Erythrodermic CD8+ pseudolymphoma during infliximab treatment in a patient with psoriasis: Use of cyclosporine as a rescue therapy
Authors: Gilles Safa, Karine Luce, Laure Darrieux, Laurent Tisseau, Nicolas Ortonne
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Cutaneous CD8+ pseudolymphoma has been reported in HIV-infected patients in association with a reactive cutaneous infiltration of HIV-specific CD8+ cytotoxic T cells.1Bachelez H. Hadida F. Gorochov G. Massive infiltration of the skin by HIV-specific cytotoxic CD8+ cells.N Engl J Med. 1996; 335: 61-62Crossref PubMed Scopus (30) Google Scholar The diagnostic features include extensive plaques or erythroderma mimicking mycosis fungoides or Sézary syndrome, eosinophilia, and a dermal CD8+ cytotoxic T-lymphocyte infiltrate without T-cell receptor rearrangement.2Schartz N.E. De La Blanchadière A. Alaoui S. Morel P. Sigaux F. Vignon-Pennamen D. et al.Regression of CD8+ pseudolymphoma after HIV antiviral triple therapy.J Am Acad Dermatol. 2003; 49: 139-141Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 3Ingen-Housz-Oro S. Sbidian E. Ortonne N. Penso-Assathiany D. Chambrin V. Bagot M. et al.HIV-related CD8+ cutaneous pseudolymphoma: efficacy of methotrexate.Dermatology. 2013; 226: 15-18Crossref PubMed Scopus (10) Google Scholar Herein, we describe an HIV-negative patient with psoriasis in whom erythrodermic CD8+ pseudolymphoma developed after treatment with infliximab.A 32-year-old white woman had a 3-year history of biopsy-proven severe pustular psoriasis that was unresponsive to topical corticosteroids and narrowband ultraviolet B phototherapy. After screening for infection, neoplasm, and autoimmunity, all of which were negative, the patient was given infliximab at a dose of 5 mg/kg at weeks 0, 2, and 6, and then every 2 months. Her psoriasis improved and at least a 50% reduction in body surface area compared to baseline was observed after 12 weeks. Eleven months later, severe pruritic erythroderma associated with palmoplantar hyperkeratosis and generalized lymphadenopathy developed. Serologic and/or serum DNA detection studies for Bartonella henselae, cytomegalovirus, Epstein-Barr virus, HIV, and Toxoplasma gondii were negative.Two lesional skin biopsies showed a papillary dermal lymphocytic infiltrate composed of small- and medium-sized cells with mild epidermotropism. Immunohistochemistry showed an overwhelming predominance of CD2+, CD3+, CD5+, CD7+, and CD8+ T cells in the infiltrate. Scattered eosinophils were also observed. Immunostaining of CD8 T cells showed TiA-1 and granzyme B expression, indicating their cytotoxic lineage. Clonal T-cell receptor and immunoglobulin heavy chain gene rearrangements were not detected. Direct immunofluorescence was negative. Immunophenotyping performed on lymph node and bone marrow biopsy specimens showed a polyclonal CD8 T-cell infiltrate. A blood cell count showed 1992 CD4+ T cells/mm3, 3916 CD8+ T cells/mm3, and 1160 eosinophils/mm3. The CD4/CD8 ratio was 0.51, and there were no circulating Sézary cells.A diagnosis of erythrodermic CD8+ pseudolymphoma was made, and infliximab was discontinued. Despite infliximab withdrawal, the erythroderma persisted, and the use of topical and systemic corticosteroids followed by methotrexate was unsuccessful (Fig 1). Because of worsening skin symptoms associated with edema, chills, and overall deterioration in the patient's condition, treatment with cyclosporine at doses up to 5 mg/kg/day was initiated. The patient's condition dramatically improved and she was in complete clinical remission within 4 months (Fig 2). The CD4/CD8 ratio improved to 0.85.Fig 2Erythrodermic CD8+ pseudolymphoma resolved after 4 months of cyclosporine.View Large Image Figure ViewerDownload Hi-res image Download (PPT)As far as we know, in addition to our case, there have been only 2 other reported cases of cutaneous pseudolymphoma associated with anti-tumor necrosis factor (TNF) therapy. One was induced by adalimumab and subsequently the same eruption resulted from infliximab treatment4Imafuku S. Ito K. Nakayama J. Cutaneous pseudolymphoma induced by adalimumab and reproduced by infliximab in a patient with arthropathic psoriasis.Br J Dermatol. 2012; 166: 675-678Crossref PubMed Scopus (28) Google Scholar; the other case was induced by etanercept.5Guis S. Schiano de Colella J.M. Bonnet N. Andrac-Meyer L. Balandraud N. Mattei J.P. et al.Cutaneous pseudolymphoma associated with a TNF-alpha inhibitor treatment: etanercept.Eur J Dermatol. 2008; 18: 474-476PubMed Google Scholar However, unlike the present case, erythroderma was not associated with the reported cases, which could explain why the pseudolymphomatous reaction resolved after withdrawal of the drug in both cases. Moreover, in the second case described, relapse did not occur after the administration of another TNF inhibitor, adalimumab. Because our patient developed an erythrodermic reaction, treatment with TNF inhibitors was halted. Cyclosporine was used as rescue therapy and resulted in dramatic improvement without any significant side effects. To the Editor: Cutaneous CD8+ pseudolymphoma has been reported in HIV-infected patients in association with a reactive cutaneous infiltration of HIV-specific CD8+ cytotoxic T cells.1Bachelez H. Hadida F. Gorochov G. Massive infiltration of the skin by HIV-specific cytotoxic CD8+ cells.N Engl J Med. 1996; 335: 61-62Crossref PubMed Scopus (30) Google Scholar The diagnostic features include extensive plaques or erythroderma mimicking mycosis fungoides or Sézary syndrome, eosinophilia, and a dermal CD8+ cytotoxic T-lymphocyte infiltrate without T-cell receptor rearrangement.2Schartz N.E. De La Blanchadière A. Alaoui S. Morel P. Sigaux F. Vignon-Pennamen D. et al.Regression of CD8+ pseudolymphoma after HIV antiviral triple therapy.J Am Acad Dermatol. 2003; 49: 139-141Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 3Ingen-Housz-Oro S. Sbidian E. Ortonne N. Penso-Assathiany D. Chambrin V. Bagot M. et al.HIV-related CD8+ cutaneous pseudolymphoma: efficacy of methotrexate.Dermatology. 2013; 226: 15-18Crossref PubMed Scopus (10) Google Scholar Herein, we describe an HIV-negative patient with psoriasis in whom erythrodermic CD8+ pseudolymphoma developed after treatment with infliximab. A 32-year-old white woman had a 3-year history of biopsy-proven severe pustular psoriasis that was unresponsive to topical corticosteroids and narrowband ultraviolet B phototherapy. After screening for infection, neoplasm, and autoimmunity, all of which were negative, the patient was given infliximab at a dose of 5 mg/kg at weeks 0, 2, and 6, and then every 2 months. Her psoriasis improved and at least a 50% reduction in body surface area compared to baseline was observed after 12 weeks. Eleven months later, severe pruritic erythroderma associated with palmoplantar hyperkeratosis and generalized lymphadenopathy developed. Serologic and/or serum DNA detection studies for Bartonella henselae, cytomegalovirus, Epstein-Barr virus, HIV, and Toxoplasma gondii were negative. Two lesional skin biopsies showed a papillary dermal lymphocytic infiltrate composed of small- and medium-sized cells with mild epidermotropism. Immunohistochemistry showed an overwhelming predominance of CD2+, CD3+, CD5+, CD7+, and CD8+ T cells in the infiltrate. Scattered eosinophils were also observed. Immunostaining of CD8 T cells showed TiA-1 and granzyme B expression, indicating their cytotoxic lineage. Clonal T-cell receptor and immunoglobulin heavy chain gene rearrangements were not detected. Direct immunofluorescence was negative. Immunophenotyping performed on lymph node and bone marrow biopsy specimens showed a polyclonal CD8 T-cell infiltrate. A blood cell count showed 1992 CD4+ T cells/mm3, 3916 CD8+ T cells/mm3, and 1160 eosinophils/mm3. The CD4/CD8 ratio was 0.51, and there were no circulating Sézary cells. A diagnosis of erythrodermic CD8+ pseudolymphoma was made, and infliximab was discontinued. Despite infliximab withdrawal, the erythroderma persisted, and the use of topical and systemic corticosteroids followed by methotrexate was unsuccessful (Fig 1). Because of worsening skin symptoms associated with edema, chills, and overall deterioration in the patient's condition, treatment with cyclosporine at doses up to 5 mg/kg/day was initiated. The patient's condition dramatically improved and she was in complete clinical remission within 4 months (Fig 2). The CD4/CD8 ratio improved to 0.85. As far as we know, in addition to our case, there have been only 2 other reported cases of cutaneous pseudolymphoma associated with anti-tumor necrosis factor (TNF) therapy. One was induced by adalimumab and subsequently the same eruption resulted from infliximab treatment4Imafuku S. Ito K. Nakayama J. Cutaneous pseudolymphoma induced by adalimumab and reproduced by infliximab in a patient with arthropathic psoriasis.Br J Dermatol. 2012; 166: 675-678Crossref PubMed Scopus (28) Google Scholar; the other case was induced by etanercept.5Guis S. Schiano de Colella J.M. Bonnet N. Andrac-Meyer L. Balandraud N. Mattei J.P. et al.Cutaneous pseudolymphoma associated with a TNF-alpha inhibitor treatment: etanercept.Eur J Dermatol. 2008; 18: 474-476PubMed Google Scholar However, unlike the present case, erythroderma was not associated with the reported cases, which could explain why the pseudolymphomatous reaction resolved after withdrawal of the drug in both cases. Moreover, in the second case described, relapse did not occur after the administration of another TNF inhibitor, adalimumab. Because our patient developed an erythrodermic reaction, treatment with TNF inhibitors was halted. Cyclosporine was used as rescue therapy and resulted in dramatic improvement without any significant side effects.