Predictors of severe hemolytic anemia and its impact on major outcomes in systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

OBJECTIVE: To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. METHODS: Factors associated with time to severe AIHA (hemoglobin level ≤7 g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression. RESULTS: Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111 days (IQR 43-450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02-4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01-1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91-6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality. CONCLUSIONS: Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.

Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation.

OBJECTIVE: To assess the effect of tubulointerstitial inflammation (TII) and interstitial fibrosis and tubular atrophy (IFTA) on kidney survival in lupus nephritis (LN). METHODS: Two hundred eighty five patients with biopsy-proven LN were retrospectively studied. Kidney survival was defined as the time from initial biopsy to end-stage kidney disease (ESKD), dialysis, or transplant. Kidney survival analysis was performed by the Kaplan-Meier method and the statistical difference between survival curves compared by the log-rank test. Cumulative incidence functions with competing risk of death for kidney survival were also graphed. Multivariable Cox proportional hazards regression and competing-risk analyses were performed to identify independent predictors of ESKD. RESULTS: Fifty-seven patients (20%) progressed to ESKD during a median time of 4.2 (2.0-55.2) months after biopsy. TII was present in 206 (72.3%) biopsies, while IFTA in 99 (34.7%) biopsies. Patients with moderate-to-severe IFTA had worse kidney survival than those with none or mild IFTA in both the Kaplan-Meier (p = 0.018) and the competing-risk analyses (p = 0.017). Patients with class IV ± V LN had worse kidney survival than those with non-class IV LN by the Kaplan-Meier method (p = 0.050), but not in the competing-risk analysis (p = 0.154). Worse kidney survival was also found among those with fibrous crescents than those without, in both the Kaplan-Meier (p = 0.010) and the competing-risk (p = 0.011) analyses. By multivariable Cox regression analysis, older age (HR 1.04, 95% CI 1.01-1.07) and class IV ± V LN (HR 5.06, 95% CI 1.82-14.09) were associated with higher risk of ESKD after adjusting for sex, ethnicity, TII, and IFTA. By competing-risk analyses, class IV ± V LN (SHR 3.32, 95% CI 1.25-8.83) and no response to immunosuppressive therapy (SHR 4.55, 95% CI 1.54-13.41) were associated with a higher risk of ESKD, while eGFR >90 mL/min/1.73 m2 (SHR 0.98 for each ml/min/1.73 m2, 95% 0.97-0.99) with a lower risk. CONCLUSIONS: Patients with moderate-to-severe IFTA had worse kidney survival than those with none or mild IFTA. Worse kidney survival was also found among those with class IV LN and fibrous crescents versus those without IV LN and fibrous crescents, respectively.

Organ damage in systemic lupus erythematosus / Daño orgánico en lupus eritematoso sistémico

ABSTRACT Damage reflects the irreversible changes that occur in systemic lupus erythematosus (SLE) patients as a consequence of the disease, its treatment or comorbidities. The pattern of damage increases in a steady linear fashion over time. At least half of all patients with SLE will have some form of organ damage 10 years after their diagnosis. Factors associated with the occurrence of damage include older age, disease duration, male gender, non-Caucasian ethnicity, disease activity, corticosteroid use, poverty, hypertension and abnormal illness behaviors. In contrast, antimalarials are protective against damage. Since damage predicts further damage and mortality, prevention of damage accrual should be a major therapeutic goal in SLE. Novel therapies for SLE that achieve better control of the disease and with corticosteroid-sparing properties, may lead to improved outcomes in patients as they will reduce damage accrual and improve survival.

RESUMEN El daño refleja los cambios irreversibles que se producen en los pacientes con lupus eritematoso sistémico (LES) como consecuencia de la enfermedad, de su tratamiento o por causa de comorbilidades. El patrón de dano aumenta de forma lineal, constante a lo largo del tiempo. Al menos la mitad de todos los pacientes con LES presentará alguna forma de daño orgánico 10 años después de haber sido diagnosticados. Entre los factores asociados con el desarrollo de dano encontramos la edad avanzada, la duración de la enfermedad, el sexo masculino, la etnia no caucásica, la actividad de la enfermedad, el uso de corticoesteroides, la pobreza, la hipertensión y comportamientos anormales de la enfermedad; por otra parte, los antimaláricos protegen contra el dano de la enfermedad. Puesto que la presencia de daño es un predictor de danno adicional y de mortalidad, la prevención de acumulación de dano deberá ser un objetivo terapéutico fundamental en LES. Los tratamientos novedosos para el LES que logren un mejor control de la enfermedad y que tengan propiedades ahorradoras de corticoesteroides, podrían lograr mejores desenlaces en los pacientes, pues reducirían el daño acumulado y mejorarían la sobrevida.

Kidney transplantation outcomes in lupus nephritis: A 37-year single-center experience from Latin America.

OBJECTIVE: We assessed patient and graft outcomes and prognostic factors in kidney transplantation in patients with end-stage kidney disease (ESKD) secondary to lupus nephritis (LN) undergoing kidney transplantation from August 1977 to December 2014 in a Latin American single center. METHODS: The primary endpoint was patient survival, and the secondary endpoints were death-censored graft survival for the first renal transplant and the rate of recurrent LN (RLN). Kaplan-Meier method was used for survival analysis. Factors predicting patient and death-censored graft survivals were examined by Cox proportional-hazards regression analyses. RESULTS: 185 patients were retrospectively evaluated. Patient survival rates were 88% at one year, 82% at three years, 78% at five years, and 67% at ten years. Death-censored graft survival for the first renal transplant was 93% at one year, 89% at three years, 87% at five years, and 80% at ten years. RLN was diagnosed in 2 patients (1.08%), but no graft was lost because of RLN. Thirty-nine (21.1%) patients died, and 65 (35.1%) patients experienced graft loss during the follow-up. By multivariable analyses, older recipient age and 1-month posttransplantation eGFR <45 ml/min/1.73m2 were associated with lower patient survival and an increased risk of graft loss, while induction immunosuppressive therapy exerted a protective effect on patients' survival. In the subgroup of patients in whom disease activity was measured at the time of transplantation, a higher SLEDAI score was also associated with lower patient survival and an increased risk of graft loss. CONCLUSION: In a mostly Mestizo population, kidney transplantation is an excellent therapeutic alternative in LN patients with ESKD. Older recipient age, an eGFR <45 ml/min/1.73m2 at one month posttransplantation, and disease activity at the time of transplantation are predictive of a lower patient and death-censored graft survival, while induction immunosuppressive therapy has a protective effect on patient survival. RLN is rare and does not influence the risk of graft loss.

Understanding Risk Factors for Poor Outcomes in a Multiethnic Longitudinal Cohort: The LUMINA (Lupus in Minorities: Nature vs. Nurture) Experience (LUMINA LXXXII).

The Lupus in Minorities: Nature Vs Nurture (LUMINA) cohort has placed Hispanics on the lupus map in the United States. Texan Hispanic and African American patients experience, overall, worse outcomes than the Caucasian and Puerto Rican Hispanic patients. The genetic component of ethnicity is important early in the disease course whereas socioeconomic factors become more important subsequently. The role of hydroxychloroquine in preventing damage accrual and reducing mortality in lupus patients is a major contribution of LUMINA.

Novel clinical presentation of a CRX rod-cone dystrophy.

We describe a novel clinical presentation of a CRX rod-cone dystrophy in a single family. Two boys ages 6 and 12 years presented with clinical and optical coherence tomography features suggestive of X-linked retinoschisis, but with optic nerve swelling without increased intracranial pressure. One patient had an electronegative electroretinogram (ERG) and the other had rod-cone dysfunction. Neither had retinoschisin (RS1) gene mutations. Biological mother and sister presented with retinal pigment epithelium (RPE) changes and abnormal cone-rod ERG responses. On further testing, next generation sequencing with array comparative genomic hybridisation showed a deletion in exon 4 of the CRX gene. Cystoid maculopathy in young male children can be difficult to distinguish from RS1-associated schisis. Phenotypic variants within a family must prompt a thorough retinal dystrophy evaluation even with electronegative ERG in the presenting child. This novel phenotype for CRX presents with optic nerve swelling and cystoid maculopathy in men, and RPE changes in women.

Systemic lupus erythematosus: The search for the ideal biomarker.

During the last decades, there has been an increased interest in the discovery and validation of biomarkers that reliably reflect specific aspects of lupus. Although many biomarkers have been developed, few of them have been validated and used in clinical practice, but with unsatisfactory performances. Thus, there is still a need to rigorously validate many of these novel promising biomarkers in large-scale longitudinal studies and also identify better biomarkers not only for lupus diagnosis but also for monitoring and predicting upcoming flares and response to treatment. Besides serological biomarkers, urinary and cerebrospinal fluid biomarkers have emerged for assessing both renal and central nervous system involvement in systemic lupus erythematosus, respectively. Also, novel omics techniques help us to understand the molecular basis of the disease and also allow the identification of novel biomarkers which may be potentially useful for guiding new therapeutic targets.

Ergotism, a relatively unknown mimic of vasculitis: A case report and review of literature / Ergotismo: un imitador poco conocido de vasculitis. Reporte de caso y revisión de la literatura

ABSTRACT Introduction: Ergotism is a vasospasm that affects visceral and peripheral muscle arteries. Classically, symmetrical involvement of lower limb arteries is described, and is often associated with a history of chronic consumption of ergotamine derived medications (Cafergot). Case report: A 22 year-old healthy man with infectious mononucleosis syndrome, who presented with a sudden onset of paraesthesias in the lower limbs, as well as livedo reticularis. The initial diagnosis was a medium-sized vessel vasculitis (polyarteritis nodosa). The symptoms were preceded by the administration of Cafergot for headache treatment, and resolved spontaneously. The magnetic resonance angiography (MRA) of the lower limbs showed occlusion of peroneal arteries, with filiform distal flow. Other infectious, autoimmune and cardiovascular origins were ruled out. Discussion: Ergotism is an important differential diagnosis in the study of the patient with vasculitis, especially in acute onset presentations. Its treatment is the suspension of the causal drug, with vasodilator and surgical vascular procedures, if necessary. Conclusions: Ergotism is an imitator of vasculitis, especially in young patients with a history of difficult to control migraine. The concomitant administration of CYP3A4 inhibitors (mainly, protease inhibitors and macrolides) enhances the toxic effects of ergot.

RESUMEN Introducción: El ergotismo es un vasoespasmo que afecta las arterias musculares periféricas y viscerales. Clásicamente se describe la afectación simétrica de las arterias de las extremidades inferiores, a menudo asociada con el consumo crónico de medicamentos derivados de ergotamina (Cafergot®). Caso clínico: Varón sano de 22 anos con síndrome de mononucleosis, presentó parestesias en las extremidades inferiores y livedo reticularis de forma súbita, el diagnóstico inicial fue una vasculitis de mediano vaso (poliarteritis nodosa). Los síntomas fueron precedidos por la administración de Cafergot® para el tratamiento de cefalea, y se resolvieron espontáneamente. La angiografía por resonancia magnética (ARM) de las extremidades inferiores mostró oclusión de las arterias peroneas, con flujo distal filiforme. Se descartaron otras etiologías infecciosas, autoinmunes y cardiovasculares. Discusión: Los ergotismos son un diagnóstico diferencial importante en el estudio del paciente con vasculitis, especialmente en presentaciones de inicio agudo. Su tratamiento es la suspensión del fármaco causal, vasodilatadores y procedimientos vasculares quirúrgicos, si es necesario. Conclusiones: El ergotismo es un imitador de vasculitis, especialmente en pacientes jóvenes con antecedentes de migrana de difícil control. La administración concomitante de inhibidores del CYP3A4 (principalmente, inhibidores de proteasa y macrólidos) potencia los efectos tóxicos del ergot.

Factors affecting quality of life in patients with systemic lupus erythematosus: important considerations and potential interventions.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have a better survival than decades ago; nevertheless, they still experience a low health-related (HR) quality of life (QoL). Areas covered: After defining QoL and HRQoL, we review the need to assess it, its elements, how to measure it, its predictors, and its impact and potential interventions to improve it. Expert commentary: Physicians assessments of disease activity and damage do not capture the patients' perspective of their health, and these differences could lead to nonadherence to therapy. Based on that, a comprehensive evaluation of SLE should include the assessment of HRQoL or the sum of the physical, psychological, and social perception of wellbeing, influenced by the patient's illness. The most consistent predictors of low HRQoL are older age, poverty, lower educational level, behavioral issues, some clinical manifestations, and comorbidities. HRQoL impacts negatively on dealing with stress, intimal relationship, home and job-related activities, and treatment adherence. At the present, there are no successful specific therapeutic strategies aimed at improving it.

Pseudotumor cerebri syndrome in a pregnant woman with systemic lupus erythematous.

Systemic lupus erythematous is a chronic multi-systemic autoimmune disease that affects multiple organ systems, including the central nervous system. Pseudotumor cerebri is a disorder associated with increased intracranial pressure in the absence of a space-occupying lesion or other identifiable cause that affects young and obese women.We present the case of a pregnant woman with both pseudotumor cerebri and a new diagnosis of active systemic lupus erythematous.

Síndrome de seudotumor cerebral en una mujer embarazada y con lupus eritematoso sistémico / Pseudotumor cerebri syndrome in a pregnant woman with systemic lupus erythematous

Resumen El lupus eritematoso sistémico es una enfermedad autoinmunitaria crónica que afecta múltiples sistemas orgánicos, incluido el sistema nervioso central. El seudotumor cerebral es un síndrome clínico que se caracteriza por aumento de la presión intracraneal en ausencia de lesiones que ocupen espacio u otra causa detectable, que afecta con frecuencia a mujeres jóvenes y obesas. Se presenta el caso de una mujer con diagnóstico de seudotumor cerebral y lupus eritematoso sistémico diagnosticado de novo durante el embarazo.

Abstract Systemic lupus erythematous is a chronic multi-systemic autoimmune disease that affects multiple organ systems, including the central nervous system. Pseudotumor cerebri is a disorder associated with increased intracranial pressure in the absence of a space-occupying lesion or other identifiable cause that affects young and obese women. We present the case of a pregnant woman with both pseudotumor cerebri and a new diagnosis of active systemic lupus erythematous.

The evolving concept of SLE comorbidities.

INTRODUCTION: The survival of SLE patients has improved significantly over the past few decades placing them at increased risk of cardiovascular disease (CVD), malignancies, and osteoporosis, among other comorbidities. The aim of this review was to assess the incidence and prevalence of comorbidities in these patients as well as their prevention and treatment focusing in CVD, malignancies and osteoporosis. Areas covered: We focused on CVD, malignancies and osteoporosis as SLE comorbidities. A literature search (PubMed database) was performed using the words 'comorbidities', 'cardiovascular disease', 'osteoporosis', 'malignancy', 'cancer' and 'lupus' between January 1976 and December 2016. No language restrictions were placed. More than 100 full-length articles were reviewed. Expert commentary: The therapeutic approach in SLE should aim not only at achieving disease remission but also at treating all conditions affecting the patients and, consequently, their outcomes. These patients should be treated as coronary artery disease (CAD) equivalent with rigorous modifiable CV risk factors management in addition to the optimal treatment of their lupus. Furthermore, modifiable osteoporosis traditional risk factors and SLE-related risk factors should be modified to ameliorate bone loss and fracture risk. Cancer preventive measures (smoking cessation and screening programs for cervical cancer) constitute also essential components of the management of these patients.

Paquimeningitis, aortitis y nefritis simulando arteritis temporal / Pachymeningitis, aortitis and nephritis simulating temporal arteritis

Resumen Se presenta el caso de un hombre de 65 años con cuadro clínico de cefalea y velocidad de sedimentación globular elevada en quien se sospechó arteritis de células gigantes (ACG), pero durante el proceso diagnóstico se le documentó paquimeningitis, hiperproteinorraquia y biopsia de arteria temporal reportada como normal. La búsqueda de otras enfermedades sistémicas que explicaran el cuadro clínico evidenció además la presencia de aortitis, glomerulonefritis y anticuerpos anticitoplasma de neutrófilos (ANCA) positivos, lo cual permitió hacer el diagnóstico de granulomatosis con poliangeítis (GP). Se presenta el análisis y enfoque diagnóstico de esta inusual asociación de paquimeningitis, aortitis y glomerulonefritis. (Acta Med Colomb 2016; 40: 259-265).

Abstract The case of a 65-year-old man with a clinical picture of headache and elevated erythrocyte sedimentation rate in whom giant cell arteritis (GCA) was suspected, but that during the diagnostic process was documented as pachymeningitis, hyperproteinorrachia and temporal artery biopsy reported as normal, is presented. The search for other systemic diseases that could explain the clinical picture also revealed the presence of aortitis, glomerulonephritis and anti-neutrophil cytoplasmic antibodies (ANCA), and allowed to make the diagnosis of granulomatosis with poliangeítis (GPA). The analysis and diagnostic approach of this unusual association of pachymeningitis, aortitis and glomerulonephritis is reported. (Acta Med Colomb 2016; 40:259-265).

Correlación entre la actividad clínica por DAS-28 y ecografía en pacientes con artritis reumatoide / Correlation between clinical activity measured by DAS-28 and ultrasound in patients with rheumatoid arthritis

INTRODUCCIÓN: La artritis reumatoide es una enfermedad multifactorial, sistémica, crónica, autoinmune e inflamatoria, que afecta fundamentalmente las articulaciones. La ultrasonografía/ecografía ha demostrado utilidad en la detección de sinovitis subclínica; sin embargo, la mayoría de la evidencia disponible es en pacientes en remisión y la evidencia para la correlación con el índice de actividad clínica (DAS-28), en Colombia, es limitada. OBJETIVOS: Establecer la correlación entre la actividad clínica medida por DAS-28 y la ecografía, en pacientes con artritis reumatoide. MATERIALES Y MÉTODOS: Cuarenta pacientes con diagnóstico de artritis reumatoide que iniciaron terapia biológica o leflunomida, fueron incluidos en el estudio descriptivo, longitudinal, prospectivo para evaluar la correlación entre el DAS-28 y la ecografía, en la consulta basal y a los 4 meses.RESULTADOS: Se encontró; correlación entre el índice de actividad clínico de la enfermedad (DAS-28) y el índice de actividad ecográfico (DAS ecográfico), tanto por escala de grises (r=0,943,p<0,01) como por Power Doppler(r =0,946, p <0,01); también se encontró; correlación entre el DAS ecográfico por escala de grises y el DAS ecográfico por Power Doppler (r= 0,953 ,p <0,01). CONCLUSIONES: La ecografía es de utilidad en la detección de inflamación subclínica y los resultados son concluyentes cuando se compara el número de articulaciones inflamadas en la evaluación clínica, con el conteo obtenido en la evaluación ecográfica. La evaluación ecográfica sugiere que las manos son las articulaciones con mejor rendimiento para la medición del grado de sinovitis en la artritis reumatoide

NTRODUCTION: Rheumatoid arthritis is a multifactorial, systemic, chronic, autoimmune, and inflammatory disease that mainly affects the joints. Ultrasound has shown to be useful in detecting subclinical synovitis; however, most of the available evidence is in patients on remission, and the evidence on a correlation with the clinical activity measured by DAS-28, in our midst, is limited. OBJECTIVE: To establish the correlation between clinical activity measured by DAS-28 and ultrasound in patients with rheumatoid arthritis. MATERIALS AND METHODS: A total of 40 patients diagnosed with rheumatoid arthritis who were started on biological therapy or leflunomide were included in the descriptive, longitudinal, prospective study to evaluate the correlation between DAS-28 and ultrasound at baseline visit and 4 months later. RESULTS: A correlation was found between DAS-28 and ultrasound, both by using the grayscale (r = 0.943, p <.01) and the power Doppler (r = 0.946, p <.01). There was also a correlation between the ultrasound DAS by grayscale and ultrasound DAS by power Doppler (r = 0.953, p<.01). CONCLUSIONS: Ultrasound is a useful tool for detecting sub-clinical inflammation and the results are conclusive when comparing the number of swollen joints in the clinical evaluation with the count obtained in the ultrasound assessment. Ultrasound evaluation suggests that the hands are the joints with better performance for measuring the grade of synovitis in rheumatoid arthritis

Scleritis associated with relapsing polychondritis.

AIMS: To evaluate ocular disease characteristics and successful therapeutic regimens in patients with scleritis associated with relapsing polychondritis (RP). To compare these features with those seen in patients with scleritis associated with other systemic immune-mediated diseases (SIMD). METHODS: Electronic health records of 13 scleritis patients associated with RP were analysed and compared with those of 113 scleritis patients associated with other SIMD seen at two tertiary referral centres. RESULTS: Scleritis in patients with RP was often bilateral (92.3%), diffuse (76.9%), recurrent (84.6%), sometimes with decreased vision (46.2%), anterior uveitis (38.5%), peripheral keratitis (15.4%) and ocular hypertension (30.8%). Patients with scleritis associated with RP more often had bilateral scleritis (p=0.001), necrotising scleritis (23.1%; p=0.02), recurrences (p=0.001) and decreased vision (three of the six with legal blindness; p=0.012), as compared with patients who had scleritis associated with other SIMD. Nine patients (69.2%) had one or more SIMD other than RP, including systemic vasculitis (4) or other autoimmune disease (8); they antedated RP by 9 years (range 2-21 years). Successful therapy included cyclophosphamide (5), methotrexate (3), azathioprine (3), mycophenolate mofetil (2), infliximab (2) and adalimumab (1). CONCLUSIONS: Scleritis may be the first manifestation whose study leads to the diagnosis of RP. Scleritis associated with RP is more often bilateral, necrotising, recurrent and associated with decrease of vision than scleritis associated with other SIMD. About 69.2% of patients will have an additional SIMD disorder. Scleritis associated with RP most often will require immunomodulatory therapy. Occasionally, scleritis with RP may appear while using antitumor necrosis factor α agents.