clinical and histopathological features in our case would be a spectrum of the most progressed form, which might initially have developed as either PXE-like PDE or WFPN. We believe that FEP is crucial concept for unifying PXElike PDE, WFPN and overlapping conditions, including our advanced case with a long-lasting history. Disclosure. Financial support: none. Conflict of interest: none. Department of Dermatology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
Naoki OISO Maiko KATO Akira KAWADA
1. Rongioletti F, Izakovic J, Romanelli P, Lanuti E, Miteva M. Pseudoxanthoma elasticume-like papillary dermal elastolysis: A large case series with clinicopathological correlation. J Am Acad Dermatol 2012; 67: 128-35. 2. Rongioletti F, Rebora A. Pseudoxanthoma elasticumelike papillary dermal elastolysis. J Am Acad Dermatol 1992; 26: 648-50. 3. Shimizu H, Kimura S, Harada T, Nishikawa T. White fibrous papulosis of the neck: a new clinicopathologic entity? J Am Acad Dermatol 1989; 20: 1073-7. 4. Jagdeo J, Ng C, Ronchetti IP, Wilkel C, Bercovitch L, Robinson-Bostom L. Fibroelastolytic papulosis. J Am Acad Dermatol 2004; 51: 958-64. 5. Balus L, Amantea A, Donati P, Fazio M, Giuliano MC, Bellocci M. Fibroelastolytic papulosis of the neck: a report of 20 cases. Br J Dermatol 1997; 137: 461-6. 6. Song YC, Oh BH, Ko JH, et al. A case of fibroelastolytic papulosis on the neck of a young man. Ann Dermatol 2011; 23: 193-7. 7. Cannavò SP, Rongioletti F, Guarneri F, et al. Fibroelastolytic papulosis of the neck: two new cases with an ultrastructural study. G Ital Dermatol Venereol 2007; 142: 607-11. 8. Ohnishi Y, Tajima S, Ishibashi A, Inazumi T, Sasaki T, Sakamoto H. Pseudoxanthoma elasticum-like papillary dermal elastolysis: report of four Japanese cases and an immunohistochemical study of elastin and fibrillin-1. Br J Dermatol 1998; 139: 141-4. 9. Dahlback K, Ljungquist A, Lofberg H, Dahlback B, Engvall E, Sakai LY. Fibrillin immunoreactive fibers constitute a unique network in the human dermis: immunohistochemical comparison of the distributions of fibrillin, vitronectin, amyloid P component, and orcein stainable structures in normal skin and elastosis. J Invest Dermatol 1990; 94: 284-91. 10. Revelles JM, Machan S, Pielasinski U, et al. Pseudoxanthoma elasticum-like papillary dermal elastolysis: immunohistochemical study using elastic fiber cross-reactivity with an antibody against amyloid P component. Am J Dermatopathol 2012; 34: 637-43.
angina and hypertension. After coronary artery bypass graft surgery he developed sternal dehiscence and high-grade fever; his white blood cell count was 10,100/mL and Creactive protein was 8.8 mg/dL. Teicoplanin (400 mg/day) was started because a wound swab grew methicillinresistant Staphylococcus aureus (MRSA). His teicoplanin trough levels were monitored to stay within the therapeutic range (10-20 mg/mL). However, 13 days after the start of teicoplanin treatment, palpable purpura developed over his lower extremities (figures 1A,B). Pitting edema was present on his bilateral lower legs and feet. He had no abdominal or other symptoms and was free of arthritic pain. A biopsy specimen taken from a purpuric lesion showed lymphocytes, neutrophils, nuclear debris in the vicinity of the capillaries and extravasated erythrocytes in the papillary dermis. Although there was no obvious fibrin deposit, the vessel in the affected skin displayed endothelial cell swelling with extravasation of red blood cells (figures 1C,D). The histopathological diagnosis was LCV. Direct immunofluorescence (DIF) studies were negative for immunoglobulin (Ig) G, IgA, IgM and C3 deposits on the vessel wall. We did not test C4d and C5b-9 in DIF
A
C
B
D
doi:10.1684/ejd.2014.2470
Teicoplanin-induced purpuric eruption with leukocytoclastic vasculitis Although several drugs, especially -lactam antibiotics, are associated with leukocytoclastic vasculitis (LCV), only one patient with LCV induced by the glycopeptide teicoplanin has been reported to date [1]. We here present the second case. This 88-year-old Japanese man manifested purpuric eruption on his lower extremities. His medical history included EJD, vol. 24, n◦ 6, November-December 2014
Figure 1. A, B) Multiple purpuric eruptions on the lower legs. B) Close-up image of the boxed region. C, D) Histopathological findings on the purpuric lesion. D) Enlarged image of the boxed region. Black arrows, black and white arrowheads are vessel endothelial cell swelling with extravasation of red blood cells, nuclear debris and extravasation of red blood cells, respectively. Bars, 30 m.
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studies. Laboratory tests showed a white blood cell count of 8,120/mL with a normal differential count, a platelet count of 510,000/mL and normal liver and kidney functions. Serum IgA and anti-neutrophil cytoplasmic antibodies were within normal limits. Urinalysis revealed no abnormality. The skin lesions disappeared completely 7 days after the discontinuation of teicoplanin and he suffered no relapse. Teicoplanin, a glycopeptide antibiotic that shares a similar structure and function with vancomycin, is widely used to treat MRSA infections. While its profile is safer than that of vancomycin, it has been reported to elicit adverse drug reactions such as red man syndrome, fever, thrombocytopenia and skin rash, including purpura with LCV [1, 2]. In our review of the literature we found 8 reports of purpuric eruptions with LCV induced by vancomycin; the patients were from the USA, France, the Netherlands, Greece and Australia [3-5]. The only previously-reported patient with teicoplanin-induced LCV was from the UK [1]; ours is the first Asian patient. The clinicopathological features and the spontaneous recovery after discontinuation of teicoplanin support the diagnosis of teicoplanin-induced LCV. Based on the therapeutic trough level, like vancomycin-induced LCV, the disease induced by teicoplanin does not appear to be dose-dependent [4]. While the sequential administration of teicoplanin after vancomycin-induced adverse drug reactions may increase the incidence of drug reactions elicited by teicoplanin due to the cross-reactivity of these drugs [2, 6], our patient had not undergone prior treatment with vancomycin. LCV is thought to be attributable to the deposition of immune complexes on vessel walls and the consequent activation of complement pathways [3]. However, the elicitation of immune complex responses in glycopeptideinduced LCV remains to be confirmed [7]. To our knowledge, this is the first report of glycopeptide (teicoplanin/vancomycin)-induced LCV in an Asian patient. In Japan, the annual use of vancomycin is lower than in the USA but higher than in European countries [8, 9]. Of 10 patients with glycopeptide-induced LCV, 7 were from European countries. There are racial differences in the response to drugs used to treat various diseases [10]. At present it is not known whether genetic factors are involved in glycopeptide-induced LCV and additional studies are needed to elucidate its pathogenesis. Disclosure. Acknowledgement: We thank Kanayo Gunshin for technical assistance. Financial support: none. Conflict of interest: none. Department of Dermatology Kagoshima University Graduate School of Medical and Dental Sciences 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
Youhei UCHIDA Yuko HIGASHI Takuro KANEKURA
1. Logan SA, Brown M, Davidson RN. Teicoplanin-induced vasculitis with cutaneous and renal involvement. J Infect 2005; 51: e185-6. 2. Hsiao SH, Chou CH, Lin WL, et al. High risk of cross-reactivity between vancomycin and sequential teicoplanin therapy. J Clin Pharm Ther 2012; 37: 296-300.
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3. Pongruangporn M, Ritchie DJ, Lu D, Marschall J. Vancomycinassociated leukocytoclastic vasculitis. Case Rep Infect Dis 2011: 356370. doi: 10.1155/2011/356370. Epub 2011 Jun 30. 4. Felix-Getzik E, Sylvia LM. Vancomycin-induced leukocytoclastic vasculitis. Pharmacother 2009; 29: 846-51. 5. Bataille S, Daumas A, Tasei AM, et al. Vancomycin-induced Henoch-Schönlein purpura: A case report. J Med Case Rep 2012; 6: 106. 6. Marshall C, Street A, Galbraith K. Glycopeptide-induced vasculitis - cross-reactivity between vancomycin and teicoplanin. J Infect 1998; 37: 82-3. 7. Sanchez-Borges M, Thong B, Blanca M, et al. Hypersensitivity reactions to non beta-lactam antimicrobial agents, a statement of the WAO special committee on drug allergy. World Allergy Organ J 2013; 6: 18. 8. Keiichi H. Resistance to glycopeptides. In: Crossley KB, Jefferson KK, Archer GL, Fowler VG, eds. Staphylococci in Human Disease. 2nd edn. Chichester: Wiley-Blackwell Scientific Publications 2009; 9.1739.209. 9. Kirst HA, Thompson DG, Nicas TI. Historical yearly usage of vancomycin. Antimicrob Agents Chemother 1998; 42: 1303-4. 10. Wood AJ. Racial differences in the response to drugs - Pointers to genetic differences. N Engl J Med 2001; 344: 1394-6. doi:10.1684/ejd.2014.2425
Pigmentary mosaicism of the hypopigmented type (hypomelanosis of Ito): hypopigmented lesions with serrated and irregular borders Hypomelanosis of Ito (HI) was first reported in 1952 [1]. In 1992, Ruiz-Maldonado et al. proposed diagnostic criteria for HI [2]. It is typically characterized by more than two hypopigmented segments with extracutaneous manifestations, i.e. nervous and/or musculoskeletal abnormalities [2]. Most patients have linear unilateral or bilateral lesions but patchy lesions may also occur [2]. Extracutaneous abnormalities include mental and motor retardation, seizures, microcephaly, hypotonia and sensorineural hearing loss [2]. The term pigmentary mosaicism (PM) is used now rather than HI, because hypopigmented lesions may present within areas of hyperpigmentation [3, 4]. PM is a cutaneous sign of post-zygotic anomalies of many different pigmentation-associated genes [5]. Thus, HI has been currently redefined as PM of the hypopigmented or Ito type (hypopigmented PM). A 10-year-old Japanese boy with congenital sensorineural hearing loss was referred to us with congenital asymptomatic hypopigmented lesions on the back and right side of the neck. The parents had no history of pigmentary disorders or parental consanguinity. Auditory brain stem response at 10 months of age showed absolute threshold of hearing: 60- and 90- decibel hearing levels in the right and left ears, respectively. Physical examination revealed linear and patchy hypopigmented macules along Blaschko’s lines with serrated and irregular borders on the right side of the neck to the upper chest (arrows, figures 1A,B), the right nape to the upper back (bold arrows, figure 1C) and left nape (arrow, figure 1C). The left side of the neck had normal color (figure 1D). EJD, vol. 24, n◦ 6, November-December 2014
Naoki OISO Maiko KATO Akira KAWADA
1. Rongioletti F, Izakovic J, Romanelli P, Lanuti E, Miteva M. Pseudoxanthoma elasticume-like papillary dermal elastolysis: A large case series with clinicopathological correlation. J Am Acad Dermatol 2012; 67: 128-35. 2. Rongioletti F, Rebora A. Pseudoxanthoma elasticumelike papillary dermal elastolysis. J Am Acad Dermatol 1992; 26: 648-50. 3. Shimizu H, Kimura S, Harada T, Nishikawa T. White fibrous papulosis of the neck: a new clinicopathologic entity? J Am Acad Dermatol 1989; 20: 1073-7. 4. Jagdeo J, Ng C, Ronchetti IP, Wilkel C, Bercovitch L, Robinson-Bostom L. Fibroelastolytic papulosis. J Am Acad Dermatol 2004; 51: 958-64. 5. Balus L, Amantea A, Donati P, Fazio M, Giuliano MC, Bellocci M. Fibroelastolytic papulosis of the neck: a report of 20 cases. Br J Dermatol 1997; 137: 461-6. 6. Song YC, Oh BH, Ko JH, et al. A case of fibroelastolytic papulosis on the neck of a young man. Ann Dermatol 2011; 23: 193-7. 7. Cannavò SP, Rongioletti F, Guarneri F, et al. Fibroelastolytic papulosis of the neck: two new cases with an ultrastructural study. G Ital Dermatol Venereol 2007; 142: 607-11. 8. Ohnishi Y, Tajima S, Ishibashi A, Inazumi T, Sasaki T, Sakamoto H. Pseudoxanthoma elasticum-like papillary dermal elastolysis: report of four Japanese cases and an immunohistochemical study of elastin and fibrillin-1. Br J Dermatol 1998; 139: 141-4. 9. Dahlback K, Ljungquist A, Lofberg H, Dahlback B, Engvall E, Sakai LY. Fibrillin immunoreactive fibers constitute a unique network in the human dermis: immunohistochemical comparison of the distributions of fibrillin, vitronectin, amyloid P component, and orcein stainable structures in normal skin and elastosis. J Invest Dermatol 1990; 94: 284-91. 10. Revelles JM, Machan S, Pielasinski U, et al. Pseudoxanthoma elasticum-like papillary dermal elastolysis: immunohistochemical study using elastic fiber cross-reactivity with an antibody against amyloid P component. Am J Dermatopathol 2012; 34: 637-43.
angina and hypertension. After coronary artery bypass graft surgery he developed sternal dehiscence and high-grade fever; his white blood cell count was 10,100/mL and Creactive protein was 8.8 mg/dL. Teicoplanin (400 mg/day) was started because a wound swab grew methicillinresistant Staphylococcus aureus (MRSA). His teicoplanin trough levels were monitored to stay within the therapeutic range (10-20 mg/mL). However, 13 days after the start of teicoplanin treatment, palpable purpura developed over his lower extremities (figures 1A,B). Pitting edema was present on his bilateral lower legs and feet. He had no abdominal or other symptoms and was free of arthritic pain. A biopsy specimen taken from a purpuric lesion showed lymphocytes, neutrophils, nuclear debris in the vicinity of the capillaries and extravasated erythrocytes in the papillary dermis. Although there was no obvious fibrin deposit, the vessel in the affected skin displayed endothelial cell swelling with extravasation of red blood cells (figures 1C,D). The histopathological diagnosis was LCV. Direct immunofluorescence (DIF) studies were negative for immunoglobulin (Ig) G, IgA, IgM and C3 deposits on the vessel wall. We did not test C4d and C5b-9 in DIF
A
C
B
D
doi:10.1684/ejd.2014.2470
Teicoplanin-induced purpuric eruption with leukocytoclastic vasculitis Although several drugs, especially -lactam antibiotics, are associated with leukocytoclastic vasculitis (LCV), only one patient with LCV induced by the glycopeptide teicoplanin has been reported to date [1]. We here present the second case. This 88-year-old Japanese man manifested purpuric eruption on his lower extremities. His medical history included EJD, vol. 24, n◦ 6, November-December 2014
Figure 1. A, B) Multiple purpuric eruptions on the lower legs. B) Close-up image of the boxed region. C, D) Histopathological findings on the purpuric lesion. D) Enlarged image of the boxed region. Black arrows, black and white arrowheads are vessel endothelial cell swelling with extravasation of red blood cells, nuclear debris and extravasation of red blood cells, respectively. Bars, 30 m.
689
studies. Laboratory tests showed a white blood cell count of 8,120/mL with a normal differential count, a platelet count of 510,000/mL and normal liver and kidney functions. Serum IgA and anti-neutrophil cytoplasmic antibodies were within normal limits. Urinalysis revealed no abnormality. The skin lesions disappeared completely 7 days after the discontinuation of teicoplanin and he suffered no relapse. Teicoplanin, a glycopeptide antibiotic that shares a similar structure and function with vancomycin, is widely used to treat MRSA infections. While its profile is safer than that of vancomycin, it has been reported to elicit adverse drug reactions such as red man syndrome, fever, thrombocytopenia and skin rash, including purpura with LCV [1, 2]. In our review of the literature we found 8 reports of purpuric eruptions with LCV induced by vancomycin; the patients were from the USA, France, the Netherlands, Greece and Australia [3-5]. The only previously-reported patient with teicoplanin-induced LCV was from the UK [1]; ours is the first Asian patient. The clinicopathological features and the spontaneous recovery after discontinuation of teicoplanin support the diagnosis of teicoplanin-induced LCV. Based on the therapeutic trough level, like vancomycin-induced LCV, the disease induced by teicoplanin does not appear to be dose-dependent [4]. While the sequential administration of teicoplanin after vancomycin-induced adverse drug reactions may increase the incidence of drug reactions elicited by teicoplanin due to the cross-reactivity of these drugs [2, 6], our patient had not undergone prior treatment with vancomycin. LCV is thought to be attributable to the deposition of immune complexes on vessel walls and the consequent activation of complement pathways [3]. However, the elicitation of immune complex responses in glycopeptideinduced LCV remains to be confirmed [7]. To our knowledge, this is the first report of glycopeptide (teicoplanin/vancomycin)-induced LCV in an Asian patient. In Japan, the annual use of vancomycin is lower than in the USA but higher than in European countries [8, 9]. Of 10 patients with glycopeptide-induced LCV, 7 were from European countries. There are racial differences in the response to drugs used to treat various diseases [10]. At present it is not known whether genetic factors are involved in glycopeptide-induced LCV and additional studies are needed to elucidate its pathogenesis. Disclosure. Acknowledgement: We thank Kanayo Gunshin for technical assistance. Financial support: none. Conflict of interest: none. Department of Dermatology Kagoshima University Graduate School of Medical and Dental Sciences 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan
Youhei UCHIDA Yuko HIGASHI Takuro KANEKURA
1. Logan SA, Brown M, Davidson RN. Teicoplanin-induced vasculitis with cutaneous and renal involvement. J Infect 2005; 51: e185-6. 2. Hsiao SH, Chou CH, Lin WL, et al. High risk of cross-reactivity between vancomycin and sequential teicoplanin therapy. J Clin Pharm Ther 2012; 37: 296-300.
690
3. Pongruangporn M, Ritchie DJ, Lu D, Marschall J. Vancomycinassociated leukocytoclastic vasculitis. Case Rep Infect Dis 2011: 356370. doi: 10.1155/2011/356370. Epub 2011 Jun 30. 4. Felix-Getzik E, Sylvia LM. Vancomycin-induced leukocytoclastic vasculitis. Pharmacother 2009; 29: 846-51. 5. Bataille S, Daumas A, Tasei AM, et al. Vancomycin-induced Henoch-Schönlein purpura: A case report. J Med Case Rep 2012; 6: 106. 6. Marshall C, Street A, Galbraith K. Glycopeptide-induced vasculitis - cross-reactivity between vancomycin and teicoplanin. J Infect 1998; 37: 82-3. 7. Sanchez-Borges M, Thong B, Blanca M, et al. Hypersensitivity reactions to non beta-lactam antimicrobial agents, a statement of the WAO special committee on drug allergy. World Allergy Organ J 2013; 6: 18. 8. Keiichi H. Resistance to glycopeptides. In: Crossley KB, Jefferson KK, Archer GL, Fowler VG, eds. Staphylococci in Human Disease. 2nd edn. Chichester: Wiley-Blackwell Scientific Publications 2009; 9.1739.209. 9. Kirst HA, Thompson DG, Nicas TI. Historical yearly usage of vancomycin. Antimicrob Agents Chemother 1998; 42: 1303-4. 10. Wood AJ. Racial differences in the response to drugs - Pointers to genetic differences. N Engl J Med 2001; 344: 1394-6. doi:10.1684/ejd.2014.2425
Pigmentary mosaicism of the hypopigmented type (hypomelanosis of Ito): hypopigmented lesions with serrated and irregular borders Hypomelanosis of Ito (HI) was first reported in 1952 [1]. In 1992, Ruiz-Maldonado et al. proposed diagnostic criteria for HI [2]. It is typically characterized by more than two hypopigmented segments with extracutaneous manifestations, i.e. nervous and/or musculoskeletal abnormalities [2]. Most patients have linear unilateral or bilateral lesions but patchy lesions may also occur [2]. Extracutaneous abnormalities include mental and motor retardation, seizures, microcephaly, hypotonia and sensorineural hearing loss [2]. The term pigmentary mosaicism (PM) is used now rather than HI, because hypopigmented lesions may present within areas of hyperpigmentation [3, 4]. PM is a cutaneous sign of post-zygotic anomalies of many different pigmentation-associated genes [5]. Thus, HI has been currently redefined as PM of the hypopigmented or Ito type (hypopigmented PM). A 10-year-old Japanese boy with congenital sensorineural hearing loss was referred to us with congenital asymptomatic hypopigmented lesions on the back and right side of the neck. The parents had no history of pigmentary disorders or parental consanguinity. Auditory brain stem response at 10 months of age showed absolute threshold of hearing: 60- and 90- decibel hearing levels in the right and left ears, respectively. Physical examination revealed linear and patchy hypopigmented macules along Blaschko’s lines with serrated and irregular borders on the right side of the neck to the upper chest (arrows, figures 1A,B), the right nape to the upper back (bold arrows, figure 1C) and left nape (arrow, figure 1C). The left side of the neck had normal color (figure 1D). EJD, vol. 24, n◦ 6, November-December 2014
