Case Report
Disseminated fusariosis in a patient with bone marrow aplasia
Danielle Ferreira Chagas
, Lucia Martins Diniz, Elton Almeida Lucas, Paulo Sergio Emerich Nogueira
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Dermatology Service, Hospital Universitário Cassiano Antonio Moraes, Universidade Federal do Espírito Santo, Vitória, ES, Brazil
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"nombre" => "Elton Almeida" "apellidos" => "Lucas" ] 3 => array:2 [ "nombre" => "Paulo Sergio Emerich" "apellidos" => "Nogueira" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Dermatology Service, Hospital Universitário Cassiano Antonio Moraes, Universidade Federal do Espírito Santo, Vitória, ES, Brazil" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1473 "Ancho" => 1667 "Tamanyo" => 260397 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A, Chest tomography showing a pattern of parenchymal consolidation with intermingled air bronchograms, notably in the posterior region of the pulmonary fields (black arrows). (B, C, and D) CT scan of the sinuses showing diffuse veiling of the paranasal sinuses, characterized by material with soft tissue density filling the maxillary (red arrow), sphenoid (yellow arrow), and frontal sinuses (blue arrow), and the ethmoidal cells (white arrow).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Fusariosis is an opportunistic, cosmopolitan disease caused by filamentous, hyaline fungi of the <span class="elsevierStyleItalic">Fusarium</span> genus, widely distributed in nature as soil and plant saprobes.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It rarely affects immunocompetent individuals; when it does, the infection usually remains superficial, causing onychomycosis and keratitis, related to direct inoculation.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In immunocompromised patients, especially those with hematological cancer, in particular acute myeloid leukemia, and after bone marrow transplantation, invasive fungal infections are associated with 70% mortality.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In disseminated infections, 80% of patients develop skin lesions, which may be the only early manifestation of the disease.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In its disseminated form, fusariosis is a rare infection, with an incidence of 0.06% to 0.2% in the United States and Europe; in hematological patients, however, it is associated with high morbimortality, due to the increased incidence and the low effectiveness of treatments.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This report describes a case of disseminated fusariosis with cutaneous involvement in an immunocompromised patient due to bone marrow aplasia.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Case report</span><p id="par0025" class="elsevierStylePara elsevierViewall">Female patient, 29 years old, previously healthy, admitted to a tertiary hospital due to the sudden onset of petechiae in the lower limbs two months before, associated with fever of recent onset. On admission, she was diagnosed with pancytopenia and severe febrile neutropenia (neutrophils below 100 cells/mm<span class="elsevierStyleSup">3</span>), and broad-spectrum antibiotic therapy (meropenem and vancomycin) was initiated.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In the investigation, a bone marrow biopsy was performed; the histopathology showed bone marrow hypoplasia of the three hematopoietic cell lines, with only 5% of cells. In addition, all serologies (including parvovirus B19) were requested, and all infectious hypotheses were discarded; therefore, the diagnosis of idiopathic bone marrow aplasia was reached.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The patient had persistent fever despite antibiotic therapy, but without bacterial growth in blood cultures. Due to hemodynamic instability, the patient was taken to the intensive care unit, and amphotericin B was indicated at a dose of 5 mg/kg/day, due to febrile neutropenia unresponsive to antibiotic therapy.</p><p id="par0040" class="elsevierStylePara elsevierViewall">After the seventh day of hospitalization, the patient presented a painful, erythematous-violet macula in the left upper limb, which after one week evolved with central necrosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). A lesion biopsy was performed; the histopathology was compatible with leukocytoclastic vasculitis and numerous hyphae were seen on the vessel wall (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Direct examination of material from the skin lesion revealed filamentous fungi. Culture in Sabouraud’s medium with chloramphenicol from the skin fragment and subsequent microculture of the colony evidenced the growth of <span class="elsevierStyleItalic">Fusarium</span> spp. (<a class="elsevierStyleCrossRefs" href="#fig0015">Figs 3 and 4</a>). After the results of these tests, amphotericin B was associated with voriconazole, and the patient initially benefited from this association.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The dermatological examination also showed paronychia in the second and third left fingers and exuberant livedo reticularis in all lower limbs, extending to the abdomen (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The image examination of the sinuses revealed extensive shadowing of the maxillary, frontal, sphenoid, and ethmoid sinuses, which was attributed to invasive sinusitis (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>). The otorhinolaryngology team performed a biopsy of the sinuses and a direct examination of the nasal cavity. Surgical treatment through debridement was not possible due to persistent thrombocytopenia and lesion angioinvasion. Histopathology and direct examination were similar to the findings of the skin lesion. She also had extensive bilateral diffuse pulmonary infiltrate consistent with invasive pneumonia.</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Throughout the period of neutropenia, the patient received transfusions and stimulating factor for granulocytic colonies, but did not present any bone morrow response. After four weeks, she developed refractory septic shock and, despite supportive measures, died 54 days after hospitalization.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">Fusariosis is the second most frequent invasive fungal infection in patients with hematological neoplasms; <span class="elsevierStyleItalic">Fusarium solani</span> is the most common, virulent, and resistant species, presenting the highest mortality, confirmed in the case presented.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The infection starts by inhaling conidia or by direct contact with materials contaminated by spores.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Studies indicate that disseminated cases are usually acquired by inhalation with subsequent dissemination to other organs such as the kidneys, liver, eyes, spleen, and brain.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,8</span></a> In the reported case, skin lesions preceded sinusitis and pneumonia, suggesting hematogenous spread of cutaneous focus. The infection is classified as disseminated when two or more organs are involved, as seen in the case reported, in which the patient presented sinusitis and pneumonia, confirmed by image examination and the presence of skin lesions.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The most common presentation is persistent fever unresponsive to broad-spectrum antibiotic therapy in a neutropenic patient, such as the patient studied. Typical skin involvement shows painful erythematous-violet macules or papules, the center of which evolves to necrosis, usually on the extremities; all these findings were observed in the present case. The dermatological examination also showed livedo reticularis in the entire lower limb reaching the abdomen, which probably occurred due to intravascular proliferation of the fungus leading to occlusion and necrosis of the microvasculature, although the authors have not found any reports of this phenomenon in the literature.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,8,9</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The diagnosis requires the isolation of <span class="elsevierStyleItalic">Fusarium</span> spp.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In the present case, hyphae were observed in the histopathology of the skin and sinuses, confirmed by the growth of fungi in the culture of samples collected at these sites. In histopathological examination, fungi characteristically present angiolymphatic invasion by septate, hyaline, and branched hyphae.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Culture identification is important to help differentiate fusariosis from other hyalohyphomycoses. The <span class="elsevierStyleItalic">Fusarium</span> genus is identified in the culture by multiple canoe-shaped hyaline macroconidia.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> However, species identification requires molecular methods.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Invasive and generalized infections respond poorly to antifungal therapy, partly due to drug resistance, but mainly due to the lack of an effective response from the host, which led to our patient's unfavorable outcome, who remained with persistent neutropenia. Therefore, treatment is based on systemic antifungals and reversal of immunosuppression. The ideal treatment should be guided by the antifungal sensitivity test, which is available in only a few centers; therefore, most authors recommend combined therapy for severe cases, with voriconazole and amphotericin B, the scheme used in the present patient.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,8,10</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The patient had severe neutropenia related to bone marrow aplasia, and the authors found in the literature three cases of disseminated fusariosis associated with this hematological disease, all of which also had a fatal outcome.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Financial support</span><p id="par0090" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Authors’ contributions</span><p id="par0095" class="elsevierStylePara elsevierViewall">Danielle Ferreira Chagas: Conception and planning of the study; elaboration and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Lucia Martins Diniz: Approval of the final version of the manuscript; conception and planning of the study; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Elton Almeida Lucas: Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Paulo Sergio Emerich Nogueira: Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1410351" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1290400" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Financial support" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Authors’ contributions" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-10-08" "fechaAceptado" => "2019-12-15" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1290400" "palabras" => array:4 [ 0 => "Fusariosis" 1 => "Immunosuppression" 2 => "Mycoses" 3 => "Neutropenia" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Fusariosis is a superficial or systemic infection, which occurs mainly in immunocompromised hosts, especially in patients with hematological neoplasia; 70%–75% of the cases present cutaneous manifestations. The disseminated form is rare and difficult to diagnose; even with specific treatment, the evolution is usually fatal. Currently, it is considered an emerging disease; in some centers, it is the second most common cause of invasive mycosis, after aspergillosis. The authors describe a case of a female patient with idiopathic bone marrow aplasia and disseminated fusariosis, who initially appeared to benefit from voriconazole and amphotericin B; however, due to persistent neutropenia, her clinical condition deteriorated with fatal evolution.</p></span>" ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">How to cite this article: Chagas DF, Diniz LM, Lucas EA, Nogueira PSE. Disseminated fusariosis in a patient with bone marrow aplasia. An Bras Dermatol. 2020; 95. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.abd.2019.12.008">https://doi.org/10.1016/j.abd.2019.12.008</span></p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Study conducted at the Hospital Universitário Cassiano Antônio Moraes, Universidade Federal do Espírito Santo, Vitória, ES, Brazil.</p>" ] ] "multimedia" => array:6 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2087 "Ancho" => 2091 "Tamanyo" => 309038 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, An erythematous-violaceous macula on the left upper limb. B, After one week, the lesion evolved to ulceration with a necrotic center and slight erythema around it.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1098 "Ancho" => 2084 "Tamanyo" => 273125 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histopathological examination of a lesion of the left upper limb, showing multiple septate, hyaline, and branched hyphae with angiolymphatic invasion. (A, Hematoxylin & eosin, ×10; B, Grocott, ×40).</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2560 "Ancho" => 2041 "Tamanyo" => 315617 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A, Skin fragment culture in Sabouraud’s medium with chloramphenicol: white powdery filamentous colony; B, Lilac-colored pigmentation on the reverse side.</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 746 "Ancho" => 2084 "Tamanyo" => 188617 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A, Direct examination of the skin lesion showing a large number of filamentous fungi; B, Microculture of the colony stained by lactophenol cotton blue, with macroconidia featuring characteristic canoe-type morphology.</p>" ] ] 4 => array:8 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1105 "Ancho" => 2084 "Tamanyo" => 153775 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A, Paronychia in the second and third left fingers; B, Exuberant livedo reticularis affecting the entire lower limb.</p>" ] ] 5 => array:8 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1473 "Ancho" => 1667 "Tamanyo" => 260397 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A, Chest tomography showing a pattern of parenchymal consolidation with intermingled air bronchograms, notably in the posterior region of the pulmonary fields (black arrows). (B, C, and D) CT scan of the sinuses showing diffuse veiling of the paranasal sinuses, characterized by material with soft tissue density filling the maxillary (red arrow), sphenoid (yellow arrow), and frontal sinuses (blue arrow), and the ethmoidal cells (white arrow).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Disseminated fusariosis by Fusarium proliferatum in a patient with aplastic anaemia receiving primary posaconazole prophylaxis ‒ case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Ricna" 1 => "M. Lengerova" 2 => "M. Palackova" 3 => "M. Hadrabova" 4 => "I. Kocmanova" 5 => "B. 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