Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review

Abstract Background Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. Method A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. Results Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. Conclusion Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Hemorragia pulmonar en enfermedades del tejido conectivo y comparación con lo descripto en la literatura / Pulmonary hemorrhage in connective tissue diseases and comparison with previous literature reports

Introducción: La hemorragia pulmonar difusa se caracteriza clínicamente por la presencia de disnea y hemoptisis, infiltrados alveolares bilaterales y difusos en la Rx de tórax y caída brusca de los valores de hemoglobina. Esta hemorragia puede ocurrir en el contexto de una enfermedad autoinmune (poliangeítis microscópica, enfermedad de Wegener, LES, síndrome de Goodpasture), síndrome antifosfolípidos, enfermedades infecciosas (leptospirosis y neumonía necrotizante), uremia, insuficiencia cardíaca congestiva, infarto pulmonar, desórdenes de la coagulación y secundaria a drogas (penicilamina). Dada su alta mortalidad y la escasez de síntomas (mucho mayor en pacientes inmunocomprometidos) es necesario un alto índice de sospecha y un rápido tratamiento. Objetivo: Comparar las manifestaciones clínicas, radiológicas y de laboratorio de los pacientes con hemorragia de pulmón con otras series publicadas. Material y métodos: Estudio retrospectivo y descriptivo, realizado revisando las historias clínicas de los pacientes con diagnóstico de hemorragia de pulmón secundaria a enfermedades autoinmunes. Criterios de inclusión (adaptados de Barile y cols.): caída en la hemoglobina de por lo menos 1,5 g/dl o anemia (Hb menor o igual a 11 g/dl), ambas relacionadas al evento; insuficiencia respiratoria de comienzo agudo; hemoptisis; infiltrados en ¾ de los campos pulmonares; hipoxemia y lavado bronquioloalveolar con al menos 20% de macrófagos con hemosiderina o sangre por tubo endotraqueal. Criterios de exclusión: infecciones, tromboembolismo de pulmón, falta de confirmación por lavado bronquioloalveolar o tubo endotraqueal. Resultados: 19 pacientes con hemorragia de pulmón. 5 de ellos excluidos por la presencia de tromboembolismo de pulmón en uno y ausencia de método confirmatorio de hemorragia de pulmón en 4...

Introduction: Pulmonary or diffuse alveolar hemorrhage is clinicallycharacterized by the presence of dypsnea and hemoptysis, bilateraland diffuse alveolar infiltrates on chest X-ray and sudden drop in bloodhemoglobin. This hemorrhage may occur in the setting of autoimmunediseases (microscopic polyarteritis, Wegener’s disease, systemic lupuserythematosus, Goodpasture syndrome), antiphospholipid syndrome,infectious diseases (such as leptospirosis and necrotizing pneumonia),uremia, congestive heart failure, pulmonary infarction, coagulation disordersand hemorrhages secondary to drugs (such as penicilamina).Due to its high mortality and the paucity of symptoms (mostly in theinmunocompromise patients), it is necessary a high index of suspiciousto promptly treat...(AU)Objective: To compare the clinical, radiological and lab tests findings ofthe patients selected with the published series.Material and Method: A retrospective and descriptive analysis wasperformed on the records of all patients with a diagnosis of pulmonaryhemorrhage secondary to autoimmune diseases. Inclusion criteria(adapted of Barile et al): Fall in hemoglobin of at least 1.5 g/dl or anemia(hemoglobin 11 g/dl or less), both related to the event, respiratoryfailure of rapid onset, hemoptysis, dense infiltrates in ¾ or more of thelung fields, hypoxemia and bronchoalveolar lavage, with at least 20% ofmacrophages with hemosiderin inside or the presence of blood in endotrachealtube. Exclusion criteria: Pulmonary infections, tromboembolismdisease, lack of confirmation by method of pulmonary haemorrhage...

Asociación de lupus eritematoso sistémico y esclerosis múltiple: esclerosis lupoide. Descripción de cuatro casos / Asociation between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis

La esclerosis múltiple (EM) y el lupus eritematoso sistémico (LES) con o sin síndrome antifosfolípido son enfermedades autoinmunes. Se ha descrito en varias ocasiones la asociación de estas enfermedades o se ha descrito el cuadro clínico de la EM con características de laboratorio de LES. Cuando afectan al sistema nervioso central pueden hacerlo en forma definida para cada enfermedad pero también pueden hacerlo en forma interpuesta o combinada de las dos enfermedades, a lo que se le ha llamado esclerosis lupoide, haciendo que en algunos casos sea difícil la diferenciación de las dos enfermedades y por lo tanto direccionar el tratamiento. Presentamos cuatro casos de esclerosis lupoide, discutimos acerca de las características clínicas y de laboratorio de esta entidad y hacemos una diferenciación de la esclerosis múltiple y de la afectación neurológica del LES, especialmente por imágenes y resultados de laboratorio.

Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoinmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.

Manifestaciones clínicas tempranas de LES / Early clinical manifestations of SLE

El estudio de formas tempranas de presentación del lupus eritematoso sistémico (LES) permite optimizar su diagnóstico y tratamiento. Se revisaron las historias clínicas de pacientes con edad ≥12 años que cumplían con ≥4criterios del Colegio Americano de Reumatología (ACR). El término “presentación temprana del LES” se asignó al primer año de evolución de la enfermedad, comenzando con la fecha cuando el(los) primer(os) criterio(os) fue(ron) reportado(s) en la historia clínica. Los pacientes fueron agrupados si satisfacían cualquier combinación de ≥4, 2-3 ó 1 criterio(s) para la clasificación del LES a través del primer año de la enfermedad. El impacto sobre el diagnóstico temprano del LES fue estimado de acuerdo a la actitud del médico de atención primaria para descartar tempranamente la enfermedad. 115 pacientes fueron admitidos al estudio. Al final del primer año de evolución de la enfermedad, 68 (59,13%) reunieron <4 criterios vs. 47 (40,86%) que reunieron ≥4 criterios del CAR (p=0,05). Los pacientes que reunieron <4 criterios alcanzaron el mínimo número de criterios para LES (≥4) dentro de los siguientes 10 años (promedio 4,9 años). De los 68 pacientes que alcanzaron <4 criterios, 31 (45,58%) reunieron dos o tres criterios y 37 (54,41%) tan sólo un criterio (p=0,46). El más frecuente de los criterios solitarios fue el síndrome inflamatorio poliarticular, 26 (70,20%) comparado con un conjunto de manifestaciones cutáneas, hematológicas, neurológicas, cardiopulmonares, renales y falso VDRL positivo, 11 (29,72%) (p=0,01). Los pacientes con un número insuficiente de criterios para LES son más frecuentes que aquellos con ≥4 criterios positivos al final del primer año de presentación de la enfermedad. La manifestación de un solo criterio (comparado con los que tenían ≥2) se asoció con un retardo en el diagnóstico temprano del LES de por lo menos 1 año

The study of early systemic lupus erythematosus (SLE) presentation can optimize its diagnosis and treatment. The clinical charts of those patients ≥12 years old complied with ≥ 4 criteria for SLE of the American College of Rheumatology (ACR) were reviewed. The term “early presentation of SLE” corresponded to the first year of evolution of the disease, starting with the date when the first(s) criterion/criteria were reported in the chart. The patients were grouped if they complied with a combination of ≥4, 2-3 or 1 ACR criteria for the classification of SLE through the first year of disease. The impact over the early diagnosis of SLE was estimated according to the early performance of the primary care doctor in ruling out the disease. 115 patients were included. At the end of the first year, 68 patients (59.13%) met <4 ACR criteria vs. 47 (40.86%) who met ≥4 (p=0.05). Patients who met <4 criteria fulfilled ≥4 criteria within the next 10 years (mean= 4.9 years). Of the 68 cases with <4 ACR criteria, 31 (45.58%) met two or three criteria and 37 (54.41%) met one solitary criterion (p=0.46). The most frequent early single onset ACR criterion for SLE was the polyarticular inflammatory syndrome, 26 (70.20%) followed by a group of other single criterion that included cutaneous, hematologic, neurologic, cardiopulmonary, renal, and false-positive VDRL, 11 cases (29.72%) (p=0.01). An early solitary criterion-compared with those patients with ≥2- was associated with a lack of documentation in the medical chart- of constitutional symptoms, indication of serum antibodies and referral to specialist. Patients with an insufficient quota of ACR criteria for SLE exceeded those with ≥4 positive criteria at the end of the first year of the disease. Patients with a single criterion of presentation compared with those patients who started with ≥2 early criteria-were associated with a delay in the early diagnosis of SLE by at least one year

Avaliação do comprometimento ósseo no lúpus eritematoso sistêmico / Bone tissue evaluation on sistemic erythematosus lupus patients

Objetivos: O objetivo primário deste estudo é determinar o impacto do LES sobre a densidade mineral óssea. Os objetivos secundários foram: correlacionar a densidade mineral óssea com a duração da doença, o número de órgãos envolvidos,uso de corticosteróides e de imunos supressores e um índice de atividade lúpica.Métodos: Foram estudados 40 prontuários de pacientes que são acompanhados no ambulatório Conjunto Hospitalar deSorocaba (CHS). Os seguintes dados foram analisados: duração da doença, sistemas acometidos, uso de corticóides e/ouimunos supressores, exames laboratoriais, densitometria ósseae SLEDAI.Resultados: Foram analisadas as correlações entre o número de desvios padrão que a densidade óssea das pacientes estudadas se afastava das médias esperadas para a idade (zescore)e as seguintes variáveis: número de órgãos/sistemas envolvidos, duração de doença, uso crônico de corticosteróides,uso de imunossupressores e índice de atividade de doença(SLEDAI). Não se observou correlação estatística em nenhuma das análises realizadas. A correlação que mais se aproximou da significância estatística foi entre o z-escore e o uso crônico de corticóides.Conclusão: Conclui-se, portanto, que houve impacto significativo do lúpus eritematoso sistêmico ou sua terapêutica na densidade óssea dos pacientes estudados. Entre os fatores que podem ter contribuído para esse impacto é a monitorização da densidade óssea e a intervenção precoce quando necessário.(AU)

Objective: The primary objective of this study is to determine the impact of LES on bone mineral density. The secondary objectives were to correlate bone mineral density with duration of the disease, number of involved organs, use of corticosteroids and immuno suppressive agents and an lupusactivity index. Methods: Forty charts of patients who are followed at the Conjunto Hospitalar de Sorocaba (CHS) were reviewed. The following data were analyzed: duration of the disease, and systems ill, use of corticosteroids and / or immuno suppressants agents, laboratory tests, bone densitometry and SLEDAI. Results: The correlations between the number of standard deviations between patients bone mineral density and a control population for the same age group (z-score) and the following variables: number of involved systems, duration of illness, chronic use of corticosteroids or immuno suppressive agents and activity of disease (SLEDAI). There was no statistical correlation in any of the analyses. The correlation that most approached the statistical significance was between the z-scores and chronic use of steroids.(AU)

Hemorragia alveolar secundaria a lupus eritematoso generalizado, tratada con factor VII recombinante activado: reporte de un caso y revisión de la literatura / Alveolar hemorrhage secondary to generalized systemic lupus erithematosus treated with recombinant activated factor VII: case report and literature review

La hemorragia alveolar es una complicación grave del lupus eritematoso generalizado (LEG), asociada a una elevada mortalidad. El tratamiento de esta complicación se apoya en el uso de corticoesteroides, ciclofosfamida; en algunas series, se recomienda el uso de metrotexate, azatioprina y plasmaféresis. En la literatura se encuentra un solo caso informado en el cual se informa el empleo del factor VII recombinante activado (FVIIra) como opción terapéutica para la hemorragia secundaria a alveolitos, refractaria al tratamiento habitual. Presentamos el caso de una paciente que desarrolló hemorragia alveolar grave con diagnóstico previo de LEG y que se manejó con FVIIra.

Alveolar hemorrhage is a severe complication of systemic lupus erithematosus (SLe) associated with high mortality. Treatment includes administration of steroids and cyclophosphamide. Additionally, some reports have recommended the use of plasmapheresis, azathioprine and methotrexate. There is a single case reported in the literature in which recombinant activatedfactor VII (rFVIIa) was used to control severe hemorrhage secondary to alveolitis unresponsive to standard treatment. We report the case of a patient with SLE who developed severe alveolar hemorrhage unresponsive to standard measures, but who was successfully treated with rFVIIa.

A Case of Chronic Inflammatory Demyelinating Polyneuropathy in Lupas Nephritis / 대한신장학회잡지

Systemic lupus erythematosus(SLE) is a multisys-temic disease. Peripheral neuropathy occurs in about 10% of patients with SLE. Chronic inflammatory demyelinating polyneurpathy has been reported rarely in SLE. We experienced a case of chronic inflammatory polyneuropathy in lupus nephritis. 32-year-old housewife presented to chronic progressive muscle weakness and heavy proteinuria. Kidney biopsy showed compatible with lupus nephritis (WHO Class V, membranous nephropathy). Nerve conduction studies showed reduction in conduction velocity and sural nerve biopsy revealed demyeli-nating polyneuropathy. Steroid therapy led to improvement in clinical symptoms and proteinuria.