Letter to the Editor
Respiratory failure caused by amyloid myopathy
Miopatía amiloidea como causa de insuficiencia respiratoria
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Teresa Cibeira, Jose María Nicolás" "autores" => array:4 [ 0 => array:3 [ "nombre" => "David" "apellidos" => "Nicolás" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Pedro" "apellidos" => "Castro" "email" => array:1 [ 0 => "pcastro@clinic.ub.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "M. Teresa" "apellidos" => "Cibeira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Jose María" "apellidos" => "Nicolás" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Clínic, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Área de Vigilancia Intensiva, Servicio de Medicina Interna, Hospital Clínic, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Clínic, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Miopatía amiloidea como causa de insuficiencia respiratoria" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report the case of a 75-year-old patient diagnosed with multiple myeloma (MM) IgA-lambda stage <span class="elsevierStyleSmallCaps">II</span>-A, with anaemia, serum monoclonal component of 9.5<span class="elsevierStyleHsp" style=""></span>g/l and proteinuria. Bortezomib and dexamethasone was administered, obtaining a partial response. A year later, the patient presented with clinical features of intense asthenia and progressive weakness of all 4 limbs as well as dyspnoea at rest over a 2-month period. Physical examination showed a baseline oxygen saturation of 89%, bibasal fine crackles and predominantly proximal flaccid tetraparesia (3/5 in upper limbs and 2/5 in lower limbs). No muscle pseudohypertrophy or macroglossia was observed. Laboratory tests showed normal serum creatinine, creatine kinase, albumin, sodium and potassium, and elevated lactate dehydrogenase (724<span class="elsevierStyleHsp" style=""></span>U/l, RN: 250–450), low total protein (54<span class="elsevierStyleHsp" style=""></span>g/l, RN: 63–80) and mild anaemia (Hb 10.4<span class="elsevierStyleHsp" style=""></span>g/dl). Immunofixation showed an IgA-lambda monoclonal component of 10<span class="elsevierStyleHsp" style=""></span>g/l and 24<span class="elsevierStyleHsp" style=""></span>h proteinuria in urine of 2118<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>mg/l. A bone marrow aspirate showed infiltration by plasma cells (67%) with abnormal phenotype. In the chest CT abnormal muscle density was found in both deltoid muscles, and the echocardiography showed a concentric left ventricular hypertrophy. Finally, a bronchoscopy was performed, during which the patient had a respiratory arrest requiring endotracheal intubation and mechanical ventilation, being transferred to the intensive care unit (ICU).</p><p id="par0010" class="elsevierStylePara elsevierViewall">On admission the patient presented with a discrete respiratory acidosis compensated in arterial blood gases (FiO<span class="elsevierStyleInf">2</span> 0.35, pH 7.40, pCO<span class="elsevierStyleInf">2</span> 46.8<span class="elsevierStyleHsp" style=""></span>mmHg, pO<span class="elsevierStyleInf">2</span> 95.5<span class="elsevierStyleHsp" style=""></span>mmHg, standard bicarbonate 28.9<span class="elsevierStyleHsp" style=""></span>mmol/l), with an examination after sedation similar to that performed at admission, with proximal tetraparesia which did not seem to affect respiratory mechanics. The patient was extubated after a successful spontaneous breathing test within the first 24<span class="elsevierStyleHsp" style=""></span>h. However, after 24<span class="elsevierStyleHsp" style=""></span>h, the patient presented with a new hypoventilation episode, with rapidly progressive hypercapnic respiratory failure, reintubation being necessary. Despite being well fixed to the ventilator and with minimum oxygen requirements, it still required the gradual increase of support pressure to avoid hypercapnia.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Congo red staining was performed in subcutaneous fat, this being negative, and a biopsy in the deltoid muscle, in which a massive deposit of Congo red positive material was observed in muscle vessels, perimysium and endomysium, positive for light chain lambda by immunohistochemistry. Light chain amyloid myopathy was then diagnosed, with respiratory failure secondary to probable involvement of inspiratory muscles (diaphragm and chest muscles).</p><p id="par0020" class="elsevierStylePara elsevierViewall">At 48<span class="elsevierStyleHsp" style=""></span>h, the patient had an unrecoverable multiple organ failure and died 3 days after ICU admission. The macroscopic post-mortem study highlighted an oedematous and shiny texture in the gastrointestinal tract, lungs, heart, peripheral muscle, diaphragm and vascular structures, whose microscopic study showed massive deposits of positive Congo red material.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Light chain amyloidosis is a disease characterized by tissue deposition of monoclonal light chains produced by a clonal population of plasma cells. Its prevalence in patients with MM is 15%, although some studies have shown that up to 38% of patients with MM have asymptomatic amyloid deposits in one or another tissue.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Its presentation and clinical features are very heterogeneous, the most common symptoms being weight loss, peripheral oedema and asthenia. Periorbital bruising or macroglossia occur in less than 10–15% of patients.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> The organs most often affected are the kidneys (70%) and heart (50%), followed by the liver, peripheral and autonomic nervous system, and gastrointestinal tract.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> In our case, some data pointed to the possibility of a muscle disease, including proximal weakness and deltoid signal alteration as observed on the CT scan. Muscle involvement by amyloidosis is very rare, and only 89 cases have been described in the literature to date. The most common form of presentation was proximal weakness (90%), with macroglossia, pseudohypertrophy (34%) and dysphagia (22%) being less frequent. The progression of all cases was poor with a median survival of 21.7 months from diagnosis.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> Respiratory failure due to amyloid deposition in the diaphragm and inspiratory muscles has only been described in 3 other cases to date<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">5–7</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). At the time of diagnosis all manifested clinical features associated with amyloid myopathy, as macroglossia, proximal weakness or dysphagia, and required mechanical ventilation, confirmed by muscle biopsy. The progression led to death in all cases, with inability to withdraw mechanical ventilation and death during ICU hospitalization, between 10 and 20 days after admission.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Respiratory failure due to amyloid myopathy is a rare entity. This disease should be suspected in patients with monoclonal gammopathy who have respiratory failure. The classic findings, e.g. macroglossia and pseudohypertrophy, or positive subcutaneous fat biopsy, may not be present at the time of diagnosis, and in those cases muscle biopsy would be the most appropriate test for a definitive diagnosis.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as: Nicolás D, Castro P, Cibeira MT, Nicolás JM. Miopatía amiloidea como causa de insuficiencia respiratoria. Med Clin (Barc). 2016;146:e25–e26.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">F: female; MM: multiple myeloma; NA: not available; M: male; MV: mechanical ventilation.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Search made through PubMed in July 2014 in English and Spanish literature.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author, reference and year \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age (years) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MM \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Presenting symptoms \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Organs with evidence of amyloid infiltration \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MV \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Progression \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Survival<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> (days) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Streeten et al.,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> 1986 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Macroglossia, proximal weakness, cough, arthralgia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diaphragm, oesophagus, rectum, tongue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Santiago et al.,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> 1987 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Weakness, dysphagia and dyspnoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diaphragm, skeletal muscles, heart, tongue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ashe et al.,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> 1992 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Weakness, weight loss, malaise \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diaphragm, intercostal muscles and psoas, ileum, jejunum, heart, tongue \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Current case \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Proximal weakness, fatigue, respiratory failure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diaphragm, intercostal muscles, gastrointestinal tract, liver, heart \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1110613.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">From ICU admission.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Published cases of respiratory failure secondary to diaphragmatic amyloid infiltration.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary systemic amyloidosis with delayed progression to multiple myeloma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.V. 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