Question 5 of 16

(demo test)

This patient has pemphigoid gestationis (PG): note the herpetiform vesiculobullous eruption which appears independent of abdominal striae and involves the umbilicus.

PG is an inflammatory dermatologic disorder of pregnancy that generally presents in the 2nd or 3rd trimester or immediately after giving birth. Clinically, patients present with a blistering rash that generally starts in the periumbilical region but can ultimately include skin of the entire body. Patients may also develop painful, erythematous plaques. This then progresses to a herpetiform vesiculobullous eruption like the one pictured in this patient. 

Its underlying cause is the development of IgG1 autoantibodies that target the transmembrane hemidesmosomal collagen, BP180 (NC16A segment). It is a Type II hypersensitivity reaction and direct immunofluorescence (DIF) demonstrates linear C3 deposition along the basement membrane zone in 100% of patients. Liner IgG is seen in only ~30% of patients. The development of autoantibodies may be due to cross-reactivity between placental tissue and skin. 

Of note, BPAG2 (BP180; collagen XVII) is also targeted by autoantibodies in patients with bullous pemphigoid, mucous membrane pemphigoid (cicatricial), and linear IgA bullous dermatosis (LABD). (Schmidt et al. Adv Dermatol 2000)

Additional important information about pemphigoid gestationis:

• There is an increased risk of premature birth and small for gestational age (SGA) births, and the risk correlates with the severity of disease.
• The disease may flare abruptly at the time of delivery and is likely to recur with subsequent pregnancy, menstruation, or with oral contraception use.
• Patients with a history of pemphigoid gestationis are at increased risk for developing Graves’ disease.
• Newborns may develop skin involvement related to the passive transfer of maternal antibodies and this resolves spontaneously.
• The differential diagnosis includes polymorphic eruption of pregnancy (formerly PUPPP). Polymorphic eruption of pregnancy commonly affects the striae with sparing of the periumbilical area .
  
• Systemic corticosteroids are the mainstay of therapy.

The other pregnancy dermatosis that needs to be considered in this case is polymorphic eruption of pregnancy (PEP). PEP was formerly referred to as pruritic urticarial papules and plaques of pregnancy or PUPPP. 

PEP is the most common dermatosis of pregnancy. Clinical features include pruritic urticarial papules and plaques that first appear within the striae distensae and spare the umbilicus. The eruption spreads to involve the trunk and extremities, but tends to spare the face, palms, and soles. In contrast to PEP, PG tends to occur earlier in gestation, appears independent of abdominal striae, and often involve the umbilicus. The eruption often evolves over time and becomes more polymorphic and may include the following morphologies: wheels, diffuse erythema, eczematous, vesicular, targetoid, etc. (Maglie et al. G Ital Dermatol Venereol 2018)

PEP is benign and self-limited with no risk to the mother or fetus. It is most common in primiparous females in the latter 3^rd trimester, but may also occur postpartum. It is also more common in multiple gestation pregnancies. It is unlikely to recur in subsequent pregnancies (possibly related to the development of immune tolerance).

The pathogenesis of PEP is unknown. However, several hypotheses have been proposed including the following:

• Rapid stretching and tearing of the dermis exposes dermal antigens, eliciting an allergic-type reaction
• Peripheral chimerism (deposition of fetal DNA), that mostly occurs during the 3^rd trimester and favors areas of damaged collagen and increased vascularity increases immune reactivity
• High levels of progesterone (as is seen in multiple gestation pregnancies) and increased progesterone receptor immunoreactivity
• Placental hormonal-type substance induces fibroblast proliferation in maternal skin

PEP typically responds to topical corticosteroids (pregnancy category C) and oral antihistamines (chlorpheniramine safe) and spontaneously resolves within a month of delivery. (Chouk et al. StatPearls 2019)

Clinical Pearl: Pemphigoid gestationis (PG) is an inflammatory dermatologic disorder of pregnancy that generally presents in the 2nd or 3rd trimester or immediately after giving birth. There is an increased risk of premature birth and small for gestational age (SGA) births, and the risk correlates with the severity of disease. It may flare abruptly at the time of delivery and is likely to recur with subsequent pregnancy, menstruation, or with oral contraception use. Systemic corticosteroids are the mainstay of therapy.

Other references:

(Maglie et al. G Ital Dermatol Venereol 2018)

(Cohen et al. J Dermatol Treat 2018)

Photos courtesy of: 

Tarek Shaath, MD @ DermEducate