Bruno Laganà

Neuropsychiatric lupus syndromes: relationship with antiphospholipid antibodies.

The authors assessed the prevalence of neuropsychiatric manifestations occurring in patients with systemic lupus erythematosus (NPSLE), according to the American College of Rheumatology standardized definitions for NPSLE, and evaluated the relationship between NPSLE and antiphospholipid antibodies. Sixty-one consecutive SLE patients were studied. Neuropsychiatric manifestations consistent with the diagnosis of NPSLE occurred in 44 (72%). Patients with NPSLE showed significantly higher levels of anticardiolipin antibodies.

Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFα blockers: Safety and immunogenicity

Twenty-eight patients with low-moderate, stable rheumatoid arthritis (RA), under treatment with tumor necrosis factor (TNF) alpha blockers, were immunized at least once with non-adjuvanted trivalent influenza vaccine during three consecutive influenza seasons. Antibodies toward A influenza antigens significantly increased and reached protective levels, still detectable 6 months after vaccination, both in RA patients and healthy controls. Response to B antigen instead was only observed from the second year for healthy controls and in the third year for patients. No significant difference in disease activity and anti-nuclear antibodies was observed as a consequence of vaccine administration, whereas T regulatory cells showed a significant increase 30 days after immunization in RA patients. This study confirms safety of influenza vaccine administration in RA patients treated with TNFalpha blockers. The cohort follow-up revealed the overcoming of poor B vaccine antigen immunogenicity via repeated vaccinations. Finally, protective antibody response was still observed 6 months after vaccination.

Heart rate variability and cardiac autonomic function in systemic lupus erythematosus.

Rheumatoid Arthritis (RA) is a chronic disease with significant morbidity and functional disability. The traditional treatment for RA relied on the use of NSAIDs early in the disease course, followed by disease-modifying agents later. More recently, the disease-modifying anti-rheumatic drugs (DMARDs) have become the mainstay of RA therapy because of the recognition of their superior efficacy/toxicity profile. The antimalarial drugs, chloroquine and hydroxychloroquine, are some of the most commonly used DMARDs in the management of RA. They have been shown to be significantly more effective than NSAIDs alone in several clinical trials, and have a benign toxicity profile. A combination of hydroxychloroquine with methotrexate appears to reduce significantly the hepatic toxicity of methotrexate. In this review, we summarize the efficacy and toxicity profiles of the antimalarial drugs in rheumatoid arthritis.The cardiac autonomic function was evaluated in 23 patients with Systemic Lupus Erythe matosus (SLE) without clinical expression of dysautonomia and in 14 healthy volunteer subjects as a control group, by analysis of Heart Rate Variability (HRV) from 24 h ambula tory electrocardiography. All the patients were taking corticosteroids and 10 of them also Ciclosporin A (CsA). The following parameters of HRV were performed: Time domain: standard deviation of the RR intervals average (SDNN) and percentage of RR adjacent intervals differing from each other more than 50 msec (pNN50). Frequency domain: low frequencies (LF) and high frequencies (HF). Significant lower values were detected in SLE patients vs controls: SDNN = 69.40 vs 127.72; pNN50 = 16.44 vs 25.95; LF = 8.34 vs 34.97; HF = 3.21 vs 12.18. The incidence of autonomic dysfunction in our SLE population evaluated by considering intervals of nor mality is approximately 78% for SDNN; 17% for pNN50; 91% for LF and, finally, 56% for HF. The analysis of HRV may be a valuable technique in the study of the incidence of dysautonomia for these patients.

Technetium-99m sestamibi single-photon emission tomography detects subclinical myocardial perfusion abnormalities in patients with systemic lupus erythematosus

Abstract. In patients with systemic lupus erythematosus, involvement of the cardiovascular system is the third leading cause of death. However, although autopsy studies have demonstrated a high incidence of abnormalities in both the myocardium and coronary vessels, clinical manifestations have been reported in only a small percentage of cases. The aim of this study was to evaluate myocardial perfusion in asymptomatic lupus patients using technetium-99m sestamibi single-photon emission tomography (SPET). Twenty-eight patients without overt cardiac involvement and risk factors were studied with 99mTc-sestamibi SPET at rest and after dipyridamole infusion. Perfusion abnormalities were detected in 18 cases: six had persistent defects, three had reversible defects, seven had both persistent and reversible defects, and two showed rest defects which normalized on dipyridamole images (”reverse redistribution pattern”). Coronary angiography was performed in eight patients with positive 99mTc-sestamibi SPET, and showed normal epicardial vessels in all the cases. These results indicate that 99mTc-sestamibi SPET reveals a high prevalence (18 out of 28 patients in this study, i.e. 64%) of myocardial perfusion abnormalities in asymptomatic lupus patients, probably due to the primary immunological damage of this autoimmune disease. In conclusion, rest/dipyridamole 99mTc-sestamibi SPET can be a useful non-invasive method to identify subclinical myocardial involvement in systemic lupus erythematosus, and patients potentially at risk of later cardiac events.

Biomarkers of good EULAR response to the B cell depletion therapy in all seropositive rheumatoid arthritis patients: Clues for the pathogenesis

Objective To find out whether a high number of auto-antibodies can increase the probability of a “good-EULAR response” and to identify the possible biomarkers of response in seropositive rheumatoid arthritis (RA) patients undergoing the B cell depletion therapy (BCDT). Patients and Methods One hundred and thirty-eight patients with long standing RA (LSRA), 75% non or poorly responsive to one or more TNFα blockers, all seropositive for at least one autoantibody (AAB) (RF-IgM, RF-IgA, RF-IgG, anti-MCV, ACPA-IgG, ACPA-IgA, ACPA-IgM) received one full course of BCDT. The major outcomes (moderate or good-EULAR response) were assessed after 6 months of therapy. The IL6 and BAFF levels were also determined. Results At a 6-month follow-up, 33 (23.9%) of the RA patients achieved a good EULAR response. Having up to 5-AABs positivity increased the chances for treatment response. After a logistic regression analysis, however, only 4 baseline factors arose as associated with a good-EULAR response: no steroid therapy (OR = 6.25), a lymphocyte count <1875/uL (OR = 10.74), a RF-IgG level >52.1 IU/ml (OR = 8.37) and BAFF levels <1011 pg/ml (OR = 7.38). When all the AABs, except for RF-IgM and ACPA-IgG, were left in the analysis, the two final predictors were no-steroid therapy and low lymphocyte count. Discussion The number of AABs increased the chances of being a “good-EULAR” responder. The only predictors, however, at the baseline of a good response in this seropositive cohort of RA patients were 2 simple variables – no steroids and lymphocyte count – and two laboratory assays – IgG-RF and BAFF.

Viscosupplementation in the management of ankle osteoarthritis: a review

IntroductionOsteoarthritis (OA) is a disease of synovial joints and is the most common cause of chronic pain. Viscosupplementation (VS) with hyaluronic acid (HA) is largely used for knee osteoarthritis therapy but the evidence for its usefulness in ankle osteoarthritis is limited. The objective of this review is to assess the efficacy of viscosupplementation treatment of ankle osteoarthritis in the current literature.MethodsThe following databases were searched: Medline (period 2006–2008), Database of Abstract on Reviews and Effectiveness and Cochrane Database of Systematic Reviews. Reference lists of relevant articles were controlled for additional references. The search terms Review, Viscosupplementation (VS), Osteoarthritis (OA), Hyaluronic acid (HA), Hyaluronan, Sodium hyaluronate, Ankle OA, Ankle joint were used to identify all studies relating to the use of VS therapy for the ankle OA. Methodological quality of included studies was assessed by assigning level of evidence as previously defined by the Centre for Evidence Based Medicine (CEBM).ResultSeven articles concerning the efficacy of a total of 275 patients undergoing VS treatment for ankle OA were included. One European study, one Taiwanese study, one Italian study, one Turkish study and three American studies with level of evidence ranging from I to IV evaluated the following products: Hyalgan®, Synvisc®, Supartz®, Adant®.ConclusionViscosupplementation is used widely in knee OA and is included in the professional guidelines for treatment of the disease in this joint. The potential for treating osteoarthritis of the ankle joint by viscosupplementation has been suggested in the literature, however, no dosing studies have been published to date, and dosing in the ankle joint remains an area for discussion. Viscosupplementation could potentially provide an useful alternative in treating such patients with painful ankle OA.

Higher risk of tuberculosis reactivation when anti-TNF is combined with immunosuppressive agents: a systematic review of randomized controlled trials

Abstract Objective. Treatment with tumour necrosis factor antagonists (anti-TNF) has been recognized as a risk factor for tuberculosis (TB) reactivation. Our aim was to evaluate risk of TB reactivation in rheumatologic and non-rheumatologic diseases treated with the same anti-TNF agents with and without concomitant therapies. Methods. We searched for randomized controlled trials (RCTs) evaluating infliximab, adalimumab, and certolizumab in both rheumatologic and non-rheumatologic diseases until 2012. Results were calculated as pooled rates and/or pooled odd ratios (OR). Results. Overall, 40 RCTs with a total of 14,683 patients (anti-TNF: 10,010; placebo: 4673) were included. TB reactivation was 0.26% (26/10,010) in the anti-TNF group and 0% (0/4673) in the control group, corresponding to an OR of 24.8 (95% CI 2.4–133). TB risk was higher when anti-TNF agents were combined with methotrexate or azathioprine as compared with either controls (24/4241 versus 0/4673; OR 54; 95% CI 5.3–88) or anti-TNF monotherapy (24/4241 versus 2/5769; OR 13.3; 95% CI 3.7–100). When anti-TNF was used as monotherapy, TB risk tended to be higher than placebo (2/5769 versus 0/4673; OR 4; 95% CI 0.2–15.7). Conclusions. TB risk with anti-TNF agents appeared to be increased when these agents were used in combination with methotrexate or azathioprine as compared with monotherapy regimen. TB risk seemed to be higher than placebo, even when monotherapy is prescribed.

Mixed cryoglobulinemia secondary to visceral Leishmaniasis.

We describe a case of type II mixed cryoglobulinemia, with monoclonal IgMkappa rheumatoid factor, associated with visceral leishmaniasis caused by Leishmania infantum. Involvement of Leishmania antigen(s) in the formation of cryoprecipitable immune complexes was suggested by the fact that cryoglobulinemic vasculitis subsided after antiparasite therapy and that anti-Leishmania antibodies, as well as rheumatoid factor, were enriched in the cryoprecipitate. We observed 2 additional patients with visceral leishmaniasis and cryoglobulinemic vasculitis. All 3 patients had seemingly contracted leishmaniasis in Italy, were hepatitis C virus negative, and were initially diagnosed as having autoimmune disorders. These findings indicate that Leishmania can be an etiologic agent of type II mixed cryoglobulinemia. This parasitosis should be taken into consideration in the differential diagnosis of vasculitides in endemic areas.

Rituximab ameliorated severe hearing loss in Cogan's syndrome: a case report

BackgroundRituximab is a monoclonal antibody inducing depletion of B lymphocytes and presently approved for the treatment of non-Hodgkins lymphoma and rheumatoid arthritis. Here is the first report of the use of this drug in a case of Cogans syndrome (CS).Case Presentationa 25-year-old Italian woman was referred with conjunctival hyperaemia, interstitial keratitis, moderate bilateral sensorineural hearing loss accompanied by tinnitus, dizziness, nausea and vertigo, poorly responsive to oral and topical steroidal therapy. Diagnosis of typical CS was made. The administration of a combined immunosuppressive treatment resolved ocular inflammation, dizziness, nausea, and vertigo but gave little results in controlling progressive hearing loss. A noticeable improvement in hearing function was documented by pure tone audiometry after infusion of Rituximab.Discussionin CS, hearing function is often the most difficult parameter to control with therapy. A positive effect of Rituximab on was observed in our case. The drug also allowed to significantly reduce the number of adjuvant immunosuppressive medications.

Lupus Carditis: Evaluation with Technetium-99m MIBI Myocardial SPECT and Heart Rate Variability:

The objective of this paper was to investigate the incidence of myocardial perfusion defects in patients with systemic lupus erythematosus (SLE) associated with dysauto nomic alterations. Twenty patients without any sign or symptoms of heart disease, selected from a larger population of patients with SLE, underwent technetium-99m sestamibi (Tc-99m MIBI) single photon emission computed tomography (SPECT), at rest and after dipyridamole infusion; they also underwent heart rate variability (HRV) exam ination by a 24 hour ambulatory electrocardiography, analyzing in the time domain the standard deviation of the R-R intervals average (SDNN) and the percentage of R-R adjacent intervals differing from each other more than 50 msec (pNN50); in the frequency domain the low (LF) and high frequencies (HF) were analyzed. Twenty healthy volunteers served as control group for heart rate variability. At MIBI-SPECT examina- tion, the scan was found abnormal in 15 patients and normal in five: three patients demonstrated reversible defects in the anteroseptal region, four had irreversible defects in a region (two in the anteroseptal region and two in the lateral region), two had rest defects in two different regions (lateral and inferior, lateral and anteroseptal) that improved during dipyridamole scan, and six had both reversible and irreversible defects: four in a single segment (three anteroseptal and one lateral, and two in two different regions, particularly anteroseptal and lateral, lateral and inferior). All 20 patients showed significantly lower HRV parameters in comparison with the control group, except for pNN50, which indicates decreased physiologic periodic fluctuations of the autonomic nervous system. In six patients who underwent coronary angiography, the epicardial vessels were found completely normal. In view of the high incidence of myocardial hypoperfusion in patients with HRV alterations, the authors hypothesize that autonomic dysfunction may be associated with microvascular disease or metabolic alteration. They also believe that MIBI scintigraphy is a suitable technique in detecting myocardial damage in SLE patients free of clinical manifestation.