Correspondence
Idiopathic Eosinophilia
N Engl J Med 2000; 342:659-661March 2, 2000
- Article
To the Editor:
Some of the cases reported by Simon et al. (Oct. 7 issue)1 as idiopathic eosinophilia could have been diagnosed as T-cell lymphoma or the Sézary syndrome from the inception. Although the authors considered a diagnosis of the Sézary syndrome in eight patients who presented with erythroderma and pruritus, they excluded that diagnosis because they did not observe the “classic” CD4+CD7–CD25– immunophenotype. Certainly, Sézary cells should express CD4; however, CD7 can be detected in patients with the Sézary syndrome,2 and some of their patients were negative for CD7 or were not analyzed for CD7. The expression of CD25 is not a defining feature of the Sézary syndrome, and the level of its expression on the cell membrane is often low or highly variable.3 The strong expression of CD25 identified in some of the patients who were reported to have idiopathic eosinophilia and the detection of T-cell clonality should have prompted a search for retroviral infections, especially with human T-cell lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV). Adult T-cell lymphoma or leukemia is characterized by high levels of CD25 expression, and affected patients can also present with generalized erythroderma. Severe skin disease associated with eosinophilia and lymphadenopathy has also been reported in patients infected with HIV and human T-cell lymphotropic virus type II.4
Some of the patients included in the study had overwhelming features of T-cell lymphoma or the Sézary syndrome. In addition to the clinical features at presentation, such features included cutaneous or nodal histologic features, the presence of detectable T-cell–receptor clones, and the presence of more than 1000 abnormal circulating T cells per cubic millimeter. Furthermore, bone marrow and peripheral eosinophilia have been detected in 38 percent of patients with cutaneous T-cell lymphoma or the Sézary syndrome, especially patients with advanced disease.5 The diagnosis of idiopathic eosinophilia should be made after the Sézary syndrome and other T-cell lymphomas have been excluded. Admittedly, the Sézary syndrome is often a slowly evolving condition that may be difficult to diagnose in the early stages. Thus, patients identified as having idiopathic eosinophilia should be closely monitored for lymphoproliferative disorders.
5 ReferencesJoan Guitart, M.D.
Northwestern University Medical School, Chicago, IL 606111
Simon H-U ,Plotz SG ,Dummer R ,Blaser K . Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med 1999;341:1112-1120
Full Text | Web of Science | Medline2
Russell-Jones R ,Whittaker S . T-cell receptor gene analysis in the diagnosis of Sezary syndrome. J Am Acad Dermatol 1999;41:254-259
CrossRef | Web of Science | Medline3
Meissner K ,Loning T ,Rehpenning W . Mycosis fungoides and Sezary syndrome: diagnostic and prognostic relevance of cellular antigen expression. Hautarzt 1991;42:84-91
Web of Science | Medline4
Kaplan MH ,Hall WW ,Susin M , et al. Syndrome of severe skin disease, eosinophilia, and dermatopathic lymphadenopathy in patients with HTLV-II complicating human immunodeficiency virus infection. Am J Med 1991;91:300-309
CrossRef | Web of Science | Medline5
Graham SJ ,Sharpe RW ,Steinberg SM ,Cotelingam JD ,Sausville EA ,Foss FM . Prognostic implications of a bone marrow histopathologic classification system in mycosis fungoides and the Sezary syndrome. Cancer 1993;72:726-734
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To the Editor:
In a retrospective series of 60 patients with idiopathic eosinophilia, Simon et al. demonstrated that 16 patients had an underlying T-cell disorder characterized by the expansion of a circulating population of interleukin-5–producing T cells with an aberrant surface phenotype. In most patients, the abnormal T cells expressed activation markers. In her accompanying editorial, Bain1 suggested that this series of patients may not be fully representative of patients with the hypereosinophilic syndrome, since most patients in the study were recruited from dermatology clinics.
We have studied circulating T cells in nine consecutive patients who fulfilled the diagnostic criteria for the idiopathic hypereosinophilic syndrome and who were recruited from internal medicine departments of academic hospitals in Belgium. We identified three patients with a clonal population of CD3–CD4+ interleukin-5–producing T cells with the phenotype of activated memory T cells.2 Interestingly, the clinical manifestations in all three patients were almost exclusively restricted to the skin. Skin involvement may be a common manifestation in patients with eosinophilia who have an underlying T-cell disorder.
Simon et al. suggest that in some instances, disrupted Fas-mediated apoptosis could be involved in the expansion of the aberrant T cells, which lacked surface Fas receptors (CD95) in eight of the patients they studied. They conclude that treatment with interferon alfa-2b may be beneficial in such patients through the induction of apoptosis in these CD95– T cells. However, it has recently been shown that interferon could be an important survival factor for activated T cells,3 and we have observed that this cytokine inhibits spontaneous apoptosis of the clonal interleukin-5–producing T cells from two of our patients. We therefore believe that monotherapy with interferon alfa-2b may actually be detrimental in some patients with eosinophilia who have a clonal T-cell disorder by favoring further expansion of the aberrant population. In this regard, Simon et al. report that T-cell lymphoma subsequently developed in one patient treated with interferon alfa-2b. T-cell lymphoma developed in the first patient in our series, who also received interferon alfa-2b.
3 ReferencesFlorence Roufosse, M.D.
Liliane Schandené, Ph.D.
Elie Cogan, M.D., Ph.D.
Hôpital Erasme, B-1070 Brussels, Belgium1
Bain BJ . Eosinophilia -- idiopathic or not? N Engl J Med 1999;341:1141-1143
Full Text | Web of Science | Medline2
Cogan E ,Schandene L ,Crusiaux A ,Cochaux P ,Velu T ,Goldman M . Clonal proliferation of type 2 helper T cells in a man with the hypereosinophilic syndrome. N Engl J Med 1994;330:535-538
Full Text | Web of Science | Medline3
Marrack P ,Kappler J ,Mitchell T . Type I interferons keep activated T cells alive. J Exp Med 1999;189:521-530
CrossRef | Web of Science | Medline
To the Editor:
Simon et al. reported clonal T-cell populations in patients with idiopathic eosinophilia. In adult T-cell lymphoma or leukemia caused by HTLV-I infection, eosinophilia occurs in up to 20 percent of patients1 and is mediated by interleukin-5 produced by the clonal population of leukemic cells.2 Simon et al. did not mention the HTLV-I status or the racial background of their four patients with clonal T cells. This information is also important in evaluating patients with eosinophilia who do not have T-cell cancers, because chronic and smoldering subtypes of adult T-cell lymphoma or leukemia have been identified.3 We believe that tests for antibodies against HTLV-I or the proviral HTLV-I genome in the clonal T cells of patients with persistent eosinophilia may contribute to our understanding of idiopathic eosinophilia.
3 ReferencesRitsuro Suzuki, M.D.
Masao Seto, M.D.
Shigeo Nakaura, M.D.
Aichi Cancer Center, Nagoya 464-8681, Japan1
Murata K ,Yamada Y ,Kamihira S , et al. Frequency of eosinophilia in adult T-cell leukemia/lymphoma. Cancer 1992;69:966-971
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Noma T ,Nakakubo H ,Sugita M , et al. Expression of different combinations of interleukins by human T cell leukemic cell lines that are clonally related. J Exp Med 1989;169:1853-1858
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Shimoyama M . Diagnostic criteria and classification of clinical subtypes of adult T-cell leukemia-lymphoma: a report from the Lymphoma Study Group (1984-87). Br J Haematol 1991;79:428-437
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Author/Editor Response
The authors reply:
To the Editor: In response to Dr. Guitart: we believe that in three of our patients the eosinophilia with abnormal T-cell subpopulations represented a precursor of cutaneous T-cell lymphoma. However, using the revised European–American classification of lymphoid neoplasms1 and the classification of the European Organization for Research and Treatment of Cancer for primary cutaneous lymphomas,2 we gave only one patient a diagnosis of the Sézary syndrome. None of the other patients met the criteria for the diagnosis of cutaneous T-cell lymphoma. Moreover, in most assays of peripheral blood, clonal populations were found only in purified abnormal T cells. For these reasons, 15 of the 16 patients we described were not given a diagnosis of cutaneous T-cell lymphoma when they were originally studied.
Suzuki et al. and Guitart question whether the reported cases were related to HTLV-I or HIV infection. All patients were white residents of Switzerland and Germany, a group in which HTLV-I infection is extremely rare. Lesional skin samples from Swiss and German patients with cutaneous T-cell lymphoma were negative for HTLV-I proviral DNA.3 In blood smears, no cells with hyperlobated nuclei were observed. These negative findings render HTLV-I–related cutaneous lymphoma unlikely. In addition, the clinical course over a period of several years, the elevated CD4+ T-cell counts in most patients, and the lack of susceptibility to infection do not support the hypothesis that HIV infection is involved.
Roufosse et al. ask about interferon alfa-2b therapy in the hypereosinophilic syndrome, since interferon appears to promote the survival of normal antigen-activated T cells in an animal model. We presented evidence of the presence in our patients of abnormal T-cell populations that secrete interleukin-5. Interferon alfa-2b reduces the secretion of interleukin-5 in type 2 helper T cells4 and has well-documented efficacy in cutaneous T-cell lymphoma5 and other lymphomas. Thus, it is reasonable to suggest the need for prospective clinical studies of interferon alfa-2b therapy in such patients.
5 ReferencesHans-Uwe Simon, M.D.
Swiss Institute of Allergy and Asthma Research, CH-7270 Davos, SwitzerlandReinhard Dummer, M.D.
University of Zurich, CH-8091 Zurich, Switzerland1
Harris NL ,Jaffe ES ,Stein H , et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994;84:1361-1392
Web of Science | Medline2
Willemze R ,Kerl H ,Sterry W , et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 1997;90:354-371
Web of Science | Medline3
Boni R ,Davis-Daneshfar A ,Burg G ,Fuchs D ,Wood GS . No detection of HTLV-I proviral DNA in lesional skin biopsies from Swiss and German patients with cutaneous T-cell lymphoma. Br J Dermatol 1996;134:282-284
CrossRef | Web of Science | Medline4
Schandene L ,Del Prete GF ,Cogan E , et al. Recombinant interferon-alpha selectively inhibits the production of interleukin-5 by human CD4+ T cells. J Clin Invest 1996;97:309-315
CrossRef | Web of Science | Medline5
Dummer R ,Haffner AC ,Hess M ,Burg G . A rational approach to the therapy of cutaneous T-cell lymphomas. Onkologie 1996;19:226-230
CrossRef | Web of Science
- Citing Articles (1)
Citing Articles
1
Catherine H. Lee, Adam J. Mamelak, Eric C. Vonderheid. (2007) Erythrodermic cutaneous T cell lymphoma with hypereosinophilic syndrome: Treatment with interferon alfa and extracorporeal photopheresis. International Journal of Dermatology 46:11, 1198-1204
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