Dr Julie George Consultant ,Internal Medicine, TTSH Visiting consultant, Obstetric Medicine, KKWCH • Physiological changes in • Dermatoses specific to pregnancy Family • Dermatoses in the non-pregnant population that physicians may flare or remit in pregnancy perspective • Conditions that need a Referral to a specialist Hormonal Vascular Immunologic Estrogen High strong maternal cell-mediated immune Progesterone estrogen function are blunted in exchange for a Melanocyte stimulating levels more dominant hormone humoral immune response and Th2 production that includes IL-4 and IL-10. Stimulates Blood vessels melanocytes IL-4 plays a key role in the generation dilate and of immunoglobulin E (IgE) produced by proliferate + B lymphocytes, and this may be Increased pertinent in the pathogenesis of atopic capillary eruption of pregnancy permeability

Changes in skin, nails,mucous Dermatoses specific to pregnancy membranes

Melasma Spider angiomas

Pyogenic granuloma gingivitis Maternal and Fetal risk Maternal and Fetal risk absent: present: (rare but recur in ( more common) subsequent ) • Polymorphic eruption of pregnancy • Pemphigoid gestastionis (PG) (PEP/PUPPP:Pruritic urticarial papules and plaques of pregnancy) • Intrahepatic cholestasis of pregnancy (ICP) • Atopic eruption of pregnancy (AEP ) includes • Pustular psoriasis of Eczema Pregnancy (Impetigo Prurigo of pregnancy (PP) and herpetiformis) Pruritic follicultis of pregnancy (PFP) Clinical Presentation: Incidence: The atopic eruption of AEP commonly • most common dermatosis of starts at an earlier point in pregnancy pregnancy in the first or second trimester of the • Accounts for 50% of all pruritic first pregnancy. dermatoses of pregnancies Patients may have a family history of atopy Only 20% had had the lesions before Pathophysiology: they became pregnant • The condition is thought to be triggered by pregnancy and It has been reclassified to include refer to the specific diseases that previously were immunologic changes implied considered as separate entities: by the shift from Th1 production • eczema in pregnancy to Th2 production. • prurigo of pregnancy (PP) and • pruritic folliculitis of pregnancy (PFP) Eczematous type occurs in two- thirds of cases • Macculo-pappular erythematous, pruritic rash • affecting typical sites of atopic including • face, neck, and flexural surfaces. Pruritic folliculitis (PFP) • acneiform eruption consisting of multiple, pruritic, small follicular papules or pustules distributed on the back, arms, chest, and abdomen • More common in second trimester Prurigo of pregnancy is characterized • by pruritic and often excoriated papules and nodules • on the extensor surfaces of the legs and upper arms, and,frequently, on the abdomen • Can occur in all 3 trimesters Diagnosis: Clinical Treatment : Serology, histopathology, and immunoflorescence are not specific, Low- to midpotency topical and correlation with increased IgE is corticosteroids in combination with marginal, at best antihistamines (chlorpheniramine and diphenhydramine) Prognosis: AEP is a benign that resolves in the early post-partum period and does not carry any fetal risk. Prurigo may recur in subsequent pregnancies Incidence: 1:120-240 pregnancies • Second to eczema as the common causes of dermatosis in pregnancy Pathophysiology: Unclear hypothesis suggests that connective tissue damage caused by rapid weight gain and abnormal distention may play a role Clinical presentation: Hormonal and immunological Primigravid women with factors may play a role multiple gestations, during the last trimester Clinical Presentation: • Presents with severely pruritic urticarial papules that typically start on the abdomen within the striae and spread to the extremities. • These urticarial papules then often coalesce into plaques. • Periumbilical sparing is a classic finding • Spares face, palms and soles • The rash progresses to become • The rash resolves spontaneously more polymorphic, and vesicles about 4–6 weeks after initial and erythematous targetoid lesions onset. develop in approximately half of Differential diagnosis: cases. • Pemphigoid gestationis Diagnosis: Clinical Direct and indirect immunofluorescence studies are negative in PEP.

Treatment: • Control the pruritus and skin lesions with topical corticosteroids. • In severe cases, systemic corticosteroids are effective.

Prognosis: Does not typically recur in subsequent pregnancies Fetal risk: Nil Incidence: 1:10-50,000 pregnancies

Pathophysiology: Autoimmune disorder exclusive to pregnancy : NC16A placental antigen is presented to the maternal immune system by abnormally expressed HLAclass II molecules that trigger an immune response (IgG antibodies) against the NC16A domain of collagen

Clinical Presentation: Usually 2nd/ 3rd trimester Occasionally in 1st trimester or postpartum flare Clinical features : • intensely pruritic urticarial plaques and annular plaques in the periumbilical area, • followed by a vesicobullous eruption beginning centrally on the abdomen and spreading outwards to involve the extremities. • The palms, soles, back, and chest may be affected, however, involvement of the face and mucous membranes is rare. Bullae formation may occur anytime from a few days to many weeks after the onset of urticarial plaques. Diagnosis: Skin biopsy with Direct immunofluorescence (DIF) microscopy of a sample of perilesional skin can show tissue-bound immunoreactants. Linear deposition of the complement component protein C3 along the basement membrane zone Serum enzyme-linked immunosorbent assay (ELISA) studies are also helpful in diagnosis.

Differential Diagnosis: PUPPP, (PEP) erythema multiforme drug reactions Treatment:

Mild cases: topical steroids, antihistamines More severe cases : systemic steroids The steroids may be tapered with disease improvement but should be maintained at a sufficiently high dosage until birth to prevent a flare that commonly occurs around the time of delivery.

IVIg and cyclosporine in refractory cases Prognosis : Pemphigoid gestastionis tends to remit immediately postpartum, but some refractory cases require longer-term therapy Recurs in subsequent pregnancies May skip pregnancies (8% ) Flares with use of OCP (25%) Fetal Risk: Prematurity and small-for-gestational age (SGA) occur with greater frequency. Occasional vesicles and bullae are seen in newborn. Incidence: variable (common in Southeast Asia, South America, and Scandinavian countries) • 70 of every 10,000 pregnancies in the United States.

Pathophysiology: • multifactorial etiology involving genetics, hormones, diet, and underlying liver, biliary, or pancreatic conditions • the primary genes of interest are those that encode biliary proteins including ABCB4, ATP8B1, and ABCB11.31 Clinical Presentation: • usually occurs during the late second or third trimester and resolves after delivery. • characterized by severe pruritus without skin lesions all over the body, including the palms and soles • excoriations, erosions, and scabbing • pruritus is worse at night and will often precede any other physical or laboratory abnormalities • After delivery the pruritus resolves Cholestasis patients have a reduced ability to absorb fat-soluble vitamins Differential Diagnosis: (A,D and K). • Acute Fatty Liver of Pregnancy This may lead to Vitamin K deficiency. • Cholelithiasis There is a risk of maternal intra- or • Other Dermatitis postpartum hemorrhage • Hepatitis in Pregnancy • Preeclampsia Diagnosis: Clinical Raised Serum bile acids ( not available in Singapore) Transaminitis (usually not above 4 x normal) Hyperbilirbinemia (10-20%) Prognosis: Treatment: • Recurrence rate in subsequent pregnancies of up to 60% • Ursodeoxycholic acid • Cholelithiasis and cholesterol (UDCA)(15mg/kg) : reduces gallstones are increased in pruritis, decreases the biliary patients with ICP secretion of endogenous and • Avoid Oral Contraceptive pills toxic levels of bile acids, Fetal Risk: decrease the risk for harm to the • in 20–60% of cases • Vit K supplements • intrapartal Other drugs: cholestyramine, indicated by meconium stained • phenobarbital, and ultraviolet B in 20–30% of light, dexamethasone cases • Early delivery in severe cases • fetal death in 1–2% of cases. Incidence: Rare variant of generalized pustular psoriasis, 130 cases described to date

Pathophysiology: Unknown

Clinical Presentation: Typically third trimester Patients do not have a personal or family h/o prior psoriasis Lesions resolve postpartum PPP may recur with subsequent pregnancies with increased severity • constitutional symptoms are often PPP typically presents during noted including: • the third trimester with symmetric • malaise, fever, delirium, diarrhea, erythematous plaques studded with vomiting, and symptoms of tetany sterile pustules at the margins of • It is often associated with the plaques in a circinate pattern. hypocalcemia,leucocytosis and • The eruption tends to begin in raised ESR. flexural areas and spread centrifugally with new pustules at the margins while older central pustules dry with desquamative scale or crusts • Subungual pustules may lead to onycholysis • Mucous membranes including the esophagus may have erosive or exfoliative plaques Diagnosis: Clinical plus Skin biopsy : demonstrates spongiform pustules with neutrophils. Psoriasiform hyperplasia and parakeratosis can also be seen. Imunofluorescence is negative

Differentials: impetigo, dermatitis herpetiformis, and acute generalized exanthematous pustulosis

. Treatment: • Systemic corticosteroids: Prednisolone (max dose 60-80 mg/day) • Cyclosporine : 2-3 mg/kg may be used • Infliximab : safe in pregnancy

Prognosis: • Maternal prognosis is usually Fetal prognosis favorable with early treatment and is less predictable, even in close monitoring of serum calcium treated patients. levels to prevent sequelae of Intrauterine fetal demise, hypocalcemia such as seizures and , and neonatal tetany. death have all been reported Topical Steroids Antihistamines

Low potency: Hydrocortisone 0.5-1% • Chlorpheniramine Betamethasone valerate cream 0.025- 4 mg tds 0.1% Triamcinolone acetonide 0.025% • Loratidine 10 mg om Medium potency: • Cetrizine 10 mg om Triamcinolone acetonide 0.1% Mometasone 0.1% High potency : Clobetasol propionate 0.05% Betamethasone valerate ointment 0.1% Betamethasone dipropionate ointment/cream 0.05% Triamcinolone acetonide 0.5%

• Psoriasis: Course in pregnancy is variable Improves in 40 to 60 percent of women Worsens in 10 to 20 percent Remains stable in the remainder Flares in 50 percent of women postpartum Women should plan pregnancy when they are in remission Topical steroids, narrow band UVB phototherapy, cyclosporin and sulfasalazine can be used in pregnancy. • Eczema: variable • Malignant melanoma: tends to be activated (Any suspicious naevi should be referred for excision) • When in doubt of diagnosis (ie unsure that it is just PEP/Atopic eruption of pregnancy)

• When initial treatment fails

• When you see pustules/ bullae ( Pustular psoriasis or pemphigus gestationis) as biopsy is needed

• Flare of an underlying chronic dermatologic condition ( eczema/ psoriasis)

• Suspicion of drug allergy ( urticarial rash, mucosal lesions, vasculitic rash, haemorrhagic bullae) • Atopic eruptions (AEP) and Polymorphic eruptions of pregnancy (PEP) are the most common pregnancy related dermatoses that could be diagnosed clinically, treated with topical steroids and are not associated with maternal or fetal morbidity • Patients suspected of pemphigoid gestationis or pustular psoriasis should be referred for biopsy, confirm diagnosis and treatment. • Suspect Intrahepatic cholestasis of pregnancy in patients with extensive pruritus and no primary skin lesions. • Antenatal fetal monitoring would be needed for Pemphigus gestationis, intrahepatic cholestasis of pregnancy and pustular psoriasis of pregnancy. • Specific dermatoses of pregnancy and their treatment.Stephanie Lehroff et al,Dermatologic Therapy, Vol. 26, 2013, 274–284 • The skin disorders of pregnancy: A family physician’s guide. Matthew Bremmer et al,The Journal of family practice,feb 2010,Vol59,no 2,89-96 • Physiologic changes and dermatoses of pregnancy. Laurel Naversen Geraghty et al, International Journal of 2011, 50, 771–782 • Update on dermatoses of pregnancy.Emily Warshauer et al, International Journal of Dermatology 2013, 52, 6–13