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Herpes gestationis: Clinical features of immunologically proved cases
Herpes gestationis: Clinical features of immunologically proved cases J.
A. CARRUTHERS,
F.R.C.P.(C.)
Landon, England Clinical features of eight immunopathologically proved cases of herpes gestationis (HG) are presented. They are compared with those of an earlier, clinically defined series. The important features of the disease are identical in the two groups, particularly the worsening with subsequent pregnancies, absence of intervening HG-free pregnancies, and the exacerbation with delivery and estrogens. The immunopathologic investigations are a reliable, diagnostic aid in differentiating HG from other dermatoses of pregnancy with which it may, at times, be confused. (AM. J. 0BSTET. GYNECOL. 131: 865, 1978.)
HER PES GESTA TIONI S (HG) is a pruritic, bullous disease of pregnancy. The typical case develops widespread pruritis and bullae (Fig. 1) during pregnancy or in the first 72 hours of the puerperium. This usuaiiy occurs in the first or second pregnancy and recurs with subsequent pregnancies. generaiiy in a more severe form. A similar eruption has been described in infants born of affected mothers and aiso in patients with hydatidiform mole and choriocarcinoma. Pruritus and pruritic skin eruptions are common during pregnancy. The typical case of HG can readily be differentiated from among these but many cases are not so easily diagnosed. Because of the inevitability of recurrence of HG with future pregnancies and its tendency to be increasingly severe, it is important to differentiate this condition from other similar eruptions. 1n 1973, Provost and Tomasi 4 described new immunopathologic findings in HG. They described complement deposition at the dermoepidermaljunction of the patient's periiesionai skin. and aiso a circuiaiing factor capable of fixing complement at the same site in normal human skin (Fig. 2). A number of smaii series have been reported by a few workers confirming these findings and that, among the pruntiC builous dermatoses of pregnancv, they are specific for HG. Since 1973. we have cunfirrned the diagnosis of HG in eight patients who have had a total of 14 affected
From St. John\ Hospital for Di1eases of the Skin. Rneivedfor publication December 27, 1977. Accepted February J-1, 1978. Rejn-int requests: Dr.]. A. Carruthers, Division of Dermatology, Department of Medicine, Faculty of Medicine, The University of British Columbia, 865 W. 1Oth Az•c .. Var1rouver, B. C., Canada V5Z I L7. 0002-937R/78108131-0865$00.30/0
©
1978 The C. V. Mosby Co.
pregnancies. Because the condition is being redefined by these immunopathologic findings. it seems of value to compare the clinical findings in our cases with those of an eariier, dinicaiiv defined series.-· Patients
Four of these patients were seen at St. John's Hospital and their clinical and immunopathologic features have been reported elsewhere. 1 All of th('se four patients showed complement deposition
Comment Russell and Thorne's'' excellent paper de~crihed II palienls \vho had a total of 27 afft·( ted prcgnaulie . . . including one set of twins. Their series wa'i largely retrospective, their cases occurring front 1925 to ] 950 at the London Hospital. Only three of these patients were treated with systemic corticosteroids and. of course, none was investigated immunopathologica!lv. Reference to Table l shows that the clinical features of the two series are almost identical. The condition usually occurs in the first or second pregnancy. and then inevitably recurs in subsequent pregnancies. The only case of HG in which affected pregnancies alternated with unaffected was described hv Milron"-who.
865
866 Carruthers
August l5, l\!7H Am. J. Obstet. Gvnecol.
Table I. Clinical features summarized and compared to those of the patient's reported by Russell and Thorne5 Russell and Thorne•
Maternal age (yr.) at delivery of of first affected pregnancy (mean) Pregnancy of onset: 1M 2nd
16-33 (26)
19-43 (29)
5 2
4 5
4 2
4
3rd 5th 9th HG in subsequent pregnancies: 2nd ~d
Fig. 1. Herpes gestationis eruption in a patient 36 weeks
pregnant: fresh and excoriated blisters are seen on an edematous, erythematous base. incidentally, coined the name "herpes gestationis" and who helped to found St. John's Hospital. The initial onset is ante partum in the majority of cases, usually in the midtrimester, but the onset in subsequent pregnancies is almost always during pregnancy and may occur within days of conception. Exacerbation after delivery was more common among the recent series and seems to be one of the characteristic features of the disease. Its absence in a number of Russell and Thorne's patients might indicate a deficiency in the records, although they have obviously tried to avoid this. Alternatively, this may be an indication that some of their patients did not have HG. We believe that puerperal exacerbation, while not inevitable, does occur in the vast majority of affected pregnancies, unless suppressed by systemic corticosteroid administration. Neither of these series suggests that ~here is a high incidence of abortion, stillbirth, or fetal abnormality in affected pregnancies. The only casualty in the St. John's series was due to a therapeutic abortion in an unmarried mother. An interesting observation is the
4th 5th 6th 0 Unaffected Time of onset in first pregnancy (wk.): Antepartum 6 Range (mean) 16-36 (26) Postpartum 2 Time of onset in second pregnancy (wk.): Antepartum 4 Range (mean) 3-28 (14) () Postpartum Length of gestation in affected pregnancies: "Term" 12 36-37 wk. I 31-35 wk. 21-30 wk. 10-20 wk. 1* Sex of infants: Male 8 Female 4 I Stillborn/terminated I Unknown Puerperal exacerbation or onset: Within 3 days of delivery 12 No exacerbation 1 Notes incomplete With menstruation 3 I With estrogens/progestogens Final clearance (wk.) of HG l-26 (13) after first affected pregnancy (mean)
7
3 I I
0
7 13-29 (26)
4 6 8-28 7 (18) ()
20
2 2 3 13 4 6 5 14
6 6 2 3
3-16 (7.5)
*Therapeutic abortion.
preponderance of male over female infants: 13 of 17 and 8 of 12. The series are small but this may be an important observation . The symptoms may clear within a few days of delivery or may continue for some time. The majority of patients in both series were clear within a year. However, in two cases in the recent series, both after three affected pregnancies and both having been treated with systemic corticosteroids, the disease has persisted
Volume 1:\1 Number R
Herpes gestationis 867
over 2 years postpartum. This is longer than any of the London Hospital series which included four patients with three or more affected pregnancies. Indeed, these two cases have persisted longer than the previous longest standing case. 2 It is possible that steroid treatment, while suppressing the clinical manifestations of the condition, may be prolonging it. Since HG shows a tendency to spontaneous remission, particularly in the latter months of pregnancy, it would be wise to use systemic corticosteroid therapy with some reluctance. In conclusion, it is reassuring to see that our immunopathologically defined cases correspond well with those of Russell and Thorne's classic series. Such small differences as exist may not be significant. Certainly the important features of HG, the worsening with subsequent pregnancies, absence of intervening HG-free pregnancies, and the exacerbation with delivery and estrogens are marked in both series. Immunopathologic investigations are a usefui aid to the ciinician in making this important diagnosis in clinicallv difficult or mild cases.
Fig. 2. Indirect complement immunofluorescence in herpes gestationis: the circulating "HG factor" is shown to deposit complement at the dermoepidermaljunction (arrow) of normal human skin. ( x 200.)
REFERENCES
J. A., Black, M. M., and Ramnarain, N.: Immunopathological studies in herpes gestationis, Br. J. Dermatol. 96: 35, 1976. 2. Fox, E. C.: Herpes gestationis (dermatitis herpetiformis), Arch. Dermatol. Syph. 70: 331, 1954. 3. Milton, .J. L.: Diseases of the Skin, London, 1872, Robert Hardwicke . p. 208. I. Carruthers,
4. Provost, T. T., and Tomasi, T. B.: Evidence for complement activation via the classical pathway in skin disease I, J. Clin. Invest. 52: 1779, 1973. 5. Russell, B., and Thome, N. A.: Herpes gestationis, Br. J. Dermatol. 69: 339, 1957.
A. CARRUTHERS,
F.R.C.P.(C.)
Landon, England Clinical features of eight immunopathologically proved cases of herpes gestationis (HG) are presented. They are compared with those of an earlier, clinically defined series. The important features of the disease are identical in the two groups, particularly the worsening with subsequent pregnancies, absence of intervening HG-free pregnancies, and the exacerbation with delivery and estrogens. The immunopathologic investigations are a reliable, diagnostic aid in differentiating HG from other dermatoses of pregnancy with which it may, at times, be confused. (AM. J. 0BSTET. GYNECOL. 131: 865, 1978.)
HER PES GESTA TIONI S (HG) is a pruritic, bullous disease of pregnancy. The typical case develops widespread pruritis and bullae (Fig. 1) during pregnancy or in the first 72 hours of the puerperium. This usuaiiy occurs in the first or second pregnancy and recurs with subsequent pregnancies. generaiiy in a more severe form. A similar eruption has been described in infants born of affected mothers and aiso in patients with hydatidiform mole and choriocarcinoma. Pruritus and pruritic skin eruptions are common during pregnancy. The typical case of HG can readily be differentiated from among these but many cases are not so easily diagnosed. Because of the inevitability of recurrence of HG with future pregnancies and its tendency to be increasingly severe, it is important to differentiate this condition from other similar eruptions. 1n 1973, Provost and Tomasi 4 described new immunopathologic findings in HG. They described complement deposition at the dermoepidermaljunction of the patient's periiesionai skin. and aiso a circuiaiing factor capable of fixing complement at the same site in normal human skin (Fig. 2). A number of smaii series have been reported by a few workers confirming these findings and that, among the pruntiC builous dermatoses of pregnancv, they are specific for HG. Since 1973. we have cunfirrned the diagnosis of HG in eight patients who have had a total of 14 affected
From St. John\ Hospital for Di1eases of the Skin. Rneivedfor publication December 27, 1977. Accepted February J-1, 1978. Rejn-int requests: Dr.]. A. Carruthers, Division of Dermatology, Department of Medicine, Faculty of Medicine, The University of British Columbia, 865 W. 1Oth Az•c .. Var1rouver, B. C., Canada V5Z I L7. 0002-937R/78108131-0865$00.30/0
©
1978 The C. V. Mosby Co.
pregnancies. Because the condition is being redefined by these immunopathologic findings. it seems of value to compare the clinical findings in our cases with those of an eariier, dinicaiiv defined series.-· Patients
Four of these patients were seen at St. John's Hospital and their clinical and immunopathologic features have been reported elsewhere. 1 All of th('se four patients showed complement deposition
Comment Russell and Thorne's'' excellent paper de~crihed II palienls \vho had a total of 27 afft·( ted prcgnaulie . . . including one set of twins. Their series wa'i largely retrospective, their cases occurring front 1925 to ] 950 at the London Hospital. Only three of these patients were treated with systemic corticosteroids and. of course, none was investigated immunopathologica!lv. Reference to Table l shows that the clinical features of the two series are almost identical. The condition usually occurs in the first or second pregnancy. and then inevitably recurs in subsequent pregnancies. The only case of HG in which affected pregnancies alternated with unaffected was described hv Milron"-who.
865
866 Carruthers
August l5, l\!7H Am. J. Obstet. Gvnecol.
Table I. Clinical features summarized and compared to those of the patient's reported by Russell and Thorne5 Russell and Thorne•
Maternal age (yr.) at delivery of of first affected pregnancy (mean) Pregnancy of onset: 1M 2nd
16-33 (26)
19-43 (29)
5 2
4 5
4 2
4
3rd 5th 9th HG in subsequent pregnancies: 2nd ~d
Fig. 1. Herpes gestationis eruption in a patient 36 weeks
pregnant: fresh and excoriated blisters are seen on an edematous, erythematous base. incidentally, coined the name "herpes gestationis" and who helped to found St. John's Hospital. The initial onset is ante partum in the majority of cases, usually in the midtrimester, but the onset in subsequent pregnancies is almost always during pregnancy and may occur within days of conception. Exacerbation after delivery was more common among the recent series and seems to be one of the characteristic features of the disease. Its absence in a number of Russell and Thorne's patients might indicate a deficiency in the records, although they have obviously tried to avoid this. Alternatively, this may be an indication that some of their patients did not have HG. We believe that puerperal exacerbation, while not inevitable, does occur in the vast majority of affected pregnancies, unless suppressed by systemic corticosteroid administration. Neither of these series suggests that ~here is a high incidence of abortion, stillbirth, or fetal abnormality in affected pregnancies. The only casualty in the St. John's series was due to a therapeutic abortion in an unmarried mother. An interesting observation is the
4th 5th 6th 0 Unaffected Time of onset in first pregnancy (wk.): Antepartum 6 Range (mean) 16-36 (26) Postpartum 2 Time of onset in second pregnancy (wk.): Antepartum 4 Range (mean) 3-28 (14) () Postpartum Length of gestation in affected pregnancies: "Term" 12 36-37 wk. I 31-35 wk. 21-30 wk. 10-20 wk. 1* Sex of infants: Male 8 Female 4 I Stillborn/terminated I Unknown Puerperal exacerbation or onset: Within 3 days of delivery 12 No exacerbation 1 Notes incomplete With menstruation 3 I With estrogens/progestogens Final clearance (wk.) of HG l-26 (13) after first affected pregnancy (mean)
7
3 I I
0
7 13-29 (26)
4 6 8-28 7 (18) ()
20
2 2 3 13 4 6 5 14
6 6 2 3
3-16 (7.5)
*Therapeutic abortion.
preponderance of male over female infants: 13 of 17 and 8 of 12. The series are small but this may be an important observation . The symptoms may clear within a few days of delivery or may continue for some time. The majority of patients in both series were clear within a year. However, in two cases in the recent series, both after three affected pregnancies and both having been treated with systemic corticosteroids, the disease has persisted
Volume 1:\1 Number R
Herpes gestationis 867
over 2 years postpartum. This is longer than any of the London Hospital series which included four patients with three or more affected pregnancies. Indeed, these two cases have persisted longer than the previous longest standing case. 2 It is possible that steroid treatment, while suppressing the clinical manifestations of the condition, may be prolonging it. Since HG shows a tendency to spontaneous remission, particularly in the latter months of pregnancy, it would be wise to use systemic corticosteroid therapy with some reluctance. In conclusion, it is reassuring to see that our immunopathologically defined cases correspond well with those of Russell and Thorne's classic series. Such small differences as exist may not be significant. Certainly the important features of HG, the worsening with subsequent pregnancies, absence of intervening HG-free pregnancies, and the exacerbation with delivery and estrogens are marked in both series. Immunopathologic investigations are a usefui aid to the ciinician in making this important diagnosis in clinicallv difficult or mild cases.
Fig. 2. Indirect complement immunofluorescence in herpes gestationis: the circulating "HG factor" is shown to deposit complement at the dermoepidermaljunction (arrow) of normal human skin. ( x 200.)
REFERENCES
J. A., Black, M. M., and Ramnarain, N.: Immunopathological studies in herpes gestationis, Br. J. Dermatol. 96: 35, 1976. 2. Fox, E. C.: Herpes gestationis (dermatitis herpetiformis), Arch. Dermatol. Syph. 70: 331, 1954. 3. Milton, .J. L.: Diseases of the Skin, London, 1872, Robert Hardwicke . p. 208. I. Carruthers,
4. Provost, T. T., and Tomasi, T. B.: Evidence for complement activation via the classical pathway in skin disease I, J. Clin. Invest. 52: 1779, 1973. 5. Russell, B., and Thome, N. A.: Herpes gestationis, Br. J. Dermatol. 69: 339, 1957.