Renal amyloidosis in a female with familial Mediterranean fever: clinical response to treatment with colchicine and infliximab
AMILOIDOSIS RENAL EN MUJER CON FIEBRE MEDIATERRANEA FAMILIAR: RESPUESTA CLÍNICA AL TRATAMIENTO CON COLCHICINA E INFLIXIMAB.
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"identificador" => "affa" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "SERVICIO DE NEFROLOGIA, HOSPITAL GENERAL DE SEGOVIA Segovia, Segovia, España, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "SERVICIO DE ANATOMIA PATOLOGICA, HOSPITAL RAMON Y CAJAL, MADRID MADRID España, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "AMILOIDOSIS RENAL EN MUJER CON FIEBRE MEDIATERRANEA FAMILIAR: RESPUESTA CLÍNICA AL TRATAMIENTO CON COLCHICINA E INFLIXIMAB." ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Fig. 1a" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "14218078_f1a_374.jpg" "Alto" => 179 "Ancho" => 256 "Tamanyo" => 8066 ] ] ] ] "textoCompleto" => "<p class="elsevierStylePara">Dear Editor:</p><p class="elsevierStylePara">Familial Mediterranean fever (FMF) is an autoinflammatory, autosomal recessive inherited disorder, characterised by recurrent attacks of fever and serositis.<span class="elsevierStyleSup">1</span> The identification of mutations in the MEFV gene has been of major assistance in early diagnosis in the majority of cases. Among the possible mutations, M694V is the most common, and is the mutation responsible for the most severe cases in heterozygous carriers.<span class="elsevierStyleSup">2</span> The most significant long term complication is chronic renal failure caused by AA amyloidosis.<span class="elsevierStyleSup">3</span>We describe the case of a female in which this disease presented itself in the form of nephrotic syndrome. Furthermore, we carry out a clinical follow-up of the response obtained after one year of combined colchicine and infliximab therapy.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Clinical case study</span></p><p class="elsevierStylePara">38 year old female, originally from Armenia, with no relevant personal history and a family history of father with nephropathy, who died at 50 years of age, and maternal aunt also with nephropathy. The patient was assessed for nephrotic syndrome in the nephrology department. In the assessment the patient described, in addition to oedemae in the lower extremities and palpebrae, nonspecific lumbar pain. During the assessment for nephrotic syndrome, the patient required numerous admissions for hydropic decompensation. A renal biopsy was carried out, with the discovery of eight glomeruli per section plane. These all showed a massive and diffuse deposit of congo red-positive amorphous, acellular and eosinophilous matter (figure 1A). The immunohistochemical study showed congo red positivity for AA (figure 1B), this being the definitive diagnosis of amyloidosis AA. Given the family history of nephropathy, the patient¿s country of origin and the presence of secondary amyloidosis, a genetic study was carried out which showed the presence of M680I and M694V mutations in heterozygosis in the MEFV gene associated with FMF. Treatment with colchicine was started at a dose of 0.5mg every 8hrs/day and infliximab at a dose of 5mg/kg IV, in basal form, for two weeks, and thereafter every two months. The patient¿s subsequent progress after establishing the treatment regime is detailed in table 1.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Discussion</span></p><p class="elsevierStylePara">FMF manifests clinically in the form of attacks of fever, peritonitis, pleuritis or polyarthritis.<span class="elsevierStyleSup">1</span> As a consequence of these inflammatory episodes, development of renal amyloidosis is common, worsening the prognosis.<span class="elsevierStyleSup">3</span> Gingold-Belfer et al.<span class="elsevierStyleSup">4</span> describe the case of a female patient in whom nephrotic syndrome was the primary manifestation of FMF, detected via the presence of an M694V mutation. Similarly, in our patient the diagnosis of FMF was also made via an assessment for nephrotic syndrome, since her symptoms did not relate to the classic symptoms of FMF and thus its presence was not suspected. In the case which we have described, our attention was drawn to the already advanced stage of the disease at diagnosis, with findings of severe nephrotic syndrome and AA amyloid deposits in the kidney. Furthermore, the presence of two mutations was detected, one of which (M694V) is the most common and that which is found in the most severe cases<span class="elsevierStyleSup">2</span> such as ours.</p><p class="elsevierStylePara">With regard to treatment, colchicine is the drug typically used to treat this condition.<span class="elsevierStyleSup">3</span> In cases of intolerance (diarrhoea) or inefficacy, other therapeutic options are considered.<span class="elsevierStyleSup">5 </span>TNF-alpha is a proinflammatory cytokine which can play a role in FMF as well as the development of secondary amyloidosis.<span class="elsevierStyleSup">6</span> TNF inhibitors can therefore be of use in FMF.<span class="elsevierStyleSup">7</span> This is reflected in some publications, where it is described how anti-TNF-alphas, including infliximab, reduce the frequency of FMF attacks and, therefore, bring about a recovery from proteinuria.<span class="elsevierStyleSup">6,7</span> Considering that our patient did not tolerate antiproteinuric drugs (ACEI, ARA II), and given the severity of proteinuria and deterioration of renal function, as well as the biopsy findings which demonstrated amyloidosis, we decided to use a combined treatment of colchicine and infliximab to assess her progress. This combined therapy has achieved a subjective improvement in the patient (there has been no hydropic decompensation throughout the year, nor admission for any other motive), as well as a recovery of renal function and a stabilisation in the proteinuria with an increase of albumin in the plasma. It is possible that this only partial response which we have obtained with combined therapy could be due to the fact that the disease presented itself without the typical symptoms, and it was its first complication (renal amyloidosis) that allowed us to reach a diagnosis, indicating that the disease was already advanced at the time of diagnosis. However, it could also be due to the fact that the patient was a carrier of the M694V mutation, which is associated with the most severe cases.</p><p class="elsevierStylePara">With regard to the tolerance and safety of infliximab, we have detected no adverse effect with this medication or any infectious complications during the period of its administration, indicating a good level of tolerance. In conclusion, an unusual presentation of FMF could delay diagnosis and, therefore, worsen the prognosis in these patients. For those cases in which amyloidosis is the manner through which a diagnosis of FMF is reached, a combined therapy of colchicine and infliximab could be of use at least to achieve a stabilisation of the disease.</p><p class="elsevierStylePara"><a href="grande/14218078_f1a_374.jpg" class="elsevierStyleCrossRefs"><img src="14218078_f1a_374.jpg"></img></a></p><p class="elsevierStylePara">Figure 1a. </p><p class="elsevierStylePara"><a href="grande/14218078_f1b_374.jpg" class="elsevierStyleCrossRefs"><img src="14218078_f1b_374.jpg"></img></a></p><p class="elsevierStylePara">Figure 1b. </p><p class="elsevierStylePara"><a href="grande/14218078_t1_375.jpg" class="elsevierStyleCrossRefs"><img src="14218078_t1_375.jpg" alt="Development of the analytic parameters alongside combined therapy (colchicine+infliximab)"></img></a></p><p class="elsevierStylePara">Table 1. Development of the analytic parameters alongside combined therapy (colchicine+infliximab)</p>" "pdfFichero" => "P-E-S-A142-EN.pdf" "tienePdf" => true "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Fig. 1a" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "14218078_f1a_374.jpg" "Alto" => 179 "Ancho" => 256 "Tamanyo" => 8066 ] ] ] 1 => array:7 [ "identificador" => "fig2" "etiqueta" => "Fig. 1b" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "14218078_f1b_374.jpg" "Alto" => 215 "Ancho" => 259 "Tamanyo" => 14125 ] ] ] 2 => array:8 [ "identificador" => "fig3" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "14218078_t1_375.jpg" "Alto" => 230 "Ancho" => 827 "Tamanyo" => 34945 ] ] "descripcion" => array:1 [ "en" => "Development of the analytic parameters alongside combined therapy (colchicine+infliximab)" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Sohar E, Gafni J, Pras M, Heller H. 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| 2024 July | 47 | 27 | 74 |
| 2024 June | 52 | 36 | 88 |
| 2024 May | 69 | 36 | 105 |
| 2024 April | 65 | 32 | 97 |
| 2024 March | 42 | 23 | 65 |
| 2024 February | 36 | 42 | 78 |
| 2024 January | 43 | 32 | 75 |
| 2023 December | 35 | 24 | 59 |
| 2023 November | 59 | 33 | 92 |
| 2023 October | 34 | 34 | 68 |
| 2023 September | 44 | 33 | 77 |
| 2023 August | 43 | 22 | 65 |
| 2023 July | 67 | 29 | 96 |
| 2023 June | 73 | 25 | 98 |
| 2023 May | 94 | 28 | 122 |
| 2023 April | 82 | 22 | 104 |
| 2023 March | 80 | 23 | 103 |
| 2023 February | 43 | 22 | 65 |
| 2023 January | 46 | 19 | 65 |
| 2022 December | 76 | 32 | 108 |
| 2022 November | 39 | 20 | 59 |
| 2022 October | 44 | 30 | 74 |
| 2022 September | 52 | 25 | 77 |
| 2022 August | 69 | 38 | 107 |
| 2022 July | 59 | 34 | 93 |
| 2022 June | 63 | 25 | 88 |
| 2022 May | 58 | 46 | 104 |
| 2022 April | 66 | 47 | 113 |
| 2022 March | 73 | 45 | 118 |
| 2022 February | 91 | 40 | 131 |
| 2022 January | 37 | 40 | 77 |
| 2021 December | 42 | 50 | 92 |
| 2021 November | 48 | 33 | 81 |
| 2021 October | 68 | 51 | 119 |
| 2021 September | 30 | 36 | 66 |
| 2021 August | 53 | 30 | 83 |
| 2021 July | 33 | 32 | 65 |
| 2021 June | 51 | 21 | 72 |
| 2021 May | 52 | 31 | 83 |
| 2021 April | 119 | 23 | 142 |
| 2021 March | 32 | 19 | 51 |
| 2021 February | 54 | 9 | 63 |
| 2021 January | 38 | 11 | 49 |
| 2020 December | 32 | 8 | 40 |
| 2020 November | 23 | 8 | 31 |
| 2020 October | 16 | 10 | 26 |
| 2020 September | 19 | 9 | 28 |
| 2020 August | 27 | 8 | 35 |
| 2020 July | 31 | 7 | 38 |
| 2020 June | 15 | 5 | 20 |
| 2020 May | 27 | 17 | 44 |
| 2020 April | 28 | 16 | 44 |
| 2020 March | 16 | 10 | 26 |
| 2020 February | 28 | 15 | 43 |
| 2020 January | 33 | 24 | 57 |
| 2019 December | 33 | 24 | 57 |
| 2019 November | 32 | 16 | 48 |
| 2019 October | 33 | 7 | 40 |
| 2019 September | 24 | 11 | 35 |
| 2019 August | 27 | 10 | 37 |
| 2019 July | 33 | 20 | 53 |
| 2019 June | 24 | 8 | 32 |
| 2019 May | 22 | 13 | 35 |
| 2019 April | 84 | 33 | 117 |
| 2019 March | 24 | 14 | 38 |
| 2019 February | 32 | 15 | 47 |
| 2019 January | 29 | 14 | 43 |
| 2018 December | 43 | 27 | 70 |
| 2018 November | 103 | 12 | 115 |
| 2018 October | 84 | 10 | 94 |
| 2018 September | 62 | 7 | 69 |
| 2018 August | 39 | 10 | 49 |
| 2018 July | 36 | 10 | 46 |
| 2018 June | 53 | 13 | 66 |
| 2018 May | 44 | 11 | 55 |
| 2018 April | 37 | 7 | 44 |
| 2018 March | 54 | 10 | 64 |
| 2018 February | 53 | 10 | 63 |
| 2018 January | 47 | 7 | 54 |
| 2017 December | 52 | 9 | 61 |
| 2017 November | 21 | 3 | 24 |
| 2017 October | 27 | 9 | 36 |
| 2017 September | 25 | 9 | 34 |
| 2017 August | 26 | 8 | 34 |
| 2017 July | 28 | 5 | 33 |
| 2017 June | 31 | 4 | 35 |
| 2017 May | 28 | 4 | 32 |
| 2017 April | 30 | 4 | 34 |
| 2017 March | 23 | 42 | 65 |
| 2017 February | 26 | 7 | 33 |
| 2017 January | 25 | 4 | 29 |
| 2016 December | 41 | 2 | 43 |
| 2016 November | 41 | 6 | 47 |
| 2016 October | 74 | 14 | 88 |
| 2016 September | 99 | 5 | 104 |
| 2016 August | 147 | 1 | 148 |
| 2016 July | 150 | 5 | 155 |
| 2016 June | 102 | 0 | 102 |
| 2016 May | 105 | 0 | 105 |
| 2016 April | 67 | 0 | 67 |
| 2016 March | 69 | 0 | 69 |
| 2016 February | 74 | 0 | 74 |
| 2016 January | 96 | 0 | 96 |
| 2015 December | 108 | 0 | 108 |
| 2015 November | 70 | 0 | 70 |
| 2015 October | 60 | 0 | 60 |
| 2015 September | 73 | 0 | 73 |
| 2015 August | 59 | 0 | 59 |
| 2015 July | 43 | 0 | 43 |
| 2015 June | 36 | 0 | 36 |
| 2015 May | 54 | 0 | 54 |
| 2015 April | 5 | 0 | 5 |
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