COVID-19 first lockdown and outpatient hospital setting: a single center, real life study focusing on pattern changes in patients' ethnicities and treated dermatoses.

BACKGROUND: During the first Italian lockdown period, the imponent amount of hospital COVID-19 patients forced the healthcare system to re-organize visits but no information are available on outpatient ethnical patterns. Here we evaluated healthcare management changes on dermatological outpatient non-surgical settings visits during the SARS-CoV-2 pandemic. METHODS: In this retrospective study we collected data of scheduled, performed and not-performed visits, together with patients' characteristics (i.e., age, gender) with a particular attention for ethnicities among the outpatients accessing during the first Italian lockdown (March 5-April 30, 2020). Then, we compared these data with the corresponding ones in 2019 (before COVID-19 pandemic). RESULTS: During the Italian lockdown the dermatological department registered a great decrement (-83.5%, P<0.001) in visits compared to the corresponding time period in 2019. Performed and scheduled visits to non-oncological stable patients together with emergency accesses to dermatology decreased. Non-Italian patients decreased accesses, especially the South East Asians (-70.4%) and North Africans (-90.0%). CONCLUSIONS: Hospitals policy and mass media deeply condition the public opinion, and this aspect may explain a different access to the hospital among non-Italian patients. Telemedicine should be promoted especially among non-Italian communities in Italy to overgo patients' skepticism and incentivize prevention and early treatment in dermatological conditions.

Antihistamines-refractory chronic pruritus in psoriatic patients undergoing biologics: aprepitant vs antihistamine double dosage, a real-world data.

BACKGROUND: Psoriasis-related pruritus (PRP) in patients under systemic treatment is challenging. The risk to switch anti-psoriatic drugs and to lose response to previous therapy is high, thus dermatologists prefer to add an anti-pruritic agent. OBJECTIVES: To evaluate the effect of anti-histamines and aprepitant in treating PPR of psoriatic patients undergoing systemic anti-psoriatic therapies. METHODS: A pilot observational open-label study was performed on responsive psoriatic patients with PPR under treatment. Initial therapy included oral rupatadine (10 mg/day for 30 days). In case of the Epworth Sleepiness Scale (ESS) was above 14, patients were switched to aprepitant (80 mg/day for 7 days), otherwise, rupatadine dosage was increased (20 mg/day for 7 days). Clinical evaluation was performed at the baseline (T0) and after 7 days (T7). RESULTS: We enrolled 40 patients with PPR, 20 in each group. Age, gender, Psoriatic arthritis (PsA) and the itch - VAS, were matched. At T7, aprepitant displayed higher improvements than rupatadine (itch - VAS = 4 [3-5] vs 8.5 [8-9], p < .01, DLQI = 14 [13-16] vs. 18 [16-21], p < .01 and ESS = 5 [4-7] vs 15 [14-16], p < .01). Doubling the rupatadine dosage from 10 mg to 20 mg/day only slightly improve itch (itch - VAS = 9 [8-10] vs 9 [8-9], p = .03), conversely no modifications in the quality of life (DLQI = 18 [17-20] vs 18 [17-21], p = .73) and increased sleepiness (ESS = 10 [9-11] vs 15 [14-16], p < .01). CONCLUSIONS: Aprepitant may be a valid alternative in PPR patients with ESS >14 under antihistamines.

SARS-CoV-2 Infection Induces Psoriatic Arthritis Flares and Enthesis Resident Plasmacytoid Dendritic Cell Type-1 Interferon Inhibition by JAK Antagonism Offer Novel Spondyloarthritis Pathogenesis Insights.

Objective: Bacterial and viral infectious triggers are linked to spondyloarthritis (SpA) including psoriatic arthritis (PsA) development, likely via dendritic cell activation. We investigated spinal entheseal plasmacytoid dendritic cells (pDCs) toll-like receptor (TLR)-7 and 9 activation and therapeutic modulation, including JAK inhibition. We also investigated if COVID-19 infection, a potent TLR-7 stimulator triggered PsA flares. Methods: Normal entheseal pDCs were characterized and stimulated with imiquimod and CpG oligodeoxynucleotides (ODN) to evaluate TNF and IFNα production. NanoString gene expression assay of total pDCs RNA was performed pre- and post- ODN stimulation. Pharmacological inhibition of induced IFNα protein was performed with Tofacitinib and PDE4 inhibition. The impact of SARS-CoV2 viral infection on PsA flares was evaluated. Results: CD45+HLA-DR+CD123+CD303+CD11c- entheseal pDCs were more numerous than blood pDCs (1.9 ± 0.8% vs 0.2 ± 0.07% of CD45+ cells, p=0.008) and showed inducible IFNα and TNF protein following ODN/imiquimod stimulation and were the sole entheseal IFNα producers. NanoString data identified 11 significantly upregulated differentially expressed genes (DEGs) including TNF in stimulated pDCs. Canonical pathway analysis revealed activation of dendritic cell maturation, NF-κB signaling, toll-like receptor signaling and JAK/STAT signaling pathways following ODN stimulation. Both tofacitinib and PDE4i strongly attenuated ODN induced IFNα. DAPSA scores elevations occurred in 18 PsA cases with SARS-CoV2 infection (9.7 ± 4 pre-infection and 35.3 ± 7.5 during infection). Conclusion: Entheseal pDCs link microbes to TNF/IFNα production. SARS-CoV-2 infection is associated with PsA Flares and JAK inhibition suppressed activated entheseal plasmacytoid dendritic Type-1 interferon responses as pointers towards a novel mechanism of PsA and SpA-related arthropathy.

COVID-19 related masks increase severity of both acne (maskne) and rosacea (mask rosacea): Multi-center, real-life, telemedical, and observational prospective study.

Masks are essential for COVID-19 prevention, but recently they were suggested to modify cutaneous facial microenvironment and trigger facial dermatoses. To evaluate mask-related rosacea and acne (maskne) in untreated patients during lockdown. In this multi-center, real-life, observational prospective study, we enrolled stable, untreated acne and rosacea patients that wore masks during lockdown at least 6 h/day. They underwent two teledermatological consultations, at the baseline and after 6 weeks. Clinical, pharmacological, and psychological data were recorded. A total 66 patients, 30 (median age: 34.0 [30.25-29.75] yoa) with acne and 36 patients (median age: 48 [43-54] years) with rosacea, were enrolled in this study. After 6 weeks of mask and quarantine, patients with acne displayed an increased Global Acne Grading Scale (GAGS) score in mask-related areas (P < .0001). Likewise, after 6 weeks of mask and quarantine, patients with rosacea displayed a worsen in both physican (P < .0001) and patient (P < .0001) reported outcomes. Remarkably, patients reported also a statistically significant decrease in their quality of life (P < .0001). Masks appear to trigger both acne and rosacea flares. Additional studies are needed to generate evidence and inform clinical decision-making.

T Cell Subpopulations in the Physiopathology of Fibromyalgia: Evidence and Perspectives.

Fibromyalgia is one of the most important "rheumatic" disorders, after osteoarthritis. The etiology of the disease is still not clear. At the moment, the most defined pathological mechanism is the alteration of central pain pathways, and emotional conditions can trigger or worsen symptoms. Increasing evidence supports the role of mast cells in maintaining pain conditions such as musculoskeletal pain and central sensitization. Importantly, mast cells can mediate microglia activation through the production of proinflammatory cytokines such as IL-1ß, IL-6, and TNFα. In addition, levels of chemokines and proinflammatory cytokines are enhanced in serum and could contribute to inflammation at systemic level. Despite the well-characterized relationship between the nervous system and inflammation, the mechanism that links the different pathological features of fibromyalgia, including stress-related manifestations, central sensitization, and dysregulation of the innate and adaptive immune responses is largely unknown. This review aims to provide an overview of the current understanding of the role of adaptive immune cells, in particular T cells, in the physiopathology of fibromyalgia. It also aims at linking the latest advances emerging from basic science to envisage new perspectives to explain the role of T cells in interconnecting the psychological, neurological, and inflammatory symptoms of fibromyalgia.

Neutrophilic Dermatoses and Their Implication in Pathophysiology of Asthma and Other Respiratory Comorbidities: A Narrative Review.

Neutrophilic dermatoses (ND) are a polymorphous group of noncontagious dermatological disorders that share the common histological feature of a sterile cutaneous infiltration of mature neutrophils. Clinical manifestations can vary from nodules, pustules, and bulla to erosions and ulcerations. The etiopathogenesis of neutrophilic dermatoses has continuously evolved. Accumulating genetic, clinical, and histological evidence point to NDs being classified in the spectrum of autoinflammatory conditions. However, unlike the monogenic autoinflammatory syndromes where a clear multiple change in the inflammasome structure/function is demonstrated, NDs display several proinflammatory abnormalities, mainly driven by IL-1, IL-17, and tumor necrosis factor-alpha (TNF-a). Additionally, because of the frequent association with extracutaneous manifestations where neutrophils seem to play a crucial role, it was plausible also to consider NDs as a cutaneous presentation of a systemic neutrophilic condition. Neutrophilic dermatoses are more frequently recognized in association with respiratory disorders than by chance alone. The combination of the two, particularly in the context of their overlapping immune responses mediated primarily by neutrophils, raises the likelihood of a common neutrophilic systemic disease or an aberrant innate immunity disorder. Associated respiratory conditions can serve as a trigger or may develop or be exacerbated secondary to the uncontrolled skin disorder. Physicians should be aware of the possible pulmonary comorbidities and apply this knowledge in the three steps of patients' management, work-up, diagnosis, and treatment. In this review, we attempt to unravel the pathophysiological mechanisms of this association and also present some evidence for the role of targeted therapy in the treatment of both conditions.

Allergological and toxicological aspects in a multiple chemical sensitivity cohort.

BACKGROUND: Multiple chemical sensitivity (MCS) is a chronic condition characterized by an exaggerated response to toxicants. We ascertained the prevalence of allergy to metals and toxicological aspects in MCS patients. METHODS: We conducted a retrospective review of medical records of 41 patients with MCS. We performed patch testing (n = 21) for dental series and did lymphocyte transformation test (n = 18) for metals. We measured mercury in samples of blood (n = 19), urine (n = 19), saliva (n = 20), and scalp hair (n = 17) to investigate the association between mercury levels and cases of MCS. RESULTS: The prevalence of metal immune hypersensitivity in a subset of 26 patients was 92.3 percent. Elevations of mercury occurred in 81.2 percent (26 of 32). The mean (±SD) in blood concentrations of mercury was 7.6 ± 13.6 µg/L; mean in urine was 1.9 ± 2.5 µg/L; mean in scalp hair was 2.2 ± 2.5 µg/g; mean in saliva was 38.1 ± 52.1 µg/L. Subgroup analyses showed that elevation of mercury levels in biological matrices were associated with mercury amalgams in patients with MCS (22 patients), compared with controls (8 patients) (odds ratio 11 : 95 percent confidence interval 1.5 to 81.6; P = 0.023). CONCLUSIONS: Our data show an increased prevalence of metal allergy and elevation of mercury levels in bioindicators among patients with MCS.

Effect of thimerosal, methylmercury, and mercuric chloride in Jurkat T Cell Line.

Mercury is a ubiquitous environmental toxicant that causes a wide range of adverse health effects in humans. Three forms of mercury exist: elemental, inorganic and organic. Each of them has its own profile of toxicity. The aim of the present study was to determine the effect of thimerosal, a topical antiseptic and preservative in vaccines routinely given to children, methyl mercury, and mercuric chloride on cellular viability measured by MTT in Jurkat T cells, a human T leukemia cell line. The treatment of Jurkat T cells with thimerosal caused a significant decrease in cellular viability at 1 µM (25%, p<0.05; IC50: 10 µM). Methyl mercury exhibited a significant decrease in cellular viability at 50 µM (33%, p<0.01; IC50: 65 µM). Mercuric chloride (HgCl2) did not show any significant change in cellular survival. Our findings showed that contrary to thimerosal and methyl mercury, mercuric chloride did not modify Jurkat T cell viability.

Metal sensitivity in patients with orthopaedic implants: a prospective study.

BACKGROUND: Sensitization to orthopaedic implant materials is an unpredictable event that might affect implant performance. OBJECTIVES: In candidates for hip or knee joint prosthesis implantation, to evaluate preoperative assessments for identifying patients with metal sensitivity, to determine the percentage of patients who developed metal sensitivity at 1 year after prosthesis implantation, and to examine the clinical relevance of patch tests and lymphocyte transformation tests (LTT-MELISA®) for the evaluation of metal sensitization. PATIENTS AND METHODS: A total of 100 patients referred for total hip or total knee arthroplasty were assessed preoperatively and then at 1 year post-implantation by means of patch tests with the metals present in the implant alloys. In a pilot study, 20 patients also underwent both patch testing and a lymphocyte transformation test (LTT-MELISA®) for the same metals. RESULTS: Only 72 of 100 patients were patch tested both before and after surgery, and 12 of 20 also underwent LTT-MELISA® before and after surgery. Of 31/100 patients with an apparent history of nickel sensitivity determined during preoperative assessment of subjects, 12 tested negative on both tests, and 4 with a negative history of nickel sensitivity tested positive. One year post-implantation (72 patients), 5 patients who had initially tested negative for a metal allergy became positive for at least one or more metal constituents of the prosthesis on at least one or the other test. CONCLUSIONS: Given the discrepancies between the information obtained while taking patient histories and test results, preoperative history-taking alone appears to be insufficient for identifying patients with metal sensitivity. Moreover, the increase in the percentage of patients who tested positive for metal sensitivity 1 year post-implantation suggests the possibility of prosthesis-induced sensitization. Therefore, objective determination of metal sensitivity at preoperative assessment should be considered in planning arthroplasty intervention, as it would help the surgeon in selecting the most appropriate prosthesis for the patient and could benefit implant performance.