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Epstein-barr Virus-associated Lymphoproliferative Disease After Long-standing Cyclosporine Therapy For Psoriasis: A Case Of Spontaneous Regression

Lelievre, 2005Lymphoma

Lelièvre, J. D., Sacre, K., Adle-Biassette, H., Molinier-Frenkel, V., Gaulard, P., & Papo, T. (2005). Epstein-Barr virus-associated lymphoproliferative disease after long-standing cyclosporine therapy for psoriasis: a case of spontaneous regression. Journal of the American Academy of Dermatology, 52(2 Suppl 1), 24–27. https://doi.org/10.1016/j.jaad.2004.06.043

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Abstract

Posttransplant lymphoproliferative disorders are lymphoid proliferations or lymphomas, usually associated with Epstein-Barr virus infection, that develop as the consequence of immunodepression. These disorders usually affect patients receiving high doses of cyclosporine in the context of bone marrow or organ transplantations. Posttransplant lymphoproliferative disorders can regress when cyclosporine is discontinued. Such lymphoproliferations rarely occur for patients receiving low-dose cyclosporine treatments for autoimmune disorders. In the following report, we describe a patient with psoriasis vulgaris treated with long-term low-dose cyclosporine who developed an acute Epstein-Barr virus-associated clonal lymphoproliferative disorder associated with hemophagocytic syndrome. This lymphoproliferative disorder resembling classic posttransplant lymphoproliferative disorder regressed when cyclosporine was discontinued.

Case Details

Disease Location

Splenomegaly, axillary, inguinal, and cervical lymph nodes

Personal Characteristics

52 -year-old male, caucasian 1986 was enrolled in a cyclosporine therapy for psoriasis vulgaris. Methotrexate was given before for 6 months but was discontinued because of hepatic side effects. The cyclosporine resulted in a complete disappearance of dermatologic lesions

Clinical Characteristics

In may 2001 was referred for a 3-week fever with sweats, asthenia, and weight loss physical exam disclosed splenomegaly and axillary, inguinal and cervical lymphadenopathies blood cell counts showed 9.6x10^9/l white cells (6.7x10^9/l neutrophil, and 2.4x10^9/l lymphocytes), hematocrit of 0.32, and platelet count of 115x10^9/l. Serum lactate dehydrogenase level as 4492u/l. Creatininemis was 209 micromol/l. Baseline creatininemia was 150 micromol/l. This mild renal insufficiency was attributed to cyclosporine and was the only side effect reported to the chronic consumption of cyclosporine. C-reactive protein value was 360mg/l. Other routine biologic parameters were normal. HIV test was negative. But serologic test for ebv were consistent with ancient ebv infection. CT scan confirmed splenomegaly and showed the presence of numerous centimetric mediastinal and retroperitoneal lymph nodes. A lymphoproliferative disease was suggested and cyclosporine was stopped cervical ln biopsy lead to a diagnosis of polymorphic b-cell lymphoproliferative disease associated with ebv with evidence of a clonal disease two days later anemia and thrombopenia worsened. A marked elevation of serum ferritin was noted and mild hypertriglyceridemia. Bone marrow aspiration revealed presence of actively phagocytosing macrophages. These findings were consistent with hemophagocytosis. Histologic exam of the biopsy specimen disclosed molymorphic population of lymphoid cells consisting of atypical medium lymphocytes with plasmocytic differentiation admixed with scattered large cells displaying immunoblastic characteristics, a few plasmocytes, and small lymphocytes. Mitosis and apoptotic figures were numerous. Immunohistochemical analysis revealed the b-cell phenotype of the atypical medium cells that disclosed heterogeneous staining for cd79a, and CD138 antigens, and were positive for bob.1, b-cell transcripatiention factor. A few large cells were CD20+ and 30+ and expressed ebv/lmp-1. Numerous CD3+ t lymphocytes were admixed. In suto hybridization using eber probes showed strong nuclear staining of the atypical medium and large lymphoid cells, confirming the ebv association. Polymerase chain reaction analysis evidenced a clonal rearrangement of immunoglobulin heavy chain genes and the presence of an oligoclonal t-cell population. There features corresponded to a clonal ebv-positive polymorphic lymphoproliferative disorder

Remission Characteristics

After the transient worsening, the patients status gradually improved without additional treatment. One months later, all biologic abnormalities had disappeared. Small cervical and axillary lymph nodes were still detectable but splenomegaly had regressed. 30 months later, he had no evidence of relate and psoriasis was controlled by topical treatment

Treatment & Mechanisms

Proposed Remission Mechanisms

Discontinuation of the cyclosporine therapy

Clinical Treatment

Methotrexate, but was discontinued cyclosporine for psoriasis vulgaris topical treatment

Non-Clinical Treatment

None reported