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      Development of Two Primary Malignant Melanomas after Treatment with Adalimumab: A Case Report and Review of the Possible Link between Biological Therapy with TNF-α Antagonists and Melanocytic Proliferation

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          Abstract

          Biologics, such as tumor necrosis factor α (TNF-α) antagonists, have revolutionized treatment of several significant inflammatory autoimmune diseases. Nevertheless, issues concerning long-term safety remain to be clarified. There is growing evidence linking biological treatments with the occurrence of malignancies or reactivation of latent ones, including malignant melanoma. We report the case of a 75-year-old male patient who developed 2 primary malignant melanomas (MM) after treatment with adalimumab for rheumatoid arthritis. He was under adalimumab treatment for approximately 12 months before the diagnosis of MM on his right lower leg. After surgical removal and staging, no evidence of metastases was found. A few months later, a second MM developed on the patient’s scalp. The short duration of treatment with adalimumab and the unclear temporal relationship cannot adequately support a probable link between this double MM occurrence and the adalimumab-induced immunosuppressive state. The result of a literature search regarding the possible association between anti-TNF drugs and melanocytic proliferation is provided.

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          Skin cancers after organ transplantation.

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            Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration.

            Etanercept and infliximab are tumor necrosis factor (TNF) antagonists that have been recently approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). This study was undertaken to investigate the occurrence of lymphoproliferative disorders in patients treated with these agents. Relevant data in the MedWatch postmarket adverse event surveillance system run by the US Food and Drug Administration were reviewed. We identified 26 cases of lymphoproliferative disorders following treatment with etanercept (18 cases) or infliximab (8 cases). The majority of cases (81%) were non-Hodgkin's lymphomas. The interval between initiation of therapy with etanercept or infliximab and the development of lymphoma was very short (median 8 weeks). In 2 instances (1 infliximab, 1 etanercept), lymphoma regression was observed following discontinuation of anti-TNF treatment, in the absence of specific cytotoxic therapy directed toward the lymphoma. Although data from a case series such as this cannot establish a clear causal relationship between exposure to these medications and the risk of lymphoproliferative disease, the known predisposition of patients with RA and CD to lymphoma, the known excess of lymphoma in other immunosuppressed populations, and the known immunosuppressive effects of the anti-TNF drugs provide a biologic basis for concern and justification for the initiation of additional epidemiologic studies to formally evaluate this possible association.
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              Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists.

              Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear. To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA. A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed. Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas. Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.
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                Author and article information

                Journal
                DRM
                Dermatology
                10.1159/issn.1018-8665
                Dermatology
                S. Karger AG
                1018-8665
                1421-9832
                2010
                August 2010
                13 May 2010
                : 221
                : 1
                : 9-12
                Affiliations
                2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens, School of Medicine, ‘Attikon’ General University Hospital, Athens, Greece
                Author notes
                *A.C. Katoulis, 2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens, School of Medicine, ‘Attikon’ General University Hospital, 1 Rimini Street, GR–12461 Chaidari, Athens (Greece), Tel. +30 210 583 2396, Fax +30 210 583 2397, E-Mail alexanderkatoulis@yahoo.co.uk
                Article
                300136 Dermatology 2010;221:9–12
                10.1159/000300136
                20484878
                3c23c949-0996-4b62-b395-f883c0698648
                © 2010 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 24 July 2009
                : 03 September 2010
                Page count
                Tables: 1, References: 24, Pages: 4
                Categories
                Case and Review

                Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Biological therapy,Adalimumab,Immunosuppression,Eruptive melanocytic nevi,TNF-α antagonist,Malignant melanoma

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