Correspondence

Massive Infiltration of the Skin by HIV-Specific Cytotoxic CD8+ T Cells

N Engl J Med 1996; 335:61-62July 4, 1996

Article

To the Editor:

A 32-year-old man infected with the human immunodeficiency virus (HIV) since 1987 presented in May 1993 with scaly, erythematous skin plaques. His CD4 count was 403 per cubic millimeter. In June 1994, he was admitted because of a pruriginous erythroderma, with infiltrated, photosensitive lesions and a palmoplantar keratoderma. Examination revealed enlarged axillary and inguinocrural lymph nodes.

The laboratory findings included 1400 eosinophils per cubic millimeter, 2820 lymphocytes per cubic millimeter (89 percent were CD8+ T cells), and the presence of Sézary cells (300 per cubic millimeter). Histologic studies showed a lymphoid infiltrate with epidermotropism and microabscesses, including Sézary cells. The enzyme immunoassay and polymerase chain reaction (PCR) for human T-cell lymphotropic virus types I and II yielded negative results.

Treatment with prednisone (1 mg per kilogram of body weight per day) led to a partial remission of the cutaneous signs. At the same time, the size of the lymph nodes returned to normal but with a worsening of the CD4 lymphopenia (to 61 cells per cubic millimeter). A severe relapse of the skin symptoms occurred when the corticosteroid treatment was interrupted. Zidovudine (500 mg per day) and zalcitabine (2.25 mg per day), combined with interferon alfa (15 million units per week), led to a substantial improvement in the cutaneous symptoms, and the CD4 count rose to 470 per cubic millimeter.

The skin-infiltrating cells exhibited almost exclusively the CD3+, CD8+, T-cell receptor (TCR) α/β+ phenotype (Figure 1Figure 1Section of a Skin Specimen Immunostained with an Anti-CD8 Monoclonal Antibody (×100).), and most of the cells were activated (HLA-DR+). No expression of the natural killer markers CD56 and CD16 was found; instead, 25 percent of the cells expressed the S6F1 marker of cytotoxic T cells. Analysis of T-cell clonality in blood and skin specimens by PCR of the Vγ–Jγ gene segments showed a polyclonal pattern of the TCRγ gene rearrangements, which was also observed in a lymph node, suggesting the reactive, nonmalignant nature of the infiltration. CD8+ cell lines derived from a skin-biopsy specimen exerted strong HIV-specific cytotoxic effects (Figure 2Figure 2Results of a ⁵¹Cr-Release Assay against Autologous Cells Transformed by Epstein–Barr Virus and Infected with Vaccinia Constructs Expressing Various HIV-1 Proteins or Only the Wild-Type Vaccinia Virus, as a Control (Effector:Target Ratio, 10:1).). Moreover, by using different HLA-mismatched targets, we showed that the anti-pol specific lysis was restricted by HLA-B8.

Therefore, in spite of its presentation as an aggressive lymphoproliferative disease, this previously reported mycosis fungoides–like syndrome1,2 is not a neoplastic process but instead involves a massive infiltration of the skin by activated, oligoclonal, HIV-specific cytotoxic T cells.

Hervé Bachelez, M.D.
Hôpital Saint-Louis, 75010 Paris, France

Fabienne Hadida, Ph.D.
Guy Gorochov, M.D.
Hôpital de la Pitié–Salpétrière, 75013 Paris, France

2 References

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   Zhang P, Chiriboga L, Jacobson M, et al. Mycosis fungoideslike T-cell cutaneous lymphoid infiltrates in patients with HIV infection. Am J Dermatopathol 1995;17:29-35
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Citing Articles (8)

Citing Articles

1. 1

   H. Bachelez. (2009) The Uncertain Status of Cutaneous Pseudolymphoma. Actas Dermo-Sifiliográficas 100, 33-37
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2. 2

   U. R. Hengge, R. Mota, A. Marini. (2006) Häufige und seltene dermatologische Erkrankungen bei HIV-Patienten. Der Hautarzt 57:11, 975-987
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3. 3

   E. Poszepczynska-Guigné, M. Jagou, J. Wechsler, M.T. Dieng, J. Revuz, M. Bagot. (2006) Lymphome T cutané épidermotrope CD8+ cytotoxique d’évolution très agressive. Annales de Dermatologie et de Vénéréologie 133:3, 253-256
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4. 4

   Karl Wilkins, Jacqueline C. Dolev, Ryan Turner, Philip E. LeBoit, Timothy G. Berger, Toby A. Maurer. (2005) Approach to the treatment of cutaneous malignancy in HIV-infected patients. Dermatologic Therapy 18:1, 77-86
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5. 5

   (2000) HIV-1 and an HTLV-II–Associated Cutaneous T-Cell Lymphoma. New England Journal of Medicine 343:4, 303-304
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6. 6

   G. S. Ogg. (2000) Detection of antigen-specific cytotoxic T lymphocytes: significance for investigative dermatology. Clinical and Experimental Dermatology 25:4, 312-316
   CrossRef

7. 7

   Suzanne Friedler, Mary T.. Parisi, Elaine Waldo, Rosemary Wieczorek, Gurdip Sidhu, M. Joyce Rico. (1999) Atypical cutaneous lymphoproliferative disorder in patients with HIV infection. International Journal of Dermatology 38:2, 111-118
   CrossRef

8. 8

   B.J. Bain. (1998) Lymphomas and reactive lymphoid lesions in HIV infection. Blood Reviews 12:3, 154-162
   CrossRef