Clues to the aetiology and pathogenesis of herpes gestationis

Abstract

In a study of twenty-five patients with herpes gestationis we found that 80% possessed the HLA antigen DR3, which confers increased immune responsiveness and a predisposition to 'auto-immune disease'. In five patients the development of herpes gestationis coincided with a change in sexual partner, suggesting that the development of herpes gestationis may depend on exposure to an antigen derived from the father. This might share determinants with a component of the basement membrane zone of skin. Although anti-basement membrane zone antibodies are present in HG it is not clear whether they play a pathogenic role. The infrequency of neonatal involvement and the lack of correlation between immunofluorescence findings and clinical activity in our patients suggested that the antibodies might be a result of tissue damage rather than its cause. Two patients in our study were exceptional in that episodes of herpes gestationis were followed by normal pregnancies. In these patients the relationship of their DR antigens to those of the fetus may have been important in determining whether or not the pregnancy would be affected by herpes gestationis.

Pemphigoid gestationis: new insights into the pathogenesis lead to novel diagnostic tools

“…HLA-DR3 was found in 61-85% of patients with PG and the combined presence of both HLA-DR3 and DR4 was reported in 43 -45% of cases 13,16 . Equally important are paternal histocompatibility antigens.…”

“…Provided the paternity remains the same, PG generally recurs with subsequent pregnancies, and when it does, the disease begins earlier and lasts longer 1,5 . However, several pregancies skipped by PG despite unchanged paternity have been described 7,13,14 . The explanation for this phenomenon remains uncertain.…”

“…Nursing may affect the duration of the disease postpartum. It was reported that breastfeeding patients had a significantly shorter duration of eruption than bottlefeeding ones 13 . Provided the paternity remains the same, PG generally recurs with subsequent pregnancies, and when it does, the disease begins earlier and lasts longer 1,5 .…”

“…Several lines of evidence suggest an important role of placental antigens for initiation of the autoimmune response: (1) PG occurs only during pregnancy or in patients with choriocarcinoma and hydatiform mole 8,9 ; (2) No case of vesiculobullous eruption similar to PG has been reported in men with choriocarcinoma (unlike the tumour in women, which develops from gestational tissue with both maternal and paternal antigens represented, choriocarcinoma in men is totally derived from syngeneic tissue) 6 ; (3) Circulating autoantibodies in patients with PG bind to the dermalepidermal junction of skin and amnion 52,53 ; (4) BP180 is present not only in the epidermis but also in the amnion 54 ; (5) Abnormal expression of MHC class II molecules by cells of the amniochorionic stroma has been demonstrated in patients with PG 55,56 ; (6) In cases, in which by chance or altered paternity the mother and the fetus have identical HLA-D phenotypes, unaffected or skipped pregnancies occur 13 . Based on these data, two possible mechanisms for the initiation of an autoimmune response in PG have been proposed.…”

“…Subsequent flareups may occur with menstruation or with the use of oestrogen-and/or progesteronebased oral contraceptives 5,6,13 . Skin lesions usually clear within three months after delivery without scarring or milia formation 1 .…”