Clinical and Experimental Dermatology 1992; 17: 443-445.
Pemphigoid gestationis—response to chemical oophorectomy with goserehn M.P.GARVEY, S.E.HANDFIELD-JONES* AND St Thomas's Hospital, London SEI 7EH, UK
St John's Dermatology Centre,
Accepted for publication 20 January 1992
Summary
Pemphigoid gestationis is a rare bullous disorder affectmg 1 in 50000 pregnancies.' Systemic steroids have heen the mainstay of therapy sinee the initial report of their use by Lindemann et al. in i952.^ Topicai steroids are rareiy usefui. The use of dapsone gives generaiiy discouraging resuits.'-^ Gold and methotrexate were each ineffective in a singie ease reported by Fine and Omura.^ Piasmaphere.sis has been reported as extremely usefui on two occasions,'-'' but its u.se is limited hy iogistics and expense. The disease is known to be hormone sensitive: 20-50% of women with the disease who use the orai contraceptive deveiop an exacerbation.' Exacerbations have been noted with both oestrogens and progestogens. As our patient suffered from persisting disease with premenstruai flares, the iogical treatment was to try oophorectomy. Reversibie 'chemieai' oophorectomy using the new depot preparation of LHRH anaiogue seemed most appropriate.
The vesicuiar eruption recurred a short time iater when her generai practitioner prescribed the orai contraceptive. The eruption persisted for 30 months until the contraceptive pili was diseontinued. In 1980, during her second pregnancy, the eruption flared at 8 weeks gestation and persisted until she had a spontaneous abortion at 16 weeks. The disease remained in remission untii the 12th week of her third pregnancy in 1981, when she suffered from a severe reiapse. During this flare she was seen by a dermatoiogist and the diagnosis of pemphigoid gestationis was made. Her skin biopsy showed subepidermai buiiae. Direet immunofiuorescence showed bright iinear, basement-membrane zone fluorescence, with C3 and to a iesser extent with IgG. Indirect immunofluorescenee using the Cj showed basement-membrane zone staining to a titre of 1 in 64 on intact skin, and 1 in 254 on split skin. Blood tests inciuding fufl blood count, iiver, renai and thyroid function were normai. Systemic steroids were commenced at this time in i981, and she remained on prednisoione in doses varying from 20 to 80 mg/day, untii she was admitted to hospitai in January for re-investigation. On admission to hospital she had a Cushingoid appearance and had an extensive urticariai rash on her trunk and iimbs (Fig. i). Biisters were seen both on normai skin and on edges of the urticariai iesions. Skin biopsies were repeated and confirmed the eariier histoiogicai and immunofluorescent features of pemphigoid gestationis.
Case report
Treatment and progress
This 46-year-old Caucasian femaie had a i7-year history of pemphigoid gestationis which was unremitting for 10 years since her last pregnancy in 1981. The eruption began in 1973 during her first pregnancy. Peri-umbilicai pruritic vesicies occurred at 32 weeks gestation and resoived spontaneously at 36 weeks. The disease flared 24 h post-partum and lasted for 5 weeks.
Chemical oophorectomy was achieved using a once monthly subcutaneous depot injection of 3 6 mg goserelin. Seriai measurements of her l'SH, LH and oestradioi leveis confirmed chemieai oophorectomy had oecurred and she deveioped amenorrhoea (Fig. 2). Within 3 months of initiating therapy with gosereiin the eruption started to improve. The dose of prednisoione was graduaiiy reduced and eventuaiiy discontinued after
A 46-year-old Caucasian female presented in January 1991 with a 17-year history of severe pemphigoid gestationis. She had been on systemic steroids for 10 years since her last pregnancy in 1981 and required doses of 2080 mg prednisolone daily to eontrol her disease. A chemicai oophorectomy was induced using a new iutenizing hormone reieasing hormone (LHRH) analogue known as goserelin. A complete remission occurred within 6 months of initiating this treatment and the systemie steroids were discontinued.
* To whom correspondence shouid be addressed.
443
444
M.P.GARVEY, S.E.HANDFIELD-JONES AND M.M.BLACK Discussion Gosereiin is a new LHRH anaiogue, avaiiabie as a depot preparation of 3-6 mg for subcutaneous administration once monthiy. A singie dose of 36 mg gosereiin wiii suppress iutenizing hormone secretion for 5 weeks.'^ It is used mainiy in the treatment of prostatic carcinoma. Other LHRH anaiogues, e.g. busereiin have been used in treatment of endometriosis, uterine fibroids and poiycystic ovarian disease.'' Naturai LHRH stimuiates the synthesis and secretion of LH and FSH from the pituitary giand. These in turn stimuiate the synthesis and reiease of gonadai steroids in both sexes. The pituitary response to LHRH varies with dosage, frequency of administration and duration of exposure. Gosereiin is a superactive anaiogue of LHRH and has a ionger duration of action. By persistent binding to the pituitary receptors, it can, at monthiy dose frequeney, produce a paradoxicai inhibitory effeet on gonadai function. However, like aii LHRH anaiogues, gosereiin possesses agonist activity and so there is an initiai surge in FSH and LH and consequentiy oestradioi levels during the first 2 weeks on initiating treatment,'' however, there was no evidence of this in our patient. Regular monthly injections maintain constant pituitary suppression of FSH and LH release. The treatment with LHRH anaiogues seems to be without major side-effects in the short-term, other than those reiated to low oestrogen leveis, e.g. hotflushes.**The subcutaneous injection into the anterior abdominai wall is simpie and virtually painless.^ In treatment with LHRH analogues ovarian function and fertility is preserved upon cessation of treatment.'"" Still uncertain is the rate and degree of loss of bone mineral, and the effect on lipid metabolism of proionged LHRH analogue treatment. We conciude that a trial of reversible 'chemical' oophorectomy using goserelin in patients with prolonged pemphigoid gestationis may be a valuable treatment in the future.
Figure L Showing extensive urtication and excoriated bullae.
500
400 _ Plasma 300 _ Oestradioi (pmol/l) 200 100 _
Disease activity
References
Prednisolone
0
1
2
3
4
5
6
7
Time from slari of gosereiin treatment (months)
Figure 2. Graph showing fall in plasma oestradioi levels, disease activity and prednisolone dosage following the start of goserelin therapy.
6 months. The pemphigoid gestationis is in complete remission now and she remains on her monthly subcutaneous injection of goserelin. She suffers from mild hot flushes.
1. Shornick JK, Bangert JL, Freeman RG, Gillam JN, Herpes Gestationis: clinical and histological features of 28 czscs. Journal of the American Academy of Dermatotogy 1983; 8: 214-224. 2. Lindemann C, Engstrom WW, Flynn RT. Herpes Gestationis: Results of treatment with adrenocorticotrophic hormone and cortisone. American Journat of Obstetrics and Gynecotogy 1952; 63: 167-170,
3. Holmes R, Black MM, Williamson DM, Scutt RWB. Herpes Gestationis and bullous pemphigoid. A disease spectrum. British Journal of Dermatology 1980; 103: 533-541. 4. Fine JD, Omura EF. Herpes Gestationis, Persistent disease activity 11 years post partum. Archives of Dermatology 1985; 121: 924-926, 5. Van de Weil A, Hart HC, Flinterman J, Kerckhaert JA, Du Boeuff JA, Immof JW. Plasma exchange in Herpes Gestationis. British Medical Journal 1980; 281: 1041-1042,
PEMPHIGOID GESTATIONIS
445
6, Carruthers JA, Ewins AR. Herpes Gestationis: Studies on the L.H.R.H. analogues in gynecology: a review. British Journal of hmding cbaracteristics, activity, and pathogenic significance of Obstetrics and Gynaecology 1986; 93: 431-454, the complement fixing factor, Clinieal and Experimental Immuno- 10, Leniay A, Maheux R, Faure N, Jean C, Fazehas A, Reversible logy 1978; 31: 38-44. hypogonadism induced by L.H.R.H, agonist (Busereiin) as a new 7, Holmes RC, Black MM, Jurecka W et al. Clues to the aetioiogy therapeutic approach to endometriosis. Eertility and Sterility and pathogenesis of Herpes Gestationis, British Journal of 1984; 41: 863-871, Dermatology 1983; 109: 131-139, 11. Franssen AMHW et al. Endometriosis: Treatment with gonado8, Thomas E, Jenkins J, Lcnton E, Cook I, Fndocrine effects of tropin—releasing hormone agonist Busereiin, Eertility and SteriGoserelin. British .Medical Journal 1986; 293: 1407-1408, lity 1989; 51: 401. 9, McLachlan RI, Healy DL, Burger HG. Clinical aspects of
Pemphigoid gestationis—response to chemical oophorectomy with goserehn M.P.GARVEY, S.E.HANDFIELD-JONES* AND St Thomas's Hospital, London SEI 7EH, UK
St John's Dermatology Centre,
Accepted for publication 20 January 1992
Summary
Pemphigoid gestationis is a rare bullous disorder affectmg 1 in 50000 pregnancies.' Systemic steroids have heen the mainstay of therapy sinee the initial report of their use by Lindemann et al. in i952.^ Topicai steroids are rareiy usefui. The use of dapsone gives generaiiy discouraging resuits.'-^ Gold and methotrexate were each ineffective in a singie ease reported by Fine and Omura.^ Piasmaphere.sis has been reported as extremely usefui on two occasions,'-'' but its u.se is limited hy iogistics and expense. The disease is known to be hormone sensitive: 20-50% of women with the disease who use the orai contraceptive deveiop an exacerbation.' Exacerbations have been noted with both oestrogens and progestogens. As our patient suffered from persisting disease with premenstruai flares, the iogical treatment was to try oophorectomy. Reversibie 'chemieai' oophorectomy using the new depot preparation of LHRH anaiogue seemed most appropriate.
The vesicuiar eruption recurred a short time iater when her generai practitioner prescribed the orai contraceptive. The eruption persisted for 30 months until the contraceptive pili was diseontinued. In 1980, during her second pregnancy, the eruption flared at 8 weeks gestation and persisted until she had a spontaneous abortion at 16 weeks. The disease remained in remission untii the 12th week of her third pregnancy in 1981, when she suffered from a severe reiapse. During this flare she was seen by a dermatoiogist and the diagnosis of pemphigoid gestationis was made. Her skin biopsy showed subepidermai buiiae. Direet immunofiuorescence showed bright iinear, basement-membrane zone fluorescence, with C3 and to a iesser extent with IgG. Indirect immunofluorescenee using the Cj showed basement-membrane zone staining to a titre of 1 in 64 on intact skin, and 1 in 254 on split skin. Blood tests inciuding fufl blood count, iiver, renai and thyroid function were normai. Systemic steroids were commenced at this time in i981, and she remained on prednisoione in doses varying from 20 to 80 mg/day, untii she was admitted to hospitai in January for re-investigation. On admission to hospital she had a Cushingoid appearance and had an extensive urticariai rash on her trunk and iimbs (Fig. i). Biisters were seen both on normai skin and on edges of the urticariai iesions. Skin biopsies were repeated and confirmed the eariier histoiogicai and immunofluorescent features of pemphigoid gestationis.
Case report
Treatment and progress
This 46-year-old Caucasian femaie had a i7-year history of pemphigoid gestationis which was unremitting for 10 years since her last pregnancy in 1981. The eruption began in 1973 during her first pregnancy. Peri-umbilicai pruritic vesicies occurred at 32 weeks gestation and resoived spontaneously at 36 weeks. The disease flared 24 h post-partum and lasted for 5 weeks.
Chemical oophorectomy was achieved using a once monthly subcutaneous depot injection of 3 6 mg goserelin. Seriai measurements of her l'SH, LH and oestradioi leveis confirmed chemieai oophorectomy had oecurred and she deveioped amenorrhoea (Fig. 2). Within 3 months of initiating therapy with gosereiin the eruption started to improve. The dose of prednisoione was graduaiiy reduced and eventuaiiy discontinued after
A 46-year-old Caucasian female presented in January 1991 with a 17-year history of severe pemphigoid gestationis. She had been on systemic steroids for 10 years since her last pregnancy in 1981 and required doses of 2080 mg prednisolone daily to eontrol her disease. A chemicai oophorectomy was induced using a new iutenizing hormone reieasing hormone (LHRH) analogue known as goserelin. A complete remission occurred within 6 months of initiating this treatment and the systemie steroids were discontinued.
* To whom correspondence shouid be addressed.
443
444
M.P.GARVEY, S.E.HANDFIELD-JONES AND M.M.BLACK Discussion Gosereiin is a new LHRH anaiogue, avaiiabie as a depot preparation of 3-6 mg for subcutaneous administration once monthiy. A singie dose of 36 mg gosereiin wiii suppress iutenizing hormone secretion for 5 weeks.'^ It is used mainiy in the treatment of prostatic carcinoma. Other LHRH anaiogues, e.g. busereiin have been used in treatment of endometriosis, uterine fibroids and poiycystic ovarian disease.'' Naturai LHRH stimuiates the synthesis and secretion of LH and FSH from the pituitary giand. These in turn stimuiate the synthesis and reiease of gonadai steroids in both sexes. The pituitary response to LHRH varies with dosage, frequency of administration and duration of exposure. Gosereiin is a superactive anaiogue of LHRH and has a ionger duration of action. By persistent binding to the pituitary receptors, it can, at monthiy dose frequeney, produce a paradoxicai inhibitory effeet on gonadai function. However, like aii LHRH anaiogues, gosereiin possesses agonist activity and so there is an initiai surge in FSH and LH and consequentiy oestradioi levels during the first 2 weeks on initiating treatment,'' however, there was no evidence of this in our patient. Regular monthly injections maintain constant pituitary suppression of FSH and LH release. The treatment with LHRH anaiogues seems to be without major side-effects in the short-term, other than those reiated to low oestrogen leveis, e.g. hotflushes.**The subcutaneous injection into the anterior abdominai wall is simpie and virtually painless.^ In treatment with LHRH analogues ovarian function and fertility is preserved upon cessation of treatment.'"" Still uncertain is the rate and degree of loss of bone mineral, and the effect on lipid metabolism of proionged LHRH analogue treatment. We conciude that a trial of reversible 'chemical' oophorectomy using goserelin in patients with prolonged pemphigoid gestationis may be a valuable treatment in the future.
Figure L Showing extensive urtication and excoriated bullae.
500
400 _ Plasma 300 _ Oestradioi (pmol/l) 200 100 _
Disease activity
References
Prednisolone
0
1
2
3
4
5
6
7
Time from slari of gosereiin treatment (months)
Figure 2. Graph showing fall in plasma oestradioi levels, disease activity and prednisolone dosage following the start of goserelin therapy.
6 months. The pemphigoid gestationis is in complete remission now and she remains on her monthly subcutaneous injection of goserelin. She suffers from mild hot flushes.
1. Shornick JK, Bangert JL, Freeman RG, Gillam JN, Herpes Gestationis: clinical and histological features of 28 czscs. Journal of the American Academy of Dermatotogy 1983; 8: 214-224. 2. Lindemann C, Engstrom WW, Flynn RT. Herpes Gestationis: Results of treatment with adrenocorticotrophic hormone and cortisone. American Journat of Obstetrics and Gynecotogy 1952; 63: 167-170,
3. Holmes R, Black MM, Williamson DM, Scutt RWB. Herpes Gestationis and bullous pemphigoid. A disease spectrum. British Journal of Dermatology 1980; 103: 533-541. 4. Fine JD, Omura EF. Herpes Gestationis, Persistent disease activity 11 years post partum. Archives of Dermatology 1985; 121: 924-926, 5. Van de Weil A, Hart HC, Flinterman J, Kerckhaert JA, Du Boeuff JA, Immof JW. Plasma exchange in Herpes Gestationis. British Medical Journal 1980; 281: 1041-1042,
PEMPHIGOID GESTATIONIS
445
6, Carruthers JA, Ewins AR. Herpes Gestationis: Studies on the L.H.R.H. analogues in gynecology: a review. British Journal of hmding cbaracteristics, activity, and pathogenic significance of Obstetrics and Gynaecology 1986; 93: 431-454, the complement fixing factor, Clinieal and Experimental Immuno- 10, Leniay A, Maheux R, Faure N, Jean C, Fazehas A, Reversible logy 1978; 31: 38-44. hypogonadism induced by L.H.R.H, agonist (Busereiin) as a new 7, Holmes RC, Black MM, Jurecka W et al. Clues to the aetioiogy therapeutic approach to endometriosis. Eertility and Sterility and pathogenesis of Herpes Gestationis, British Journal of 1984; 41: 863-871, Dermatology 1983; 109: 131-139, 11. Franssen AMHW et al. Endometriosis: Treatment with gonado8, Thomas E, Jenkins J, Lcnton E, Cook I, Fndocrine effects of tropin—releasing hormone agonist Busereiin, Eertility and SteriGoserelin. British .Medical Journal 1986; 293: 1407-1408, lity 1989; 51: 401. 9, McLachlan RI, Healy DL, Burger HG. Clinical aspects of
