Impact of rheumatoid arthritis on sexual function.

Sexuality is a complex aspect of the human being's life and is more than just the sexual act. Normal sexual functioning consists of sexual activity with transition through the phases from arousal to relaxation with no problems, and with a feeling of pleasure, fulfillment and satisfaction. Rheumatic diseases may affect all aspects of life including sexual functioning. The reasons for disturbing sexual functioning are multifactorial and comprise disease-related factors as well as therapy. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by progressive joint destruction resulting from chronic synovial inflammation. It leads to various degrees of disability, and ultimately has a profound impact on the social, economic, psychological, and sexual aspects of the patient's life. This is a systemic review about the impact of RA on sexual functioning.

[Cryptococcal meningitis and systemic lupus erythematosus: a case report and review]. / Criptococosis meníngea y lupus eritematoso sistémico: reporte de un caso y revisión de la literatura.

Cryptococcal meningitis is an uncommon but well-known and frequently fatal complication of systemic lupus erythematosus (SLE). The clinical manifestations are unspecific and frequently are confused with lupus activity. A patient with cryptococcal meningitis and SLE, who responded well to amphotericin deoxycholate therapy, is reported. In a review through MEDLINE of the Spanish and English literature, 57 cases of SLE and cryptococcal meningitis were found. Simultaneous presentation of both diseases has been reported in only three cases. This temporal coexistence suggests that specific underlying immune defects associated with SLE directly predisposes to mycotic infections.

Neurological adverse events associated with anti-tumor necrosis factor α treatment.

Anti-tumor necrosis factor alpha (TNF-alpha) drugs have been successfully used for the treatment of rheumatic autoimmune diseases including rheumatoid arthritis (RA), psoriatic arthritis, psoriasis, ankylosing spondylitis (AS), juvenile chronic arthritis, and Crohn's disease. However, they have been associated with different neurological disorders, including alterations of peripheral nerves, multiple sclerosis (MS), optic neuritis (ON) and acute transverse myelitis (ATM). This article reviews the most current aspect regarding neurological adverse events associated with anti-TNF-alpha drugs with emphasis on the possible explanations for this relation and the pathogenic mechanism of TNF-alpha in neurological disorders.

Criptococosis meníngea y lupus eritematoso sistémico: reporte de un caso y revisión de la literatura / Cryptococcal meningitis and systemic lupus erythematosus: a case report and review

Cryptococcal meningitis is an uncommon but well-known and frequently fatal complication of systemic lupus erythematosus (SLE). The clinical manifestations are unspecific and frequently are confused with lupus activity. A patient with cryptococcal meningitis and SLE, who responded well to amphotericin deoxycolate therapy, is reported. In a review through MEDLINE of the Spanish and English literature, 57 cases of SLE and cryptococcal meningitis were found. Simultaneous presentation of both diseases has been reported in only three cases. This temporal coexistence suggests that specific underlying immune defects associated with SLE directly predisposes to mycotic infections.

La meningitis por Cryptococcu neoformans es una inusual pero reconocida fatal complicación en los pacientes con lupus eritematoso sistémico (LES). Se presenta con un cuadro clínico inespecífico y frecuentemente se confunde con la actividad lúpica. Se reporta un caso de un paciente diagnosticado con meningitis por C. neoformans, al comienzo de LES, que fue tratada satisfactoriamente con anfotericina B deoxicolato. En la revisión de la literatura en español e inglés a través de MEDLINE, se encontró que han sido reportados 57 casos de pacientes con LES y criptococosis meníngea, de los cuales hay solamente 3 casos cuya infección se presentó simultáneamente con el LES. La presentación simultánea de criptococosis meníngea y LES enfatiza la posibilidad de que defectos inmunológicos intrínsecos en pacientes con LES sean los directamente responsables de la predisposición a adquirir infecciones micóticas.

A patient with multiple blisters in the skin and mucous membranes.

A case is presented of a patient who was referred to the rheumatology department with symptoms of systemic lupus erythematosus and bullous disease. A 55-year-old woman with 2 year history of blistering involving the hands and face, presented with new lesions on the thorax, feet, toes, inferior lip, and tongue accompanied by pruritus. The patient also had joint pain without inflammation of the knees, ankles, and hands. After the investigations the patient was diagnosed with a blistering disorder, specifically epidermolysis bullosa acquisita. The patient completely recovered following treatment with topical and oral corticosteroids, and colchicine.

[Autoimmune diseases associated with transverse myelitis. Review]. / Mielitis transversa asociada a enfermedades autoinmunes. Revisión.

Transverse myelitis (TM) is an inflammatory process involving restricted areas of the spinal cord. The usually dramatic presentation with rapidly progressive symptoms involving motor, sensory and autonomic functions makes acute TM a medical emergency. Acute TM has been cited as a rare and unusual complication of systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS), but early diagnosis and aggressive treatment might improve the prognosis. This review of the literature (MEDLINE), showed that, within autoimmune diseases, acute transverse myelitis is mainly associated with SLE and SS. Previous studies seem to indicate that the presence of antiphospholipid antibodies might play a role in the etiology of TM. Although no uniform therapeutic protocol exists, and the prognosis is usually poor, early aggressive treatment (usually with EV pulses of methylprednisolone and cyclophosphamide) might improve the prognosis.

Mielitis transversa asociada a enfermedades autoinmunes: revisión / Autoimmune diseases associated to transverse myelitis: review

La mielitis transversa (MT), es un proceso inflamatorio que afecta un área restringida del cordón espinal. La presentación, usualmente dramática, con una rápida progresión de los síntomas que involucran las funciones motoras, sensitivas y autonómicas, hace de la MT aguda una emergencia médica. Aunque su asociación con el lupus eritematoso sistémico (LES) y el síndrome de Sjõgren (SS), ha sido reportada como rara, y no existe acuerdo con respecto al tratamiento de estos pacientes, los diferentes autores si enfatizan el hecho que un diagnóstico precoz y tratamiento agresivo, mejoran el pronóstico. En la revisión de la literatura (MEDLINE) se encontró que las principales enfermedades autoinmunes asociadas a la MT aguda son el LES y el SS. Además, se establece que los anticuerpos antifosfolipídicos (aAP) podrían tener un papel etiológico en la MT. Aunque no existen protocolos terapéuticos uniformes para el tratamiento de estos pacientes y el pronóstico, en muchos casos es pobre, ha sido postulado que el tratamiento temprano y agresivo (usualmente con bolos de esteroides y ciclofosfamida) puede ser crucial para una respuesta adecuada.

Transverse myelitis (TM) is an inflammatory process involving restricted areas of the spinal cord. The usually dramatic presentation with rapidly progressive symptoms involving motor, sensory and autonomic functions makes acute TM a medical emergency. Acute TM has been cited as a rare and unusual complication of systemic lupus erythematosus (SLE) and Sjõgren’s syndrome (SS), but early diagnosis and aggressive treatment might improve the prognosis. This review of the literature (MEDLINE), showed that, within autoimmune diseases, acute transverse myelitis is mainly associated with SLE and SS. Previous studies seem to indicate that the presence of antiphospholipid antibodies might play a role in the etiology of TM. Although no uniform therapeutic protocol exists, and the prognosis is usually poor, early aggressive treatment (usually with EV pulses of methylprednisolone and cyclophosphamide) might improve the prognosis.

The impact of rheumatic diseases on sexual function.

Sexuality is a complex aspect of the human being's life and is more than of only the sexual act. Normal sexual functioning consists of sexual activity with transition through the phases from arousal to relaxation with no problems, and with a feeling of pleasure, fulfillment and satisfaction. Rheumatic diseases may affect all aspects of life including sexual functioning. The reasons for disturbing sexual functioning are multifactorial and comprise disease-related factors as well as therapy. In rheumatoid arthritis and ankylosing spondylitis patients, pain and depression could be the principal factors contributing to sexual dysfunction. On the other hand, in women with Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis sexual dysfunction is apparently most associated to vaginal discomfort or pain during intercourse. Finally, sexual dysfunction in patients with fibromyalgia could be principally associated with depression, but the characteristic symptoms of fibromyalgia (generalized pain, stiffness, fatigue and poor sleep) may contribute to the occurrence of sexual dysfunction. The treatment of sexual dysfunction will depend on the specific patient's symptoms, however, there are some general recommendations including: exploring different positions, using analgesics drug, heat and muscle relaxants before sexual activity and exploring alternative methods of sexual expression. This is a systemic review about the impact of several rheumatic diseases on sexual functioning. There are no previous overviews about this topic so far.

Sacroiliac pain in a dialysis patient.

The case is reported of a 47-year-old man with a history of chronic renal failure, treated with peritoneal dialysis, who presented with acute sacroiliac joint pain secondary to a pelvic abscess. Initially a diagnosis of infectious sacroiliitis of the left sacroiliac joint was suspected, but following investigation a pain referable to the sacroiliac joint was suspected. The patient recovered with a combination of antibiotics for the pelvic abscess and non-steroidal anti-inflammatory drugs.

Tyrosine kinases as targets in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation and proliferation of inflammatory cells in the synovial (joint) lining, resulting in the formation of pannus tissue, which invades and destroys adjacent cartilage and bone. In RA macrophages, B cells, mast cells, fibroblast-like synoviocytes (FLSs) and CD4+ T lymphocytes become activated and contribute to synovial inflammation and joint destruction. It has been showed that different tyrosine kinases participate in the activation of those cells having important participation in the physiopathology of RA. Therefore, the tyrosine kinases inhibitors could be the next step in the treatment of patients with RA. This review focuses on recent advances on the role of tyrosine kinases and their inhibitors in the physiopathology of RA.

Macrophage activation syndrome: a frequent but under-diagnosed complication associated with rheumatic diseases.

Macrophage activation syndrome (MAS) or hemophagocytic syndrome is a severe complication of chronic rheumatic diseases especially in systemic-onset juvenile rheumatoid arthritis (JRA). Although the cause of MAS is unknown, dysregulation of macrophage-lymphocyte interactions with subsequent increases in the levels of both T cell-derived and macrophage-derived cytokines could be involved in this syndrome, leading to an intense systemic inflammatory reaction, which accounts for the main clinical picture. Patients usually present with an acute febrile illness, hepatosplenomegaly, lymphadenopathy, cutaneous and mucosal bleeding, pancytopenia, and central nervous system, cardiac, and renal involvement. Treatment of MAS in patients with rheumatic diseases has not been standardized yet, but it commonly includes a variety of agents such as high-dose corticosteroids, cyclosporine, cyclophosphamide, etoposide, and intravenous immunoglobulin (IVIG). This article reviews the current literature about the pathogenesis, clinical manifestation, diagnosis, and treatment of this severe complication associated with rheumatic diseases.

Upregulation of angiotensin II-AT1 receptors during statin withdrawal in vascular smooth muscle cells.

Acute discontinuation of statins induces vascular dysfunction and increases cardiovascular events. The mechanisms underlying these events are under investigation. We showed an increase in angiotensin II (AngII) signaling after acute statin withdrawal. We investigated whether AngII-AT1-receptor expression (AT1-R mRNA) and receptor protein (AT1-R) levels mediate increased AngII signaling. In rat aortic vascular smooth muscle cells (VSMC), simvastatin (0.3 to 3 microM for 24 hours) resulted in concentration-dependent inhibition of AngII-stimulated phosphorylation of extracellular-signal regulated kinase 1/2 ERK1/2 (-67 +/- 5% with 3 microM; P < 0.001) and decreased AT1-R mRNA (-34 +/- 8% with 3 microM; P < 0.01) and AT1-R protein (-32 +/- 6% with 3 microM; P < 0.01). Removal of simvastatin led to a rebound increase in mRNA-AT1-R (+39 +/- 2%, P < 0.01), AT1-R protein (+46 +/- 2%; P < 0.01), and AngII-mediated phosphorylation of ERK1/2 (+36 +/- 3%; P < 0.01). The increase in receptor expression was present at 1 hour and lasted for 4 hours, whereas increased AT1-R protein and AngII signaling started at 2 hours and lasted for nearly 2 hours. In summary, increased AngII signaling after statin withdrawal is most likely due to increases in AT1-R number due to increased transcription. The increase in AngII activity may contribute to the vascular dysfunction associated with statin withdrawal.

A case of laryngeal paracoccidioidomycosis masquerading as chronic obstructive lung disease.

Paracoccidioidomycosis (South American blastomycosis) is a systemic infection caused by a dimorphic fungus (Paracoccidioides brasiliensis). It is common in the rural areas of Latin America. The majority of the reported cases come from Brazil, Colombia and Venezuela. Paracoccidioidomycosis is the most important systemic mycosis of the tropical Americas and can affect any organ, causing symptomatic or asymptomatic lesions. Paracoccidioidomycosis can mimic other diseases, which must be considered in making the differential diagnosis. Patients get infected by inhaling mycelia found in the natural environment or rarely from traumatic inoculation via mucous membranes. The most common lesions frequently occur in the buccal pharynx mucosa. Others lesions occur in the larynx, adrenal glands, liver, bones, gastrointestinal tract, lungs and nervous system.

Effects of statin treatment and withdrawal on angiotensin II-induced phosphorylation of p38 MAPK and ERK1/2 in cultured vascular smooth muscle cells.

Abrupt discontinuation of 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase inhibitors (statins) is associated with increased cardiovascular risk. To investigate the molecular mechanisms determining the increased cardiovascular risk after statin withdrawal, we studied the effects of statin treatment and withdrawal on angiotensin II (AII) actions in rat aortic vascular smooth muscle cells (VSMC) in culture. In VSMC, AII stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and of p38 mitogen-activated protein kinase (p38 MAPK), with an EC50% of 0.86 and 3 nM, respectively. Maximal stimulation was observed after 5-10 min of exposure to AII. Pretreatment with 1-3 microM simvastatin for 24h inhibited AII-mediated stimulation of ERK1/2 and p38 MAPK phosphorylation; without affecting the levels on non-phosphorylated MAPK. Washout of simvastatin produced a rebound increase above control levels of AII-mediated phosphorylation of ERK1/2 and p38 MAPK. As previously reported for other agonists, the rebound increase of AII effects was observed from 1 to 3h after statin withdrawal, and was lost at later times. The basal levels of phosphorylation and the amount of non-phosphorylated kinases were unaffected by statin withdrawal. Similar effects were observed with lovastatin. Our results suggest that statins modulate AII effects in VSMC, and that transient increases in AII effects mediated via the MAPK pathway may play a role in the vascular dysfunction associated with statin withdrawal.

Immunomodulatory effects of statins and autoimmune rheumatic diseases: novel intracellular mechanism involved.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, known as statins, are the most commonly prescribed agents for the treatment of hypercholesterolemia. However, the effects of statins may extend beyond their influences on serum cholesterol levels resulting in cholesterol-independent or pleiotropic effects. Clinical, animal and in vitro studies suggest that statins have additional clinical uses because of their anti-inflammatory and immunomodulatory effects, in part due to their capacity to interfere with the mevalonate pathway and inhibit prenylation of Rho family GTPases. This review focuses on the molecular mechanisms of the anti-inflammatory and immunomodulatory effects of statins. In base to all these information, we suggest that statins could have similar inhibitory effects on MAPKs pathways in cells from RA patients, including osteoclasts and fibroblasts.