Registry of the Spanish Network for Systemic Sclerosis: Survival, Prognostic Factors, and Causes of Death.

Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan-Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors.

Differential expression pattern of microRNAs in CD4+ and CD19+ cells from asymptomatic patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to investigate the pattern of microRNA (miRNA) expression in CD19+ and CD4+ cells from asymptomatic patients with systemic lupus erythematosus (SLE). METHODS: A screening of the expression of 377 miRNAs was performed in human CD4+ and CD19+ cells isolated from the peripheral blood by using a TaqMan Human MicroRNA Array. Validation of differential expression pattern of those was performed using TaqMan assays in these cell populations obtained from a larger cohort of patients and controls. RESULTS: According to the screening assays, three miRNAs were differentially expressed (p value <0.1) in cell populations from both patients and controls: hsa-miR-143, hsa-miR-224 and hsa-miR-576-5p for CD4+ cells, and hsa-miR-10a, hsa-miR-31 and hsa-miR-345 for CD19+ cells. After validation, significant differences (p value <0.05) were confirmed only for hsa-miR-143 and hsa-miR-224 in CD4+ cells and for hsa-miR-10a and hsa-miR-345 in CD19+ cells. In all cases, the miRNAs were over expressed in SLE patients compared with healthy donors. CONCLUSIONS: Our results support a different pattern of miRNA expression in SLE patients.

Screening for PAH in patients with systemic sclerosis: focus on Doppler echocardiography.

It is well established that patients with CTDs such as SSc carry a considerable risk of developing pulmonary arterial hypertension (PAH). Such SSc-PAH patients have an even worse prognosis than patients with only one of these two conditions. In view of the high incidence and prevalence of PAH in SSc, and the available treatment options that improve quality of life, exercise capacity and possibly survival, systematic screening has been recommended. The present article reviews current recommendations from PAH guidelines, focusing on studies that used Doppler echocardiography for screening, and describes limitations associated with the procedure. Furthermore, characteristics and parameters used to identify patients at high risk of developing PAH are summarized.

Diagnóstico y tratamiento de la hipertensión pulmonar / Diagnosis and treatment of pulmonary hypertension

La hipertensión arterial pulmonar es un proceso idiopático o puede estar asociado a otras circunstancias como enfermedades del tejido conectivo, cardiopatías congénitas, hipertensión portal, exposición a inhibidores del apetito u otras drogas, o a agentes infecciosos como en el virus de la inmunodeficiencia humana (VIH). En la mayor parte de los pacientes se llega al diagnóstico como resultado de la valoración de sus síntomas, mientras que otros son diagnosticados fortuitamente o durante la revisión sistemática de individuos asintomáticos pertenecientes a grupos de riesgo. Se revisan los métodos de valoración útiles para el diagnóstico de la hipertensión arterial pulmonar. Un algoritmo diagnóstico puede servir de guía en dicha evaluación, aunque puede ser modificado de acuerdo con circunstancias clínicas específicas. El número de opciones terapéuticas se ha incrementado en los últimos años. Se revisa la utilización de los bloqueadores de los canales de calcio, prostaciclina y análogos, antagonistas de los receptores de la endotelina, inhibidores de la fosfodiesterasa-5 y del tratamiento combinado y se proporcionan recomendaciones específicas acerca del tratamiento actual

Pulmonary arterial hypertension is an idiopathic process or can be associated with another circumstances (connective tissue diseases, congenital heart disease, portal hypertension, exposure to appetite suppressants or anoher drugs or infectious agents such as HIV). Most patients are diagnosed as the result of an evaluation of symptoms, whereas others are diagnosed incidentally or during screening of asymptomatic populations at risk. We reviews systematic screening for the approach to diagnosing pulmonary arterial hypertension. A diagnostic algorithm can guide the evaluation but it can be modified according to specific clinical circumstances. The number of therapeutic options has increased.in the last years. We reviews the use of calcium-channel blockers, prostacyclin (and analogues), endothelin-receptor antagonists, and phosphodiesterase-5 inhibitors, and the use of combination therapy, and provides specific recommendations about the actual treatment (AU)

[Vogt-Koyanagi-Harada disease. Characteristics of a series of Andalusian patients]. / Enfermedad de Vogt-Koyanagi-Harada. Características de un grupo de pacientes andaluces.

BACKGROUND: To describe the characteristics of a series of patients diagnosed of Vogt-Koyanagi-Harada disease (VKHD) and controlled by an Uveitis Unit (composed of ophthalmologists and internists) in our population. PATIENTS AND METHOD: Retrospective descriptive study of 11 patients with VKHD (5 males and 6 women; median age at diagnosis 32.6 years old) followed-up between 1980 and 2003. RESULTS: All patients suffered panuveitis and/or exudative retinal detachment. Extraocular signs were present in all cases: neurological in 63.7% (aseptic meningitis and/or focal symptoms), cutaneous in 81.8% (vitiligo, whiteness, poliosis, alopecia), neurosensorial hypoacusis (50% of patients with audiometry), and general symptoms in 25%. They all received systemic corticosteroids. Cyclosporine was added in 5 patients (45.4%) with posterior uveitis, and azathioprine in 2 of them for iridocyclitis. The final visual acuity was 0.5 or better in 81.8% of cases, but 2 patients had an unfavourable evolution (one, who had cataract and band keratopathy in the left eye and severe visual worsening, needed right vitrectomy, and the other suffered severe ocular hypotension). Complications developed in 2 other patients: cataract and glaucoma in one, and synechiae without glaucoma in the other. CONCLUSIONS: We found less frequency of exudative retinal detachment and greater frequency of cutaneous signs than the communicated. A significant percentage of cases needed immunosuppressive agents. Final visual acuity was good in the majority of patients.

Frecuencia de anticuerpos antinucleares en ancianos sanos / Frequency of antinuclear antibodies in the healthy elderly

Fundamento: Conocer la frecuencia de anticuerpos antinucleares (AAN) en población anciana en Andalucía. Pacientes y métodos: Se estudiaron 100 ancianos sanos (edad media, 81,6 años) y un grupo control de 199 donantes de sangre (edad media, 33,5 años). Los AAN se determinaron mediante inmunofluorescencia indirecta (IFI; sustratos triple de rata y HEp-2), los anticuerpos anti-ENA mediante contrainmunoelectroforesis y los anticuerpos anti-ADNn con IFI (Crithidia luciliae). Resultados: En ancianos, el título de AAN fue > 1/40 en el 51 por ciento y > 1/160 en el 36 por ciento (sustrato triple de rata), y > 1/40 en el 74 por ciento y > 1/160 en el 64 por ciento (sustrato HEp-2). El patrón más frecuente fue el moteado fino. Los anticuerpos anti-ADNn y antiENA fueron negativos. En controles, la frecuencia de AAN > 1/40 (HEp-2) fue del 7,5 por ciento (p < 0,001). Conclusión: La alta frecuencia de AAN en ancianos obliga a valorarlos con cautela en ausencia de indicios clinicobiológicos de enfermedad autoinmunitaria. (AU)

[Comparative study of misoprostol and nifedipine in the treatment of Raynaud's phenomenon secondary to systemic diseases. Hemodynamic assessment with Doppler duplex]. / Estudio comparativo de misoprostol y nifedipino en el tratamiento del fenómeno de Raynaud secundario a enfermedades sistémicas. Valoración hemodinámica mediante Doppler-dúplex.

OBJECTIVE: To evaluate the mid-term efficiency and therapeutic safety at a mid term of the orally administered misoprostol, a synthetic PGE1, analogue, compared with nifedipine for the treatment of RP secondary to autoimmune systemic diseases. METHODS: A double blind, crossover study was designed. Patients were randomly distributed to receive either retard nifedipine (20 mg/12 hourly) and misoprostol (200 micrograms/12 hourly) in 10-day periods (washing period with placebo for 10 days). At the end of each period a clinical assessment was obtained on the frequency and severity of symptoms as well as on secondary drug reactions. Simultaneously, blood flow changes in radial artery were Doppler-duplex investigated (pulsatility index, resistance index). RESULTS: Twenty patients were studied (15 women and 5 men). The mean basal daily frequency of attacks was 4.8 +/- 2.0 compared with 2.4 +/- 1.4 with nifedipine (p < 0.001) and 2.6 +/- 1.2 with misoprostol (p < 0.001). The mean basal severity of attacks, according to a pre-established scale decreased from 3.7 +/- 0.6 to 1.9 +/- 0.9 with nifedipine (p < 0.001) and to 2.0 +/- 1.0 with misoprostol (p < 0.001). The mean basal value of blood flow in radial artery was 24.9 +/- 14.4 ml/min; with nifedipine it increased to 43.0 +/- 19.2 ml/min (p < 0.001) and with misoprostol to 46.9 +/- 19.2 ml/min (p < 0.001). Five patients (25%) had secondary effects with nifedipine and three (15%) with misoprostol; in no case had therapy to be discontinued. CONCLUSIONS: Misoprostol was similar to nifedipine for the treatment of Raynaud phenomenon secondary to systemic diseases and can be a therapeutic alternative for these patients.

[The use of interferon alfa-2r in the treatment of autoimmune uveitis (primary or associated with Behçet's disease)]. / Utilización de interferón alfa 2r en el tratamiento de las uveítis autoinmunes (primarias o asociadas a enfermedad de Behçet).

BACKGROUND: The improvement in ocular inflammation in patients with cyclosporine A resistant Behçet disease (CyA) during therapy of severe aphthosis with recombinant interferon-alpha 2b (IFN alpha) prompted its evaluation for treatment of refractory autoimmune uveitis. METHOD: IFN alpha was used in 18 patients with posterior uveitis, nine with Behçet disease and nine with primary uveitis (mean evolution time 3.8 years) previously treated with corticosteroids (18), CyA (16) and azathioprine (1). The dose was 5 MU/day (4 weeks) and then twice weekly (12 weeks) maintaining the previous therapy. Evaluations were made at the start of the study, two weeks and two months and a cross-sectional study in February 1995. RESULTS: At the early phase both vitreal cellularity (p = 0.01) and macular edema (p = 0.003) improved; at the late phase improvements were noted in vitreal cellularity (p < 0.0001), macular (p < 0.0001) and papillar edema (p = 0.04) and visual acuity (p = 0.006). In February 1995 (mean evolution time 30 months), ten patients (56%) remain without treatment with inactive disease, six (33%) with CyA and two (11%) with CyA and IFN alpha. Improvements in vitreal cellularity (p = 0.0001), macular edema (p = 0.0001) and visual acuity (p = 0.013) were still present although macular ischemia was more severe than at the beginning (p = 0.035). The most important adverse reactions (late reactions) included depression (three cases) and thyroid changes (two cases). CONCLUSIONS: IFN alpha is an important therapeutic alternative for posterior uveitis refractory to corticosteroid therapy (included CyA).

[Serologic and molecular HLA typing in patients from Andalucia with Behçet's disease. Genetic and clinical correlations]. / Tipificación HLA serológica y molecular en pacientes andaluces con enfermedad de Behçet. Correlaciones geneticoclínicas.

BACKGROUND: HLA typing was performed in 67 patients with Behçet's disease from Andalucia, Spain to: 1) analyze the association of class I and II molecules with Behçet's disease in Spain; 2) study the clinical correlations and 3) evaluate its diagnostic and/or prognostic role. PATIENTS AND METHODS: 1) Serologic typing (microlymphocytotoxicity): class I molecules in 67 patients and class II molecules in 47 patients (controls: 223 healthy volunteers). 2) Oligotyping (PCR-SSO): class II molecules (DQB1 and generic DRB1) in 47 patients and 189 controls. 3) STATISTICAL ANALYSIS: chi square test (dicotomic variables) and Student t test (continuous variables), and calculation of the relative risk by the Wolff and Haldane formulas. RESULTS: The HLA B51 antigen was the most frequently observed in the whole series (p = 0.003) in males with ocular disease (p = 0.0001) and in patients with cutaneous (p = 0.001) and digestive involvement (p = 0.05). The HLA B51-positive males were younger at disease onset (p = 0.01) with neurologic involvement being infrequent (p = 0.03). The HLA B51 antigen was associated with neurologic (p = 0.06) and articular involvement (p = 0.05). The DQB1*0303 was associated with uveitis of bad evolution (p = 0.01). The DR11 and DQB1*0301 were more frequent in HLA B51-positive patients and the DQ5 was negatively associated with Behçet's disease, particularly in the HLA B51-positive patients. CONCLUSIONS: The study of the HLA antigens provides useful information for the diagnosis of Behçet's disease, aids in differentiating the different clinical forms and has prognostic significance.