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Subcorneal pustular dermatosis (SCPD) is an uncommon disorder, characterized by a chronic relapsing vesiculopustular eruption, mainly involving the trunk and intertriginous areas, and usually seen in women > 40 years old. Various therapies have been reported to be effective in treating SCPD, such as dapsone, systemic glucocorticoids, acitretin, etretinate, infliximab and phototherapy. We report a case of a 54-year-old woman affected by SCPD who after failure of different therapies showed a dramatic but only temporary improvement of her disease during a cycle of therapy with infliximab. In addition, an array of cytokines was simultaneously measured in suction blister fluids obtained from involved or uninvolved skin at various time intervals during the first 12 weeks of observation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to assess emergency neurology management in Italy by comparing patients admitted to the hub and spoke hospitals. Methods: Data obtained from the annual Italian national survey (NEUDay) investigating the activity and facilities of neurology in the emergency room conducted in November 2021 were considered. Information for each patient who received a neurologic consultation after accessing the emergency room was acquired. Data on facilities were also gathered, including hospital classification (hub vs spoke), number of consultations, presence of neurology and stroke unit, number of beds, availability of neurologist, radiologist, neuroradiologist, and instrumental diagnostic accessibility. Results: Overall, 1,111 patients were admitted to the emergency room and had neurological consultation across 153 facilities (out of the 260 Italian ones). Hub hospitals had significantly more beds, availability of neurological staff, and instrumental diagnostic accessibility. Patients admitted to hub hospital had a greater need for assistance (higher number of yellow/red codes at neurologist triage). A higher propensity to be admitted to hub centers for cerebrovascular problems and to receive a diagnosis of stroke was observed. Conclusions: The identification of hub and spoke hospitals is strongly characterized by the presence of beds and instrumentation mainly dedicated to acute cerebrovascular pathologies. Moreover, the similarity in the number and type of accesses between hub and spoke hospitals suggests the need to look for adequate identification of all the neurological pathologies requiring urgent treatment. [ABSTRACT FROM AUTHOR]

Natalizumab, an anti-alpha4 integrin monoclonal antibody inhibiting the adhesion of lymphocytes to the endothelium, is a widely accepted drug treatment for relapsing-remitting multiple sclerosis ( RRMS). A peripheral increase of T and B lymphocytes has already been observed as an early treatment effect. This retrospective observational study was aimed to evaluate the peripheral lymphocyte subsets during a long-term treatment follow-up. We included 23 RRMS patients treated with natalizumab for at least 24-48 months who had pretreatment lymphocyte evaluation. Baseline values of lymphocyte subsets and CD4/ CD8 ratio did not differ significantly from the 23 matched healthy subjects. The periodic (every 3-6 months) assessment of immune cell subsets was performed by flow cytometry on peripheral blood collected before drug injection. Therapy with natalizumab was confirmed to be effective during the observational period. For all patients, the increase in lymphocytes during natalizumab therapy compared to baseline at every assessment was significantly higher compared to that of overall white blood cells (2·1- and 1·3-fold, respectively, P < 0·0001). Both T cell subsets were proportionally modified and the CD4/ CD8 ratio did not change significantly, while B cells increased significantly compared to T and NK cells (3·2-, 1·88- and 1·92-fold, respectively, P < 0·0001). These changes remained constant throughout the 25-48-month period of therapy. In conclusion, effective natalizumab treatment of RRMS patients was associated with the persistence of its biological effects through a stable increase of peripheral lymphocytes, mainly B cells, and an unchanged proportion of T cell subsets in long-term follow-up. [ABSTRACT FROM AUTHOR]

Absract The present prospective study was aimed at evaluating the long-term efficacy of local electrochemotherapy ( ECT) with the intravenous administration of bleomycin, on disease progression and viral activity in classic Kaposi's sarcoma ( cKS), a vascular tumor related to human herpes virus-8 infection. Eighteen patients affected by isolate or multiple cutaneous lesions, refractory to conventional treatments, although in the absence of visceral involvement, were enrolled in a study. Follow-up visits were performed after 4 weeks and every 6 months for up to 48 months. A more extensive exploration of the immunologic status as well as of virological parameters was performed in nine patients. The results showed a significant clinical improvement in all patients after 4 weeks. A complete regression was observed in 12 patients after the first ECT, while four patients required a second treatment on the residual lesions after 4 weeks from the first intervention. The positive outcome persisted during the subsequent clinical control visits. Two patients, that showed rapidly evolving did not improve and relapsed despite a second round of ECT treatment. Effective treatment was associated with the reduction of viral load to undetectable levels. These data support the conduct of larger studies directed at validating the efficacy of ECT as a first-line therapy for cKS. [ABSTRACT FROM AUTHOR]

Background. The therapeutic management of psoriasis includes conventional treatments as well as the new generation of highly effective TNF-α inhibitors. However, psoriasis has proven to be a complex therapeutic challenge and treatment failures are not uncommon.Thus, laboratory biomarkers of disease progression/therapeutic efficacy may greatly help in the clinical management of psoriasis. Aims. To identify laboratory biomarkers for clinical management and therapeutic monitoring of psoriasis. Methods. An observational study performed on 59 patients, presenting moderate to severe psoriasis, undergoing treatment with anti-TNF-α agents (etanercept, adalimumab, and infliximab). Soluble and cellular immune/inflammatory parameters were assessed at baseline and after 12 and 24weeks of treatment. Results. Clinical efficacy was achieved in 88% of the subjects at 12 weeks, reaching 90% after 24 weeks. IL-6 and IL-22, which were elevated at baseline, were significantly reduced, in association with a significant decrease of CLA+ T cells and an increase of Treg lymphocytes. T, B, and NK cell subsets and T cell response to recall antigens did not show any evidence of immune suppression. Conclusions. Immune/inflammatory parameters including IL-6 and IL-22, CLA+ T cells, and Treg lymphocytes may prove to be valuable laboratory tools for the clinical and therapeutic monitoring of psoriasis. [ABSTRACT FROM AUTHOR]

Biological therapies are a new breakthrough in the treatment of psoriasis and psoriatic arthritis (PsA). Among these, tumour necrosis factor (TNF)-α antagonists such as infliximab and etanercept are the most promising as TNF is considered to be essential in driving cytokine cascade at sites of cutaneous and synovial inflammation in this disease. To evaluate the time-related response of serum cytokine release during infliximab monotherapy and assess serum cytokine levels in order to provide a fast, minimally invasive tool to monitor and/or predict efficacy of anti-TNF-α therapy. Twenty patients affected by PsA with Psoriasis Area and Severity Index (PASI) score between 0·4 and 42·8 were treated with infliximab for 30–42 weeks. The assessment of arthritis severity was performed using the American College of Rheumatology (ACR) criteria and ultrasonography evaluation. The treatment schedule consisted of infliximab (5 mg kg−1 intravenously) at 0, 2 and 6 weeks and every 12 weeks on an individual basis determined by therapeutic results and adverse events reported. At baseline and before every infusion blood samples were taken to assess serum cytokine levels [TNF-α, interleukin (IL-6), E-selectin, vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF), matrix metalloproteinase (MMP-2)]. Eighteen of 20 psoriatic patients achieved > 50% improvement and 14 of 20 patients attained > 75% improvement in the PASI score at 10 weeks. All arthritic patients achieved > 50% improvement (ACR-50) and 16 of 20 patients attained > 75% improvement (ACR-75) at 10 weeks. TNF-α did not decrease immediately during the first part of the study. A significant decrease was detected at week 12 ( P < 0·01). In contrast, IL-6, VEGF, FGF and E-selectin showed significant decreases after early infliximab infusions. PASI was not correlated with TNF-α in the serum but was significantly correlated with FGF, VEGF and MMP-2. Treatment was well tolerated and there were no significant adverse events in most patients, other than an urticarial reaction and an autoimmune hepatitis. Monotherapy with infliximab has to be considered an efficacious and safe treatment for PsA in comparison with traditional disease-modifying antirheumatic drugs. The resolution of cutaneous and synovial symptoms is not related to TNF-α serum levels in the initial phases. Apoptosis may play an important role in the modulation of the inflammatory response. [ABSTRACT FROM AUTHOR]

Human papilloma virus type 5 (HPV-5) has been associated closely with psoriatic skin in Polish patients, while findings from other countries have indicated a more limited prevalence. The results of the present study, in which a type-specific nested PCR was used, indicated that scales of plaque-type psoriatic skin from 54 Italian patients had a high prevalence (74.1%) of HPV-5 DNA in lesional areas, and a reduced prevalence (33.3%) in non-lesional skin (33.3%), compared to 0% of 20 healthy subjects and 3.6% in the lesional areas of 28 patients with various other dermatological diseases. Individuals negative for HPV-5 DNA had a less severe disease. No correlation was found between the presence of HPV DNA and a patient's age or sex. The data demonstrated a statistically significant association between psoriasis and HPV-5, although results in other geographical areas suggest variable virus spread or ethnic variation in virus colonisation. [ABSTRACT FROM AUTHOR]

Immunological abnormalities present in HIV- 1-infected individuals often reflect an imbalance of cytokine production. The HIV-1 gp120 has the ability to induce a number of cytokines, and to enhance immunoglobulin release by normal peripheral blood mononuclear cells (PBMC) in vitro, in the absence of IL-2 production and of lymphoproliferation. This study provides evidence that gp120 is a potent IL-10 inducer in normal PBMC cultures. The pattern of other cytokines induced by gp120 includes interferon-alpha (IFN-α) and IFN-γ, tumour necrosis factor-alpha (TNF-α), IL-6, IL-1α and -β, and not IL-2 and IL-4. These findings further define the pattern of cytokine release induced by gp120 on human resting PBMC. Furthermore, the present findings roughly parallel those observed both in the sera of patients and in the mononuclear cells from HIV+ individuals early after infection, suggesting that gp120 could be a good candidate as one of the agents responsible for cytokine dysregulation observed in HIV-1-infected individuals. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF) were measured in serum and involved and uninvolved skin blister fluids of 20 psoriatic patients and 10 healthy subjects, by enzyme immunoassay. TNF-α and IL-6 were always detectable in involved skin blister fluids, while GM-CSF was detected only in 45% of these samples. TNF-α, IL-6 and GM-CSF were detected in 95, 100 and 10% of uninvolved skin blister fluid samples, respectively. TNF-α and IL-6 were found in 50 and 30% of control blister fluids, while GM-CSF was never detected. In serum, TNF-α was detected in 75% of patients and in 70% of controls; IL-6 in 45% of patients and in no controls; and GM-CSF in 35% of patients and in 20% of the controls. The median TNF-α and IL-6 levels in involved skin were statistically higher than those of both uninvolved and control skin blister fluids. TNF-α and IL-6 levels in blister fluids obtained from both involved and uninvolved skin were higher than those of the patients' sera. GM-CSF, when present in involved skin blister fluids, showed correlated Levels with the other cytokines (TNF-α R = 0.85, P = 0.004; IL-6: R =0.72, P=0.03). TNF-α was highly correlated with IL-6 (R = 0.78, P < 0.00001) in involved skin blister fluids. TNF-α and EL-6 Levels of involved skin blister fluids showed significant correlations with the psoriasis area and severity index scores in the patients, suggesting a direct relationship between these cytokines and the clinical manifestations of the disease. Moreover, the TNF-α levels were particularly related to the erythema scores in the patients, further supporting evidence of their rote in the pathogencsis of the disease. [ABSTRACT FROM AUTHOR]