Pregnancy Dermatoses

Includes physiological skin changes in pregnancy, specific dermatoses such as intrahepatic cholestasis of pregnancy, polymorphic eruption of pregnancy (pruritic urticarial papules and plaques of pregnancy - PUPP), pemphigoid gestationalis and atopic eruption of pregnancy, as well as non-specific dermatoses ranging from infections, infestations, inflammations and immune disorders.

Powerpoint made by Dr. Jerriton, second year MD post graduate in DVL, SVMC, Pondy.

1. PREGNANCY DERMATOSES Dr. Jerriton , 2 nd Year PG DVL, SVMCH&RC. 30.10.19

2. INTRODUCTION The skin changes in pregnancy physiological (hormonal ) pregnancy specific dermatoses . changes in pre-existing skin diseases. Coincidental dermatoses .

3. INTRODUCTION The skin changes in pregnancy physiological (hormonal ) pregnancy specific dermatoses . changes in pre-existing skin diseases. Coincidental dermatoses . A few can risk fetal life and require antenatal surveillance.

4. PHYSIOLOGICAL CHANGES

5. Diffuse hyperpigmentation Selective hyperpigmentation (genitalia, axillae, recent scars, areolae) Linea nigra Melasma ( chloasma , mask of pregnancy) Darkening of ephelides and melanocytic nevia PIGMENTARY

6. LINEA NIGRA

7. LINEA NIGRA

8. CHLOASMA

9. CHLOASMA

10. Hirsutism Thickening of scalp hair Postpartum TE Postpartum AGA HAIR & NAIL Subungual hyperkeratosis Distal onycholysis Transverse grooving Brittleness Accelerated growth

11. HIRSUTISM

12. SUBUNGUAL HYPERKERATOSIS ONYCHOLYSIS

13. Gingivitis (marginal gingivitis, papillomatous hypertrophy of the gums) Jacquemier –Chadwick sign (bluish discoloration of vagina and cervix) Goodell’s sign (cervical softening) MUCOSA

14. Increased eccrine function (except palms) ( miliaria , dyshidrotic eczema, hyperhidrosis) Elevated thyroid activity with resultant relative iodine deficiency Increased sebaceous function (growth in Montgomery’s tubercles) Decreased apocrine function GLANDS

15. PROMINENT MONTGOMERY TUBERCLES

16. Spider angiomas Palmar erythema Nonpitting edema (hands, ankles, feet, face) Varicosities Gingival hyperemia or hyperplasia Pyogenic granuloma (granuloma gravidarum , pregnancy epulis ) Hemorrhoids Hemangiomas Unilateral nevoid telangiectasia VASCULAR

17. Striae distensae ( striae gravidarum ) Molluscum fibrosum gravidarum ( acrochordons ) STRUCTURAL

18. PREGNANCY DERMATOSES SPECIFIC NON- SPECIFIC ICP AEP PEP PG

19. PREGNANCY DERMATOSES SPECIFIC NON- SPECIFIC ICP AEP PEP PG Infections Infestation Inflammation Autoimmune

20. SPECIFIC PREGNANCY DERMATOSES

21. INTRAHEPATIC CHOLESTASIS OF PREGNANCY Genetically linked, hormone-dependent, reversible cholestasis. Itch without skin lesions. Third trimester. Most important pruritic gestational condition.

22. PATHOPHYSIOLOGY Key element - reduced excretion of bile acids --> increased serum levels .

23. PATHOPHYSIOLOGY Key element - reduced excretion of bile acids --> increased serum levels. Mutations in ABCB4 gene that encode bile transporter proteins .

24. PATHOPHYSIOLOGY Key element - reduced excretion of bile acids --> increased serum levels. Mutations in ABCB4 gene that encode bile transporter proteins. High levels of sex hormones prevents excretion of bile acids .

25. PATHOPHYSIOLOGY Key element - reduced excretion of bile acids --> increased serum levels. Mutations in ABCB4 gene that encode bile transporter proteins. High levels of sex hormones prevents excretion of bile acids. Cholestatic effect of estrogen and progesterone metabolites .

26. PATHOPHYSIOLOGY Key element - reduced excretion of bile acids --> increased serum levels. Mutations in ABCB4 gene that encode bile transporter proteins. High levels of sex hormones prevents excretion of bile acids. Cholestatic effect of estrogen and progesterone metabolites. Selenium deficiency.

27. CLINICAL FEATURES Sudden onset of intense, generalized pruritus that often starts on the palms and soles.

28. CLINICAL FEATURES Sudden onset of intense, generalized pruritus that often starts on the palms and soles . Secondary changes from subtle excoriations to pronounced prurigo nodularis .

29.  PRURIGO SIMPLEX TO PRURIGO NODULARIS

30. CLINICAL FEATURES (contd.) Extensor surfaces of the extremities, buttocks and abdomen - most severely affected . Jaundice (10%) - steatorrhea and subsequent vitamin K deficiency, leading to an increased risk of intra- and postpartum hemorrhage.

31. CLINICAL PROGRESS Persists until delivery and then it resolves spontaneously within days. Recurrence during subsequent pregnancies - 45–70% of patients. Recurrence with oral contraceptives is routine.

32. FETAL RISK Increase in premature births (20–60%) Intrapartum fetal distress (20–30%; e.g. meconium staining of amniotic fluid, abnormal fetal heart rate) Fetal loss (1–2%).

33. INVESTIGATIONS Serum IgE - normal Serum bile acid – 3 – 100 times elevated. LFT – TB/DB, transaminases, ALP DIF / IF – No immunoreactants HPE – non-specific

34. DIFFERENTIAL DIAGNOSIS Other causes of secondary pruritus. Viral hepatitis (HCV).

35. DIFFERENTIAL DIAGNOSIS Other causes of secondary pruritus. Viral hepatitis (HCV). TREATMENT UDCA - 15 mg/kg daily or, independent of body weight, 1 g daily orally till delivery . Intramuscular vitamin K

36. ATOPIC ERUPTION OF PREGNANCY Diagnosis of exclusion. Most common pregnancy dermatoses (50%). Benign pruritic disorder. Eczematous / papular lesions with an atopic diathesis. AD is either de novo (2/3) or pre-existing (1/3). Occurs early in pregnancy . Tendency to recur.

37. PATHOPHYSIOLOGY Due to Th2 dominant immune response in pregnancy. Th1 cytokines (INF γ , IL-12) reduce, whereas Th2 cytokines increase (IL-4, 12). AD – Th2 driven disease – exacerbates.

38. CLINICAL FEATURES E – type in 2/3, P – type in 1/3. E - lesions involve “atopic sites“ such as the face, neck, and flexural aspects of the extremities. P - lesions involve trunk and extremities, composed of either classic prurigo lesions or small erythematous papules. Other signs of AD present.

39. E & P TYPE ATOPIC ERUPTION OF PREGNANCY

40. MIXED TYPE ATOPIC ERUPTION OF PREGNANCY

41. CLINICAL PROGRESS Maternal prognosis is good. Recurs in subsequent pregnancies.

42. CLINICAL PROGRESS Maternal prognosis is good. Recurs in subsequent pregnancies. FETAL RISK None.

43. INVESTIGATIONS Serum IgE – elevated. Serum bile acid – normal. LFT – normal. DIF / IF – No immunoreactants HPE – non-specific

44. DIFFERENTIAL DIAGNOSIS PEP - late pregnancy, association with striae , no recurrence. ICP - late pregnancy, raised serum bilirubin, altered LFT. Microbial folliculitis.

45. POLYMORPHIC ERUPTION OF PREGNANCY Benign self-limiting disorder. Primigravida . Associated with multiple-gestational pregnancy . Excessive weight gain . Late pregnancy (85%) or immediate post partum (15%). No recurrence.

46. PATHOPHYSIOLOGY Abdominal distension, hormonal and immunological factors .

47. PATHOPHYSIOLOGY Abdominal distension, hormonal and immunological factors. Damage to connective tissue ( striae ) due to overstretching .

48. PATHOPHYSIOLOGY Abdominal distension, hormonal and immunological factors. Damage to connective tissue ( striae ) due to overstretching. Low serum cortisol levels .

49. PATHOPHYSIOLOGY Abdominal distension, hormonal and immunological factors. Damage to connective tissue ( striae ) due to overstretching. Low serum cortisol levels. Previously inert structures develop antigenic character - increased CD1a .

50. PATHOPHYSIOLOGY Abdominal distension, hormonal and immunological factors. Damage to connective tissue ( striae ) due to overstretching. Low serum cortisol levels. Previously inert structures develop antigenic character - increased CD1a. Deposition of fetal male DNA in the maternal skin - peripheral microchimerism .

51. CLINICAL FEATURES Pruritic erythematous and edematous papules and plaques usually first appear within the abdominal striae . Typical periumbilical sparing .

52. PUPP STARTING OVER STRIAE

53. URTICARIAL RASH IN PUPP

54. CLINICAL FEATURES (contd.) Generalization with sparing of face, palms and soles . Half will develop more polymorphic features - erythema, target lesions, tiny vesicles, and eczematous plaques.

55. CLINICAL PROGRESS Lesions resolve over an average of 4 weeks. No maternal morbidity . No recurrence. Risk of multiple-gestation pregnancy subsequently.

56. CLINICAL PROGRESS Lesions resolve over an average of 4 weeks. No maternal morbidity . No recurrence. Risk of multiple-gestation pregnancy subsequently. FETAL RISK None.

57. INVESTIGATIONS Serum IgE – normal. Serum bile acid – normal. LFT – normal. DIF / IF – No immunoreactants . HPE – non-specific; striking number of eosinophils - as in PG.

58. DIFFERENTIAL DIAGNOSIS Urticarial PG Contact dermatitis Drug eruptions Urticaria Viral exanthems

59. PEMPHIGOID GESTATIONALIS Autoimmune , bullous disorder. Late pregnancy / immediate post partum. Association with trophoblastic tumors ( choriocarcinoma , hydatidiform mole). HLA haplotypes DR3 and DR4 associated. Usually avoids first pregnancy, but recurs in subsequent pregnancies with “skipped” pregnancies.

60. PATHOPHYSIOLOGY Site of autoimmunity: placenta. Circulating complement‐fixing IgG1 antibodies bind to a 180 kDa protein, BP‐180 or BPAG 2 / collagen XVII, in the hemidesmosomes of DEJ . Leads to tissue damage & subepidermal blister formation.

61. CLINICAL FEATURES Urticarial phase. Abrupt onset of cutaneous lesions on the trunk, in particular the abdomen . No periumbilical sparing (as in PUPP) .

62. URTICARIAL RASH IN PG

63. TYPICAL PERIUMBILICAL INVOLVEMENT

64. TENSE BLISTERS OF PG

65. CLINICAL FEATURES (contd.) Rapid progression to a generalized pemphigoid -like eruption then occurs . Pruritic urticarial papules and plaques, followed by clustered ( herpetiform ) vesicles or tense bullae on an erythematous base . Spares mucous membranes.

66. CLINICAL PROGRESS Spontaneous improvement during late gestation .

67. CLINICAL PROGRESS Spontaneous improvement during late gestation. Followed by a flare at the time of delivery in 75% of patients.

68. CLINICAL PROGRESS Spontaneous improvement during late gestation. Followed by a flare at the time of delivery in 75% of patients. Such flares may be dramatic, with an explosive onset of blistering within hours .

69. CLINICAL PROGRESS Spontaneous improvement during late gestation. Followed by a flare at the time of delivery in 75% of patients. Such flares may be dramatic, with an explosive onset of blistering within hours. Disease activity spontaneously remits during the weeks to months following delivery .

70. CLINICAL PROGRESS Spontaneous improvement during late gestation. Followed by a flare at the time of delivery in 75% of patients. Such flares may be dramatic, with an explosive onset of blistering within hours. Disease activity spontaneously remits during the weeks to months following delivery. Menstrual flares / OCP flares.

71. FETAL RISK About 10 % of newborns develop mild skin involvement that resolves spontaneously within days to weeks . Increased risk of prematurity and small-for-gestational age neonates.

72. URTICARIA-LIKE & VESICULAR LESIONS IN NEONATAL PG

73. INVESTIGATIONS Serum IgE - normal Serum bile acid – normal. LFT – normal. HPE – subepidermal bullae . DIF – Linear C3 in DEJ (100%), linear IgG (30%). Complement-added indirect IF reveals the circulating anti-BMZ IgG1 autoantibodies in nearly 100% .

74. SUBEPIDERMAL BLISTER IN PG – H&E

75. INVESTIGATIONS (contd.) Antibody titre demonstration with BP180-NC16A ELISA - to follow disease activity and monitor prognosis.

76. DIFFERENTIAL DIAGNOSIS PEP – clinically difficult to differentiate this with urticarial lesions of PG. IF & ELISA are key to distinguish. Drug reactions.

77. NON-SPECIFIC PREGNANCY DERMATOSES

78. INFECTIONS Viral – HPV, HSV, VZV, HIV Infestation - Scabies Bacterial - Leprosy AUTOIMMUNE SLE P vulgaris / foliaceus INFLAMMATORY GPP Acne & Rosacea PR Urticaria Erythema nodosum

79. VIRAL INFECTIONS More severe HPV – birth canal obstruction / laryn . P apillomatosis HSV – herpes genitalis – indication for CS. VZV – Mother – pn ., enceph ., fetal varicella syn. HIV – continue ART, Pneumocystis prophylaxis with co‐ trimoxazole (HIV positive infants).

80. BACTERIA - LEPROSY Leprosy reactional states are more common. Drug resistance is common. Treated with prednisolone 40–60 mg daily for 2 weeks followed by a steady reduction in the dose.

81. INFESTATION - SCABIES Any itchy condition – to consider. First line: P ermethrin cream - repeated after 1 week. Second line: Benzyl benzoate 25% Antihistamines – CPM, loratidine , cetrizine . Lindane & ivermectin – C/I

82. Impetigo Herpatiformis Third trimester Flexures initially as erythematous patches whose margins are studded with subcorneal pustules, then generalises . INFLAMMATION - GPP

83. Impetigo Herpatiformis Third trimester Flexures initially as erythematous patches whose margins are studded with subcorneal pustules, then generalises . Rapid resolution of symptoms after delivery. Recurs in subsequent pregnancies. Fetal risk: Placental insufficiency and consequent stillbirth or neonatal death. Early induction of labor needed. INFLAMMATION - GPP

84. ACNE & ROSACEA I mproves in early pregnancy but worsens in the third trimester. Oral erythromycin and azithromycin safe (after the first trimester). Acne neonatorum - passive transfer of maternal androgens across placenta; no treatment required . Topical & oral retinoids C/I INFLAMMATION (contd.)

85. PITYRIASIS ROSEA Mimics psoriasis / tinea corporis . HHV – 6 infection Can cause neonatal hypotonia , weak motility and hyporeactivity , fetal demise in first trimester. INFLAMMATION (contd.)

86. URTICARIA Mimics pre-bullous stage of PG & PEP. Frequent in pregnancy. Difficult to control effectively. INFLAMMATION (contd.)

87. ERYTHEM NODOSUM Pregnancy & OCP are known triggers. Eruption lasts 6-8 weeks. Fever, malaise and arthralgia often occur. Rest , leg elevation, compression hosiery and analgesia. SSKI is C/I INFLAMMATION (contd.)

88. IMMUNE DISORDERS SLE Flare of LE activity (60%) Spontaneous abortion Fetal loss Pre ‐ eclampsia Preterm delivery Intrauterine growth restriction Neonatal LE – annular rash face and scalp Congenital heart block (2–3%)

89. IMMUNE DISORDERS PEMPHIGUS VULGARIS Spontaneous abortion Exacerbation of disease (TH‐2 mediated) Stillbirth CS needed if there is severe vulvo ‐vaginal disease Neonatal pemphigus with transient blistering Perinatal mortality of 12% with placental dysfunction

90. REFERENCES Rook’s Textbook of Dermatology. Fitzpatrick’s Dermatology. Bolognia’s Dermatology.