Full Text - Journal of IMAB

http://dx.doi.org/10.5272/jimab.2014206.552
Journal of IMAB
ISSN: 1312-773X
http://www.journal-imab-bg.org
Journal of IMAB - Annual Proceeding (Scientific Papers) 2014, vol. 20, issue 6
HERPES GESTATIONIS
Ivelina Yordanova 1 , Valentin Valtchev 1, Kossara Drenovska 2 , Dimitar K.
Gospodinov1, Snejina Vassileva2
1) Department of Dermatology and Venereology, Faculty of Medicine, Medical
University, Pleven, Bulgaria
2) Department of Dermatology and Venereology, Faculty of Medicine, Medical
University, Sofia, Bulgaria.
ABSTRACT
Herpes gestationis, also known as pemphigoid
gestationis (PG) is an extremely rare autoimmune bullous
dermatosis of the gestation and postpartum period. The disease was originally named herpes gestationis on the basis
of the morphological herpetiform feature of the blisters. We
report a 21-year-old woman, pregnant in the third trimester, who presented with a pruritic bullous cutaneous eruption of two weeks duration. The disease started with a red
plaque in the abdominal area accompanied by mild itching. Soonafter, blisters appeared and affected almost the
entire body. Physical examination revealed a primiparous
woman in good general state, pregnant in 36 weeks of gestation. The skin changes affected the abdomen, back of the
trunk, upper and lower extremities, hands and feet. They
were manifested by a polymorphous eruption, consisting
of erythematous urticaria-like plaques, small tense vesicles
and multiple excoriations. Mucous membranes were not affected. Routine laboratory examinations were within normal limits. Direct immunofluorescence (DIF) on
perilesional skin showed linear deposition of IgG (++) and
C3 (++) at the cutaneous basement membrane zone (BMZ).
Indirect immunofluorescence (IIF) on human esophagus
substrate revealed circulating IgG anti-BMZ antibodies at
a titer of 1:80. ELISABP180 NC16A was strongly positive.
The diagnosis of PG was confirmed and a treatment with
systemic methylprednisolone 60 mg/day was initiated, later
gradually tapered to 20 mg/day, together with topical
corticosteroids. As a result on the 10th day of the treatment
we already achieved significant improvement with reduction of erythema and itching, absence of new skin lesions.
The pregnancy ended in term with successful childbirth.
No flare of the skin disease was observed in the puerperal
period.
Key word: Pemphigoid gestationis, herpes gestationis, pregnancy, direct and indirect immunofluorescence,
methylprednisolone.
INTRODUCTION:
Herpes gestationis (HG), currently known as pemphigoid gestationis (PG), is a rare autoimmune blistering dermatosis of pregnancy with an incidence ranging up to 1:50
000 pregnancies.[1] The term PG was introduced by
Holmes and Black in 1982 and is largely used in Europe
but in the USA the former name HGis still preferred.[2, 3]
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PG typically affects pregnant women in the second or third
trimester but may appear at any time during pregnancy or
even during the immediate postpartum period.
CASE REPORT:
We present a 21-year-old woman pregnant in the third
trimester. The disease started two weeks before her admission in the Department of dermatology with red plaqueson
the abdominal skin, around the umbilicus, accompanied by
itching. Soonafter, blisters appeared on this background
and quickly spread to affect almost the entire body.
The physical examination revealed a woman in good
general condition, afebrile, pregnant at the 36 weeks of gestation. Cardiovascular and respiratory systems were without pathological changes - blood pressure 120/70 mmHg,
heart rate 80 beats/min. The neurological status was normal. The dermatological examination found pathological
skin changes affecting the skin of the abdomen, the back,
upper and lower extremities, hands and feet. The eruption
consisted of erythematous, urticaria-like plaques with small
tense vesicles upon them and multipleexcoriations. (Fig.
1a, b) The mucous membranes and skin appendages were
not affected. Routine laboratory investigations were within
normal limits. Histological examination of a biopsy specimen from a fresh vesicular lesion showed edema in the dermis, mixed perivascular inflammatory infiltrate with a predominance of eosinophils (Fig. 2). Direct immunofluorescence (DIF) on perilesional skin showed linear deposition
of IgG (++) and C3 (++) at the cutaneous basement membrane zone (BMZ) (Fig. 3). Indirect immunofluorescence
(IIF) on human esophagus substrate revealed circulating
IgG anti-BMZ antibodies at a titer of 1:80 (Fig. 4).
ELISABP180NC16A (ELISA kit, MBL, Nagoya, Japan) was
strongly positive - 88.2 U/ml (cut off <9 negative; ≥ 9 positive). Based on the data from the medical history, the clinical features and the results from the laboratory studies,the
diagnosis PG was confirmed. Treatment with systemic methylprednisolone 60 mg/daywas initiated, later gradually tapered to 20 mg/day, together with topical corticosteroids.
Significant improvement was achieved about the 10th day
of the treatment with reduction of erythema and itching and
absence of new skin lesions (Fig. 5a, b). The pregnancy
ended in term with successful childbirth. A healthy female
newborn with anthropometric parameters within the normal ranges was born. No flare of the skin disease was observed in the mother in the puerperal period.
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Fig. 2. Histopathology: A marked edema, with a
dense inflammatory infiltrate (predominantly with eosinophils) in the dermis.
Fig. 3. Direct immunofluorescence (DIF) on perilesional skin: linear deposition of IgG (++) and C3 (++) at
the cutaneous basement membrane zone (BMZ).
Fig. 4. Indirect immunofluorescence(IIF) on human
esophagus substrate: circulating IgG anti-BMZ antibodies
at a titer of 1:80.
Fig. 1a, b. Confluent urticaria-like plaques covered
with tense vesicules and excoriations on the abdomen and
back of the trunk.
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DISCUSSION:
PG is a self-limiting, autoimmune subepidermal bullous dermatosis of pregnancy. Its pathogenic mechanism remains unclear but is considered to result from lack of recognition of the fetoplacental unit by the maternal immune
system. This leads tosubsequent production of anti-placental antibodies. Similarly to bullous pemphigoid, the main
target antigen in PG is BP antigen II (also known as
BP180), in particular its non-collagenous 16A (NC16A)
domain, which is constituent of both the placenta and the
skin. The skin pathology in PG results from the ability of
the anti-placental antibodies to cross-react with the same
proteins of the skin.Blister formation results from a complex mechanism involving TH2lymphocytes, cytokines and
polymorphonuclear cells.[4, 5, 6] PG has also been reported
in association with MHC class II HLA antigens DR3 and
DR4.[1] The disease usually starts in the second or third
trimester of pregnancy and is characterized with an acute
onset of erythematous, urticarial papules and plaques that
progress to tense vesicles and blisters, followed bysevere
pruritus. The lesions usually arise on the abdomen, often
involving the umbilicus, and spread centrifugally. Recovery occurs generally in a few weeks after delivery but relapses are frequent in subsequent pregnancies.[7, 8] The diagnosis of PG relies on theappropriate clinical presentation,
the histologic findings of a subepidermal blistering and
linear C3 deposition along the BMZ, with or without deposition of IgG on DIF. ELISA BP180NC16A may be very
useful in such casesdue to its high sensitivity to detect circulating auto-antibodies against NC16A domain of BP180,
which is the major antigenic epitope in PG.[9]
The treatment of PG depends on the severity of the
disease. Mild cases may be treated with topical corticosteroids and oral antihistamines. Potent topical glucocorticoids and oral corticosteroids (prednisone 0.5-1 mg/kg/
day) are reserved for more serious cases.[1] Several cases
resistant to corticosteroid therapy have been described, but
successfully treated with intravenous immunoglobulin and
azathioprine or with adjuvant immunoadsorption.[10, 11,
12] Fetal prognosis is good, but early onset in 2nd trimester and blister formation are risk factors for prematurity and
low birth weight. Rarely the newborn may be affected by
very transitory blisters.[7]
In our case, clinical suspicion of PG was confirmed
by DIF and IIF findings, as well as by ELISA BP180NC16A,
the latter beingstrongly positive. Systemic treatment with
methylprednisolone (0,5mg/kg/day) was initiated during
the pregnancy with gradual clinical improvement until delivery. A healthy asymptomatic infant was born in term
without cutaneous lesions. To date the patient has not reported a flare.
Fig. 5a, b. 10 daysafter treatment with systemic
glucocorticosteroids: reduction of erythema and absence
of new skin eruptions.
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CONCLUSION
The presented case highlights the importance of a
timely clinical and immunohistological diagnosis of PG.
Differentiation of PG from other conditions like pruritic urticarial papules and plaques of pregnancy (PUPPP) is essential because management and outcomes differ. In casesin
which the clinical diagnosis is difficult, immunofluores-
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/ J of IMAB. 2014, vol. 20, issue 6 /
cence tests and ELISA studies for anti-BMZ antibodies are
useful in establishing the diagnosis. An interdisciplinary
approach is also of crucial importance for the benefit of
the mother and child during pregnancy, as well as during
the postpartum period.
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Please cite this article as: Yordanova I, Valtchev V, Drenovska K, Gospodinov DK, Vassileva S. Herpes gestationis.
J of IMAB. 2014 Oct-Dec;20(6):552-555. doi: http://dx.doi.org/10.5272/jimab.2014206.552
Received: 03/08/2014; Published online: 10/12/2014
Address for correspondence:
Ivelina Yordanova, PhD. MD, Assoc. Prof.
Department of Dermatology and Venereology, Faculty of Medicine, Medical
University, Pleven,
91, Gen. Vladimir Vazov str., 5800 Pleven, Bulgaria.
E-mail: [email protected],
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