Basics
Description
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 herpetiformis
- Rare pustular disorder; may be variant of pustular psoriasis; also called "generalized pustular psoriasis of pregnancy "
- Papular dermatoses
- Prurigo, pruritic folliculitis, and atopic eruption of pregnancy (AEP)
- Intrahepatic cholestasis of pregnancy (ICP)
- Rare pregnancy-related liver disorder
- Also called "cholestasis of pregnancy, " "recurrent/idiopathic jaundice of pregnancy, " and "pruritus/icterus gravidarum "
Epidemiology
- Pemphigoid gestationis
- Incidence: 1 in 50,000 pregnancies in North America (some reports as high as 1 in 1,700)
- Polymorphic eruption of pregnancy
- Incidence: 1:160 to 1:240 pregnancies
- Most common dermatosis of pregnancy
- Impetigo herpetiformis
- Incidence: Unknown; ¢ ¼200 reported cases
- Papular dermatoses
- Incidence: Prurigo of pregnancy: 1 in 300 pregnancies; pruritic folliculitis of pregnancy: 1 in 3,000 pregnancies
- Prevalence: Among pruritic dermatoses of pregnancy, AEP has a prevalence of 50%
- Intrahepatic cholestasis of pregnancy
- Prevalence: 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 gestationis
- Genetic predisposition: More common in women with HLA-DR3 or HLA-DR4 positivity
- Hormonal fluctuation implicated in flares
- Polymorphic eruption of pregnancy
- Primigravida status (80% cases)
- Controversial: Male fetus, atopy, multiple-gestation pregnancy (twins or triplets)
- Impetigo herpetiformis
- No personal/family history of psoriasis
- Papular dermatoses
- Prurigo of pregnancy: Atopy (controversial)
- Pruritic folliculitis of pregnancy: Unknown
- AEP: Personal or family history of atopy
- Intrahepatic cholestasis of pregnancy
- Genetic predisposition: (+) Family history in ¢ ¼50%
- Multiple-gestation pregnancy
Etiology
- Pemphigoid gestationis
- AI 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 pregnancy
- Unknown. 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 skin
- Possible hormonal role, link with atopy
- Impetigo herpetiformis
- Unknown; debate as to whether it is a form of pustular psoriasis or a separate entity.
- Inconsistently implicated: High levels of progesterone, hypocalcemia
- Papular dermatoses
- Prurigo of pregnancy: Unknown
- Role of atopic diathesis implicated. Some consider a subset of PEP or AEP.
- Pruritic folliculitis of pregnancy
- Maternal androgens inconsistently implicated
- Atopic eruption of pregnancy
- Genetic predisposition (nearly 100% with personal or first-degree relative with atopy)
- Intrahepatic cholestasis of pregnancy
- Unclear, thought to be multifactorial
- Genetic 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-pruritic
- Often with constitutional symptoms (fever/chills, nausea/vomiting, malaise)
- No known parity, multiple-gestation, autoimmunity or atopy associations
- Papular dermatoses
- Prurigo of pregnancy " typically at 25 " 30 weeks, but reported in all 3 trimesters
- Possible associated atopy (no parity, multiple-gestation, AI disease association)
- Pruritic folliculitis of pregnancy
- Late second or third trimester; no associations
- AEP " 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 pregnancy
- Third 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 gestationis
- Abrupt 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 pregnancy
- Begins 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 herpetiformis
- Erythematous 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 dermatoses
- Prurigo of pregnancy
- Erythematous 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 pregnancy
- Small (3 " 5 mm) erythematous papules on upper trunk. Becomes generalized with follicular, erythematous papules/pustules.
- AEP
- Prurigo and eczema-like lesions
- May have features of atopic dermatitis (xerosis, ichthyosis, hyperlinear palms, keratosis pilaris).
- Intrahepatic cholestasis of pregnancy
- No primary lesions; secondary lesions (e.g., excoriations, lichenification) from scratching
- Jaundice 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 transaminases
- Total 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 response
- Once 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-limited
- General 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 prognosis
- 15 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 gestationis
- Course: 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 pregnancy
- Course: Rapid, spontaneous resolution post-partum, often within 4 " 6 weeks. Rarely recurs.
- Risk: No maternal or fetal risk. No cutaneous manifestations in newborn.
- Impetigo herpetiformis
- Course: 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 dermatoses
- All three typically resolve spontaneously at or shortly after delivery and may recur with subsequent pregnancies.
- No maternal, fetal, or neonatal risks
- Intrahepatic cholestasis of pregnancy
- Course: 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.