Clinical Review & Education

JAMA Dermatology Clinicopathological Challenge

Papulovesicular Eruption in a Pregnant Woman

With Darier Disease
Carolyn Stull, BS; Niraj Butala, MD; Warren R. Heymann, MD

A Clinical image

B Original magnification ×100 C Original magnification ×100

Figure. A, Confluent erythema with papulovesicles on the neck and face. B and C, Histopathological images,
hematoxylin-eosin. B, Full-thickness epidermal necrosis with focal areas of suprabasal acantholysis with corp ronds, corp
grains, and parakeratosis. C, Multinucleated cells with nuclear molding and margination.

A primigravida woman in her 30s at 35 weeks’ gestation and with a

WHAT IS YOUR DIAGNOSIS?
history of Darier disease was admitted with an acute, painful eruption
on her face and neck. She reported no history of pregnancy-related com- A. Kaposi varicelliform eruption
plications. Physical examination revealed confluent erythema with kera-
totic papulovesicles distributed on the face and neck (Figure, A). Honey- B. Impetigo

colored crusts were present on the left ear and preauricular area. The
C. Pemphigoid gestationis
chest and inframammary area displayed occasional red, crusted pap-
ules. Laboratory tests revealed an elevated white blood cell count of D. Impetigo herpetiformis
17.18 × 103 μL (reference range, 4.50-11.00 × 103 μL). A shave biopsy
specimen and tissue culture were obtained from the center of an um-
bilicated papule on the neck (Figure, B and C).

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 Clinical Review & Education JAMA Dermatology Clinicopathological Challenge

Diagnosis
A. Kaposi varicelliform eruption
Microscopic Finding and Clinical Course
Histopathological examination revealed full-thickness epidermal ne-
crosis with nuclear molding, margination of chromatin, and multi-
nucleation of cells in areas affected by herpes simplex virus (HSV).
Features of Darier disease, including suprabasal acantholysis with
corps ronds and corps grains and parakeratosis, were also present.
Immunohistochemical stain for HSV 1 and 2 showed positive nuclear
staining, confirming the presence of HSV infection. Serologic test-
ing was positive for HSV-1 IgG. Tissue culture produced few Staphy-
lococcus aureus and few coagulase negative staphylococci. The pa-
tient was treated with oral clindamycin, 300 mg, every 6 hours and
intravenous acyclovir, 5mg/kg, every 8 hours for 10 days. She was
subsequently switched to oral valacyclovir, 2000 mg, twice daily for
14 days. A prophylactic dose of valacyclovir, 500 mg twice daily, was
continued for the duration of the pregnancy. She delivered a healthy
infant at term with no evidence of infection.
Discussion
Darier disease is an autosomal dominant genodermatosis charac-
terized by abnormal keratinization of skin, nails, and mucosal sur-
faces. The pathogenesis of Darier disease involves mutations in
ATP2A2, which encodes a sarcoplasmic reticulum calcium-ATPase
pump that normally maintains low levels of intracellular calcium. Clini-
cally, patients with Darier disease present in adolescence with greasy,
hyperkeratotic papules coalescing into plaques along seborrheic
surfaces. Heat, perspiration, and UV light exposure are common
exacerbating factors.
Kaposi varicelliform eruption (KVE) is a diffuse viral infection
typically caused by HSV type 1 or 2 (eczema herpeticum), or other
viruses, such as Coxsackie (eczema Coxsackium) or Vaccinia (ec-
zema vaccinatum), occurring within lesions of a preexisting skin dis-
ease. KVE is most commonly seen in patients with atopic dermati-
tis but has also been reported in association with a number of
acantholytic, papulosquamous, and autoimmune bullous
dermatoses.1,2 Patients with Darier disease are susceptible to KVE
for reasons that remain unclear. The current accepted pathogenic
theory is that defects in cell-mediated immunity and skin barrier dys-
function predispose these patients to secondary infection.3
Characteristically, patients with KVE present with clusters of
monomorphic papulovesicles that progress to painful, hemor-
rhagic, crusted, punched-out erosions. The eruption is accompa-
nied by fever and regional lymphadenopathy and is classically
confined to areas of active skin disease. The head, neck, and
chest are the most commonly affected regions. Ocular involve-
ment may occur, and should be considered an ophthalmologic
emergency.4
Prompt initiation of antiviral therapy is advised with clinical sus-
picion of KVE. High-dose intravenous acyclovir is the treatment of
choice for severe cases, while oral valacyclovir may be appropriate
for milder cases not requiring hospitalization. Antibacterial prophy-
laxis is also recommended.
Reports of KVE in the context of pregnancy, especially during
the third trimester, are rare and raise interesting questions regard-
ing the risk of maternal-fetal transmission and optimal manage-
ment of such cases. Historically, early recognition and treatment have
resulted in healthy deliveries at term without evidence of neonatal
infection.5,6 However, 1 reported case7 of KVE with delayed presen-
tation in the third trimester resulted in initiation of preterm labor and
delivery with subsequent neonatal infection. In patients with a his-
tory of genital HSV, prophylactic acyclovir beginning at 36 weeks’
gestation has been shown to reduce clinical HSV recurrence at
delivery.8 While there is insufficient evidence to support or refute
such measures in pregnant patients with a history of KVE, consid-
eration of prophylactic therapy seems prudent. Although avoid-
ance of vaginal delivery and proceeding with a cesarean delivery has
clear benefits in patients with active genital HSV infections, the use
of this procedure in patients with disseminated cutaneous infec-
tions remains unclear.
This case highlights the importance of considering KVE in pa-
tients with predisposing comorbidities and emphasizes treatment
considerations in pregnancy. Prompt diagnosis allows for early and
appropriate management and the optimization of maternal and fe-
tal outcomes.

ARTICLE INFORMATION
Author Affiliations: Lewis Katz School of Medicine,
Temple University, Philadelphia, Pennsylvania
(Stull); Division of Dermatology, Cooper Medical
School, Rowan University, Camden, New Jersey
(Butala, Heymann); Department of Dermatology,
Perelman School of Medicine at the University of
Pennsylvania, Philadelphia (Heymann).
Corresponding Author: Warren R. Heymann, MD,
Division of Dermatology, Cooper Medical School of
Rowan University, 100 Brick Rd, Ste 306, Marlton,
NJ 08053 (wrheymann@gmail.com).
Published Online: November 30, 2016.
doi:10.1001/jamadermatol.2016.4189
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank Miriam
Enriquez, MD, Cooper Medical School of Rowan
University, for her contributions in obtaining the
histologic images. No financial compensation was
provided.
Self-assessment Credit: This article is eligible for
journal-based self-assessment (1 credit) for
Maintenance of Certification (MOC) from the
American Board of Dermatology (ABD). After
completion of an activity, please log on to the ABD
website at www.abderm.org to register your
credits. This may be done after each exercise or
after accumulating many credits.
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