Denosumab for the treatment of HIV-associated osteoporosis with fractures in a premenopausal woman.

The prevalence of osteoporosis is about three times greater in people living with HIV than in the general population. Bisphosphonates are the only class of antiresorptive drugs which have proved to be safe and effective in HIV patients. However, bisphosphonates are not recommended in women of childbearing age due to an increased rate of associated neonatal complications. To the best of our knowledge no reports on the use of denosumab in HIV-infected individuals have been published so far. We describe a 38 year-old woman with HIV, osteoporosis and vertebral fractures treated with denosumab, a monoclonal antibody targeting RANKL. After four years of treatment, bone mineral density improved, no new fractures occurred, and neither HIV reactivation nor opportunistic infections were observed. We show that denosumab could be a safe and effective approach for osteoporosis in patients with HIV and could be considered in women of childbearing age.

Perivascular fibrosis and IgG4-related disease: a case report.

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized fibroinflammatory condition which can potentially involve any organ. Some characteristic histopathologic features with lymphoplasmacytic infiltrate, an increased number of IgG4+ cells, storiform fibrosis and obliterative phlebitis are the mainstay for diagnosis. Serum IgG4 levels often increase. We report the case of a patient with perivascular fibrotic lesions involving the aortic arch and the splenic hilum, with a surgical biopsy-proven diagnosis of IgG4-related disease. The patient is now undergoing a low-dose corticosteroid maintenance therapy without evidence of new localizations of the disease. This case highlights the need for increasing awareness and recognition of this new, emerging clinical condition.

Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections.

OBJECTIVES: The increased incidence of nosocomial infections by multidrug-resistant organisms has motivated the re-introduction of colistin in combination with other antimicrobials in the treatment of infections. We describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Acinetobacter baumannii who were treated with a combination of colistin and rifampicin. PATIENTS AND METHODS: Critically ill patients with pneumonia and bacteraemia caused by A. baumannii resistant to all antibiotics except colistin in medical and surgical intensive care units were enrolled. Clinical and microbiological responses and safety were evaluated. RESULTS: Twenty-nine patients (47 +/- 14 years and APACHE II score 17.03 +/- 3.68), of whom 19 were cases of nosocomial pneumonia and 10 were cases of bacteraemia, were treated with intravenous colistin sulphomethate sodium (2 million IU three times a day) in addition to intravenous rifampicin (10 mg/kg every 12 h). All A. baumannii isolates were susceptible to colistin. The mean duration of treatment with intravenous colistin and rifampicin was 17.7 (+/-10.4) days (range 7-36). Clinical and microbiological responses were observed in 22 of 29 cases (76%) and the overall infection-related mortality was 21% (6/29). Three of the 29 evaluated patients (10%) developed nephrotoxicity when treated with colistin, all of whom had previous renal failure. No cases of renal failure were observed among patients with normal baseline renal function. No neurotoxicity was noted. CONCLUSIONS: Colistin and rifampicin appears to be an effective and safe combination therapy for severe infections due to multidrug-resistant A. baumannii.

Infections and treatment of patients with rheumatic diseases.

Glucocorticoids (GCs) have many complex quantitative and qualitative immunosuppressive effects which induce cellular immunodeficiency and increase host susceptibility to various viral, bacterial, fungal and parasitic infections. As cortisol secretion is inadequate in chronic immune/inflammatory conditions, and current therapies have the aim of providing adequate (low) compensatory doses, the timing of GC administration, such as during the nocturnal turning-on phase of tumour necrosis factor (TNF) secretion, can be extremely important. The use of the lowest possible GC dose, at night, and for the shortest possible time should therefore greatly reduce the risk of infections. Infection is a major co-morbidity in rheumatoid arthritis (RA), and conventional disease-modifying anti-rheumatic drugs (DMARDs) can increase the risk of their occurrence, including tuberculosis. TNF-alpha plays a key role in the pathogenesis of RA, and the data concerning infections in RA patients treated with anti-TNF agents are controversial. Patients and physicians should vigilantly monitor for signs of infection when using anti-TNF agents. Recombinant gene technologies now make it possible to produce protein drugs that are almost identical to naturally occurring human polypeptides, including antibody (Ab) constructs; unfortunately, all human biological agents are potentially immunogenic. An increasing number of recent studies have demonstrated the safety of influenza and pneumococcal vaccines administered to patients with systemic lupus erythematosus (SLE) or RA. These vaccinations are generally immunogenic (i.e., capable of inducing a protective level of specific antibodies) but may not induce an adequate response in a substantial proportion of patients.

Efficacy and safety of anti-TNF agents in the Lombardy rheumatoid arthritis network (LORHEN).

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis and bone damages, which consist of joint destruction. Clinical trials have shown that anti-tumour necrosis factor (TNF) drugs are effective in patients with rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drugs (DMARDs). At about the same time as the European approval of the third anti-TNF agent for treating rheumatoid arthritis (RA) patients, the Italian Society of Rheumatology (Società Italiana di Reumatologia [SIR]) started a database for the registration and active follow-up of patients with RA treated with biological response modifiers. Since 1999, all patients with RA (ACR criteria) and treated with at least one dose of an anti-TNF agent at four Rheumatology Centres in Lombardy (northwest Italy) have been included in the Lombardy Rheumatology Network (LORHEN) registry in order to track the efficacy and safety of the three available TNF inhibitors during the first three years of treatment.

Anti-TNF-alpha treatment in rheumatoid arthritis with anti-Ro/SSA antibodies. Analysis of 17 cases among a cohort of 322 treated patients.

OBJECTIVE: To compare the efficacy and safety of anti-TNF-alpha treatment in RA patients with and without anti-Ro antibodies, in order to detect any change in their immunological or clinical profile. METHODS: Autoantibodies in 322 patients being treated with anti-TNF-alpha drugs were studied; 17 were found to be anti-Ro positive, while 305 were anti-Ro negative. RESULTS: Two groups, comparable in terms of sex distribution, RA duration and anti-TNF-alpha drug employed, showed symmetrical, erosive polyarticular RA with high disease activity. Anti-TNF-alpha led to significant improvement in both groups. At baseline rheumatoid factor and ANA, globally positive in 68.6% and 40%, were more frequent in anti-Ro positive sera. ANA showed a rising trend beginning in the 6th month of treatment in both groups, which was always statistically significant compared to baseline. Anti-dsDNA antibodies, measured using either CLIFT and ELISA or the Farr assay, remained stable in the first 6 months, then increased at 12th and 18th month, and subsequently declined. No difference was detected between the two groups regarding the number or cause of dropouts, but lupus-like disease was more frequent in anti-Ro positive subjects (p = 0.012). In addition, two cases of NHL were detected. CONCLUSION: Anti-TNF-alpha treatment was shown to be effective in patients with anti-Ro antibodies. Although anti-dsDNA and lupus-like disease were more frequent in anti-Ro positive patients, severe manifestations of systemic involvement were not observed. A longer follow-up is warranted to evaluate the risk of NHL in these patients.

[TNF-alpha inhibition in anti-Ro/SSA positive patients with rheumatoid arthritis: clinical and immunologic effects]. / Inibizione del TNFalpha in pazienti con anticorpi anti-Ro/SSA e artrite reumatoide: analisi clinica e sierologica.

OBJECTIVE: To analyse efficacy and safety of anti-TNFalpha treatment in 17 patients with rheumatoid arthritis (AR) and anti-Ro antibodies, in order to detect difference in clinical and immunological response. METHODS: 322 patients, affected by RA and treated with anti-TNFalpha drugs, were considered, searching every 6-12 months ANA, anti-dsDNA and anti-ENA antibodies. Seventeen were anti-Ro positive and 305 anti-Ro negative before starting treatment. RESULTS: Anti-Ro positive subjects showed active arthritis at baseline (mean DAS: 5), with frequent extra-articular features, such as ocular and oral sicca symptoms. They showed rapid and stable improvement during the treatment, with-out significant difference compared to anti-Ro negative group. A good clinical Eular response was shown in 46% of anti-Ro negative subjects, steady stable during time. On the contrary, fewer anti-Ro positive patients seem to be "good" responders. RA remission (DAS <1,6) was achieved in 9-25% of anti-Ro positive and 21-29% of anti-Ro negative, without significant difference. Antinuclear antibodies tend to increase in both groups, during the time. Anti-DNA increased to 40% of anti-Ro positive sera since 6th month, while they slightly increased in first 12 months in anti-Ro negative ones, then decreased to baseline value. No differences were shown about the frequency and reasons of anti-TNFalpha withdrawal, except for cutaneous lupus-like disease, more detected in anti-Ro positive group. CONCLUSIONS: Anti-TNFalpha drugs are effective in anti-Ro positive RA as well as other RA patients. Anti-DNA positivity and lupus-like disease were more frequently observed in anti-Ro positive group.

Body iron status in critically ill patients: significance of serum ferritin.

Serial measurements of blood haemoglobin, serum iron, serum transferrin, total iron-binding capacity, transferrin per cent saturation and serum ferritin were determined in 51 post-operative critically ill patients to investigate body iron status in severely stressed patients. The results showed decreased blood haemoglobin, serum iron, serum transferrin and transferrin saturation compared to an increase in serum ferritin levels. These results indicate that there is inadequate availability of iron to tissues (secondary to rearrangement of body iron to the advantage of the iron storage compartment), which is often present in severely critically ill patients. A positive correlation was found between the initial (ferritin) levels and SAPS (r = 0.41, p less than 0.01). In addition, the increase of ferritin concentration parallels a worsening of the clinical status in severely ill patients. This is due to enhanced release by the macrophage system. From this, we consider serum ferritin as an acute-phase protein and a useful marker of the severity of the clinical status. It appears to be useful in predicting the patient's outcome, but is not reliable in evaluating iron stores in stressed patients.

Infliximab in the treatment of adult Still's disease refractory to conventional therapy.

In this study we evaluated the efficacy of Infliximab in the treatment of adult Still's disease (ASD) refractory to conventional therapy. Three patients with chronic and active ASD unresponsive to corticosteroids and methotrexate were given intravenous Infliximab infusions at a dosage of 3 mg/kg at weeks 0, 2, 6 and then once every 8 weeks. Methotrexate was maintained in all cases at a dosage of 15 mg/week, whereas the prednisone dose was modified according to disease activity. The follow-up lasted 50 weeks and disease activity improved in all cases during Infliximab therapy. Two patients presented arthralgias and sore throat at 20 and 28 weeks, that was rapidly controlled by Infliximab reinfusion every 4 weeks. One patient relapsed at 18 weeks and dropped out at 22 weeks due to an urticarioid rash after the beginning of the fifth infusion. Infliximab may be effective in the treatment of relapse of ASD refractory to conventional therapy and requiring continuous high dose corticosteroid medication. Further studies are needed to evaluate the long-term safety, efficacy and the optimal schedule of infusion.

Autoantibodies to RNA-polymerases in Italian patients with systemic sclerosis.

OBJECTIVE: To assess the frequency and clinical correlates of the systemic sclerosis-related autoantibodies to RNA polymerases in Italian patients. METHODS: Sera from 115 patients with systemic sclerosis (SSc) and 10 patients with systemic sclerosis-overlap syndromes recruited from a single center in northern Italy were investigated for antibodies to RNA polymerase I, II, and III by means of immunoprecipitation using 35S-labeled HeLa cell antigen extract. Twenty-five normal volunteers and 91 patients with different connective tissue diseases were studied as a control group. RESULTS: Antibodies to RNA-polymerases were found in 14/115 SSc patients (12.1%). None of the normal controls and none of the patients with other connective tissue diseases, including overlap syndromes, were positive. Antibodies reacting with RNA-polymerase I and III (+/- RNA-polymerase II) were found in 9/115 patients (7.8%) and were mutually exclusive with respect to other scleroderma-related autoantibodies. Isolated anti-RNA polymerase II reactivity was found in 5 patients and was associated with anti-topoisomerase I antibodies in 4 cases. Anti-RNA-polymerase I and III antibodies were associated with diffuse cutaneous involvement and male gender. Only two patients from our series had scleroderma renal crisis, and one of them had anti-RNA polymerase antibodies. CONCLUSIONS: Anti-RNA-polymerase antibodies appear to be less frequent in Italian patients than in Caucasian patients from the United Kingdom or USA. This might be associated with the lower frequency of scleroderma renal crisis.

Anti-Ro(SS-A) 52 kDa and 60 kDa specificities in undifferentiated connective tissue disease.

UNLABELLED: Autoantibodies to Ro(SS-A) may recognize two different polypeptides, of 52 kDa and 60 kDa, respectively. We used an ELISA with purified human recombinant antigens to conduct a detailed analysis of the specificities of anti-Ro(SS-A) antibodies from 170 patients with definite diagnoses (systemic lupus erythematosus [SLE], n = 55; primary Sjögren's syndrome [PSS], n = 39; systemic sclerosis, n = 9; rheumatoid arthritis [RA], n = 10) or undifferentiated connective tissue disease (UCTD, n = 57). Most of the patients with SLE or PSS had both anti-52 kDa and -60 antibodies; isolated anti-60 kDa antibodies were found in 13% of the SLE patients and in none of the PSS patients, whereas high titers of anti-52 kDa were more common in the PSS than in the SLE patients. In the UCTD patients, the anti-Ro(SS-A) profile showed no significant correlations with clinical features but was associated with the clinical outcome. Over the mean follow-up of five years, definite SLE developed in four of the five UCTD patients with isolated anti-60 kDa vs only one of the remaining 52 patients (P < 0.0001); progression to PSS was seen in seven of the 34 patients with both anti-52 kDa and anti-60 kDa vs none of the remaining 23 patients (P = 0.03); none of the 12 patients with isolated anti-52 kDa developed a definite connective tissue disease. CONCLUSION: Our study suggests that analysis of anti-Ro(SS-A) specificity may provide useful information for predicting the course of UCTD.

[Compressive cervical myelopathy due to massive periodontoid calcium pyrophosphate crystal deposition] / Mielopatia cervicale da deposizione periodontoidea di pirofosfato di calcio.

A 77 year-old man suffering from psoriatic arthropathy presented with progressive myelopathy due to massive deposits of calcium pyrophosphate dihydrate crystals in peri-odontoid tissue. The magnetic resonance imaging and computer tomographic pictures of the involved site are shown and discussed. The clinical spectrum of crystal deposition disease involving the atlo-axial joint is briefly reviewed.

Safety of tumor necrosis factor alpha blockers in hepatitis B virus occult carriers (hepatitis B surface antigen negative/anti-hepatitis B core antigen positive) with rheumatic diseases.

OBJECTIVE: To assess the safety of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy on the course of hepatitis B virus (HBV) infection in carriers of antibodies to hepatitis B core antigen (anti-HBc) affected by chronic inflammatory arthropathies. METHODS: From January 2001 to December 2008, HBV markers were determined before the first administration of anti-TNFalpha agents in all 732 patients affected by inflammatory arthropathies treated with anti-TNFalpha at 2 outpatient rheumatologic clinics in Northern Italy. Anti-HBc-positive patients were prospectively evaluated and HBV markers and HBV DNA were assessed every 6 months, in case of aminotransferase elevation, and at the end of the study. RESULTS: At the time of recruitment, 72 patients were anti-HBc carriers, 5 of whom were positive for hepatitis B surface antigen (HBsAg) and not included in the study. The ratio of men:women was 26:41 and the mean +/- SD followup was 42.52 +/- 21.33 months. Of the patients, 25 were treated with infliximab, 23 with etanercept, and 19 with adalimumab. Fifty-one patients were treated also with methotrexate, 52 with nonsteroidal antiinflammatory drugs, and 43 with prednisone (3 with a dosage >7.5 mg/day). All anti-HBc patients were HBV DNA negative at the first observation. During followup, no patient presented HBV reactivation with viral load increase and no patient became HBsAg positive. CONCLUSION: Anti-HBc positivity in HBsAg-negative patients is a sign of previous HBV infection and does not indicate chronic hepatitis. In these patients, anti-TNFalpha therapy appears to be quite safe, as no HBV reactivation was found in our study. Nevertheless, careful monitoring is necessary.

Impact of limited cephalosporin use on prevalence of methicillin-resistant Staphylococcus aureus in the intensive care unit.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a leading pathogen causing nosocomial infections. Many studies have shown that the restricted use of antibacterials is associated with a decline in resistance. To establish whether an intervention protocol designed to limit the use of cephalosporins can lower mRSA infection rates and impact on Gram-negative bacteria susceptibility in an intensive Care Unit (ICU), we conducted a prospective, non-randomized, before-after intervention study in an 18-bed ICU in Genoa, Italy. The intervention was a hospital antibiotic control policy and the observation was routine monitoring for nosocomial infections and antibiotic use, recording periodically the incidence density and MRSA prevalence. The intervention included a new antibiotic guideline that restricted the use of cephalosporins for all ICU inpatients. The analysis showed that the intervention determined a significant reduction in cephalosporin usage (-70.3%), while fluoroquinolones, mainly ciprofloxacin, increased after introduction of the antibiotic policy (+46.5%). A significant reduction in the percentage of MRSA infections (-30%) and heterogeneous susceptibility patterns in Klebsiella pneumoniae and Pseudomonas aeruginosa were noted.

Antimicrobial use and resistance among Gram-negative bacilli in an Italian intensive care unit (ICU).

Gram-negative bacilli antimicrobial resistance remains a significant problem for patients in the intensive care unit (ICU). We performed a retrospective analysis of microbiological data and antibiotic consumption over a 4-year period (2000-2003) in an Italian ICU. Pseudomonas aeruginosa and Klebsiella pneumoniae represented approximately 40% of all isolates. The most significant trend in antimicrobial use was an increase in use of 3(rd )generation cephalosporins, imipenem, and ciprofloxacin. A significant trend toward an increase in resistance rates to piperacillin, 3( rd )generation cephalosporins and ciprofloxacin was observed for K. pneumoniae and a positive correlation between resistance and drug-usage was evident for K. pneumoniae and piperacillin, cefotaxime, ceftazidime, cefepime, and ciprofloxacin, but not for piperacillin/tazobactam. No statistically significant correlations were evidenced for P. aeruginosa. Trends in resistances were studied also for Serratia spp and Proteus spp. Isolation rates of extended-spectrum beta-lactamase (ESBL)-producing strains in pathogens studied were high, especially for K. pneumoniae (72%, 160/222) and Proteus spp (41%, 18/43). In conclusion, the study showed high resistance among Gram-negative organisms isolated in the ICU and significant ESBL production. A significant correlation between antibiotic consumption and increasing resistance was evident for K. pneumoniae.