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Dermatomyositis and its associated tumors: etiology and therapeutic strategy
Paroxysmal erubescence acts as a clinical sign of certain kinds of internal tumors
Two Other Kinds of Cutaneous Manifestations of Internal Malignancy
Paraneoplastic Pemphigus Might Be Important Type of Cutaneous Manifestation of Internal Malignancy
Reply to Pei et al.
Finger Clubbing as a Clinical Sign
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Siwang Wang, Professor Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Qing Miao and Yurong Li
Send letter to journal:
wangsiw{at}fmmu.edu.cn Siwang Wang, et al.
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Dear Editor: We read "Cutaneous Manifestations of Internal Malignancy" with great interest [1]. In this review, Dr. Thiers et al. summarized the dermatologic changes of internal cancers. The authors have pointed out that dermatomyositis acted as a potential indicator for internal cancers. However, they did not mention the etiology of dermatomyositis and the process of potential carcinogenesis. In recent years, increasing evidence reveals that dermatomyositis is a skin-related symptom that accompanies muscle inflammation. Genetic factors, such as evaluated expression of HLA-B8, HLA-DR3, HLA-DR52, HLA-DR6, and HLA-DR7 have been detected [2]. Bacterial or viral infection may facilitate the development of dermatomyositis. The incidence of dermatomyositis with malignancy is 5%-34% and the patients would get better after the control of tumors. Meanwhile, antibody testing suggests that dermatomyositis is an autoimmune disease supporting by elevated content of Jo-1, anti-PL-7, anti-PL-12, anti-Mas, anti-Fer. Generally, carcinogenesis is connected with genetic factors, while the occurrence of dermatomyositis might be associated with autoimmunity. Therefore, the relationship between genetic factors and immunity in the process of dermatomyositis should be further studied. The therapeutic strategy of dermatomyositis also calls for great attention. Until now, there is not yet a cure for myositis; for some patients, treatments can effectively control and improve symptoms. Corticosteroid and immunosuppressants are the best choice for patients without malignancy. We adopt the therapeutic strategy that cancer treatment should be given priority to muscle weakness in the tumor-associated myositis [3], and the prognosis and cutaneous symptoms significantly improved after tumor control, suggesting dermatomyositis might be induced by internal tumors. Corticosteroid and immunosuppressants should be carefully administered for the potential risk of tumor spread. Other drugs for dermatomyositis could be used during tumor treatment if the therapeutic effects of anti-tumor agents could be guaranteed. Yours sincerely, Qing Miao, MD (1)
1 Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, 17 Changle West Road, Xi'an, Shaanxi, People's Republic of China. 2 Department of Radiation Medicine, School of Military Preventive Medicine, Fourth Military Medical University, 17 Changle West Road, Xi'an, Shaanxi, People's Republic of China. Correspondence: Siwang Wang, Prof, e-mail: wangsiw@fmmu.edu.cn, Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, 17 Changle West Road, Xi'an, Shaanxi, People's Republic of China. References 1. Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59:73-98. 2. Sallum AM, Kiss MH, Silva CA, et al. MHC class I and II expression in juvenile dermatomyositis skeletal muscle. Clin Exp Rheumatol. 2009;27:519-26. 3. Fardet L, Rybojad M, Gain M, et al. Incidence, risk factors, and severity of herpesvirus infections in a cohort of 121 patients with primary dermatomyositis and dermatomyositis associated with a malignant neoplasm. Arch Dermatol. 2009;145:889-93. |
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Jin-Lian Li, Professor Department of Anatomy and K.K. Leung Brain Research Center, Fourth Military Medical University
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lijinlian{at}yahoo.com Jin-Lian Li
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Dear Editor, We read the paper entitled "Cutaneous Manifestations of Internal Malignancy" [1] with great interest. The paper showed that the internal cancers also exhibited secondary cutaneous changes besides primary symptoms. Thus, cutaneous changes might reflect internal malignancy. However, there are some points that should be addressed in the paper. Several kinds of tumor cells exhibit neuroendocrine activity. For instance, the oat cells in the small cell lung cancer, the argentaffin cells in the gastrointestinal tumors, and cancer cells in fibrosarcoma can secrete secrotonin, bradykinin, and other vasoactive substances. These ectopic secreted vasodilator substances would cause cardiovascular response and subsequently result in cutaneous change by paroxysmal telangiectasis in the face, the neck, and the upper thoracic region [2-3]. Thus, paroxysmal erubescence could be observed in patients with certain kinds of tumors. Although paroxysmal erubescence is not a specific sign of certain kinds of tumors, this cutaneous change should not be omitted during physiological examinations. The observation of paroxysmal erubescence might indicate certain kinds of internal tumors. Thank you, Jin-Lian Li, MD Department of Anatomy and K.K. Leung Brain Research Center, Fourth Military Medical University, #17 West Changle Road, Xi'an, 710032, PR China References [1] Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59:73-98. [2] Waldmann TA, Misiti J, Nelson DL, et al. Ataxia-telangiectasis: a multisystem hereditary disease with immunodeficiency, impaired organ maturation, x-ray hypersensitivity, and a high incidence of neoplasia. Ann Intern Med. 1983;99:367-379. [3] Richer CL, Selye H. A syndrome of multiple telangiectases produced by a transplantable fibrosarcoma. Cancer Res. 1956;16:856-859. |
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Xiaolong Yan, Surgeon Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Han Jing, Jian Wang, Yunfeng Ni, Yongan Zhou, Xiaofei Li
Send letter to journal:
yanxiaolong{at}fmmu.edu.cn Xiaolong Yan, et al.
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Dear Editor, The article written by Thiers et al. [1], provides an excellent overview on cutaneous manifestations associated with internal cancer. We benefited a great deal from the extensive content. However there are still two other kinds of cutaneous manifestations of internal malignancy which comply with the criteria of Curth's postulates. First, jaundice is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae, and other mucous membranes caused by hyperbilirubinemia [2]. Jaundice may result from pancreatic cancer, hepatocellular carcinoma, ampullary cancer, cholangio-carcinoma, gallbladder cancer, and malignant lymphadenopathy or metastatic lesions [3,4]. Second, necrobiotic xanthogranuloma (purpuric yellow plaques in periorbital and flexural areas) and plane xanthoma (yellow-orange macules or plaques) could accompany multiple myeloma [5,6,7,8]. The underlying mechanism may be immunological, but not yet well defined [7,8]. Yours Sincerely, Xiaolong Yan, MD, PhD (1)
1 Department of Thoracic Surgery, Tangdu Hospital, Fourth Military
Medical University, Xi'an City, Shaanxi Province 710038, China
Correspondence to: Prof. Xiaofei Li (lxfchest@fmmu.edu.cn) and Yongan Zhou(zhouya@fmmu.edu.cn); Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an City, Shaanxi Province 710038, China. References [1] Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59(2):73-98. [2] Guyton A, Hall JE. Textbook of Medical Physiology. Philadelphia, PA: Saunders; 2005. [3] Cipolletta L, Rotondano G, Marmo R, et al. Endoscopic palliation of malignant obstructive jaundice: an evidence-based review. Dig Liver Dis. 2007;39(4):375-88. [4] Bowden L. Cancer of the pancreas. CA Cancer J Clin. 1972;22(5):274-83. [5] Wood AJ, Wagner MV, Abbott JJ, et al. Necrobiotic xanthogranuloma: a review of 17 cases with emphasis on clinical and pathologic correlation. Arch Dermatol. 2009;145(3):279-84. [6] Yoon YH, Cho WI, Seo SJ. Case of multiple myeloma associated with extramedullary cutaneous plasmacytoma and pyoderma gangrenosum. Int J Dermatol. 2006;45(5):594-7. [7] Langlois S, Brochot P, Reguiai Z, et al. Necrobiotic xanthogranuloma with multiple myeloma. Case report and pathogenic hypotheses. Joint Bone Spine. 2006;73(1):120-2. [8] Ugurlu S, Bartley GB, Gibson LE. Necrobiotic xanthogranuloma: long-term outcome of ocular and systemic involvement. Am J Ophthalmol. 2000;129(5):651-7. |
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Chunyan Yao, PhD, MD Southwest Hospital, Third Military Medical University, Tangyou Zhu
Send letter to journal:
yao_yao24{at}yahoo.com Chunyan Yao, et al.
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Dear Editor, We read with interest the article by Thiers et al. about "Cutaneous Manifestations of Internal Malignancy" [1], which helps us understand the importance of cutaneous manifestations in detection of internal malignancy. The authors provide an outstanding summary of the clinical manifestations, include an update on any new knowledge regarding disease pathogenesis, and provide practical advice regarding patient management. It is reasonable to point out paraneoplastic pemphigus could be an important type of cutaneous disorders, associated with the underlying malignancy. Paraneoplastic pemphigus is an autoimmune vesiculobullous and erosive mucocutaneous disease associated with an underlying malignancy. Reported malignancies include chronic lymphocytic leukemia, non-Hodgkin's lymphoma, Castleman's disease, uterine carcinoma, and rarely solid tumors [2-4]. In some cases, although the various laboratory studies pointed to the diagnosis of paraneoplastic pemphigus, the underlying neoplasm was not detected until 6 months later by the biopsies [5]. Awareness of the mucocutaneous manifestations of paraneoplastic pemphigus, and confirmation of this diagnosis by simple laboratory techniques can facilitate the early detection of occult neoplasia [6]. In the absence of a clear diagnosis, malignancy should be suspected and extensive work-up performed. Clinicians should be highly suspicious when signs and symptoms suggestive of paraneoplastic pemphigus are present. Yours sincerely, Chunyan Yao (1)
1. Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, P. R. China 2. Department of Dermatology, Daping Hospital, Third Military Medical University, Chongqing, 400042, P. R. China Corresponding Author:
References [1] Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59:73-98. [2] Taintor AR, Leiferman KM, Hashimoto T, et al. A novel case of IgA paraneoplastic pemphigus associated with chronic lymphocytic leukemia. J Am Acad Dermatol. 2007;56:S73-S76. [3] Kaplan I, Hodak E, Ackerman L, et al. Neoplasms associated with paraneoplastic pemphigus: a review with emphasis on non-hematologic malignancy and oral mucosal manifestations. Oral Oncol. 2004;40:553-562. [4] Niimi Y, Kawana S, Hashimoto T, Kusunoki T. Paraneoplastic pemphigus associated with uterine carcinoma. J Am Acad Dermatol. 2003;48:S69-S72. [5] van der Waal RIF, Pas HH, Anhalt GJ, et al. Paraneoplastic pemphigus as the presenting symptom of a lymphoma of the tongue. Oral Oncol. 1998;34:567-570. [6] Iranzo DP, Xaubet A, Carrera C, et al. Bronchiolitis obliterans associated with paraneoplastic pemphigus: a paraneoplastic autoimmune multiorgan syndrome. Arch Bronconeumol. 2004;40:240-243. |
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Bruce H. Thiers, MD Dept of Dermatology and Dermatologic Surgery, Medical University of South Carolina
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thiersb{at}musc.edu Bruce H. Thiers, MD
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We thank Pei et al. for their comments. As pointed out in the introduction to the section on Proliferative and Inflammatory Dermatoses, among which clubbing and related disorders are included, these conditions are nonspecific and may occur both in association with and in the absence of an underlying neoplasm. Provoking factors other than malignancy may often be found on careful physical examination. Bruce H. Thiers, MD |
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Jianming Pei, MD, PhD Department of Physiology, Fourth Military Medical University, Mingxiang Ye, MS, Dinghua Yi, MD
Send letter to journal:
jmpei8{at}fmmu.edu.cn Jianming Pei, MD, PhD, et al.
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Dear Editor, Skin alterations often reflect internal neoplasms. The establishment of a relationship between an internal malignancy and a cutaneous disorder would help us in the early diagnosis of neoplasms. Clubbing fingers remain an important clinical sign. The strong association of clubbing fingers with serious disease is still a clinical enigma. Digital clubbing is associated with a variety of pulmonary and non-pulmonary diseases not restricted to lung cancer. In "Cutaneous Manifestations of Internal Malignancy" by Thiers et al., the authors mention that clubbing fingers were observed in patients with lung cancer, especially in patients with bronchiogenic carcinoma [1]. Although the authors never suggest that clubbing is a specific sign of lung cancer, it is reasonable to point out that clubbing is also linked to many other conditions. All etiologies leading to ischemia and hypoxia would induce hypertrophic osteoarthropathy. So we can often see clubbing fingers in patients with bronchiectasis, pulmonary abscess, thoracic empyema, cyanosed congenital heart disease, and infective endocarditis [2-5]. All these diseases have a negative impact on lung ventilation and pulmonary ventilation, but they don’t indicate the occurrence of neoplasm. Meanwhile, clubbing fingers are also observed in patients with liver cirrhosis and inflammatory bowel disease [6-7], which means the succedent occurrence of hepatitic carcinoma and gastrointestinal malignancy. Children suffering from intrathoracic Hodgkin’s disease also exhibit signs of clubbing fingers [8]. Interestingly, HIV infection, which easily promotes the occurrence of neoplasm, can lead to clubbing fingers as well [9]. So if clubbing fingers can reflect an internal malignancy, the authors should mention not only bronchiogenic carcinoma, but also hepatitic carcinoma, gastrointestinal malignancy, Hodgkin’s disease, and HIV infection. Thank You, 1Department of Physiology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi’an, Shaanxi, China 2Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China Correspondence: Jianming Pei, MD, PhD, Department of Physiology, Fourth Military Medical University, or Dinghua Yi, MD, PhD, Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Changle West Road, No.17, Xi’an, Shaanxi, China; e-mail: jmpei8@fmmu.edu.cn or dhyi@fmmu.edu.cn References [1] Thiers BH, Sahn RE, Callen JP. Cutaneous manifestations of internal malignancy. CA Cancer J Clin. 2009;59:73-98. [2] Spicknall KE, Zirwas MJ, English III JC. Clubbing: An update on diagnosis, differential diagnosis, pathophysiology, and clinical relevance. J Am Acad Dermatol. 2005;52:1020-1028. [3] Richet H, Casalta JP, Thuny F, et al. Development and assessment of a new early scoring system using non-specific clinical signs and biological results to identify children and adult patients with a high probability of infective endocarditis on admission. J Antimicrob Chemother. 2008;62:1434-1440. [4] Ozdemir B, Sentürk T, Kaderli AA, et al. Postoperative regression of clubbing at an unexpected rate in a patient with aortic and mitral valve replacement due to infective endocarditis. Ir J Med Sci. 2008 Oct 9. [Epub ahead of print] [5] Augarten A, Goldman R, Laufer J, et al. Reversal of digital clubbing after lung transplantation in cystic fibrosis patients: a clue to the pathogenesis of clubbing. Pediatr Pulmonol. 2002;34:378-380. [6] Koulaouzidis AK, Said EM. Clubbing in a patient with liver disease. Saudi Med J. 2007;28(3):481-482. [7] Kitis G, Thompson H, Allan RN. Finger clubbing in inflammatory bowel disease: Its prevalence and pathogenesis. Br Med J. 1979;2:825-828. [8] Kebudi R, Ayan I, Görgün O, et al. Hypertrophic osteoarthropathy and intrathoracic Hodgkin’s disease in children. Leukemia Res. 2006;30:899 -902. [9] Ddungu H, Johnson JL, Smieja M, et al. Digital clubbing in tuberculosis--relationship to HIV infection, extent of disease and hypoalbuminemia. BMC Infect Dis. 2006;6:45. |
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