to hot air during sauna-bathing [3]. However, heat-stroke burn can occur even under clothing and during a heat wave anywhere in the world. In cases of hot-air sauna burn, two patterns of skin injury, namely, mesh-like and uniform, and rhabdomyolysis have been reported. We observed livedoid patterns exclusively in major regions of burns, with a uniform pattern only on the faces of our patients. Rhabdomyolysis was minimal when estimated in terms of elevation of serum creatine kinase. During heat stress, active vasodilator tone directed towards cutaneous arterioles is enhanced [4]. Furthermore, diminished arteriolar flow can result from dehydration, hyperviscosity and/or thrombosis. Then deoxygenation is caused by decreased arteriolar perfusion, which leads to livedoid patterns [5]. It is likely that lesions were found only on the upper areas of the supine bodies because of decreased hydrostatic pressure within the cutaneous vessels of the affected areas, due to dehydration. Both patients were old and living alone and their life style might have contributed to heat stroke because they might have been unaware of the high temperatures outside. Other risk factors can be proposed: drug intake, in particular, antihypertensive drugs, which decrease cardiac-pump activity, with resultant loss of blood flow for heat exchange; clothing, such as dark-colored clothes that absorb incident radiation; parsimonious use of electricity (fan, air conditioning); frequent outdoor labor; and acute increase in ambient temperature. It is curious that such skin injury has not been reported, to our knowledge, in the literature, but the numbers of such cases might be expected to increase in the near future, with global climate change [6]. Disclosure. Financial support: none. Conflict of interest: none. 1
Department of Dermatology, Emergency and Critical Care Center, 3 Department of Neurosurgery, Faculty of Medecine, Oita University, 1-1 Idaigaoka Hasama-machi, 879-5593 Yufu, Japan 2
Yusuke NAKAMURA1 Naoko TAKEO1 Mayuko GOTO1 Yoshitaka KAI1 Yutaka HATANO1 Osamu OKAMOTO1 Sakuhei FUJIWARA1 Sanshi TANABE2 Ryuichi TAKENAKA2 Hirotaka FUDABA3 Takeshi KUBO3 Minoru FUJIKI3
1. Epstein Y, Rberts WO. The pathology of heat stroke: an integrative view of the final common pathway. Scand J Med Sci Sports 2011; 21: 742-8. 2. Vardy DA, Khoury M, Ben-Meir P, Ben-Yakar Y, Shoenfeld Y. Full skin thickness burns caused by contact with the pavement in a heatstroke victim. Burns 1989; 15: 115-6. 3. Koljonen V. Hot air sauna burns-review of their etiology and treatment. J Burn Care Res 2009; 30: 705-10. 4. Charkoudian N. Skin blood flow in adult human thermoregulation: How it works, when it does not, and why. Mayo Clin Proc 2003; 78: 603-12. 5. Gibbs MB, English JC, 3rd JC, Zirwas MJ. Livedo reticularis: An update. J Am Acad Dermatol 2005; 52: 1009-19. 6. Kalkstein LS, Greene JS. An evaluation of climate/mortality relationship in large U.S. cities and the possible impacts of a climate change. Environ Health Perspect 1997; 105: 84-93. doi:10.1684/ejd.2014.2268
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Cutaneous mucormycosis in a patient with acute lymphocytic leukemia Mucormycosis is a rare opportunistic fungal infection caused by members of the order Mucorales, typically in severely immunocompromised hosts and causing fatal infection [1-3]. We report a patient with acute lymphocytic leukemia who developed several cutaneous plaques with necrosis after chemotherapy. A 70-year-old man was admitted for chemotherapy for relapsed acute lymphocytic leukemia. On day 14 of induction chemotherapy, he displayed high fever and severe dyspnea. High-resolution computed tomography revealed infiltrates in the lung. Besides antibiotic therapy, antimycotic therapy was started with liposomal amphotericin B (2.5 mg/kg/day, i.v.) for suspected fungal infection. This was continued over 10 days but dyspnea did not improve very much. Liposomal amphotericin B was therefore stopped and voriconazole (8 mg/kg/day, i.v.) was administered. Over the next few days, the patient developed sharply demarcated plaques with necrosis on the mucosa of the lower lip and the skin of the chest (figures 1A-B). Histopathological examination revealed broad, non-septate hyphae with right-angle branching in the midst of a neutrophilic abscess (figure 1C). Periodic-acid-Schiff staining also identified the growth of fungal hyphae (figure 1D). Culture of a skin sample grew a fungus, which was shown to be of the genus Mucor. One day after diagnosis, the patient unfortunately died from severe mycotic sepsis. Microbiological cultures from bronchoalveolar lavage (BAL) performed 3 days prior to death also confirmed the presence of the genus Mucor. Mucormycosis is an uncommon opportunistic infection caused by members of the order Mucorales. These organisms exist widely in nature and are usually saprophytic,
A
B
C
D
Figure 1. A) Necrotic skin lesions on the mucosa of the lower lip. B) Necrotic skin lesion on the left chest. C) Skin biopsy taken from a necrotic skin lesion, showing characteristic broad, non-septate hyphae of Mucor in the midst of neutrophilic abscess (hematoxylin and eosin, original magnification ×250). D) Periodic-acid-Schiff staining also identified growth of fungal hyphae (original magnification ×250). EJD, vol. 24, n◦ 1, January-February 2014
growing on decaying organic materials such as vegetation, fruit, and bread [1]. In addition, they can normally be cultured from the stools, nasal passages and oral cavities of healthy persons [1]. Cutaneous mucormycoses can be broadly separated into two categories according to the manner in which the disease manifests: primary cases, in which the skin is invaded directly by the organism; and secondary cases, in which the organism is transported from a lesion in an internal organ to a skin site by hematogenous metastasis [3]. The clinical presentation differs between these two disease processes. The primary cutaneous variant is rare and invasive, involving not only the cutaneous tissue but also the underlying fat, muscle and fascial layers [5]. It typically presents as a single necrotic hemorrhagic ulcer following percutaneous inoculation of fungal spores [6]. Growth of the fungus in a pre-existing lesion produces an acute inflammatory response with pus, abscess formation, tissue swelling and necrosis. The lesions may appear red and indurated but often progress to form black eschars. We believe the present case represented secondary hematogenous spread from a pulmonary site to the skin because pulmonary involvement was clinically evident before the appearance of skin lesions, and microbiological cultures from BAL also identified the presence of the genus Mucor. This disease often causes necrotic hemorrhagic lesions because Mucor species have an ability to invade the walls of vessels and proliferate, causing thrombosis and subsequent infarction of the involved vessel, with subsequent local tissue destruction [1, 7, 8]. Given the poor prognosis, mucormycosis usually requires several simultaneous modes of therapy: surgical debridement; antifungal therapy; and improvement of immunosuppressive state [1, 2]. Amphotericin B has been the first-line drug of choice for most cases of mucormycosis [1, 2, 5]. Unfortunately, this drug has adverse effects such as nephrotoxicity and electrolyte disturbances. Furthermore, some patients do not respond. The liposomal form of amphotericin B (AmBisome® ; Gilead Sciences, Foster City, CA, USA) is associated with fewer side-effects and offers dramatically better outcomes [4]. The poor prognosis in this infection is mainly due to a failure to achieve early diagnosis, extensive involvement and the underlying condition [4]. However, early diagnosis of mucormycosis is difficult and many patients are only diagnosed post-mortem [9]. Although the standard for diagnosis of cutaneous mucormycosis is a fungal culture of full-thickness skin tissue, culture growth of Mucorales may be time-consuming. Detection of non-septate, branched hyphae in a KOH specimen or biopsy sample stained with hematoxylin and eosin should also be considered highly significant in reaching a diagnosis more rapidly. With the increasing number of diabetic patients and increased use of corticosteroids, immunosuppressants and anti-cancer agents, the incidence of cutaneous mucormycosis is increasing. Mucormycosis should be considered in the initial evaluation of cutaneous necrosis or ecthyma-like lesions, particularly in immunocompromised patients. Disclosure. Financial support: none. Conflict of interest: none.
EJD, vol. 24, n◦ 1, January-February 2014
1
Department of Dermatology, Ehime University Graduate School of Medicine, Toon, 791-0295 Ehime, Japan 2 Department of Dermatology, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
Ken SHIRAISHI1 Shiro SASAKI2 Yasushi SADAMOTO2
1. Wirth F, Perry R, Eskenazi A, et al. Cutaneous mucormycosis with subsequent visceral dissemination in a child with neutropenia: a case report and review of the pediatric literature. J Am Acad Dermatol 1997; 36: 336-41. 2. Fujimoto A, Nagao K, Tanaka K, et al. The first case of cutaneous mucormycosis caused by Rhizopus azygosporus. Br J Dermatol 2005; 153: 428-30. 3. Kobayashi M, Hiruma M, Matsushita A, et al. Cutaneous zygomycosis: a case report and review of Japanese reports. Mycoses 2001; 44: 311-5. 4. Wali YA, Lamki ZA, Kindi HA, et al. Case report. Successful outcome of invasive nasal sinus zygomycosis in a child with relapsed acute lymphoblastic leukaemia due to liposomal amphotericin B. Mycoses 2001; 44: 195-9. 5. Kerr OA, Bong C, Wallis C, et al. Primary cutaneous mucormycosis masquerading as pyoderma gangrenosum. Br J Dermatol 2004; 150: 1212-3. 6. Chambers CJ, Merin MR, Fung MA, et al. Primary cutaneous mucormycosis at sites of insulin injection. J Am Acad Dermatol 2011; 64: 79-81. 7. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000; 13: 236-301. 8. Lenane P, Keane CO, Loughlin SO. Mucor mycosis infection presenting as a non-healing ulcer in an immunocompromised patient. Clin Exp Dermatol 2003; 28: 157-9. 9. Hadaschik E, Koschny R, Willinger B, et al. Pulmonary, rhino-orbital and cutaneous mucormycosis caused by Rhizomucor pusillus in an immunocompromised patient. Clin Exp Dermatol 2012; 37: 355-7. doi:10.1684/ejd.2013.2240
Successful treatment with UVA rush hardening in a case of solar urticaria Solar urticaria (SU) is a rare idiopathic photodermatosis. The symptoms are usually observed within ten minutes after exposure to sunlight. The action spectra are different among cases, ranging from ultraviolet B (UVB) to visible light [1]. SU is commonly treated with oral antihistamines, sunscreen, plasmapheresis and/or immunosuppressants. Phototherapy with various wavelengths of light and methods has also been performed to induce a tolerant state [2-4]. However, the symptoms of SU are frequently resistant to these treatments. Recently, the effectiveness of ultraviolet A (UVA) rush hardening therapy has been reported [5, 6]. We herein describe a case of successful treatment with UVA rush hardening in a SU patient in whom irradiation of visible light strongly contributed to the development of symptoms.
117
Department of Dermatology, Emergency and Critical Care Center, 3 Department of Neurosurgery, Faculty of Medecine, Oita University, 1-1 Idaigaoka Hasama-machi, 879-5593 Yufu, Japan 2
Yusuke NAKAMURA1 Naoko TAKEO1 Mayuko GOTO1 Yoshitaka KAI1 Yutaka HATANO1 Osamu OKAMOTO1 Sakuhei FUJIWARA1 Sanshi TANABE2 Ryuichi TAKENAKA2 Hirotaka FUDABA3 Takeshi KUBO3 Minoru FUJIKI3
1. Epstein Y, Rberts WO. The pathology of heat stroke: an integrative view of the final common pathway. Scand J Med Sci Sports 2011; 21: 742-8. 2. Vardy DA, Khoury M, Ben-Meir P, Ben-Yakar Y, Shoenfeld Y. Full skin thickness burns caused by contact with the pavement in a heatstroke victim. Burns 1989; 15: 115-6. 3. Koljonen V. Hot air sauna burns-review of their etiology and treatment. J Burn Care Res 2009; 30: 705-10. 4. Charkoudian N. Skin blood flow in adult human thermoregulation: How it works, when it does not, and why. Mayo Clin Proc 2003; 78: 603-12. 5. Gibbs MB, English JC, 3rd JC, Zirwas MJ. Livedo reticularis: An update. J Am Acad Dermatol 2005; 52: 1009-19. 6. Kalkstein LS, Greene JS. An evaluation of climate/mortality relationship in large U.S. cities and the possible impacts of a climate change. Environ Health Perspect 1997; 105: 84-93. doi:10.1684/ejd.2014.2268
116
Cutaneous mucormycosis in a patient with acute lymphocytic leukemia Mucormycosis is a rare opportunistic fungal infection caused by members of the order Mucorales, typically in severely immunocompromised hosts and causing fatal infection [1-3]. We report a patient with acute lymphocytic leukemia who developed several cutaneous plaques with necrosis after chemotherapy. A 70-year-old man was admitted for chemotherapy for relapsed acute lymphocytic leukemia. On day 14 of induction chemotherapy, he displayed high fever and severe dyspnea. High-resolution computed tomography revealed infiltrates in the lung. Besides antibiotic therapy, antimycotic therapy was started with liposomal amphotericin B (2.5 mg/kg/day, i.v.) for suspected fungal infection. This was continued over 10 days but dyspnea did not improve very much. Liposomal amphotericin B was therefore stopped and voriconazole (8 mg/kg/day, i.v.) was administered. Over the next few days, the patient developed sharply demarcated plaques with necrosis on the mucosa of the lower lip and the skin of the chest (figures 1A-B). Histopathological examination revealed broad, non-septate hyphae with right-angle branching in the midst of a neutrophilic abscess (figure 1C). Periodic-acid-Schiff staining also identified the growth of fungal hyphae (figure 1D). Culture of a skin sample grew a fungus, which was shown to be of the genus Mucor. One day after diagnosis, the patient unfortunately died from severe mycotic sepsis. Microbiological cultures from bronchoalveolar lavage (BAL) performed 3 days prior to death also confirmed the presence of the genus Mucor. Mucormycosis is an uncommon opportunistic infection caused by members of the order Mucorales. These organisms exist widely in nature and are usually saprophytic,
A
B
C
D
Figure 1. A) Necrotic skin lesions on the mucosa of the lower lip. B) Necrotic skin lesion on the left chest. C) Skin biopsy taken from a necrotic skin lesion, showing characteristic broad, non-septate hyphae of Mucor in the midst of neutrophilic abscess (hematoxylin and eosin, original magnification ×250). D) Periodic-acid-Schiff staining also identified growth of fungal hyphae (original magnification ×250). EJD, vol. 24, n◦ 1, January-February 2014
growing on decaying organic materials such as vegetation, fruit, and bread [1]. In addition, they can normally be cultured from the stools, nasal passages and oral cavities of healthy persons [1]. Cutaneous mucormycoses can be broadly separated into two categories according to the manner in which the disease manifests: primary cases, in which the skin is invaded directly by the organism; and secondary cases, in which the organism is transported from a lesion in an internal organ to a skin site by hematogenous metastasis [3]. The clinical presentation differs between these two disease processes. The primary cutaneous variant is rare and invasive, involving not only the cutaneous tissue but also the underlying fat, muscle and fascial layers [5]. It typically presents as a single necrotic hemorrhagic ulcer following percutaneous inoculation of fungal spores [6]. Growth of the fungus in a pre-existing lesion produces an acute inflammatory response with pus, abscess formation, tissue swelling and necrosis. The lesions may appear red and indurated but often progress to form black eschars. We believe the present case represented secondary hematogenous spread from a pulmonary site to the skin because pulmonary involvement was clinically evident before the appearance of skin lesions, and microbiological cultures from BAL also identified the presence of the genus Mucor. This disease often causes necrotic hemorrhagic lesions because Mucor species have an ability to invade the walls of vessels and proliferate, causing thrombosis and subsequent infarction of the involved vessel, with subsequent local tissue destruction [1, 7, 8]. Given the poor prognosis, mucormycosis usually requires several simultaneous modes of therapy: surgical debridement; antifungal therapy; and improvement of immunosuppressive state [1, 2]. Amphotericin B has been the first-line drug of choice for most cases of mucormycosis [1, 2, 5]. Unfortunately, this drug has adverse effects such as nephrotoxicity and electrolyte disturbances. Furthermore, some patients do not respond. The liposomal form of amphotericin B (AmBisome® ; Gilead Sciences, Foster City, CA, USA) is associated with fewer side-effects and offers dramatically better outcomes [4]. The poor prognosis in this infection is mainly due to a failure to achieve early diagnosis, extensive involvement and the underlying condition [4]. However, early diagnosis of mucormycosis is difficult and many patients are only diagnosed post-mortem [9]. Although the standard for diagnosis of cutaneous mucormycosis is a fungal culture of full-thickness skin tissue, culture growth of Mucorales may be time-consuming. Detection of non-septate, branched hyphae in a KOH specimen or biopsy sample stained with hematoxylin and eosin should also be considered highly significant in reaching a diagnosis more rapidly. With the increasing number of diabetic patients and increased use of corticosteroids, immunosuppressants and anti-cancer agents, the incidence of cutaneous mucormycosis is increasing. Mucormycosis should be considered in the initial evaluation of cutaneous necrosis or ecthyma-like lesions, particularly in immunocompromised patients. Disclosure. Financial support: none. Conflict of interest: none.
EJD, vol. 24, n◦ 1, January-February 2014
1
Department of Dermatology, Ehime University Graduate School of Medicine, Toon, 791-0295 Ehime, Japan 2 Department of Dermatology, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
Ken SHIRAISHI1 Shiro SASAKI2 Yasushi SADAMOTO2
1. Wirth F, Perry R, Eskenazi A, et al. Cutaneous mucormycosis with subsequent visceral dissemination in a child with neutropenia: a case report and review of the pediatric literature. J Am Acad Dermatol 1997; 36: 336-41. 2. Fujimoto A, Nagao K, Tanaka K, et al. The first case of cutaneous mucormycosis caused by Rhizopus azygosporus. Br J Dermatol 2005; 153: 428-30. 3. Kobayashi M, Hiruma M, Matsushita A, et al. Cutaneous zygomycosis: a case report and review of Japanese reports. Mycoses 2001; 44: 311-5. 4. Wali YA, Lamki ZA, Kindi HA, et al. Case report. Successful outcome of invasive nasal sinus zygomycosis in a child with relapsed acute lymphoblastic leukaemia due to liposomal amphotericin B. Mycoses 2001; 44: 195-9. 5. Kerr OA, Bong C, Wallis C, et al. Primary cutaneous mucormycosis masquerading as pyoderma gangrenosum. Br J Dermatol 2004; 150: 1212-3. 6. Chambers CJ, Merin MR, Fung MA, et al. Primary cutaneous mucormycosis at sites of insulin injection. J Am Acad Dermatol 2011; 64: 79-81. 7. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000; 13: 236-301. 8. Lenane P, Keane CO, Loughlin SO. Mucor mycosis infection presenting as a non-healing ulcer in an immunocompromised patient. Clin Exp Dermatol 2003; 28: 157-9. 9. Hadaschik E, Koschny R, Willinger B, et al. Pulmonary, rhino-orbital and cutaneous mucormycosis caused by Rhizomucor pusillus in an immunocompromised patient. Clin Exp Dermatol 2012; 37: 355-7. doi:10.1684/ejd.2013.2240
Successful treatment with UVA rush hardening in a case of solar urticaria Solar urticaria (SU) is a rare idiopathic photodermatosis. The symptoms are usually observed within ten minutes after exposure to sunlight. The action spectra are different among cases, ranging from ultraviolet B (UVB) to visible light [1]. SU is commonly treated with oral antihistamines, sunscreen, plasmapheresis and/or immunosuppressants. Phototherapy with various wavelengths of light and methods has also been performed to induce a tolerant state [2-4]. However, the symptoms of SU are frequently resistant to these treatments. Recently, the effectiveness of ultraviolet A (UVA) rush hardening therapy has been reported [5, 6]. We herein describe a case of successful treatment with UVA rush hardening in a SU patient in whom irradiation of visible light strongly contributed to the development of symptoms.
117
