Síndrome de hipertensión intracraneana como manifestación inhabitual del síndrome de Sjögren. Caso clínico

Neurological manifestations such as polyneuropathy are reported in 8-49% of cases with Sjögren's Syndrome (SjS), but central nervous system involvement is seldom described. We report a 46-year-old woman with a history of SjS with distal renal tubular acidosis and autoimmune thyroiditis. She consulted in the emergency room for a five-days history of holocranial headache and explosive vomiting. Fundoscopy showed bilateral papilledema. Brain computed tomography (CT) without contrast showed diffuse encephalic edema, with effacement ofsulci and restriction ofperitruncal cisterns. Brain AngioCT ruled out thrombosis, and brain magnetic resonance (MRI) was without structural alterations or hydrocephalus. Lumbar puncture had increased cerebrospinal fluid output pressure but without cytochemical alterations, and negative gram, cultures and filmarray. The diagnosis of Intracranial Hypertension Syndrome (ICHTS) ofprobable autoimmune etiology in the context of SjS was proposed, and management with high-dose corticosteroids was initiated with favorable clinical and imaging response.

[Intracranial hypertension syndrome as an unusual manifestation of Sjögren's syndrome. Report of one case]. / Síndrome de hipertensión intracraneana como manifestación inhabitual del síndrome de Sjögren. Caso clínico.

Neurological manifestations such as polyneuropathy are reported in 8-49% of cases with Sjögren's Syndrome (SjS), but central nervous system involvement is seldom described. We report a 46-year-old woman with a history of SjS with distal renal tubular acidosis and autoimmune thyroiditis. She consulted in the emergency room for a five-days history of holocranial headache and explosive vomiting. Fundoscopy showed bilateral papilledema. Brain computed tomography (CT) without contrast showed diffuse encephalic edema, with effacement ofsulci and restriction ofperitruncal cisterns. Brain AngioCT ruled out thrombosis, and brain magnetic resonance (MRI) was without structural alterations or hydrocephalus. Lumbar puncture had increased cerebrospinal fluid output pressure but without cytochemical alterations, and negative gram, cultures and filmarray. The diagnosis of Intracranial Hypertension Syndrome (ICHTS) ofprobable autoimmune etiology in the context of SjS was proposed, and management with high-dose corticosteroids was initiated with favorable clinical and imaging response.

Enfermedad relacionada a IgG4. Serie clínica de pacientes chilenos / IGG4-related disease. Report of 52 patients

BACKGROUND: IgG4-related disease (IgG4 RD) is an immune-mediated fibro-inflammatory disorder, with tissue infiltration of IgG4+ plasma cells. It causes pseudotumors, tumors, and a wide spectrum of clinical manifestations. AIM: To report the clinical, laboratory, histopathological and treatment characteristics of a group of Chilean patients with IgG4 RD. MATERIAL AND METHODS: Review of medical records of 52 patients aged 18 to 76 years with IgG4 RD seen at six medical centers. RESULTS: Elevated IgG4 serum levels (> 135 mg/dl) were found in 18 of 44 (41%) patients. There was histological confirmation of the disease in 46 patients. The most common sites of involvement were lungs, eyes and kidneys. Eighteen (35%) patients had only one organ involved, 34 (65%) patients had two organs and 13 (25%) patients had three or more organs. The involvement of two organs was significantly more common in men (p < 0.05). In patients with only one organ involvement, the most frequent location was orbital and meningeal. All patients with kidney or lung disease had multiorgan involvement. All patients received corticosteroid therapy, 67% synthetic immunosuppressants, and 16% rituximab. CONCLUSIONS: ER-IgG4 can affect any tissue. Multiorgan involvement was more common in this series, with preference for lungs, eyes and kidneys. An excellent response to steroids is characteristic of the disease, but with a high relapse rate that requires additional immunosuppression.

[IGG4-related disease. Report of 52 patients]. / Enfermedad relacionada a IgG4. Serie clínica de pacientes chilenos.

BACKGROUND: IgG4-related disease (IgG4 RD) is an immune-mediated fibro-inflammatory disorder, with tissue infiltration of IgG4+ plasma cells. It causes pseudotumors, tumors, and a wide spectrum of clinical manifestations. AIM: To report the clinical, laboratory, histopathological and treatment characteristics of a group of Chilean patients with IgG4 RD. MATERIAL AND METHODS: Review of medical records of 52 patients aged 18 to 76 years with IgG4 RD seen at six medical centers. RESULTS: Elevated IgG4 serum levels (> 135 mg/dl) were found in 18 of 44 (41%) patients. There was histological confirmation of the disease in 46 patients. The most common sites of involvement were lungs, eyes and kidneys. Eighteen (35%) patients had only one organ involved, 34 (65%) patients had two organs and 13 (25%) patients had three or more organs. The involvement of two organs was significantly more common in men (p < 0.05). In patients with only one organ involvement, the most frequent location was orbital and meningeal. All patients with kidney or lung disease had multiorgan involvement. All patients received corticosteroid therapy, 67% synthetic immunosuppressants, and 16% rituximab. CONCLUSIONS: ER-IgG4 can affect any tissue. Multiorgan involvement was more common in this series, with preference for lungs, eyes and kidneys. An excellent response to steroids is characteristic of the disease, but with a high relapse rate that requires additional immunosuppression.

Arsenic trioxide-increased MDCK cells proliferation requires activator protein 1-mediated increase of the sodium/proton exchanger 1 activity.

The release of protons (H+) occurs via the Na+/H+ exchanger isoform 1 (NHE1) leading to a stable intracellular pH (pHi) in MDCK cells. Chronic intake of arsenic trioxide (ATO), in the drinking water, associated with higher morbidity and mortality in neoplastic tissues. ATO increased NHE1 expression and activity, resulting in intracellular alkalization and higher MDCK cells proliferation. Since the pro-proliferative transcription factor activator protein 1 (AP-1) gets activated by al alkaline intracellular pH, a phenomenon paralleled by higher NHEs activity, we asked whether ATO-increased MDCK cells proliferation involves AP-1-dependent NHE1 activation. Cells were exposed (48 h) to ATO (0.05 µmol/L), SR11302 (1 µmol/L, AP-1 inhibitor), HOE-694 (100 nmol/L, NHE1 inhibitor) and EIPA (50 µmol/L, NHE1/NHE3 inhibitor) in the presence of S3226 (10 µmol/L, NHE3 inhibitor), concanamycin A (0.1 µmol/L, V-ATPases inhibitor), and Schering (10 µmol/L, H+/K+-ATPase inhibitor). [3H]Thymidine incorporation, cell counting, wound healing assay, and AP-1 activity were determined. The pHi was measured in cells pre-loaded (10 min) with 2,7-bicarboxyethyl-5,6-carboxyfluorescein acetoxymethyl ester (12 mmol/L) and exposed to NH4Cl (20 mmol/L). Basal pHi and recovery rate (dpHi/dt), intracellular buffer capacity (ßi) and H+ flux (JH+) were determined. NHE1 protein abundance was measured by Western blotting and immunofluorescence. ATO increased the cell growth (1.5 fold), basal pHi (0.4 pHi units), dpHi/dt (1.8 fold), JH+ (1.4 fold), AP-1 activity and NHE1 protein abundance (1.3 fold). ATO also increased (1.5 fold) the nuclear/perinuclear NHE1 immunosignal. SR11302 and HOE-694 blocked ATO effects. Thus, ATO-increased proliferation resulted from AP-1-dependent NHE1 activation in MDCK cells.

Giant cell arteritis and its mimics: A comparison of three patient cohorts.

OBJECTIVE: To compare temporal artery biopsy (TAB)-positive giant cell arteritis (GCA) to TAB-negative GCA and patients with GCA mimics METHODS: PATIENTS DIAGNOSED WITH TAB-POSITIVE AND TAB-NEGATIVE GCA BETWEEN 1/1/1998 AND 12/31/2013 WERE: retrospectively identified. These two groups were compared to a cohort of patients with TAB performed between 1/1/2009 and 12/31/2010 in which the TAB was negative and alternative diagnosis was provided after a minimum of 6-months of follow-up. Baseline characteristics were compared between groups using chi-square and rank sum tests. RESULTS: 591 study subjects were identified (286 TAB-positive, 110 TAB-negative GCA and 195 TAB-negative GCA mimics) during the respective study periods. Compared to TAB-negative GCA, GCA mimics had similar rates of headache and vision loss but significantly less frequent jaw/limb claudication, arterial bruits and constitutional symptoms, as well as lower platelet levels. Compared to TAB-positive GCA patients, TAB-negative GCA were younger, had shorter time to diagnosis, met fewer 1990 ACR classification criteria and had lower frequencies of polymyalgia rheumatica, jaw claudication and temporal artery abnormalities; but, higher frequency of arm claudication and constitutional symptoms. Among 61 TAB-negative patients with advanced arterial imaging, 43 (69%) had at least one abnormality consistent with GCA. CONCLUSION: Consideration of alternative diagnoses is requisite in evaluating patients with negative TAB. Advanced imaging assists in identifying occult large-vessel vasculitis and should be employed in all TAB-negative patients with suspicion for GCA.

Efficacy of Methotrexate in Real-world Management of Giant Cell Arteritis: A Case-control Study.

OBJECTIVE: To determine the effect of methotrexate (MTX) on relapse risk and glucocorticoid (GC) use in a large single-institution cohort of patients with giant cell arteritis (GCA). METHODS: Patients diagnosed with GCA from 1998 to 2013 with confirmed evidence of temporal artery biopsy and/or radiographic evidence of large vessel vasculitis were identified. Each patient with GCA treated with adjunct MTX (case) was matched to a similar patient with GCA treated only with GC (control). GC requirements and relapse events before and after MTX initiation (or corresponding index date) were compared using rate ratios (RR). RESULTS: Eighty-three cases and 83 controls were identified and compared. No significant differences in age, demographics, laboratory variables, baseline disease characteristics, or mean initial prednisone doses were observed. Median [interquartile range (IQR)] time from GCA diagnosis to MTX initiation in cases was 39 (13-80) weeks and the median (IQR) starting dose was 13.5 (10-15) mg/week. RR comparing relapse rates before and after MTX initiation/index date were significantly reduced in both cases (RR 0.32, 95% CI 0.24-0.41) and controls (RR 0.60, 95% CI 0.43-0.86). The decrease in relapse rate was significantly greater in patients taking MTX than in those taking GC alone (p = 0.004). Rates of GC discontinuation did not differ between groups. CONCLUSION: In this large single-institution cohort, the addition of MTX to GC decreased the rate of subsequent relapse by nearly 2-fold compared to patients taking GC alone. MTX may be considered as adjunct therapy in patients with GCA to decrease the risk of further relapse events.

Predictors of relapse and treatment outcomes in biopsy-proven giant cell arteritis: a retrospective cohort study.

OBJECTIVE: To evaluate characteristics of relapse, relapse rates, treatment and outcomes among patients with biopsy-proven GCA in a large, single-institution cohort. METHODS: We conducted a retrospective review of all patients with biopsy-proven GCA from 1998 to 2013. Demographic, clinical, laboratory and treatment data at presentation and during follow-up were collected. Comparisons by relapse rate were performed using chi-square tests. Prednisone discontinuation by initial oral dose ≤40 and >40 mg/day was compared using Cox models. RESULTS: The cohort included 286 patients [74% female, mean age at diagnosis 75.0 years (s.d. 7.6), median follow-up 5.1 years). During follow-up, 73 patients did not relapse, 80 patients had one relapse and 133 had two or more relapses. The first relapse occurred during the first year in 50% of patients, by 2 years in 68% and by 5 years in 79%. More patients with established hypertension (P = 0.007) and diabetes (P = 0.039) at GCA diagnosis were in the high relapse rate group ( ≥ 0.5 relapses/year) and more females were in the low or high relapse groups than in the no relapse group (P = 0.034). Patients receiving an initial oral prednisone dose >40 mg/day were able to reach a dose of <5 mg/day [hazard ratio (HR) 1.46 (95% CI 1.09, 1.96)] and discontinue prednisone [HR 1.56 (95% CI 1.09, 2.23)] sooner than patients receiving ≤40 mg/day without an increase in observed glucocorticoid-associated adverse events. CONCLUSION: Females and patients with hypertension or diabetes at GCA diagnosis have more relapses during follow-up. Patients treated with an initial oral prednisone dose >40 mg/day achieved earlier prednisone discontinuation.

Retrospective Comparison of Open versus Endovascular Procedures for Takayasu Arteritis.

OBJECTIVE: To compare the outcomes between vascular surgery and endovascular procedures in a cohort of patients with Takayasu arteritis (TA). METHODS: A retrospective cohort study was conducted of patients with TA who underwent vascular interventions at a tertiary center between 1984 and 2009. The American College of Rheumatology criteria for TA were used to select patients. Disease activity was assessed according to the Kerr criteria. Data are reported using descriptive statistics and Kaplan-Meier methods for complication rates. RESULTS: The cohort included 66 patients with TA who underwent 119 vascular procedures (surgery 93; endovascular repair 26). The most frequent indication for vascular surgery and endovascular procedure was arm claudication (surgical group 43%, endovascular repair group 31%). In 59% of the vascular surgical procedures and in 38% of endovascular procedures, the disease was active within 1 month of intervention. The most frequent arterial lesion requiring intervention was the aorta (28%) in the vascular surgery group and the subclavian (35%) in the endovascular repair group. Early complications occurred after 15 surgeries and 4 endovascular repair procedures (p = 0.93). Late complications occurred after 34 surgical procedures and 10 endovascular repair procedures (44% vs 66%, respectively; p = 0.33). The majority of complications in both groups were restenosis. Hypertension, dyslipidemia, and higher doses of corticosteroids were associated with an increased risk of postprocedural complications and restenosis. CONCLUSION: In patients with TA, both open surgical and endovascular revascularization procedures are associated with high failure rates and frequent operative complications. Traditional cardiovascular risk factors, corticosteroid dose, and active disease are risk factors for restenosis after revascularization procedures.

Dexamethasone inhibits BAFF expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis.

Fibroblast-like synoviocytes (FLS) play a major role in the pathogenesis of rheumatoid arthritis (RA). FLS isolated from patients with RA (FLS-RA) express B cell-activating factor belonging to the TNF family (BAFF), a cytokine that has been associated with the onset and progression of RA. Glucocorticoids are powerful anti-inflammatory drugs used in the treatment of RA. In the present study, we examined the effect of dexamethasone (Dex) on constitutive and TNF-alpha- and IFN-gamma-induced BAFF expression in FLS-RA. BAFF mRNA expression and soluble BAFF were determined by RT-PCR and ELISA, respectively. The results showed that constitutive BAFF mRNA expression was inhibited by Dex in a dose- and time-dependent manner. Also, Dex inhibited the secretion of BAFF in a time-dependent manner reaching 76% of inhibition 72 h after treatment. Moreover, Dex suppressed both mRNA and protein BAFF expression induced by TNF-alpha but had no effect on IFN-gamma-induced BAFF expression. In comparison with B cells cultured alone, B cells co-cultured with FLS-RA exhibited a higher survival, which was inhibited when FLS-RA were pretreated with Dex. However, the enhanced B cell survival was reestablished by the addition of rhBAFF. Therefore, Dex is a potent inhibitor of constitutive and TNF-alpha-induced BAFF expression in FLS-RA.

[Effectiveness of infliximab in patients with inflammatory arthritis refractory to conventional treatment]. / Evaluación del tratamiento con infliximab en enfermos con artritis inflamatoria refractaria a drogas habituales.

BACKGROUND: Tumor necrosis factor antagonists are useful in the treatment of several chronic inflammatory immune mediated diseases. AIM: To assess the effects of infliximab in 21 patients with inflammatory arthropaties, refractary to conventional treatment. PATIENTS AND METHODS: Eleven patients with rheumatoid arthritis, seven with psoriatic arthritis and three with spondyloarthritis were treated. The mean duration of the diseases was 10 years. Infliximab was administered intravenously in a dose of 3 mg/kg body weight. A median of 6 doses in 8 months was administered. Effectiveness was assessed in 19 patients that received three or more doses. RESULTS: Infliximab was effective in 16 patients (10 with rheumatoid arthritis, four with psoriasis and two with spondyloarthritis) and ineffective in three. In responsive patients, a reduction in the number of inflammed joints and morning stiffness and an improvement in functional capacity was observed. Fifteen of the 16 patients perceived an improvement in their health status. This answer was concordant with concomitant medical evaluation in 15. Patients that maintained the treatment felt very well, well or regular, whereas five of six patients that discontinued the treatment felt ill. Thirteen patients had adverse effects. Treatment was discontinued in two patients due to drug induced lupus, allergy in 2, hypertension in one, high costs in three and lack of response in three. CONCLUSIONS: Infliximab reduced arthritic activity in 16 of 19 patients with severe treatment refractary arthritis.