19: Dermatoses of pregnancy

Jeff Shornick

Abstract:

Although many dermatologic conditions are affected by pregnancy, there are four predominant dermatoses that are unique to pregnancy. These are pemphigoid gestationis, polymorphic eruption of pregnancy, atopic eruption of pregnancy, and intrahepatic cholestasis of pregnancy. This chapter will review those dermatoses and their relevant mimickers.

Key terms:

pemphigoid gestationis

polymorphic eruption of pregnancy

atopic eruption of pregnancy

intrahepatic cholestasis of pregnancy

dermatoses of pregnancy

pregnancy

Chapter outline

Introduction
Pemphigoid Gestationis
Polymorphic Eruption of Pregnancy
Atopic Eruption of Pregnancy
Cholestasis of Pregnancy

Introduction

There are four accepted entities included in the dermatoses of pregnancy. They are pemphigoid gestationis (PG; also known as “herpes gestationis” or “gestational pemphigoid”); polymorphic eruption of pregnancy (PEP; also known as “pruritic urticarial papules and plaques of pregnancy” or “PUPPP”); atopic eruption of pregnancy (AEP); and intrahepatic cholestasis of pregnancy (ICP; also known as “obstetric cholestasis” or “jaundice of pregnancy”).

Nomenclature in this group is somewhat confusing because names and nomenclature have changed as understanding has evolved. Disagreement persists as to whether additional entities should be added (e.g., pustular psoriasis associated with pregnancy) or whether a given entity should be carved out as distinctive (e.g., whether or not pruritic folliculitis of pregnancy should be lumped into AEP). The best way to think about dermatoses of pregnancy is that PG, PEP, and cholestasis are all sufficiently defined to be clearly recognizable (although PEP awaits a defining biomarker), and AEP stands for everything else.

Such a classification admittedly leaves room for improvement, but that will not happen until we have a clearer understanding of mechanisms.

It is more likely that an itchy pregnant woman has something unrelated to pregnancy, such as scabies, than a specific dermatosis of pregnancy. Therefore the first differential step is always to decide whether the pregnancy is causative or coincidental.

Nearly all articles on the specific dermatoses of pregnancy include ICP, which is not really a dermatosis. ICP presents with pruritus and excoriations, but it is not really a specific dermatosis. ICP is included in the dermatoses of pregnancy because patients present with pruritus and a rash, but to the dermatologist’s eye, the rash is entirely secondary.

Some skin diseases may be worse during pregnancy (such as psoriasis and eczema herpeticum), but these are not considered among the dermatoses of pregnancy. Preexisting diseases that can be made better or worse by pregnancy are also not considered to be dermatoses of pregnancy.

Pemphigoid gestationis

Clinical features

PG is the most clinically distinct and histopathologically defined of the dermatoses of pregnancy. For patients with rash, PG is the diagnosis to exclude.

• PG is rare, occurring in approximately 1 out of every 50,000 pregnancies.
• It is mediated by an immunoglobulin (Ig)G with specificity for the 16th domain of the extracellular component of type XVII collagen (NC16A), also known as “BP180.”

• The antigen is demonstrable by direct immunofluorescence (DIF) in 100% of patients and by enzyme-linked immunosorbent assay (ELISA) to the NC16A antigen in over 90% of patients.

• It is thought that aberrant expression of this antigen in the placenta induces an immune response, and that the antibody then crossreacts with the skin.

• There are distinctive human leukocyte antigen associations in PG, strongly suggesting a genetic predisposition.
• PG typically develops during the second or third trimester, although explosive onset during the immediate postpartum period can occur in up to 25% of patients.
• First onset in the periumbilical area occurs in 50% of patients, but onset may also be on the palms, soles, or extremities.

• Facial involvement is uncommon and mucosal involvement is rare.
• The primary lesion ranges from intensely pruritic urticarial papules and plaques to tense, grouped (so-called “herpetiform”) blisters.

• Urticarial lesions without blisters can occur but are seen in fewer than 10% of cases.
• PG not infrequently improves or clears as the pregnancy progresses, but 75% of patients flare with delivery or during the immediate postpartum period, often dramatically so.
• Recurrence during use of oral contraceptives has been reported and recurrence during subsequent gestations is the rule, although skip pregnancies may occur.
• There is no increased maternal risk in PG.

• There is, however, an increased risk for premature delivery (32% before 38 weeks and 16% before 36 weeks) and a slightly increased risk for small-for-gestational-age births.

• Transient involvement in the newborn may be seen in up to 10% of cases.
• PG tends to improve over the weeks to months after delivery.

• Flares with menstruation or during use of oral contraceptives have been reported.
• Disease typically recurs during subsequent gestations, often with first onset earlier in pregnancy; however, skip pregnancies have been reported in up to 10% of cases.

Work-up

Referral to a dermatologist should be considered for work-up and treatment. A skin biopsy should be done for routine pathology and DIF.

• Histopathology usually shows an increase in eosinophils, often lined up along the dermoepidermal junction.
• DIF shows complement along the epidermal fragment of the basement membrane zone, with or without IgG. This finding is quite similar to that seen in bullous pemphigoid and is unique to the pregnancy rashes. It remains the defining characteristic of PG, occurring in 100% of cases.

Indirect immunofluorescence (IIF) is less reliable; however, ELISA for NC16A (BP180) is detectable in over 90% of cases, offering a reliable alternative to biopsy. Antibody titers do not correlate with the degree of skin involvement.

Antithyroid antibodies are increased, although their clinical relevance is unclear. Most patients are clinically euthyroid. On the other hand, the risk for subsequent autoimmune thyroid disease, especially Graves disease, is clearly increased in those with a history of PG, affecting about 10% of patients.

Differential diagnosis

The primary differential in PG is between PEP and a wide variety of diseases unrelated to pregnancy. Immunofluorescence or ELISA is the key to differentiating PG. Most typically, the relentless progression of unbearable itch associated with urticarial lesions, rapidly progressing to clustered, tense blisters, is characteristic of PG.

Initial steps in management

PG is rare; treatment guidelines are driven by expert opinion.

Because PG is not associated with significant maternal or fetal risk and because it tends to remit spontaneously postpartum, it is imperative not to create disproportionate risk from therapy.

• Topical steroids and antihistamines are rarely of benefit.
• Systemic steroids (prednisolone 0.25–0.5 mg/kg/d or prednisone 0.5–1 mg/kg/d) remain the treatment of choice.
• Many patients improve during the latter part of pregnancy, only to flare at the time of delivery. Because profound flares at delivery are common, one should be prepared to initiate or increase steroids during the immediate postpartum period.