Letter - Tropical/Infectious and parasitic dermatology
Nontuberculous mycobacteriosis (Mycobacterium chelonae): fatal outcome in a patient with severe systemic lupus erythematosus
Bárbara Elias do Carmo Barbosaa, Priscila Neri Lacerdaa, Luana Moraes Camposb, Mariângela Esther Alencar Marquesc, Silvio Alencar Marquesa, Luciana Patrícia Fernandes Abbadea,
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a Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
b Department of Dermatology, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
c Department of Pathology, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
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She reported the appearance of skin lesions two months before. Dermatological examination showed erythematous-violaceous macules, papules and nodules (more palpable than visible), indurated, painful, some fistulized and with purulent exudate drainage, distributed on the medial surface of the right thigh (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">She was admitted for investigation of lupus activity and pulmonary thromboembolism (PTE) due to her poor general condition, hematological and respiratory alterations. During hospitalization, she developed fever peaks and was treated with cefepime, imipenem, and vancomycin with no improvement of the skin lesions and the systemic clinical picture.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The skin lesion exudate was sent for a culture of bacteria, fungi and mycobacteria and blood cultures were performed. All results were negative. Serologies for HIV, hepatitis B, hepatitis C and syphilis were non-reactive and bacilloscopy was negative.</p><p id="par0025" class="elsevierStylePara elsevierViewall">A skin biopsy was performed and histopathology showed an epithelioid granulomatous inflammatory process surrounding a cystic necrotic cavity, containing neutrophils (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Ziehl-Neelsen staining showed acid-fast bacilli (AFB) in the cytoplasm of macrophages in the granulomatous process, suggesting nontuberculous mycobacteriosis (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Empirical treatment with rifampicin, ethambutol and azithromycin was initiated, but it was used for only two days, as the patient developed respiratory failure and died due to a thromboembolic event. There was no evidence of systemic mycobacterial infection (negative blood cultures).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The biopsy fragment was sent for culture and polymerase chain reaction (PCR) analysis at the Microbiology Laboratory of Instituto Lauro de Souza Lima. The culture showed the presence of fast-growing <span class="elsevierStyleItalic">Mycobacterium spp.</span> in five to six days. PCR was performed using the PCR-restriction enzyme analysis (PRA) technique, which consists of amplifying DNA with specific primers for a 441 bp sequence of the hsp65 gene. The PCR product was cleaved with the restriction enzymes <span class="elsevierStyleItalic">BstE</span>II and <span class="elsevierStyleItalic">Hae</span>III. The result of this analysis was released only after patient death and identified as <span class="elsevierStyleItalic">Mycobacterium chelonae</span>.</p><p id="par0035" class="elsevierStylePara elsevierViewall">NTM infections are those caused by pathogenic mycobacteria other than <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> or <span class="elsevierStyleItalic">M. leprae</span>, and were formerly known as atypical, anonymous, opportunistic, or unclassified mycobacteriosis.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> NTM clinical presentation depends on the species of mycobacteria and can manifest as papules, plaques, nodules, abscesses and ulcers. Histopathological patterns may include non-specific findings of subcutaneous inflammation, abscesses, granulomas, and nodules.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The incidence of skin NTM infection has increased in recent decades due to the increased use of immunosuppressive therapy and better detection methods. Histopathological analysis is not species-specific, and some of the species are slow-growing and difficult to culture, making their diagnosis difficult. <a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">A high index of suspicion for NTM infections is required in patients with SLE since the initial presentation can mimic several skin manifestations of lupus. The hypothesis should be considered in any patient with indolent skin lesions, especially if routine bacterial cultures are negative. Molecular investigation through polymerase chain reaction (PCR) can increase the sensitivity and specificity, but usually NTM is a late diagnosis and therapy will vary depending on the causative agent.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Almost all species of mycobacteria already identified are capable of causing infection of the skin and subcutaneous tissue, with the main isolated agents being <span class="elsevierStyleItalic">M. fortuitum</span>, <span class="elsevierStyleItalic">M. abscessus</span>, <span class="elsevierStyleItalic">M. chelonae</span>, <span class="elsevierStyleItalic">M. marinum</span>, <span class="elsevierStyleItalic">and M. ulcerans. M. chelonae,</span> isolated in the present case, is found in aquatic environments, soil, and surgical instruments and is characterized by rapid growth in culture. Localized infections have been reported associated with tattoos, pedicure and cosmetic procedures. Disseminated infection usually occurs in immunocompromised individuals, predominantly affecting the lower extremities.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The best therapeutic options described for <span class="elsevierStyleItalic">M. chelonae</span> are tobramycin, imipenem, clarithromycin, linezolid and cotrimoxazole. Regardless of the choice of antibiotics, therapy can last for months to over a year. Surgical intervention may also be employed.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">A fatal outcome associated with a thromboembolic phenomenon shortly after starting multidrug therapy may be a consequence of a severe infection itself, related to SLE, as well as an adverse event caused by newly introduced drugs, especially rifampicin. Rifampicin-induced coagulopathy is a rare complication, but its influence cannot be ruled out in the present report.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> It is noteworthy that the patient had a previous episode of pulmonary thromboembolism but with negative anticardiolipin, IgM and IgG lupus anticoagulant autoantibodies.</p><p id="par0065" class="elsevierStylePara elsevierViewall">This case report aimed to highlight the need to suspect the diagnosis of infections caused by NTM, as opportunistic infections are on the rise in our country. It is also important to warn about the difficulty related to the culture of these microorganisms and the high morbidity and mortality of this disease.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0070" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors’ contributions</span><p id="par0075" class="elsevierStylePara elsevierViewall">Bárbara Elias do Carmo Barbosa: Drafting and editing of the manuscript; effective participation in propaedeutics; literature review; critical review of the manuscript; approval of the manuscript.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Priscila Neri Lacerda: Drafting and editing of the manuscript; effective participation in propaedeutics; literature review; critical review of the manuscript; approval of the manuscript.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Luana Moraes Campos: Drafting and editing of the manuscript; effective participation in propaedeutics; literature review; critical review of the manuscript; approval of the manuscript.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Mariângela Esther Alencar Marques: Drafting and editing of the manuscript; effective participation in research orientation; effective participation in propaedeutics; literature review; critical review of the manuscript; approval of the manuscript.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Silvio Alencar Marques: Drafting and editing of the manuscript; effective participation in research orientation; effective participation in propaedeutics; literature review; critical review of the manuscript; approval of the manuscript.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Luciana Patrícia Fernandes Abbade: Drafting and editing of the manuscript; effective participation in research orientation; effective participation in propaedeutics; literature review; critical review of the manuscript; approval of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:2 [ "identificador" => "xack698988" "titulo" => "Acknowledgment" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-10-14" "fechaAceptado" => "2022-12-15" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil.</p>" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1109 "Ancho" => 1675 "Tamanyo" => 176847 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0125" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Erythematous-violaceous ulcerated macules and nodules, some covered by hematic crusts, located on the medial surface of the right thigh</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" => 1109 "Ancho" => 1675 "Tamanyo" => 265409 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0130" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Detail of the erythematous-violaceous ulcerated nodules, with hematic necrotic crusts</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" => 2345 "Ancho" => 1675 "Tamanyo" => 828649 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0135" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Histopathological analysis. (A) Neutrophilic granulomatous inflammatory process, with superficial and deep involvement of the dermis (Hematoxylin & eosin, ×200). (B) Epithelioid granulomatous inflammatory process surrounding a cystic necrotic cavity containing neutrophils and cell debris (Hematoxylin & eosin, ×400)</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" => 1059 "Ancho" => 1675 "Tamanyo" => 410412 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0140" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Histopathological analysis: detail showing the presence of acid-fast bacilli (AFB) forming extracellular aggregates (Ziehl Neelsen, ×400)</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lupus erythematosus: Significance of dermatologic findings" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. 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De Lord" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "BMJ Case Rep" "fecha" => "2019" "volumen" => "12" "paginaInicial" => "e231930" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Deranged haemostasis: rifampin-induced coagulopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Tiperneni" 1 => "F. Khalid" 2 => "H. Fichadiya" 3 => "A. Al-Alwan" 4 => "G. Mohan" 5 => "F. Heis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.12890/2022_003380" "Revista" => array:5 [ "tituloSerie" => "Eur J Case Rep Intern Med" "fecha" => "2022" "volumen" => "9" "paginaInicial" => "003380" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35774731" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack698988" "titulo" => "Acknowledgment" "texto" => "<p id="par0110" class="elsevierStylePara elsevierViewall">The authors would like to thank photographer Eliete Correia Soares for the photographs of the patient and researcher Ida Maria Foschiani Dias Baptista from the Microbiology laboratory of Instituto Lauro de Souza Lima.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/03650596/0000009800000006/v2_202310301240/S0365059623001587/v2_202310301240/en/main.assets" "Apartado" => array:4 [ "identificador" => "95150" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letter - Tropical/Infectious and parasitic dermatology" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03650596/0000009800000006/v2_202310301240/S0365059623001587/v2_202310301240/en/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059623001587?idApp=UINPBA00008Z" ]
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