- Email: [email protected]
Erythema elevatum diutinum associated with dermatomyositis
1000 Letters
cancer and use of TNF-a blockers, such as adalimumab. The incidence of thyroid cancer in adalimumabtreated individuals is considered rare by the US Food and Drug Administration, with a reported 0.07 events (cases of thyroid cancer) per 100 patient-years observed during 13,788 patient-years of exposure, involving a total of 4843 patients exposed to adalimumab in clinical trial participants (http://www.fda.gov/RegulatoryInformation/FOI/ HowToMakeaFOIArequest/default.htm). None of these events occurred in individuals with psoriasis. There is no follow-up information available for the few cases of thyroid cancer observed in pivotal trials by Abbott Pharmaceuticals, the parent company that produces adalimumab. The incidence of thyroid cancer in patients taking other TNF-a antagonists, such as etanercept or infliximab, is also unknown, and therefore has not been compared with that of the general population (8.7 cases per 100,000).4 A US Food and Drug Administration briefing document summarizing the safety of TNF-a antagonists stated that total malignancies, excluding lymphoma, were not increased in clinical trials using these agents, and subsequent studies have corroborated these findings.5 Reporting of spontaneous individual adverse events, additional case reports, and longitudinal observational studies may help to establish whether the risk of thyroid cancer and other solid malignancies is increased among individuals receiving TNF-a blockers. Jennifer J. Lee, MD,a Julianne A. Mann, MD,a and Andrew Blauvelt, MDa,b,c Departments of Dermatologya and Molecular Microbiology & Immunology,b Oregon Health & Science University, and the Dermatology Service,c Veterans Affairs Medical Center, Portland, Oregon Funding sources: None. Conflicts of interest: None declared. Reprint requests: Andrew Blauvelt, MD, 3710 SW US Veterans Hospital Rd, Mail Code R&D 55, Portland, OR 97239 E-mail: [email protected]
REFERENCES 1. Aust G, Heuer M, Laue S, Lehmann I, Hofmann A, Heldin NE, Scherbaum WA. Expression of tumour necrosis factor-alpha (TNF-alpha) mRNA and protein in pathological thyroid tissue and carcinoma cell lines. Clin Exp Immunol 1996;105:148-54. 2. Mitsiades N, Poulaki V, Tseleni-Balafouta S, Koutras DA, Stamenkovic I. Thyroid carcinoma cells are resistant to FAS-
J AM ACAD DERMATOL
MAY 2011
mediated apoptosis but sensitive to tumor necrosis factorrelated apoptosis-inducing ligand. Cancer Res 2000;60:4122-9. 3. Mitsiades CS, Poulaki V, Mitsiades N. The role of apoptosisinducing receptors of the tumor necrosis factor family in thyroid cancer. J Endocrinol 2003;178:205-16. 4. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 193-2002. JAMA 2006;295:2164-7. 5. US Food and Drug Administration website. Arthritis Drugs Advisory Committee. Safety update on TNF-alpha antagonists. Available at: www.fda.gov/ohrms/dockets/ac/03/briefing/3930b1.htm. Accessed January 12, 2010. doi:10.1016/j.jaad.2009.08.030
Erythema elevatum diutinum associated with dermatomyositis To the Editor: First described by Hutchinson et al,1 erythema elevatum diutinum (EED) is a rare cutaneous clinicopathologic entity characterized histologically by alterations that range from leukocytoclastic vasculitis and dense neutrophilic infiltrates, in the early stages of the lesions, to fibrosis in the late stages. EED has been associated with infections, malignancies, and autoimmune diseases.2,3 We recently observed a new case that is of particular interest because the patient developed EED associated with dermatomyositis. A 29-year-old man was admitted in October 2007 with complaints of both myalgia and muscle weakness involving the proximal part of both lower and upper limbs. He also exhibited swelling and pain exacerbated by palpation involving the lower area of his lower limb of 1 month’s duration. At admission, muscle strength was gauged for eight proximal muscles by a modification of the British Medical Research Council grading system (maximum score, 88 points); muscle strength was 65 points. The physical examination revealed one fixed nodule about 6 cm in diameter along the posterior area of the lower leg. The results of the laboratory studies were as follows: erythrocyte sedimentation rate, 64 mm/h; C-reactive protein, 52 mg/L; white blood cell count, 9.1 3 109/L; platelet count, 250 3 109/L; and creatine kinase, 770 IU/L. The results of renal and liver tests and blood electrophoresis were normal. Antistreptolysin-O titer, bacterial, viral, and parasitic serologies were all negative. Autoantibody screening was positive for antinuclear antibodies (1:1200). Electromyogram was normal. Muscle biopsy specimens showed damage consistent with dermatomyositis. An excisional biopsy of the cutaneous nodule was performed; histologic examination was consistent with EED, showing a dense neutrophilic infiltrate and leukocytoclatic vasculitis (Fig 1). Other investigations, including lung and abdominal computed tomographic scans, gastroscopy, and colonoscopy were
J AM ACAD DERMATOL
Letters 1001
VOLUME 64, NUMBER 5
Department of Internal Medicinea and Laboratory of Pathology and Cytology,b Centre Hospitalier Universitaire Rouen, Rouen, France Funding sources: None. Conflicts of interest: None declared. Correspondence to: Isabelle Marie, MD, PhD, Departement de Medecine Interne, CHU de Rouen, 76031 Rouen Cedex E-mail: [email protected] Fig 1. Histologic examination of cutaneous biopsy specimen. Note the dense neutrophilic infiltrate and leukocytoclatic vasculitis, which is consistent with erythema elevatum diutinum. (Hematoxylineeosin stain.)
normal. The diagnosis of dermatomyositis associated with EED was made. The patient began steroid therapy (at an initial dose of 1 mg/kg daily), and his condition improved rapidly with regression of clinical symptoms and normalization of biochemical features. To date, the patient remains free of clinical symptoms while taking prednisone 7 mg daily. EED has been associated with various chronic conditions, including infectious disorders, hematologic disorders, inflammatory small bowel diseases, and autoimmune diseases (especially rheumatoid arthritis), and more rarely Wegener granulomatosis, systemic lupus erythematosus, or relapsing polychondritis.2-5 We report, to the best of our knowledge, the first case of EED in a patient with dermatomyositis. The pathologic mechanisms of EED in our patient with dermatomyositis remain unclear, raising the question of whether the condition arose through a causal association. In our patient, the diagnosis of EED associated with dermatomyositis could be made, because the extensive search for other conditions associated with EED proved negative and the regression of dermatomyositis and EED manifestations took place after steroid initiation. We therefore suggest that similar pathologic mechanisms may be implicated in the onset of both disorders. In fact, EED has been speculated to bear many of the hallmarks of a circulating immune complexemediated disease.2-5 Interestingly, dermatomyositis is also considered to be an entity with immune complex etiology; in patients with dermatomyositis, the immune process has been shown to be directed against microvascular antigens and mediated by complement C5b-9 membranolytic attack complex and circulating immune complexes. Isabelle Marie, MD, PhD,a Philippe Courville, MD,b and Herve Levesque, MD, PhDa
REFERENCES 1. Hutchinson J. Illustrations of clinical surgery, vol. 1. London: J and A Churchill, Ltd; 1878 p. 42. 2. Katz SI, Gallin JL, Hertz KC, Fauci AS, Lawley TJ. Erythema elevatum diutinum: skin and systemic manifestations, immunologic studies, and successful treatment with dapsone. Medicine (Baltimore) 1977;56:443-55. 3. Yiannias JA, El-Azhary RA, Gibson LE. Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients. J Am Acad Dermatol 1992;26:38-44. 4. Wallach D, Vignon-Pennamen MD. From acute febrile neutrophilic dermatosis to neutrophilic disease: forty years of clinical research. J Am Acad Dermatol 2006;55:1066-71. 5. Yamamoto T, Nakamura S, Nishioka K. Erythema elevatum diutinum associated with Hashimoto’s thyroiditis and antiphospholipid antibodies. J Am Acad Dermatol 2005;52: 165-166. doi:10.1016/j.jaad.2009.08.037
Concurrent Hansen disease and pulmonary tuberculosis To the Editor: A 44-year-old Filipino woman presented with an enlarging anesthetic plaque on her left lateral thigh of 3 years’ duration. A review of systems revealed a 2-kg weight loss and a minimal dry cough. The patient had received a bacillus Calmette-Guerin vaccination as a child and a tuberculin skin test was positive. The physical examination revealed a well demarcated 15- 3 13-cm erythematous plaque with raised borders, central anesthesia, and few areas of hemorrhagic ulceration (Fig 1). A routine chest radiograph revealed an left upper lobe opacity with interspersed lucencies, a thickening of the apical pleurae, and few calcified granulomas (Fig 2). A punch biopsy specimen of the skin revealed chronic granulomatous infiltrates replacing 60% of the dermis and extending into the subcutis (Fig 3). Well formed granulomas were surrounded by a peripheral mantle of lymphocytes, with foci of small cutaneous nerves and early tissue necrosis. FiteFaraco stain revealed rare acid-fast bacilli (AFB) within histiocytes and within a small cutaneous nerve. P polymerase chain reaction study was
cancer and use of TNF-a blockers, such as adalimumab. The incidence of thyroid cancer in adalimumabtreated individuals is considered rare by the US Food and Drug Administration, with a reported 0.07 events (cases of thyroid cancer) per 100 patient-years observed during 13,788 patient-years of exposure, involving a total of 4843 patients exposed to adalimumab in clinical trial participants (http://www.fda.gov/RegulatoryInformation/FOI/ HowToMakeaFOIArequest/default.htm). None of these events occurred in individuals with psoriasis. There is no follow-up information available for the few cases of thyroid cancer observed in pivotal trials by Abbott Pharmaceuticals, the parent company that produces adalimumab. The incidence of thyroid cancer in patients taking other TNF-a antagonists, such as etanercept or infliximab, is also unknown, and therefore has not been compared with that of the general population (8.7 cases per 100,000).4 A US Food and Drug Administration briefing document summarizing the safety of TNF-a antagonists stated that total malignancies, excluding lymphoma, were not increased in clinical trials using these agents, and subsequent studies have corroborated these findings.5 Reporting of spontaneous individual adverse events, additional case reports, and longitudinal observational studies may help to establish whether the risk of thyroid cancer and other solid malignancies is increased among individuals receiving TNF-a blockers. Jennifer J. Lee, MD,a Julianne A. Mann, MD,a and Andrew Blauvelt, MDa,b,c Departments of Dermatologya and Molecular Microbiology & Immunology,b Oregon Health & Science University, and the Dermatology Service,c Veterans Affairs Medical Center, Portland, Oregon Funding sources: None. Conflicts of interest: None declared. Reprint requests: Andrew Blauvelt, MD, 3710 SW US Veterans Hospital Rd, Mail Code R&D 55, Portland, OR 97239 E-mail: [email protected]
REFERENCES 1. Aust G, Heuer M, Laue S, Lehmann I, Hofmann A, Heldin NE, Scherbaum WA. Expression of tumour necrosis factor-alpha (TNF-alpha) mRNA and protein in pathological thyroid tissue and carcinoma cell lines. Clin Exp Immunol 1996;105:148-54. 2. Mitsiades N, Poulaki V, Tseleni-Balafouta S, Koutras DA, Stamenkovic I. Thyroid carcinoma cells are resistant to FAS-
J AM ACAD DERMATOL
MAY 2011
mediated apoptosis but sensitive to tumor necrosis factorrelated apoptosis-inducing ligand. Cancer Res 2000;60:4122-9. 3. Mitsiades CS, Poulaki V, Mitsiades N. The role of apoptosisinducing receptors of the tumor necrosis factor family in thyroid cancer. J Endocrinol 2003;178:205-16. 4. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 193-2002. JAMA 2006;295:2164-7. 5. US Food and Drug Administration website. Arthritis Drugs Advisory Committee. Safety update on TNF-alpha antagonists. Available at: www.fda.gov/ohrms/dockets/ac/03/briefing/3930b1.htm. Accessed January 12, 2010. doi:10.1016/j.jaad.2009.08.030
Erythema elevatum diutinum associated with dermatomyositis To the Editor: First described by Hutchinson et al,1 erythema elevatum diutinum (EED) is a rare cutaneous clinicopathologic entity characterized histologically by alterations that range from leukocytoclastic vasculitis and dense neutrophilic infiltrates, in the early stages of the lesions, to fibrosis in the late stages. EED has been associated with infections, malignancies, and autoimmune diseases.2,3 We recently observed a new case that is of particular interest because the patient developed EED associated with dermatomyositis. A 29-year-old man was admitted in October 2007 with complaints of both myalgia and muscle weakness involving the proximal part of both lower and upper limbs. He also exhibited swelling and pain exacerbated by palpation involving the lower area of his lower limb of 1 month’s duration. At admission, muscle strength was gauged for eight proximal muscles by a modification of the British Medical Research Council grading system (maximum score, 88 points); muscle strength was 65 points. The physical examination revealed one fixed nodule about 6 cm in diameter along the posterior area of the lower leg. The results of the laboratory studies were as follows: erythrocyte sedimentation rate, 64 mm/h; C-reactive protein, 52 mg/L; white blood cell count, 9.1 3 109/L; platelet count, 250 3 109/L; and creatine kinase, 770 IU/L. The results of renal and liver tests and blood electrophoresis were normal. Antistreptolysin-O titer, bacterial, viral, and parasitic serologies were all negative. Autoantibody screening was positive for antinuclear antibodies (1:1200). Electromyogram was normal. Muscle biopsy specimens showed damage consistent with dermatomyositis. An excisional biopsy of the cutaneous nodule was performed; histologic examination was consistent with EED, showing a dense neutrophilic infiltrate and leukocytoclatic vasculitis (Fig 1). Other investigations, including lung and abdominal computed tomographic scans, gastroscopy, and colonoscopy were
J AM ACAD DERMATOL
Letters 1001
VOLUME 64, NUMBER 5
Department of Internal Medicinea and Laboratory of Pathology and Cytology,b Centre Hospitalier Universitaire Rouen, Rouen, France Funding sources: None. Conflicts of interest: None declared. Correspondence to: Isabelle Marie, MD, PhD, Departement de Medecine Interne, CHU de Rouen, 76031 Rouen Cedex E-mail: [email protected] Fig 1. Histologic examination of cutaneous biopsy specimen. Note the dense neutrophilic infiltrate and leukocytoclatic vasculitis, which is consistent with erythema elevatum diutinum. (Hematoxylineeosin stain.)
normal. The diagnosis of dermatomyositis associated with EED was made. The patient began steroid therapy (at an initial dose of 1 mg/kg daily), and his condition improved rapidly with regression of clinical symptoms and normalization of biochemical features. To date, the patient remains free of clinical symptoms while taking prednisone 7 mg daily. EED has been associated with various chronic conditions, including infectious disorders, hematologic disorders, inflammatory small bowel diseases, and autoimmune diseases (especially rheumatoid arthritis), and more rarely Wegener granulomatosis, systemic lupus erythematosus, or relapsing polychondritis.2-5 We report, to the best of our knowledge, the first case of EED in a patient with dermatomyositis. The pathologic mechanisms of EED in our patient with dermatomyositis remain unclear, raising the question of whether the condition arose through a causal association. In our patient, the diagnosis of EED associated with dermatomyositis could be made, because the extensive search for other conditions associated with EED proved negative and the regression of dermatomyositis and EED manifestations took place after steroid initiation. We therefore suggest that similar pathologic mechanisms may be implicated in the onset of both disorders. In fact, EED has been speculated to bear many of the hallmarks of a circulating immune complexemediated disease.2-5 Interestingly, dermatomyositis is also considered to be an entity with immune complex etiology; in patients with dermatomyositis, the immune process has been shown to be directed against microvascular antigens and mediated by complement C5b-9 membranolytic attack complex and circulating immune complexes. Isabelle Marie, MD, PhD,a Philippe Courville, MD,b and Herve Levesque, MD, PhDa
REFERENCES 1. Hutchinson J. Illustrations of clinical surgery, vol. 1. London: J and A Churchill, Ltd; 1878 p. 42. 2. Katz SI, Gallin JL, Hertz KC, Fauci AS, Lawley TJ. Erythema elevatum diutinum: skin and systemic manifestations, immunologic studies, and successful treatment with dapsone. Medicine (Baltimore) 1977;56:443-55. 3. Yiannias JA, El-Azhary RA, Gibson LE. Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients. J Am Acad Dermatol 1992;26:38-44. 4. Wallach D, Vignon-Pennamen MD. From acute febrile neutrophilic dermatosis to neutrophilic disease: forty years of clinical research. J Am Acad Dermatol 2006;55:1066-71. 5. Yamamoto T, Nakamura S, Nishioka K. Erythema elevatum diutinum associated with Hashimoto’s thyroiditis and antiphospholipid antibodies. J Am Acad Dermatol 2005;52: 165-166. doi:10.1016/j.jaad.2009.08.037
Concurrent Hansen disease and pulmonary tuberculosis To the Editor: A 44-year-old Filipino woman presented with an enlarging anesthetic plaque on her left lateral thigh of 3 years’ duration. A review of systems revealed a 2-kg weight loss and a minimal dry cough. The patient had received a bacillus Calmette-Guerin vaccination as a child and a tuberculin skin test was positive. The physical examination revealed a well demarcated 15- 3 13-cm erythematous plaque with raised borders, central anesthesia, and few areas of hemorrhagic ulceration (Fig 1). A routine chest radiograph revealed an left upper lobe opacity with interspersed lucencies, a thickening of the apical pleurae, and few calcified granulomas (Fig 2). A punch biopsy specimen of the skin revealed chronic granulomatous infiltrates replacing 60% of the dermis and extending into the subcutis (Fig 3). Well formed granulomas were surrounded by a peripheral mantle of lymphocytes, with foci of small cutaneous nerves and early tissue necrosis. FiteFaraco stain revealed rare acid-fast bacilli (AFB) within histiocytes and within a small cutaneous nerve. P polymerase chain reaction study was