ARTICLE
Herpes gestationis (HG) is a rare, autoimmune, bullous dermatosis of
pregnancy which usually resolves within 3 months after delivery [1]. It
is defined by the demonstration of autoantibody directed to a hemidesmosomal
180 kDa BP antigen (BPA) [2]. However, no information is available on
the time course of the antibody titer in HG serum after delivery or abortion.
We observed the change in antibody titer against the 180 kDa BPA before
and after abortion in a case of HG by using immunoblot analysis.
Case report
A 32-year-old woman in the sixth week of her third pregnancy was admitted
to the Ohgaki Municipal Hospital on May 8, 1995. No skin eruption had
been observed during the previous two pregnancies. One week before admission,
she noticed a few papules without vesicles on the breast and abdomen.
Five weeks later, in spite of topical steroid (betamethasone valerate)
treatment, skin lesions extended to the extremities forming a number of
egg-sized areas of erythema with vesicles (Fig.
1). There was no mucous membrane involvement. A biopsy specimen
from the erythematous lesion with vesicles demonstrated a subepidermal
bulla accompanied by numerous eosinophils (Fig.
2). Direct immunofluorescence study (IF) revealed the linear deposition
of C3, but neither IgG nor C4 at the basement membrane zone (BMZ) (Fig.
3). Indirect IF was positive at the BMZ for IgG only using normal
human skin as a substrate and the so-
called HG factor was negative. Laboratory biochemical data were all within
the normal range except eosinophilia (692/mm3, 7%).
Although topical steroid treatment and oral
administration of ketotifen fumarate (2 mg/day) were given for 5 weeks,
the lesions became worse with severe itching. Oral administration of prednisolone
(20 mg/day) alone for 2 weeks following these treatments was also ineffective.
However, the lesions improved within two weeks after elective abortion
on July 27, 1995. We could not check whether the fetus also had the same
skin eruption. After the blisters had disappeared, the dose of prednisolone
was gradually reduced to 5 mg every other day. Indirect IF showed positive
staining at the BMZ until October 14, 1995. The titer was 1:16 on June
9, July 14, August 8, August 29 and October 14, 1995. However, the serum
obtained on January 31 and April 12, 1996 did not react with the epidermis.
Immunoblot analysis using epidermal extracts as a substrate [3] showed
the presence of IgG antibody against a 180 kDa protein in her serum on
August 8, October 14, 1995 but not in that taken on January 31 and on
April 12, 1996 (Fig. 4).
This 180 kDa protein was considered to be the 180 kDa BPA, because the
BP-serum and monoclonal antibody to the 180 kDa BPA reacted with the same
peptide as examined by the concurrent immunoblot analysis. On the other
hand, the immunoblot analysis proved negative in all samples using dermal
extracts.
Discussion
Clinical features, histopathologic findings, and immunoblot analyses
results in our case were typical of herpes gestationis. It is considered
that the average duration postpartum is 4 weeks for bullous eruptions
and 60 weeks for the urticarial lesions [4]. In addition, the average
duration of the blistering disease is 12 weeks after the first involved
pregnancy and 31 weeks after the second. A few patients show disease activity
postpartum for a longer time. However two HG patients have been
reported; one patient had been suffered from eruptions for 11 years postpartum
[5], and the other patient had eruptions for 12 years until she died of
metastatic rectal carcinoma [6]. Neither had received treatment. In our
case, the skin eruptions gradually improved after the abortion but the
antibody titer did not change for at least 2 months. Holmes et al.
[6] suggested that a titer of a HG factor greater than 1:8 in immunofluorescence
(IF) indicates the possibility of prolonged postpartum disease.
The eruptions in our case were not prolonged, probably because HG factor
was not detected and the titer was 1:16 in indirect IF for IgG binding
to the BMZ.
Recurrence of the skin lesion and postpartum
flare-up may indicate the persistent presence of circulating autoantibodies
[7]. There is no study showing the antibody titers to the 180 kDa BPA
for a longer duration postpartum or after abortion. We performed
IF and immunoblot analysis for 9 months after the abortion. The antibody
to 180 kDa BPA was detected in the patient's serum for at least 2 months
but not 6 months after the abortion as shown by both immunoblotting and
indirect IF studies. It took at least 2 months for the antibody against
180 kDa BPA in the patient's serum to decrease to an undetectable level.
This fact might be due to a higher sensitivity of immunoblotting and indirect
IF studies enough to detect the minimum titers which can not cause blistering.
Alternatively, there is a possibility that there are additional factors
apart from 180 kDa BPA which may contribute to blister formation in HG.
Immunoblot analysis has demonstrated the presence of circulating IgG
autoantibodies in 89% of cases of HG, mainly of the IgG1 subclass, which
reacts with an antigen of 180 kDa [8]. This 180 kDa epidermal protein,
which is considered to be the 180 kDa BPA; hemidesmosomal component, has
been suggested to be the antigen detected by the HG factor [6], although
there are a few reports showing that some patients' serum samples bind
to a 220 kDa protein [9, 10] or a 200 kDa protein [11]. The 180 kDa BPA
was detected in our patient's serum by immunoblotting, but the HG factor
was not. Since a similar case has been recently reported, this fact can
be attributed to the greater sensitivity of immunoblotting as compared
with the indirect complement fixation IF technique. Kelly et al.
[12] reported that HG factor is an IgG1 antibody with inferred complement
binding capacity. Alternatively, although we did not perform IF using
IgG subclass antibodies, IgG4 without binding capacity might be involved.
The Fc portion of the BP-IgG was found to be crucial in mediating epidermal
injury in the mouse BP model [13].
With respect to the pathomechanisms for blister formation in BP, although
several studies have suggested that binding of BP autoantibodies to the
BMZ may be followed by complement activation, it is also postulated that
the binding of BP-IgG to the NC16A domain of 180 kDa BPA can cause the
internalization of the antigen from its pool at the lateral/apical cell
membranes into the cell. This causes the perturbation of the supply of
180 kDa BPA to the hemidesmosome formation at the basal membrane [14-16].
However, further studies will be necessary to more precisely clarify the
exact mechanisms of epidermal blister formation in BP and HG patients
[12, 13, 17].
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