Pruritus In Pregnancy : Clinical Presentation

Between 20 and 25 percent of pregnant women report itching; in most cases, this is due to Gestational Pruritus, which is characterized by no rash or abnormal liver function tests.

Skin itching can also result from a variety of dermatological diseases.

The following disorders, such as atopic dermatitis, eczema, allergic skin reactions, systemic diseases involving the skin (such as psoriasis, lymphoma, liver diseases, thyroid diseases), or even infestations like scabies, can be reported by women or they may already be afflicted with them.

There are also a number of dermatological conditions that are unique to pregnancy, such as the atopic eruption of pregnancy (also known as prurigo of pregnancy), which typically occurs in the third trimester of pregnancy and resolves after the pregnancy. Eczematous papules are visible in this condition, primarily on the flexor aspect.

Polymorphic eruption of pregnancy—previously known as pruritic urticarial papules and plaques—is another ailment. They start in the abdomen and can expand to the thighs, buttocks, and lateral aspects of the trunk. They usually appear over the stria.

There is observable periumbilical sparing. It typically occurs in the final few weeks of pregnancy and goes away following delivery. Women in their prime or who have had several pregnancies are more likely to experience this. One of the conjectures is that the abdomen skin's stretch may result in an inflammatory response or a hyposensitive delayed reaction.

Gestational pemphigoid, an uncommon and dangerous ailment, may also exist. Usually, it occurs either postpartum or in the third trimester. Vesicular exanthema is present over pruritic urticarial erythema, and as such, it may also be linked to fever. It affects periumbilical bullae and has the potential to extend to the soles, palms, and limbs.

Pruritus In Pregnancy With Abnormal Liver Function Tests

Pregnancy-specific factors such as obstetric cholestasis may exist. Pruritus or itching takes center stage as a symptom. Acute fatty liver of pregnancy is one such reason of abnormal liver tests; however, there may be other pregnancy-specific causes as well. However, the profile as a whole is very different from these situations, and itching is not the complaint.
Additionally, liver diseases such as cholelithiasis and biliary blockage can occur concurrently with pregnancy.

 The symptoms of sclerosing cholangitis or primary biliary cirrhosis in women may get worse during pregnancy.
Pregnant women with chronic hepatitis C may experience pruritus for the first time.Examining these variables becomes crucial if there is a high-risk factor, which makes understanding the patient's medical history crucial.

Intrahepatic Cholestasis Of Pregnancy (ICP)

Pathogenesis is a propensity to be affected by estrogens' cholestatic (and perhaps progesterone's) effects.  Bile acids' ability to sulfate is compromised by elevated estrogens.
The hepatic bile-acid transporters may be impacted by reproductive hormones.

Mutations that cause genetic disposition of intrahepatic cholestasis

 Mutation in the ABCB4 gene, which results in the progressive familial intrahepatic cholestasis-causing MDR-3 protein.
  Mutation in the ABCB11 gene, which produces the BSEP (bile salt exporter protein).

Prevalence of Intrahepatic Cholestasis

In the Asian-Indian region, it ranges from 1.2-1.5%.  Scandinavian nations likewise exhibit a higher incidence.
Selenium and vitamin D insufficiency may play a role, according to numerous research conducted in Scandinavia.

Clinical Presentation

 Severe limb and trunk pruritus, with a tendency to start in the third trimester, particularly on the palms and soles. At night, it is more often noted to have a higher intensity.  No excoriation (a potential rash) and no symptoms related to the constitution.

It may be linked to fat-soluble vitamins, dark urine, and steatorrhea, a condition where the body cannot properly absorb fat. Jaundice is a rare side effect that affects approximately 10% of women and rarely rises above 5 grams per deciliter.

Moderate increases in alkaline phosphatases, transaminases, and occasionally GGT.  There is an increase in AST and ALT, but often less than three times the upper limit, which is the normal level during pregnancy. seldom above 200 IU/L.

A rise in bile acids. Such unfavorable effects may result from higher bile acid concentrations in the fetal circulations and amniotic fluids.

Chorionic vein vasoconstrictions at the placental surface are brought on by elevated levels of cholinergic acid. And this may cause the fetus's flow of oxygenated blood to decrease. This reduction in oxygenated blood flow may occur suddenly or abruptly.

Clinical Approach To Pruritus

The rash could be present or absent. When there is a rash, it is important to look for signs and symptoms of a systemic illness as well as a complete medication history.  Take into consideration ailments like varicella, chicken pox, viral sickness, and drug reactions in the event of signs and symptoms of a systemic illness.

If there is no history of drug use or indications of a systemic illness, take into account dermatological problems. Due to the possibility of coincidental or pregnancy-specific skin problems. Consequently, a dermatological referral is required.

Request serum bile acids and liver function testing if there is pruritus without rash. If these are typical, proceed with symptomatic therapy. The tests need to be repeated if the symptoms continue.  Pregnancy-related additional problems may be present in cases of increased LFTs and bile acids.

Use symptom-based tests to ensure that other liver illnesses are ruled out.  Based on clinical suspicion, further investigation will be necessary.  Biliary blockage and cholelithiasis can be ruled out using an abdominal USG.  Having gallstones alone, without biliary tract dilation, is insufficient to account for abnormal LFTs.

ICP thus turns as an exclusionary diagnostic. Extensive tests such as liver autoantibodies, testing for primary biliary cirrhosis, testing for chronic active hepatitis, and looking for viral indicators are typically not necessary until symptoms appear.

 When the diagnosis of ICP is unclear, such as when there are indications of a systemic illness, such thorough examinations may be taken into consideration.

Abnormal liver function tests (LFTs) should be taken into consideration if they were present even before pregnancy, if we have significantly high liver enzymes or serum bilirubin (jaundice), if our symptoms started early, or if our LFTs are fast increasing.

Diagnosis of ICP

 If a woman has elevated peak and normal-appearing skin that is itching, this should be taken into consideration. Total bile acid content in RANDOM (non-fasting) patients is greater than 19µmol/L. The likelihood of a diagnosis increases if it is established that itchiness and elevated bile acids go away after birth.

Serum bile acid concentrations exceeding 100µmol/L are referred to as significant intracranial pressure.
While not advised for every woman, additional imaging or lab testing may be taken into consideration on a case-by-case basis.

Adverse Pregnancy Outcomes

Adverse pregnancy outcomes possible in case of the presence of ICP include-

• There’s a risk of stillbirth.
• Preterm birth chances (15% increased risks).
• Fetal distress (15 to 22% chances).
• Meconium-stained liquor (chances in 25-45% cases).
• Risks associated depend widely on serum bile acids.
• Looking at the risk stratification of stillbirth in comparison to serum bile acids are-
• When the concentration of serum bile acid is below 40µmol/L, the chance of stillbirth is comparable to background risk.
• MATERIAL RISK: Research has indicated that women with ICP have a higher risk of pre-eclampsia and GDM; regular care can significantly reduce this risk.
• There is no necrosis, inflammation, or liver damage when there is ICP. This indicates that there is no impact on the liver's ability to synthesize substances.
• The liver's ability to synthesize is unaffected. A distorted crag profile in the ICP is extremely improbable. The PT can be examined prior to birth.

Management

 The woman has to be made aware of all the potential hazards associated with her ICP diagnosis.  Following the diagnosis, there are concerns about when to deliver. Giving respite from itching becomes an aim till the birth.  Predicting which accurately becomes a goal when the likelihood of stillbirth increases, along with what needs to be examined or observed to guarantee fetal health.

Another concern is the function of bile acid lowering therapy, as well as the part medications play and how they can ease symptoms experienced by moms and stillbirths.

Maternal And Fetal Monitoring

 Report bile acids and LFTs after a week; additional testing frequency and necessity (when to start weekly testing) can be decided case-by-case. It is recommended that women keep an eye on their fetal movements and report any concerns right once. There is no proof that using fetal Dopplers, growth scans, fluid volume, or CTG to monitor fetal well-being leads to better results or predicts fetal compromise.

Role Of Drug Treatment

Since pruritus tends to be more active at night and these medications are known to have sedative effects, symptomatic therapies for pruritus include tropical emollients and antihistamines like promethazine or chlorpheniramine.  Vitamin K's role: Vitamin K is not usually administered; it is only indicated in cases of steatorrhea or prolonged Prothrombin Time. Typically, an oral, water-soluble form of vitamin K is advised.

Verify the prothrombin time before to delivery.  Inform women that there are no proven treatments for bettering pregnancy outcomes (or elevated bile acid levels), and that there is little benefit to treating maternal itchiness.The medication ursodeoxycholic acid (UDCA), also referred to as UDILIV, has been utilized for a number of non-pregnancy-related illnesses, such as cholestatic situations. In essence, the medication is hydrophilic bile acids.

To aid in secretion, the main bile is released, conjugated cholic acid in bile with taurine, glycine, etc., forming deoxycholic acid (secondary bile acid), of which 98–99% enters the enterohepatic circulation. In feces, about 2% is expelled.

Here, the ursodeoxycholic acid increases the excretion of the hepatotoxic bile acids by displacing the hydrophobic bile acid from the circulating bile acid pool.

The UDCA versus placebo RCT did not demonstrate that UDCA decreased total bile acid levels or increased the incidence of stillbirth or premature birth.  UCADA did cause a slight decrease in itching.  For certain women, it could lessen itching and lower liver and bile acid levels.  Offer UDCA seldom to mothers with ICP in an effort to prevent unfavorable perinatal outcomes.  When recommending the UCDA, a dose of 10–15 mg/kg body weight is advised; the typical beginning dose is approximately 300 mg BD, with a daily maximum of 1 mg.

Timing of Delivery

• If there are no other risk factors and a mild ICP, take into consideration planning a birth by 40 weeks.
• If you have a moderate ICP and no other risk factors, think about having a planned birth at 38–39 weeks.
• In severe ICP, take into account a planned delivery at 35–36 weeks gestation.
• In the event of any kind of ICP, ACOG advises a scheduled birth at 37–38 weeks.

Comorbid conditions (such gestational diabetes mellitus, preeclampsia, and multiple pregnancies) seem to raise the chance of stillbirth and may have an impact on when to schedule a planned birth.

Usually, the method of birth is unaffected by ICP. The obstructive factors determine the manner of birth.  If the patient has an uncomplicated ICP, there is no indication that there is an increased risk of PPH.

Postpartum Follow Up

To ensure that the ICP has resolved, a follow-up appointment should be scheduled for women with simple ICP at least four weeks following giving birth. Cholestasis in the liver when there is neither necrosis nor inflammation. After delivery, pruritus and elevated bile acids should subside.

Risk of developing immune-mediated disorders in later life; Possibility of developing hepatobiliary disease (mostly gallstones);  Consequently, standard routine testing/screening is not advised for these conditions following an episode of ICP during pregnancy.

Future Counselling

There's a 90% chance that this will happen again in subsequent pregnancies.  Oral contraceptives containing estrogen should be avoided in general.