Musculoskeletal Syndromes Associated With Malignancy

Naschitz JE. Rheumatic syndromes: clues to occult neoplasia. Curr Opin Rheumatol 2001; 13:62-66.
• Andras C, Csiki Z, Ponyi A, et al. Paraneoplastic rheumatic syndromes. Rheumatol Int 2006; 26:376-382.
Hill AB. The environment and disease: association or causation? Proc R Soc Med 1965; 58:293-300.
Villa AR, Kraus A, Alarcon-Segovia D. Autoimmune rheumatic diseases and cancer: evidence of causality? In: Shoenfeld Y, Gershwin ME, editors. Cancer and autoimmunity. Amsterdam: Elsevier; 2000. pp. 111-117.
Van Reekum R, Streiner DL, Conn DK. Applying Bradford Hill's Criteria for Causation to Neuropsychiatry. Challenges and Opportunities. Neuropsychiatry Clin Neurosci 2001; 13:318-325.
Hill CL, Zhang Y, Sigurgeirsson B, et al. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet 2001; 357:96-100.
Buchbinder R, Forbes A, Hall S, et al. Incidence of malignant disease in biopsy-proven inflammatory myopathy. A population-based cohort study. Ann Intern Med 2001; 134:1087-1095.
Fiorentino D, Callen J. Dermatomyositis. In: Williams H, Bigby M, Diepgen T, et al., editors. Evidence-based Dermatology. 2nd ed. Blackwell; 2003.
Ponyi A, Constantin T, Garami M, et al. Cancer-associated myositis: clinical features and prognostic signs. Ann N Y Acad Sci 2005; 1051:64-71.
Chen YJ, Wu CY, Shen JL. Predicting factors of malignancy in dermatomyositis and polymyositis: a case-control study. Br J Dermatol 2001; 144:825-831.
•• Levine SM. Cancer and myositis: new insights into an old association. Curr Opin Rheumatol 2006; 18:620-624. Remarkable and enlightening.
Casciola-Rosen L, Nagaraju K, Plotz P, et al. Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy. J Exp Med 2005; 201:591-601.
Okada T, Noji S, Goto Y, et al. Immune responses to DNA mismatch repair enzymes hMSh3 and hPMS1 in patients with pancreatic cancer, dermatomyositis and polymyositis. Int J Cancer 2005; 116:925-933.
Tallai B, Flasko T, Gyorgy T, et al. Prostate cancer underlying acute, definitive dermatomyositis: successful treatment with radical perineal prostatectomy. Clin Rheumatol 2006; 25:119-120.
Yoshinaga A, Hayashi T, Ishii N, et al. Successful cure of dermatomyositis after treatment of nonseminomatous testicular cancer. Int J Urol 2005; 12:593-595.
Darnell RB, DeAngelis LM. Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies. Lancet 1993; 341:21-22.
Guegan S, Poszepczynska-Guigne E, Wechsler J, et al. Severe necrotic and haemorrhagic edema of the upper limbs revealing remitting seronegative symmetrical synovitis with pitting edema. Ann Dermatol Venereol 2006; 133:795-798.
• Liozon E, Loustaud V, Fauchais AL, et al. Concurrent temporal (giant cell) arteritis and malignancy: report of 20 patients with review of the literature. J Rheumatol 2006; 33:1606-1614.
• Yanagi T, Matsumura T, Kamekura R, et al. Relapsing polychondritis and malignant lymphoma: is polychondritis paraneoplastic? Arch Dermatol 2007; 143:89-90. An update.
Ekstrom K, Hjalgrim H, Brandt L, et al. Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-degree relatives. Arthritis Rheum 2003; 48:963-970.
•• Bernatsky S, Ramsey-Goldman R, Clarke A. Malignancy and autoimmunity. Curr Opin Rheumatol 2006; 18:129-134.
Mellemkjaer L, Linet MS, Gridley G, et al. Rheumatoid arthritis and cancer risk. Eur J Cancer 1996; 32A:1753-1757.
Gridley G, McLaughlin JK, Ekbom A, et al. Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 1993; 85:307-311.
Baron JA. Epidemiology of nonsteroidal anti-inflammatory drugs and cancer. Prog Exp Tumor Res 2003; 37:1-24.
Askling J, Fored CM, Baecklund E, et al. Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists. Ann Rheum Dis 2005; 64:1414-1420.
Wolfe F, Michaud K. Lymphoma in rheumatoid arthritis: the effect of methotrexate and antitumor necrosis factor therapy in 18,572 patients. Arthritis Rheum 2004; 50:1740-1751.
•• Landgren O, Engels EA, Pfeiffer RM, et al. Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. J Natl Cancer Inst 2006; 98:1321-1330.
Martin T, Weber JC, Levallois H, et al. Salivary gland lymphomas in patients with Sjögren's syndrome may frequently develop from rheumatoid factor B cells. Arthritis Rheum 2000; 43:908-916.
Starkebaum G, Sasso EH. Hepatitis C and B cells: induction of autoimmunity and lymphoproliferation may reflect chronic stimulation through cell-surface receptors. J Rheumatol 2004; 31:416-418.
Lenze D, Berg E, Volkmer-Engert R, et al. Influence of antigen on the development of MALT lymphoma. Blood 2006; 107:1141-1148.
Mariette X, Cazals-Hatem D, Warszawki J, et al. Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood 2002; 99:3909-3915.
•• Baecklund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 2006; 54:692-701.
• Nadkarni S, Mauri C, Ehrenstein MR. Anti-TNF-{alpha} therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-{beta}. J Exp Med 2007; 204:33-39. How long is the distance from the bench to bedside?
• Saleem B, Nizam S, Emery P. Can remission be maintained with or without further drug therapy in rheumatoid arthritis? Clin Exp Rheumatol 2006; 24:S033-S036. Conclusions of this study are challenging and fervent discussions.
Van Der Kooij SM, van der Bijl AE, Allaart CF, et al. Remission induction in early rheumatoid arthritis with initial infliximab and methotrexate therapy: The Disease Course After IFX Discontinuation in The BeSt Trial [abstract]. Arthritis Rheum 2006; 54(Suppl):S302.
•• Bongartz T, Sutton AJ, Sweeting MJ, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 2006; 295:2275-2285.
•• Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006; 54:26-37.
Bernatsky S, Boivin J-F, Joseph L, et al. An international cohort study of cancer in SLE. Arthritis Rheum 2005; 52:1481-1490.
Chatterjee S, Dombi GW, Severson RK, et al. Risk of malignancy in scleroderma: a population-based cohort study. Arthritis Rheum 2005; 52:2415-2424.
Derk CT, Rasheed M, Spiegel JR, et al. Increased incidence of carcinoma of the tongue in patients with systemic sclerosis. J Rheumatol 2005; 32:637-641.
• Smedby KE, Hjalgrim H, Askling J, et al. Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J Natl Cancer Inst 2006; 98:51-60. The evidence is in agreement with previous observations.
•• Soderberg KC, Jonsson F, Winqvist O, et al. Autoimmune diseases, asthma and risk of haematological malignancies: a nationwide case-control study in Sweden. Eur J Cancer 2006; 42:3028-3033.
Saito M, Fukuda T, Shiohara T, et al. Angioimmunoblastic T-cell lymphoma: a relatively common type of T-cell lymphoma in Sjogren's syndrome. Clin Exp Rheumatol 2005; 23:888-890.
•• Askling J, Klareskog L, Blomqvist P, et al. Risk for malignant lymphoma in ankylosing spondylitis: a nationwide Swedish case-control study. Ann Rheum Dis 2006; 65:1184-1187.
Waldman SA, Terzic A. Translating MicroRNA Discovery Into Clinical Biomarkers in Cancer. JAMA 2007; 297:1923-1925.
Solans-Laque R, Perez-Bocanegra C, Salud-Salvia A, et al. Clinical significance of antinuclear antibodies in malignant diseases: association with rheumatic and connective tissue paraneoplastic syndromes. Lupus 2004; 13:159-164.
Ramos-Casals M. Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients. Lupus 2004; 13:777-783.
Brito-Zeron P, Ramos-Casals M, Nardi N, et al. Circulating monoclonal immunoglobulins in Sjögren syndrome: prevalence and clinical significance in 237 patients. Medicine 2005; 84:90-97.

processing....

Abstract and Introduction

Abstract

Purpose of review: To examine recent data about the association between rheumatic disorders and cancer. This article focuses on paraneoplastic rheumatic disorders, which usually precede by a short period of time the diagnosis of malignancy, and on malignant transformation, which occurs late in the course of rheumatic disorders. Evidence of causality between malignancies and rheumatic disorders was reviewed based on statistical indicators (standardized incidence ratios and odds ratios) and by applying Bradford Hill's criteria of causality.
Recent findings: Firm epidemiological evidence was found attesting that dermatomyositis and polymyostis may present as paraneoplastic syndromes. Several other musculoskeletal disorders may be present akin to paraneoplastic syndrome, based on clinicians' impressions, but with scarce epidemiological evidence supporting a causal determinism. In contrast, robust evidence has accumulated on the role of longstanding rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis as premalignant conditions. Evidence that systemic lupus erythematosus may evolve into lymphoma is equivocal.
Summary: The link between malignancies and rheumatic disorders may impact on clinical practice. First, paraneoplastic rheumatic syndromes can provide the clinician with hints for earlier diagnosis of occult cancer. Second, the risk of malignant transformation during the course of rheumatic disorders may motivate the search for strategies aimed at prevention.

Introduction: Cancer-associated/Paraneoplastic Disorders

Musculoskeletal disorders associated with malignancy may be classified according to the following categories: musculoskeletal disorders due to direct involvement by tumor of bones, joints, muscles; paraneoplastic syndromes; altered immune surveillance causing both the musculoskeletal and the neoplastic diseases; and adverse reactions to anticancer therapy. Paraneoplastic rheumatic disorders are those cancer-associated rheumatic syndromes that occur at a distance from the primary tumor or metastases and are induced by the malignancy through hormones, peptides, autocrine and paracrine mediators, antibodies, and cytotoxic lymphoctes. All are characterized by the relatively short interval between the appearance of the rheumatic disorder and diagnosis of its associated neoplasm, which in general does not exceed 2 years. In contrast to paraneoplastic syndromes, malignant transformation in the course of certain rheumatic disorders is the result of immune dysregulation; the time interval between the onset of the rheumatic disorder and diagnosis of the secondary malignancy may be as long as 20 years.^[1,2•]