Pruritus Gravidarum

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Continuing Education Activity

Pruritus is a common symptom in pregnancy. The causes of pruritus can be unrelated or specific to pregnancy. Pruritus specific to pregnancy must be adequately addressed and investigated as they can be signs of underlying diseases. This activity reviews pruritus gravidarum, a specific dermatosis of pregnancy, that can be related to underlying liver abnormalities. This activity will review the etiology, epidemiology, clinical features, management, and patient education pertinent to pruritus gravidarum and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

  • Identify the etiology of pruritus gravidarum.
  • Review the appropriate history, physical, and evaluation of pruritus gravidarum.
  • Outline the treatment and management options available for pruritus gravidarum.
  • Summarize interprofessional team strategies for improving care coordination and communication to improve outcomes in pruritus gravidarum.

Introduction

Pregnancy, a state of profound physiological and hormonal changes, is associated with a spectrum of changes in the skin and appendages. More than 90% of pregnant women experience one or more forms of skin changes.[1] Up to 20% of women experience pruritus during their pregnancy.[2]

Specific dermatoses of pregnancy are the afflictions of the skin that appear during pregnancy and resolve with parturition. Pruritus gravidarum is a condition of the skin in gravid women represented by itching and only secondary lesions in the form of excoriations with or without evidence of cholestasis.[3] Pruritus gravidarum and intrahepatic cholestasis of pregnancy are terms used interchangeably in the medical literature with pruritus gravidarum characterizing the patients with pruritus in the absence of primary skin changes[4]. To reiterate, there is no specific rash associated with pruritus gestationis, but many patients will have evidence of self-inflicted excoriations due to itching to attempt to relieve pruritus symptoms. Itching can range from mild to severe and most commonly affect the palms and soles. Symptoms may be worse at night. It is important for clinicians to recognize pruritus gestationis, as these patients must be evaluated for intrahepatic cholestasis of pregnancy. Most obstetric clinicians can expect to encounter intrahepatic cholestasis of pregnancy during their careers, as it is the most common liver disease specifically associated with pregnancy [5]. If patients are diagnosed with intrahepatic cholestasis of pregnancy, this information can change the treatment plan, delivery timing, antenatal evaluation of the fetus, and care of future pregnancies [6]

Etiology

A single exact etiology of pruritus gravidarum has not yet been established. Hormonal and genetic factors have been ascribed to play a strong role in its causation.[7] The disease most commonly begins in the third trimester, a time of peak hormonal concentration, and resolves with parturition. It can also reappear in subsequent pregnancies, supporting the hormonal basis for the disease causation.[7]

Pruritus gravidarum has a heterogeneous incidence with distinct ethnic and geographical differences. This ethnic and geographical pooling of cases points towards an underlying genetic basis for the disease. Heterozygous mutations in the multidrug resistance 3 genes (MDR3), also known as ABCB4, have been implicated in the disease pathogenesis.[8] The MDR3 gene encodes the transport protein- canalicular phosphatidylcholine translocase.[9]

Risk factors for intrahepatic cholestasis of pregnancy include a personal or family history of intrahepatic cholestasis in a previous pregnancy, multiple gestations, chronic hepatitis C, and advanced maternal age [10].

Epidemiology

Pruritus gravidarum has a varying incidence across the globe. Incidence rates ranging from <1 to 27.6% have been reported.[11] An incidence rate of 22.1% was seen in Chilean women of Araucanian Indian descent; the prevalence increasing directly with the degree of 'ethnic purity.'[12] In European countries, incidence rates varied between 0.5% to 1.5%, with Scandanavian women contributing to the highest incidence rates. In the US, the highest incidence of 5.6% was seen in the Hispanic population in Los Angeles;[13] a 0.32% incidence rate was seen in Connecticut.[14] In Indian-Asian and Pakistani-Asian women, the incidence was 1.2% to 1.5%.[15] A higher incidence was reported during the winter.[11]

Pathophysiology

Pruritus occurs secondary to increased levels of bile acids within the skin and in the serum. The exact mechanism by which bile acids induce pruritus is not well understood. Bile salts, due to their detergent properties, can lead to the release of histamine and proteolytic enzymes through the solubilization of lipid cellular membranes. The release of histamine and other enzymes can lead to the activation of free nerve endings, thus leading to pruritus.[16]

The levels of bile acids rise secondary to hormonal and genetic factors. Hormones like estrogen and progesterone, whose levels increase through the course of pregnancy, have a cholestatic effect and reduce the hepatic excretory function.[17] Cholestasis can also occur owing to the mutations in the MDR3 gene [18].

Histopathology

The skin biopsy findings in pruritus gravidarum are usually non-specific; epidermal ulceration is seen secondary to excoriations.[19]

History and Physical

Itching, an irritating sensation that evokes the impulse to scratch, is the predominant complaint in pruritus gravidarum. The itching begins in the late second to the early third trimester; itching onset as early as eight weeks of gestation has been described.[20] A study found the onset of symptoms to coincide with a urinary tract infection in at least 50% of women.[21]

Itching is usually intermittent at the outset and goes on to become constant. Pruritus begins first in the abdomen and spreads to involve the entire trunk and the palms and soles. The itching ranges from mild to severe and bothers the patients most in the night.[17] Icterus, if it does manifest, follows pruritus by at least four weeks in only about 20% of cases.[22] If icterus is present, patients may develop steatorrhea leading to fat malabsorption. Symptoms persist through the course of pregnancy, resolve with childbirth, and recur with subsequent gestations.[23]

The examination does not show any primary lesions in pruritus gravidarum. In fact, the diagnosis of pruritus gravidarum is rejected if any primary lesions are present.[24] Excoriations and scratch marks secondary to itching are the typical examination findings.

Evaluation

Since pruritus in the absence of primary skin lesions is the cardinal feature of pruritus gravidarum, the importance of a thorough history and a complete physical examination cannot be overemphasized.

The key laboratory finding in pruritus gravidarum is an increase in the concentration of serum bile acids. Usually, it is the first and only abnormal laboratory finding. The rise in serum bile acid levels follows pruritus.[25] Cholic acid levels increase more than chenodeoxycholic acid levels, thus skewing the cholic/chenodeoxycholic ratio. The cholic/chenodeoxycholic ratio was 3.4 in women with pruritus gravidarum as compared to 1.1 in pregnant women without the condition.[26] 

Serum aminotransferases may be increased but do not exceed 1000 unit/L, distinguishing this condition from viral hepatitis.[27] Alkaline phosphate levels, although elevated, are not specific for pruritus gravidarum due to the production of the placental isoenzyme. Hyperbilirubinemia points towards the diagnosis of intrahepatic cholestasis of pregnancy.

Ultrasonography of the liver does not show any abnormalities. Histopathology may show cholestasis without inflammation, but a liver biopsy is not needed for diagnosis.[28]

Treatment / Management

The goal of treatment should be focused on the alleviation of symptoms and the prevention of adverse outcomes in the fetus. Mild symptomatic cases may be treated with reassurance, antipruritic preparations like calamine lotion, soothing oatmeal baths, menthol in aqueous cream, and weak steroidal ointments.[29] Patients should be reassured and advised to avoid anxiety and irritating clothing.[30] A diet with low-fat content and rest should be encouraged.[21]

Patients should also be counseled regarding the temporary nature of the disease and prompt resolution of their symptoms following delivery. First-generation antihistamines like diphenhydramine, chlorpheniramine, pheniramine, or tripelennamine are safe during pregnancy and may be used as adjunctive therapy.[30]

Severe or intractable pruritus with concomitant biochemical abnormalities can be treated with ursodeoxycholic acid (UDCA). UDCA, a hydrophilic bile acid, removes other hydrophobic salts from enterohepatic circulation by replacing them. UDCA can be used at a dose of 15mg/kg/day and helps control pruritus while correcting the biochemical abnormalities. UDCA has no teratogenic effects and works faster than other drugs available.[31] It is important to note that UDCA treatment may alleviate maternal symptoms, but it does not decrease the risks to the fetus.

Other drugs that may be used include cholestyramine, S-adenosyl-D-methionine, oral corticosteroids, nonerythemogenic UVB radiation, and phenobarbital. These drugs are implicated more in the treatment of intrahepatic cholestasis of pregnancy, but since pruritus gravidarum and intrahepatic cholestasis of pregnancy share many features, these drugs are worth mentioning here.

There are increased risks of adverse fetal and neonatal outcomes in the setting of intrahepatic cholestasis of pregnancy including increased risk of preterm birth, meconium-stained amniotic fluid, neonatal depression, respiratory distress syndrome, and stillbirth [32]. In order to attempt to decrease the risk of adverse events, the American College of Obstetricians and Gynecologists (ACOG) recommends antenatal surveillance with fetal non-stress tests after viability beginning at the time of diagnosis of cholestasis and continuing once or twice weekly until delivery [33]. Per ACOG, the recommended timing of delivery is determined by the total bile acid levels in the serum. For a total bile acid level <100 micromol/L, delivery is recommended between 36 0/7 - 39 0/7 weeks of gestation. For total bile acid level 100 micromol/L or higher, delivery is recommended at 36 0/7. If the patient is diagnosed with cholestasis at a gestational age later than the recommended gestation for delivery, delivery is recommended at the time of diagnosis [34]

Differential Diagnosis

Pruritus is a common complaint of pregnancy, so it is important to rule out other causes of pruritus including but not limited to: specific dermatoses of pregnancy, atopic dermatitis [35], pemphigoid gestationis [36], erythema multiforme [37], polymorphic eruption of pregnancy [38], atopic eruption of pregnancy [39], pustular psoriasis of pregnancy[40], scabies [41], pediculosis [42], neurodermatitis [43], contact dermatitis [44], and drug eruptions[30]. If the patient has concomitant liver function abnormalities, other causes of liver dysfunction should be ruled out: viral hepatitis[45], acute fatty liver of pregnancy[46], HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome [47], and drug-induced liver damage.[48] 

Prognosis

The prognosis for pruritus gravidarum is excellent with rapid subsidence of symptoms after parturition. After 24-48 hours of delivery, pruritus and icterus typically resolve but may last up to four weeks.[17] Normalization of bile acid levels occurs in 4-6 weeks.[49] Pruritus gravidarum may recur in 40%-70% of women in subsequent pregnancies. Estrogen-containing preparations may also cause recurrences in some cases.[17][50]

Complications

Complications vary for the mother and the fetus. Complications to the mother may include malabsorption or postpartum bleeding following reduced levels of vitamin K owing to liver abnormalities.[20] A study found an increased incidence of gall bladder disease, including cholelithiasis in such patients.[51] Complications to the fetus include premature birth, intrauterine asphyxia, meconium-stained amniotic fluid, and low birth weight.[52] A study found bile acid levels 40 micromol/L or more to be statistically significant for increased adverse events in the fetus.[53] Fetal complications are believed to arise from placental anoxia.[54]

Deterrence and Patient Education

Patients should be advised to refrain from scratching to avoid secondary lesions and reduce the risk of hyperpigmentation. Patients should be asked to follow up with their clinicians when their symptoms are uncontrollable and bothersome. Patients should be reassured regarding the prognosis and the fetal risks involved. These patients should also be advised to avoid estrogen-containing oral contraceptives or use them in the lowest doses possible.

Enhancing Healthcare Team Outcomes

The management of a patient with pruritus gravidarum requires an interprofessional team consisting of an obstetrician, dermatologist, hepatologist, maternal-fetal medicine specialist, and the nursing team. The management team must focus on making the patient as comfortable as possible while monitoring the fetus of any complications. The patient should be counseled appropriately regarding the complications of the disease. Patient preferences for delivery and management options should be discussed beforehand and considered appropriately while making management decisions.


Article Details

Article Author

Biplov Adhikari

Article Author

Heather Hall

Article Editor:

Moien AB Khan

Updated:

8/22/2021 6:21:19 PM

PubMed Link:

Pruritus Gravidarum

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