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Pregnancy, Dermatoses

Basics

Description

- Pemphigoid gestationis - Genetic predisposition: More common in women with HLA-DR3 or HLA-DR4 positivity - Hormonal fluctuation implicated in flares

- Intrahepatic cholestasis of pregnancy - Unclear, thought to be multifactorial - Genetic predisposition, hormonal factors, environmental and/or dietary factors

There are 5 dermatoses considered specific to pregnancy. All tend to occur later in pregnancy and to resolve postpartum.

  • Pemphigoid gestationis (PG) " Also called "herpes gestationis "Rare autoimmune (AI) blistering disorder that is intensely pruritic; resembles bullous pemphigoid clinically and histologically
  • Polymorphic eruption of pregnancy (PEP)Pruritic papulo-urticarial inflammatory disorder; also called "pruritic urticarial papules and plaques of pregnancy " (PUPPP)
  • Impetigo herpetiformisRare pustular disorder; may be variant of pustular psoriasis; also called "generalized pustular psoriasis of pregnancy "
  • Papular dermatosesPrurigo, pruritic folliculitis, and atopic eruption of pregnancy (AEP)
  • Intrahepatic cholestasis of pregnancy (ICP)Rare pregnancy-related liver disorderAlso called "cholestasis of pregnancy, " "recurrent/idiopathic jaundice of pregnancy, " and "pruritus/icterus gravidarum "

Epidemiology

  • Pemphigoid gestationisIncidence: 1 in 50,000 pregnancies in North America (some reports as high as 1 in 1,700)
  • Polymorphic eruption of pregnancyIncidence: 1:160 to 1:240 pregnanciesMost common dermatosis of pregnancy
  • Impetigo herpetiformisIncidence: Unknown; ¢ ¼200 reported cases
  • Papular dermatosesIncidence: Prurigo of pregnancy: 1 in 300 pregnancies; pruritic folliculitis of pregnancy: 1 in 3,000 pregnanciesPrevalence: Among pruritic dermatoses of pregnancy, AEP has a prevalence of 50%
  • Intrahepatic cholestasis of pregnancyPrevalence: Higher prevalence in South America (28% among Araucanian Indian in Chile; 9% in Bolivia), Scandinavia (2.4%)Lower prevalence in North America, Australia, and Europe (0.1 " 1.5%)

Risk Factors

  • Pemphigoid gestationisGenetic predisposition: More common in women with HLA-DR3 or HLA-DR4 positivityHormonal fluctuation implicated in flares
  • Polymorphic eruption of pregnancyPrimigravida status (80% cases)Controversial: Male fetus, atopy, multiple-gestation pregnancy (twins or triplets)
  • Impetigo herpetiformisNo personal/family history of psoriasis
  • Papular dermatosesPrurigo of pregnancy: Atopy (controversial)Pruritic folliculitis of pregnancy: UnknownAEP: Personal or family history of atopy
  • Intrahepatic cholestasis of pregnancyGenetic predisposition: (+) Family history in ¢ ¼50%Multiple-gestation pregnancy

Etiology

  • Pemphigoid gestationisAI disorder in genetically predisposed pts, possibly triggered by hormonal factors.Autoantibody targets component of basement membrane; immune complex deposition results in complement-mediated destruction of basement membrane and subepidermal blister formation.
  • Polymorphic eruption of pregnancyUnknown. Theories include:Maternal immunoreactivity: Abdominal distention causes damage to collagen within striae, triggering an inflammatory response.Fetal cell microchimerism: Migration and persistence of fetal cells in maternal skinPossible hormonal role, link with atopy
  • Impetigo herpetiformisUnknown; debate as to whether it is a form of pustular psoriasis or a separate entity.Inconsistently implicated: High levels of progesterone, hypocalcemia
  • Papular dermatosesPrurigo of pregnancy: UnknownRole of atopic diathesis implicated. Some consider a subset of PEP or AEP.Pruritic folliculitis of pregnancyMaternal androgens inconsistently implicatedAtopic eruption of pregnancyGenetic predisposition (nearly 100% with personal or first-degree relative with atopy)
  • Intrahepatic cholestasis of pregnancyUnclear, thought to be multifactorialGenetic predisposition, hormonal factors, environmental and/or dietary factors

Diagnosis

History

All pregnancy dermatoses are pruritic, with the exception of impetigo herpetiformis.

  • Questions to ask: Gestational age at onset, parity, personal/family history of dermatoses in pregnancy, AI diseases, atopy
  • Pemphigoid gestationis " Typically second or third trimester (34% of patients each trimester, respectively); can also occur during first trimester (18%) or postpartum (14%).Often associated with AI diseases. Reported with trophoblastic tumors, hydatiform moles, choriocarcinoma. No association with parity, multiple-gestation pregnancy, or atopy.
  • Polymorphic eruption of pregnancy " typically late third trimester; can occur postpartum (15%) or late second trimester (rare).Often with first pregnancy, multiple-gestation pregnancies, personal/family history atopy (no association with AI diseases)
  • Impetigo herpetiformis " typically second half of pregnancy (most commonly third trimester), but can occur in first trimester or postpartum.Typically NON-pruriticOften with constitutional symptoms (fever/chills, nausea/vomiting, malaise)No known parity, multiple-gestation, autoimmunity or atopy associations
  • Papular dermatosesPrurigo of pregnancy " typically at 25 " 30 weeks, but reported in all 3 trimestersPossible associated atopy (no parity, multiple-gestation, AI disease association)Pruritic folliculitis of pregnancyLate second or third trimester; no associationsAEP " typically before third trimester (75%)80% with atopic skin changes for first time during pregnancy; 20% with exacerbation of preexisting atopic dermatitis.Strong association with personal/family history of atopy (no association with parity, multiple-gestation, other AI diseases).
  • Intrahepatic cholestasis of pregnancyThird trimester; associated with multiple-gestation pregnancy (no association with parity, autoimmunity, or atopy)Pruritus starts on palms/soles then becomes generalized, persistent, pruritus " worse at night. +/ " mild GI symptoms.

Physical Exam

  • Pemphigoid gestationisAbrupt onset of intensely pruritic urticarial papules/plaques (50% begin on abdomen, adjacent or within umbilicus); may become targetoid/polycyclic and spread centrifugally.Rapidly progresses to generalized tense fluid-filled bullae (>5 mm) in days to weeks.Face, mucous membranes, striae spared
  • Polymorphic eruption of pregnancyBegins with intensely pruritic urticarial papules within/adjacent to abdominal striae, which coalescence into urticarial plaques.50% progress to develop polymorphous features, including pseudovesiculation over striae or urticarial lesions, targetoid lesions, annular/polycyclic wheals, or small bullae only rarely (due to coalescing vesicles).Note: Face, palms and soles, periumbilical skin classically (but not always) spared
  • Impetigo herpetiformisErythematous plaques with small, clustered pustules ( "herpetiform " distribution) studding margins. As plaques expand outward, pustules remain on leading edge, leaving central eroded/crusted central plaques.Face, hands, feet spared (rarely involves mucous membranes, esophagus, nail beds)
  • Papular dermatosesPrurigo of pregnancyErythematous papules and nodules on extensor surfaces of limbs and/or trunk. Can become polymorphic with crusted, excoriated, eczematous lesions; occasionally follicular papules (not blisters).Pruritic folliculitis of pregnancySmall (3 " 5 mm) erythematous papules on upper trunk. Becomes generalized with follicular, erythematous papules/pustules.AEPPrurigo and eczema-like lesionsMay have features of atopic dermatitis (xerosis, ichthyosis, hyperlinear palms, keratosis pilaris).
  • Intrahepatic cholestasis of pregnancyNo primary lesions; secondary lesions (e.g., excoriations, lichenification) from scratchingJaundice in 10% of cases

Tests

  • Specific tests to confirm diagnosis of PG, impetigo herpetiformis, and ICP
  • Diagnosis of other types of pregnancy dermatoses based only on clinical criteria
  • 2 skin biopsies " lesional and peri-lesional " used to confirm diagnosis of PG and impetigo herpetiformis.
  • Serum bile acids and transaminasesTotal bile acids >11 mmol/L in absence of primary skin lesions is diagnostic for ICP.Check transaminases in any pregnant female with pruritus

Differential Diagnosis

  • Above pregnancy-specific dermatoses
  • Other bullous AI diseases: Bullous lupus, linear IgA dermatosis, bullous pemphigoid
  • Contact dermatitis (bullous or eczematous)
  • Infestations such as scabies
  • Dermatoses unrelated to pregnancy
  • Other skin or internal causes of pruritus

Treatment

Pemphigoid Gestationis

First Line

  • Prednisone (1,2)[C] " response in few days; 20 " 40 mg/day titrated to clinical responseOnce blister formation suppressed, taper (5 " 10 mg/day) or discontinue (2)[C].Some increase dose prior to delivery to prevent anticipated postpartum flare (2)[C].No evidence that any treatment can prevent fetal risks associated with PG, which seem milder than previously thought (2)[C].Prednisone relatively safe, but avoid dexamethasone/betamethasone (2)[C].Most advocate against early delivery because fetal risks appear mild (2)[C].If neonate affected, local wound care (1,2)[C].Breastfeeding may decrease duration (1)[C].

Polymorphic Eruption of Pregnancy

First Line

  • Symptomatic treatment (1,2,3)[C] and reassurance that self-limitedGeneral measures: Emollients on wet skin, antipruritic topical agents (menthol-containing)Mid-potency topical steroid ointment, first-generation oral antihistamines

Second Line

  • Oral prednisone; phototherapy (2)[C]

Impetigo Herpetiformis

First Line

  • Oral prednisone: Initiate at 15 " 40 mg/day; can increase to 60 " 80 mg/day (1,3)[C]

Second-Line

Other

  • Monitor and treat hypocalcemia to prevent tetany or seizures (1)[C]. After delivery, consider agents used in psoriasis as anticipate flare with steroid tapering (1)[C].

Papular Dermatoses

Prurigo of Pregnancy

First Line

  • Symptomatic relief (1,2)[C]General measures (emollients on wet skin)Moderately potent topical steroids (can be intralesional or under occlusion)Oral antihistamines that are safe in gestation

Second Line

  • Phototherapy (UVB) (2)[C]Rarely a short course of oral prednisone may be necessary if recalcitrant pruritus

Pruritic Folliculitis of Pregnancy

First Line

  • Benzoyl peroxide (pregnancy category C), mild-to-moderate topical steroids, topical antipruritic medications (e.g., menthol-containing)

Atopic Eruption of Pregnancy

First Line

  • Topical antipruritic agents (menthol-containing), mild-to-moderate topical steroids

Second Line

  • Oral antihistamines, prednisone, or phototherapy for more severe cases

Intrahepatic Cholestasis of Pregnancy

  • Goal: Decrease bile acid levels in order to sustain pregnancy and diminish prevalence of fetal risks and maternal symptoms

First Line

  • Ursodeoxycholic acid (1,2,3)[A]Only treatment to decrease maternal pruritus and improve fetal prognosis; off-label despite unquestionable positive effect on fetal prognosis15 mg/kg/day (or 1 g/day independent of body weight) (1)[C]

Second Line

  • Other antipruritic drugs (cholestyramine, dexamethasone, antihistamines, anion exchange resins, S-adenosylmethionine)

Other

  • Monitor bilirubin and transaminases. Possible induction of labor at 36 weeks per obstetrician (1,2)[C]

Issues for Referral

  • To dermatologist for definitive diagnosis
  • To obstetrician or obstetric medicine internist

Ongoing Care

Prognosis

  • Pemphigoid gestationisCourse: Variable course; alternating exacerbations with remissions during pregnancy. 50 " 75% flare at delivery. Self-limited; spontaneously remits weeks to months after delivery without therapy. Recurrences postpartum associated with menses (up to 18 months) or oral contraceptives (OCPs) (20 " 50%) common. Recurs during subsequent pregnancies with earlier onset and increased severity (5 " 8% skip pregnancies).Maternal risk: Increased risk of Graves ' (10%)Fetal risk: Increased risk of premature delivery and small-for-gestational age; borderline increase in spontaneous abortions. Secondary to mild placental insufficiency; debate regarding cause (disease vs. corticosteroids). Risk not reduced with treatment.Neonate risk: 10% with cutaneous symptoms; typically mild, resolves in days to weeks. Increased risk for skin infections. Risk for adrenal insufficiency if mother with high/long courses of systemic steroids.
  • Polymorphic eruption of pregnancyCourse: Rapid, spontaneous resolution post-partum, often within 4 " 6 weeks. Rarely recurs.Risk: No maternal or fetal risk. No cutaneous manifestations in newborn.
  • Impetigo herpetiformisCourse: Typically resolves postpartum. May recur in subsequent pregnancies.Maternal risk: None; good prognosis even if severe.Fetal risk: Extent of fetal risk is somewhat controversial. Risks include stillbirth, neonatal death, fetal abnormalities; mainly due to placental insufficiency. Risks not reduced with successful control of maternal disease with systemic steroids.Neonate risk: No cutaneous manifestations
  • Papular dermatosesAll three typically resolve spontaneously at or shortly after delivery and may recur with subsequent pregnancies.No maternal, fetal, or neonatal risks
  • Intrahepatic cholestasis of pregnancyCourse: Resolve within 1 " 2 days to up to 1 " 2 weeks postpartum. Possible recurrence in subsequent pregnancies or with OCP use.Maternal risk: Good prognosis; increased risk of cholelithiasis.Fetal risk: High prevalence of impaired fetal prognosis " premature delivery with increased rate of cesarean section and meconium staining, intrauterine fetal distress, stillbirth. Disease severity correlates with fetal prognosis. No risk for fetal malformation.Neonate risk: High-risk antepartal fetal hemorrhage with concomitant extrahepatic cholestasis, vitamin K deficiency.

References

1Roth M. Pregnancy dermatoses: Diagnosis, management, and controversies. Am J Clin Dermatol. 2011;12(1):25 " 41. [View Abstract]2Kroumpouzos G. Specific dermatoses of pregnancy: Advances and controversies. Expert Rev Dermatol. 2010;5(6):633 " 648.3Tunzi M, Gray G. Common skin conditions during pregnancy. Am Fam Physician. 2007;75(2):211 " 218. [View Abstract]

Additional Reading

1Chin CC, Wang SH, Kirtsching G. Systemic review of the safety of topical corticosteroids in pregnancy. J Am Acad Dermatol. 2010;62(4):694 " 705.

Codes

ICD9

  • 054.10 Genital herpes, unspecified
  • 646.80 Other specified complications of pregnancy, unspecified as to episode of care or not applicable
  • 692.9 Contact dermatitis and other eczema, unspecified cause
  • 696.1 Other psoriasis
  • 691.8 Other atopic dermatitis and related conditions
  • 704.8 Other specified diseases of hair and hair follicles
  • 646.70 Liver and biliary tract disorders in pregnancy, unspecified as to episode of care or not applicable
  • 576.8 Other specified disorders of biliary tract

ICD10

  • L40.1 Generalized pustular psoriasis
  • O26.40 Herpes gestationis, unspecified trimester
  • O26.86 Pruritic urticarial papules and plaques of pregnancy (PUPPP)
  • L28.2 Other prurigo
  • L73.9 Follicular disorder, unspecified
  • O26.619 Liver and biliary tract disord in pregnancy, unsp trimester
  • K83.1 Obstruction of bile duct

SNOMED

  • 239101008 pregnancy eruption (disorder)
  • 86081009 Herpes gestationis (disorder)
  • 88697005 papular dermatitis of pregnancy (disorder)
  • 200973000 pustular psoriasis (disorder)
  • 239103006 prurigo of pregnancy (disorder)
  • 239104000 pruritic folliculitis of pregnancy (disorder)
  • 235888006 cholestasis of pregnancy (disorder)

Clinical Pearls

  • Pruritus is the leading symptom in most dermatoses of pregnancy and should be investigated and treated.