Letter to the Editor
Autoimmune pitfalls in treatment with TNFα inhibitors
Los escollos autoinmunes en el tratamiento de pacientes con anti-TNFα
Rita Fonseca
, Eva Mariz, Miguel Bernardes, Lúcia Costa
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Rheumatology Departmente, São João Hospital, Oporto, Portugal
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From case-reports published in the literature and some data available from registries, it seems more common in rheumatoid arthritis patients under infliximab<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a>. However, as new drugs are becoming available, new cases have been reported.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In our cohort, from 401 rheumatic patients (with rheumatoid arthritis, spondylarthritis and psoriatic arthritis) exposed to anti-TNFα agents, only three of them developed drug induced lupus after a mean time of exposure of 4.11<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.71 months.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The first case is a 52-year-old male patient suffering from ankylosing spondylitis for 7 years and treated with infliximab (450<span class="elsevierStyleHsp" style=""></span>mg, 8/8 weeks). After 20 months of treatment, he started complaining of asthenia, fever, dyspnoea and arthralgia. The chest X-ray showed bilateral pleural effusion. Laboratory investigation revealed normal blood cell count, raised erythrocyte sedimentation rate (ESR) (87<span class="elsevierStyleHsp" style=""></span>mm, normal <20<span class="elsevierStyleHsp" style=""></span>mm/h) and c-reactive protein (CRP) (76.6<span class="elsevierStyleHsp" style=""></span>mg/L, normal <0.3<span class="elsevierStyleHsp" style=""></span>mg/L). Additionally he had positive ANA (1/640, homogeneous pattern), positive anti-DsDNA (263<span class="elsevierStyleHsp" style=""></span>UI/mL, normal <200), complement consumption (C3 76<span class="elsevierStyleHsp" style=""></span>mg/dL, normal >83 and C4 11<span class="elsevierStyleHsp" style=""></span>mg/dL, normal >12). Anti-histone antibodies, anti-cardiolipin antibodies and other anti-extractable nuclear antigens were negative. The diagnosis of infliximab-induced lupus was stablished and infliximab was discontinued. Prednisolone 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day, was started; after four weeks all symptoms had resolved, and after two months, autoantibodies were negative and complement levels returned to normal. Three months later, he started etanercept (50<span class="elsevierStyleHsp" style=""></span>mg/week) without any adverse events.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The second case is a 60-year-old male patient, with an 8-year history of rheumatoid arthritis (RA), under adalimumab (40<span class="elsevierStyleHsp" style=""></span>mg every other week) in association with oral methotrexate (20<span class="elsevierStyleHsp" style=""></span>mg/week). Baseline laboratory investigations showed positive ANA (1/100, homogeneous pattern), in the absence of other clinical or laboratory manifestations suggestive of lupus, and negative anti-DsDNA. After 3 months of treatment, he presented arthralgia, asthenia, anorexia, malar rash and hand cutaneous vasculitis. Laboratory investigation showed normal cell blood count, positive ANA (1/320 homogeneous pattern), positive anti-DsDNA (326.2<span class="elsevierStyleHsp" style=""></span>UI/mL), complement consumption (C3 79<span class="elsevierStyleHsp" style=""></span>mg/dL, and C4 10<span class="elsevierStyleHsp" style=""></span>mg/dL). The other autoantibodies tested, namely anti-histone antibodies, were negative. Within four weeks of adalimumab suspension, rapid reduction of the clinical symptoms and biological parameters was seen and antibodies disappeared after three months.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The third case is a 44 year-old female patient, with an 11-year history of RA treated with adalimumab (40<span class="elsevierStyleHsp" style=""></span>mg every other week) in association with leflunomide (20<span class="elsevierStyleHsp" style=""></span>mg/day). At baseline, clinical manifestations suggestive of lupus were absent and ANA and anti-DsDNA were negative. After four years of treatment, she developed photosensitivity, malar rash, disseminated sub-cutaneous lupus rash, asthenia, low grade fever and arthralgia. Laboratory investigation revealed leukopenia (3560/mm<span class="elsevierStyleSup">3</span>), ESR 60<span class="elsevierStyleHsp" style=""></span>mm/h, CRP 55.6<span class="elsevierStyleHsp" style=""></span>mg/L, positive ANA (1/320, homogeneous pattern), positive anti-dsDNA (233<span class="elsevierStyleHsp" style=""></span>UI/mL) and positive anti-histone antibody. Complement levels were within normal range and the other antibodies tested were negative. Adalimumab was suspended and after 6 weeks all symptoms disappeared and autoantibodies turned negative. She started golimumab (50<span class="elsevierStyleHsp" style=""></span>mg/month) without recurrence.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Herein, we reported three rare cases of anti-TNF-induced lupus, two of them induced by adalimumab, which have been very rarely described in literature<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a>.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The three cases described mirror the clinical heterogeneity that these patients can present. Since the raise of autoantibodies during the treatment can occur, and, anti-histone antibodies can be negative, the most important features to identify such patients are the clinical symptoms. It is advisable to stop the drug and, despite some controversy, the switch to other anti-TNF can be done without reccurence.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "What is the utility of routine ANA testing in predicting development of biological DMARD-induced lupus and vasculitis in patients with rheumatoid arthritis? Data from a single-centre cohort" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Takase" 1 => "S.C. Horton" 2 => "A. Ganesha" 3 => "S. Das" 4 => "A. McHugh" 5 => "P. 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Massone" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0961203313517153" "Revista" => array:6 [ "tituloSerie" => "Lupus" "fecha" => "2014" "volumen" => "23" "paginaInicial" => "201" "paginaFinal" => "203" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24356614" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A case of infliximab-induced lupus in a patient with ankylosing spondylitis: is it safe switch to another anti-TNF-α agent?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T. Santiago" 1 => "M.G. Santiago" 2 => "J. Rovisco" 3 => "C. Duarte" 4 => "A. Malcata" 5 => "J.A.P. da Silva" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-013-2361-9" "Revista" => array:7 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2013" "volumen" => "32" "paginaInicial" => "1819" "paginaFinal" => "1822" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23955767" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0003999314001415" "estado" => "S300" "issn" => "00039993" ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/1699258X/0000001300000003/v1_201704290027/S1699258X16300985/v1_201704290027/en/main.assets" "Apartado" => array:4 [ "identificador" => "17506" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas al editor" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/1699258X/0000001300000003/v1_201704290027/S1699258X16300985/v1_201704290027/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X16300985?idApp=UINPBA00004M" ]
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| 2023 Febrero | 31 | 35 | 66 |
| 2023 Enero | 48 | 18 | 66 |
| 2022 Diciembre | 44 | 38 | 82 |
| 2022 Noviembre | 38 | 31 | 69 |
| 2022 Octubre | 44 | 35 | 79 |
| 2022 Septiembre | 30 | 31 | 61 |
| 2022 Agosto | 32 | 46 | 78 |
| 2022 Julio | 37 | 38 | 75 |
| 2022 Junio | 35 | 39 | 74 |
| 2022 Mayo | 43 | 59 | 102 |
| 2022 Abril | 41 | 50 | 91 |
| 2022 Marzo | 43 | 38 | 81 |
| 2022 Febrero | 45 | 43 | 88 |
| 2022 Enero | 52 | 36 | 88 |
| 2021 Diciembre | 41 | 43 | 84 |
| 2021 Noviembre | 48 | 51 | 99 |
| 2021 Octubre | 111 | 57 | 168 |
| 2021 Septiembre | 61 | 51 | 112 |
| 2021 Agosto | 68 | 63 | 131 |
| 2021 Julio | 43 | 44 | 87 |
| 2021 Junio | 51 | 33 | 84 |
| 2021 Mayo | 52 | 50 | 102 |
| 2021 Abril | 136 | 110 | 246 |
| 2021 Marzo | 72 | 43 | 115 |
| 2021 Febrero | 49 | 29 | 78 |
| 2021 Enero | 48 | 28 | 76 |
| 2020 Diciembre | 32 | 26 | 58 |
| 2020 Noviembre | 74 | 26 | 100 |
| 2020 Octubre | 31 | 18 | 49 |
| 2020 Septiembre | 58 | 37 | 95 |
| 2020 Agosto | 51 | 25 | 76 |
| 2020 Julio | 70 | 32 | 102 |
| 2020 Junio | 63 | 23 | 86 |
| 2020 Mayo | 59 | 13 | 72 |
| 2020 Abril | 63 | 27 | 90 |
| 2020 Marzo | 90 | 25 | 115 |
| 2020 Febrero | 75 | 25 | 100 |
| 2020 Enero | 92 | 19 | 111 |
| 2019 Diciembre | 90 | 20 | 110 |
| 2019 Noviembre | 50 | 16 | 66 |
| 2019 Octubre | 50 | 15 | 65 |
| 2019 Septiembre | 78 | 27 | 105 |
| 2019 Agosto | 46 | 23 | 69 |
| 2019 Julio | 40 | 16 | 56 |
| 2019 Junio | 45 | 22 | 67 |
| 2019 Mayo | 51 | 44 | 95 |
| 2019 Abril | 24 | 23 | 47 |
| 2019 Marzo | 28 | 22 | 50 |
| 2019 Febrero | 23 | 16 | 39 |
| 2019 Enero | 29 | 32 | 61 |
| 2018 Diciembre | 76 | 64 | 140 |
| 2018 Noviembre | 96 | 15 | 111 |
| 2018 Octubre | 82 | 13 | 95 |
| 2018 Septiembre | 33 | 10 | 43 |
| 2018 Agosto | 24 | 11 | 35 |
| 2018 Julio | 18 | 7 | 25 |
| 2018 Mayo | 4 | 0 | 4 |
| 2018 Abril | 48 | 9 | 57 |
| 2018 Marzo | 63 | 7 | 70 |
| 2018 Febrero | 53 | 8 | 61 |
| 2018 Enero | 35 | 7 | 42 |
| 2017 Diciembre | 42 | 10 | 52 |
| 2017 Noviembre | 36 | 12 | 48 |
| 2017 Octubre | 26 | 8 | 34 |
| 2017 Septiembre | 24 | 13 | 37 |
| 2017 Agosto | 23 | 13 | 36 |
| 2017 Julio | 32 | 12 | 44 |
| 2017 Junio | 210 | 64 | 274 |
| 2017 Mayo | 232 | 67 | 299 |
| 2017 Abril | 21 | 24 | 45 |
| 2017 Marzo | 0 | 11 | 11 |
| 2017 Febrero | 0 | 7 | 7 |
| 2017 Enero | 0 | 9 | 9 |
| 2016 Diciembre | 0 | 26 | 26 |
| 2016 Noviembre | 0 | 26 | 26 |
| 2016 Octubre | 0 | 38 | 38 |
| 2016 Septiembre | 10 | 16 | 26 |
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