Case report
CLIPPERS Syndrome After Vaccination. An Unusual ASIA Presentation
Síndrome de CLIPPERS posterior a vacunación. Una presentación inusual de ASIA
a Department of Neurology, Hospital de Especialidades «Dr. Antonio Fraga Mouret»,Centro Médico Nacional La Raza del Instituto Mexicano del Seguro Social, Mexico City, Mexico
b Department of Internal medicine, Hospital de Especialidades «Dr. Antonio Fraga Mouret», Centro Médico Nacional La Raza del Instituto Mexicano del Seguro Social, Mexico City, Mexico
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An Unusual ASIA Presentation" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "168" "paginaFinal" => "170" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Juan Saénz-Silva, Alberto Ordinola Navarro" "autores" => array:2 [ 0 => array:3 [ "nombre" => "Juan" "apellidos" => "Saénz-Silva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Alberto" "apellidos" => "Ordinola Navarro" "email" => array:1 [ 0 => "albertoordinolamd@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Neurology, Hospital de Especialidades «Dr. Antonio Fraga Mouret»,Centro Médico Nacional La Raza del Instituto Mexicano del Seguro Social, Mexico City, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Internal medicine, Hospital de Especialidades «Dr. Antonio Fraga Mouret», Centro Médico Nacional La Raza del Instituto Mexicano del Seguro Social, Mexico City, Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de CLIPPERS posterior a vacunación. Una presentación inusual de ASIA" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 946 "Ancho" => 1000 "Tamanyo" => 116422 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">(A, B) MRI of the brain T2 Flair at presentation with hyperintense lesions (arrows). (C) MRI of the brain T1 post-gadolinium at presentation, showing foci of pontine “peppering” enhancement lesion highly suggestive of a perivascular distribution. (D) MRI of the brain T1 post-gadolinium at one-month follow-up showing full recovery after corticosteroids treatment.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) were first described a decade ago<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a>; until date, there are a limited number of reports and these diseases are underdiagnosed.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Clippers is characterized by the perivascular infiltration of T-cell lymphocytes in the pontine centric area and the pons but can involve other brain parts.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> The pathogenesis is still poorly understood; however, it has been described after a potential immune triggering event.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Being neurological manifestations part of the spectrum of ASIA highlights the importance of knowing this disease. We described a CLIPPERS Syndrome after the influenza vaccination.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical observation</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 35-year-old previously healthy man started with ataxia in gait six days following influenza vaccination, with increased symptomatology and binocular diplopia in the next five weeks.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The neurological examination revealed the following remarkable findings: cranial nerves with slight limitation in the abduction of the left eye, with multidirectional nystagmus, motor system, with normal force, hyperreflexia of the four extremities, cerebellum with severe dysmetria in the four extremities, he presented broad-based gait and postural instability. A magnetic resonance imaging (MRI) was performed, which showed hyperintense lesions in the pontine region cerebellar peduncles and cerebellum (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A, B), with “peppering” enhancement after contrast administration (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Biochemical data: ANAs, anti-DNA, rheumatoid factor, HIV, VDRL, oligoclonal bands and AQP4 were negative. The CSF study showed no alterations; cultures and PCR for tuberculosis were negative. Infectious diseases, malignancy and additional systemic involvement, were ruled out; therefore, on suspicion of CLIPPERS syndrome, the patient received methylprednisolone 5<span class="elsevierStyleHsp" style=""></span>g (1<span class="elsevierStyleHsp" style=""></span>g daily) with total clinical improvement. He was discharged with azathioprine 2.5<span class="elsevierStyleHsp" style=""></span>mg/kg/day and prednisone 1.0<span class="elsevierStyleHsp" style=""></span>mg/kg/day with a tapering strategy, decreasing dose of 10<span class="elsevierStyleHsp" style=""></span>mg every two weeks, until 30<span class="elsevierStyleHsp" style=""></span>mg, and then 5<span class="elsevierStyleHsp" style=""></span>mg every two weeks until discontinued. At 1-month follow-up, the MRI lesions showed total resolution (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>D).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">We presented a patient with clinical manifestations of cerebellum affection and enhancement in the MRI, with the influenza vaccine as the only triggering factor.</p><p id="par0035" class="elsevierStylePara elsevierViewall">CLIPPERS syndrome may be underdiagnosed due to the lack of knowledge of the disease. The manifestations of the reported cases are heterogeneous, but in general, the typical presentation is the brainstem and cerebellum subacute symptoms.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3,4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The CLIPPERS syndrome has been characterized by hallmark lesions in MRI, punctate and curvilinear “peppering” lesions. Although this imaging pattern is very suggestive of this syndrome, it is mandatory to rule out differential diseases, such as infectious, malignancies or rheumatology conditions, since these can mimic the lesions.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Remarkably, several reports mention CLIPPERS as a pre-lymphoma state or as an initial manifestation of a systemic disease; besides the need for research in that field, follow-up of these patients would lead to a prompt diagnosis and timely interventions.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">There are several reports of neurological affection after influenza vaccination with a time range of 2–60 days, which have been reported as an ASIA. Since the Influenza vaccine has several adjuvants, this may trigger an immune reaction in some predisposed subjects.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">This situation draws attention in the COVID-19 vaccination era, where there are reports of ASIA and immune-mediated diseases after different COVID-19 vaccines, highlighting neurological disorders.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The patient met two ASIA diagnostic major criteria<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a>; he was previously healthy, was exposed to an adjuvant and developed manifestations of neurology disease, besides that the perivascular inflammatory cell infiltrates and response to corticosteroids strongly suggest autoimmune disease.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,6,9</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Of interest, Tobin et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> reviewed the characteristics of 35 patients in Mayo Clinic with suspected CLIPPERS, of the 22/23 confirmed patients presented a complete response to corticosteroid treatment, and at follow-up, most of them continued on immunomodulatory therapy, of note, our patient, has continued with azathioprine, maintenance dose 1.5<span class="elsevierStyleHsp" style=""></span>mg/kg/day for 18 months without relapses. The treatment time is still unclear, but reviews show a trend of maintaining immunomodulatory therapy for at least 12 months.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0065" class="elsevierStylePara elsevierViewall">These days, where there is a COVID-19 vaccination program worldwide, and autoimmune reactions have been reported with different vaccines,<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a> the knowledge of CLIPPERS syndrome as an unusual ASIA presentation and high response to the corticosteroids may lead to a timely diagnosis, appropriate treatment, and follow up with better outcomes for patients.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Informed consent</span><p id="par0070" class="elsevierStylePara elsevierViewall">Informed consent was obtained from the patient.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Funding</span><p id="par0075" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflict of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">None reported.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1858674" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1615924" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1858675" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1615925" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical observation" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Informed consent" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 11 => array:2 [ "identificador" => "xack655100" "titulo" => "Acknowledgments" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-08-05" "fechaAceptado" => "2021-10-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1615924" "palabras" => array:5 [ 0 => "CLIPPERS" 1 => "ASIA" 2 => "Neurology manifestations" 3 => "Vaccine-related event" 4 => "Influenza" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1615925" "palabras" => array:5 [ 0 => "CLIPPERS" 1 => "ASIA" 2 => "Manifestaciones neurológicas" 3 => "Eventos relacionados a vacunación" 4 => "Influenza" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) were described a decade ago. There are a limited number of reports and these diseases are still underdiagnosed.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We presented a 35 years-old patient with clinical manifestations of cerebellum affection and enhancement in the MRI, with the influenza vaccine as the only triggering factor.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Infectious diseases, malignancy, and additional systemic involvement were ruled out; therefore, on suspicion of CLIPPERS syndrome, the patient received corticosteroid therapy with an adequate response.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The knowledge of CLIPPERS syndrome as an unusual ASIA presentation and high response to the corticosteroids may lead to a timely diagnosis, appropriate treatment, and follow up with better outcomes for patients.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La inflamación linfocítica crónica con realce perivascular pontino que responde a los esteroides (CLIPPERS) y el síndrome autoinmune/inflamatorio inducido por adyuvantes (ASIA) se describieron hace una década. Hay un número limitado de reportes y estas enfermedades aún están infra diagnosticadas.</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Presentamos un paciente de 35 años con cuadro clínico de afectación del cerebelo y realce en la RM, con la vacuna anti-influenza como único factor desencadenante.</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se descartaron enfermedades infecciosas, malignidad y afectación sistémica, por lo tanto, ante sospecha de síndrome de CLIPPERS, recibió tratamiento con corticoesteroides con una respuesta adecuada.</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El conocimiento del síndrome de CLIPPERS como una presentación inusual de ASIA y su alta respuesta a los corticosteroides puede conducir a un diagnóstico oportuno, un tratamiento adecuado y un seguimiento con mejores resultados para los pacientes.</p></span>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 946 "Ancho" => 1000 "Tamanyo" => 116422 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">(A, B) MRI of the brain T2 Flair at presentation with hyperintense lesions (arrows). (C) MRI of the brain T1 post-gadolinium at presentation, showing foci of pontine “peppering” enhancement lesion highly suggestive of a perivascular distribution. (D) MRI of the brain T1 post-gadolinium at one-month follow-up showing full recovery after corticosteroids treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.J. Pittock" 1 => "J. Debruyne" 2 => "K.N. Krecke" 3 => "C. Giannini" 4 => "J. van den Ameele" 5 => "V. 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Jara" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/thy.2021.0142" "Revista" => array:3 [ "tituloSerie" => "Thyroid" "fecha" => "2021" "paginaInicial" => "10" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0090" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune-mediated disease flares or new-onset disease in 27 subjects following mRNA/DNA SARS-CoV-2 vaccination" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Watad" 1 => "G. De Marco" 2 => "H. Mahajna" 3 => "A. Druyan" 4 => "M. Eltity" 5 => "N. 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Lodice" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/practneurol-2020-002857" "Revista" => array:2 [ "tituloSerie" => "CLIPPERS Pract Neurol" "fecha" => "2020" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0100" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.O. Tobin" 1 => "Y. Guo" 2 => "K.N. Krecke" 3 => "J.E. Parisi" 4 => "C.F. Lucchinetti" 5 => "S.J. Pittock" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/brain/awx200" "Revista" => array:6 [ "tituloSerie" => "Brain" "fecha" => "2017" "volumen" => "140" "paginaInicial" => "2415" "paginaFinal" => "2425" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29050399" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack655100" "titulo" => "Acknowledgments" "texto" => "<p id="par0085" class="elsevierStylePara elsevierViewall">We thank the patient for granting permission to publish this information.</p><p id="par0090" class="elsevierStylePara elsevierViewall">All authors contributed equally and met the ICMJE authorship criteria.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/1699258X/0000001900000003/v1_202303071056/S1699258X21002564/v1_202303071056/en/main.assets" "Apartado" => array:4 [ "identificador" => "93553" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Caso clínico" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/1699258X/0000001900000003/v1_202303071056/S1699258X21002564/v1_202303071056/en/main.pdf?idApp=UINPBA00004M&text.app=https://www.reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X21002564?idApp=UINPBA00004M" ]
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