Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

PARKIN overexpression in human mesenchymal stromal cells from Wharton's jelly suppresses 6-hydroxydopamine-induced apoptosis: Potential therapeutic strategy in Parkinson's disease.

BACKGROUND AIMS: Stem cell transplantation is an excellent option for regenerative or replacement therapy. However, deleterious microenvironmental and endogenous factors (e.g., oxidative stress) compromise ongoing graft survival and longevity. Therefore, (transient or stable) genetically modified cells may be reasonably thought to resist oxidative stress-induced damage. Genetic engineering of mesenchymal stromal cells (MSCs) obtained from Wharton's jelly tissue may offer some therapeutic potential. PARKIN is a multifunctional ubiquitin ligase able to protect dopaminergic cells against stress-related signaling. We, therefore, evaluated the effect of the neurotoxicant 6-hydroxydopamine (6-OHDA) on regulated cell death signaling in MSCs and investigated whether overexpression of PARKIN in MSCs was capable of modulating the effect of 6-OHDA. METHODS: We transiently transfected Wharton's jelly-derived MSCs with an mCherry-PARKIN vector using the Lipofectamine LTX method. Naïve MSCs and MSCs overexpressing PARKIN were exposed to increasing concentrations of 6-OHDA. We used light and fluorescence microscopy, flow cytometry, immunocytochemistry staining, in-cell Western and Western blot analysis. RESULTS: After 12-24 h of 6-OHDA exposure, we detected dichlorofluorescein (DCF)-positive cells (80%) indicative of reactive oxygen species (H2O2) production, reduced cell viability (40-50%), decreased mitochondrial membrane potential (ΔΨm, ~35-45%), DNA fragmentation (18-30%), and G1-arrested cell cycle in the MSCs. 6-OHDA exposure increased the expression of the transcription factor c-JUN, increased the expression of the mitochondria maintenance Phosphatase and tensin homologue-induced putative kinase 1 (PINK1) protein and increased the expression of pro-apoptotic PUMA, caspase-3 and apoptosis-inducing factor (AIF). 6-OHDA exposure also significantly augmented the oxidation of the oxidative stress sensor, DJ-1. Overexpression of PARKIN in MSCs not only significantly reduced the expression of cell death and oxidative stress markers but also significantly reduced DCF-positive cells (~50% reduction). DISCUSSION: 6-OHDA induced apoptosis in MSCs via generation of H2O2, activation of c-JUN and PUMA, mitochondrial depolarization and nuclei fragmentation. Our findings suggest that PARKIN protects MSCs against 6-OHDA toxicity by partly interacting with H2O2, reducing the expression of c-JUN, PUMA, AIF and caspase-3, and maintaining the mitochondrial ΔΨm.

Predictors of remission, erosive disease and radiographic progression in a Colombian cohort of early onset rheumatoid arthritis: a 3-year follow-up study.

The objective of the study is to find predictors of remission, radiographic progression (RP), and erosive disease in a cohort of patients with early onset rheumatoid arthritis (EORA) that followed a therapeutic protocol aiming at remission, in a real world tight-control setting. EORA patients were enrolled in a 3-year follow-up study. Clinical, biological, immunogenetic, and radiographical data were analyzed. Radiographs were scored according to Sharp-van der Heijde (SvdH) method. RP was defined by an increase of 3 units in 36 months. Remission was defined as DAS28 <2.6. A stepwise multiple logistic regression model was used to identify independent predictors of the three target outcomes. One hundred twenty-nine patients were included. Baseline disease activity was high. Significant overall improvement was observed, but only 33.3 % achieved remission. At 36 month, 50.4 % (65) of patients showed erosions. RP was observed in 62.7 % (81) of cases. Statistical analysis showed that baseline SvdH score was the only predictive factor associated with the three outcomes evaluated. Lower HAQ-DI and absence of autoantibodies were predictive of remission. Higher levels of ESR and presence of erosions at entry were predictive of RP. Independent baseline predictors of incident erosive disease were anti-CCP and RF positivity, symptom duration at baseline >3 months, and presence of HLA-DRB1 shared epitope. Radiographic damage at baseline was the main predictor of outcomes. Autoantibodies, HAQ and ESR at baseline, symptom duration before diagnosis, and HLA-DRB1 status had influence on clinical course and development of structural joint damage in Colombian RA patients.

Lupus in Latin-American patients: lessons from the GLADEL cohort.

The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American professionals taking care of these patients to spearhead the creation of the G: rupo L: atino A: mericano D: e E: studio del L: upus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.

Erosive arthropathy: clinical variance in lupus erythematosus and association with anti-CCP case series and review of the literature.

OBJECTIVE: To describe the occurrence of erosive arthropathy in systemic lupus erythematosus (SLE) and its relationship to anti-CCP antibodies. METHODS: Retrospective medical record review of a case series of five female patients with SLE and erosive arthropathies. RESULTS: The initial disease presentation in all patients was a polyarthritis. Anti-CCP antibodies were detected in 4 out of 5 (80%) patients, 2 of whom had a positive rheumatoid factor. CONCLUSION: Erosive arthritis was strongly associated with the presence of anti-CCP antibodies in these patients with SLE, who presented with polyarthritis. Anti-CCP in patients with SLE may be a marker of a more severe joint disease.

Osteomesopicnosis asociada a litiasis renal, informe de un caso. Diagnóstico diferencial de las enfermedades osteoesclerosantes axiales / Osteomesopycnosis associated to renal lithiasis, report of one case. Differential diagnosis of axial osteosclerosant diseases

La osteomesopicnosis, junto a la picnodisostosis, osteodistrofia renal, hiperostosis con osteoesclerosis con aumento de la fosfatasa alcalina y osteopetrosis, forman parte de un grupo de enfermedades poco frecuentes, que se caracterizan por la osteoesclerosis, especialmente del esqueleto axial, con lesiones típicamente en forma de parches, comprometiendo además la pelvis, a nivel de los acetábulos, los bordes superiores e inferiores de los cuerpos vertebrales de la región lumbar y la región proximal de fémur y del húmero. Es de carácter benigno y heredada en forma autosómica dominante. La primera descripción de esta entidad la realizaron Simon, Cazalis, Dryll, et al en 1979. El nombre de la enfermedad fue propuesto por Maroteaux en 1980. En este artículo presentamos una breve descripción de las enfermedades óseas con osteoesclerosis, presentamos nuestra casuística de enfermedades con alteraciones morforradiológicas, describimos un caso de osteomesopicnosis asociado a litiasis renal y proponemos una clasificación para enfermedades osteoesclerosantes del esqueleto axial junto a un enfoque práctico para el diagnóstico diferencial de estas enfermedades

Osteomesopyknosis joined to the pycnodysostosis, renal osteodystrophia, hyperostosis with osteosclerosis with increase of the alkaline phosphatase and osteopetrosis, makes part of a group of not very frequent illnesses that are characterized by the osteosclerosis, especially of the axial skeleton, with lesions typically in form of patches, also committing the pelvis, at level of the acetabulums, the superior and inferior borders of the vertebral bodies of the lumbar region, the region femur proximal and of the humerus. It is of benign character and inherited in dominant autonomous form. The first description of this entity carried out it Simon, Cazalis, Dryll, et al in 1979. The name of the illness was proposed by Maroteaux in 1980. In this article we present a brief description of the bony illnesses with osteosclerosis, we present our casuistry of illnesses with morfo-radiological alterations, we describe a case of osteomesopyknosis associated to renal lithiasis and we propose a classification for illnesses osteosclerosants of the axial skeleton join to a practical focus for the differential diagnosis of these illnesses

Localized nodular vasculitis: a new variant of localized cutaneous polyarteritis nodosa?

Cutaneous polyarteritis nodosa (PAN) was first described by Lindberg in 1931. This initial description was followed by many case reports and series, including those of Díaz-Pérez and Winkelmann, who used a strict definition based on cutaneous involvement, and Chen and Daoud who classified the condition into three well differentiated groups. The cutaneous form of PAN is distinct from the systemic form due to its chronic, recurrent, benign nature, the absence of internal organ involvement, and the presence of inflammation in medium and small vessels of the deep dermis and panniculus. In the present article we report our findings for 12 patients with a variant of cutaneous PAN consisting of painful erythematous nodular lesions not preceded or followed by livedo reticularis, that were located exclusively on the lower third of the legs and responded slowly to treatment with corticosteroids and immunosuppressants.

Estudio de la osteomalacia y raquitismo en diferentes períodos históricos en colombia / Study of osteomalacia in diferent historical periods in Colombia

Dividimos el trabajo en tres etapas. En la primera buscamos la recopilación de la información sobre raquitismo y osteomalacia desde finales del siglo XIX hasta 1960. En la segunda etapa revisamos los archivos estadísticos de la Unidad de Reumatología del Hospital San Juan de Dios desde su creación en 1967, y los pacientes que se consultaban desde esa época. La tercera etapa fue dividida en dos sub-etapas, la primera sub-etapa se refiere al estudio prospectivo del foco de raquitismo en el municipio de Suárez en 1991, y la segunda sub-etapa trata sobre los casos prospectivos desde 1984 hasta Marzo del 2000 en la Clínica de Fracturas de Barranquilla, el Hospital San Juan de Dios de Bogotá, y los casos remitidos a uno de los investigadores. En la primera etapa sólo encontramos la tesis del Dr. Francisco Sorzano, publicada en 1899. Estudió 6 casos de raquitismo secundario, hipovitaminosis D y de desnutrición proteico calórica. Se utilizan por primera vez el aceite de hígado de bacalao y sales de calcio y fosfatos. A partir de 1960 se estudian 7 familias y se describen por primera vez en Colombia el raquitismo hipofosfatémico ligado al cromosoma X, es el caso de cuatro familias con raquitismo hipofosfatémico y dos familias con raquitismo hipocalcémico. En 1991 describimos el clúster más grande del mundo, aproximadamente 400 pacientes, pero sólo informamos sobre 64 pacientes. Demostramos qué es un raquitismo dependiente de vitamina D tipo IIB; es estudiado con más detenimiento el receptor de la vitamina D, el cual fue encontrado normal, aunque el defecto se encuentra a nivel posttranslacional. De forma prospectiva, a partir de 1984 estudiamos 19 pacientes con raquitismo y osteomalacia, asociadas a diferentes etiologías e introducimos los estudios de desintometría ósea, los niveles polares de vitamina D, hormona paratiroidea (PTH), y las iso-enzimas de la fosfatasa alcalina (AU)

Takayasu arteritis in Colombia.

Takayasu arteritis has been recognized in Colombia just recently, and so far we do not have any report concerning its presentation here. In this first report, some issues related to the presentation of the disease are indicated and compared with those found in the medical literature. No differences were found in age and sex. Most of the cases were diagnosed during an inactive phase of the disease with advanced manifestations due to vascular lesion which suggests the existence of some genetic factor influencing such a presentation, or may be the consequence of a delay in diagnosing the disease during initial and active stages due to not suspecting it. Comparing the vessels which are affected among other races and countries, we can find both differences and similarities. With the purpose of discovering the demographic, clinical, angiographic and laboratorial characteristics of Takayasu arteritis in Colombia, the present study was carried out by studying 35 clinical cases in different medical centers of the country.

Buerger's disease at the 'San Juan De Dios' Hospital, Santa Fe De Bogota, Colombia.

OBJECTIVES: To know the clinical characteristics in the presentation of Buerger's disease in San Juan de Dios Hospital, Bogota, Colombia, between 1986 and 1996, and compare them with a previous series from the same Hospital and another reported in international literature; To determine the changes in the form of appearance of the disease. METHODS: We reviewed the clinical information of 22 patients with diagnosis of Buerger's disease, observed between 1986 and 1993, and we added the information of the clinical histories of eight other patients with equal diagnosis, observed between 1994 and 1996 in our Unit. RESULTS: We observed 30 patients: 28 men (93%) and two women (7%), with a ratio M:F of 14:1, with an average age of 39+10 years (range from 18 to 52 years). Sixty percent were younger than 40 years and only the 10% were older than 50 years. The most frequent reasons for consultation were: pain in rest in the affected extremity, gangrene and ulceration in more than 50%. Raynaud's phenomenon in 30%, and the related surgical history in 40%. The pedal pulse was the most compromised followed by popliteal, poster or tibial and femoral. We did not observe the presence of thrombophlebitis. Eighty percent showed compromise of more than one extremity. All of them were active smokers. Three patients showed IgG anticardiolipine antibodies at high level. CONCLUSIONS: The clinical characteristics are similar to those reported, we find also a reduction of the disease diagnosis. It calls to our attention that no thrombophlebitis was found in the present series and the less compromise of the upper extremities with a frequent femoral compromise. All this points toward a change in the natural history of the disease.

Polyarticular Sporothrix schenckii Infection In an Immunocompetent Host.

Septic arthritis is an unusual complication of Sporothrix schenckii infection. Its diagnosis can be very difficult, mainly because of low clinical suspicion, special media needed for its culture, and low density of the organism in biopsy specimens. We present a case of a woman with disseminated Sporothrix schenckii infection and polyarthritis. Although rare, this wide dissemination of fungus and polyarthritis occurred in an initially immunocompetent patient. Steroid therapy given for suspected vasculitis might have worsened her condition.

Turner's Syndrome and Psoriatic Arthritis.

Gonadal dysgenesis, or Turner's syndrome, is a common X chromosome genetic disorder with characteristic clinical and radiological features. Psoriasis is a common skin disorder that can be associated with arthritis. This report describes a 34-year-old woman with both diseases. Radiological features of Turner's syndrome are described with illustrations of how some changes might be confused with those of rheumatic disease. Although psoriatic arthritis has not been previously reported, other autoimmune diseases have been associated with Turner's syndrome.

Arterial fibrodysplasia causing occlusive vascular disease simulating primary vasculitis.

We report a case of arterial fibrodysplasia causing vascular disease with ulceronecrotic lesions in lower extremities. The arteriography showed a beaded pattern in both arteries and veins; laboratory test findings were within normal value ranges; the biopsy reported medial hyperplasia involving the arterial and venous walls. Arterial fibrodysplasia should be considered as a differential diagnosis in patients complaining of recurrent occlusive vascular episodes without systemic manifestations, normal laboratory test results, and radiological patterns suggestive of fibrodysplasia. This is the first report of medial hyperplasia in digital arteries and venous wall involvement.