Relapses in patient with microscopic polyangiitis with persistently positive antimyeloperoxidase for 4 years using maintenance immunosuppressants
Recaídas en paciente con poliangeitis microscópica con anti-mpo persistentemente positivo durante 4 años y con inmunosupresores de mantenimiento
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"apellidos" => "Molina" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital General de Segovia, Spain, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital General de Segovia, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Servicio de Análisis Clínicos, Hospital General de Segovia, Spain, " "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] 3 => array:3 [ "entidad" => "Servicio de Análisis Clínicos, Hospital General de Segovia, " "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "affd" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recaídas en paciente con poliangeitis microscópica con anti-mpo persistentemente positivo durante 4 años y con inmunosupresores de mantenimiento" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10818_108_17660_en_t110818.jpg" "Alto" => 213 "Ancho" => 600 "Tamanyo" => 143191 ] ] "descripcion" => array:1 [ "en" => "Evolution of ANCA titre, kidney function parameters, immunosuppressive treatment and relapses" ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor, </span></p><p class="elsevierStylePara">Anti-neutrophil cytoplasmic antibodies (ANCA) are antibodies directed against neutrophil granulocytes and monocytes.<span class="elsevierStyleSup">1</span> These ANCA are essential markers and help to classify small-vessel vasculitides, such as Wegener’s granulomatosis (WG), microscopic polyangiitis (MP) and renal-limited vasculitides, which are classified as ANCA-associated systemic vasculitides.<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">The diagnosis can be confirmed when ANCA are detected. This means that treatment with steroids and immunosuppressants can be started without delay.<span class="elsevierStyleSup">3</span> In contrast to anti-glomerular basement membrane antibody (anti-GBM) disease, these vasculitides are chronic diseases with a high relapse rate which leads to increased morbidity/mortality.<span class="elsevierStyleSup">4</span> Thus, a diagnosis of relapse in a patient with ANCA-associated small-vessel vasculitis with persistently negative ANCA titre at the moment of a possible relapse should be questioned, requiring either histological proof of disease activity or exclusion of other diagnoses.<span class="elsevierStyleSup">5</span> On the other hand, whether persistently positive levels of ANCA or an increase in their levels can predict vasculitis disease activity is more controversial.<span class="elsevierStyleSup">4,5</span></p><p class="elsevierStylePara">We describe here the case of a patient diagnosed with MP with positive ANCA at the time of diagnosis. The patient did not have any relapses for 7 years while the ANCA were negative and then had 2 relapses in the following 4 years with persistently positive ANCA and while under immunosuppressive maintenance therapy.</p><p class="elsevierStylePara">The patient was a 74-year-old male diagnosed with ANCA-positive MP (anti-myeloperoxidase [anti-MPO] antibodies at a titre of 320U/ml, negative anti-PR3 antibodies) in September 1999. He was treated with oral prednisone at 1mg/kg and monthly pulses of 750mg of cyclophosphamide for 6 months. He also had a medical history of tuberculosis in his youth; spondyloarthrosis and osteoporosis; collapse at D10 vertebra as a complication of steroid treatment; chronic hepatitis with positive HBs-Ag, and positive anti-HBe coinciding with the diagnosis of vasculitis. The patient had been asymptomatic for 7 years with stable kidney function (oscillations of serum creatinine with a range of 1.3-1.8mg/dl), persistently negative ANCA and without immunosuppressive maintenance therapy. From the seventh year following diagnosis of MP, we started to detect positive ANCA (positive anti-MPO). The follow-up of the evolution of the ANCA, kidney function parameters and the immunosuppressive treatment established is shown in Table 1.</p><p class="elsevierStylePara">A year and an half after detecting the positive ANCA, the patient was admitted for a respiratory infection without pulmonary consolidation which was treated with levofloxacin. During this hospitalisation, plasma creatinine was 1.4mg/dl, proteinuria 0.28g/24h, C-reactive protein 13mg/dl and an ANCA titre that oscillated between 410 and 429U/ml was found.</p><p class="elsevierStylePara">The first relapse of the disease was found two years and 3 months after the ANCA had become positive and while the patient was undergoing immunosuppressive treatment with oral cyclophosphamide at 50mg/day. The patient had anti-MPO at a titre of 367U/ml and the relapse appeared as acute non-oliguric renal failure (creatinine peak at a maximum of 6.6mg/dl), microscopic haematuria and pulmonary haemorrhage in the right lung (Figure 1) that responded to treatment with 500mg pulses of 6-methylprednisone i.v. (three doses) followed by oral prednisone at 1mg/kg/day and 500g pulses of cyclophosphamide. Two months after this first relapse, the patient was admitted to hospital for another respiratory infection without pulmonary consolidation that responded well to levofloxacin.</p><p class="elsevierStylePara">The second relapse of the disease was detected four years after the reappearance of the ANCA. This was also seen in the deterioration of kidney function (serum creatinine peak at 4.1mg/dl) and microscopic haematuria and with anti-MPO titres of 126U/ml. The patient responded well to treatment with 500mg pulses of 6-methylprednisolone followed by a descending dosage of oral prednisone starting at 1mg/kg/day and treatment with mycophenolate mofetil at a dose of 500mg/day. The patient was asymptomatic three months after this second relapse with a serum creatinine level of 2.7mg/dl, persistent microhaematuria (20-25 red blood cells/field), a C-reactive protein of 0.7mg/dl and an anti-MPO titre of 13U/ml.</p><p class="elsevierStylePara">Relapses are the main problem of vasculitides given that they cause mortality and morbidity to increase: chronic organ damage (renal failure) and increased cumulative immunosuppressive therapy toxicity.<span class="elsevierStyleSup">4,6</span> Although the value of ANCA is well established in the diagnosis of these diseases, the usefulness of measuring ANCA titres in assessing disease activity is more controversial.<span class="elsevierStyleSup">7</span> Increased anti-PR3 is associated with a relapse in patients with WG, whereas, persistently high anti-MPO in MP is more contentious. Lurati and Spertini analysed the predictive value of ANCA as a relapse marker in a retrospective study that included 36 patients (23 with WG and 13 with MP). They studied the prognostic potential of an acute increase in the ANCA titre compared to a persistently positive level of ANCA: persistently high ANCA (over 6 months) were not found to be significantly associated with disease relapse in their study, and the predictive value of an acute increase in the ANCA titre was related to the size of the increase.<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">In our case, the patient had two relapses over a period of 4 years, during which the anti-MPO titres remained persistently high and, furthermore, the patient was undergoing immunosuppressive maintenance therapy. Also, the relapses occurred regardless of the level of anti-MPO detected: although the first relapse occurred with anti-MPO levels above 350U/ml, the anti-MPO levels had been above 400U/ml a few months before at the time of a respiratory infection, and at this point no relapse had been noted. In the second relapse, the anti-MPO level had been similar to the previous month’s levels (<150U/ml). Ayada et al also described a similar case to ours with anti-MPO titres that had been persistently positive for 6 years. The anti-MPO levels were not valuable for predicting relapse early.<span class="elsevierStyleSup">9</span></p><p class="elsevierStylePara">While monitoring ANCA in patients with vasculitis may be helpful for the clinician and may be useful to make a decision on whether to start immunosuppressive treatment, the final decision must be based on clinical and histological parameters in addition to other analytical parameters.<span class="elsevierStyleSup">9</span> In our case, considering that the patient had only received induction therapy when the disease was diagnosed, and still did not have symptoms to consider disease activity (stable kidney function without proteinuria), preventative immunosuppressive therapy was started when the ANCA reappeared 7 years after the diagnosis and the patient had the first relapse 2 years after starting this treatment.</p><p class="elsevierStylePara">Activation of T-cells, genetic and exogenous causes and infections have been included among the factors associated with relapse. In our case, the patient had been admitted to hospital for a respiratory infection with a maximum peak of anti-MPO within normal levels, although the vasculitis activity was seen seven months later.</p><p class="elsevierStylePara">Furthermore, the reason for preventing relapses is to avoid chronic organ damage. In our case, it can be seen that after the relapse, a progressive worsening of kidney function along with an increased proteinuria was noted.</p><p class="elsevierStylePara">To conclude, persistently positive anti-MPO in patients with MP may not be very useful for predicting relapse, even more so if the patients are undergoing immunosuppressive maintenance therapy, although clinical monitoring must be even stricter in patients with persistently positive anti-MPO titres.</p><p class="elsevierStylePara"><a href="grande/10818_108_17660_en_t110818.jpg" class="elsevierStyleCrossRefs"><img src="10818_108_17660_en_t110818.jpg" alt="Evolution of ANCA titre, kidney function parameters, immunosuppressive treatment and relapses"></img></a></p><p class="elsevierStylePara">Table 1. Evolution of ANCA titre, kidney function parameters, immunosuppressive treatment and relapses</p><p class="elsevierStylePara"><a href="grande/10818_108_17661_en_fa_10818.jpg" class="elsevierStyleCrossRefs"><img src="10818_108_17661_en_fa_10818.jpg" alt="Pulmonary haemorrhage in the right hemithorax (A) before treatment and (B) after receiving immunosuppressive treatment."></img></a></p><p class="elsevierStylePara">Figure 1a. Pulmonary haemorrhage in the right hemithorax (A) before treatment and (B) after receiving immunosuppressive treatment.</p><p class="elsevierStylePara"><a href="grande/10818_108_17662_en_f1b_10818.jpg" class="elsevierStyleCrossRefs"><img src="10818_108_17662_en_f1b_10818.jpg" alt="Pulmonary haemorrhage in the right hemithorax (A) before treatment and (B) after receiving immunosuppressive treatment."></img></a></p><p class="elsevierStylePara">Figure 1b. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 7 | 18 |
| 2024 October | 59 | 39 | 98 |
| 2024 September | 32 | 17 | 49 |
| 2024 August | 74 | 43 | 117 |
| 2024 July | 47 | 27 | 74 |
| 2024 June | 81 | 39 | 120 |
| 2024 May | 111 | 23 | 134 |
| 2024 April | 70 | 32 | 102 |
| 2024 March | 57 | 25 | 82 |
| 2024 February | 54 | 29 | 83 |
| 2024 January | 44 | 22 | 66 |
| 2023 December | 35 | 26 | 61 |
| 2023 November | 62 | 31 | 93 |
| 2023 October | 53 | 26 | 79 |
| 2023 September | 51 | 31 | 82 |
| 2023 August | 58 | 19 | 77 |
| 2023 July | 66 | 17 | 83 |
| 2023 June | 64 | 23 | 87 |
| 2023 May | 60 | 28 | 88 |
| 2023 April | 41 | 9 | 50 |
| 2023 March | 47 | 21 | 68 |
| 2023 February | 41 | 15 | 56 |
| 2023 January | 47 | 16 | 63 |
| 2022 December | 62 | 22 | 84 |
| 2022 November | 56 | 29 | 85 |
| 2022 October | 59 | 35 | 94 |
| 2022 September | 46 | 19 | 65 |
| 2022 August | 57 | 39 | 96 |
| 2022 July | 30 | 40 | 70 |
| 2022 June | 56 | 30 | 86 |
| 2022 May | 48 | 27 | 75 |
| 2022 April | 42 | 54 | 96 |
| 2022 March | 70 | 49 | 119 |
| 2022 February | 83 | 59 | 142 |
| 2022 January | 50 | 26 | 76 |
| 2021 December | 53 | 31 | 84 |
| 2021 November | 36 | 38 | 74 |
| 2021 October | 66 | 34 | 100 |
| 2021 September | 40 | 34 | 74 |
| 2021 August | 40 | 26 | 66 |
| 2021 July | 84 | 28 | 112 |
| 2021 June | 49 | 22 | 71 |
| 2021 May | 72 | 29 | 101 |
| 2021 April | 124 | 72 | 196 |
| 2021 March | 115 | 32 | 147 |
| 2021 February | 75 | 19 | 94 |
| 2021 January | 70 | 38 | 108 |
| 2020 December | 30 | 13 | 43 |
| 2020 November | 31 | 14 | 45 |
| 2020 October | 32 | 14 | 46 |
| 2020 September | 39 | 10 | 49 |
| 2020 August | 49 | 16 | 65 |
| 2020 July | 39 | 10 | 49 |
| 2020 June | 31 | 14 | 45 |
| 2020 May | 44 | 6 | 50 |
| 2020 April | 39 | 17 | 56 |
| 2020 March | 51 | 16 | 67 |
| 2020 February | 47 | 22 | 69 |
| 2020 January | 64 | 16 | 80 |
| 2019 December | 69 | 13 | 82 |
| 2019 November | 40 | 19 | 59 |
| 2019 October | 26 | 8 | 34 |
| 2019 September | 65 | 22 | 87 |
| 2019 August | 42 | 8 | 50 |
| 2019 July | 45 | 20 | 65 |
| 2019 June | 41 | 11 | 52 |
| 2019 May | 40 | 9 | 49 |
| 2019 April | 79 | 39 | 118 |
| 2019 March | 43 | 19 | 62 |
| 2019 February | 35 | 10 | 45 |
| 2019 January | 58 | 16 | 74 |
| 2018 December | 96 | 35 | 131 |
| 2018 November | 170 | 14 | 184 |
| 2018 October | 173 | 18 | 191 |
| 2018 September | 92 | 13 | 105 |
| 2018 August | 59 | 15 | 74 |
| 2018 July | 63 | 16 | 79 |
| 2018 June | 88 | 6 | 94 |
| 2018 May | 82 | 21 | 103 |
| 2018 April | 86 | 5 | 91 |
| 2018 March | 113 | 5 | 118 |
| 2018 February | 76 | 8 | 84 |
| 2018 January | 68 | 10 | 78 |
| 2017 December | 62 | 10 | 72 |
| 2017 November | 62 | 4 | 66 |
| 2017 October | 37 | 6 | 43 |
| 2017 September | 60 | 9 | 69 |
| 2017 August | 59 | 10 | 69 |
| 2017 July | 64 | 5 | 69 |
| 2017 June | 50 | 13 | 63 |
| 2017 May | 62 | 9 | 71 |
| 2017 April | 48 | 9 | 57 |
| 2017 March | 33 | 5 | 38 |
| 2017 February | 59 | 5 | 64 |
| 2017 January | 27 | 9 | 36 |
| 2016 December | 48 | 7 | 55 |
| 2016 November | 73 | 9 | 82 |
| 2016 October | 135 | 8 | 143 |
| 2016 September | 185 | 4 | 189 |
| 2016 August | 179 | 8 | 187 |
| 2016 July | 156 | 6 | 162 |
| 2016 June | 112 | 0 | 112 |
| 2016 May | 117 | 0 | 117 |
| 2016 April | 103 | 0 | 103 |
| 2016 March | 86 | 0 | 86 |
| 2016 February | 114 | 0 | 114 |
| 2016 January | 105 | 0 | 105 |
| 2015 December | 129 | 0 | 129 |
| 2015 November | 101 | 0 | 101 |
| 2015 October | 85 | 0 | 85 |
| 2015 September | 87 | 0 | 87 |
| 2015 August | 76 | 0 | 76 |
| 2015 July | 51 | 0 | 51 |
| 2015 June | 33 | 0 | 33 |
| 2015 May | 52 | 0 | 52 |
| 2015 April | 5 | 0 | 5 |
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