Subcorneal pustular dermatosis and mycoplasma pneumoniae respiratory infection.

Sir, Subcorneal pustular dermatosis (SPD) is an uncommon, chronic/recurrent, pustular eruption characterized by subcorneal sterile pustules involving mainly the abdomen and the large folds. Originally described in 1956 by Sneddon & Wilkinson (1), the condition can be ascribed to the complex group of neutrophilic dermatoses (2). The pathophysiology underlying SPD is presently unknown, but the disease has frequently been described in association with systemic disorders, i.e. myeloproliferative disorders, inflammatory bowel diseases and rheumatoid arthritis (3). We report a case of SPD possibly triggered by a Mycoplasma (M.) pneumoniae respiratory infection

1,4-Disubstituted-[1,2,3]triazolyl-Containing Analogues of MT-II: Design, Synthesis, Conformational Analysis, and Biological Activity

Side chain-to-side chain cyclizations represent a strategy to select a family of bioactive conformations by reducing the entropy and enhancing the stabilization of functional ligand-induced receptor conformations. This structural manipulation contributes to increased target specificity, enhanced biological potency, improved pharmacokinetic properties, increased functional potency, and lowered metabolic susceptibility. The CuI-catalyzed azide–alkyne 1,3-dipolar Huisgen’s cycloaddition, the prototypic click reaction, presents a promising opportunity to develop a new paradigm for an orthogonal bioorganic and intramolecular side chain-to-side chain cyclization. In fact, the proteolytic stable 1,4- or 4,1-disubstituted [1,2,3]triazolyl moiety is isosteric with the peptide bond and can function as a surrogate of the classical side chain-to-side chain lactam forming bridge. Herein we report the design, synthesis, conformational analysis, and functional biological activity of a series of i-to-i+5 1,4- and 4,1-disubstituted [1,2,3]triazole-bridged cyclopeptides derived from MT-II, the homodetic Asp5 to Lys10 side chain-to-side chain bridged heptapeptide, an extensively studied agonist of melanocortin receptors

Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6–positive and HLA-Cw6–negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLACw6–positive and HLA–Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile

Italian Guidelines in diagnosis and treatment of alopecia areata

Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration. The Italian Study Group for Cutaneous Annexial Disease of the Italian Society of dermatology proposes these Italian guidelines for diagnosis and treatment of Alopecia Areata deeming useful for the daily management of the disease. This article summarizes evidence-based treatment associated with expert-based recommendations

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Targetoid Skin Lesions in a Child: Acute Hemorrhagic Oedema of Infancy and Its Differential Diagnosis

Acute hemorrhagic oedema of infancy (AHEI) is a cutaneous leukocytoclastic small-vessel vasculitis presenting with localized purpuric large skin plaques that are frequently associated with fever and oedema. It must be promptly differentiated from a number of diseases with similar dermatologic manifestations with potentially severe clinical courses that require adequate monitoring and prompt therapy to avoid the risk of a negative evolution. A 15-month-old girl with a negative personal medical clinical history was admitted for the sudden appearance of petechiae on the soft palate. The patient was moderately febrile during the following two days, with a maximum ear temperature of 38.3 °C. The fever disappeared on the third day, whereas the hemorrhagic rash progressively increased and extended to the limbs, face and auricles associated with a strong oedematous component. Moreover, on the second day of hospitalization, bilateral oedema of the metacarpophalangeal joints with joint pain appeared. The blood and serological tests showed an increase in C-reactive protein concentration (3.58 mg/dL) in the absence of leukocytosis and with a normal platelet count (180,000/mm3). The examination of the peripheral smear showed the presence of some large mononuclear elements with hyperbasophile cytoplasm. No alterations in platelet morphology were evidenced. The skin manifestations progressively diminished and disappeared spontaneously within 3 weeks, leaving no sequelae. Conclusion: This case shows the classic skin lesions of AHEI that require differentiation from those of more severe diseases that need prompt recognition and therapy. In this case, the age of the patient, the lack of systemic involvement and the favorable clinical course without therapy were typical. However, as these patients may present to the emergency department with an impressive clinical picture, the condition must be promptly diagnosed to avoid unnecessary diagnostic procedures and to reassure parents

A Terbinafine Sensitive <i>Trichophyton indotineae</i> Strain in Italy: The First Clinical Case of <i>tinea corporis</i> and onychomycosis

Trichophyton indotineae is an emerging dermatophyte species that plays a relevant role in human healthcare. It has been associated with severe chronic skin infections and a high level of terbinafine resistance. T. indotineae is endemic to India, Iran, and Iraq but several cases have been reported in Europe, recently. In this manuscript, the authors report the first clinical description of a tinea corporis and onychomycosis due to T. indotineae. The patient was a 42-year-old female from India that has lived in Umbria (Central Italy) for the last two years. Firstly, a dermatological examination suggested dermatophytosis: mycology isolation from cultures and macro- and microscopical features identified the colonies as belonging to the T. mentagrophytes/T. interdigitale species complex. Subsequently, ITS1/ITS4 end-point PCR and Sanger sequencing identified the strain as T. indotineae. Lastly, a DermaGenius® Resistance Multiplex real-time PCR assay was carried out, targeting the mutations in the SQLE gene to establish terbinafine resistance or susceptibility of the strain. The melting curve observed was compatible with wild-type positive control, identifying the strain as T. indotineae terbinafine-sensitive. An oral terbinafine treatment was associated with a topical ciclopirox nail solution, resulting in remission in its clinical manifestation. On 3 July 2023, the local Prevention Service notified the case to the Ministry of Health that then reported the information at national and international levels

Diagnosis and management of cutaneous and anogenital lichen sclerosus: recommendations from the Italian Society of Dermatology (SIDeMaST)

Lichen sclerosus (LS) is a disabling chronic inflammatory disease of skin and genital mucous membrane causing itch, pain, dysuria and restriction of micturition, and significant sexual dysfunction and dyspareunia both in women and men. If left untreated, LS is associated with a high degree of sclerosis and scarring, as well as with an elevated risk of cancer in the genital area. Although a central role of autoimmunity is suggested, the pathogenesis of LS is still not clearly understood and the disease remains difficult to treat. The goals of treatment of LS are to alleviate symptoms and discomfort, prevent anatomical changes and prevent malignant transformation. This guideline has been developed by an Italian group of experts. It summarizes evidence-based and expert- based recommendations. The highest level of evidence favors the use of topical high potency corticosteroids; second and third lines' treatments include topical calcineurin inhibitors and topical retinoids, respectively. Surgical treatment has become the treatment of choice in male genital LS with persistent phimosis not responsive to medical treatment. The aim of this paper is to offer evidencebased and easily applicable recommendations for the management of LS

Solvent independent conformational propensities of [1,2,3]triazolyl-bridged PTHrP-derived cyclo-nonapeptide analogues

The recently introduced Cu(I)-catalyzed azide–alkyne 1,3-dipolar Huisgen cycloaddition as a prototypic “click chemistry reaction” presented an opportunity for introducing the 1,4-disubstituted-[1,2,3]triazolyl moiety as a new isostere for peptide bonds in the backbone. Previous study in our lab focused on the synthesis of a model i-to-i+4 side chain-to-side chain 1,4- and 4,1-disubstituted-[1,2,3]triazolyl-bridged cyclo-nonapeptide I (Scheme 1) as analogues of its structurally related helical i-to-i+4 lactam-bridged cyclo-nonapeptide [Lys13(&amp; 1),Asp17(&amp; 2)]parathyroid hormone related peptide (PTHrP)(11–19)NH21 a truncated version of the α-helical and potent parathyroid hormone receptor 1 agonist [Lys13(&amp; 1),Asp17(&amp; 2)]PTHrP(1-34)NH2,2,3 Nα-Ac-Lys-Gly-Lys(&amp; 1)-Ser-Ile-Gln-Asp(&amp; 2)-Leu-Arg-NH2]. Systematic [1,2,3]triazolyl-containing bridge structure–conformation relationship studies in hexafluoroacetone/water mixture included incorporation of bridges varied in size and position and orientation of the triazolyl ring within the bridge. These studies revealed that the size of methylene bridge flanking triazolyl moiety is critical to reproduce in the heterodetic cyclo-nonapeptides. The conformational features of the analogues cyclo-nonapeptide in which Lys13 and Asp17 are bridged by the isosteric lactam. Here, we extend our conformational analysis to dimethyl sulfoxide/water mixture in an effort to characterize inherent conformational properties of the heterodetic cyclopeptides that are solvent independent. Our present study shows that the physicochemical properties of the structure-supporting solvent cannot override the effect of the size of methylene bridge to form helical mimetic structures. Moreover, we prove that [1,2,3]triazolyl ring is not a simple bioisostere of lactam bond, but it affects the secondary structure of the peptide, in relation to its positioning orientatio