Scientific letters
Mediterranean spotted fever in a patient with Crohn's disease under adalimumab: First case report and review of the literature
Fiebre botonosa en un paciente con enfermedad de Crohn con tratamiento de adalimumab: Observación clínica y revisión de la literatura
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Nunes, Guilherme Macedo" "autores" => array:3 [ 0 => array:4 [ "nombre" => "João" "apellidos" => "Santos-Antunes" "email" => array:1 [ 0 => "joao.claudio.antunes@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 1 => array:3 [ "nombre" => "Amadeu C.R." "apellidos" => "Nunes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Guilherme" "apellidos" => "Macedo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Gastroenterology Department, Faculty of Medicine, Hospital de São João, Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fiebre botonosa en un paciente con enfermedad de Crohn con tratamiento de adalimumab: Observación clínica y revisión de la literatura" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 517 "Ancho" => 775 "Tamanyo" => 39555 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Eschar of the tick bite on the left shoulder.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 49 years old man with Crohn's disease and ankylosing spondylitis had been treated with adalimumab 40<span class="elsevierStyleHsp" style=""></span>mg every other week, with clinical remission. After 18 months of starting adalimumab and only three days after last subcutaneous injection, a diffuse pruriginous maculopapular rash was elicited in the abdomen, chest and upper and lower limbs (including palms and soles). He simultaneously had headache, malaise, myalgia and high-grade fever (39.5<span class="elsevierStyleHsp" style=""></span>°C). He came on to our Emergency Department five days after the first symptoms. Upon admission, he was febrile (39.2<span class="elsevierStyleHsp" style=""></span>°C), with no other findings on physical evaluation besides the rash and the presence of a small raspberry lesion on the left shoulder. Blood analysis showed elevated C-reactive protein (60.4<span class="elsevierStyleHsp" style=""></span>mg/L), without leucopenia or thrombocytopenia. Abdominal ultrasound was unremarkable.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Our patient lived in an urban apartment, but he had recently spent two weeks in a rural area, with contact with several farm animals (chickens, dogs and horses), until three days before admission. The lesion on the left shoulder was consistent with a tick bite (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). He was treated with doxycycline (100<span class="elsevierStyleHsp" style=""></span>mg bid) for spotted fever, with an excellent clinical and analytical response. He was discharged on the fifth day without fever and with no rash, and the lesion on the left shoulder was almost completely resolved; blood inflammatory markers returned to normal.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Mediterranean spotted fever (MSF) is a tick-borne disease caused by <span class="elsevierStyleItalic">Rickettsia conorii</span>. Although mortality rates for MSF are low and generally range from 0% to 3%,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> a delay in the diagnosis or inadequate treatment can increase the rates of morbidity and mortality. Serology for <span class="elsevierStyleItalic">Rickettsia</span> is frequently negative at presentation,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> but in our case IgM for this agent was positive. Additionally, given the epidemiological context and the anamnesis (namely the classic triad of rash involving palms and soles, eschar and fever) the diagnosis of MSF, an infection endemic in European southern countries like Portugal, must be assumed promptly, especially in the summer when tick bites are much more common. It is important to notice that the triad is not always present, and the eschar may not be observed in up to 40% of the cases.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Blood analysis is unspecific; usually inflammatory markers are elevated, and leucopenia or thrombocytopenia may occur in nearly 20% of the patients.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Little is known concerning this type of infections, namely regarding more serious outcomes and treatment implications, in patients with inflammatory bowel disease (IBD), since there are no reported cases. Furthermore, the clinical course and outcome of MSF (and other tick-borne illnesses) in patients under anti-TNF agents is unknown. TNF is a key cytokine in the defense against intracellular pathogens, as <span class="elsevierStyleItalic">Rickettsia conorii</span>,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> so one could anticipate a more serious disease. The only reported case of a rickettsiosis in this context is a Rocky Mountain spotted fever (by <span class="elsevierStyleItalic">Rickettsia ricketsii</span>) in a patient with rheumatoid arthritis under adalimumab (with prior exposure to etanercept), with good outcome.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Crohn's disease and the immunosuppressive treatments that are commonly applied in these patients raise the risk for opportunistic infections and can contribute to a poorer outcome of infectious diseases in general. The authors present a very unusual case of a zoonosis in a context of anti-TNF-alpha therapy for Crohn's disease. This is the first report of a MSF in a patient under adalimumab. In an era in which immunosuppressants and biologics are the mainstay of Crohn's disease therapy, it is expected that this type of drugs will been increasingly applied in patients living in rural areas. Therefore, zoonotic illnesses in patients under anti-TNF therapies may become more frequent, and it is very important to know how to manage them. The clinical challenge is to know whether these patients could have a worse outcome than general population, requiring different therapeutic strategies. It is unknown if adalimumab must be stopped and for how long, since there are no guidelines for this kind of infections in the context of IBD. We think that anti-TNF agents must be temporarily suspended because TNF is important in the defense from these intracellular organisms. In our case, we chose to prescribe standard antibiotic treatment and stop adalimumab until one week after concluding the antibiotic regimen. Promptly recognition and treatment without delays was decisive for this excellent outcome.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 517 "Ancho" => 775 "Tamanyo" => 39555 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Eschar of the tick bite on the left shoulder.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous findings in a case of mediterranean spotless fever due to <span class="elsevierStyleItalic">Rickettsia conorii</span>, with gangrene of multiple toes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Fernandez-Flores" 1 => "E. De Cabo-Lopez" 2 => "F.J. Diaz-Galvez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/DAD.0b013e31828cafbe" "Revista" => array:6 [ "tituloSerie" => "Am J Dermatopathol" "fecha" => "2014" "volumen" => "36" "paginaInicial" => "e22" "paginaFinal" => "e25" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23719481" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mediterranean spotted fever: clinical and laboratory characteristics of 415 Sicilian children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Colomba" 1 => "L. Saporito" 2 => "V.F. Polara" 3 => "R. Rubino" 4 => "L. Titone" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2334-6-60" "Revista" => array:5 [ "tituloSerie" => "BMC Infect Dis" "fecha" => "2006" "volumen" => "6" "paginaInicial" => "60" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16553943" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mediterranean spotted fever" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Rovery" 1 => "D. Raoult" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.idc.2008.03.003" "Revista" => array:6 [ "tituloSerie" => "Infect Dis Clin North Am" "fecha" => "2008" "volumen" => "22" "paginaInicial" => "515" "paginaFinal" => "530" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18755388" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Release of soluble tumor necrosis factor receptors in Mediterranean spotted fever rickettsiosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "W.V. Kern" 1 => "J. Oristrell" 2 => "F. Segura-Porta" 3 => "P. Kern" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Diagn Lab Immunol" "fecha" => "1996" "volumen" => "3" "paginaInicial" => "233" "paginaFinal" => "235" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8991643" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rocky Mountain Spotted Fever in a patient treated with anti-TNF-alpha inhibitors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.M. Mays" 1 => "R.A. Gordon" 2 => "K.C. Durham" 3 => "W.J. LaPolla" 4 => "S.K. Tyring" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Dermatol Online J" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24021367" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02105705/0000003800000006/v1_201506151329/S0210570514001812/v1_201506151329/en/main.assets" "Apartado" => array:4 [ "identificador" => "9030" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas científicas" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/02105705/0000003800000006/v1_201506151329/S0210570514001812/v1_201506151329/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570514001812?idApp=UINPBA00004N" ]
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