- Email: [email protected]
Erythema nodosum and lung cancer
336
Letters to the editor / Joint Bone Spine 73 (2006) 329–337
Three of the FMF patients were complicated with vasculitic disorders (two patients with HSP, and one patient with PAN). Interestingly, all of them had at least one D allele of the ACE gene. Presence of the D allele was previously associated with the development of cardiovascular disorders and the severity of renal involvement in HSP, although conflicting data exist [11– 13]. However, since the incidence of the II polymorphism is low in both FMF patients without vasculitis and healthy controls, this observation could be a simple coincidence. In conclusion, our study suggested that there is no association between the ACE gene polymorphism and development of FMF. However, investigating the ACE gene polymorphism in FMF patients carrying different MEFV gene mutations, and also in FMF patients with no known MEFV mutation would be more informative for the role of the ACE gene in the pathogenesis of FMF (either as a modifier of the MEFV gene or a second susceptibility gene involved in the FMF phenotype). Moreover ACE gene polymorphism can also be investigated in increased number of FMF patients who are complicated with vasculitis in order to see whether the D allele of the ACE gene is associated with the vascular component of FMF. References [1]
Ben-Chetrit E, Levy M. Enigmas in familial Mediterranean fever (FMF). Clin Exp Rheumatol 2001;19:S1–5 (Suppl 24). [2] Kiraz S, Ertenli I, Arici M, Calguneri M, Haznedaroglu I, Celik I, et al. Effects of colchicine on inflammatory cytokines and selectins in familial Mediterranean fever. Clin Exp Rheumatol 1998;16:721–4. [3] Ruiz-Ortega M, Lorenzo O, Suzuki Y, Ruperez M, Egido J. Proinflammatory actions of angiotensins. Curr Opin Nephrol Hypertens 2001;10: 321–9. [4] Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–6. [5] Danser AH, Schalekamp MA, Bax WA, van den Brink AM, Saxena PR, Riegger GA, et al. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 1995;92: 1387–8. [6] Ozturk MA, Calguneri M, Kiraz S, Ertenli I, Ozbalkan Z, Onat AM, et al. Angiotensin converting enzyme gene polymorphism in Behçet’s disease. Clin Rheumatol 2004;23:142–6. [7] Haznedaroğlu IC, Öztürk MA. Towards the understanding of the local hematopoietic bone marrow renin–angiotensin system. Int J Biochem Cell Biol 2003;35:876–80. [8] Ruiz-Ortega M, Ruperez M, Lorenzo O, Esteban V, Blanco J, Mezzano S, et al. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int Suppl 2002;82:12–22. [9] Rahman ST, Lauten WB, Khan QA, Navalkar S, Parthasarathy S, Khan BV. Effects of eprosartan versus hydrochlorothiazide on markers of vascular oxidation and inflammation and blood pressure (renin–angiotensin system antagonists, oxidation, and inflammation). Am J Cardiol 2002;89:686–90. [10] Costerousse O, Allegrini J, Lopez M, Alhenc-Gelas F. Angiotensin Iconverting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochem J 1993;290:33–40. [11] Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, et al. A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 1995;332:706–11. [12] Yoshioka T, Xu YX, Yoshida H, Shiraga H, Muraki T, Ito K. Deletion polymorphism of the angiotensin converting enzyme gene predicts per-
sistent proteinuria in Henoch-Schönlein purpura nephritis. Arch Dis Child 1998;79:394–9. [13] Amoroso A, Danek G, Vatta S, Crovella S, Berrino M, Guarrera S, et al. Polymorphisms in angiotensin-converting enzyme gene and severity of renal disease in Henoch-Schönlein patients. Nephrol Dial Transplant 1998;13:3184–8.
Öztürk Meral Çalgüneri Department of Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey M. Akif Öztürk* Department of Rheumatology, Faculty of Medicine, Gazi University, Ankara, Turkey E-mail address: [email protected] (M.A. Öztürk). Sedat Kiraz İhsan Ertenli A. Mesut Onat Kemal Üreten Zeynep Özbalkan Department of Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey İbrahim C. Haznedaroğlu Department of Hematology, Faculty of Medicine, Hacettepe University, Ankara, Turkey Received 15 April 2005; accepted 19 August 2005 Available online 01 December 2005 *Corresponding author. Tel.: +90 312 395 1065. 1297-319X/$ - see front matter © Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2005.08.001
Erythema nodosum and lung cancer Keywords: Erythema nodosum; Cancer
Lung cancer is the most common cause of paraneoplastic syndromes. These may occur as the presenting manifestation, coincide with a recurrence, or develop at the terminal phase. A broad spectrum of paraneoplastic disorders occurs in association with lung cancer. The target organ may be the blood, nervous system, bone, endocrine glands, or skin. Paraneoplastic skin diseases known to occur in patients with lung cancer include woolly hypertrichosis, erythema gyratum repens, acrokeratosis (Basex syndrome), dermatomyositis, and Sweet syndrome [1,2]. We report a case of recurrent erythema nodosum in a patient with lung cancer. This 43-year-old male nonsmoker had no history of disease except for allergic rhinitis. He presented with a 2-month history of erythema nodosum over the shins that had failed to respond to indomethacin or potassium iodide. A nagging cough with blood-tinged sputum antedated the skin lesions by 1 month.
Letters to the editor / Joint Bone Spine 73 (2006) 329–337
Erythematous dermal and hypodermal nodules were found over the shins. The nodules were tender to palpation. Serum Creactive protein was 15 mg/dl and the erythrocyte sedimentation rate was 28 mm/h. The peripheral eosinophil count was increased to 1.47 × 109 per l. Results were normal from the other standard blood tests. A chest radiograph disclosed widening of the hilar area, partial atelectasis, and a distal density in the lover left lobe. Findings were normal or negative from an angiotensin-converting enzyme assay, an intradermal tuberculin test, and serological tests for atypical pneumonia. Computed tomography of the chest visualized a mass in the left lower lobe. The peribronchial and hilar lymph nodes draining the lobe were enlarged. A biopsy was obtained during fiberoptic bronchoscopy. Histology showed a non-small-cell carcinoma. The tumor was removed surgically. Postoperative chemotherapy produced a good initial response. Concomitantly, the erythema nodosum resolved. Erythema nodosum is the most common form of panniculitis seen in clinical practice. It may be idiopathic or secondary to a variety of causes (drugs, infections, systemic diseases, and malignancies). Erythema nodosum has been reported in patients with hematological malignancies (lymphomas) or solid tumors such as cancer of the colon, cervix, pancreas, and liver, as well as carcinoid tumor [3–10]. About 50 cases of erythema nodosum associated with malignancies have been reported. The skin lesions may antedate the symptoms of cancer by several months and may lead to the diagnosis of the cancer. Arguments that support a causal link include the simultaneous development of the two conditions, the absence of other causes of erythema nodosum, and the resolution of the skin lesions when effective anticancer treatment is given. That erythema nodosum can occur as a paraneoplastic disease has important prognostic and therapeutic implications. The appearance, histological nature, and distribution of the skin lesions are indistinguishable from those in erythema nodosum due to other causes or for which no cause is detectable. However, paraneoplastic erythema nodosum responds poorly to conventional treatment (antiinflammatory agents and potassium iodide). In our patient, the relapses suggested the presence of a malignancy, in accordance with many previous case-reports [3,6–10]. Patients with relap-
337
sing or treatment-resistant erythema nodosum should be investigated for malignant disease [3,6–10]. References [1] Cohen PR, Kurzrock R. Mucocutaneous paraneoplastic syndromes. Semin Oncol 1997;88:449–56. [2] Yamamoto T, Furuse Y, Nishioka K. Sweet’s syndrome with small cell carcinoma of the lung. J Dermatol 1994;21:125–7. [3] Matsuoka LY. Neoplastic erythema nodosum. J Am Acad Dermatol 1995;32:361–3. [4] Bonci A, Di Lernia V, Merli F, Lo Scocco G. Erythema nodosum and Hodgkin’s disease. Clin Exp Dermatol 2000;26:408–11. [5] Thomson GT, Keystone EC, Sturgeon JF, Fornasier V. Erythema nodosum and non-Hodgkin lymphoma. J Rheumatol 1990;17:383–5. [6] Lillo A, Gil MJ, Jimenez R, Monferrer R. Eritema nodoso y adenocarcinoma de colon. Med Clin (Barc) 1997;108:318. [7] Altomare GF, Capella GL. Paraneoplastic erythema nodosum in a patient with carcinoma of the uterine cervix. Br J Dermatol 1995;132:667–8. [8] Virshup AM, Saiwinski AJ. Polyarthritis and subcutaneous nodules associated with carcinoma of the pancreas. Arthritis Rheum 1973;16:388–92. [9] Glinkov S, Krasnaliev I, Atanassova M, Arnaudov P, Kirov K, Glinkova V. Hepatocellular carcinoma associated with paraneoplastic erythema nodosum and polyarthritis. J Hepatol 2003;39:656–7. [10] Lin JT, Chen PM, Huang DF, Kwang WK, Lo K, Wang WS. Erythema nodosum associated with carcinoid tumour. Clin Exp Dermatol 2004;29: 426–7.
Noemí Busquets Perez Berta Bernad Javier Narváez* José Valverde Department of Rheumatology (planta 10-2), Hospital Universitario de Bellvitge, Feixa Llarga, s/n, 08907, Hospitalet de Llobregat, Barcelona, Spain E-mail address: [email protected] (J. Narváez). Received 7 March 2005; accepted 8 June 2005 Available online 01 December 2005 *Corresponding author. 1297-319X/$ - see front matter © Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2005.10.009
Letters to the editor / Joint Bone Spine 73 (2006) 329–337
Three of the FMF patients were complicated with vasculitic disorders (two patients with HSP, and one patient with PAN). Interestingly, all of them had at least one D allele of the ACE gene. Presence of the D allele was previously associated with the development of cardiovascular disorders and the severity of renal involvement in HSP, although conflicting data exist [11– 13]. However, since the incidence of the II polymorphism is low in both FMF patients without vasculitis and healthy controls, this observation could be a simple coincidence. In conclusion, our study suggested that there is no association between the ACE gene polymorphism and development of FMF. However, investigating the ACE gene polymorphism in FMF patients carrying different MEFV gene mutations, and also in FMF patients with no known MEFV mutation would be more informative for the role of the ACE gene in the pathogenesis of FMF (either as a modifier of the MEFV gene or a second susceptibility gene involved in the FMF phenotype). Moreover ACE gene polymorphism can also be investigated in increased number of FMF patients who are complicated with vasculitis in order to see whether the D allele of the ACE gene is associated with the vascular component of FMF. References [1]
Ben-Chetrit E, Levy M. Enigmas in familial Mediterranean fever (FMF). Clin Exp Rheumatol 2001;19:S1–5 (Suppl 24). [2] Kiraz S, Ertenli I, Arici M, Calguneri M, Haznedaroglu I, Celik I, et al. Effects of colchicine on inflammatory cytokines and selectins in familial Mediterranean fever. Clin Exp Rheumatol 1998;16:721–4. [3] Ruiz-Ortega M, Lorenzo O, Suzuki Y, Ruperez M, Egido J. Proinflammatory actions of angiotensins. Curr Opin Nephrol Hypertens 2001;10: 321–9. [4] Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–6. [5] Danser AH, Schalekamp MA, Bax WA, van den Brink AM, Saxena PR, Riegger GA, et al. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 1995;92: 1387–8. [6] Ozturk MA, Calguneri M, Kiraz S, Ertenli I, Ozbalkan Z, Onat AM, et al. Angiotensin converting enzyme gene polymorphism in Behçet’s disease. Clin Rheumatol 2004;23:142–6. [7] Haznedaroğlu IC, Öztürk MA. Towards the understanding of the local hematopoietic bone marrow renin–angiotensin system. Int J Biochem Cell Biol 2003;35:876–80. [8] Ruiz-Ortega M, Ruperez M, Lorenzo O, Esteban V, Blanco J, Mezzano S, et al. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int Suppl 2002;82:12–22. [9] Rahman ST, Lauten WB, Khan QA, Navalkar S, Parthasarathy S, Khan BV. Effects of eprosartan versus hydrochlorothiazide on markers of vascular oxidation and inflammation and blood pressure (renin–angiotensin system antagonists, oxidation, and inflammation). Am J Cardiol 2002;89:686–90. [10] Costerousse O, Allegrini J, Lopez M, Alhenc-Gelas F. Angiotensin Iconverting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochem J 1993;290:33–40. [11] Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, et al. A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 1995;332:706–11. [12] Yoshioka T, Xu YX, Yoshida H, Shiraga H, Muraki T, Ito K. Deletion polymorphism of the angiotensin converting enzyme gene predicts per-
sistent proteinuria in Henoch-Schönlein purpura nephritis. Arch Dis Child 1998;79:394–9. [13] Amoroso A, Danek G, Vatta S, Crovella S, Berrino M, Guarrera S, et al. Polymorphisms in angiotensin-converting enzyme gene and severity of renal disease in Henoch-Schönlein patients. Nephrol Dial Transplant 1998;13:3184–8.
Öztürk Meral Çalgüneri Department of Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey M. Akif Öztürk* Department of Rheumatology, Faculty of Medicine, Gazi University, Ankara, Turkey E-mail address: [email protected] (M.A. Öztürk). Sedat Kiraz İhsan Ertenli A. Mesut Onat Kemal Üreten Zeynep Özbalkan Department of Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Turkey İbrahim C. Haznedaroğlu Department of Hematology, Faculty of Medicine, Hacettepe University, Ankara, Turkey Received 15 April 2005; accepted 19 August 2005 Available online 01 December 2005 *Corresponding author. Tel.: +90 312 395 1065. 1297-319X/$ - see front matter © Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2005.08.001
Erythema nodosum and lung cancer Keywords: Erythema nodosum; Cancer
Lung cancer is the most common cause of paraneoplastic syndromes. These may occur as the presenting manifestation, coincide with a recurrence, or develop at the terminal phase. A broad spectrum of paraneoplastic disorders occurs in association with lung cancer. The target organ may be the blood, nervous system, bone, endocrine glands, or skin. Paraneoplastic skin diseases known to occur in patients with lung cancer include woolly hypertrichosis, erythema gyratum repens, acrokeratosis (Basex syndrome), dermatomyositis, and Sweet syndrome [1,2]. We report a case of recurrent erythema nodosum in a patient with lung cancer. This 43-year-old male nonsmoker had no history of disease except for allergic rhinitis. He presented with a 2-month history of erythema nodosum over the shins that had failed to respond to indomethacin or potassium iodide. A nagging cough with blood-tinged sputum antedated the skin lesions by 1 month.
Letters to the editor / Joint Bone Spine 73 (2006) 329–337
Erythematous dermal and hypodermal nodules were found over the shins. The nodules were tender to palpation. Serum Creactive protein was 15 mg/dl and the erythrocyte sedimentation rate was 28 mm/h. The peripheral eosinophil count was increased to 1.47 × 109 per l. Results were normal from the other standard blood tests. A chest radiograph disclosed widening of the hilar area, partial atelectasis, and a distal density in the lover left lobe. Findings were normal or negative from an angiotensin-converting enzyme assay, an intradermal tuberculin test, and serological tests for atypical pneumonia. Computed tomography of the chest visualized a mass in the left lower lobe. The peribronchial and hilar lymph nodes draining the lobe were enlarged. A biopsy was obtained during fiberoptic bronchoscopy. Histology showed a non-small-cell carcinoma. The tumor was removed surgically. Postoperative chemotherapy produced a good initial response. Concomitantly, the erythema nodosum resolved. Erythema nodosum is the most common form of panniculitis seen in clinical practice. It may be idiopathic or secondary to a variety of causes (drugs, infections, systemic diseases, and malignancies). Erythema nodosum has been reported in patients with hematological malignancies (lymphomas) or solid tumors such as cancer of the colon, cervix, pancreas, and liver, as well as carcinoid tumor [3–10]. About 50 cases of erythema nodosum associated with malignancies have been reported. The skin lesions may antedate the symptoms of cancer by several months and may lead to the diagnosis of the cancer. Arguments that support a causal link include the simultaneous development of the two conditions, the absence of other causes of erythema nodosum, and the resolution of the skin lesions when effective anticancer treatment is given. That erythema nodosum can occur as a paraneoplastic disease has important prognostic and therapeutic implications. The appearance, histological nature, and distribution of the skin lesions are indistinguishable from those in erythema nodosum due to other causes or for which no cause is detectable. However, paraneoplastic erythema nodosum responds poorly to conventional treatment (antiinflammatory agents and potassium iodide). In our patient, the relapses suggested the presence of a malignancy, in accordance with many previous case-reports [3,6–10]. Patients with relap-
337
sing or treatment-resistant erythema nodosum should be investigated for malignant disease [3,6–10]. References [1] Cohen PR, Kurzrock R. Mucocutaneous paraneoplastic syndromes. Semin Oncol 1997;88:449–56. [2] Yamamoto T, Furuse Y, Nishioka K. Sweet’s syndrome with small cell carcinoma of the lung. J Dermatol 1994;21:125–7. [3] Matsuoka LY. Neoplastic erythema nodosum. J Am Acad Dermatol 1995;32:361–3. [4] Bonci A, Di Lernia V, Merli F, Lo Scocco G. Erythema nodosum and Hodgkin’s disease. Clin Exp Dermatol 2000;26:408–11. [5] Thomson GT, Keystone EC, Sturgeon JF, Fornasier V. Erythema nodosum and non-Hodgkin lymphoma. J Rheumatol 1990;17:383–5. [6] Lillo A, Gil MJ, Jimenez R, Monferrer R. Eritema nodoso y adenocarcinoma de colon. Med Clin (Barc) 1997;108:318. [7] Altomare GF, Capella GL. Paraneoplastic erythema nodosum in a patient with carcinoma of the uterine cervix. Br J Dermatol 1995;132:667–8. [8] Virshup AM, Saiwinski AJ. Polyarthritis and subcutaneous nodules associated with carcinoma of the pancreas. Arthritis Rheum 1973;16:388–92. [9] Glinkov S, Krasnaliev I, Atanassova M, Arnaudov P, Kirov K, Glinkova V. Hepatocellular carcinoma associated with paraneoplastic erythema nodosum and polyarthritis. J Hepatol 2003;39:656–7. [10] Lin JT, Chen PM, Huang DF, Kwang WK, Lo K, Wang WS. Erythema nodosum associated with carcinoid tumour. Clin Exp Dermatol 2004;29: 426–7.
Noemí Busquets Perez Berta Bernad Javier Narváez* José Valverde Department of Rheumatology (planta 10-2), Hospital Universitario de Bellvitge, Feixa Llarga, s/n, 08907, Hospitalet de Llobregat, Barcelona, Spain E-mail address: [email protected] (J. Narváez). Received 7 March 2005; accepted 8 June 2005 Available online 01 December 2005 *Corresponding author. 1297-319X/$ - see front matter © Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2005.10.009