Subclinical synovitis impact on the progression of lupus joint disease: A 10-year longitudinal multicenter study.

OBJECTIVE: To determine the effect of subclinical synovitis on the progression of joint disease in a cohort of patients with systemic lupus erythematosus over a mean follow-up of 10 years. METHODS: A longitudinal follow-up of 96 patients diagnosed with lupus was performed. All patients were considered clinically free of joint disease or with minimal joint impairment at baseline and were studied through ultrasound study of their dominant hand to assess the prevalence of subclinical synovitis. Now, over 10 years after we contacted them and reviewed their evolution to determine the impact of had or had not been diagnosed with subclinical synovitis in their current joint condition. RESULTS: Thirty-one of the 91 reached patients developed clinical progression in their joint manifestations (at least one ordinal degree of worsening). Of these, 23 (74,9%) had demonstrated subclinical synovitis at baseline. In the group of patients who did not progress clinically, 46 (76,6%) did not have this finding at the start of follow-up (p < .01, OR 9,44 95%CI 3,46-25,74). The patients in whom clinical progression was demonstrated had worse combined ultrasound scores than the rest of the patients: 6,41 SD 1,45 vs. 1,15 SD 0,97 (p < .01). CONCLUSIONS: The finding of subclinical synovitis in patients with systemic lupus erythematosus is associated with the development of joint disease progression both clinically and ultrasonographically.

Nuevas dianas terapéuticas en el lupus sistémico (parte 2/2) / New targets in systemic lupus (part 2/2)

Glucocorticoides, aspirina, antipalúdicos e inmunosupresores convencionales constituyen la base del tratamiento del lupus eritematoso sistémico (LES). Hasta recientemente, los 3 primeros eran los únicos agentes aprobados para su tratamiento. El mejor conocimiento de la fisiopatología del sistema inmunitario ha permitido identificar nuevas dianas terapéuticas. De hecho, belimumab, un anticuerpo monoclonal humano inhibidor de BLyS, se ha convertido hace pocos meses en el primer fármaco aprobado para el tratamiento del LES desde 1957, lo que subraya las dificultades de todo tipo, incluyendo las económicas y organizativas, inherentes a los ensayos clínicos sobre esta enfermedad. Otras muchas moléculas se encuentran en distintas fases de desarrollo y en poco tiempo dispondremos de resultados concretos. En esta revisión repasamos el mecanismo de acción y los datos clínicos más relevantes de estas moléculas (AU)

Glucocorticoids, aspirin, conventional antimalarials and immunosuppressants are the mainstay of treatment of Systemic Lupus Erythematosus (SLE). Until recently, the first three were the only agents approved for treatment. A better understanding of the pathophysiology of the immune system has identified new therapeutic targets. In fact, belimumab, a human monoclonal antibody to BLyS inhibitor has become, in recent months, the first drug approved for the treatment of SLE since 1957, underscoring difficulties of all kinds, including economic and organizational ones inherent to clinical trials on this disease. Many other molecules are in various stages of development and soon will have concrete results. In this review, we examined the mechanism of action and most relevant clinical data for these molecules (AU)

Nuevas dianas terapéuticas en el lupus sistémico (parte 1/2) / New therapeutic targets in systemic lupus

Glucocorticoides, aspirina, antipalúdicos e inmunosupresores convencionales constituyen la base del tratamiento del lupus eritematoso sistémico (LES). Hasta recientemente, los 3 primeros eran los únicos agentes aprobados para su tratamiento. El mejor conocimiento de la fisiopatología del sistema inmunitario ha permitido identificar nuevas dianas terapéuticas. De hecho, belimumab, un anticuerpo monoclonal humano inhibidor de BLyS, se ha convertido hace pocos meses en el primer fármaco aprobado para el tratamiento del LES desde 1957, lo que subraya las dificultades de todo tipo, incluyendo las económicas y organizativas, inherentes a los ensayos clínicos sobre esta enfermedad. Otras muchas moléculas se encuentran en distintas fases de desarrollo y en poco tiempo dispondremos de resultados concretos. En esta revisión repasamos el mecanismo de acción y los datos clínicos más relevantes de estas moléculas (AU)

Glucocorticoids, aspirin, antimalarials and conventional immunosuppressants are the mainstay of treatment of Systemic Lupus Erythematosus (SLE). Until recently, the first three were the only agents approved for treatment. A better understanding of the pathophysiology of the immune system has identified new therapeutic targets. In fact, belimumab, a human monoclonal antibody to BLyS inhibitor has become, in recent months, the first drug approved for the treatment of SLE since 1957, underscoring difficulties of all kinds, including economic and organizational ones inherent to clinical trials on this disease. Many other molecules are in various stages of development and soon will have concrete results. In this review, we examined the mechanism of action and most relevant clinical data for these molecules (AU)

New therapeutic targets in systemic lupus.

Glucocorticoids, aspirin, antimalarials and conventional immunosuppressants are the mainstay of treatment of Systemic Lupus Erythematosus (SLE). Until recently, the first three were the only agents approved for treatment. A better understanding of the pathophysiology of the immune system has identified new therapeutic targets. In fact, belimumab, a human monoclonal antibody to BLyS inhibitor has become, in recent months, the first drug approved for the treatment of SLE since 1957, underscoring difficulties of all kinds, including economic and organizational ones inherent to clinical trials on this disease. Many other molecules are in various stages of development and soon will have concrete results. In this review, we examined the mechanism of action and most relevant clinical data for these molecules.

New targets in systemic lupus (part 2/2).

Glucocorticoids, aspirin, conventional antimalarials and immunosuppressants are the mainstay of treatment of Systemic Lupus Erythematosus (SLE). Until recently, the first three were the only agents approved for treatment. A better understanding of the pathophysiology of the immune system has identified new therapeutic targets. In fact, belimumab, a human monoclonal antibody to BLyS inhibitor has become, in recent months, the first drug approved for the treatment of SLE since 1957, underscoring difficulties of all kinds, including economic and organizational ones inherent to clinical trials on this disease. Many other molecules are in various stages of development and soon will have concrete results. In this review, we examined the mechanism of action and most relevant clinical data for these molecules.

Enhanced phosphoinositide 3-kinase δ activity is a frequent event in systemic lupus erythematosus that confers resistance to activation-induced T cell death.

Systemic lupus erythematosus (SLE) is a human chronic inflammatory disease caused by the action of autoreactive T and B cells. Class I phosphoinositide-3-kinases (PI3K) are enzymes that trigger formation of 3-poly-phosphoinositides that induce cell survival. Enhanced PI3K activation is a frequent event in human cancer. Nonetheless, in a genetic model with enhanced activation of class I(A) PI3K in T cells, mice show a greater tumor index but die of a lupus-like disease. In this study, we studied the potential PI3K involvement in human SLE. The PI3K pathway was frequently activated in SLE patient PBMC and T cells (∼70% of cases), more markedly in active disease phases. We examined the mechanism for PI3K pathway activation and found enhanced activation of PI3Kδ in SLE peripheral blood T cells. The magnitude of PI3K pathway activation in patients paralleled activated/memory T cell accumulation. We examined potential tolerance mechanisms affected by increased PI3K activity; SLE patients showed reduced activation-induced cell death of activated/memory T cells. Moreover, the defective activation-induced cell death in SLE T cells was corrected after reduction of PI3Kδ activity, suggesting that PI3Kδ contributes to induction of enhanced SLE memory T cell survival. These observations point to PI3Kδ as a target of clinical interest for SLE.

Lesión quística en calcáneo. Lipoma intraóseo / Cystic lesion of the calcaneus. Intraosseous lipoma

Presentamos 2 casos de lipoma intraóseo de calcáneo, en un varón de 38 años con dolor en talón y una mujer de 27 años sin dolor en talón. La radiografías simples mostraban una lesión quística en el calcáneo, bien definida y con márgenes esclerosos. La tomografía computarizada mostró una lesión de baja densidad bien delimitada con valores de atenuación idénticos al tejido adiposo. Los hallazgos en la resonancia magnética mostraron en las imágenes T1 y T2 potenciadas una intensidad de señal similar al tejido graso subcutáneo, y en T2-STIR una señal de baja intensidad con supresión completa que indica la presencia de grasa normal. Hasta hace poco, los lipomas intraóseos sólo se podían diagnosticar con anatomía patológica, pero ahora es fácil realizar el diagnóstico radiológico con resonancia magnética (AU)

We report two cases of intraosseous lipoma in the calcaneus of a 38 year old man, complaining about heel pain and a 27 year old woman with no pain. Plain radiographs showed a well-defined cystic lesion in the calcaneus with sclerotic margins. Computed tomography (CT) detected a well-defined, low-density lesion with attenuation values equal to adipose tissue. Magnetic resonance (MR) findings show similar signal intensity with subcutaneous adipose tissue on T1-weighted and T2-weighted images, and STIR-T2 imaging showing low signal intensity with complete suppression indicating the presence of normal fat. As a result, at first intraosseous lipomas could only be identified pathologically, but now it is easy to perform radiological diagnosis using MR (AU)

[Cystic lesion of the calcaneus. Intraosseous lipoma]. / Lesión quística en calcáneo. Lipoma intraóseo.

We report two cases of intraosseous lipoma in the calcaneus of a 38 year old man, complaining about heel pain and a 27 year old woman with no pain. Plain radiographs showed a well-defined cystic lesion in the calcaneus with sclerotic margins. Computed tomography (CT) detected a well-defined, low-density lesion with attenuation values equal to adipose tissue. Magnetic resonance (MR) findings show similar signal intensity with subcutaneous adipose tissue on T1-weighted and T2-weighted images, and STIR-T2 imaging showing low signal intensity with complete suppression indicating the presence of normal fat. As a result, at first intraosseous lipomas could only be identified pathologically, but now it is easy to perform radiological diagnosis using MR.