Correspondence Clinical Letter
Clinical Letter Red nail folds and Gottron’s sign in a patient with leukemic infiltration of pelvic muscles
DOI: 10.1111/ddg.12616
Dear Editors, A 22-year-old man presented with erythematous lesions on the dorsum of both hands, along with red nail folds and right shoulder pain that had slowly worsened over seven months. The skin lesions were asymptomatic and had proven unresponsive to previous topical corticosteroid treatment. His past medical and family history were unremarkable. Over the previous seven months, he had lost 4.5 kg. On physical examination, the patient showed slightly swollen red nail folds without visible telangiectasia; erythematous macular lesions were found around the metacarpophalangeal and interphalangeal joints (Figure 1a). While routine laboratory tests displayed normal values for a complete blood count, renal function, C-reactive protein, and erythrocyte sedimentation rate, the following parameters were elevated: AST 107 IU/L (normal range: 13–34 IU/L), ALT 75 IU/L (normal range: 5–46 IU/L), lactate dehydrogenase 609 IU/L (normal range: 119–247 IU/L), creatine kinase (CK) 4 530 IU/L (normal range: 44–245 IU/L), and aldolase 92.3 IU/L (normal range: 0–7.6 IU/L). Further lab workup, including anti-Jo-1
Figure 1 Red nail folds and Gottron’s sign over the metacarpophalangeal and interphalangeal joints (inset, close-up of the nail fold of the ring finger) (a). Skin biopsy of the nail fold shows mild infiltration of monocytes and histiocytes in the upper dermis adjacent to dilated capillaries (hematoxylin and eosin stain, original magnification x 100) (b).
antibodies, anti-Scl-70 antibodies, and anti-Sm antibodies, was unremarkable, except for a positive antinuclear antibody test at 1 : 640 (normal range: < 1 : 40) with a speckled pattern. Histopathology of a biopsy taken from one of the erythematous nail fold lesions showed mild infiltration of monocytes and histiocytes in the upper dermis, adjacent to dilated capillaries, without any marked infiltration of abnormal cell (Figure 1b). Moreover, electromyography and a nerve conduction study, performed on the right upper arm, revealed generalized myopathy. The patient was diagnosed with dermatomyositis and subsequently underwent whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) in search of an underlying malignancy. The imaging study showed a marked increase in FDG uptake in the right iliopsoas, gluteus, and obturator internus muscles, in the right iliac bone and sacrum (maximum standardized uptake value [SUVmax] = 5.5) (Figure 2a, b) as well as in ipsilateral inguinal lymph nodes (SUVmax = 4.7) (Figure 2c). However, FDG uptake was not significantly increased in any part of the right shoulder or the apparent skin lesions. Subsequent ultrasound-guided biopsy of the PET-positive inguinal lymph node and iliopsoas muscle showed diffuse proliferation
Figure 2 Whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) reveals increased FDG uptake in the right iliopsoas, gluteus, and obturator internus muscles (arrowheads) as well as inguinal lymph nodes (arrows). Coronal views of the FDG PET image (a) and horizontal views of the PET/CT scan (b, c). Ultrasound-guided biopsy of a PET-positive inguinal lymph node shows diffuse proliferation of monomorphic medium-sized immature blastic cells (hematoxylin and eosin stain, original magnification x 200) (d).
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
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Correspondence Clinical Letter
of monomorphic medium-sized immature blastic cells with a CD20+, CD79a+, CD3-, myeloperoxidase+, and TdT+ immunophenotype, consistent with biphenotypic acute leukemia (Figure 2d). A bone marrow biopsy revealed 30 % cellularity without remarkable abnormal cell infiltration. The patient was treated with a cyclophosphamide, adriamycin, vincristine, daunorubicin, and prednisone (hyper-CVAD) chemotherapy regimen in combination with methotrexate (MTX). After three cycles of hyper-CVAD with MTX, both his general and cutaneous symptoms had substantially improved; he then received three more cycles. On follow-up PET/CT performed three months after the final round of chemotherapy, FDG uptake in the lymph nodes and pelvic muscles were markedly reduced compared to initial findings. The patient achieved clinical remission after six cycles of the hyper-CVAD regimen, and is now on maintenance therapy with weekly methotrexate and mercaptopurine. Here, we report the case of a patient, initially presenting with shoulder pain as well as red nail folds and Gottron’s sign on both hands, who was eventually diagnosed with dermatomyositis associated with biphenotypic acute leukemia involving the pelvic muscles. The cutaneous lesions along with distinct elevations in serum CK and aldolase levels were clinically suggestive of dermatomyositis [1–4]. Markedly swollen red nail folds have been reported in patients with chronic lymphocytic leukemia. Biopsies from such lesions typically exhibit diffuse leukemic cell infiltration in the dermis and subcutis [5, 6]. By contrast, the skin lesions in our case showed neither FDG uptake on PET/CT scan nor any histologic evidence of atypical cell infiltration. Moreover, although the pathologic features of interface dermatitis were missing, the nail fold biopsy revealed upper dermal perivascular inflammation, which might be suggestive of dermatomyositis. Clinical and pathologic differences are thus possibly a result of disease duration and the type of leukemia associated with dermatomyositis [4, 7]. Due to their cost effectiveness, FDG PET and PET/CT are frequently used in the diagnosis of dermatomyositis and polymyositis [8]. FDG uptake in proximal muscles can be quantitatively measured to highlight areas of muscular inflammation. In conjunction with PET/CT, this technique helps detect appropriate regions for muscle biopsy with a sensitivity of 90 % and a specificity of 100 % [8]. Furthermore, myositis-associated underlying malignancies may also be effectively identified by FDG PET and PET/CT imaging [9]. While the efficacy of PET/CT in detecting occult malignancies is comparable to broad cancer screening methods, it holds the advantage of being able to scan the entire body with a single test [9]. Although the marked elevations in serum CK and aldolase in our patient resulted from either leukemic infiltration of the pelvic muscles or inflammatory myopathy, we think that FDG PET and PET/CT imaging may be clini-
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cally useful as baseline studies in patients with red nail folds and Gottron’s sign of unspecified origin. Conflict of interest None.
Min Ju Choi1, Sang-Won Lee2, Yoo Hong Min2, Jae-Hoon Lee3, Sung Bin Cho1 (1) Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea (2) Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (3) Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea
Correspondence to Sung Bin Cho, MD, PhD Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine 50 Yonsei-ro, Seodaemun-gu Seoul, Korea E-mail: [email protected]
References 1
2
3 4 5
6
7
8
9
Mugii N, Hasegawa M, Matsushita T et al. Association etween nail-fold capillary findings and disease activity in b dermatomyositis. Rheumatology (Oxford) 2011; 50: 1091–8. Iaccarino L, Ghirardello A, Bettio S et al. The clinical features, diagnosis and classification of dermatomyositis. J Autoimmun 2014; 48–49: 122–7. Jung P, Trautinger F. Capillaroscopy. J Dtsch Dermatol Ges 2013; 11: 731–6. Kaufmann J, Hunzelmann N, Genth E, Krieg T. The clinical spectrum of dermatomyositis. J Dtsch Dermatol Ges 2005; 3: 181–94. Saburi Y, Gotoh K, Ohtsuka E, Yamaguchi K. Swollen nail folds due to leukemic cell infiltration in a case of chronic lymphocytic leukemia. Intern Med 2004; 43: 1 008. Yag ˇci M, Sucak GT, Haznedar R. Red swollen nail folds and nail deformity as presenting findings in chronic lymphocytic leukaemia. Br J Haematol 2001; 112: 1. Wagner G, Fenchel K, Back W et al. Leukemia cutis – epidemiology, clinical presentation, and differential diagnoses. J Dtsch Dermatol Ges 2012; 10: 27–36. Tanaka S, Ikeda K, Uchiyama K et al. [18F]FDG uptake in proximal muscles assessed by PET/CT reflects both global and local muscular inflammation and provides useful information in the management of patients with polymyositis/dermatomyositis. Rheumatology (Oxford) 2013; 52: 1271–8. Mahmood S, Rodríguez Martínez de Llano S. 18F-FDG PET detection of unknown primary malignancy in dermatomyositis. Clin Nucl Med 2012; 37: e204–5.
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
Clinical Letter Red nail folds and Gottron’s sign in a patient with leukemic infiltration of pelvic muscles
DOI: 10.1111/ddg.12616
Dear Editors, A 22-year-old man presented with erythematous lesions on the dorsum of both hands, along with red nail folds and right shoulder pain that had slowly worsened over seven months. The skin lesions were asymptomatic and had proven unresponsive to previous topical corticosteroid treatment. His past medical and family history were unremarkable. Over the previous seven months, he had lost 4.5 kg. On physical examination, the patient showed slightly swollen red nail folds without visible telangiectasia; erythematous macular lesions were found around the metacarpophalangeal and interphalangeal joints (Figure 1a). While routine laboratory tests displayed normal values for a complete blood count, renal function, C-reactive protein, and erythrocyte sedimentation rate, the following parameters were elevated: AST 107 IU/L (normal range: 13–34 IU/L), ALT 75 IU/L (normal range: 5–46 IU/L), lactate dehydrogenase 609 IU/L (normal range: 119–247 IU/L), creatine kinase (CK) 4 530 IU/L (normal range: 44–245 IU/L), and aldolase 92.3 IU/L (normal range: 0–7.6 IU/L). Further lab workup, including anti-Jo-1
Figure 1 Red nail folds and Gottron’s sign over the metacarpophalangeal and interphalangeal joints (inset, close-up of the nail fold of the ring finger) (a). Skin biopsy of the nail fold shows mild infiltration of monocytes and histiocytes in the upper dermis adjacent to dilated capillaries (hematoxylin and eosin stain, original magnification x 100) (b).
antibodies, anti-Scl-70 antibodies, and anti-Sm antibodies, was unremarkable, except for a positive antinuclear antibody test at 1 : 640 (normal range: < 1 : 40) with a speckled pattern. Histopathology of a biopsy taken from one of the erythematous nail fold lesions showed mild infiltration of monocytes and histiocytes in the upper dermis, adjacent to dilated capillaries, without any marked infiltration of abnormal cell (Figure 1b). Moreover, electromyography and a nerve conduction study, performed on the right upper arm, revealed generalized myopathy. The patient was diagnosed with dermatomyositis and subsequently underwent whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) in search of an underlying malignancy. The imaging study showed a marked increase in FDG uptake in the right iliopsoas, gluteus, and obturator internus muscles, in the right iliac bone and sacrum (maximum standardized uptake value [SUVmax] = 5.5) (Figure 2a, b) as well as in ipsilateral inguinal lymph nodes (SUVmax = 4.7) (Figure 2c). However, FDG uptake was not significantly increased in any part of the right shoulder or the apparent skin lesions. Subsequent ultrasound-guided biopsy of the PET-positive inguinal lymph node and iliopsoas muscle showed diffuse proliferation
Figure 2 Whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) reveals increased FDG uptake in the right iliopsoas, gluteus, and obturator internus muscles (arrowheads) as well as inguinal lymph nodes (arrows). Coronal views of the FDG PET image (a) and horizontal views of the PET/CT scan (b, c). Ultrasound-guided biopsy of a PET-positive inguinal lymph node shows diffuse proliferation of monomorphic medium-sized immature blastic cells (hematoxylin and eosin stain, original magnification x 200) (d).
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
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Correspondence Clinical Letter
of monomorphic medium-sized immature blastic cells with a CD20+, CD79a+, CD3-, myeloperoxidase+, and TdT+ immunophenotype, consistent with biphenotypic acute leukemia (Figure 2d). A bone marrow biopsy revealed 30 % cellularity without remarkable abnormal cell infiltration. The patient was treated with a cyclophosphamide, adriamycin, vincristine, daunorubicin, and prednisone (hyper-CVAD) chemotherapy regimen in combination with methotrexate (MTX). After three cycles of hyper-CVAD with MTX, both his general and cutaneous symptoms had substantially improved; he then received three more cycles. On follow-up PET/CT performed three months after the final round of chemotherapy, FDG uptake in the lymph nodes and pelvic muscles were markedly reduced compared to initial findings. The patient achieved clinical remission after six cycles of the hyper-CVAD regimen, and is now on maintenance therapy with weekly methotrexate and mercaptopurine. Here, we report the case of a patient, initially presenting with shoulder pain as well as red nail folds and Gottron’s sign on both hands, who was eventually diagnosed with dermatomyositis associated with biphenotypic acute leukemia involving the pelvic muscles. The cutaneous lesions along with distinct elevations in serum CK and aldolase levels were clinically suggestive of dermatomyositis [1–4]. Markedly swollen red nail folds have been reported in patients with chronic lymphocytic leukemia. Biopsies from such lesions typically exhibit diffuse leukemic cell infiltration in the dermis and subcutis [5, 6]. By contrast, the skin lesions in our case showed neither FDG uptake on PET/CT scan nor any histologic evidence of atypical cell infiltration. Moreover, although the pathologic features of interface dermatitis were missing, the nail fold biopsy revealed upper dermal perivascular inflammation, which might be suggestive of dermatomyositis. Clinical and pathologic differences are thus possibly a result of disease duration and the type of leukemia associated with dermatomyositis [4, 7]. Due to their cost effectiveness, FDG PET and PET/CT are frequently used in the diagnosis of dermatomyositis and polymyositis [8]. FDG uptake in proximal muscles can be quantitatively measured to highlight areas of muscular inflammation. In conjunction with PET/CT, this technique helps detect appropriate regions for muscle biopsy with a sensitivity of 90 % and a specificity of 100 % [8]. Furthermore, myositis-associated underlying malignancies may also be effectively identified by FDG PET and PET/CT imaging [9]. While the efficacy of PET/CT in detecting occult malignancies is comparable to broad cancer screening methods, it holds the advantage of being able to scan the entire body with a single test [9]. Although the marked elevations in serum CK and aldolase in our patient resulted from either leukemic infiltration of the pelvic muscles or inflammatory myopathy, we think that FDG PET and PET/CT imaging may be clini-
582
cally useful as baseline studies in patients with red nail folds and Gottron’s sign of unspecified origin. Conflict of interest None.
Min Ju Choi1, Sang-Won Lee2, Yoo Hong Min2, Jae-Hoon Lee3, Sung Bin Cho1 (1) Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea (2) Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (3) Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea
Correspondence to Sung Bin Cho, MD, PhD Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine 50 Yonsei-ro, Seodaemun-gu Seoul, Korea E-mail: [email protected]
References 1
2
3 4 5
6
7
8
9
Mugii N, Hasegawa M, Matsushita T et al. Association etween nail-fold capillary findings and disease activity in b dermatomyositis. Rheumatology (Oxford) 2011; 50: 1091–8. Iaccarino L, Ghirardello A, Bettio S et al. The clinical features, diagnosis and classification of dermatomyositis. J Autoimmun 2014; 48–49: 122–7. Jung P, Trautinger F. Capillaroscopy. J Dtsch Dermatol Ges 2013; 11: 731–6. Kaufmann J, Hunzelmann N, Genth E, Krieg T. The clinical spectrum of dermatomyositis. J Dtsch Dermatol Ges 2005; 3: 181–94. Saburi Y, Gotoh K, Ohtsuka E, Yamaguchi K. Swollen nail folds due to leukemic cell infiltration in a case of chronic lymphocytic leukemia. Intern Med 2004; 43: 1 008. Yag ˇci M, Sucak GT, Haznedar R. Red swollen nail folds and nail deformity as presenting findings in chronic lymphocytic leukaemia. Br J Haematol 2001; 112: 1. Wagner G, Fenchel K, Back W et al. Leukemia cutis – epidemiology, clinical presentation, and differential diagnoses. J Dtsch Dermatol Ges 2012; 10: 27–36. Tanaka S, Ikeda K, Uchiyama K et al. [18F]FDG uptake in proximal muscles assessed by PET/CT reflects both global and local muscular inflammation and provides useful information in the management of patients with polymyositis/dermatomyositis. Rheumatology (Oxford) 2013; 52: 1271–8. Mahmood S, Rodríguez Martínez de Llano S. 18F-FDG PET detection of unknown primary malignancy in dermatomyositis. Clin Nucl Med 2012; 37: e204–5.
© 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2015/1306
