Herpes Simplex Virus Associated Erythema Multiforme (HAEM) is Mechanistically Distinct from Drug-Induced Erythema Multiforme: Interferon-γ is Expressed in HAEM Lesions and Tumor Necrosis Factor-α in Drug-Induced Erythema Multiforme Lesions  Hisashi Kokuba, Laure Aurelian, Joseph Burnett  Journal of Investigative Dermatology  Volume 113, Issue 5, Pages 808-815 (November 1999) DOI: 10.1046/j.1523-1747.1999.00754.x Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Immunoperoxidase staining of frozen skin tissues with Pol antibody. (A) Intranuclear staining (arrows) in HAEM lesional skin (day 2 after lesion onset) stained with Pol antibody (×100). Magnification (×300) shown in inset. (B) Healed HAEM lesional skin stained with Pol antibody does not reveal nuclear staining. Magnification (×200) shown in inset. Similar results were obtained for normal skin adjacent to the HAEM lesion. Journal of Investigative Dermatology 1999 113, 808-815DOI: (10.1046/j.1523-1747.1999.00754.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 In situ reverse transcriptase–PCR of HAEM lesional skin. (A) IFN-γ primers reveal positive cytoplasmic signals in infiltrating cells in the upper dermis and at the epidermis–dermis junction (arrow) (×100). (B) Magnification of area in panel A identified by arrow (×400). (C) In situ reverse transcriptase–PCR of HAEM lesional skin with TNF-α primers is negative (×100). Journal of Investigative Dermatology 1999 113, 808-815DOI: (10.1046/j.1523-1747.1999.00754.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Immunoperoxide staining with IFN-γ and TNF-α antibodies. HAEM lesional skin was stained with IFN-γ antibody (×200) (A) or TNF-α antibody (× 200) (B) and normal skin was stained with IFN-γ antibody (×200) (C). TNF-α staining of the normal skin was negative. Journal of Investigative Dermatology 1999 113, 808-815DOI: (10.1046/j.1523-1747.1999.00754.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Photomicrographs of HSV lesional skin. (A) Immunoperoxidase staining with IFN-γ antibody evidences mononuclear and intercellular staining (arrows) (×200). (B) Immunoperoxidase staining with TNF-α antibody is negative (×100). Journal of Investigative Dermatology 1999 113, 808-815DOI: (10.1046/j.1523-1747.1999.00754.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Immunoperoxidase staining of lesional skin from drug-induced EM with antibody to TGF-β, IFN-γ, or TNF-α. (A) TGF-β, (B) IFN-γ, (C) TNF-α. TNF-α staining is within keratinocytes, mononuclear cells, and intercellular spaces in the upper dermis and at the epidermis–dermis junction (×200). Journal of Investigative Dermatology 1999 113, 808-815DOI: (10.1046/j.1523-1747.1999.00754.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Immunoperoxidase staining with TGF-β antibody. (A) HAEM lesional skin (×200). (B) HSV lesional skin (×100). Journal of Investigative Dermatology 1999 113, 808-815DOI: (10.1046/j.1523-1747.1999.00754.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 7 Photomicrograph of lesional skin (×200). (A) Hematoxylin and eosin staining of acute HAEM lesional skin. (B, C) Immunoperoxidase staining of section in (A) with antibody to p21waf. The identity of the floating cells within bulla is unknown, but they demonstrate intranuclear signals (B, arrow). Cytoplasmic signals are seen in epidermis other than bulla (C, arrow). (D) Immunoperoxidase staining of HSV lesional skin with antibody to p21waf. Cytoplasmic and intranuclear (arrow) signals are seen. Journal of Investigative Dermatology 1999 113, 808-815DOI: (10.1046/j.1523-1747.1999.00754.x) Copyright © 1999 The Society for Investigative Dermatology, Inc Terms and Conditions