Letter to the Editor
Alemtuzumab and autoimmune polyglandular syndrome with type 1 diabetes mellitus
Alemtuzumab y síndrome poliglandular autoinmune con diabetes mellitus tipo 1
a Servicio de Neurología, Complexo Hospitalario Universitario de Ourense, Ourense, Spain
b Grupo de Investigación Neurociencias Clínicas, Instituto de Investigaciones Sanitarias Galicia-Sur, SERGAS-UVIGO, Vigo, Pontevedra, Spain
c Servicio de Endocrinología y Nutrición, Complexo Hospitalario Universitario de Ourense, Ourense, Spain
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"apellidos" => "García Estévez" "email" => array:1 [ 0 => "daniel.apolinar.garcia.estevez@sergas.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "I." "apellidos" => "Pinal Osorio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Pato Pato" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Neurología, Complexo Hospitalario Universitario de Ourense, Ourense, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Grupo de Investigación Neurociencias Clínicas, Instituto de Investigaciones Sanitarias Galicia-Sur, SERGAS-UVIGO, Vigo, Pontevedra, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Complexo Hospitalario Universitario de Ourense, Ourense, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Alemtuzumab y síndrome poliglandular autoinmune con diabetes mellitus tipo 1" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Alemtuzumab is an anti-CD20 monoclonal antibody used to treat multiple sclerosis (MS) with high clinical and/or radiological activity.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This immune reconstitution therapy is known to be associated with adverse autoimmune effects, with autoimmune thyroid diseases (AITD) such as Hashimoto thyroiditis and Graves-Basedow disease being the most frequent.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Other autoimmune alterations associated with treatment with alemtuzumab for MS, although less prevalent, are glomerulonephritis, immune thrombocytopenic purpura, and vitiligo. In recent years, such other autoimmune diseases as Lambert-Eaton syndrome<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and type 1 diabetes mellitus (DM1) have also been reported in association with alemtuzumab treatment.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a patient with MS who, while receiving treatment with alemtuzumab, developed autoimmune diabetes, with autoimmunity defined by positive results in tests for different pancreatic antibodies.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Our patient is a 42-year-old man who was diagnosed with MS in 2007, after presenting neuritis optica. He had no personal or family history of other autoimmune diseases. Due to the high risk of progressive multifocal leukoencephalopathy, treatment with natalizumab was switched for alemtuzumab. At 11 months after receiving the first course of alemtuzumab, he presented hyperthyroidism, with positive test results for antithyroid antibodies (anti–thyroid peroxidase and anti–thyroid stimulating hormone). After the thyroid dysfunction was controlled, he received a second cycle of alemtuzumab, 17 months after the first course. Subsequently, in the light of clinical progression of pyramidal and cognitive symptoms, a third cycle of alemtuzumab was administered at 13 months after the second cycle. Finally, at 25 months after the last cycle, he was diagnosed with DM1, and presence of pancreatic antibodies (ICA, anti-GAD64/65K, anti-IA-2) was detected.</p><p id="par0020" class="elsevierStylePara elsevierViewall">AITD is the most frequent autoimmune complication in patients with MS receiving alemtuzumab,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> whereas autoimmune DM is exceptional.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> In fact, autoimmune DM is not included as an adverse autoimmune effect in alemtuzumab follow-up studies.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Despite the possibility that a new autoimmunity may be generated after immune reconstitution treatment, there is always uncertainty as to whether alemtuzumab is the cause or whether the association is coincidental, with different autoimmune diseases occurring in a patient with a certain genetic predisposition. The presence of DM1 is a frequent adverse immune reaction in patients under oncological treatment with monoclonal antibodies acting as immune checkpoint inhibitors; these patients also show presence of pancreatic antibodies and a genetic predisposition through HLA-DR4.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">An epidemiological study performed in Sardinia, a Mediterranean region with a high risk of developing MS and DM1, revealed that patients with MS present a high risk of developing DM1, with greater risk among patients with MS who had family members also affected by the disease.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Another epidemiological study conducted in the United States reported that DM1 presents a prevalence of 0.92% among patients with MS and that this percentage did not significantly differ from that observed in the general population. It also reported that diabetes usually manifests before diagnosis of MS, with a mean duration of diabetes of 17 years, with family history of the disease in 36% of cases.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Between 3.9% and 24% of patients with DM1 also present AITD, and 24% of adult patients with latent autoimmune DM present thyroid antibodies. However, between 1% and 10% of patients with AITD but not DM1 present pancreatic antibodies.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">From an endocrine viewpoint, our patient presents autoimmune polyglandular syndrome type 3 (APS-3). Specifically, he presents 3 autoimmune diseases that correspond with 2 types of APS-3: type 3, with AITD associated with DM1, and type 3C, in which AITD is associated with MS.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Given the strong association between AITD and autoimmune diabetes, and the fact that risk of DM1 in patients with AITD is proportionate to the number of positive pancreatic antibodies,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> we consider it potentially beneficial to determine these pancreatic antibodies early in patients with MS and AITD treated with alemtuzumab to monitor for the development of diabetes mellitus. Furthermore, our clinical case supports previous reports of DM1 as a new adverse autoimmune reaction to treatment with alemtuzumab.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "⋆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: García Estévez DA, Pinal Osorio I, Pato Pato A. Alemtuzumab y síndrome poliglandular autoinmune con diabetes mellitus tipo 1. Neurología. 2024. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.nrl.2023.07.001">https://doi.org/10.1016/j.nrl.2023.07.001</span></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" => "Alemtuzumab vs. interferon beta-1a in early multiple sclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "The CAMMS223 Trial Investigators" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0802670" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2008" "volumen" => "359" "paginaInicial" => "1786" "paginaFinal" => "1801" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18946064" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 0 | 8 |
| 2024 October | 28 | 4 | 32 |
| 2024 September | 31 | 3 | 34 |
| 2024 August | 38 | 8 | 46 |
| 2024 July | 25 | 9 | 34 |
| 2024 June | 24 | 8 | 32 |
| 2024 May | 23 | 2 | 25 |
| 2024 April | 36 | 5 | 41 |
| 2024 March | 21 | 13 | 34 |
| 2024 February | 5 | 8 | 13 |
