Clinical Challenge: Pregnant Woman With Intense Pruritus - MPR

Clinical Challenge: Pregnant Woman With Intense Pruritus

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A 21-year-old pregnant woman presents at 28-weeks’ gestation with intense pruritus and blisters that began on her abdomen. Her medical history is significant for type 1 diabetes mellitus, which was diagnosed at 12 years of age; she is currently taking insulin and prenatal vitamins. Physical examination reveals red plaques and papules on her abdomen, affecting the periumbilical area, as well as on her thorax, arms, legs, and back. Several lesions contain blisters of various size.  No lesions are found on her head, neck, or mucosa. A diagnostic biopsy is performed.

Histologic examination of the biopsy revealed a subepidermal blister containing eosinophils and a mixed perivascular infiltrate. Direct immunofluorescence demonstrated linear deposition of complement C3 along the basement membrane zone BMZ, confirming the suspected diagnosis of pemphigoid gestationis (PG), formerly called...

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Histologic examination of the biopsy revealed a subepidermal blister containing eosinophils and a mixed perivascular infiltrate. Direct immunofluorescence demonstrated linear deposition of complement C3 along the basement membrane zone BMZ, confirming the suspected diagnosis of pemphigoid gestationis (PG), formerly called herpes gestationis.

PG is part of a family of pemphigoid disorders, a group of autoimmune blistering conditions that are caused by an immune response against a different hemidesmosomal protein of the epidermal BMZ.1 PG is a rare disorder that is unique to pregnancy, affecting approximately 1 in 50,000 pregnancies.2,3 Although it may develop any time during pregnancy, PG most commonly presents in the second or third trimester.3 Clinical improvement is often noted shortly before delivery; a flare may happen soon after delivery and then resolves within 6 months postpartum in the majority of cases.3,4

The pathogenesis of PG is affected by genetic and hormonal factors. In normal pregnancies, there is a state of homeostasis between the mother and fetus, whereby the mother tolerates the genetically and immunologically different fetal tissue.3 Women who develop PG have abnormal placental expression of human leukocyte antigens (HLA)-DR3 and DR4 genotypes; this combined with aberrant presentation of collagen XVII trigger activation of the mother’s immune system.4,5 Placental proteins previously tolerated are subsequently recognized as foreign resulting in the production of anti-placental immunoglobulin G (IgG) autoantibodies that cross-react with proteins present in the mother’s skin.4

Clinical and histologic findings of PG depend on the stage of the disease. Early lesions are characterized by intense pruritus with polymorphic or urticarial papules and plaques that may develop vesicles and bullae as the disease evolves.Characteristically, lesions originate in the periumbilical region then extend outward to the trunk and extremities. The face and mucous membranes are classically spared.

Biopsy of an early lesion will show dermal edema with perivascular infiltrates of lymphocytes and eosinophils.Subsequently, an eosinophilic spongiosis develops that evolves into clinical blisters that are subepidermal histologically. Eosinophils are present within the blister fluid and a mixed perivascular infiltrate of eosinophils and lymphocytes persists in the dermis.3

The diagnosis of PG is confirmed by identification of linear C3 deposition along the BMZ by direct immunofluorescence. Between 25% and 50% of patients also have IgG deposition along the BMZ.The diagnosis can also be made by identifying, and even quantifying, the circulating anti-BP180 autoantibodies via indirect immunofluorescence using an enzyme-linked immunosorbent assay (ELISA). Several reports claim that serum autoantibodies levels parallel disease activity.3,6

Hormonal fluctuations during pregnancy typically affect the course of PG. Progesterone levels that are elevated in the last few weeks of pregnancy can notably depress antibody production; conversely, higher estrogen levels enhance antibody production.4 Progesterone also exhibits an immunosuppressive effect and may inhibit or modify PG.4 These effects could explain why PG usually improves just before delivery, followed by an immediate postpartum flare as progesterone levels return to normal.3

Most cases of PG are self-limited, resolving postpartum, without scarring. However, it may recur in subsequent pregnancies, with the use of oral contraceptives, or with menstrual cycles.4 In rare cases, PG may persist for years, transforming to bullous pemphigoid.5 Although autoimmune in nature, PG is not significantly associated with the development of other autoimmune conditions, except for Grave’s disease, which occurs in approximately 10% of patients with PG.4

In most cases of PG there is no risk for pregnancy loss, but complications include prematurity and small gestational age because of immunologically mediated placental insufficiency.5 Transient neonatal blistering is observed in up to 10% of newborns, a result of passive transfer of maternal IgG.4,5

Pruritus is common in pregnancy. A common pregnancy-associated skin condition that mimics PG is polymorphic eruption of pregnancy (PEP), previously called pruritic papules and plaques of pregnancy (PUPP). PEP presents similarly, but instead of starting in the periumbilical area, it begins within the striae of the thighs or abdomen and does not blister. In comparison to PG, PEP does not pose any maternal or fetal risks, resolves within 10 days of childbirth, and is not expected to recur in subsequent pregnancies.5 Furthermore, there is no antibody or complement deposition in PEP.

The mainstay of treatment for PG is symptomatic control of pruritus. This can be attained with topical corticosteroids and antihistamines. More severe cases may require systemic steroids and refractory cases may require intravenous immunoglobulin therapy (IVIG).  Postpartum persistent cases may need cyclosporine, azathioprine, or dapsone.3

The patient in this case was successfully treated with low-dose prednisone while carefully monitoring her blood sugars.  Steroids could be tapered shortly after the delivery of a full-term, well-developed baby boy.

Urmila Sivagnanalingam, BS, MSc, is a medical student at Virginia Commonwealth University in Richmond, Virginia. Julia R. Nunley, MD, is a professor of dermatology at the Medical College of Virginia Hospitals, Virginia Commonwealth University in Richmond, Virginia.

References

  1. Sadik CD, Lima AL, Zillikens D. Pemphigoid gestationis: Toward a better understanding of the etiopathogenesisClin Dermatol. 2016;34(3):378-382. doi:10.1016/j.clindermatol.2016.02.010
  2. Bechtel MA. Pruritus in pregnancy and its managementDermatol Clin. 2018;36(3):259-265. doi:10.1016/j.det.2018.02.012
  3. Intong LR, Murrell DF. Pemphigoid gestationis: pathogenesis and clinical featuresDermatol Clin. 2011;29(3):447-ix. doi:10.1016/j.det.2011.03.002
  4. Semkova K, Black M. Pemphigoid gestationis: current insights into pathogenesis and treatment. Eur J Obstet Gynecol Reprod Biol. 2009;145(2):138-144. doi:10.1016/j.ejogrb.2009.05.012
  5. Warshafsky C, Tron VA, Robertson D, Kives S. Pemphigoid gestationis: A case presentationJ Cutan Med Surg. 2018;22(4):435-438. doi:10.1177/1203475418760459
  6. Barnadas MA, Rubiales MV, González MJ, et al. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence testing in a bullous pemphigoid and pemphigoid gestationisInt J Dermatol. 2008;47(12):1245-1249. doi:10.1111/j.1365-4632.2008.03824.x

This article originally appeared on Clinical Advisor