Case report
Colchicine use in isolated renal AA amyloidosis
Uso de colchicina en amiloidosis AA renal aislada
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Hematoxylin-eosin stain, original magnification ×20. (B) The glomerular deposits stain positively with Congo red. Typical apple-green birefringence when viewed with polarized light, original magnification ×40. (C) Immunohistochemical stain show amyloid AA deposits within the glomeruli, original magnification ×40.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Carlos F. Meneses, César A. Egües, Miren Uriarte, Joaquín Belzunegui, Marta Rezola" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Carlos F." "apellidos" => "Meneses" ] 1 => array:2 [ "nombre" => "César A." 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Meneses, César A. Egües, Miren Uriarte, Joaquín Belzunegui, Marta Rezola" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Carlos F." "apellidos" => "Meneses" "email" => array:1 [ 0 => "carlosfrancisco.menesesvillalba@osakidetza.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] 1 => array:4 [ "nombre" => "César A." "apellidos" => "Egües" "email" => array:1 [ 0 => "cesarantonio.egueesdubuc@osakidetza.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:4 [ "nombre" => "Miren" "apellidos" => "Uriarte" "email" => array:1 [ 0 => "miren.uriarteecenarro@osakidetza.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:4 [ "nombre" => "Joaquín" "apellidos" => "Belzunegui" "email" => array:1 [ 0 => "joaquinmaria.belzuneguiotano@osakidetza.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:4 [ "nombre" => "Marta" "apellidos" => "Rezola" "email" => array:1 [ 0 => "marta.rezolabajineta@osakidetza.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Rheumatology, Universitario Donostia, San Sebastián, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pathology of Hospital, Universitario Donostia, San Sebastián, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Uso de colchicina en amiloidosis AA renal aislada" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 799 "Ancho" => 3256 "Tamanyo" => 360625 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Glomerular deposition of amorphous and eosinophilic amyloid. Hematoxylin-eosin stain, original magnification ×20. (B) The glomerular deposits stain positively with Congo red. Typical apple-green birefringence when viewed with polarized light, original magnification ×40. (C) Immunohistochemical stain show amyloid AA deposits within the glomeruli, original magnification ×40.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Case</span><p id="par0005" class="elsevierStylePara elsevierViewall">A 45-year-old woman with stable chronic renal insufficiency and proteinuria was admitted with acute onset of dyspnea and chest pain. Complementary tests demonstrated pulmonary embolism secondary to deep venous thrombosis. Anamnesis revealed chronic malar rash and alopecia. The laboratory test showed a normal blood cells counts, <span class="elsevierStyleSmallCaps">C-</span>reactive protein (PCR) 68<span class="elsevierStyleHsp" style=""></span>mg/dl, erythrocyte sedimentation rate (ESR) 78<span class="elsevierStyleHsp" style=""></span>mm/h, serum creatinine 2.52<span class="elsevierStyleHsp" style=""></span>mg/dl, proteinuria 1.2<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h. Antinuclear antibodies (ANA) shown positive at low titer (1:80). Anti-dsDNA, anti-mitochondrial, anti-neutrophil cytoplasmic and anticardiolipin antibodies as well as lupic anticoagulant were shown to be negative. C3, C4 and coagulation studies had been shown to be normal. Serum proteins, immunoglobulins and Bence-Jones proteins came back negative.</p><p id="par0010" class="elsevierStylePara elsevierViewall">After a dermatological evaluation including cutaneous biopsy the malar rash resulted in rosacea. The renal biopsy revealed AA amyloidosis with Congo red staining and immunohistochemistry positive tests (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A–C). A subcutaneous fat tissue and rectal mucosa biopsy showed no signs of amyloid deposition. Bone marrow aspiration, transthoracic echocardiography and full body computer tomography did not identify any signs of amyloid infiltration in other organs. In addition, a genetic study was performed to rule out transthyretin-related hereditary amyloidosis, which came back negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">We diagnosed renal AA amyloidosis without underlying disease and empirically started treatment with colchicine 1<span class="elsevierStyleHsp" style=""></span>mg/day. At the beginning of the treatment, the patient showed SAA levels of 49.1<span class="elsevierStyleHsp" style=""></span>mg/dl. Soon after the initiation, we observed titers lowering down to a normal range. After three months, there was an increase of SAA. So we decided to increase colchicine to 1.5<span class="elsevierStyleHsp" style=""></span>mg/day. Now 12 months later, the SAA levels remain within normal ranges. The proteinuria has improved to levels of 180<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h. The patient is asymptomatic and currently has routine checkups.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">Systemic amyloidosis is a disease resulting in a localized or diffuse deposition of insoluble fibrils in extracellular tissues.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Immunohistologic study usually reveals AA amyloid (the type of protein associated with chronic inflammation) or AL amyloid (secondary to multiple myeloma).<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,6</span></a> Both processes produce pro inflammatory cytokines (IL-1, IL6 and TNF-α) which induce hepatic SAA synthesis.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,7</span></a> Serum SAA is an acute phase reactant, which after a proteolytic process deposits in various organs in a form of fibrils. Serum SAA titers are associated with the amount of tissue amyloid and the prognosis.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">AA amyloidosis occurs associated with chronic arthritis, infections and Familiar Mediterranean Fever.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In some cases it occurs as an isolated form.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> When amyloidosis is secondary to inflammatory arthritis the treatment consists of using immunosuppressant agents or biological treatments (anti-TNF or IL-1 antagonists).<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,7,8</span></a> In cases of amyloidosis secondary to Familiar Mediterranean Fever colchicine has been widely used.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In our patient, there are no signs of underlying disease identifying limited treatment options. Chronic mild proteinuria and renal insufficiency secondary to glomerular sclerosis made complicated the response to treatment, so we decided to measure levels of SAA.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> There are some published cases of renal AA amyloidosis with nephrotic syndrome treated with colchicine. In one of these cases, after using colchicine 1<span class="elsevierStyleHsp" style=""></span>mg per day, the proteinuria completely resolved after four months of treatment and renal function parameters returned to normal as well. A similar case reports rapid improvement of proteinuria down to 50% after 2<span class="elsevierStyleHsp" style=""></span>mg colchicine treatment.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Therefore, we started treatment with colchicine. In subsequent follow-up visits, we observed a dramatic decrease of SAA remaining within normal range during three months of treatment. Later, we observed a new increase of SAA. We decided to increase colchicine to 1.5<span class="elsevierStyleHsp" style=""></span>mg/day reaching normal titers over 12 months.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflict of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare no funding from any organization.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres528616" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec548855" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres528615" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec548854" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Case" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Funding" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-06-11" "fechaAceptado" => "2014-09-26" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec548855" "palabras" => array:6 [ 0 => "Colchicine" 1 => "Serum A amyloid protein" 2 => "SAA" 3 => "Amyloidosis" 4 => "Renal AA amyloidosis" 5 => "Congo red" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec548854" "palabras" => array:6 [ 0 => "Colchicina" 1 => "Proteína sérica amiloide A" 2 => "SAA" 3 => "Amiloidosis" 4 => "Renal AA amiloidosis" 5 => "Rojo congo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We present the case of a 45-year-old woman, with two-year history of chronic renal insufficiency and proteinuria. A kidney biopsy showed the presence of AA amyloidosis (positive Congo red staining and immunohistochemistry). There was no evidence of amyloid deposits in other organs and there was no underlying disease. AA amyloidosis normally is secondary to chronic inflammatory or infectious diseases. High levels of IL-1, IL-6 and TNF-α play a role in the pathogenesis of amyloidosis and induce the synthesis of serum amyloid A protein (SAA), a precursor of tissue amyloid deposits. We empirically treated the patient with a low dose colchicine. The patient responded well. Colchicine has been used for the treatment of Familiar Mediterranean Fever and related auto-inflammatory diseases. To monitor treatment responses, we measured SAA finding low titers. Soon after treatment onset there were signs of improvement pertaining to proteinuria and stabilization of renal function.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Se presenta el caso de una paciente de 45 años de edad con insuficiencia renal crónica y proteinuria. La biopsia renal demostró una amiloidosis tipo AA con un estudio de extensión negativo para depósitos en otros órganos. No se detectó enfermedad asociada. La amiloidosis tipo AA se asocia habitualmente a una enfermedad crónica inflamatoria o infecciosa. Las interleucinas IL1, IL-6 y TNF son responsables de la síntesis hepática de la proteína sérica amiloide A (SAA), precursor del amiloide que se deposita en los tejidos. Ante la imposibilidad de tratar una amiloidosis sin evidencia de enfermedad subyacente, instauramos empíricamente tratamiento con colchicina con buenos resultados. La colchicina es eficaz para el tratamiento de la fiebre mediterránea familiar y otros procesos inflamatorios. Se midieron niveles de la SAA en sangre que inicialmente fueron muy elevados alcanzándose niveles normales al poco tiempo de tratamiento con mejoría de la proteinuria, manteniéndose estable la función renal.</p></span>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 799 "Ancho" => 3256 "Tamanyo" => 360625 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Glomerular deposition of amorphous and eosinophilic amyloid. Hematoxylin-eosin stain, original magnification ×20. (B) The glomerular deposits stain positively with Congo red. Typical apple-green birefringence when viewed with polarized light, original magnification ×40. (C) Immunohistochemical stain show amyloid AA deposits within the glomeruli, original magnification ×40.</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" => "Advances in the treatment of amyloidosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.V. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 9 | 14 |
| 2024 October | 31 | 35 | 66 |
| 2024 September | 55 | 14 | 69 |
| 2024 August | 76 | 29 | 105 |
| 2024 July | 70 | 30 | 100 |
| 2024 June | 72 | 34 | 106 |
| 2024 May | 60 | 35 | 95 |
| 2024 April | 75 | 25 | 100 |
| 2024 March | 63 | 32 | 95 |
| 2024 February | 34 | 24 | 58 |
| 2024 January | 65 | 25 | 90 |
| 2023 December | 31 | 25 | 56 |
| 2023 November | 35 | 21 | 56 |
| 2023 October | 56 | 34 | 90 |
| 2023 September | 45 | 43 | 88 |
| 2023 August | 40 | 11 | 51 |
| 2023 July | 45 | 33 | 78 |
| 2023 June | 46 | 22 | 68 |
| 2023 May | 52 | 24 | 76 |
| 2023 April | 50 | 8 | 58 |
| 2023 March | 57 | 30 | 87 |
| 2023 February | 47 | 20 | 67 |
| 2023 January | 60 | 21 | 81 |
| 2022 December | 83 | 33 | 116 |
| 2022 November | 66 | 35 | 101 |
| 2022 October | 69 | 28 | 97 |
| 2022 September | 87 | 31 | 118 |
| 2022 August | 72 | 34 | 106 |
| 2022 July | 53 | 44 | 97 |
| 2022 June | 44 | 34 | 78 |
| 2022 May | 76 | 48 | 124 |
| 2022 April | 75 | 40 | 115 |
| 2022 March | 72 | 51 | 123 |
| 2022 February | 58 | 34 | 92 |
| 2022 January | 54 | 21 | 75 |
| 2021 December | 38 | 46 | 84 |
| 2021 November | 51 | 46 | 97 |
| 2021 October | 57 | 49 | 106 |
| 2021 September | 39 | 49 | 88 |
| 2021 August | 51 | 28 | 79 |
| 2021 July | 33 | 34 | 67 |
| 2021 June | 36 | 22 | 58 |
| 2021 May | 52 | 36 | 88 |
| 2021 April | 174 | 106 | 280 |
| 2021 March | 65 | 26 | 91 |
| 2021 February | 44 | 29 | 73 |
| 2021 January | 48 | 31 | 79 |
| 2020 December | 47 | 21 | 68 |
| 2020 November | 55 | 18 | 73 |
| 2020 October | 41 | 12 | 53 |
| 2020 September | 53 | 17 | 70 |
| 2020 August | 35 | 20 | 55 |
| 2020 July | 23 | 16 | 39 |
| 2020 June | 38 | 20 | 58 |
| 2020 May | 27 | 17 | 44 |
| 2020 April | 18 | 12 | 30 |
| 2020 March | 18 | 6 | 24 |
| 2020 February | 1 | 0 | 1 |
| 2020 January | 1 | 0 | 1 |
| 2019 March | 1 | 0 | 1 |
| 2018 May | 2 | 2 | 4 |
| 2018 April | 33 | 10 | 43 |
| 2018 March | 28 | 5 | 33 |
| 2018 February | 26 | 8 | 34 |
| 2018 January | 31 | 8 | 39 |
| 2017 December | 30 | 13 | 43 |
| 2017 November | 31 | 13 | 44 |
| 2017 October | 32 | 10 | 42 |
| 2017 September | 29 | 14 | 43 |
| 2017 August | 51 | 14 | 65 |
| 2017 July | 47 | 16 | 63 |
| 2017 June | 54 | 8 | 62 |
| 2017 May | 51 | 15 | 66 |
| 2017 April | 41 | 43 | 84 |
| 2017 March | 45 | 22 | 67 |
| 2017 February | 38 | 12 | 50 |
| 2017 January | 28 | 8 | 36 |
| 2016 December | 42 | 18 | 60 |
| 2016 November | 33 | 11 | 44 |
| 2016 October | 52 | 14 | 66 |
| 2016 September | 46 | 5 | 51 |
| 2016 August | 30 | 3 | 33 |
| 2016 July | 22 | 5 | 27 |
| 2015 December | 3 | 0 | 3 |
| 2015 November | 1 | 12 | 13 |
| 2015 October | 3 | 13 | 16 |
| 2015 September | 4 | 0 | 4 |
| 2015 August | 6 | 35 | 41 |
| 2015 July | 23 | 28 | 51 |
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