IMMUNOLOGIC BASIS OF SKIN DISEASE

Rhett J. Drugge, MD

Graft-Versus Host Disease, This event is secondary to allogeneic engraftment of bone marrow derived cells. The most common clinical setting is following bone marrow transplant, although GVHD may be seen following any type of organ engraftment, including blood transfusions of non-irradiated cells in immunocompromised hosts. (post-mortem, escutcheon , thigh , thigh 2 )

Histology features: minimal hyperkeratosis, vacuolar interface dermatitis, satellite lymphocytes induce dyskeratosis (apoptosis ) and pigment incontinence. (H&E, 1 , 2 )

Pathogenesis: GVHD fits a classical model of cell mediated immunity. Apoptosis is triggered in keratinocytes by the expression of the FAS receptor and subsequent interaction with the FAS ligand on T-cells (Markusse , Ju ).

Classification--GVHD occurs in acute and chronic variants.

Acute GVHD is defined as occuring within three month of the engraftment.

Stage 1 (mild): a skin rash over less than 25% of the body.

Stage 2 (moderate): a skin rash over a more than 25% of the body accompanied by mild liver or stomach and intestinal disorders.

Stage 3 (severe): redness of the skin, similar to a severe sunburn, and moderate liver, stomach and intestinal problems.

Stage 4 (life-threatening): blistering, peeling skin, and severe liver, stomach, and intestinal problems.

Chronic GVHD is defined as occuring more that three months after the engraftment event. This disease is similar to scleroderma and eosinophilic fasciitis in its clinical manifestations. Eosinophilic fasciitis has also been seen after bone marrow transplant (Markusse ).

Antibody-Mediated Disorders

Vitiligo, (patient advocacy , email patient support list) This condition is associated with an undefined immunologic mechanism. Possible pathogenic mechanism include antibody mediated immunity. Patients with vitiligo have been found to have circulating antibodies to melanocytes which effect in vitro complement-mediated cytolysis (Cui , Norrris ). Persistent viral infections such as HIV have been postulated to be trigger factors for the development of vitiligo (Duvic , Tojo ). Vitiligo is also seen in association with other defects of cell mediated immunity such as atopy. Nevomelanocytic destruction in normal and neoplastic nevomelanocytic lesions are seen commonly and are associated with vitiliginous changes. Clinical nomenclature for these conditions are Sutton's nevus (leukoderma centrifugm aquisita) and regression with respect to melanoma (Wagner , Gross , Kossard , Nordlund ). Vitiligo autoantibodies from humans have been demonstrated to be effective against melanoma in a mouse model (Fishman ).

Classification: site dependent

Localized, Dermatomal, Generalized, acral, orificial, psoriasiform

Treatment: The therapeutic success of epidermal grafting for vitiligo is limited primarily to suffby the koebner phenomenon (Hatchtome ).

Apoptosis, a highly selective form of "cell suicide" with characteristic morphological and biochemical features: chromatin condensation, formation of apoptotic bodies, and DNA fragmentation by activation of endonucleases.

The National Vitiligo Foundation, Inc. Contact: Cheryl McInnis, Executive Director Address: P.O. Box 6337, Tyler, TX 75711-6337, Telephone: (903) 534-2925, Fax: (903) 534-8075, email: 73071.33@compuserve.com

VITILIGO on listserv@SJUVM.STJOHNS.EDU - Vitiligo Discussion

VITILIGO is an open, unmoderated discussion list for people connected with vitiligo. This can be any connection at all, from medical practitioners, to friends of patients with vitiligo. The list will be a refuge for those with vitiligo, as well as a means for information dissemination. The intended purpose of the list will change over time as we get to know its capabilities. Archives of VITILIGO mail items are kept in monthly files. You may obtain a list of files in the archives by sending the command INDEX VITILIGO in the BODY of e-mail to listserv@SJUVM.STJOHNS.EDU on the Internet. To subscribe, send the following command in the BODY of mail to listserv@SJUVM.STJOHNS.EDU on the Internet: SUB VITILIGO yourfirstname yourlastname. To contact the owner of the list send mail to Eric Fricker

Durham-Pierre DG Walters CS Halder RM Pham HN Vanderpool EA, Natural killer cell and lymphokine-activated killer cell activity against melanocytes in vitiligo. J Am Acad Dermatol (1995 Jul) 33(1):26-30.

Cui J Arita Y Bystryn JC, Cytolytic antibodies to melanocytes in vitiligo. J Invest Dermatol (1993 Jun) 100(6):812-5

Norris DA Kissinger RM Naughton GM Bystryn JC, Evidence for immunologic mechanisms in human vitiligo: patients' sera induce damage to human melanocytes in vitro by complement-mediated damage and antibody-dependent cellular cytotoxicity.In: J Invest Dermatol (1988 Jun) 90(6):783-9

Duvic M Rapini R Hoots WK Mansell PW, Human immunodeficiency virus-associated vitiligo: expression of autoimmunity with immunodeficiency? J Am Acad Dermatol (1987 Oct) 17(4):656-62

Tojo N Yoshimura N Yoshizawa M Ichioka M Chida M Miyazato I Taniai S Marumo F Matubara O Kato T et al, Vitiligo and chronic photosensitivity in human immunodeficiency virus infection. Jpn J Med (1991 May-Jun) 30(3):255-9

Wagner RF Jr Nathanson L Paraneoplastic syndromes, tumor markers, and other unusual features of malignant melanoma. : J Am Acad Dermatol (1986 Feb) 14(2 Pt 1):249-56

Gross DJ Singer PG Schosser RH Adult-onset leukoderma and malignant melanoma [letter] Arch Dermatol (1990 Sep) 126(9):1240-1

Kossard S Commens C, Hypopigmented malignant melanoma simulating vitiligo. J Am Acad Dermatol (1990 May) 22(5 Pt 1):840-2

Nordlund JJ, Hypopigmentation, vitiligo, and melanoma. New data, more enigmas. Arch Dermatol (1987 Aug) 123(8):1005-8

Fishman P Azizi E Shoenfeld Y Sredni B Yecheskel G Ferrone S Zigelman R Chaitchik S Floro S Djaldetti M, Vitiligo autoantibodies are effective against melanoma. Cancer (1993 Oct 15) 72(8):2365-9

Markusse HM Dijkmans BA Fibbe WE, Eosinophilic fasciitis after allogeneic bone marrow transplantation. J Rheumatol (1990 May) 17(5):692-4 T. Brunner, R. J. Mogil, D. LaFace, N. J. Yoo, A. Mahboubi, F. Echeverri, S. J. Martin, W. R. Force, D. H. Lynch, C. F. Ware & ... Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas [Medline ]

S. T. Ju, D. J. Panka, H. Cui, R. Ettinger, M. el-Khatib, D. H. Sherr, B. Z. Stanger & A. Marshak-Rothstein, Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation , Nature 373: 444-448 (1995) [Medline ]

Hatchome N Kato T Tagami H Therapeutic success of epidermal grafting in generalized vitiligo is limited by the Koebner phenomenon. J Am Acad Dermatol (1990 Jan) 22(1):87-91.