HG expresses a broader clinical range than previously thought. Disease may be mild and nonvesicular during one pregnancy, followed by explosive vesiculobullous disease during another. On the other hand, patients with extensive HG during one pregnancy may experience mild or even subclinical disease during a subsequent gestation. The broad range of clinical signs and the lack of demonstrable fetal or maternal risk associated with HG have important ramifications for patients desirous of further children. There is a genetic predisposition to HG. DRB1*0301 (HLA-DR3) is increased and 90% of patients express either DRB1*0301 (HLA-DR3) or DRB1*0401/040X (HLA-DR4). Ninety percent of patients also carry a C4 null allele, which may be due to linkage dysequilibrium with DRB1*0301 or DRB1*0401/040X. The disease appears to be mediated by an IgG1 specific for a 180-kD component of hemidesmosomes. This protein is distinct from the 240-kD hemidesmosomal antigen seen in BP and is coded for by a different cDNA on a different chromosome. Abnormal expression of class II MHC occurs in the placental villi of those with HG, suggesting ongoing immunologic stimulation. This has led some investigators to believe that the primary immunologic event is taking place within the placenta and that the skin is an immunologic bystander.