title: Occult herpes simplex virus colonization of bullous dermatitides.
abstract: BACKGROUND
  Acantholytic disorders, including pemphigus vulgaris, chronic benign familial pemphigus (Hailey-Hailey disease, superficial pemphigus), Darier disease, and Grover transient acantholytic dermatosis, as well as other vesiculo-bullous disorders, including bullous pemphigoid, epidermolysis bullosa, and atopic dermatitis, are prone to florid infections by herpes simplex virus (HSV)-I and -II, and, more rarely, by varicella-zoster virus (VZV). As these infections are difficult to recognize clinically and histologically, their frequency remains unknown. A possible occult viral colonization has never been documented in these disorders. The manner in which the primary bullous disorders are contaminated by herpesviridae remains unclear.
  
  
  OBJECTIVE
  To retrospectively assess the possible presence of HSV and VZV in a series of biopsies of acantholytic disorders and bullous pemphigoid.
  
  
  METHODS
  The typical alpha-herpesviridae-related cytopathic signs were searched for by conventional microscopy in skin biopsies of patients with bullous pemphigoid (n = 20), pemphigus vulgaris (n = 19), Darier disease (n = 18), chronic benign familial pemphigus (n = 3), and Grover transient acantholytic dermatosis (n = 3). Immunohistochemistry (IHC) targeted specific HSV-I, HSV-II, and VZV antigens. Polymerase chain reaction (PCR) was used for detecting HSV- and VZV-specific DNA sequences.
  
  
  RESULTS
  No cytopathic signs suggestive of HSV or VZV infection were detected. However, IHC revealed HSV antigens in Darier disease (1/18, HSV-I), Grover transient acantholytic dermatosis (1/3, HSV-I), pemphigus vulgaris (1/19, HSV-I), and bullous pemphigoid (2/20, HSV-I and HSV-II). In these IHC-positive cases, PCR amplified specific HSV primers in Darier disease (1/18), pemphigus vulgaris (1/19), and bullous pemphigoid (1/20). VZV antigens and nucleic acids were never identified. The HSV antigens were nearly always restricted to the upper part of the granular layer and thus differed from the usual HSV distribution during cutaneous infection. Negative and positive controls yielded consistently positive and negative results, respectively.
  
  
  CONCLUSIONS
  This report shows for the first time that clinically and histologically occult HSV colonization may occur in Darier disease, Grover transient acantholytic disease, pemphigus vulgaris, and bullous pemphigoid. Given the frequent use of immunosuppressive treatments for primary bullous disorders, greater awareness of HSV colonization and infection is recommended in these patients.
authors.affiliation: Department of Dermatopathology, University Hospital of Liège, Liège, Belgium. af.nikkels@chu.ulg.ac.be
authors.forename: Arjen F
authors.initials: AF
authors.lastname: Nikkels
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Michael
authors.initials: M
authors.lastname: Herfs
authors.forename: Gérald E
authors.initials: GE
authors.lastname: Pierard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005260:Female; D014645:Herpesvirus 3, Human / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D018139:Simplexvirus / Q000302:isolation & purification*; D012872:Skin Diseases, Vesiculobullous / Q000821:virology*