Carcinoma de pulmón como disparador de una respuesta autoinmune: un desafío médico / Lung cancer acting as a trigger of autoimmunity: a medical challenge

RESUMEN Existe una relación compleja, dinámica y bidireccional entre la autoinmunidad y el cáncer. Si bien los mecanismos carcinogénicos y fisiopatológicos de las enfermedades autoinmunes no están claramente dilucidados, existe una base inmunológica común relacionada con la expresión de autoantígenos por parte de las células tumorales que desencadenan una respuesta antitumoral, facilitando el desarrollo de síndromes paraneoplásicos reumáticos y enfermedades autoinmunes reumáticas en población genéticamente susceptible. Se presenta un caso de un hombre que debutó con un síndrome pulmón riñón y se diagnosticó cáncer de pulmón y lupus eritematoso sistémico de forma simultánea.

A B S T R A C T There is a complex, dynamic, and bidirectional connection between autoimmunity and cancer. The underlying mechanisms of carcinogenesis and physiopathological aspects of autoimmune diseases are not fully understood. However, there is a common immunological base related to expression of autoantigens by tumour cells that cause an anti-cancer immune response, thereby, triggering the development of paraneoplastic rheumatic syndromes and autoimmune rheumatic diseases in a genetically predisposed population. The case is reported of a 57 year-old man presenting with pulmonary renal syndrome, and who was diagnosed lung cancer and systemic lupus erythematosus at the same time.

Síndrome pulmón-riñón: serie de 12 casos / Pulmonary renal syndrome: series of 12 cases

El síndrome pulmón-riñón es una entidad infrecuente, que comprende un gran espectro de patologías, como las vasculitis asociadas a ANCA y la enfermedad por anticuerpos antimembrana basal glomerular entre otras. Se describen en esta serie 12 casos donde las entidades más prevalentes fueron las antes mencionadas, observándose además un caso de lupus y uno de granulomatosis con poliangeítis, que se encuentran dentro de las causas menos frecuentes. La forma de presentación clínica inicial fue simultánea renal y pulmonar en 5/12 pacientes y renal en 7/12 de los mismos. El diagnóstico temprano de dichas patologías basándose en criterios clínicos, radiológicos, de laboratorio e histológicos, permite instaurar terapéuticas tempranas como la inmunosupresión y plasmaféresis, pudiendo prevenir complicaciones tales como las infecciones y la insuficiencia renal crónica terminal, siendo las primeras la principal causa de muerte (AU)

Pulmonary-renal syndrome is an infrequent condition. It includes a wide variety of conditions such as ANCA (antineutro-phil cytoplasmic autoantibody) associated with systemic vasculitis and anti-GBM (anti-glomerular basement membrane) disease among others. In this series we describe twelve cases, in which the most prevalent diseases were the above mentioned as well as one case of lupus and one of granulomatosis with polyangiitis (these being less frequent causes). The clinical presentation was both renal and pulmonary simultaneously in five of twelve patients and renal in seven of twelve patients. Early diagnosis of this condition on the basis of clinical, radiological, histological and analytic criteria allows early treatments such as immunosuppression and plasma exchange, thus avoiding complications such as infections (the main cause of death) and terminal chronic renal failure (AU)

A Pediatric Case of a D-Penicillamine Induced ANCA-associated Vasculitis Manifesting a Pulmonary-Renal Syndrome

D-penicillamine has been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting as rapidly progressive glomerulonephritis or pulmonary-renal syndrome mostly in adults. We report a pediatric case of D-penicillamine induced ANCA-associated vasculitis that manifests as a pulmonary-renal syndrome with a mild renal manifestation. A 13-year-old girl who has been taking D-penicillamine for five years under the diagnosis of Wilson disease visited the emergency room because of hemoptysis and dyspnea. She had diffuse pulmonary hemorrhage, microscopic hematuria, and proteinuria. Myeloperoxidase ANCA was positive, and a renal biopsy revealed pauci-immune crescentic glomerulonephritis. Under the diagnosis of D-penicillamine-induced ANCA-associated vasculitis, D-penicillamine was switched to trientine, and the patient was treated with plasmapheresis, glucocorticoid, cyclophosphamide, and mycophenolate mofetil. Pulmonary hemorrhage improved rapidly followed by the disappearance of the hematuria and proteinuria five months later.

Síndrome pulmón riñón, reporte de caso y revisión de la literatura / Pulmonary-renal syndrome, case report and literature review / Síndrome Pulmão-Rim, relato de um caso e revisão da literatura

Resumen: El complejo del síndrome pulmón riñón (SPR) se define como la combinación de hemorragia alveolar difusa acompañada de glomerulonefritis rápidamente progresiva, dentro del protocolo de diagnóstico se requieren niveles de anticuerpos anticitoplasma de neutrófilos (ANCA), broncoscopia, tomografía de tórax y estudio de sedimento urinario, es más común que se manifieste en el sexo masculino entre la edad de 40 y 55 años, siendo infrecuente en población joven. Se han descrito tres formas principales, la granulomatosis con poliangeítis, síndrome de Churg Strauss y síndrome de Goodpasture (SGP). En cualquiera de sus presentaciones se asocia a una elevada tasa de mortalidad que requiere manejo multidisciplinario con soporte ventilatorio, sustitución de la función renal, manejo específico con esteroide sistémico y terapia inmunosupresora. La introducción de la ciclofosfamida en combinación con esteroides anunció una alternativa en el tratamiento de las vasculitis observando disminución en la mortalidad en comparación con los glucocorticoides como monoterapia. El objetivo de este artículo es presentar el caso de un paciente con SPR y revisar la patogénesis, el abordaje diagnóstico y tratamiento, haciendo énfasis en la importancia del manejo multidisciplinario en la unidad de cuidados intensivos.

Abstract: The complex syndrome lung-kidney or pulmonary renal syndrome (PRS) is defined as the combination of diffuse alveolar hemorrhage accompanied by rapidly progressive glomerulonephritis, within the diagnostic protocol levels of anti-cytoplasm (ANCA), bronchoscopy, chest tomography and study required urinary sediment, occurs more commonly in males between 40 and 55 years, being rare in young people, described three main forms granulomatosis with polyangiitis, Churg Strauss syndrome Goodpasture (SGP), in any of its presentations is associated with a high mortality rate requiring multidisciplinary management with ventilatory support, replacement of renal function, specific management with systemic steroid and immunosuppressive therapy. The introduction of cyclophosphamide in combination with steroids announced an alternative in the treatment of vasculitis finding decrease mortality compared with glucocorticoids as monotherapy. The aim of this paper is to present the case of a patient with PSR, review the pathogenesis, diagnosis and treatment approach, emphasizing the importance of multidisciplinary management in the Intensive Care Unit.

Resumo: A complexa síndrome do Pulmão-Rim (SPR) é definida como a combinação de hemorragia alveolar difusa e glomerulonefrite rapidamente progressiva, dentro do protocolo de diagnóstico é necessário níveis de anticorpos anti citoplasmáticos de neutrófilos (ANCA), broncoscopia, tomografia torácica e estudo do sedimento urinário. A síndrome é mais frequente em homens entre 40 e 55 anos, sendo raro na população jovem. Descreveu-se três formas principais: Granulomatose com Poliangeíte, Síndrome de Churg Strauss e síndrome de Good-Pasture (SGP), em qualquer das suas apresentações é associada com uma alta taxa de mortalidade, requerendo uma abordagem multidisciplinar com suporte respiratório, substituição da função renal, tratamento específico com esteróide sistêmico e terapia imunossupressora. A introdução da ciclofosfamida combinada com esteróides é uma alternativa no tratamento da vasculite, diminuindo a mortalidade, em comparação aos glucocorticóides como monoterapia. O objetivo deste artigo é apresentar o caso de um paciente com SPR, revisar a patogênese, a abordagem diagnóstica e o tratamento, enfatizando a importância do tratamento multidisciplinar na unidade de terapia intensiva.

Crioglobulinemia esencial como causa de síndrome pulmón-riñón / Essential cryoglobulinemia as cause of lungkidney synd

Resumen La crioglobulinemia es una entidad poco frecuente y hace parte de los diagnósticos diferenciales delsíndrome pulmón-riñón; a continuación se presenta el caso de una paciente quien ingresa por lesiones petequiales, artralgias y úlcera en miembro inferior derecho; posteriormente cursando con deterioro dela función renal y luego falla respiratoria secundaria a hemorragia alveolar diagnósticada por imágenesy lavado broncoalveolar manejada con plasmaféresis presentando mejoría clínica, descartando etiologíaautoinmune, infecciosa y neoplásica como causa del cuadro actual, documentando únicamente la presencia de crioglobulinemia esencial. (Acta Med Colomb 2014; 39: 72-76).

Abstract Cryoglobulinemia is a rare entity and is part of the differential diagnosis of pulmonary-renal syndrome. This study reports the case of a patient admitted by petechial lesions, arthralgias and ulcer on the right lower limb, subsequently associated with impaired renal function and later respiratory failure secondary to alveolar hemorrhage, diagnosed by images and bronchoalveolar lavage and managed with plasmapheresis, presenting clinical improvement, discarding autoimmune, infectious and neoplastic etiology as the cause of the current clinical picture, documenting only the presence of essential cryoglobulinemia. (Acta Med Colomb 2014; 39: 72-76).

Approach to the patient with pulmonary-renal syndrome caused by antithyroid drug-induced ANCA-associated vasculitis / 中华内分泌代谢杂志

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) refers to the groups of potentially life-threatening autoimmune disease.Antithyroid drug is one of the causes.Usually the involved organs are skin,kidney,and (or) lung.Early diagnosis and treatment of AAV is essential.Timely cessation of antithyroid drugs is the first step.If necessary,glucocorticoids and (or) immunosuppressive agents should be used to delay the progression of the disease.

Pulmonary renal syndrome in a case of wegener´s granulomatosis.

We report a case of a 42-year-old patient who presented with Wegener’s granulomatosis complicated by pulmonary renal syndrome, i.e., diffuse alveolar haemorrhage and rapidly progressive crescentic glomerulonephritis. The patient was treated with plasmapheresis and immunosuppressive drugs — intravenous cyclophosphamide and methyl prednisolone. The clinical, haematological and biochemical parameters improved substantially and remission is achieved.

Malignant Hypertension with an Unusual Presentation Mimicking the Immune Mediated Pulmonary Renal Syndrome

A 27-year-old man presented at the emergency room with hemoptysis. His blood pressure was 180/100 mm Hg, and he had no history of hypertension. Chest radiographs showed bilateral infiltration, suggestive of alveolar hemorrhage. His laboratory data were consistent with acute kidney injury. His serum creatinine level increased abruptly; therefore, renal biopsy was performed. Steroid pulse therapy was administered because of a strong suspicion of immune-mediated pulmonary renal syndrome. Renal biopsy showed proliferative endarteritis, fibrinoid necrosis, and intraluminal thrombi in the vessels without crescent formation or necrotizing lesions. Steroid pulse therapy rapidly tapered and stopped. His serum creatinine level gradually decreased with strict blood pressure control. Ten months after discharge, his blood pressure was approximately 120/80 mm Hg with a serum creatinine level of 1.98 mg/dL. Pulmonary renal syndrome is generally caused by an immune-mediated mechanism. However, malignant hypertension accompanying renal insufficiency and heart dysfunction causing end-organ damage can create a pulmonary hemorrhage, similar to pulmonary renal syndrome caused by an immune-mediated mechanism. The present case shows that hypertension, a common disease, can possibly cause pulmonary renal syndrome, a rare condition.

Síndrome pulmón-riñón / Pulmonary-renal syndrome

El síndrome pulmón-riñón se define como una combinación de hemorragia alveolar difusa y glomerulonefritis. La coexistencia de estas dos afecciones clínicas se produce por enfermedades con distintos mecanismos patogénicos. Las vasculitis sistémicas primarias y el síndrome de Goodpasture son las etiologías más frecuentes. El lupus eritematoso sistémico, otras colagenopatías, las vasculitis con anticuerpos anticitoplasma de los neutrófilos negativos y las secundarias a drogas son causas mucho menos comunes. El diagnóstico temprano basado en criterios clínicos, radiológicos, de laboratorio e histológicos, permite iniciar el tratamiento disminuyendo su elevada morbi-mortalidad. La terapéutica se basa en altas dosis de corticoides, inmunosupresores, inhibidores del factor de necrosis tumoral y plasmaféresis.

The pulmonary-renal syndrome is defined as a combination of diffuse alveolar hemorrhage and glomerulonephritis. The coexistence of these two clinical conditions is due to diseases with different pathogenic mechanisms. Primary systemic vasculitis and Goodpasture syndrome are the most frequent etiologies. Systemic lupus erythematosus, connective tissue diseases, negative anti neutrophil cytoplasmic antibody vasculitis and those secondary to drugs are far less common causes. An early diagnosis based on clinical, radiologic, laboratory and histologic criteria enables early treatment, thus diminishing its high morbility-mortality rate. Therapy is based on high doses of corticosteroids, immunosuppressants, tumor necrosis factor inhibitors and plasmapheresis.

Concomitancia de anticuerpos antimembrana basal y ANCA en el síndrome riñón-pulmón / Concomitance of glomerular basement membrane antibodies and ANCA in pulmonary - renal syndrome

La enfermedad antimembrana basal glomerular (anti-MBG) es una condición que se manifiesta clínicamente como glomerulonefritis rápidamente progresiva y hemorragia alveolar, también llamada Síndrome Riñón- Pulmón. Se asocia a la presencia de autoanticuerpos dirigidos contra el colágeno tipo IV de la membrana basal glomerular. Las vasculitis sistémicas asociadas a ANCA también pueden manifestarse como Síndrome Riñón-Pulmón, cuadro clínico a veces indistinguible de la enfermedad anti-MBG. La concomitancia de ANCA y anticuerpos anti-MBG en el Síndrome Riñón-Pulmón es del orden de un 30 por ciento, según distintos reportes de la literatura. El perfil clínico, el pronóstico y el rol fisiopatológico de cada anticuerpo en este grupo de pacientes todavía son materia de investigación. El mecanismo patogénico inicial parece ser el daño mediado por ANCA, que puede inducir la aparición de anticuerpos anti-MBG, los que perpetúan el daño en el glomérulo.

Anti-glomerular basement membrane (anti-MBG) disease is a condition that is manifested clinically as rapidly progressive glomerulonephritis and alveolar hemorrhage, also known as Pulmonary-Renal Syndrome. It is associated with the presence of autoantibodies directed against type IV collagen of the glomerular basement membrane. Systemic vasculitis associated with ANCA may also manifest as Pulmonary-Renal Syndrome, sometimes clinically indistinguishable from the anti-MBG disease.The concomitance of ANCA and anti-MBG antibodies in the Pulmonary-Renal Syndrome is about 30 percent, according to various reports in literature. The clinical profile, prognosis and physiopathologic roles of each antibody in this group of patients is still under investigation. The pathogenic mechanism appears to be the initial damage mediated by ANCA, which may induce the appearance of anti-MBG, those who perpetuate the glomerulus damage.