1. Canadian Society of Internal Medicine Annual Meeting Quebec City, October 2012 Pregnancy-specific dermatoses Annabelle Cumyn, MD, MHPE Obstetric Internist CHU Sainte Justine CHUS

2. Canadian Society of Internal Medicine Annual Meeting Quebec City, October 2012 Annabelle Cumyn; Pregnancy-specific dermatoses – October 17 th, 2012 The following presentation represents the views of the speaker at the time of the presentation. This information is meant for educational purposes, and should not replace other sources of information or your medical judgment. A selection of slides from this talk will be available on the CSIM website in PDF format.

3. Canadian Society of Internal Medicine Annual Meeting Quebec City, October 2012 Annabelle Cumyn; Pregnancy-specific dermatoses – October 17 th, 2012 The speaker has received fees/honoraria from the following sources: none Some of the drugs, devices, or treatment modalities mentioned in this presentation are: Steroid-based creams! Conflict Disclosures

4. Caveat lector Not a dermatologist Obstetric Internist www.gemoq.ca @gemoq

5. Objectives 1. Differentiate clinically and histologically the major dermatoses of pregnancy 2. Counsel the patient about the fetal risks of those diseases. 3. Consider the major differential diagnosis of cholestasis of pregnancy. 4. Prescribe the appropriate treatment, topical or oral, for the major dermatoses of pregnancy.

6. Hyperpigmentation Spider angioma, telangiectasia, palmar erythema Gingivial hyperemia, pyogenic granuloma Hypertrichosis, telogen effluvium Increased hormone levels Oedema Vascular expansion Striae gravidarum Abdominal distension Milaria, hyperhydrosis Glandular function Increased brittleness, onycholysis Transverse grooving Nails changes

7. Pruritus 20% reported pruritus as early as T1 44% developed a rash Obstetric Medicine 2010;3:25-29.

8. Classification of pregnancy-specific dermatoses PSD Polymorphic eruption pregnancy PEP Atopic eruption of pregnancy AEP Prurigo of pregnancy Pruritic folliculitis of pregnancy Eczema of pregnancy Intrahepatic cholestasis of pregnancy ICP Pemphigoid gestationis PG

9. PSD Common features Heterogeneous pruritic conditions Occur during pregnancy or immediately pp Incomplete understanding of pathophysiology: Hormonal and immunological changes Inflammatory features IMPORTANT DISTINCTION: 2 benign but can be distressing 2 associated with maternal and fetal complications

10. Useful clues PEPAEPICPPG Primiparous 73%44%47%48% Multiple 16%1%0% Recurrence 7%34%88%9% Early 3%75%20%29% Abdomen 98%68%36%95% Only pruritus 00100%0 Only excoriations 00100%0

11. Polymorphic eruption of pregnancy PEP AKA: PUPPP, toxaemic rash of pregnancy, late onset prurigo of pregnancy Common 1:160 pregnancies Hallmark features Third trimester and first month post-partum Primiparous, male fetuses, gestational diabetes Related to excessive abdominal distension Starts within striae distensae: severely pruritic urticarial papules → coalesce into plaques → spreads to buttocks and thighs (spares umbilicus)

13. PEP course and treatment Self-limited Does not tend to recur Unaffected fetus Oral antihistamines Topical corticosteroids Short course of prednisone 20-40mg po qd in tapering doses

14. Atopic eruption of pregnancy AEP AKA as atopic dermatitis (not always atopic!) Common Starts early Includes eczema of pregnancy, prurigo of pregnancy, pruritic folliculitis, papular dermatitis of pregnancy P versus E type Ddx: atopic dermatitis/eczema; pityriasis rosea; contact dermatitis

15. AEP Hallmark features: Intensively itchy First-third trimesters Severe dryness of skin P-type: maculo-papular changes or prurigo-type nodules E-type: eczematous changes (often face and neck) Can also see 2-4 mm pustules (like acne vulgaris) Resolves 2-3 months post-partum

17. AEP diagnostic features Signs of atopy: Family history Airway hyperactivity Allergic rhinitis Allergic conjunctivitis Food allergies Facial features: “shiners”, Denni-Morgan lines Serum IgE levels ↑ in 20-70%

18. AEP treatment Unaffected fetus Emollients are very important Decrease use of soaps, baths Low to mid potency topical corticosteroids Systemic steroids in severe cases Beware of superimposed infections

19. Intrahepatic cholestasis of pregnancy ICP Prevalence: 1:150 pregnancies Hallmark features Pruritus palms and soles with rapid generalization Icterus in 10%, steatorrhea is rare abnormal LFTs in 70% (AST/ ALT > tbili) Second and third trimester, multiple gestation Resolves rapidly pp IMPORTANCE: Measure bile acids and repeat LFT’s Meconium, fetal arrhythmia, PTL, IUFD Treatment includes delivery plan Tends to recur next pregnancy and with OCP

21. ICP fetal impact Cardiotocographic abnormalities: Reduced variability Tachycardia, bradycardia Fetal tachyarrhythmia (atrial flutter at 220-230bpm) Prematurity (up to 1/2) Intrapartal fetal distress (up to 1/3) Meconial staining of amniotic fluid IUFD (1/100)

22. World J Gastroenterol 2009; 15(17):2049-66.

23. Bile salts measurement Cholic acid, chenodeoxycholic acid, taurine, autotaxin Bile acids levels Mild ICP <4 µmol/L Moderate ICP 4-40 Severe ICP>40 1-2% increased risk for every 1 µmol/L above 40

24. ICP treatment RCT 2012 BMJ 2012;344:e3799 Ursodeoxycholic acid (UCDA) vs placebo Less pruritus ALT lower Early delivery vs expectant No difference in rate in c/s or major neonatal outcomes UDCA 10-15mg/kg/day bid or tid (max 2g/day) Diphenhydramine 25-50mg po q 4-6hrs Hydroxyzine 25mg po q 6-8hrs

25. Approach to fetal monitoring NO single intervention has been shown to predict or prevent adverse fetal outcomes Elective delivery at 37 or 38 weeks ? Monitoring PR interval

26. ICP standards RCOG guidelines 2011 Leaflet for patient Infection screen: hepatitis A,B,C, EBV, CMV Autoimmune work-up: ANA, Anti-smooth muscle, AMA Serial LFTs q 1-2 weeks Liver ultrasound Delivery plan: maximum 38 weeks gestation Post-natal follow-up until normalization

27. Pemphigoid gestationis PG Rare 1:2,000-50,000 pregnancies Hallmark features: Periumbilical pruritis → papulo-urticarial rash (abdomen initially) → Bullae and blisters on plaques after 1-2 weeks Second and third trimester (also pp) Associated with other autoimmune disorders IMPORTANCE: Biopsy beside bulla; speak to pathologist re direct immunofluorescence Treatment Fetal impact Flare-up at delivery and risk of recurrence

32. PG obstetrical outcome SGA babies: if diagnosis in T1 or T2 Prematurity: if diagnosis in T2 and blisters present 5-10% neonates with mild skin lesions with spontaneous resolution

33. PG treatment Pre bullous stage: topical corticosteroids and oral antihistamines Bullous stage: prednisone 20-40mg po daily Start taper 1 week after appearance of last lesion Maintain on 5-10mg po daily until delivery Breastfeeding Refractory cases: Immunopheresis/ IVIG Azathioprine up to 1mg/kg/day Dapsone

34. Pustular psoriasis of pregnancy Rare:>200 cases described AKA impetigo herpetiformis Hallmark features Systemic symptoms, third trimester, rapid resolution pp Widespread tiny pustules on erythemato-squamous plaques IMPORTANCE: Maternal complications (hypocalcemia) Associated with placental dysfunction, IUFD Requires systemic treatment Possible recurrence

36. PPP treatment Prednisone 20-30mg po daily Supportive fluids, calcium Fetal monitoring Early delivery Beware of bacterial superinfection Refractory cases: Prednisone 60-80mg po daily UVA cyclosporine

38. Emollient creams With urea 3-10% Antipruritic additives: menthol, polidocanol Cocoa and shea butter Wheat or oat based bath products Avoid almond-based oils

39. Topical steroid creams Pregnancy 1 systematic review (7 studies) + 2 studies since No increased risk of: Cleft lip/palate or other malformations Prematurity SGA babies (except for 1 study at high doses) IUFD Lactation Few studies; low excretion; careful if treating areola

40. PotencyNameVehicleDose I Super high II High III HighTriamcinolone acetonide Βmethasone Amcinonide O, C O, C, L, F C, L 0.5 0.05 0.1 IV MediumHydrocortisone Triamcinolone Mometasone furoate O O, C C, L, S 0.2 0.1 V Lower-midHydrocortisone butyrate Fluticasone O, C, L, S C, L 0.1 0.05 VI LowFluocinoloneC, S0.01 VII Super low

43. Antihistamines Pregnancy: Diphenhydramine 25-50mg po q 4-6 hours Hydroxyzine 25mg po q 6-8 hours Cetirizine 5-10mg po qd Loratidine 10mg po qd Lactation: Diphenhydramine: maximal dose=0.3% of pediatric dose Loratidine: 1% of maternal dose

44. Clinical case #1 34 y.o woman G2P0 32 weeks gestation Followed for gestational diabetes At follow-up appointment complains of itchy red spots on her mid abdomen Worried because it has extended to legs and chest

46. Clinical case #2 28 y.o woman G2P0A1 32 weeks gestation Pruritic lesions started 2-3 weeks ago Started on abdomen and spread to trunk and arms Describes initial red patches that grew Comes today because getting worse

49. Date of download: 10/13/2012 Copyright © 2012 American Medical Association. All rights reserved. From: Usefulness of BP180 NC16a Enzyme-Linked Immunosorbent Assay in the Serodiagnosis of Pemphigoid Gestationis and in Differentiating Between Pemphigoid Gestationis and Pruritic Urticarial Papules and Plaques of Pregnancy Arch Dermatol. 2005;141(6):705-710. doi:10.1001/archderm.141.6.705 Pemphigoid gestationis (A and B) and polymorphic urticarial papules and plaques of pregnancy (C and D) are similar clinically and histologically (hematoxylin-eosin, original magnification ×10). Both conditions manifest with a pruritic urticated erythematous eruption. On histologic examination, common features include focal spongiosis, edema of the papillary dermis, and a superficial to middle dermal, predominately perivascular, mixed inflammatory infiltrate. Immunofluorescence studies are necessary to differentiate between pemphigoid gestationis and polymorphic urticarial papules and plaques of pregnancy. Figure Legend :

51. Thank you

52. Review articles Recent developments in the specific dermatoses of pregnancy. Clin and Experimental Dermatology 2011;37:1-5. Dermatosis of pregnancy- clues to diagnosis, fetal risk and therapy. Ann Dermatol. 2011;23(3):265-275. Geenes V, Williamson C. Intrahepatic cholestatis of pregnancy. World J Gastroenterol 2009; 15(17):2049-66.