Clusterin serum level: how does it affect psoriatic patients?

Psoriasis is a chronic inflammatory skin disease with systemic involvement that might predispose to many psoriasis-related comorbidities, such as metabolic syndrome and cardiovascular disorders. Clusterin (Clu), also known as apolipoprotein J (ApoJ), is a highly conserved disulfide-linked heterodimeric glycoprotein implicated in a great variety of physiological and pathophysiological processes including lipid transportation, tissue remodeling, senescence, cell interaction, stress response, inflammation, apoptosis, diabetes mellitus and metabolic syndrome. Serum levels of Clu were assessed in 15 patients with moderate-to-severe psoriasis defined by the presence of a Psoriasis Area and a Severity Index (PASI) value of 10 or more. It was found that the Clu value was significantly higher in patients than in healthy subjects (p <0.001). Our data confirm that the association of psoriatic disease with some comorbidities, especially metabolic and cardiovascular disease, might support the correlation with increased circulating Clu. In particular, it should be pointed out that, according to the recent literature, the Clu could also have a protective role in the comorbidity of psoriasis patients. In addition, it has been published that Clu protects cardiomyocytes against ischemic cell death and is a potential therapeutic agent in the treatment of myocardial infarction; therefore it can be assumed that an artificial enhancement of Clu in the blood could limit the severity of damage also in respect to skin lesions. Although the increase in serum level of Clu was found in all patients with psoriasis, more studies on a larger cohort of patient samples is necessary to confirm the significance of high serum levels of clusterin/ApoJ and to suggest the use of this glycoprotein as an additional new marker in psoriasis pathogenesis. It could be a possibility to improve the prognosis in patients with psoriasis.

Anaphylactic reaction after the concomitant intravenous administration of corticosteroids and gastroprotective drugs: two case reports.

Corticosteroids are therapeutic drugs widely used in cases of allergic, inflammatory and autoimmune diseases, but sometimes allergic hypersensitivity reactions have been reported as a rare adverse effect of the corticosteroids themselves. Moreover, glucocorticoids can induce gastric lesions; that’s why they are sometimes administered intravenously together with some drugs such as proton pump inhibitors (PPI) or inhibitors of histamine-2 receptors (antiH2) working as gastric protectors. Although it is difficult to establish which drug was responsible in case of hypersensitivity reactions, as hypersensitivity reactions following to the use of PPI or anti-H2 have been already described in literature. Here we describe two cases of immediate-type hypersensitivity triggered from the administration of a corticosteroid plus a gastroprotective agent and the diagnostic check up required in both these patients.

Exhaled breath condensate, nasal eosinophil cationic protein level and nasal cytology during immunotherapy for cypress allergy.

Interest in cypress allergy is widely rising: an increasing number of studies have pointed out the efficacy of immunotherapy to reduce cypress-related symptoms and drug use. Cypress immunotherapy is well tolerated, but there are few studies dealing with its sub-clinical effects on the airways. The aim of this investigation is to assess the effects of immunotherapy on airways by the analysis of exhaled breath condensate (EBC), nasal lavage fluid (NAL) and nasal cytology. Fifteen mono-sensitized to cypress pollen patients have been observed, among them 9 have been treated with sub-cutaneous immunotherapy (SCIT), 3 with sub-lingual immunotherapy (SLIT) and 3 which were not treated underwent EBC, NAL and nasal cytology out of the pollen season. 8-isoprostane in EBC, Eosinophil cationic protein (ECP) and inflammatory cells in nasal cytology were also evaluated. The median value of 8-isoprostane in EBC was 18.58 pg/ml in patients who did not undergo immunotherapy, 49.38 pg/ml in SCIT patients and 13.41 pg/ml in SLIT subjects. The median value of ECP in nasal lavage was higher in non- treated subjects (27.3 mg/l) than in those treated with SCIT (1 mg/l)(p less than 0,05) or SLIT (2.6 mg/l). All nasal cytology specimens did not show any sign of inflammation. In conclusion SLIT seems to be well tolerated and to reduce significantly the levels of ECP in nasal lavage. In addition the levels of 8-isoprostane in EBC among SCIT patients were unexpectedly high and need to be further evaluated.

An approach to urticaria in the elderly patients.

The guidelines for the management of urticaria in adults and children have been published in outstanding position papers. By contrast, the onset of urticaria in the elderly has not yet had a clear definition. In order to approach diagnosis and treatment in a population of elderly patients, we have performed an epidemiological study on a population of elderly people observed in the Immuno Allergology Unit in Bari University Hospital. The patients underwent skin prick test for food allergy and laboratory and instrumental tests. From the data it resulted that 49% of cases have had urticaria because of adverse drug reactions (ADRs), 16% of cases were positive to food, while in 21% of cases systemic and metabolic diseases (SMDs) have been diagnosed. If we consider the young controls, urticaria for ADR was present in 48% of cases; however, in 28% it was possible to make the diagnosis of food allergy, 12% cases had a SMD. Our results show that the main cause of urticaria in the elderly is related to drug assumption because of the high number of drugs taken, followed by internal pathologies correlated to the typical immune and metabolic changes of the elderly. Furthermore, from the observation of our data it was possible to give guidelines for the treatment of urticaria in geriatric age.

Treatment of psoriasis with different dosage regimens of etanercept: preliminary results from the Tαranta Plastic Study Group.

This pilot open-label study is aimed to assess clinical response in psoriasis patients receiving diverse dose regimens of etanercept, consisting of the same global cumulative dose of etanercept administered over different treatment periods. Eligible patients were assigned sequentially in a 1:1 ratio to receive: etanercept 50 mg once weekly (QW) or 50 mg twice weekly (BIW) for 12 weeks. The final analysis included a total of 72 patients. At week 12 the Psoriasis Area and Severity Index (PASI) and Skindex-29 scores notably improved in both treatment arms, without significant differences between the two groups. The rate of patients attaining a PASI improvement >or= 50% (PASI 50) at week 12 was 92% in the high-dose group. In these patients, etanercept dosage was decreased to 50 mg QW from week 13, with persistence of the PASI 50 response at week 24 in all cases. Thereafter, treatment was discontinued up to week 36 and almost 30 % of patients experienced a gradual relapse of their psoriasis within this period. In the low-dose group, the PASI 50 response was observed in 75% of patients. These responders continued to be treated with etanercept 50 mg QW up to week 36 with persistence of the PASI 50 in 100% of cases at week 24 and 93% at week 36. In the low-dose regimen, 8 patients who did not respond at week 12 underwent dose escalation to 50 mg BIW for a further 12 weeks. At week 24, six of these patients gained the PASI 50 response, 4 of whom maintained the response up to week 36, after treatment discontinuation from week 24. Our results confirm that etanercept is very effective and well-tolerated in psoriasis and that the drug dosages and treatment duration may be modulated and adapted to clinical needs in a flexible way.

Incidence of allergic diseases in an elderly population.

Recent years have shown a progressive increase of allergic disease in the elderly population worldwide. Naturally, this phenomenon has coincided with attempts to guarantee the best possible quality of life for this age group. As a result, diseases that were previously overlooked are attracting ever greater attention. An epidemiological study of allergic manifestations in the elderly conducted in all consecutive patients referred to an Allergology Unit over a three-month period at the beginning of 2008 showed that 15% belonged to the elderly population and among these, 51.8 % were suffering from an allergic reaction to drugs. Skin manifestations, including both urticaria and eczema, accounted for 71.4% of cases but only in 13.8% of these patients was there a diagnosis of an allergic reaction made and the allergen responsible individuated. Rhinitis was present in 16.8 % of the patients and food allergy in 8 %. Certainly, age-induced modifications in the immunological system can be responsible for allergic reactions. In fact, non specific immunity components such as the production of mucus or a reduced function of the T- and IL-2 cells can induce the onset of symptoms referable to allergic disease. Further studies are ongoing to gain a better understanding of the pathogenic mechanisms that could justify the development in the elderly population of a cytokine phenotype that is more prone to develop allergic manifestations, and to assess the true incidence of respiratory, food and drug allergies in this stage of life.

Clinical data and inflammation parameters in patients with cypress allergy treated with sublingual swallow therapy and subcutaneous immunotherapy.

The clinical efficacy of immunotherapy, either by high dose sublingual-swallow therapy (SLIT) or subcutaneous immunotherapy (SCIT), has been demonstrated in patients with pollinosis but few studies have been carried out analysing differences in these treatments in terms of an improvement of clinical and allergic phlogosis parameters. The aim of this double-blind placebo-controlled study is to investigate the efficacy of high dose SLIT and SCIT using a purified standardized Juniperus ashei extract in a population of allergic patients monosensitized to cypress. Forty patients with cypress-allergic rhino conjunctivitis were administered therapeutic or placebo SLIT or SCIT for 12 months. Laboratory parameters were studied, namely the eosinophil cationic protein (ECP) level in nasal lavage and in serum, as well as the number of eosinophils (EOS) in peripheral blood and in nasal lavage and the level of eosinophil chemotactic activity (ECA). These parameters were correlated with clinical symptoms, evaluated by means of the clinical symptoms score (CSS). After SCIT and SLIT the levels of ECP and ECA were reduced in nasal lavage. We also observed a significant reduction in the values of ECP in serum in the patients treated with SLIT. EOS were unchanged in peripheral blood, but significantly reduced in nasal lavage. These data were in accordance with the improvement of clinical symptoms, supported by the close correlation between CSS and laboratory parameters. Our data confirm a clinical improvement correlated with a decline in inflammation parameters after one year of immunotherapy, supporting the hypothesis that treatment with a major allergen of cypress is able to change the course of allergic rhinitis.

A multicenter open-label experience on the response of psoriasis to Adalimumab and effect of dose escalation in non-responders: the Aphrodite project.

There is much evidence to show the efficacy of adalimumab, a human monoclonal antibody targeting tumour necrosis factor-alpha, in the treatment of plaque psoriasis. In this open-label experience, 147 high-need patients suffering from plaque psoriasis, with a mean Psoriasis Area and Severity Index (PASI) of 18.8, and concomitant psoriatic arthritis (PsA) received subcutaneous injections of 40 mg of adalimumab every other week (EOW). This was actually the dosage regimen recommended for PsA, as the drug had not then been approved for psoriasis at the time of the patients enrolment. At week 12, an improvement of at least 50 percent of the PASI (PASI-50) was observed in 111 (77 percent) patients. Continuation of treatment in responders with adalimumab 40 mg EOW led to a sustained response, with the PASI-50 achieved by 97 percent of patients in the as-treated analysis at week 24 (PASI-75 in 82 percent and PASI-90 in 45 percent out of 109 patients who received EOW injections up to week 24). Thirty subjects who failed to attain the PASI-50 response at week 12 were treated with adalimumab 40 mg every week for a further 12 weeks. At week 24, 80 percent of these patients obtained a PASI-50 response after dose escalation. Tolerability was good in the majority of patients. Only two patients discontinued treatment because of an adverse event (repeated flu-like episodes and a pleuropericarditis of unknown origin, respectively).

Sensitization, asthma and allergic disease in young soccer players.

BACKGROUND: The aim of this study was to identify the prevalence of allergic disease in young soccer players compared to age-matched students and to evaluate if this prevalence changes as the intensity of training increases. METHODS: A modified ECRHS questionnaire was administered to 194 soccer players divided by age as Beginners (8-11 years), Juniors (12-16 years) and Under 21 (17-20 years) to evaluate the prevalence of allergic diseases and symptoms as well as drug consumption. Subjects with a positive personal history of allergic diseases underwent skin prick and/or patch tests. Age-matched students (n = 136) were used as a control group. RESULTS: The prevalence of allergic diseases was 34.5% in soccer players and 31.6% in control subjects (n.s.). Skin sensitization to inhalant allergens was detected in 14.4% of symptomatic soccer players and in 19.2% of control students (n.s.). Patch tests were positive in 35.7% of soccer players and 23.0% of controls with allergic dermatitis (n.s.). The prevalence of allergic diseases did not significantly change in relation to the intensity of training. Although the relative prevalence of sensitization to perennial allergens and asthma was less frequent in soccer players than in controls, and the occurrence of exercise-induced bronchoconstriction was similar in the two groups, soccer players used twice as many anti-allergic and anti-asthmatic drugs as control students. CONCLUSIONS: An increasingly intensive training programme is not associated with greater risk of allergic disease in soccer players. Therapy regimens of allergic athletes and exercisers should be monitored more closely to guarantee adequate treatment yet avoid inappropriate drug use and doping practices.

Hypersensitivity reactions to last generation chimeric, humanized [correction of umanized] and human recombinant monoclonal antibodies for therapeutic use.

A new class of drugs, produced with the hybridoma technique, has been introduced and employed to treat many immunological diseases. This class consists of recombinant monoclonal antibodies, which can be chimeric, humanized or human. Predictably, there has been a rise in adverse hypersensitivity reactions to these therapeutic agents, whose pathogenic mechanisms are not yet well understood. Specific IgE has been demonstrated in a very few cases, and only in some of these recombinant antibodies. Skin tests are not done as a clinical routine screening. In the present article the mechanisms underlying hypersensitivity reactions to these drugs are analyzed, also in the light of the personal experience and that reported in the literature, with the aim of identifying potential risk factors and means of prevention of these reactions. For some drugs, infusion reactions may be prevented thanks to the the use of premedication. Moreover, symptoms of acute hypersensitivity during infusion can be successfully managed in the majority of cases by slowing the speed of administration. All these findings seem to confirm that the pathogenesis is not related to a true immediate (IgE-mediated) hypersensitivity in most cases. When the substitution of the drug that has triggered a hypersensitivity reaction is required, this is only possible if such an alternative drug exists (i.e., replacement of a chimeric antibody with a humanized or human antibody sharing the same target). As an alternative, desensitization protocols have been employed to induce a state of temporary tolerance to the drug in some cases, yielding successful results for infliximab and trastuzumab.

Antiinflammatory effects of H1-antihistamines: clinical and immunological relevance.

Signs supporting antiinflammatory effects of H1-antihistamines were first reported long ago, but their clinical relevance remains controversial, especially with respect to their ability to inhibit the release of histamine and other preformed mediators. Experimental studies have documented that H1-antihistamines may affect several inflammatory events, including chemotaxis and the survival of eosinophils, the expression of adhesion molecules, and the release of chemokines and cytokines from different sources, thus highlighting the potential for a modulation of chronic inflammation and immune responses. Interestingly, a specific inhibitory effect on Th2-type cytokine secretion has been demonstrated for some new generation antihistamines. The mechanisms responsible for the antiinflammatory activity of H1-antihistamines are still unclear, but are presumed to be both receptor-dependent and receptor-independent. Recent findings have indicated the ability of these drugs to down-regulate intracellular signaling pathways, i.e., NF-kappaB. In this article, the current knowledge and novel findings about the antiinflammatory action and mechanisms of H1-antihistamines are briefly reviewed and critically analyzed, from the standpoint of possible clinical implications with special reference to skin disorders.

Is there an association between antiphospholipid antibodies and psoriasis?

Ever increasing evidence supports the association between psoriasis and cardiovascular risk. Antiphospholipid antibodies (APAs), which can occur in many autoimmune diseases, are considered prothrombotic and have been associated with atherosclerosis. The aim of this study is to evaluate the prevalence and levels of APAs in psoriasis patients. Fifty patients with moderate to severe plaque psoriasis and 48 healthy subjects were investigated for lupus anticoagulant (LAC) by screening and confirmatory coagulation tests, as well as for antibodies against cardiolipin or beta2-glycoprotein I. Levels of APAs and LAC-related parameters were similar for patients with psoriasis and normal controls (p>0.05). APAs were found in only one psoriatic patient (2%) and in none of the controls. LAC was detected in 2 patients (4%) and in one subject of the control group (2.1%). These results suggest that the prevalence of APAs is not increased in plaque psoriasis as compared to the control group. The increased cardiovascular risk observed in psoriatic patients is therefore likely to be correlated to factors different from APAs.

Efalizumab in moderate-to-severe plaque psoriasis: a retrospective case series analysis from clinical practice.

Efalizumab is an anti-CD11a humanized monoclonal antibody which is safe and effective for the treatment of plaque psoriasis. We performed a retrospective analysis on -high-need- patients with moderate-to-severe psoriasis treated with Efalizumab monotherapy for more than 2 years. Chart review of patient records also concerned information about rebound, relapse, and retreatment after temporary interruption, as well as transitioning from Efalizumab to alternative treatments. Of the 52 patients who completed the initial 12 weeks of treatment, 65% attained the PASI-50 response at week 12. A notable improvement of skin lesions on critical sites, such as palmoplantar surfaces or genitals, was also observed. Continuous treatment resulted in a sustained response in the majority of patients, with a PASI-75 response in nearly 88% of those Efalizumab-treated in the long term (week 72 onwards) and a PASI-90 in 77% of patients by weeks 120-132. In general, the treatment was well tolerated, with mild-to-moderate flu-like symptoms as the most frequent adverse events, particularly after the first two doses. Increase of leukocyte and/or lymphocyte counts was the most common laboratory test alteration during treatment, also in the long term. In our case series, Efalizumab was safe and well-tolerated even in patients with relevant comorbidities, including one patient with HBsAg carriage and five patients with latent TB.

Local and systemic reactions occurring during immunotherapy: an epidemiological evaluation and a prospective safety-monitoring study.

The efficacy of specific immunotherapy in allergic patients with IgE-mediated rhino-conjunctivitis, asthma and allergic reaction for stinging insects suggests the opportunity of improving technical procedures to minimize risk and optimise the safety of immunotherapy. This study investigated both local and systemic reactions, occurring in a population of 218 patients undergoing immunotherapy, in an attempt to correlate them with some parameters as well as age, sex and allergenic extracts. The epidemiological evaluation was based on the administration of a questionnaire to 218 patients in order to assess possible reactions to immunotherapy. The following data were evaluated: personal data, diagnosis, specific allergens, adverse reactions undergone during treatment, number of reactions and symptoms. The patients were followed-up by the medical staff of the Section of Allergological and Immunological Disease (SAID), University of Bari (Bari-Italy) for compilation of questionnaires. We found a correlation between female sex and adverse reactions. Among 107 patients referring reactions to the immunotherapy, 71 patients (66.3%) presented only local reactions; 11 patients (10.3%) systemic reactions and 25 patients (23.4%) systemic reactions associated with local reactions. Parietaria was mostly involved in patients with local reactions, instead, in patients with systemic reactions the prevalent allergens seem to be Dermatophagoides and grass-pollen. Rhinitis was the most frequent diagnosis for patients who have presented both local and systemic reactions. In our study, we had frequently mild systemic reactions and some cases of respiratory difficulties, while it is evident that in our group of patients no cases of anaphylaxis occurred. In addition, we considered some events before the administration of immunotherapy, such as assumption of drugs, meals, exposure to sun, stress or physical activity and the percentage of adverse reactions. On the light of a small number of fatality, immunotherapy represents a safer therapy for allergic diseases; nevertheless, our data suggest that safety is strictly correlated with prescriptions by specialists, administration by trained physicians and accurate follow-up of patients. In particular it is recommended to avoid some events before the administration of immunotherapy, above all the assumption of drugs and physical exercise.

Statistical evaluation and parameters of phlogosis in patients sensitized to cypress.

To assess the increasing sensitivity to cypress, we evaluated a group of allergic subjects living in Apulia who had been referred for respiratory symptoms to the Section for Allergic and Immunological Diseases (SAID) of Bari University Hospital in the period between January and March 2006, and compared them with a group evaluated during the same months of 2003. We submitted all patients to Skin Prick Tests (SPT) and Radio-Allergo-Sorbent Tests (RAST). Our data show that the percentage of people sensitised to cypress has increased from 28.6 percent (2003) to 65.5 percent (2006). By contrast, we observed no variations in sensitisation to other substances. Since according to data furnished by the Italian Association of Areobiology (AIA), Monitoring Center of Brindisi 1, there was a variation in the quantity of pollen grains in 2006 as compared to 2003, it seems conceivable that an increase in the amount of pollen grains, together with other factors may influence the increasing sensitization, like the volume and the brittleness of the grain. In addition, other allergo-immunologic parameters are evaluated in order to better evaluate this allergic phlogosis.

Latex allergy and sensitization in cities: a survey in a population at risk.

The constant increase in allergic diseases in western countries is correlated with changes in lifestyle and with the deterioration of the air inhaled by the inhabitants because of the growing concentrations of pollutant substances present. Within a population at risk, i.e., the inhabitants of cities, a group of subjects at even higher risk was selected, whose job exposes them to automobile exhaust fumes for many hours a day. All the study subjects underwent allergological screening and spirometry. The results obtained show an overall increase of respiratory allergic diseases but no increased sensitisation to latex. It therefore seems plausible that, besides social and lifestyle changes, the deterioration of the quality of the air could be considered responsible, at least in part, for the growing numbers of allergic subjects. This study offers an opportunity to reconsider the validity of the hygiene hypothesis as an explanation for the increase of allergic disease in western countries, although recent reports have indicated that a sedentary lifestyle may also contribute, together with environmental degradation, to the notably increased prevalence of allergic diseases in large cities in industrialized nations.

Risk factors for sensitization to AnisakiS simplex: a multivariate statistical evaluation.

Anisakis simplex is a nematode belonging to the Anisakidae family. The ingestion of third stage larvae in uncooked or undercooked seafood may cause human diseases known as anisakiasis and anisakidosis. A total of 400 (159 atopic and 241 non-atopic) subjects living in an area of southern Italy (Bari district) were consecutively evaluated to identify the association of some factors (sex, age, atopy, consumption of uncooked seafood and sensitization to dust mites) with the risk of Anisakis simplex sensitization. Patients were investigated on history of atopy and allergic diseases and were skin prick tested with commercial allergen extracts of Anisakis simplex, Acarus siro, Lepidoglyphus destructor, Tyrophagus putrescentiae, Glycyphagus domesticus, Euroglyphus maynei, Dermatophagoides pteronyssinus and Dermatophagoides farinae. Our results suggest that atopic subjects have a lower risk of Anisakis allergy than non-atopic subjects and show the association of Anisakis simplex sensitization with the consumption of uncooked seafood (anchovies and squid), increasing age and sensitization to Glycyphagus domesticus.