, which and bilirubin. Bilirubin may be mildly indicator is also called Besnier’s prurigo gestationis, to moderately elevated (2–5 mg/dL). of intrahepatic involves bite-like papules that resemble (Jaundice is seen only at the higher lev- scabies. Pruritic folliculitis of pregnancy els of bilirubin.) Our patient’s tests, for cholestasis of is characterized by red, follicle-based instance, revealed that her ALT and AST pregnancy papules. These 2 conditions differ from were both over 300; her total bilirubin ICP in that there is no cholestasis and was elevated at 2.1. liver studies are normal. (In ICP, there is Serum levels of bile acid correlate with an elevation in liver enzymes and serum the severity of pruritus. Our patient’s bile bile acids.) acids were elevated and her hepatitis pan- • Scabies infestation can occur dur- el was negative. Her ultrasound showed ing pregnancy. The mite burrows in the gallstones, but we saw no obstruction. An skin and produces severe itching between ICP patient’s lipid profile may show mild the fingers and in skin folds. Look for elevations in total cholesterol and triglyc- burrows and the typical distribution be- erides, as was the case for our patient. tween the fingers, on the wrists, in the Malabsorption of fat may cause axilla, and around the waist. A positive vitamin K deficiency resulting in a pro- scraping viewed under the microscope longed prothrombin time. Liver biopsy is

www.jfponline.com vol 56, No 11 / November 2007 915 ds n rou unnecessary in suspected cases of ICP, but induced in the 38th week in mild cases of would show cholestatic changes such as ICP, and in the 36th week in severe cases dilated bile canaliculi, bile pigment in the (SOR: C).2 photo parenchyma, and minimal inflammation.

z Ursodiol for our patient, Skin biopsy is not helpful in ICP labor was induced In suspected cases of ICP, skin biopsy We treated our patient with oral ursodiol will only reveal a spectrum of non- and topical 1% hydrocortisone cream. specific findings. It is, however, help- Her bile acids and transaminase levels ful if you suspect pemphigoid gesta- dropped and her pruritus improved— tionis, since it will reveal subepidermal though it did not completely resolve un- blisters. Similarly, biopsy for direct im- til after delivery. Our obstetrics depart- munofluorescence is nonspecific in ICP, ment recommended weekly non-stress but helpful in pemphigoid gestationis. tests starting at the 34th week of gesta- tion. The non-stress tests were reactive. Due to the severity of her condition, la- z Soothing baths can help, bor was induced at 36 weeks. ursodiol is most effective Our patient had a healthy baby girl Mild cholestasis responds to symptomat- without complications. After delivery, ic treatment with soothing baths, topical the itching went away completely and antipruritics, emollients, and primrose her skin began to heal from all of those oil, among others. Antihistamines are excoriations. Our patient is planning an rarely effective. Anion exchange resins, elective cholecystectomy in the coming such as cholestyramine, can be helpful, months because she doesn’t want to take too; they bind bile acids and decrease a chance that she might have problems their enterohepatic circulation.2 with her gallstones in the future. n Patients who do not respond to cho- fast track lestyramine, or who cannot tolerate it, Correspondence may be treated with ursodeoxycholic Barbara Orr, MD, Loma Linda Professional Plaza, 25455 Ursodiol has Barton road, suite 206A, loma linda, CA 92354; acid (ursodiol). The research indicates [email protected] replaced that ursodiol works faster than chole- Disclosure cholestyramine styramine, has a more sustained effect on The authors reported no potential conflict of interest rel- as the first-line pruritus, and is more effective in improv- evant to this article. agent for ing the biochemical abnormalities of ICP References (strength of recommendation [SOR]: A, 1. Galaria NA, mercurio mG. dermatoses of preg- intrahepatic nancy. The Female Patient 2003. Available at: based on good-quality patient-oriented www.femalepatient.com/html/arc/sel/may03/028_ cholestasis evidence). Ursodiol is considered safe for 05_024.asp. Accessed on October 8, 2007. both mother and .5 For all of these 2. Kroumpouzos G. Intrahepatic cholestasis of preg- of pregnancy nancy: what’s new. European Academy of Dermatol- reasons, ursodiol has replaced cholestyr- ogy and Venereology 2002; 16:316-318. amine as the first-line agent for ICP. 3. Ambros-Rudolph CM, müllegger rr, vaughan Jones sA, et al. The specific dermatoses of preg- Doses range from 1 g/day to high doses nancy revisited and reclassified: results of a retro- of 1.5 to 2.0 g/d.6 The dose is maintained spective two-center study on 505 pregnant patients. until delivery. Davies et al5 suggest that the J Am Acad Dermatol 2006; 54:395–404. 4. Odom R, James, W. Andrews’ Diseases of the Skin. 10th use of ursodiol can reduce fetal mortality ed. Philadelphia, PA: WB Saunders Company; 2006. associated with ICP (SOR: C, based on 5. Davies mH, da silva rCMA, Jones sr et al. Fetal consensus, usual practice, opinion, dis- mortality associated with cholestasis of pregnancy and the potential benefit of therapy with ursodeoxy- ease-oriented evidence, case series). cholic acid. Gut 1995; 37:580–584. Weekly non-stress tests beginning 6. Mazzella G, Nicola r, Francesco A, et al. ursode- at the 34th week of gestation are advis- oxycholic acid administration in patients with cho- lestasis of pregnancy: Effects on primary bile acids in able (SOR: C).2 Labor may need to be babies and mothers. Hepatology 2001; 33:504–508.

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