Pregnancy-Associated "Cutaneous Type" Pemphigus Vulgaris

Pregnancy-Associated

 

Javier Rangel, MD

Perm J 2016 Winter;20(1):e101-e102

https://doi.org/10.7812/TPP/15-059

Abstract

The development of pemphigus, including pemphigus vulgaris (PV) and pemphigus foliaceus, during pregnancy is rare. PV manifests with mucosal and/or cutaneous erosions with flaccid bullae that are histologically characterized by suprabasilar acantholysis. In contrast, pemphigus foliaceus manifests with cutaneous-only involvement and superficial epidermal acantholysis. Enzyme-linked immunosorbent assay specific for autoantibodies against desmoglein 1 and desmoglein 3 aids in the diagnosis and differentiation between pemphigus subtypes. High-dose systemic corticosteroids are first-line agents in management of PV, yet their potential long-term use raises complex management issues associated with pregnancy and fetal risk. Here we report a rare case of cutaneous-limited PV in association with pregnancy.

Case Report

A 24-year-old woman, 15 weeks pregnant, presented to the Dermatology Clinic with a 1-month history of cutaneous erosions and blisters. The patient denied any prior skin disease and was otherwise well. Examination revealed crusted erosions, areas of denuded epidermis, and scattered flaccid and clear fluid-filled bullae (Figures 1A and 1B) confined to the trunk and extremities. Conjunctival, oral, and vaginal mucosae were spared. Histopathology demonstrated suprabasilar and intraepidermal acantholysis (Figures 2A and 2B), direct immunofluorescence showed intercellular deposition of complexes IgG and C3, and enzyme-linked immunosorbent assay1 detected desmoglein (Dsg) 1 and Dsg 3 at 65 units and 285 units, respectively. Indirect immunofluorescence of intact human skin and monkey esophagus demonstrated increased cell surface antibody titers at 1:1280 and 1:2560, respectively. Prednisone 30mg (0.75mg/kg) daily and high-potency topical steroids were started. At follow-up examination, the patient demonstrated rapid improvement with re-epithelialization of previously involved areas. A slow prednisone taper was continued throughout the antenatal period. Repeat serologies in the third trimester demonstrated Dsg 3 titers decreased to 88 units and Dsg 1 normalized to 13 units. At 36 weeks gestation, the patient delivered a healthy female infant without cutaneous involvement; however, umbilical cord blood enzyme-linked immunosorbent assay demonstrated elevated Dsg 3 at 28 units and normal Dsg 1 at 3 units. Several months postpartum, the patient continued to have active disease despite systemic steroids. A trial of rituximab was pursued as a steroid-sparing agent. At her last follow-up, the patient was in successful remission.

Pregnancy-Associated

Pregnancy-Associated

Discussion

Pemphigus is an immunobullous disease characterized by mucosal and/or cutaneous erosions and blisters associated with circulating anti-Dsg antibodies. Pemphigus developing in association with pregnancy is rare, with fewer than 50 published reports.2,3 Infants of mothers with pemphigus can have various outcomes, ranging from stillbirth to transient lesions,2,3 probably caused by transplacental crossover of pathogenic anti-Dsg antibodies. Adverse outcomes have been correlated with poor maternal disease control and higher Dsg antibody titers from maternal serum or umbilical cord blood.4 A recent review of treatments for autoimmune blistering disorders in pregnancy supports safe use of topical/systemic steroids and azathioprine. A few case reports suggest that rituximab, intravenous immunoglobulin, and dapsone may be safe as well.5 Fetal involvement is more common in pemphigus vulgaris (PV) than pemphigus foliaceus.4,5 This phenomenon may be explained by differing patterns of Dsg distribution in fetal versus adult epidermis, with Dsg 3 predominance throughout the fetal epidermis likely conferring protection from anti-Dsg 1 antibodies by the desmoglein compensation theory.4

Yoshida et al6 have proposed the term “cutaneous type” PV for this rare presentation without apparent mucosal involvement. The authors proposed that a combination of weak pathogenic anti-Dsg 3 and potent anti-Dsg 1 autoantibodies might explain the sites of blister formation in patients with cutaneous-only PV. In our case, a diagnosis of PV was established on the basis of histology, positive direct immunoflourescence, and elevated Dsg 1 and Dsg 3 serologies with higher Dsg 3 titers.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

References
1.    Zone JJ. The value of desmoglein 1 and 3 antibody ELISA testing in patients with pemphigus. Arch Dermatol 2009 May;145(5):585-7. DOI: https://doi.org/10.1001/archdermatol.2009.50.
2.    Bialynicki-Birula R, Dmochowski M, Maj J, Gornowicz-Porowska J. Pregnancy-triggered maternal pemphigus vulgaris with persistent gingival lesions. Acta Dermatovenerol Croat 2011;19(3):170-5.
3.    Kalayciyan A, Engin B, Serdaroglu S, Mat C,
Aydemir EH, Kotogyan A. A retrospective analysis of patients with pemphigus vulgaris associated with pregnancy. Br J Dermatol 2002 Aug;147(2):396-7. DOI: https://doi.org/10.1046/j.1365-2133.2002.48299.x.
4.    Goldberg NS, DeFeo C, Kirshenbaum N. Pemphigus vulgaris and pregnancy: risk factors and recommendations. J Am Acad Dermatol 1993 May;28(5 Pt 2):877-9. DOI: https://doi.org/10.1016/0190-9622(93)70123-B.
5.    Braunstein I, Werth V. Treatment of dermatologic connective tissue disease and autoimmune blistering disorders in pregnancy. Dermatol Ther 2013 Jul-Aug;26(4):354-63. DOI: https://doi.org/10.1111/dth.12076.
6.    Yoshida K, Takae Y, Saito H, et al. Cutaneous type pemphigus vulgaris: a rare clinical phenotype of pemphigus. J Am Acad Dermatol 2005 May;52(5):839-45. DOI: https://doi.org/10.1016/j.jaad.2005.01.106.

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