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La amiloidosis es una enfermedad heterogénea, de origen hereditario o adquirido, que se caracteriza por el depósito anormal de proteínas fibrilares en diversos tejidos. Esta enfermedad puede manifestarse de manera localizada o sistémica, lo que genera una amplia variabilidad en su presentación clínica y, frecuentemente, retrasa el diagnóstico. Por ello, es fundamental la identificación temprana de los signos y síntomas para mejorar el pronóstico. El primer posicionamiento mexicano sobre la amiloidosis cardíaca tiene como objetivo resumir las principales características de la enfermedad y sus subtipos, identificando datos de alarma que incrementen la sospecha de su presencia. Además, busca ofrecer un algoritmo diagnóstico que integre los estudios de imagen y de laboratorio disponibles en nuestro país, con el fin de simplificar la toma de decisiones y llegar a un diagnóstico de manera rápida, práctica y actualizada, basado en recomendaciones sustentadas en evidencia científica. Una vez confirmado el diagnóstico, se abordan los distintos retos terapéuticos, tanto farmacológicos como no farmacológicos, ya que los pacientes no responden al tratamiento convencional de insuficiencia cardíaca. Por ello, el tratamiento debe ser individualizado para cada paciente, teniendo en cuenta la presencia de otras comorbilidades. Finalmente, se presentan los principales factores pronósticos que guiarán un tratamiento adecuado, incluyendo los resultados del asesoramiento genético.

Amyloidosis is a heterogeneous, hereditary or acquired disease characterized by the abnormal deposition of fibrillar proteins in various tissues. The disease can be either localized or systemic, leading to significant variability in its clinical presentation and often causing diagnostic delays. For this reason, early identification of signs and symptoms is essential to improve prognosis. The first Mexican position paper on cardiac amyloidosis aims to summarize the main features of the disease and its subtypes, identifying warning signs that increase clinical suspicion. Additionally, it provides a diagnostic algorithm incorporating the imaging and laboratory studies available in our country, to streamline decision-making and facilitate a fast, practical, and up-to-date diagnosis based on evidence-based recommendations. Once the diagnosis is confirmed, the various therapeutic challenges of this disease, both pharmacological and non-pharmacological, are discussed, as patients do not respond to conventional heart failure treatments. Therefore, treatment must be individualized for each patient, considering the presence of other comorbidities. Finally, the key prognostic factors are outlined to guide appropriate treatment, including results from genetic counseling.

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OBJECTIVE: To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis. METHOD: Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies. RESULTS: Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT. CONCLUSIONS: OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.

OBJETIVO: Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL. MÉTODO: Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas. RESULTADOS: De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO. CONCLUSIONES: El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.

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Light chain (AL) amyloidosis is a form of systemic amyloidosis, causing organ dysfunction, mainly affecting the heart and kidney. Patient-tailored and risk-adapted decision making is critical in AL amyloidosis management. There is limited real-world evidence data from Argentina and Latin America regarding the treatment approaches for AL amyloidosis. This retrospective cohort study aimed to describe the treatment patterns and outcomes in adult patients (>18 years) diagnosed with AL amyloidosis at the Hospital Italiano in Buenos Aires, Argentina, using a 10-yearfollow-up data (June 1, 2010 to May 31, 2019) from the institutional registry of amyloidosis (IRA). The study population had a mean age of 63 years and 54.4% weremale. Heart and kidney were the most frequently affected organs. Of the 90 eligible patients included in the study, 70underwent treatment. Bortezomib-based regimen was the preferred first-line treatment (75.7% patients). Overall,54.4% of the patients presented a deep response (complete or very good partial response). Median overall survival (OS) was 5years, the 1-year OS and progression free survival rates were 80% (95% confidence interval [CI]: 68-87) and 80% (95%CI 68-87)), respectively. This study provides vital real-world evidence for the long-term treatment patterns and survival in a large cohort of AL amyloidosis patients in Argentina.

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INTRODUCTION: Immunoglobulin light chain (AL) amyloidosis is a rare disease. Treatment is challenging, justified in part by systemic compromise and limited scientific evidence. OBJECTIVES: Develop evidencebased recommendations that allow adequate treatment of patients with amyloidosis AL. METHODS: A list of PICO format questions focused on the effectiveness and safety of amyloidosis AL treatment was generated. PubMed, Cochrane and Epistemonikos were searched. The levels of evidence and grades of recommendation were based on the GRADE system. RESULTS: 11 recommendations were generated. In selected patients with amyloidosis AL, autologous hematopoietic stem cell transplantation (ASCT) is recommended after induction with bortezomibbased regimens and conditioning with melphalan, since it could deepen the hematological and organ response, its durability and improve survival. In patients not eligible for ASCT, first-line treatment with bortezomib-based regimens is recommended, since it is likely to achieve a higher rate of hematological and organ response and improve survival. In patients with a contraindication or inaccessibility to bortezomib, treatment with alkylating agents and corticosteroids is recommended, since they are likely to achieve haematological and organ response and improve survival. DISCUSSION: These treatment recommendations are based on the available evidence and the experience of the panel of experts, in a scenario of limited available resources, according to developing countries.

Introducción: La amiloidosis por cadenas livianas de inmunoglobulinas (AL) es una enfermedad poco frecuente. El tratamiento implica un desafío, justificado en parte por el compromiso sistémico y la evidencia científica escasa. Objetivos: Elaborar recomendaciones basadas en la evidencia que permitan realizar un adecuado tratamiento de pacientes con amiloidosis AL. Métodos: Se generó un listado de preguntas con formato PICO centradas en la efectividad y seguridad del tratamiento de la amiloidosis AL. Se realizó la búsqueda en PubMed, Cochrane y Epistemonikos. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE. Resultados: Se generaron 11 recomendaciones. En pacientes con amiloidosis AL seleccionados, se recomienda el trasplante autólogo de células progenitoras hematopoyéticas (TCPH) posterior a una inducción con esquemas basados en bortezomib y el acondicionamiento con melfalán, ya que podría profundizar la respuesta hematológica, de órgano, su durabilidad y mejorar la supervivencia. En pacientes no elegibles para TCPH, se recomienda el tratamiento de primera línea con esquemas basados en bortezomib, dado que es probable que logre mayor tasa de respuesta hematológica, de órgano y mejore la supervivencia. En pacientes con contraindicación o inaccesibilidad al bortezomib, se recomienda el tratamiento con agentes alquilantes y corticoides, dado que es probable que logren la respuesta hematológica, de órgano y mejoren la supervivencia. Discusión: Estas recomendaciones de tratamiento se basan en la evidencia disponible y la experiencia del panel de expertos, en un escenario de recursos disponibles limitados, acorde a los países en vías de desarrollo.

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Amyloidosis is a disease caused by extracellular deposition of insoluble protein fibrils, that results in changes in tissue architecture and consequently modification of the organ structure. Cardiac involvement is common in amyloidosis. Two major types of systemic amyloidosis affect the myocardium ­ immunoglobulin light chain and transthyretin amyloidosis ­ each leading to different prognosis. Early detection and diagnosis of cardiac amyloidosis are the main objectives in the assessment of the disease. New techniques of magnetic resonance imaging have minimized the need for biopsies for the diagnosis. Late gadolinium enhancement technique, and more recently T1 mapping, have allowed a simplified evaluation of amyloid deposits and extracellular volume. The aim of this review was to describe basic concepts and updates of the use of magnetic resonance imaging for the diagnosis amyloidosis and evaluation of its severity

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Background Advanced cardiac imaging permits optimal targeting of cardiac treatment but needs to be faster, cheaper, and easier for global delivery. We aimed to pilot rapid cardiac magnetic resonance ( CMR ) with contrast in a developing nation, embedding it within clinical care along with training and mentoring. Methods and Results A cross-sectional study of CMR delivery and clinical impact assessment performed 2016-2017 in an upper middle-income country. An International partnership (clinicians in Peru and collaborators from the United Kingdom, United States, Brazil, and Colombia) developed and tested a 15-minute CMR protocol in the United Kingdom, for cardiac volumes, function and scar, and delivered it with reporting combined with training, education and mentoring in 2 centers in the capital city, Lima, Peru, 100 patients referred by local doctors from 6 centers. Management changes related to the CMR were reviewed at 12 months. One-hundred scans were conducted in 98 patients with no complications. Final diagnoses were cardiomyopathy (hypertrophic, 26%; dilated, 22%; ischemic, 15%) and 12 other pathologies including tumors, congenital heart disease, iron overload, amyloidosis, genetic syndromes, vasculitis, thrombi, and valve disease. Scan cost was $150 USD, and the average scan duration was 18±7 minutes. Findings impacted management in 56% of patients, including previously unsuspected diagnoses in 19% and therapeutic management changes in 37%. Conclusions Advanced cardiac diagnostics, here CMR with contrast, is possible using existing infrastructure in the developing world in 18 minutes for $150, resulting in important changes in patient care.

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Amyloidosis of the gastrointestinal tract is usually a systemic disease. Localized gastrointestinal amyloidosis without evidence of extraintestinal involvement or an associated plasma cell dyscrasia is uncommon and does not usually cause death. We report a case of a patient with localized gastrointestinal amyloidosis who presented with protein-losing enteropathy and a fatal upper gastrointestinal bleed.

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 Hepatic involvement in AL amyloidosis may present as acute liver failure. Historically, liver transplantation in these cases has achieved poor outcomes due to progress of amyloidosis and non-hepatic organ damage. In the era of bortezomib treatment, the prognosis of AL amyloidosis has been markedly improved and may also result in better post-transplant outcomes. We present a case of isolated acute liver failure caused by AL amyloidosis, bridged to transplantation with bortezomib and treated with sequential orthotopic liver transplantation (OLT) and autologous stem cell transplantation. The patient is in stable remission 3 years after OLT.

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Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt-Hogg-Dubé); other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management.

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Oral primary localized amyloidosis should be considered in the diagnosis of oral white lesions such as hyperplastic candidosis, lichen planus and lichenoid reactions; it is not associated with antiretroviral therapy use, systemic involvement or malignant transformation.

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La amiloidosis cutánea es un tipo de amiloidosis localizada que se diferencia de la sistémica en que el depósito de la sustancia amiloide se halla exclusivamente en la piel. Dentro de las amiloidosis cutáneas localizadas se encuentra la variante maculosa, que afecta a mujeres adultas y se caracteriza por la presencia de máculas hiperpigmentadas pruriginosas ubicadas en espalda. Es frecuente de observaren algunas áreas geográficas (Asia, América del Sur y América Central).Presentamos cinco pacientes (cuatro mujeres y un varón) con amiloidosis macular, todas de igual localización cutánea...

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Primary hepatic amyloidosis (PHA) is characterized by abnormal deposition of monoclonal immunoglobulin light chains (AL) in the liver. This rare condition is frequently undiagnosed or misdiagnosed and can be associated with poor prognosis. At present, the precise pathogenesis is not fully understood. Despite that hepatomegaly and elevated alkaline phosphatase (ALP) are present in most patients with PHA, no specific clinical markers have been identified. Staining of hepatic tissues with Congo Red is often regarded as the "gold standard". Pharmacological therapy should aim to rapidly reduce the supply of misfolded amyloidogenic AL. High-dose intravenous melphalan (HDM) and autologous stem cell transplantation (ASCT) appear to be the most appropriate therapy but controversies still exist.

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MATERIAL AND METHODS: In a 30-year period in a single institution, 23 cases of systemic immunoglobulin light chain amyloidosis (AL) were identified, within a group of 1,388 individuals with some form of a hematological malignancy. RESULTS: AL is 14 times less frequent in Mexico than in Caucasians and it represents 15% of all monoclonal gammopathies. Median age was 57 years (range 39-98); there were 11 males and 12 females. The histologic diagnosis was done in the periumbilical fat in 39%, the bone marrow in 30%, the kidney in 13%, the gastrointestinal tract in 13% and in a lymph node in one case. The nephrotic syndrome was present in 61% of cases, heart failure in 35%, sensorimotor peripheral neuropathy in 26% and weight loss in 6%. Anemia was present in 14% of cases at diagnosis; median hemoglobin was 11 g/dL. An abnormal monoclonal spike in the peripheral blood was present in 70% of cases; it had a median of 1.2 g/dL (range 0.2-3.6); there were 7 cases of light-chain only disease and five in whom an abnormal paraproteinemia was not found. Six cases were associated with overt multiple myeloma. Seventeen individuals (74%) were followed for more than 3 months (range 90 to 5190 days, median 210); their overall survival (OS) was 71% at 173 months, whereas the median OS has not been reached, being above 173 months. Eight patients were treated with melphalan/predisone and five were given high dose chemotherapy and an autologous stem cell transplantation; the others were given other treatments. CONCLUSIONS: AL is less frequent in Mexican mestizos and probably underrecognized; the clinical features of the disease are not significantly different from those informed from other populations.