ORGANUM
The exact aetiology of obstetric cholestasis is uncertain; however, there appears to be a genetic predisposition to sensitivity to oestrogen, which causes abnormalities in liver function. In addition, it has been speculated that hormonal, environmental and dietary factors are involved. There are some known risk factors:
Certain ethnicities
South American, South Asian and Northern European
Past history of obstetric cholestasis and the predominant risk factors for obstetric cholestasis
The disease is shown more in first-degree relatives, and a higher risk of disease recurrence with subsequent pregnancies - this supports a genetic susceptibility hypothesis. ICP is noted to be more prevalent in women with a low level of selenium and vitamin D.
OC is the most common liver disease related to pregnancy - incidence varies but is around 0.2% to 2% of all pregnancies. It is more common in South American and northen European continents.
Oestrogen reduces the expression of nuclear hepatic bile acid receptors and hepatic biliary canalicular transport proteins in genetically susceptible women causing impairment of hepatic bile acid hemostasis and subequent increased level of bile acids.
Obstetric cholestasis presents with intense itching, especially on the palms of the hands and soles of the feet in the second or third trimester. It usually starts after the 30th week of pregnancy. There is rarely a rash associated with itching, but excoriation marks are frequently present. Rarely, pare stools, dark urine and jaundice are noted. Other symptoms of cholestasis are:
Nausea
Anorexia
Fatigue
RUQ
Dark urine
Pale stools
May be present. Clinical jaundice is rare but may present in patients (14% to 25% after 1 to 4 weeks of the onset of pruritus. Some patients also complain of insomnia secondary to pruritis. Generally, physical examination is unremarkable expect for excoriation marks from the itching. Pruritis is a cardinal symptom of OC and may precede biochemical abnormalities. In patients who undergo IVF, ovarian hyperstimulation can cause transient symptoms in the first trimester compared to persistent symptoms in the second and third trimester in ICP. Family history of liver dysfunctions during pregnancy in other female relatives requires inclusion because of the role of genetics in pathophysiology.
Some women experience similar symptoms when taking the combined oral contraceptive pill or in the second half of the menstrual cycle.
The diagnosis is confirmed by a rise in bile acids and/or raised liver transaminases where other pathology (autoimmune disease, gallstones and viral infection) has been excluded. The most sensitive marker for ICP is the total serum bile acid using a cut-off value of 10mmol/L. The risk of fetal complications increase in severe cholestasis with increased serum bile acid levels, usually over 40mmol/L. Other liver function tests, including ALT and AST are usually mildly elevated and do not exceed two times the upper limit of normal value in pregnancy. Serum ALP can be elevated physiologically due to placental production but has little diagnostic siginifiance in ICP. Elevated billirubin can present in 25% of cases but rarely exceeds 6mg/dL. High prothrombin time can be present because of vitamin K deficiency (decreased fat-soluble vitamins), but postpartum haemorrhage is rare.
The pruritus of obstetric cholestasis can be difficult to treat. Topical emollients are safe for use in pregnancy but provide little symptomatic relief. Antihistamines are sometimes used for their sedative ability but have little impact on the itch itself. Ursodeoxycholic acid has been shown to improve both pruritus and liver function, but long-term safety data are lacking. In spite of this, it is the mainstay of antenatal treatment. In view of the potential risk of clotting abnormalities, oral water-soluble vitamin K supplementation can be used, particularly for those women whose clotting tests suggests an abnormality.
UDCA is started at 300mg BID and can be increased to 300mg three times a day until delivery. Usually, maternal symptoms will alleviate in about two weeks, and the bile acid levels will decline in two or three weeks. If there is no improvement in patients symptoms or bile acid levels, the dose can be titrated every week or two to a maximum dose of 21 mg/kg/day. UDCA is well tolerated by most patients - some of the common side effects are nausea, vomiting and diarrhea. It has no determinetal impact on the fetus.
For patients with no improvement of ICP, refractory to UDCA, other medications such as rifampin, cholestryamine and S-adenosyl-L-methionine are options. Rifampin increases bile acid detoxification and excretion and can be an adjunct to UDCA. Cholestryamine is an anion exhcange resin that decreases the ileal absopriton of bile salts, thereby increasing their fecal excretion.
The best way to monitor the antenatally has not yet been established. Methods such as serial growth ultrasound scans and CTGs that can detect problems with placental functions are not predicitive of at-risk fetuses in obstetric cholestasis. Consequently, delivery once fetal maturation is reached is often recommended to reduce the small risk of late stillbirth.
Postnatally, women are usually advised to avoid oestrogen-containing contraceptives, which can precipitate a recurrence of symptoms.
Pemphigoid gestatonis
Tense blisters, small bumps, hives and intense itching
Starts around navel before spreading to limbs in mid-pregnancy or shortly after delivery
Head face and mouth are not affected