Pruritus in pregnancy

Pruritus affects upto 20% of pregnant women.
There are conditions unique to pregnancy that involve pruritus as a leading symptom.

This is called dermotoses of pregnancy.

May produce risk to mother and foetus.
Approach to skin lesions in pregnancy: Pruritus related to pregnancy, Pruritus not related to pregnancy

1. Prof. Rokeya Begum DIRECTOR Surgiscope Fertility Centre Laparoscopic & Hysteroscopic Surgeon Pruritus in pregnancy

2. Pruritus affects upto 20% of pregnant women. May produce risk to mother and foetus .

3. Pruritus related to pregnancy Pruritus not related to pregnancy Approach to skin lesions in pregnancy

4. There are conditions unique to pregnancy that involve pruritus as a leading symptom. This is called dermotoses of pregnancy.

5. Dermatoses of pregnancy Intrahepatic cholestasis of pregnancy/obstetric cholestasis(ICP ). Pemphigoid gestationis (PG ). Pruritic urticarial papules and plaques of pregnancy(PUPPP ). Atopic eruption of pregnancy.

6. Pregnancy Related Atopic eruption of pregnancy Pruritic urticarial papules and plaques of pregnancy ( PUPPP ) Pemphigoid gestationis Unrelated to pregnancy Scabies Urticaria Drug eruptions allergy Rash Obstetric Cholestasis Exacerbation of underlying liver disease No Rash Approach to Pruritus

7. PUPPP Pruritic urticarial papules and plaques of pregnancy ( PUPPP ) Syn : PUPPP(4%) Papules within the striae Umbilical sparing Self limiting More common in primid.3 rd trimester Good prognosis M:F.3:1 No recurrence

8. Atopic Eruption in Pregnancy (AEP) Most common skin condition (50%) Prurigo,pruritic folliculitis in pregnancy Ig E levels Good prognosis,recurrence 50% Corticosteroids + antihistamines AEP

9. Phemphigoid Gestationis (PG) Herpes gestationis Autoimmune (3%),2 nd /3 rd trimester Skin biopsy for confirmation Flare at time delivery and post partum Steroids & antihistamines IUGR,preterm 10%-cutaneous involve of newborn Post partum flare,recurrence PG

10. ICP

11. PUPPP Prurutic lesions wiithin striae - progress to papules Periumbilical sparing PG Popules & plaques abdomen (umbilical) Progress to blisters AEP Common,develops early ,History of atopy,Eczematous or papular lesions-trunks OC Pruritis,no rash Pregnancy Specific Dermatological Condition

12. Fever Maculopapular rash Cephalocaudal Dengue

13. Contact dermatitis Atopic dermatitis Drug induced Urticaria / Dermographism Dermographism

14. Appropriate doses of LMWH Use booking weight I atrogenic

15. Erythematous papules and plaques with a silver scale 40-60% improve in pregnancy Psoriasis

16. Intrahepatic cholestasis of pregnancy/obstetric cholestasis This is a multifactorial condition of pregnancy characterized by pruritus in the absence of a skin rash with abnormal liver function tests and both resolve after birth.

17. Incidence * Unique to pregnancy * In UK 0.7 of all pregnant women. * Worldwide 0.2-2%

18. Risk factors Asian Multifetal pregnancy Invitro fertilization Older women H/O gall stone Hepatitis C infection. Sisters of affected women.

19. Pathogenesis

20. Bile acid Synthesis in hepatocyte from cholesterol Cholic acid Cholesterol Chenodeoxy cholic acid Glycocholic acid Taurocholic acid Emulsification of fat and fat soluble vitamin Glycocheno deoxycholic acid Taurocheno deoxycholic acid Lithocholic acid Entero hepatic Circular 95% Deconjugation by Bacteria Secondary bile acid Deoxycholic acid Primary bile acid

21. Bile acid homeostasis Bile acid are inherently toxic – homeostasis is highly regulated by gene encode a receptor known as Farnesoid X receptor(FXR) Receptor - down regulation of synthesis - uptake of bile acid - upregulation of export.

22. Bile acid homeostasis is disturbed in intrahepatic cholestasis of pregnancy.

23. Sulfated progesterone metabolites are partial agonists for FXR  Inhibiting the induction of its target genes.  Inhibit hepatic uptake of bile acid.  Efflux of bile acid Reproductive hormone

24. Oestrogen Reducing the expression and function of several bile acid transport protein in the liver including – a)Bile acid efflux protein. b) Bile salt export pump (BSEP)

25. Environmental factors Low Selenium intake Low Vit D Hepatitis C infection

26. Defect in excretion of bile acid resulting elevated bile acid level in serum.

27. Symptoms 1. Second or Third trimester. 2. Sudden onset. 3. Severe pruritus. 4. Starts on palms and soles quickly generalised . 5. Pruritus persists throughout pregnancy and is worst at night. 6. Sleep disturbances 7. Constitutional symptoms of cholestasis- a) dark urine b) pale stool c) right upper quadrant pain. d) Jaundice is rare (<10% of pregnancy)

28. Diagnosis 1. Pruritus starting from palms and soles without rash. 2. Confirmed by measuring serum bile acid. Normal level- up to 11 µ mol /L 3. Alanine amino transferase and Aspartate amino transferase – level increase

29. Bile acid measurement cannot done in Bangladesh. Diagnosis based on- a) Typical pruritus b) Abnormal live function tests c) Resolve after delivery-6 weeks. 4.Alkaline phosphatase 5. Gamma glutamyl transferase raised in 20% 6. bilirubin –raised in 10%

30. Other investigations a) USG of liver to exclude gall stone. 13% b) Gestational diabetes and hepatitis c virus has to be excluded. c) Coagulation profile d) PET and acute fatty live.

31. Non pregnancy associated causes of abnormal liver function tests- May present for the first time in pregnancy. Viral hepatitis Antoimmune hepatitis Biliary obstruction Drug induced live injury Primary biliary cirohosis .

32. Suspected case Viral marker – Hepatitis A, B, C, E CMV EBV Auto anibody – i. A nti smooth muscle antibody-chronic active hepatitis ii. Anti mitochondrial antibody – primary biliary cirrhosis.

33. Perinatal outcome 1. Preterm birth- - Spontaneous - Iatrogenic 2. Meconium staining of amniotic fluid 3. Foetal distress 4. Sudden IUD

34. Preterm birth Obstetricians should be aware (and should advise women) that the incidence of premature birth, especially iatrogenic, is increased. Spontaneous preterm birth (range 4-12%) Iatrogenic preterm birth (range 7–25%)

35. Cirlulating bile acid Increase gut motility Meconium stain liquor Mechanism

36. Increase myometrial contractilily and enhanced sensitivity to oxytocin Preterm labour

37. Bile acid Particularly taurocholic acid Toxic to cardiomyocytic cell C ardiac arrhythmias D eath

38. Marked Vasoconstriction in the placental chorionic veins causing event resulting foetal death.

39. Management 1. Counselling - Risk to the foetus 2. Surveillance -liver function test- - Prothrombin time - bile acid weekly

40. 3. Foetal well being - CTG - USG - growth - liquor volume - umbilical artery doppler blood flow.

41. 4. Pharmacological treatment- a) Topical emollients - calamine lotion and aqueous cream with menthol . b) Antihistamines- - Chlorpheniramine ( piriton 4mg TDS) - Promathazine ( phanergan ) 25mg at night

42. Topical emollients (calamine lotion and aqueous cream with menthol). Safe but their efficacy is unknown

43. c) Ursodeoxycholic acid (UDCA) - Naturally occuring hydrophilic bile acid . - Improves pruritus and liver function. - Lack of robust data concerning protection against still birth and safety to the foetus and neonate.

44. Doses 1000-1500mg/day in 2 to 3 divided doses.

45. Rifampicin – choleretic antibiotic Improves symptoms

46. Enhance bile acid detoxification as well as bilirubin conjugation by combination of rifampicin and UDCA Reduce pruritus and enhance bile acid excretion

47. Dexa methasone * 10mg orally for 7 days and then stopping over 3 days. * The general concern about adverse foetal and neonatal neurological effects of repeated course of maternally administered dexa methasone limit the potential use of dexamethasone.

48. Vitamin K Increase fat excretion affects the absorption of fat soluble vitamin includes vitamin-K Prothrombin time is prolonged. Water soluble formulation of vitamin K 10mg/day/orally start at 34 weeks of pregnancy or at the time of diagnosis

49. Strategy for delivery Elective early delivery was offered at 37-38 weeks of gestation. Severe ICP i,e total serum bile acid level of more than 40 µ mol /L or high transaminase level

50. Mode of delivery Spontaneous Induction of labour result in an increase rate of emergency C/S.

51. Maternal morbidity Intense pruritus and Consequent sleep deprivation . Increase Rate Of CS. Increase Risk Of PPH . If cholestasis lasts for several wks , liver dysfunction may result in: - Decreased vitamin K re-absorption or -Decreased prothrombin production, leading to a prolongation of the prothrombin time.

52. Postnatal followup Symptoms and biochemical abnormalities resolve rapidly following delivery. LFTS checked 6 weekly after delivery. Elevated level -referred to hepatologist .

53. Recurrent in next pregnancy Exposure to reproductive hormone like pill . Future health

54. Take a good history Systematically approach obstetric & non obstetric causes (autoimmune ) Common causes are AEP & PUPP Pruritus is common,may precede abnormal LFT If unsure-skin biopsy (HPE & direct immunofluorence) SKIN Take home message