Effectiveness and safety of medium-dose prednisone in giant cell arteritis: a retrospective cohort study of 103 patients.

OBJECTIVES: To compare the effectiveness and safety of medium-dose (MD) and high-dose (HD) prednisone regimens and to identify factors related to remission with a target maintenance dose of prednisone in patients with giant cell arteritis (GCA). METHODS: Retrospective cohort study conducted in an autoimmune diseases unit. Patients received ≤ 30 mg (MD group) or >30 mg (HD group) of daily prednisone as monotherapy or combined with methylprednisolone pulses and/or methotrexate, at the discretion of the physician. The primary endpoint was time to clinical and biological remission receiving a prednisone maintenance dose ≤ 7.5 mg/day. Factors related to the primary endpoint were identified by Cox regression analysis. RESULTS: Overall, 103 patients (MD=53, HD=50) were followed for a median (95%CI) of 2.85 (2.57-3.52) years. Both groups exhibited similar baseline features except for ocular ischaemic manifestations (MD=21%, HD=48%, p=0.004). Patients in the MD group had a shorter time to the primary endpoint (MD=186 [147-223], HD=236 [177-276] days, HR=1.70 [1.12-2.57], p=0.01) with no increase in relapses (MD=39%, HD=50%, p=0.29) or GCA complications (MD=11%, HD=16%, p=0.49). Cumulative prednisone doses at 6 months were 2.47 ± 0.70 g for MD patients and 3.86 ± 1.85 g for HD patients (p<0.001). Adverse effects were more frequent among HD recipients (MD=43%, HD=66%, p=0.02). The only independent factor associated with the primary endpoint was the use of methylprednisolone pulses (HR=2.21 [1.31-3.71], p=0.003). CONCLUSIONS: MD prednisone regimen may be an effective and safe alternative to HD prednisone regimen in GCA. Induction with methylprednisolone pulses predicts a better response, allowing for a less intensive prednisone regimen.

Aproximación diagnóstica a las uveítis / Uveitis: diagnostic approach

Mujer de 32 años, sin antecedentes epidemiológicos relevantes salvo contacto tuberculoso en la infancia, remitida desde el Servicio de Oftalmología para valorar estudio de enfermedad sistémica. Refiere miodesopsias y disminución de agudeza visual en ambos ojos de varios meses de evolución, acompañados de artralgias y tos seca, sin otra sintomatología extraocular. La exploración oftalmológica muestra agudeza visual de 0,3 en el ojo derecho y 0,4 en el ojo izquierdo. En la exploración de la cámara anterior se observa una uveítis anterior bilateral granulomatosa con discreta inflamación (Tyndall 1+). Se observa vitritis (3+) bilateral, con exudados en banco de nieve y flebitis periférica. La angiografía con fluoresceína no muestra signos de vasculitis central, y la tomografía de coherencia óptica confirma la existencia de edema macular quístico bilateral. La autofluorescencia es normal. ¿Cómo debe ser evaluada inicialmente esta paciente para decidir cuál es el estudio sistémico más adecuado teniendo en cuenta las manifestaciones oftalmológicas?(AU)

A 32 year-old woman was referred from the Ophthalmology Department to rule out a possible systemic disease. Her only past medical history of relevance was a tuberculosis contact during childhood. She complained of floaters and progressive blurring of vision in both eyes for some months, as well as arthralgia and cough. Her visual acuity was 0.3 in the right eye and 0.4 in the left eye. Biomicroscopy showed bilateral anterior granulomatous uveitis (1+ cells). Funduscopy showed bilateral vitritis 3+, snow banking and peripheral phlebitis. Fluorescein angiography did not show central vasculitis, and optical coherence tomography showed bilateral cystoid macular oedema. Fundus autofluorescence was normal. How would you initially assess this patient in order to decide which systemic examination should be performed, bearing in mind the ophthalmological manifestations?(AU)

[Uveitis: diagnostic approach]. / Aproximación diagnóstica a las uveítis.

A 32 year-old woman was referred from the Ophthalmology Department to rule out a possible systemic disease. Her only past medical history of relevance was a tuberculosis contact during childhood. She complained of floaters and progressive blurring of vision in both eyes for some months, as well as arthralgia and cough. Her visual acuity was 0.3 in the right eye and 0.4 in the left eye. Biomicroscopy showed bilateral anterior granulomatous uveitis (1+ cells). Funduscopy showed bilateral vitritis 3+, snow banking and peripheral phlebitis. Fluorescein angiography did not show central vasculitis, and optical coherence tomography showed bilateral cystoid macular oedema. Fundus autofluorescence was normal. How would you initially assess this patient in order to decide which systemic examination should be performed, bearing in mind the ophthalmological manifestations?

Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases.

OBJECTIVES: To analyse the safety and efficacy of the off-label use of rituximab in patients with severe, refractory systemic autoimmune diseases. METHODS: In 2006, the Study Group on Autoimmune Diseases of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases refractory to standard therapies (failure of at least two immunosuppressive agents). RESULTS: One hundred and ninety-six patients with systemic autoimmune diseases treated with rituximab have been included in the Registry (158 women and 38 men, mean age 43 years). Systemic autoimmune diseases included systemic lupus erythematosus (107 cases), inflammatory myopathies (20 cases), ANCA-related vasculitides (19 cases), Sjögren's syndrome (15 cases) and other diseases (35 cases). A therapeutic response was evaluable in 194 cases: 99 (51%) achieved a complete response, 51 (26%) a partial response and 44 (23%) were classified as non-responders. After a mean follow-up of 27.56+/-1.32 months, 44 (29%) out of the 150 responders patients relapsed. There were 40 adverse events reported in 33 (16%) of the 196 patients. The most frequent adverse events were infections, with 24 episodes being described in 19 patients. Thirteen (7%) patients died, mainly due to disease progression (7 cases) and infection (3 cases). CONCLUSIONS: Although not yet licensed for this use, rituximab is currently used to treat severe, refractory systemic autoimmune diseases, with the most favourable results being observed in Sjögren's syndrome, inflammatory myopathies, systemic lupus erythematosus and cryoglobulinemia.

Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences.

OBJECTIVES: We aimed to establish the prevalence, predictors and clinical consequences of vitamin D deficiency in patients with SLE. METHODS: Cross-sectional study including patients fulfilling ACR criteria for the classification of SLE. Serum 25(OH)D levels at 30 and 10 ng/ml were the cut-off values for vitamin D insufficiency and vitamin D deficiency, respectively. SLE activity was measured by SLEDAI and irreversible organ damage by the SLICC-ACR index. Fatigue was quantified using a 0-10 visual analogue scale (VAS). RESULTS: Ninety-two patients (90% women, 98% white) were included in the study. Sixty-nine (75%) and 14 (15%) patients presented with vitamin D insufficiency and deficiency, respectively. Female sex (P = 0.001), treatment with HCQ (P = 0.014) and treatment with calcium and vitamin D (P = 0.049) predicted higher levels of 25(OH)D. Photosensitivity [odds ratio (OR) 3.5] and photoprotection (OR 5.7) predicted vitamin D insufficiency and deficiency, respectively. Higher age (OR 0.95) and HCQ use (OR 0.29) protected against vitamin D deficiency. Patients with vitamin D deficiency had a higher degree of fatigue as quantified by a 0-10 VAS (mean 5.32 vs 4.03, P = 0.08). No relation was seen between vitamin D insufficiency or deficiency and disease duration, SLEDAI or SLICC-ACR indexes. CONCLUSIONS: Vitamin D insufficiency and deficiency are common in patients with SLE and are associated with sun avoidance. HCQ prevented vitamin D deficiency. Vitamin D deficiency was related to a higher degree of fatigue. Vitamin D levels had no relation with SLE severity.

Antimalarials may influence the risk of malignancy in systemic lupus erythematosus.

BACKGROUND: Recent studies suggest that antimalarials have antineoplastic properties. OBJECTIVE: To investigate whether antimalarials decrease the risk of cancer in systemic lupus erythematosus (SLE). METHODS: An observational prospective cohort study was carried out. 235 patients were included in the study at the time of diagnosis (American College of Rheumatology criteria). The end point was the diagnosis of cancer. Kaplan-Meier cancer-free survival curves for patients treated and not treated with antimalarials were compared. A Cox proportional hazards model was fitted, with cancer as the dependent variable. Age at diagnosis, gender, treatment with azathioprine, cyclophosphamide and methotrexate, smoking, Systemic Lupus International Collaborating Clinics (SLICC) Damage Index 6 months after diagnosis, year of diagnosis and treatment with antimalarials were entered as independent variables. RESULTS: 209 (89%) patients were women. 233 (99%) patients were white. Mean (SD) age at diagnosis was 37 (16) years. Median (range) follow-up was 10 (1-31) years. 156 (66%) patients had ever received antimalarials. 2/156 (1.3%) ever-treated patients compared with 11/79 (13%) never-treated patients had cancer (p<0.001). Cumulative cancer-free survival in treated and not treated patients was 0.98 and 0.73, respectively (p<0.001). Adjusted hazard ratio for cancer among malaria drug users compared with non-users was 0.15 (95% CI 0.02 to 0.99). CONCLUSIONS: This study launches the hypothesis of a protective action of antimalarials against cancer in patients with SLE. This effect should be confirmed in larger multicentre studies.

Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus.

Antimalarials have shown beneficial effects on systemic lupus erythematosus (SLE) activity. Our aim was to investigate whether antimalarials protect against thrombosis and influence survival in SLE patients. A prospective cohort including 232 patients with SLE were included in the study at the time of lupus diagnosis. End points were documented thrombosis and death due to any cause. A Cox regression-multiple-failure time survival analysis model was fitted to establish the effect of antimalarials on the development of thrombosis. Kaplan-Meier survival curves and propensity score adjusted-Cox regression analysis were performed to investigate the effect of antimalarials use on survival. Of our subjects, 204 patients (88%) were women. 230 patients (99%) were white. 150 patients (64%) had ever received antimalarials. Median time on antimalarials was 52 months (range three to 228 months). The Cox multiple-failure time survival analysis showed that taking antimalarials was protective against thrombosis (HR 0.28, 95% CI 0.08-0.90), while aPL-positivity (HR 3.16, 95% CI 1.45-6.88) and previous thrombosis (HR 3.85, 95% CI 1.50-9.91) increased the risk of thrombotic events. Twenty-three patients died, 19 of whom (83%) had never received antimalarials. No patient treated with antimalarials died of cardiovascular complications. Cumulative 15-year survival rates were 0.68 for never versus 0.95 for ever treated patients (P < 0.001). Age at diagnosis and propensity score-adjusted HR for antimalarials ever versus never users was 0.14 (95% CI 0.04-0.48). Our study shows a protective effect of antimalarials against thrombosis and an increased survival of SLE patients taking these drugs. These data support the routine use of antimalarials in all patients with SLE.

High risk of tuberculosis in systemic lupus erythematosus?

The incidence and severity of tuberculosis (TB) in patients with systemic lupus erythematosus (SLE) varies greatly among different series. In addition, prospective data are scarce. The aim of this study is to analyse the frequency and severity of TB in our cohort of lupus patients. We analysed data from a prospective database of a single center cohort of 232 patients with SLE (ACR criteria). Prophylaxis with isoniazid was not regularly administered. We identified all cases of TB diagnosed during 10 years (January 1994 to December 2003). The following variables were analysed: annual incidence of TB, location of infection and response to therapy. Data from published series reporting on the incidence of TB among SLE patients were extracted. Three patients (1.3%) suffered clinically manifest TB in 1603 patient-years of follow-up, resulting in an incidence of 187 cases/100,000 patient-years (95% CI 39-547). The pooled annual incidence of TB infection in our area during this period was 30/100,000 individuals. We recorded two cases of pulmonary TB and one case of tuberculous pleurisy. All patients had good response to therapy. The annual incidence of TB among SLE patients in other series, most of them from developing countries, varied between 150/100,000 patients in Turkey and 2450/100,000 patients in India. Of note, high prevalence of extrapulmonary forms as well as elevated TB-associated mortality was reported in most series. TB was more frequent in SLE patients than expected in the general population. We did not see any cases of disseminated infection and all patients had good response to treatment. Our data compare favourably in terms of incidence, severity and outcome with those from highly endemic areas.

Antiphospholipid antibodies predict early damage in patients with systemic lupus erythematosus.

The aim of this study was to determine whether the different autoantibodies predict early damage in patients with systemic lupus erythematosus (SLE). The patients comprised a prospective inception cohort of 205 patients with SLE, 154 on follow-up for at least five years after diagnosis. Eight patients who died before the fifth year of disease course were included in analyses comprising survival. Organ damage was measured using the Systemic Lupus International Collaborating Clinics--American College of Rheumatology damage index (SDI). Endpoints were the development of some (SDI > or = 1) or severe (SDI > 2) damage at five years after diagnosis or the combined outcome 'SDI > or = 1 or death at five years'. Autoantibodies [anti-DNA, anti-Ro, anti-La, anti-Sm, anti-U1RNP, any anti-ENA and antiphospholipid (aPL)] were included in univariate and multivariate analysis. 'Age at diagnosis' was also included as an independent variable in multivariant analyses. Sapporo criteria were used to define aPL positivity. Eighty-four patients (54.5%) had accrued damage at five years, 17 patients (11.0%) having severe damage. Patients with aPL had damage in a higher proportion (63.2% any damage, 17.6% severe damage). Only aPL were related to damage in univariate analysis (P = 0.03). In logistic regression models, aPL were the only independent predictors of damage at five years (OR 1.94, 95% CI 1.01-3.73), severe damage at five years (OR 3.34, 95% CI 1.11-10.03) and increasing damage since diagnosis (OR 2.46, 95% CI 1.24-4.87). No autoantibody was a predictor of the outcome 'SDI > or = 1 or death at five years'. The conclusion was that aPL predict early damage in patients with SLE.

Homocysteine, antiphospholipid antibodies and risk of thrombosis in patients with systemic lupus erythematosus.

Cardiovascular disease is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Antiphospholipid syndrome (APS) is one of the most important causes of thrombosis in SLE. In addition, an association between hyperhomocysteinemia and increased cardiovascular risk has also been reported. Our aim is to analyse the association of thrombosis with plasma total homocysteine (ptHcy), antiphospholipid antibodies (aPL) and other vascular risk factors in SLE patients. Fasting plasma levels of ptHcy, vitamin B12, folate, total cholesterol and creatinine were measured in 117 SLE patients. Clinical and immunological data were obtained from our prospective computerized database. aPL-positivity was defined according to Sapporo criteria. There was no association between aPL and ptHcy. ptHcy was higher in patients with arterial (median 13.02 versus 10.16 micromol/L, P = 0.010) but not venous thrombosis. In the subgroup analysis, this association was only seen in aPL-negative patients. In logistic regression, aPL (OR 6.60, 95% CI 1.86-23.34) and ptHcy (OR 1.10, 95% CI 1.01-1.19) were independently associated with arterial thrombosis. However, when hypertension, smoking and plasma total cholesterol were added to the model, only aPL (OR 7.38, 95% CI 2.02-26.91) and hypertension (OR 7.70, 95% CI 2.33-25.39), but not ptHcy, remained independently related to arterial events. aPL was the only variable independently related to venous thrombosis (OR 7.68, 95% CI 1.60-36.86). ptHcy concentrations are higher in SLE patients with arterial thrombosis. No interaction between homocysteine and aPL was found. Raised ptHcy may be a marker of increased vascular risk in aPL-negative SLE patients. The role of homocysteine as a marker of vascular risk may depend on the presence of traditional risk factors, although a modest intrinsic effect cannot be entirely excluded.

[Otomastoiditis caused by Aspergillus in AIDS]. / Otomastoiditis por Aspergillus en el SIDA.

BACKGROUND: Aspergillus otomastoiditis is an infrequent infection that occurs in most cases in immunocompromised hosts. Although fungal infections are common in AIDS patients, few cases of Aspergillus otomastoiditis have been reported. METHODS: Two clinical cases of AIDS patients with Aspergillus otomastoiditis are reported, and a review of the literature is performed. RESULTS: Clinical presentation in both cases was similar to those of other diseases involving middle and internal ear. Infection was linked to severe immunosuppression (C3 group). CONCLUSIONS: Aspergillus otomastoiditis is an infrequent infection in AIDS patients. Different routes by which Aspergillus obtains access to the middle ear have been proposed (tympanogenic, meningogenic, hematogenous and direct spread from paranasal sinuses or external auditory canal). Otorrhea, otalgia, hearing loss and facial nerve involvement are common findings. Bone destruction and invasion of brain or skull base may occur. CT or MRI are necessary to evaluate the extent of the disease. Etiologic diagnosis requires histopathologic confirmation on deep tissue biopsy or isolation from blood cultures or fistula exudates, because Aspergillus is a common saprophytic fungus in external auditory canal. Concurrent infections (i.e. Pseudomonas aeruginosa) frequently delay the correct diagnosis. Aggressive surgical resection and intravenous antifungal chemotherapy (amphotericin B or itraconazole) are the main therapeutic options. Outcome is poor as a consequence of severity, delay of etiologic diagnosis and difficulty of aggressive surgical approach in compromised patients. In patients with AIDS a low CD4 cell count would favour invasive Aspergillus infection, implying a worse outcome.