Case and Research Letters
Immunoglobulin A Antiphospholipid Antibodies in Patients With Chilblain-like Lesions During the COVID-19 Pandemic
Presencia de anticuerpos antifosfolípidos IgA en pacientes con lesiones pernióticas asociadas a COVID-19
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Gomez-Biedma" "autores" => array:2 [ 0 => array:4 [ "nombre" => "M.A." "apellidos" => "Cuenca Saez" "email" => array:1 [ 0 => "acuencas58@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "S.L." "apellidos" => "Gomez-Biedma" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital General de Almansa, Albacete, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Análisis Clínicos, Hospital General de Almansa, Albacete, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Presencia de anticuerpos antifosfolípidos IgA en pacientes con lesiones pernióticas asociadas a COVID-19" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 864 "Ancho" => 900 "Tamanyo" => 53185 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Progression to blisters and crusts.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Owing to the information provided in the media about a possible association between skin lesions and SARS-CoV-2, we received many patients with self-limiting purpuric acral lesions during the month of April 2020.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This situation paves the way for several lines of study, in which laboratory analysis can play an essential role and in which differences in the behavior of the virus in the body can be explained in many settings by cutaneous manifestations, both at diagnosis and during follow-up. We consider that, during the initial stage of the infection, the mucous membrane may play a key role with respect to immunoglobulin (Ig) A antibodies.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We retrospectively reviewed the cases of 11 patients with chilblain-like lesions<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> seen at Hospital de Almansa, Albacete, Spain (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Some of the patients had had clinical manifestations associated with SARS-CoV-2 infection up to 2 weeks before the onset of the skin lesions. Patients were aged 2 to 40 years. The lesions comprised acral erythematous purpuric macules and papules<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> accompanied by edema and occasionally progressing to blisters, vesicles, pseudopustules, and crusts (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">We requested the following analyses: complete blood count, liver enzymes, ferritin, antinuclear antibody, lupus anticoagulant, immunoglobulins, and anticardiolipin IgA, IgG, and IgM.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> We also analyzed anti-ß<span class="elsevierStyleInf">2</span>-glycoprotein antibodies and complement C3 and C4 and ran a lateral-flow immunochromatographic assay (COVID-19 IgG/IgM Rapid Test Cassette, Zhenjiang Orient Gene Biotech Co., Ltd).</p><p id="par0025" class="elsevierStylePara elsevierViewall">The Cov2019 polymerase chain reaction (PCR) assay, which is based on nasopharyngeal swab specimens, was performed in 2 cases where the patients had active symptoms and yielded a positive result in 1. The IgM/IgG rapid test, which was performed in all cases, yielded positive results in only 3 patients, 1 of whom had active disease (PCR+), and 2 asymptomatic patients, who had had self-limiting infection for 2 weeks, after which time they presented with chilblains. Laboratory tests revealed reduced complement C3 in 5 patients. All 5 had increased IgA anticardiolipin antibody; while this increase was slightly high, it was not considered positive according to the reference parameters of the external laboratory.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Analysis of the similarities between SARS CoV-2 infection and dermatologic syndromes involving antibodies enables conclusions to be drawn with respect to the following:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0035" class="elsevierStylePara elsevierViewall">The viral etiology of autoimmune diseases,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> as well as genetic and environmental diseases. Infection by SARS-CoV-2 is followed by a first stage of viral infection and a second stage that is similar to acute and transient autoimmune syndrome (in a genetically predisposed patient).</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</span><p id="par0040" class="elsevierStylePara elsevierViewall">Generation of autoantibodies: SARS-CoV-2 takes advantage of the body’s machinery to replicate. Microparticles (i.e., phospholipids such as phosphatidylserine), which are found on the cell membrane, stimulate production of autoantibodies. Exposure in blood vessels can lead to transient antiphospholipid syndrome, as reported in the literature,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and could account for the skin lesions, as in antiphospholipid syndrome and chilblain lupus.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3.</span><p id="par0045" class="elsevierStylePara elsevierViewall">Generation of IgA against the mucous membrane, where the first contact with the virus is made,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,8</span></a> thus explaining why the immune response has no memory (self-limiting conditions) and why only a few patients present memory IgG. It would also account for the severe symptoms that affect the mucous membranes, such as odynophagia, dysphagia, anosmia, and loss of taste, all of which are common in autoimmune diseases.</p></li></ul></p><p id="par0050" class="elsevierStylePara elsevierViewall">It is important to take into account the role of IgA autoantibodies in resolution of infection, especially in patients with mild symptoms, since SARS-CoV-2 affects the respiratory mucous membranes in the early stages of infection. This analysis could pave the way for early diagnostic and therapeutic strategies.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The Ministry of Health document<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> of April 24 on interpretation of diagnostic tests for SARS-CoV-2, distinguishes between 4 stages:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">1.</span><p id="par0060" class="elsevierStylePara elsevierViewall">Presymptomatic stage (PCR+).</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">2.</span><p id="par0065" class="elsevierStylePara elsevierViewall">Initial stage (1-7 days). PCR+, with potentially positive IgA/IgM levels. Both symptomatic and asymptomatic individuals can transmit the infection.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">3.</span><p id="par0070" class="elsevierStylePara elsevierViewall">Second stage (8-14 days). IgA returns to negative values, and PCR may yield a negative result. IgM is positive and IgG may be positive. During this stage, the infection has usually resolved in asymptomatic individuals and in those with mild symptoms, and the risk of infection is minimal.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">4.</span><p id="par0075" class="elsevierStylePara elsevierViewall">Third stage (> 15 days). The PCR result may be positive and there may be an increase in IgG and IgM antibody levels. The infection has resolved in asymptomatic individuals and in those with mild symptoms. The infection is not considered to have resolved in severely ill patients until after 50 days.</p></li></ul></p><p id="par0080" class="elsevierStylePara elsevierViewall">In the patients reviewed here, anticardiolipin antibody tests were performed 4 to 8 weeks after onset of skin conditions owing to the difficulty associated with the pandemic.</p><p id="par0085" class="elsevierStylePara elsevierViewall">In conclusion, the presence of antiphospholipid antibodies, whether in the context of systemic lupus erythematosus or primary antiphospholipid syndrome, has been associated with the development of chilblains. In this case, it would involve antiphospholipid syndrome secondary to acute and transient infection by coronavirus or another virus. This surprising clinical picture is atypical because it has a clear association with infection during the previous days,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and not with extreme cold temperatures. In addition, although it has a temporal association with the pandemic, clear evidence of SARS-Cov-2 infection was only detected in 3 cases. The transient increases in immunoglobulins highlight the need for laboratory tests in the initial stage (i.e., the most infective stage). Furthermore, microparticles (phospholipids, glycoproteins) generate antibodies/autoantibodies, which disappear rapidly if they are IgA.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0090" class="elsevierStylePara elsevierViewall">No grants were received from the public, commercial, or nonprofit sectors.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of Interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of Interest" ] 2 => array:2 [ "identificador" => "xack516475" "titulo" => "Acknowledgments" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Cuenca Saez MA, Gomez-Biedma SL. Presencia de anticuerpos antifosfolípidos IgA en pacientes con lesiones pernióticas asociadas a COVID-19. Actas Dermosifiliogr. 2021;112:290–292.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1093 "Ancho" => 900 "Tamanyo" => 77867 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Typical image of chilblains that was common to all patients.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 864 "Ancho" => 900 "Tamanyo" => 53185 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Progression to blisters and crusts.</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" => "Cutaneous manifestations in COVID-19: a first perspective" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. 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I am also grateful to the patients and, more than ever, to health professionals for their unceasing willingness to fight the current pandemic.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000011200000003/v1_202103020923/S1578219021000093/v1_202103020923/en/main.assets" "Apartado" => array:4 [ "identificador" => "6157" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case and Research Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000011200000003/v1_202103020923/S1578219021000093/v1_202103020923/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219021000093?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 10 | 18 |
| 2024 October | 71 | 94 | 165 |
| 2024 September | 131 | 31 | 162 |
| 2024 August | 202 | 48 | 250 |
| 2024 July | 196 | 44 | 240 |
| 2024 June | 126 | 52 | 178 |
| 2024 May | 100 | 44 | 144 |
| 2024 April | 106 | 29 | 135 |
| 2024 March | 90 | 34 | 124 |
| 2024 February | 122 | 43 | 165 |
| 2024 January | 82 | 30 | 112 |
| 2023 December | 85 | 20 | 105 |
| 2023 November | 102 | 33 | 135 |
| 2023 October | 85 | 25 | 110 |
| 2023 September | 77 | 28 | 105 |
| 2023 August | 51 | 22 | 73 |
| 2023 July | 90 | 29 | 119 |
| 2023 June | 101 | 23 | 124 |
| 2023 May | 172 | 19 | 191 |
| 2023 April | 177 | 19 | 196 |
| 2023 March | 258 | 28 | 286 |
| 2023 February | 233 | 23 | 256 |
| 2023 January | 250 | 40 | 290 |
| 2022 December | 207 | 39 | 246 |
| 2022 November | 78 | 29 | 107 |
| 2022 October | 64 | 28 | 92 |
| 2022 September | 73 | 32 | 105 |
| 2022 August | 99 | 45 | 144 |
| 2022 July | 67 | 43 | 110 |
| 2022 June | 45 | 45 | 90 |
| 2022 May | 134 | 44 | 178 |
| 2022 April | 238 | 36 | 274 |
| 2022 March | 398 | 58 | 456 |
| 2022 February | 732 | 44 | 776 |
| 2022 January | 785 | 50 | 835 |
| 2021 December | 395 | 40 | 435 |
| 2021 November | 225 | 63 | 288 |
| 2021 October | 139 | 61 | 200 |
| 2021 September | 96 | 61 | 157 |
| 2021 August | 137 | 41 | 178 |
| 2021 July | 173 | 31 | 204 |
| 2021 June | 141 | 41 | 182 |
| 2021 May | 206 | 64 | 270 |
| 2021 April | 758 | 216 | 974 |
| 2021 March | 506 | 96 | 602 |
| 2021 February | 382 | 68 | 450 |
| 2021 January | 104 | 21 | 125 |
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