Catastrophic antiphospholipid syndrome in Mexico. Literature review.

Catastrophic antiphospholipid syndrome (CAPS) is a rare entity, approximately 600 cases have been reported around the world, and the prevalence in Mexico is unknown. OBJECTIVE: To determine the estimated prevalence of CAPS in Mexico. MATERIAL AND METHODS: A literature search of isolated clinical cases or case series was conducted in diverse search engines, using the terms: "Catastrophic Antiphospholipid Syndrome" and "Mexico" in May 2022. RESULTS: We found a series of retrospective cases in autopsies that included 12 cases, two reports that included 2 cases each, and reports of 11 isolated clinical cases; these publications were generated between 2003 and 2020. In total, we collected data on 27 cases of CAPS, of which 16 correspond to primary antiphospholipid syndrome, 10 are associated with systemic lupus erythematosus, and 1 case corresponds to systemic sclerosis. The estimated prevalence rate in the Mexican population in 2022 is 2 cases per 10,000,000 inhabitants. The estimated mortality was 68% in this case series. CONCLUSION: Cases of catastrophic antiphospholipid syndrome in Mexico are underreported; identifying them will help improve current diagnostic and therapeutic strategies used in the country, encouraging the implementation of triple therapy and, in refractory cases, the use of eculizumab, to reduce current mortality.

Cost-effectiveness analysis of treatments for the first episode of catastrophic antiphospholipid syndrome: A study based on the catastrophic antiphospholipid syndrome registry.

BACKGROUND: Treatments for catastrophic antiphospholipid syndrome (CAPS) rose from recommendations and consensus of international experts based on case series or case reports. We aimed to evaluate the treatment scheme with the best cost-effectiveness ratio associated with lower mortality as a high-impact clinical benefit. METHODS: The CAPS Registry was used as our source of structured data on the different therapeutic strategies, their frequency, and their effectiveness (survival). Starting from around 50 different schemes, we identified those with a mortality of less than 33% within the 18 most frequently utilized. After applying the efficiency frontier method, we included two schemes to conduct a cost-effectiveness analysis from the Colombian healthcare sector perspective. Scheme 1 (Glucocorticoids + Anticoagulation + Anti-aggregation + Intravenous IgG immunoglobulin) and scheme 2 (Glucocorticoids + Anticoagulation + Anti-aggregation + Plasma exchange) were compared in terms of costs and survival. Deterministic and probabilistic sensitivity analyses (Monte Carlo simulation) were conducted to evaluate model robustness and uncertainty. RESULTS: Our analysis uses the information corresponding to 427 cases from the CAPS registry, the majority being women (68.8%), with a mean age of 45.7 years and bearing general mortality of 38.17% (female: 38.4%, male: 37.5%). Scheme 2 was the cost-effective strategy over scheme 1. The results were robust on discrete sensitivity analysis and probability sensitivity analysis (Monte Carlo simulation). CONCLUSION: To our knowledge, this is the first economic evaluation focused on the treatment of CAPS. For the Colombian health system, schemes 1 and 2 have similar behavior; nevertheless, scheme 2 represents the best cost-effectiveness ratio. This treatment approach is highly susceptible to the allocation of resources by the system and beneficial in terms of health outcomes.

Catastrophic antiphospholipid syndrome / Síndrome antifosfolípido catastrófico

ABSTRACT The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by the development of thrombotic events and/or obstetric morbidity in the presence of antiphospholipid antibodies (aPL), such as the lupus anticoagulant (LA), anticardiolipin antibodies (aCL) or anti- β 2-glycoprotein I antibodies (a β2 GPI). In 1992, Ronald A. Asherson described a very aggressive clinical variant of this syndrome characterized by the development of multiple thrombotic manifestations, simultaneously or in a short period of time. The term catastrophic APS was proposed and since then it is known by this name.

RESUMEN El síndrome antifosfolípido (SAF) es una enfermedad sistêmica autoinmune, caracterizada por el desarrollo de eventos trombóticos y/o morbilidad obstétrica en presencia de anticuerpos antifosfolípidos (aPL), tales como el anticoagulante lúpico (AL), los anticuerpos anticardiolipina (aCL) o anticuerpos anti- β2-glicoproteína I (aβ2GPI). En 1992, Ronald A. Asherson describió una variante clínica muy agresiva de este síndrome, caracterizada por el desarrollo de múltiples manifestaciones trombóticas, de manera simultánea o dentro de un corto periodo de tiempo. Se propuso entonces el término SAF catastrófico y desde entonces se le ha conocido por ese nombre.

Pediatric catastrophic antiphospholipid syndrome patient evolving to systemic lupus erythematosus.

OBJECTIVES: We aim to describe a rare case of a young patient with a catastrophic antiphospholipid syndrome (cAPS) who evolved to systemic lupus erythematosus (SLE).Methodology: Case report description. CASE REPORT: A 15 years old girl came to the emergency department with acute peritonitis secondary to ischemic perforation of the sigmoid. Angiotomography was suggestive of a thrombotic occlusion of the upper mesenteric artery. Laboratory tests revealed a positive lupus anticoagulant and antinuclear antibodies. A cAPS diagnosis was determined based on more than three different sites of thrombosis (lung, kidney, spleen and sigmoid) in less than one week with a lupus anticoagulant. She was treated with intravenous methylprednisolone 1 mg/kg/day associated with intravenous heparin followed by intravenous immunoglobulin. She had a very good outcome with a total improvement and was discharged from the hospital after 2 months. After 12 weeks, the lupus anticoagulant remained positive. After two months, a systemic lupus erythematosus was diagnosed. She was treated with increasing dose of prednisone and azathioprine 100 mg/day and hydroxychloroquine were added to the treatment. After 2 weeks, she was asymptomatic. She is currently well, asymptomatic using hydroxychloroquine, azathioprine and warfarin. CONCLUSION: This article reports a very unusual presentation which is rarely reported and clinicians should be alert to the possibility that CAPS may be the presenting event for SLE patients, condition known in adults and should also be remembered in pediatric scenario.

Síndrome antifosfolípido catastrófico "seronegativo" en pediatría: caso clínico / "Seronegative" catastrophic antiphospholipid syndrome in pediatrics: clinical case

INTRODUCCIÓN: El síndrome antifosfolípido es una trombofilia adquirida autoinmune, caracterizada por trombosis arteriales y/o venosas. En raras ocasiones este cuadro puede tener una presentación catastrófica, de elevada mortalidad, con presencia de microangiopatia y compromiso de tres o más órganos. OBJETIVO: Describir la presentación clínica y evolución de una paciente pediátrica con síndrome antifosfolípido catastrófico, con forma de inicio seronegativa, cuya respuesta a terapia agresiva fue favorable. CASO CLÍNICO: Paciente femenina adolescente, que debutó cuadro de una semana de evolución de dolor, incremento del volumen abdominal y edema en extremidades inferiores. Se diagnosticó lupus eritematoso generalizado y se descartó proceso neoplásico. Durante su evolución pre sentó diversos eventos trómboticos, al inicio con presencia de anticuerpos antifosfolípido negativos, que posteriormente fueron positivos. Cursó con deterioro multisistémico secundario a trombosis multiorgánica, requirió soporte hemodinámico y ventilatorio. Se manejó con heparina de bajo peso molecular, plasmaféresis, anticoagulación, inmunosupresión y bolos de rituximab con excelente respuesta. CONCLUSIONES: Consideramos este caso de interés por tratarse de un diagnóstico infrecuente en la edad pediátrica y cuya sospecha, manejo intensivo y oportuno, puede cambiar el pronóstico sombrío y de alta mortalidad de estos pacientes.

INTRODUCTION: The antiphospholipid syndrome is an acquired autoimmune thrombophilia, characterized by arterial and/or venous thrombosis. Rarely, this condition can have a catastrophic presenta tion, with high mortality, and presence of microangiopathy and involvement of three or more organs. OBJECTIVE: To describe the clinical presentation and evolution of a pediatric patient with catastrophic antiphospholipid syndrome, with a seronegative onset form, whose response to aggressive therapy was favorable. CLINICAL CASE: Adolescent female, with a one-week history of pain, increased abdo minal volume and edema in the lower extremities. Generalized lupus erythematosus was diagnosed and the neoplastic process was ruled out. During its evolution, she presented various thrombotic events, initially with the presence of negative antiphospholipid antibodies, which were subsequently positive. The patient presented multisystemic failure secondary to multiorgan thrombosis, required hemodynamic and ventilatory support. It was managed with low molecular weight heparin, plas mapheresis, anticoagulation, immunosuppression and boluses of rituximab with excellent response. CONCLUSIONS: We consider this case interesting because it is an infrequent diagnosis in the pediatric age and whose suspicion, timely and aggressive intensive management, can change the poor progno sis and high mortality of these patients.

Catastrophic antiphospholipid syndrome. Case report and literature review / Síndrome antifosfolípidos catastrófico. Reporte de caso y revisión bibliográfica.

The present document is the report of a case of a very rare clinical entity, which presents with acute multiorganic failure after a thrombotic storm related to antiphospholipid antibodies, the so-called catastrophic antiphospholipid syndrome, which began as a recurrent picture of mesenteric thrombosis, with a previous history of venous insufficiency and distal ulcers probably associated with an unidentified antiphospholipid; deserving management in intensive care and the consultation by the world expert, Dr. Ricard Cervera who confirmed the diagnosis and recommend treating as such entity, the patient's evolution was satisfactory so far. Final recommendations for diagnosis and current treatment options such as rituximab or eculizumab are made. The present case was added to the international registry that currently houses around 500 cases worldwide (International CAPS Registry).

Se reporta un caso de una condición clínica sumamente rara, la cual cursa con falla multiorgánica aguda posterior a una tormenta trombótica relacionada con anticuerpos antifosfolípidos, el denominado síndrome antifosfolípidos (SAF) catastrófico, el cual comenzó como un cuadro recurrente de trombosis mesentérica, con antecedentes de insuficiencia venosa y úlceras distales probablemente asociadas a un SAF no identificado, ameritando manejo en terapia intensiva y la consulta por el experto mundial Dr. Ricard Cervera, quien confirmó el diagnóstico y recomendó tratar como tal. La evolución del paciente fue satisfactoria hasta el momento. Se hacen recomendaciones finales de diagnóstico y se comentan las opciones de tratamiento actuales, como rituximab o eculizumab. El presente caso fue agregado al registro internacional de SAF catastrófico (International CAPS Registry), que actualmente alberga alrededor de 500 casos en todo el mundo.

Therapeutic plasma exchange in rheumatic diseases: a university hospital experience.

INTRODUCTION: Each day, evidence accumulates related to the use of therapeutic plasma exchange (TPE) in patients with rheumatic diseases. San Ignacio University Hospital has recorded all of the TPE sessions performed by the institution's apheresis group. OBJECTIVE: To describe the TPE experience of patients with rheumatologic diseases in a hospital setting. METHODS: Descriptive, observational, retrospective analysis. This study included analyses of the TPE sessions that were performed in patients with rheumatic diseases from November 2009 to November 2013. RESULTS: The apheresis group performed 136 sessions in 27 patients. The mean patient age was 43 years (SD 18.5), and 59.3% of the patients were female. Regarding the diagnosis, the most frequents ones where: ANCA-associated vasculitis followed by systemic lupus erythematosus and catastrophic antiphospholipid syndrome. The average number of sessions per patient was 5 (SD 1.8), and the average plasma exchange per patient was 1.3 plasma volume replacement units. The most used replacement solution was frozen fresh plasma (FFP; 63.2% of the sessions). Of all the sessions, 4.4% presented complications, and the majority of the complications were related to vascular access. Fifteen patients required renal replacement therapy (RRT) secondary to the same cause that created the need for TPE, 3 patients required RRT due to causes other than the TPE diagnostic intervention and 1 patient had undergone chronic dialysis. CONCLUSIONS: TPE is a therapeutic alternative that is needed for the management of patients with rheumatic diseases with renal involvement and those who are refractory to conventional management. Our clinical results were in agreement with the global literature.

Therapeutic plasma exchange in rheumatic diseases: a university hospital experience / Troca plasmática terapêutica em doenças reumáticas: a experiência de um hospital universitário

Abstract Introduction: Each day, evidence accumulates related to the use of therapeutic plasma exchange (TPE) in patients with rheumatic diseases. San Ignacio University Hospital has recorded all of the TPE sessions performed by the institution's apheresis group. Objective: To describe the TPE experience of patients with rheumatologic diseases in a hospital setting. Methods: Descriptive, observational, retrospective analysis. This study included analyses of the TPE sessions that were performed in patients with rheumatic diseases from November 2009 to November 2013. Results: The apheresis group performed 136 sessions in 27 patients. The mean patient age was 43 years (SD 18.5), and 59.3% of the patients were female. Regarding the diagnosis, the most frequents ones where: ANCA-associated vasculitis followed by systemic lupus erythematosus and catastrophic antiphospholipid syndrome. The average number of sessions per patient was 5 (SD 1.8), and the average plasma exchange per patient was 1.3 plasma volume replacement units. The most used replacement solution was frozen fresh plasma (FFP; 63.2% of the sessions). Of all the sessions, 4.4% presented complications, and the majority of the complications were related to vascular access. Fifteen patients required renal replacement therapy (RRT) secondary to the same cause that created the need for TPE, 3 patients required RRT due to causes other than the TPE diagnostic intervention and 1 patient had undergone chronic dialysis. Conclusions: TPE is a therapeutic alternative that is needed for the management of patients with rheumatic diseases with renal involvement and those who are refractory to conventional management. Our clinical results were in agreement with the global literature.

Resumo Introdução: Diariamente acumulam-se evidências relacionadas com o uso da troca plasmática terapêutica (TPT) em pacientes com doenças reumáticas. O Hospital Universitário San Ignacio registrou todas as sessões de TPT feitas pelo grupo de aférese dessa instituição. Objetivo: Descrever a experiência do Hospital Universitário San Ignacio na TPT em pacientes com doenças reumatológicas. Métodos: Análise observacional, retrospectiva, descritiva. Incluiu análises das sessões de TPT feitas em pacientes com doenças reumáticas de novembro de 2009 a novembro de 2013. Resultados: O grupo de aférese fez 136 sessões em 27 pacientes. A idade média foi de 43 anos (DP 18,5) e 59,3% eram do sexo feminino. Quanto ao diagnóstico, os mais frequentes foram: vasculite associada ao anticorpo anticitoplasma de neutrófilos (ANCA) seguida de lúpus eritematoso sistêmico e síndrome antifosfolipídica catastrófica. A quantidade média de sessões por paciente foi de cinco (DP 1,8) e a média de troca plasmática por paciente foi de 1,3 unidade de substituição do volume de plasma. A solução de substituição mais usada foi o plasma fresco congelado (PFC, 63,2% das sessões). De todas as sessões, 4,4% apresentaram complicações, a maioria delas relacionadas com o acesso vascular. Quinze pacientes necessitaram de terapia de substituição renal (TSR) secundária à mesma causa que levou à necessidade de TPT; três pacientes necessitaram de TSR em decorrência de outras causas além da intervenção diagnóstica de TPT e um paciente tinha sido submetido à diálise crônica. Conclusões: A TPT é uma opção terapêutica necessária para o manejo de pacientes com doenças reumáticas com envolvimento renal e daqueles que são refratários ao tratamento convencional. Os resultados clínicos do presente estudo estão de acordo com o que é encontrado na literatura global.

Catastrophic antiphospholipid syndrome: A case with unusual findings revealed in autopsy and a brief literature update.

Catastrophic antiphospholipid syndrome (CAPS) is a rare and life-threatening disease. It is characterized by multiple arterial and/or venous thrombotic events, including the microcirculation, occurring in a short period, and can affect any system. Catastrophic antiphospholipid syndrome can occur in individuals with known APS under treatment, or it can be its first manifestation; in most cases, there is a triggering factor that can be identified. In this case report, we report a case of CAPS with multiple thromboses at unusual sites, including the lungs, coronary arteries, stomach, thyroid, gastrocnemius muscles, lymph nodes, and bladder, in a patient with previous diagnosis of systemic lupus erythematosus.

Síndrome antifosfolípido catastrófico / Catastrophic antiphospholipid syndrome

El síndrome antifosfolípido está definido por la combinación de manifestaciones clínicas trombóticas y/u obstétricas y un título persistentemente alto y significativo de anticuerpos antifosfolípidos. La presencia de múltiples trombos en lechos vasculares pequeños que lleva a falla multiorgánica, simultáneamente o en menos de 1 semana, define al síndrome antifosfolípido catastrófico el cual conlleva alta mortalidad; sin embargo, la sospecha diagnóstica y la institución temprana del tratamiento, definitivamente inciden en el pronóstico de éstos pacientes(AU)

Antiphospholipid syndrome is defined by the combination of thrombotic and/or obstetric clinical manifestations and a persistently high and significant title of antiphospholipid antibodies. The presence of multiple thrombi in small vascular beds leading to multi-organ failure that occurs simultaneously or in less than 1 week, and defines the catastrophic antiphospholipid syndrome which carries high mortality, The suspected diagnosis and early treatment affects the prognosis of these patients(AU)

Síndrome antifosfolípido catastrófico: caso clínico / Catastrophic antiphospholipid syndrome: clinical case

El síndrome antifosfolípido (SAF) fue descrito y caracterizado durante la segunda mi-tad del siglo XX inicialmente como un fenómeno protrombótico secundario en con-texto de otras enfermedades del tejido conectivo, principalmente lupus. Sin embargo, el estudio de pacientes con enfermedad primaria impulsó a distintos consensos, tan-to clínicos como de laboratorio para su correcta identificación. Entre los pacientes con SAF destaca la forma de presentación catastrófica, de baja prevalencia, pero impor-tante por su mal pronóstico, caracterizada por el compromiso de múltiples sistemas en corto tiempo. Presentamos el caso de una paciente del Hospital Clínico San Borja-Arriarán con diag-nóstico de SAF primario, que presentó en su evolución la forma catastrófica. Este caso sirve de base para una revisión del proceso diagnóstico del SAF en relación a otras patologías reumatológicas y las características propias del SAF catastrófico.

Antiphospholipid syndrome (APS) was described and characterized during the second half of the 20th century initially as a secondary prothrombotic phenome-non in the context of other connective tissue diseases, mainly lupus. However, the study of patients with primary disease prompted different consensus, both clin-ical and laboratory for their correct identification. Among patients with APS, the catastrophic presentation is of low prevalence, but important because of its poor prognosis, characterized by the commitment of multiple systems in a short time. We present the case of a patient from the San Borja-Arriaran Clinic Hospital with di-agnosis of primary APS, which presented the catastrophic form in its evolution. This case serves as a basis for a review of the diagnostic process of APS in relation to other rheumatologic pathologies and the characteristics of catastrophic APS.

Antiphospholipid Antibodies: From General Concepts to Its Relation with Malignancies.

Antiphospholipid syndrome (APS) is an adquired autoimmune pro-thrombotic disease characterized by arterial and/or venous thrombosis and/or fetal losses associated with the persistent presence of antiphospholipid antibodies (aPL) detectable by solid phase assays (anticardiolipin (aCL) and anti-ß2 glycoprotein I, ß2GPI) and/or functional coagulation test (lupus anticoagulant (LA)). Most patients with typical APS manifestations have the presence of one or more of conventional aPL, but, some patients might exhibit clinical features related with APS but with persistent negative determinations of "classic" aPL (seronegative APS). Expanding the network of autoantibodies in patients highly suspected of having APS but who have normal results from a conventional test using new antibodies (i.e., phosphatidylserine/prothrombin and ß2GPI domain 1) would increase the diagnosis. Thrombosis is one of the leading causes of death among patients with cancer, representing up to 15% of all deaths. Cancer increases the risk of thrombosis and chemotherapy is further associated with a higher risk of thrombosis. In addition, aPL may contribute to an increased risk of thrombosis in patients with malignancies, although the levels do not seem to reflect their pathogenicity. Several malignancies, particularly hematological and lymphoproliferative malignancies, may indeed be associated with the generation of aPL but do not necessarily enhance the thrombophilic risk in these patients.

Hyperferritinemic syndrome: Still's disease and catastrophic antiphospholipid syndrome triggered by fulminant Chikungunya infection: a case report of two patients.

There are four medical conditions characterized by high levels of ferritin, the macrophage activation syndrome (MAS), adult onset Still' s disease (AOSD), catastrophic antiphospholipid syndrome (CAPS), and septic shock, that share similar clinical and laboratory features, suggesting a common pathogenic mechanism. This common syndrome entity is termed "the hyperferritinemic syndrome." Here, we describe two different cases of hyperferritinemic syndrome triggered by Chikungunya fever virus infection: a 21-year-old female with SLE and a 32-year-old male patient who developed AOSD after the coinfection of dengue and Chikungunya viruses.

The role of infectious diseases in the catastrophic antiphospholipid syndrome.

Catastrophic antiphospholipid syndrome (CAPS), also called "Asherson syndrome", is a variant of the antiphospholipid syndrome (APS) that occurs in less than 1% of APS cases. The etiology of CAPS is uncertain; however, several triggering factors have been recognized. The most common of these are infectious diseases, particularly those of the respiratory tract. CAPS pathogenesis is incompletely understood, but several theories have been proposed, such as the molecular mimicry theory, which describes the production of anti-ß2-glycoprotein I (GP1) antibody in response to infection. The process is complex and involves the activation of Toll-like receptor 4 (TLR-4), which triggers a cytokine storm, followed by endothelial alterations that induce a procoagulant state.