Aug 10, 2017 - In adults, an association between IgA vasculitis and cancer â ... Could the leuko- cytoclastic vasculitis that was observed on exami- nation of ...
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logical response was due to the lower volume or Debra L. Waters, Ph.D. to the interference effect. Accordingly, the com- University of Otago bination exercise program improved functional Dunedin, New Zealand status the most, indicating no interference effect. Clifford Qualls, Ph.D. We agree that a confidence interval of the differ- University of New Mexico School of Medicine ence includes more information than P values in Albuquerque, NM Since publication of their article, the authors report no fursimple situations. Although, like P values, confidence intervals alone do not establish clinical ther potential conflict of interest. importance, one needs some clinical idea of mini- 1. Villareal DT, Chode S, Parimi N, et al. Weight loss, exercise, mally important differences.4 The 95% confi- or both and physical function in obese older adults. N Engl J 2011;364:1218-29. dence interval for the difference in the change in Med 2. Bowman K, Delgado J, Henley WE, et al. Obesity in older PPT scores between the combination group and people with and without conditions associated with weight loss: either exercise group was 0.5 to 2.7 (in each follow-up of 955,000 primary care patients. J Gerontol A Biol Sci Med Sci 2017;72:203-9. comparison); the information needed to compute 3. Wilson JM, Marin PJ, Rhea MR, Wilson SM, Loenneke JP, the confidence intervals between groups is pro- Anderson JC. Concurrent training: a meta-analysis examining interference of aerobic and resistance exercises. J Strength Cond vided in Table 2 of our article. Res 2012;26:2293-307.
Dennis T. Villareal, M.D.
4. Revicki D, Hays RD, Cella D, Sloan J. Recommended meth-
ods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol 2008;61:102-9.
Baylor College of Medicine Houston, TX dennis.villareal@bcm.edu
DOI: 10.1056/NEJMc1708176
Case 14-2017: A Man with Pain and Swelling of the Left Calf and a Purpuric Rash To the Editor: In the discussion of Case 142017 (May 11 issue),1 a patient who had Crohn’s disease and was receiving adalimumab therapy presented with IgA vasculitis. An underlying cancer perhaps should have been considered, despite the absence of “constitutional symptoms, lymphadenopathy, or a testicular mass.” In adults, an association between IgA vasculitis and cancer — especially pulmonary, prostatic, and renal carcinomas but also hematologic cancer — has been described.2,3 Adalimumab therapy has also been associated with cancer; for example, in a prospective registry, the risk of lymphoma was two to three times as high among patients who were receiving adalimumab as it was among those who were not.4 However, a meta-analysis has suggested that anti–tumor-necrosis-factor (TNF) therapy is not associated with an increased risk of cancer in patients with inflammatory bowel diseases, although there may have been an increase in skin cancer and lymphoma among those patients.5 The data in the meta-analysis are from cohort studies, postmarketing registries, and meta-
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analyses of randomized trials, all with methodologic weaknesses.5 François Rodrigues, M.D. Sophie Georgin‑Lavialle, M.D., Ph.D. Claude Bachmeyer, M.D. Hôpital Tenon Paris, France claude.bachmeyer@tnn.aphp.fr No potential conflict of interest relevant to this letter was reported. 1. Case Records of the Massachusetts General Hospital (Case 14-2017). N Engl J Med 2017;376:1868-77. 2. Pertuiset E, Lioté F, Launay-Russ E, Kemiche F, CerfPayrastre I, Chesneau AM. Adult Henoch-Schönlein purpura associated with malignancy. Semin Arthritis Rheum 2000;29:360-7. 3. Podjasek JO, Wetter DA, Pittelkow MR, Wada DA. HenochSchönlein purpura associated with solid-organ malignancies: three case reports and a literature review. Acta Derm Venereol 2012;92:388-92. 4. Mariette X, Tubach F, Bagheri H, et al. Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry. Ann Rheum Dis 2010;69:400-8. 5. Williams CJ, Peyrin-Biroulet L, Ford AC. Systematic review with meta-analysis: malignancies with anti-tumour necrosis factor-α therapy in inflammatory bowel disease. Aliment Pharmacol Ther 2014;39:447-58. DOI: 10.1056/NEJMc1707419
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Correspondence
To the Editor: Miloslavsky et al. discuss the approach to a rash and left-calf swelling in a young man with Crohn’s disease who had been treated with adalimumab for 3 years. Could the leukocytoclastic vasculitis that was observed on examination of skin-biopsy specimens have been caused by adalimumab use rather than primary IgA vasculitis? If vasculitis induced by a TNF-α inhibitor had been the diagnosis, then the need for prednisone may have been obviated, since the disorder would have resolved with discontinuation of adalimumab. This entity was among the diagnostic considerations outlined by Dr. Moy in her discussion of the pathological material and has been reported in the literature.1-3 The diagnosis would not only adhere to the principle of Occam’s razor but also perhaps better explain the crusting of the nares. Further evidence supporting this possibility is the use of a dose of adalimumab that was higher than the usually recommended dose (injections weekly rather than every other week) in this patient. Was the adalimumab discontinued upon the initiation of prednisone? Christopher Kandel, M.D. Gabor Kandel, M.D. University of Toronto Toronto, ON, Canada christopher.kandel@mail.utoronto.ca No potential conflict of interest relevant to this letter was reported. 1. Ramos-Casals M, Brito-Zerón P, Muñoz S, et al. Autoim-
mune diseases induced by TNF-targeted therapies: analysis of 233 cases. Medicine (Baltimore) 2007;86:242-51. 2. Sokumbi O, Wetter DA, Makol A, Warrington KJ. Vasculitis associated with tumor necrosis factor-α inhibitors. Mayo Clin Proc 2012;87:739-45. 3. Saint Marcoux B, De Bandt M. Vasculitides induced by TNFalpha antagonists: a study in 39 patients in France. Joint Bone Spine 2006;73:710-3. DOI: 10.1056/NEJMc1707419
The discussants reply: Rodrigues and colleagues highlight the possibility of an underlying neoplasm, since both IgA vasculitis and treatment with TNF inhibitors may be associated with cancer. Small case series have reported an association between IgA vasculitis and cancer; however, epidemiologic studies have not been adequate to definitively connect these two entities and the frequency of this association is not known. Furthermore, most patients with cancer and IgA vasculitis have been older than 60 years of age.1 This patient was
22 years of age, had several possible precipitating factors for IgA vasculitis, and had no signs or symptoms of cancer, and therefore, the possibility of a neoplasm was unlikely in our opinion. The association between cancer (particularly skin cancer and lymphoma) and the administration of TNF-α inhibitors has been the subject of several studies with conflicting results, as Rodrigues and colleagues point out. For example, a recent nationwide, registry-based cohort study in Denmark that included 489,000 patients with inflammatory bowel disease did not show an increased risk of cancer in patients treated with TNF-α inhibitors.2 Moreover, conditions that are treated with TNF inhibition, such as rheumatoid arthritis and inflammatory bowel disease, are associated with an increased risk of cancer that is independent of TNF-directed therapy.3 Kandel and Kandel call attention to the important possibility of adalimumab-induced IgA vasculitis. Several small case series have described this association, but again, robust epidemiologic studies are needed before the link can be validated.4 For the reasons outlined in the case discussion, particularly the striking upper respiratory tract infection that preceded the onset of the patient’s syndrome and the fact that he had been receiving adalimumab for 3 years, we thought that the most likely explanation for the illness was IgA vasculitis that was triggered by an antecedent upper respiratory tract infection. Eli M. Miloslavsky, M.D. John H. Stone, M.D., M.P.H. Massachusetts General Hospital Boston, MA Since publication of their article, the authors report no further potential conflict of interest. 1. Zurada JM, Ward KM, Grossman ME. Henoch-Schönlein purpura associated with malignancy in adults. J Am Acad Dermatol 2006;55:Suppl:S65-S70. 2. Nyboe Andersen N, Pasternak B, Basit S, et al. Association between tumor necrosis factor-α antagonists and risk of cancer in patients with inflammatory bowel disease. JAMA 2014;311: 2406-13. 3. Chakravarty EF, Genovese MC. Associations between rheumatoid arthritis and malignancy. Rheum Dis Clin North Am 2004;30:271-84. 4. Saint Marcoux B, De Bandt M. Vasculitides induced by TNFalpha antagonists: a study in 39 patients in France. Joint Bone Spine 2006;73:710-3. DOI: 10.1056/NEJMc1707419 Correspondence Copyright © 2017 Massachusetts Medical Society.
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