Clinical and Experimental Dermatology
Fever and skin lesions in an immunocompromised patient E. del Alcazar,1 A. Jaka,1 N. Camino,2 G. Gancho3 and A. Tuneu1 Departments of 1Dermatology, 2Haematology, and 3Pathology, Hospital Universitario Donostia, Donostia-San Sebastian, Spain doi: 10.1111/ced.12483
Clinical findings A 59-year-old man was diagnosed with acute nonlymphoblastic leukaemia in April 2013. Two months later, during the second cycle of chemotherapy with fludarabine, cytarabine, granulocyte colonystimulating factor (G-CSF) and idarubicin, he developed febrile neutropenia refractory to antibiotics, and widespread skin lesions. On physical examination, several erythematous plaques, some with a necrotic centre, were seen on the patient’s face, back, arms and legs (Fig. 1a,b). There was no onychomycosis or cellulitis. The patients’ medical history included diffuse large B-cell non-Hodgkin lymphoma in 2007, which had been treated with chemotherapy, radiotherapy and bone marrow autotransplantation.
(a)
(b)
Histopathological findings Histological examination of a skin biopsy revealed an ulcerated epidermis and the presence of septate hyphae in the deep dermis and subcutaneous tissue with invasion of blood vessels (Fig. 2a). Staining with periodicacid–Schiff and Grocott–Gomori methenamine silver was positive (Fig. 2b). Blood and skin cultures established the final diagnosis. What is your diagnosis?
Figure 1 (a) Three erythematous papules with central pustule
located on the back. (b) Plaque with necrotic centre and erythematous border on the right leg.
Correspondence: Dr Elena del Alc azar, Department of Dermatology, Hospital Universitario Donostia, Donostia-San Sebasti an, Spain E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 3 May 2014
ª 2014 British Association of Dermatologists
Clinical and Experimental Dermatology (2015) 40, pp219–221
219
D CP
CED
CPD • Clinicopathological case
D
CP
Clinicopathological case
(a)
(b)
Figure 2 (a) Biopsy showing septate hyphae in the deep dermis and subcutaneous tissue (haematoxylin and eosin, original magnifica-
tion 9 20). (b) Biopsy showing numerous hyphae (Grocott–Gomori methenamine silver, original magnification 9 20).
Diagnosis Disseminated fusariosis caused by Fusarium solani.
Discussion Fusarium spp. (Fig 2b) are filamentous fungi that are found in nature as saprobes in soil and as plant pathogens.1–3 In humans, they can cause a wide range of infections, from localized and superficial disease in immunocompetent patients to invasive and disseminated infections in immunocompromised patients.1,4–6 The three species of Fusarium spp. that most commonly cause disease in humans are Fusarium solani, Fusarium oxysporum and Fusarium moniliforme. Fusarium solani is the most virulent and the most frequently found in humans, responsible for approximately 50% of cases.1,2 Local infections in immunocompetent patients are uncommon, and usually present as keratitis, onychomycosis, cellulitis, abscesses and/or infection of chronic ulcers.1,6 In these cases, a previous skin lesion, such as a wound, ulcer or burn, can be found.2,6 Disseminated fusariosis in immunocompromised patients with severe neutropenia represents a serious problem, especially in those with acute leukaemia or those who have undergone bone marrow transplantation.1–6 The majority of patients present with fever refractory to antibiotics, with sinopulmonary infections being the most common, although skin lesions are present in over 70% of patients. The skin may be the portal of entry (e.g. through onychomycosis or trauma), or may be affected as a secondary organ
220
Clinical and Experimental Dermatology (2015) 40, pp219–221
(mestastasic dermal lesions) due to haematological dissemination. Onychomycosis, associated or not with paronychia, may be the primary focus of infection, and it is therefore important to exclude its presence in immunocompromised patients.5,6 The disseminated skin lesions can be classified into six categories: (i) red or grey macules, (ii) red or grey papules, (iii) macules or papules with central necrosis, (iv) purpuric papules, (v) pustules and (vi) subcutaneous nodules.5 Several types of lesions tend to manifest simultaneously, indicating different stages of infection. Pathogenesis is probably multifactorial. The infection begins by inhalation of Fusarium spp. conidia or by direct inoculation to the skin. Subsequently, the conidia must germinate into hyphae in order to establish invasive infection when a suitable environment is offered. Hyphae must avoid oxidative cytotoxic destruction by neutrophils, and Fusarium toxins (fumonisins and trichothecenes) play a key role in the development of the infection. Furthermore, Fusarium spp. are angiothropic and angioinvasive fungi, and are thus able to cause ischaemia and tissue necrosis.1,3 The definitive diagnosis is based on the growth of the fungus in skin or blood cultures, as histological examinations cannot differentiate between Fusarium and Aspergillus. Treatment consists of intravenous antifungal agents such as high doses of liposomal amphotericin B and/or azole drugs (itraconazole, voriconazole or posaconazole) together with G-CFS, as it is essential to correct the neutropenia in order to fight the infection.1–4,6 Surgery can be used in resistant localized lesions or to remove necrotic tissue. Unfortunately, treatment
ª 2014 British Association of Dermatologists
D CP Clinicopathological case
has limited effectiveness because Fusarium spp. are quite resistant to antifungal agents, and mortality can reach 80–90%.5 Our patient was treated initially with liposomal amphotericin B, voriconazole and G-CSF. Three weeks later, he developed multiple subcutaneous nodules and panuveitis in his right eye. The infection resolved after 2 months of treatment, but the patient died 5 months later due to a relapse of his leukaemia.
Learning points
•
Fusarium spp. are facultative pathogens that can affect both immunocompetent (causing superficial and mild infections) and immunocompromised (causing disseminated and severe infections) patients. • Fusariosis frequently affects the skin, either as a portal of entry (e.g. onychomycosis or trauma) or as a secondary organ (mestastasic skin lesions) due to haematological dissemination. • Metastasic skin lesions caused by disseminated fusariosis are highly polymorphic. • The most characteristic form is a red or grey macule with a central ulceration or black eschar (target-like necrosis lesion). • A diagnosis of disseminated fusariosis should be considered in patients with blood disorders who have neutropenia, antibiotic-resistant fever and necrotic lesions.
ª 2014 British Association of Dermatologists
References 1 Muhammed M, Anagnostou T, Desalermos A et al. Fusarium infection: report of 26 cases and review of 97 cases from the literature. Medicine (Baltimore) 2013; 92: 305–16. 2 Cooke NS, Feighery C, Armstrong DK et al. Cutaneous Fusarium solani infection in childhood acute lymphoblastic leukaemia. Clin Exp Dermatol 2009; 34: e117–19. 3 Huang WW, Gray C, Bowers R et al. Painful necrotic nodules in an immunocompromised patient. Arch Dermatol 2010; 146: 439–44. 4 Musa MO, Al Eisa A, Halim M et al. The spectrum of Fusarium infection in immunocompromised patients with haematological malignancies and in non-immunocompromised patients: a single institution experience over 10 years. Br J Haematol 2000; 108: 544–8. 5 Bodey GP, Boktour M, Mays S et al. Skin lesions associated with Fusarium infection. J Am Acad Dermatol 2002; 47: 659–66. 6 Nucci M, Anaissie E. Cutaneous infection by Fusarium species in healthy and immunocompromised hosts: implications for diagnosis and management. Clin Infect Dis 2002; 35: 909–20.
Clinical and Experimental Dermatology (2015) 40, pp219–221
221
Fever and skin lesions in an immunocompromised patient E. del Alcazar,1 A. Jaka,1 N. Camino,2 G. Gancho3 and A. Tuneu1 Departments of 1Dermatology, 2Haematology, and 3Pathology, Hospital Universitario Donostia, Donostia-San Sebastian, Spain doi: 10.1111/ced.12483
Clinical findings A 59-year-old man was diagnosed with acute nonlymphoblastic leukaemia in April 2013. Two months later, during the second cycle of chemotherapy with fludarabine, cytarabine, granulocyte colonystimulating factor (G-CSF) and idarubicin, he developed febrile neutropenia refractory to antibiotics, and widespread skin lesions. On physical examination, several erythematous plaques, some with a necrotic centre, were seen on the patient’s face, back, arms and legs (Fig. 1a,b). There was no onychomycosis or cellulitis. The patients’ medical history included diffuse large B-cell non-Hodgkin lymphoma in 2007, which had been treated with chemotherapy, radiotherapy and bone marrow autotransplantation.
(a)
(b)
Histopathological findings Histological examination of a skin biopsy revealed an ulcerated epidermis and the presence of septate hyphae in the deep dermis and subcutaneous tissue with invasion of blood vessels (Fig. 2a). Staining with periodicacid–Schiff and Grocott–Gomori methenamine silver was positive (Fig. 2b). Blood and skin cultures established the final diagnosis. What is your diagnosis?
Figure 1 (a) Three erythematous papules with central pustule
located on the back. (b) Plaque with necrotic centre and erythematous border on the right leg.
Correspondence: Dr Elena del Alc azar, Department of Dermatology, Hospital Universitario Donostia, Donostia-San Sebasti an, Spain E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 3 May 2014
ª 2014 British Association of Dermatologists
Clinical and Experimental Dermatology (2015) 40, pp219–221
219
D CP
CED
CPD • Clinicopathological case
D
CP
Clinicopathological case
(a)
(b)
Figure 2 (a) Biopsy showing septate hyphae in the deep dermis and subcutaneous tissue (haematoxylin and eosin, original magnifica-
tion 9 20). (b) Biopsy showing numerous hyphae (Grocott–Gomori methenamine silver, original magnification 9 20).
Diagnosis Disseminated fusariosis caused by Fusarium solani.
Discussion Fusarium spp. (Fig 2b) are filamentous fungi that are found in nature as saprobes in soil and as plant pathogens.1–3 In humans, they can cause a wide range of infections, from localized and superficial disease in immunocompetent patients to invasive and disseminated infections in immunocompromised patients.1,4–6 The three species of Fusarium spp. that most commonly cause disease in humans are Fusarium solani, Fusarium oxysporum and Fusarium moniliforme. Fusarium solani is the most virulent and the most frequently found in humans, responsible for approximately 50% of cases.1,2 Local infections in immunocompetent patients are uncommon, and usually present as keratitis, onychomycosis, cellulitis, abscesses and/or infection of chronic ulcers.1,6 In these cases, a previous skin lesion, such as a wound, ulcer or burn, can be found.2,6 Disseminated fusariosis in immunocompromised patients with severe neutropenia represents a serious problem, especially in those with acute leukaemia or those who have undergone bone marrow transplantation.1–6 The majority of patients present with fever refractory to antibiotics, with sinopulmonary infections being the most common, although skin lesions are present in over 70% of patients. The skin may be the portal of entry (e.g. through onychomycosis or trauma), or may be affected as a secondary organ
220
Clinical and Experimental Dermatology (2015) 40, pp219–221
(mestastasic dermal lesions) due to haematological dissemination. Onychomycosis, associated or not with paronychia, may be the primary focus of infection, and it is therefore important to exclude its presence in immunocompromised patients.5,6 The disseminated skin lesions can be classified into six categories: (i) red or grey macules, (ii) red or grey papules, (iii) macules or papules with central necrosis, (iv) purpuric papules, (v) pustules and (vi) subcutaneous nodules.5 Several types of lesions tend to manifest simultaneously, indicating different stages of infection. Pathogenesis is probably multifactorial. The infection begins by inhalation of Fusarium spp. conidia or by direct inoculation to the skin. Subsequently, the conidia must germinate into hyphae in order to establish invasive infection when a suitable environment is offered. Hyphae must avoid oxidative cytotoxic destruction by neutrophils, and Fusarium toxins (fumonisins and trichothecenes) play a key role in the development of the infection. Furthermore, Fusarium spp. are angiothropic and angioinvasive fungi, and are thus able to cause ischaemia and tissue necrosis.1,3 The definitive diagnosis is based on the growth of the fungus in skin or blood cultures, as histological examinations cannot differentiate between Fusarium and Aspergillus. Treatment consists of intravenous antifungal agents such as high doses of liposomal amphotericin B and/or azole drugs (itraconazole, voriconazole or posaconazole) together with G-CFS, as it is essential to correct the neutropenia in order to fight the infection.1–4,6 Surgery can be used in resistant localized lesions or to remove necrotic tissue. Unfortunately, treatment
ª 2014 British Association of Dermatologists
D CP Clinicopathological case
has limited effectiveness because Fusarium spp. are quite resistant to antifungal agents, and mortality can reach 80–90%.5 Our patient was treated initially with liposomal amphotericin B, voriconazole and G-CSF. Three weeks later, he developed multiple subcutaneous nodules and panuveitis in his right eye. The infection resolved after 2 months of treatment, but the patient died 5 months later due to a relapse of his leukaemia.
Learning points
•
Fusarium spp. are facultative pathogens that can affect both immunocompetent (causing superficial and mild infections) and immunocompromised (causing disseminated and severe infections) patients. • Fusariosis frequently affects the skin, either as a portal of entry (e.g. onychomycosis or trauma) or as a secondary organ (mestastasic skin lesions) due to haematological dissemination. • Metastasic skin lesions caused by disseminated fusariosis are highly polymorphic. • The most characteristic form is a red or grey macule with a central ulceration or black eschar (target-like necrosis lesion). • A diagnosis of disseminated fusariosis should be considered in patients with blood disorders who have neutropenia, antibiotic-resistant fever and necrotic lesions.
ª 2014 British Association of Dermatologists
References 1 Muhammed M, Anagnostou T, Desalermos A et al. Fusarium infection: report of 26 cases and review of 97 cases from the literature. Medicine (Baltimore) 2013; 92: 305–16. 2 Cooke NS, Feighery C, Armstrong DK et al. Cutaneous Fusarium solani infection in childhood acute lymphoblastic leukaemia. Clin Exp Dermatol 2009; 34: e117–19. 3 Huang WW, Gray C, Bowers R et al. Painful necrotic nodules in an immunocompromised patient. Arch Dermatol 2010; 146: 439–44. 4 Musa MO, Al Eisa A, Halim M et al. The spectrum of Fusarium infection in immunocompromised patients with haematological malignancies and in non-immunocompromised patients: a single institution experience over 10 years. Br J Haematol 2000; 108: 544–8. 5 Bodey GP, Boktour M, Mays S et al. Skin lesions associated with Fusarium infection. J Am Acad Dermatol 2002; 47: 659–66. 6 Nucci M, Anaissie E. Cutaneous infection by Fusarium species in healthy and immunocompromised hosts: implications for diagnosis and management. Clin Infect Dis 2002; 35: 909–20.
Clinical and Experimental Dermatology (2015) 40, pp219–221
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