Letters to the Editor
Candida antigen, Aspergillus antigen and 1,3-beta-D-glucan were all negative. Because the pulmonary lesions were resistant to broad-spectrum antibacterials and voriconazole, liposomal amphotericin B (started at 3 mg/kg per day, later changed to 3 mg/kg every other day and continued) was administrated and the nodular infiltrates diminished. Four months later, although anti-thymocyte globulin improved steroid-refractory aGVHD, her bone marrow testing showed t-MDS transforming to myeloid leukemia (AML) with her chest CT revealing worsening of the pneumonia. Salvage chemotherapy for t-MDS was started while the dose of corticosteroids and tacrolimus was reduced with the intent to induce allogenic immune effect, and liposomal amphotericin B was returned to daily administration (3 mg/kg per day). Three weeks later, she presented a painful purpura with subcutaneous induration on her right lower limb (Fig. 1a). Skin punch biopsy showed massive hemorrhage and partial necrosis in the dermis and fat tissue, and aggregates of nonseptate broad hyphae with wide-angle branches invading blood vessels (Fig. 1b,c). Debridement of the skin lesion was performed. Direct microscopy of the necrotic tissue stained with Parker ink added to potassium hydroxide revealed nonseptate broad hyphae (Fig. 1d). The tissue was cultured on a Sabouraud’s dextrose agar medium at 25°C, producing whitish cotton-like colonies in 3 days (Fig. 1e). The microscopic view of the colonies (Fig. 1f) was consistent with the features of the Rhizopus genus. Susceptibility testing using E-test strips demonstrated a minimum inhibitory concentration for amphotericin B of 2 lg/mL, voriconazole and itraconazole of over 32 lg/mL in 24 h. The gene sequence of the internal transcribed spacer region of nuclear ribosomal DNA isolated from the colonies was identical to that of R. oryzae. She died of disseminated mucormycosis with t-MDS/AML 2 weeks after skin biopsy.
Mucormycosis infections are characterized by extensive angioinvasion that results in vessel thrombosis and subsequent tissue necrosis. Ischemic necrosis of the infected tissue can prevent leukocytes and antifungal agent penetration to the foci of infection.3 In our case, despite early initiation of empiric therapy with liposomal amphotericin B against suspected pulmonary fungal infection, it eventually developed into disseminated disease and reached a definitive diagnosis from the skin lesion.
CONFLICT OF INTEREST:
The authors have no conflict of
interest to declare.
Mai KANEMARU,1 Saki TASHIMA,1 Akiko YAMAZAKI,1 Koji MASUDA,1 Hisao NAGOSHI,2 Tsutomu KOBAYASHI,2 Junya KURODA,2 Masataro HIRUMA,3 Masafumi TANIWAKI,2 Norito KATOH1 1
Department of Dermatology, Kyoto Prefectural University of Medicine, Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, and 3Ochanomizu Institute for Medical Mycology and Allergology, Tokyo, Japan 2
doi: 10.1111/1346-8138.12715
REFERENCES 1 Spellberg B, Ibrahim AS. Recent advances in the treatment of mucormycosis. Curr Infect Dis Rep 2010; 12: 423–429. 2 Roden MM, Zaoutis TE, Buchanan WL et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005; 41: 634–653. 3 Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis 2012; 54(Suppl 1): 16–22.
Deep venous thrombosis in patients with Behc ß et’s disease Dear Editor, We report two cases of young patients in whom deep venous thrombosis (DVT) was the key clinical finding for the diagnosis of Behc ß et’s disease (BD). Case 1 was a 21-year-old woman who was referred to our department with a 1-year history of recurrent erythema on the right lower leg. We made the diagnosis of erythema nodosum (EN). Treatment with oral non-steroidal anti-inflammatory drugs (NSAIDs) improved the erythema. At 18 months after the first visit, she returned to our department with edema and multiple painful erythematous nodules on the right lower leg (Fig. 1a). Skin biopsy from an erythematous nodule showed lobular and septal panniculitis and thickening of the blood vessel walls,
with moderate inflammatory cell infiltrates (data not shown). Based on the histopathological findings, we diagnosed the erythematous nodules as EN-like lesions. Ultrasonography performed to determine the cause of the edema revealed DVT in the right femoral vein (Fig. 1b). She had past history of oral aphthae and vulvar ulcers. From these findings, we made the diagnosis of BD based on the International Criteria for Behc ß et’s Disease.1 She was treated with oral warfarin at 4 mg/day; at 16 months after therapy, there were no abnormal clinical signs. Case 2 was a 29-year-old man who presented with a 1-year history of erythema on both legs. The initial examination revealed painful erythematous nodules on the right thigh (Fig. 1c). Based on the histopathological findings (data not
Correspondence: Kentaro Izumi, M.D., Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo 060-8638, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
101
Letters to the Editor
(a)
(c)
(b)
(d)
In these cases, DVT was the key clinical feature suggesting the diagnosis of BD. Venous thrombosis is the major complication of BD. Superficial venous thrombophlebitis is the most common vascular symptom of BD.2 In contrast, DVT has not been regarded to be a major complication of BD, and very few cases have been reported in the dermatological published work.2 In previous reports, the prevalence of DVT in BD patients was found to range 4–38.9%, which is much higher than expected.2,3 Therefore, 6.8% cases of BD had vascular involvement at or before BD diagnosis, which is commonly observed in men around the age 30 years.2 DVT can cause pulmonary embolism, which is the third leading cause of cardiovascular-associated death.4 In addition, DVT can develop sporadically, as well as in relation with other diseases, including BD.5 Therefore, clinicians should keep in mind that acute edema and swelling of the legs are key features suggesting DVT associated with BD.
CONFLICT OF INTEREST:
None.
(e)
Keita HORIE, Kentaro IZUMI, Wataru NISHIE, Toshifumi NOMURA, Yukiko NOMURA, Ken ARITA, Hiroshi SHIMIZU Figure 1. (a) Physical examination of case 1 revealed edema and erythema nodosum-like lesions on the right leg. (b) Ultrasonography of case 1 shows thrombosis (arrows). RT-CFV, right common femoral vein. (c) Physical examination of case 2 revealed erythematous nodules on the right thigh. (d) Remarkable edema presented on the right lower leg (arrows). (e) Thrombosis (arrow) in the left femoral vein was detected by contrast-enhanced computed tomography scanning of case 2. shown), we initially diagnosed the eruptions as polyarteritis nodosa. A year after the first visit, severe edema occurred on the right leg (Fig. 1d). Contrast-enhanced computed tomography of both legs revealed DVT in the right femoral vein (Fig. 1e). He had also suffered recurrent oral aphthae and genital ulceration. In addition, iritis and positive human leukocyte antigen-B51 were found. From these findings, we made the final diagnosis of BD. We started administration of heparin at 12 000 U/L, then switched to oral warfarin at 6 mg/day and oral NSAIDs. The edema on the right leg soon improved, and there have been no signs of clinical deterioration at 1 year after therapy.
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan doi: 10.1111/1346-8138.12741
REFERENCES 1 International Team for the Revision of the International Criteria for Behcet’s Disease (2006). Revision of the international criteria for Behcet’s disease (ICBD). Clin Exp Rheumatol 2006; 24(Suppl. 42): S13. 2 Sarica-Kucukoglu R, Akdag-Kose A, Kayaball M et al. Vascular involvement in Behcß et’s disease: a retrospective analysis of 2319 cases. Int J Dermatol 2006; 45: 919–921. 3 Houman MH, Ben GI, Khiari Ben Salah I et al. Deep vein thrombosis in Behcß et’s disease. Clin Exp Rheumatol 2001; 19: S48–S50. 4 Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008; 21: 914–918. pez JA, Kearon C, Lee AY. Deep venous thrombosis. Hematology 5 Lo Am Soc Hematol Educ Program 2004; 1: 439–456.
Angiosarcoma of the scalp in a patient with systemic sclerosis Dear Editor, Systemic sclerosis (SSc) is a chronic systemic disease characterized by widespread fibrosis of the skin, vasculopathy and autoimmunity. Although SSc is often associated with various
malignant tumors, including lung and breast cancers and lymphoma, association with skin cancer is rare. We report a case of cutaneous angiosarcoma that developed in a patient with SSc.
Correspondence: Yasuhiro Fujisawa, M.D., Ph.D., Department of Dermatology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki 305-8575, Japan. Email: [email protected]
102
© 2014 Japanese Dermatological Association
Candida antigen, Aspergillus antigen and 1,3-beta-D-glucan were all negative. Because the pulmonary lesions were resistant to broad-spectrum antibacterials and voriconazole, liposomal amphotericin B (started at 3 mg/kg per day, later changed to 3 mg/kg every other day and continued) was administrated and the nodular infiltrates diminished. Four months later, although anti-thymocyte globulin improved steroid-refractory aGVHD, her bone marrow testing showed t-MDS transforming to myeloid leukemia (AML) with her chest CT revealing worsening of the pneumonia. Salvage chemotherapy for t-MDS was started while the dose of corticosteroids and tacrolimus was reduced with the intent to induce allogenic immune effect, and liposomal amphotericin B was returned to daily administration (3 mg/kg per day). Three weeks later, she presented a painful purpura with subcutaneous induration on her right lower limb (Fig. 1a). Skin punch biopsy showed massive hemorrhage and partial necrosis in the dermis and fat tissue, and aggregates of nonseptate broad hyphae with wide-angle branches invading blood vessels (Fig. 1b,c). Debridement of the skin lesion was performed. Direct microscopy of the necrotic tissue stained with Parker ink added to potassium hydroxide revealed nonseptate broad hyphae (Fig. 1d). The tissue was cultured on a Sabouraud’s dextrose agar medium at 25°C, producing whitish cotton-like colonies in 3 days (Fig. 1e). The microscopic view of the colonies (Fig. 1f) was consistent with the features of the Rhizopus genus. Susceptibility testing using E-test strips demonstrated a minimum inhibitory concentration for amphotericin B of 2 lg/mL, voriconazole and itraconazole of over 32 lg/mL in 24 h. The gene sequence of the internal transcribed spacer region of nuclear ribosomal DNA isolated from the colonies was identical to that of R. oryzae. She died of disseminated mucormycosis with t-MDS/AML 2 weeks after skin biopsy.
Mucormycosis infections are characterized by extensive angioinvasion that results in vessel thrombosis and subsequent tissue necrosis. Ischemic necrosis of the infected tissue can prevent leukocytes and antifungal agent penetration to the foci of infection.3 In our case, despite early initiation of empiric therapy with liposomal amphotericin B against suspected pulmonary fungal infection, it eventually developed into disseminated disease and reached a definitive diagnosis from the skin lesion.
CONFLICT OF INTEREST:
The authors have no conflict of
interest to declare.
Mai KANEMARU,1 Saki TASHIMA,1 Akiko YAMAZAKI,1 Koji MASUDA,1 Hisao NAGOSHI,2 Tsutomu KOBAYASHI,2 Junya KURODA,2 Masataro HIRUMA,3 Masafumi TANIWAKI,2 Norito KATOH1 1
Department of Dermatology, Kyoto Prefectural University of Medicine, Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, and 3Ochanomizu Institute for Medical Mycology and Allergology, Tokyo, Japan 2
doi: 10.1111/1346-8138.12715
REFERENCES 1 Spellberg B, Ibrahim AS. Recent advances in the treatment of mucormycosis. Curr Infect Dis Rep 2010; 12: 423–429. 2 Roden MM, Zaoutis TE, Buchanan WL et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005; 41: 634–653. 3 Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis 2012; 54(Suppl 1): 16–22.
Deep venous thrombosis in patients with Behc ß et’s disease Dear Editor, We report two cases of young patients in whom deep venous thrombosis (DVT) was the key clinical finding for the diagnosis of Behc ß et’s disease (BD). Case 1 was a 21-year-old woman who was referred to our department with a 1-year history of recurrent erythema on the right lower leg. We made the diagnosis of erythema nodosum (EN). Treatment with oral non-steroidal anti-inflammatory drugs (NSAIDs) improved the erythema. At 18 months after the first visit, she returned to our department with edema and multiple painful erythematous nodules on the right lower leg (Fig. 1a). Skin biopsy from an erythematous nodule showed lobular and septal panniculitis and thickening of the blood vessel walls,
with moderate inflammatory cell infiltrates (data not shown). Based on the histopathological findings, we diagnosed the erythematous nodules as EN-like lesions. Ultrasonography performed to determine the cause of the edema revealed DVT in the right femoral vein (Fig. 1b). She had past history of oral aphthae and vulvar ulcers. From these findings, we made the diagnosis of BD based on the International Criteria for Behc ß et’s Disease.1 She was treated with oral warfarin at 4 mg/day; at 16 months after therapy, there were no abnormal clinical signs. Case 2 was a 29-year-old man who presented with a 1-year history of erythema on both legs. The initial examination revealed painful erythematous nodules on the right thigh (Fig. 1c). Based on the histopathological findings (data not
Correspondence: Kentaro Izumi, M.D., Department of Dermatology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo 060-8638, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
101
Letters to the Editor
(a)
(c)
(b)
(d)
In these cases, DVT was the key clinical feature suggesting the diagnosis of BD. Venous thrombosis is the major complication of BD. Superficial venous thrombophlebitis is the most common vascular symptom of BD.2 In contrast, DVT has not been regarded to be a major complication of BD, and very few cases have been reported in the dermatological published work.2 In previous reports, the prevalence of DVT in BD patients was found to range 4–38.9%, which is much higher than expected.2,3 Therefore, 6.8% cases of BD had vascular involvement at or before BD diagnosis, which is commonly observed in men around the age 30 years.2 DVT can cause pulmonary embolism, which is the third leading cause of cardiovascular-associated death.4 In addition, DVT can develop sporadically, as well as in relation with other diseases, including BD.5 Therefore, clinicians should keep in mind that acute edema and swelling of the legs are key features suggesting DVT associated with BD.
CONFLICT OF INTEREST:
None.
(e)
Keita HORIE, Kentaro IZUMI, Wataru NISHIE, Toshifumi NOMURA, Yukiko NOMURA, Ken ARITA, Hiroshi SHIMIZU Figure 1. (a) Physical examination of case 1 revealed edema and erythema nodosum-like lesions on the right leg. (b) Ultrasonography of case 1 shows thrombosis (arrows). RT-CFV, right common femoral vein. (c) Physical examination of case 2 revealed erythematous nodules on the right thigh. (d) Remarkable edema presented on the right lower leg (arrows). (e) Thrombosis (arrow) in the left femoral vein was detected by contrast-enhanced computed tomography scanning of case 2. shown), we initially diagnosed the eruptions as polyarteritis nodosa. A year after the first visit, severe edema occurred on the right leg (Fig. 1d). Contrast-enhanced computed tomography of both legs revealed DVT in the right femoral vein (Fig. 1e). He had also suffered recurrent oral aphthae and genital ulceration. In addition, iritis and positive human leukocyte antigen-B51 were found. From these findings, we made the final diagnosis of BD. We started administration of heparin at 12 000 U/L, then switched to oral warfarin at 6 mg/day and oral NSAIDs. The edema on the right leg soon improved, and there have been no signs of clinical deterioration at 1 year after therapy.
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan doi: 10.1111/1346-8138.12741
REFERENCES 1 International Team for the Revision of the International Criteria for Behcet’s Disease (2006). Revision of the international criteria for Behcet’s disease (ICBD). Clin Exp Rheumatol 2006; 24(Suppl. 42): S13. 2 Sarica-Kucukoglu R, Akdag-Kose A, Kayaball M et al. Vascular involvement in Behcß et’s disease: a retrospective analysis of 2319 cases. Int J Dermatol 2006; 45: 919–921. 3 Houman MH, Ben GI, Khiari Ben Salah I et al. Deep vein thrombosis in Behcß et’s disease. Clin Exp Rheumatol 2001; 19: S48–S50. 4 Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008; 21: 914–918. pez JA, Kearon C, Lee AY. Deep venous thrombosis. Hematology 5 Lo Am Soc Hematol Educ Program 2004; 1: 439–456.
Angiosarcoma of the scalp in a patient with systemic sclerosis Dear Editor, Systemic sclerosis (SSc) is a chronic systemic disease characterized by widespread fibrosis of the skin, vasculopathy and autoimmunity. Although SSc is often associated with various
malignant tumors, including lung and breast cancers and lymphoma, association with skin cancer is rare. We report a case of cutaneous angiosarcoma that developed in a patient with SSc.
Correspondence: Yasuhiro Fujisawa, M.D., Ph.D., Department of Dermatology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba City, Ibaraki 305-8575, Japan. Email: [email protected]
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© 2014 Japanese Dermatological Association
