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Year : 2012  |  Volume : 78  |  Issue : 2  |  Page : 199-201

A case of herpes gestationis: Follow-up study of autoantibodies using enzyme-linked immunosorbent assay and immunoblotting

Shunpei Fukuda, Norito Ishii, Takahiro Hamada, Bungo Ohyama, Naoya Momosaki, Tadashi Karashima, Takekuni Nakama, Daisuke Tsuruta, Takashi Hashimoto 
 Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan

Correspondence Address:
Takashi Hashimoto
Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology 67 Asahimachi, Kurume, Fukuoka, 830-0011
Japan




How to cite this article:
Fukuda S, Ishii N, Hamada T, Ohyama B, Momosaki N, Karashima T, Nakama T, Tsuruta D, Hashimoto T. A case of herpes gestationis: Follow-up study of autoantibodies using enzyme-linked immunosorbent assay and immunoblotting.Indian J Dermatol Venereol Leprol 2012;78:199-201


How to cite this URL:
Fukuda S, Ishii N, Hamada T, Ohyama B, Momosaki N, Karashima T, Nakama T, Tsuruta D, Hashimoto T. A case of herpes gestationis: Follow-up study of autoantibodies using enzyme-linked immunosorbent assay and immunoblotting. Indian J Dermatol Venereol Leprol [serial online] 2012 [cited 2019 Nov 17 ];78:199-201
Available from: http://www.ijdvl.com/text.asp?2012/78/2/199/93646


Full Text

Sir,

Herpes gestationis (HG) is a rare autoimmune-mediated bullous disease that occurs during pregnancy and post partum, and may exacerbate after delivery. [1] IgG autoantibodies in HG bind to the 16 th noncollagenous domain (NC16a) of bullous pemphigoid antigen 180 (BP180), which is also recognized by bullous pemphigoid (BP). [2] We herein present a case of HG in which we examined the correlation among the results of enzyme-linked immunosorbent assay (ELISA), immunoblotting and disease activity along the time course.

A 27-year-old Japanese female in the 36 th week of her first pregnancy had a pruritic infiltrative erythema on the extremities. After delivery in the 38 th week of her pregnancy, she developed widespread infiltrative erythema with small tense vesicles on the extremities and back [Figure 1]a. The patient also showed pruritic vesicles on the palms and soles, resembling dyshidrosis. The skin of her newborn baby was normal. A skin biopsy specimen taken from a lesion on the thigh revealed subepidermal blisters with perivascular eosinophilic and lymphocytic inflammatory infiltrate [Figure 1]b. Direct immunofluorescence of the perilesional skin showed linear IgG and C3 deposits along the basement membrane zone (BMZ) [Figure 1]c. Indirect and complement immunofluorescence using normal human skin as a substrate revealed circulating IgG anti-BMZ autoantibodies at a titer of 1:10. Indirect and complement immunofluorescence of the normal human skin split by 1 mol/L NaCl showed positive reaction (1:10) on the epidermal side of the split for IgG antibodies and C3 [Figure 1]d. Immunoblotting using normal human epidermal extract revealed IgG antibodies to BP180 (data not shown). Immunoblotting using the recombinant protein of BP180 NC16a demonstrated that circulating IgG antibodies reacted with this protein. The BP180 ELISA index was positive (index: 79.42). These clinical and immunologic features lead us to the diagnosis of HG.{Figure 1}

Initial treatment with topical steroid for a week was not effective. At that time, antihistamine was not added because the patient refused to take it. Subsequently, a combination therapy with topical steroid and oral antihistamine (the patient agreed to take this) was started, and this modality was effective: new vesicles discontinued to develop and eruptions resolved gradually. At the 50 th day after delivery, the patient went into remission. The BP180 ELISA index decreased along with the improvement of skin lesions (index: 41.09 at the 50 th day after delivery), and became negative (index: 5.79) at the 120 th day after delivery [Figure 2]a. On indirect immunofluorescence, the antibody titer gradually turned negative over the course of the improvement of skin lesions (IgG anti-BMZ antibody titer on indirect immunofluorescence using normal human skin became negative at the 21 st day after delivery, while that on indirect immunofluorescence using salt-split skin was still positive at a titer of 1:10 at the 21 st day after delivery, but became negative at the 50 th day after delivery). On immunoblotting, IgG antibodies against the BP180NC16a recombinant protein were clearly detected at the 5 th , 12 th and 50 th days after delivery but were not detected at the 120 th day after delivery [Figure 2]b.{Figure 2}

HG is a rare autoimmune bullous disease typically characterized by the onset of pruritic vesiculobullous lesions during the latter period of pregnancy or the puerperium. The onset of HG is usually in the second or third trimester, but could also be in the first trimester. Exacerbation with delivery occurs in 75-80% of HG cases. [1] To date, there is no therapeutical consensus for HG. Mild cases of HG are usually treated with topical steroids in combination with antihistamines. Refractory HG cases have been successfully treated by systemic steroids, cyclosporine, intravenous immunoglobulin or plasmapheresis.

Several studies demonstrated that the BP180 ELISA titer was a sensitive monitoring measurement of disease activity in BP patients. [3] Recently, the ELISA titers of antibodies to BP180 NC16a were reported to fluctuate in parallel with the disease activity in HG patients. [4] In our patient, the BP180 ELISA scores also correlated with the disease activity. To further verify the ELISA results, we also performed immunoblotting of BP180 NC16a recombinant protein, which was a prototype method before the development of BP180 ELISA. [5] The immunoblotting clearly showed positive reactivity at the 5 th , 12 th and 50 th day after delivery, which disappeared completely at the 120 th day after delivery. Thus, results of both ELISA and immunoblotting correlated well with the disease activity along the disease course.

In summary, we present a case of HG in which the disease activity correlated well with anti-BP180 antibody levels measured by ELISA. We suggest that BP180 NC16a ELISA is a useful tool for monitoring the disease activity not only in BP but also in HG.

References

1Shornick JK. Herpes gestationis. J Am Acad Dermatol 1987;17:539-56.
2Giudice GJ, Emery DJ, Zelickson BD, Anhalt GJ, Liu Z, Diaz LA. Bullous pemphigoid and herpes gestationis autoantibodies recognize a common non-collagenous site on the BP180 ectodomain. J Immunol 1993;151:5742-50.
3Kobayashi M, Amagai M, Kuroda-Kinoshita K, Hashimoto T, Shirakata Y, Hashimoto K, et al. BP180 ELISA using bacterial recombinant NC16a protein as a diagnostic and monitoring tool for bullous pemphigoid. J Dermatol Sci 2002;30:224-32.
4Sitaru C, Powell J, Messer G, Bröcker EB, Wojnarowska F, Zillikens D. Immunoblotting and enzyme-linked immunosorbent assay for the diagnosis of pamphigoid gestationis. Obstet Gynecol 2004;103:757-63.
5Matsumura K, Amagai M, Nishikawa T, Hashimoto T. The majority of bullous pemphigoid and herpes gestationis serum samples react with the NC16a domain of the 180-kDa bullous pemphigoid antyigen. Arch Dermatol Res 1996;288:507-9.

 

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