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Background IL-23 inhibitors are the latest class of biologic drugs approved for moderate-to-severe psoriasis. Objectives to investigate real-life safety and efficacy of tildrakizumab. Methods demographic data, medical history, psoriasis disease history, PASI, DLQI, BSA, NAPSI were recorded at weeks 0, 12, 24, 36. Results PASI, BSA, DLQI and NAPSI all decreased rapidly during the 36 week follow-up period. PASI score reduced from 12.28 to 4.65 by week 12, followed by a further decrease to 1.18 at week 36 Multiple logistic regression showed that smoking, BMI ≥30, ≥3 comorbidities, previous systemic traditional or biologic drugs, psoriatic arthritis nor difficult-to-treat areas influenced the reduction of PASI and NAPSI scores during treatment with tildrakizumab ( P > .05). Conclusions we assessed a good performance of tildrakizumab in patients with multiple comorbidities, multi-failure, elderly patients, and in subjects with psoriatic arthritis.

Advances in biologic treatments have led to a new therapeutic frontier for moderate-to-severe psoriasis. Nevertheless, the efficacy of anti-TNFα decreases with time, requiring adjustments to maintain valuable Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) responses. To evaluate the efficacy and safety of adalimumab dose escalation (40 mg, subcutaneous, once a week for 24 weeks) in psoriatic adult patients with secondary loss of response (PASI ≥50 to ≤75 or PASI≥75 and DLQI ≥5). A multicentre, observational study involving different Italian third-level referral centres for psoriasis enrolled a total of 64 adult patients with moderate-to-severe psoriasis who were treated with adalimumab and experienced a secondary loss of response. Primary end-points were PASI< 75 or PASI ≥50 to ≤ 75 with DLQI ≤ 5, and the secondary end-point was the ability to maintain a therapeutic response, resuming adalimumab every other week. At Week 16 and Week 24, 29/64 (45.3%) and 35/64 (54.6%) responded based on PASI, and mean DLQI was 4.9 and 4.09, respectively. At Week 36 and Week 48, 45.3% and 28.1% patients achieved the second end-point, respectively. No adverse events were recorded except for one patient with recurrent tonsillitis. Adalimumab escalation could be considered in cases with loss of response before switching to alternative biologic therapy.

Background/objectives Non-invasive skin imaging features of main skin inflammatory and autoimmune diseases have been reported, although a comprehensive review of their correlation with histopathologic features is currently lacking. Therefore, the aim of this paper was to review the correlation of dermoscopic, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) criteria of main inflammatory and autoimmune skin diseases with their corresponding histopathologic criteria correlation. Methods Studies on human subjects affected by main inflammatory and autoimmune diseases, defining the correlation of dermoscopic, RCM or OCT with histopathologic criteria, were included in the review. Five groups of diseases were identified and described: psoriasiform, spongiotic and interface dermatitis, bullous diseases and scleroderma. Results Psoriasiform dermatitis was typified by white scales, corresponding to hyperkeratosis, and vessels, observed with RCM and OCT. Spongiosis, corresponding to dark areas within the epidermis with RCM and OCT, was the main feature of spongiotic dermatitis. Interface dermatitis was characterised by dermoepidermal junction obscuration. Blisters, typical of bullous diseases, were visualised as dark areas with RCM and OCT while scleroderma lesions were characterised by dermoscopic fibrotic beams, related to dermal thickness variations, with specific OCT and histopathologic correlations. Conclusions Although the role of RCM and OCT has yet to be defined in clinical practice, non-invasive skin imaging shows promising results on inflammatory and autoimmune skin diseases, due to the correlation with histopathologic features.

BACKGROUND Comedogenesis is defined as the process of the development of a new comedo, which is of great importance for the understanding of acne. OBJECTIVE To evaluate the formation and evolution of acne lesions from clinically unaffected skin of patients with mild-moderate acne to characterize the morphological changes and natural resolution by means of in vivo reflectance confocal microscopy (RCM) and dynamic optical coherence tomography (D-OCT). METHODS Ten patients with mild-moderate acne, not assuming any topical or systemic therapy, comprised between 12 and 30 years of age, were recruited. A target area of 4 × 4 mm of the face, without acne lesions at baseline, was selected. A set of standardized clinical pictures, RCM and D-OCT images were acquired weekly for 6 weeks and evaluated. RESULTS Seventy full sets of clinical, RCM and D-OCT images were analysed. The appearance of acne lesion is preceded by an increase of large bright follicles in the area corresponding to infundibular keratinization, followed by increment of inflammation parameter, such as increased of small bright cells upon RCM and vascular network upon D-OCT, which return to normal after the resolution of acute inflammation. CONCLUSION Acne skin dynamics is complex and seems characterized by the early increase in the number of dysmorphic pilosebaceous units and the hyperkeratinization of the acroinfundibulum of the pilosebaceous duct prior to the occurrence of inflammatory events around the follicle. The processes of hyperkeratinization and inflammatory phenomena may generate a pathologic vicious cycle, which characterizes acne through progressive worsening and a self-sustainment mechanism.

This open-label multicentre trial evaluated the efficacy and safety of oral dimethyl fumarate (DMF) in patients with moderate-to-severe plaque psoriasis in real-life clinical practice over 52 weeks. Disease severity and improvement were assessed using the psoriasis area severity index (PASI), body surface area (BSA) affected, and Physician Global Assessment (PGA). Quality of life (QoL) was assessed using the Dermatology Life Quality Index (DLQI) questionnaire. The visual analogue scale (VAS) was used to quantify pruritus and measure treatment satisfaction. A total of 141 patients were included, being 66.7% male, aged 49.1 ± 14.7 years and with disease duration of 16 ± 12.1 years. After 52 weeks, mean PASI decreased from 15.9 ± 6.8 to 1.5 ± 2 and 87.7%, 56.9% and 24.6% of patients achieved PASI 75/90/100 response, respectively. BSA decreased from 26.5 ± 14.8% to 2.7 ± 3.5% at 52 weeks, and 81.5% of patients had a PGA 0-1. DLQI scores decreased from 9.4 ± 6.4 to 2.1 ± 3.3, and VAS of pruritus decreased from 53 ± 28.4 to 19.1 ± 26.2 at Week 52. VAS for treatment satisfaction was 79.4 ± 29.4 at Week 52. A total of 34.2% of patients had an AE leading to permanent discontinuation. These findings show that DMF can significantly improve indices of disease severity, pruritus and QoL, with high levels of patient satisfaction and similar safety profile to other fumarates.

Background: Diagnosis of oral white lesions might be challenging. These lesions represent a wide spectrum of diseases with different etiology and prognosis. Oral white lesions can be categorized into two major groups, congenital and acquired, according to their development, and in four subgroups: lesions which can be scraped off or not and lesions with special pattern or not. Objectives: The aim of this manuscript is to review, from diagnosis to treatment, the current knowledge on oral white lesions with specific pattern. Methods: A review on oral white lesions with specific pattern was conducted on PubMed and Scopus from inception to January 2021. Results: Among acquired lesions with specific pattern two clinical entities are mostly represented: Oral lichenoid reactions and Lupus erythematosus. The etiology of both diseases is still not known but their pathogenesis is mainly immunological. At present the mucoscopic features of those disease have been described only in few case reports or case series. Immunomodulatory therapies are often the agents of choice for their treatment. Conclusions: The collaboration of dermatologists and dentists as a team is important for early diagnoses and effective treatments. Mucoscopy is a promising technique which may reveal important features for the differentiation of OLP and LE oral white lesions.

Since December 2019, the pandemic coronavirus disease (2019‐nCoV; COVID‐19) has changed the approach to all dermatological diseases; in particular, psoriatic patients undergoing immunosuppressive drugs, such as biologics, can potentially show an increase risk of infection (1). However, few reports are available on the course of COVID‐19 infection in psoriatic patients treated with biological drugs (2). We describe a case series of four psoriatic patients treated with biologics who had a risk contact with COVID‐19.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Several medical treatments, with varying degrees of efficacy, have been developed. However, in most cases of advanced HS, the definitive treatment option is often represented by surgical excisions. Objective: Surgical techniques, reconstructive approach, and local wound care should be accurately designed in order to obtain the best result. In this review we analyze the possible surgical treatments and local wound care. Methods: A MEDLINE search was performed on the various surgical treatments, reconstructive techniques, and local wound care. Results: Surgical treatment is a common therapeutic modality for HS. Different surgical reconstructive techniques and post-surgical wound care approaches are described for the management of HS patients. Conclusions: There were few high-quality evidence-based studies evaluating the surgical management of HS. Many disparate HS severity scores were used in these studies, making comparisons between them difficult. Nonetheless, research on different surgical approaches and wound care management has increased substantially in the past decade and it has given patients more surgical therapeutic strategies. The description of the best combinations and timing of surgery, wound care, and medical therapies will be a matter of future research for the definition of the optimal management of the HS patient.

Background Psoriasis is a chronic, relapsing disease often associated with comorbidities. While its associations with cardiovascular and metabolic factors have been investigated, little is known about its association with impairment of renal function. Materials and methods We performed a cohort study of 219 psoriatic patients in which we evaluated chronic kidney disease (CKD) and eGFR as well as albuminuria according to their KDIGO stratification risk criteria. We also evaluated circulating immunoglobulins (IgG, IgA, IgM), C3-C4 levels and the urinary albumin-to-creatinine ratio. We divided the patients into two groups, according to the presence or absence of known and established CKD risk factors. Results In our population, the risk of CKD was moderate in 17.35 % of patients, high in 5.02 % and very high in 3.66 %. The risk prevalence for CKD was slightly greater in the group without established risk factors than the risk prevalence reported in NHANES 1999-2006. The presence of psoriatic arthritis, duration of psoriasis (≥ 21 years) and magnitude of the PASI score showed a positive correlation with the urinary albumin-to-creatinine ratio. Conclusions We found an association between microalbuminuria and the duration of psoriasis, as well as with psoriatic arthritis. Moreover, patients with microalbuminuria exhibited a higher Kidney Disease Improving Global Outcome stratification risk.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Several medical treatments, with varying degree of efficacy, have been developed. However, in most cases of advanced (HS), the definitive treatment option is often represented by surgical excisions. Surgical techniques, reconstructive approach, and local wound care should be accurately designed in order to obtain the best result. In this letter, we analyzed the possible surgical treatments and local wound care. A literature review was performed on the various surgical treatments, reconstructive techniques, and local wound care. Surgical treatment is a common therapeutic modality for HS. Different surgical reconstructive techniques and postsurgical wound care approaches are described for the management of HS patients. There were few high-quality evidence-based studies evaluating the surgical management of HS. Many disparate HS severity scores were used in these studies making comparison between them difficult. Nonetheless, research into different surgical approaches and wound care management has increased substantially in the past decade and has given patients more surgical therapeutic strategies. The description of the best combinations and timing of surgery, wound care and medical therapies, will be a matter of future research for the definition of the optimal management of HS patient.

Introduction Whether biologic therapies enhance the risk of coronavirus 2019 (COVID-19) or affect the disease outcome in patients with chronic plaque psoriasis remains to be ascertained. Objective We sought to investigate the incidence of hospitalization and death for COVID-19 in a large sample of patients with plaque psoriasis receiving biologic therapies compared with the general population. Methods This is a retrospective multicenter cohort study including patients with chronic plaque psoriasis (n = 6501) being treated with biologic therapy and regularly followed up at the divisions of dermatology of several main hospitals in the Northern Italian cities of Verona, Padua, Vicenza, Modena, Bologna, Piacenza, Turin, and Milan. Incidence rates of hospitalization and death per 10,000 person-months with exact mid-p 95% CIs and standardized incidence ratios were estimated in the patients with psoriasis and compared with those in the general population in the same geographic areas. Results The incidence rate of hospitalization for COVID-19 was 11.7 (95% CI, 7.2-18.1) per 10,000 person-months in patients with psoriasis and 14.4 (95% CI, 14.3-14.5) in the general population; the incidence rate of death from COVID-19 was 1.3 (95% CI, 0.2-4.3) and 4.7 (95% CI, 4.6-4.7) in patients with psoriasis and the general population, respectively. The standardized incidence ratio of hospitalization and death in patients with psoriasis compared with those in the general population was 0.94 (95% CI, 0.57-1.45; P = .82) and 0.42 (95% CI, 0.07-1.38; P = .19), respectively. Conclusions Our data did not show any adverse impact of biologics on COVID-19 outcome in patients with psoriasis. We would not advise biologic discontinuation in patients on treatment since more than 6 months and not infected with severe acute respiratory syndrome coronavirus 2 to prevent hospitalization and death from COVID-19.

Noninvasive techniques for nail imaging would be useful for confirming diagnosis and monitoring treatment response at the microscopic level in patients with nail psoriasis. However, the use of ultrasound and high-resolution magnetic resonance imaging in nail evaluation is limited. Optical coherence tomography (OCT) produces high-resolution images of transversal tissue sections and represents an optimal approach to the study of the nail. This study used a multibeam OCT instrument to produce speckled variance OCT (SV-OCT) blood-flow images, which were used to measure the degree of change over successive scans. Nail changes, inflammation and response to therapy were evaluated in a 75-year-old female patient with psoriasis who had severe acrodermatitis continua of Hallopeau of the hands, treated for 4 weeks with 40 mg adalimumab (administered subcutaneously every other week) and 25 mg prednisone (administered orally, daily). SV-OCT provided a detailed assessment of the nail structures in relation to inflammation of psoriatic tissues. Restoration of the normal anatomy of the nail apparatus was apparent following adalimumab treatment; SV-OCT evaluation correlated with clinical appearance. SV-OCT may have a diagnostic role and provide an objective tool to assess clinical and subclinical inflammation in nail psoriasis.

BACKGROUND Malignant melanoma is an aggressive skin cancer, which can lead to metastasis development. Vascularization enhancement is fundamental for tumor growth, worsening the prognosis. Dynamic optical coherence tomography (D-OCT) enables the in vivo evaluation of vascular patterns in skin lesions. OBJECTIVE In vivo evaluation of the melanoma vessel morphology by means of D-OCT and correlation with Breslow index. METHODS Retrospective analysis of histologically proven melanomas, evaluated by D-OCT at three different depths (150, 300 and 500 μm), was performed. Vessels were classified according to morphology (dots, blobs, coiled, line, curved, serpiginous), distribution (regular, irregular) and the presence/type of branches. The data were correlated with Breslow thickness. RESULTS A total of 127 melanomas were evaluated. Dotted vessels were recorded at all depths, and their irregular distribution was associated with lesions thicker than 1.0 mm (from 75% to 91%), compared with thin ones (42%) at 150 μm (P = 0.031), and from 33% to 57% vs 18% at 300 μm (P = 0.021). Serpiginous and branching vessels with bulges were predominantly seen in melanomas thicker than 2 mm at 150 μm (from 14% to 27%, P

Biologic therapy in psoriatic patients with multiple comorbidities is challenging due to worsening of associated diseases and possible side effects of concomitant medications.We describe three patients with multiple comorbidities documenting successful treatment of psoriasis with secukinumab following failure of multiple conventional and biologic DMARDs.The first case is an obese 59-year-old woman (HBV + with latent tuberculosis) with arterial hypertension and 12-year history of breast cancer. The second is a 45-year-old obese man (HCV + with occult HBV infection on therapy with multiple antipsychotics and taking methadone for opioid dependence), while the last is a 39-year-old man with severe obesity, non-alcoholic hepatosteatosis, and NYHA class II heart failure. All three patients had undergone previous conventional (methotrexate, cyclosporine, retinoids, and phototherapy) and multiple biologic treatments (one or more of the following: adalimumab, ustekinumab, etanercept, infliximab originator, and biosimilar) that were discontinued for inefficacy and/or adverse effects. All patients underwent therapy with secukinumab, which was associated with sustained clinical benefits and no clinically relevant safety findings.The present three cases add further evidence that secukinumab is effective and well tolerated in difficult to treat psoriatic patients with multiple comorbidities, namely HBV, latent TBC infection, and hepatic impairment.

We describe the case of an 84-years old woman referred to our clinic without an established diagnosis in 2015 for the presence of multiple cervical ulcers since 2013, when she underwent vascular surgery of the carotid arteries. The ulcers had infiltrated and actively inflamed violaceous borders; they were itchy and showed signs of scratching. The patient had already been prescribed different antibiotic treatments, without any clinical improvement. Multiple biopsies had also been performed, but histology was not diagnostic, showing a non-specific dermal inflammatory infiltrate. Despite optimal wound care treatment, we observed a dramatic worsening of the skin lesions, spreading from the neck to the vertex, especially at sites of minor trauma (for example, starting from scratch lesions). The presence of pathergy, which consists in the occurrence of lesions at sites of trauma, suggested the diagnosis of pyoderma gangrenosum. Systemic glucocorticoid therapy was then prescribed, with quick improvement and nearly completes clinical remission. Our case confirms the importance of anamnesis and detailed collection of symptoms associated with the clinical manifestations in dermatological dermatoses such as pyoderma gangrenosum where imaging, histology and laboratory findings are often not very helpful for a correct diagnosis.

Laura Bigi,1 Giovanna Galdo,2 Anna Maria Cesinaro,3 Cristina Vaschieri,1 Alessandra Marconi,4 Carlo Pincelli,4 Fabrizio Fantini5 1Department of Surgical, Medical, Dental and Morphological Sciences, Dermatologic Clinic University of Modena and Reggio Emilia, Modena, 2Plastic Surgery Unit, IRCCS-CROB, Rionero in Vulture (Pz), 3Department of Pathology, 4Department of Surgical, Medical, Dental and Morphological Sciences, Laboratory of Cutaneous Biology, University of Modena and Reggio Emilia, Modena, 5Dermatology Unit, Azienda Ospedaliera “A.Manzoni”, Lecco, Italy Background: Electrochemotherapy (ECT) is increasingly used in the treatment of primary and secondary skin tumors, but little is known about the pathologic mechanism responsible for tumor cell destruction in humans. Knowledge of detailed mechanism of host response after ECT may improve the treatment efficacy related to patient selection and technique refinements.Aim: The aim of the study was to investigate the histopathology and mechanism of cell death after ECT in cutaneous melanoma metastases. Methods: Skin biopsy specimens were sequentially obtained after ECT of cutaneous melanoma metastases, during a follow-up period of 2 months. Results from histologic evaluation and immunohistochemical characterization of the inflammatory infiltrate (CD3, CD4, CD8, CD56, Granzyme-B) were compared with a panel of apoptosis-related markers.Main outcome measures: Evidence of the mechanism of tumor cell damage, identification of histological and immunohistochemical signs of apoptosis and/or necrosis underlining a possible time course of tumor destruction and inflammatory reaction after ECT.Results: Early signs of epidermal degeneration, an increase of the inflammatory infiltrate, and initial tumor cell morphological changes were already detected 10 min after ECT. The cell damage progression, as demonstrated by histological and immunohistochemical evidence using apoptotic markers (TUNEL and caspase-3 staining), reached a climax 3 days after treatment, to continue until 10 days after. Scarring fibrosis and complete absence of tumor cells were observed in the late biopsy specimens. A rich inflammatory infiltrate with a prevalence of T-cytotoxic CD3/CD8-positive cells was detected 3 h after ECT and was still appreciable 3 months later.Conclusion: This study attempts to define the time course and characteristics of tumor response to ECT. The observations suggest both a direct necrotic cell damage and a rapid activation of apoptotic mechanisms that occur in the early phases of the cutaneous reaction to ECT. A persistent immune response of T-cytotoxic lymphocytes could possibly explain the long-term local tumor control. Keywords: electrochemotherapy, melanoma, metastasis, apoptosis

Current treatment for melanoma of the lower limb includes excision of the primary tumor with ilioinguinal lymphadenectomy in the case of lymph node metastases [1–4]. Robotic deep pelvic lymphadenectomy (RDPL) is a welldescribed procedure of staging and treatment of gynecologic and urologic malignancies. Herein we present our initial report of RDPL in malignant melanoma. To our knowledge only one report is present in literature [5], but no follow-up was performed. Clinical staging were performed using total body tomography. The patients were given cephalosporins and antithrombotic prophylaxis with low-weight heparins. The patients were placed on spreader bars in 30–35 Trendelenburg position. The Da Vinci robot (Intuitive Surgical, CA, USA) was docked in standard fashion, with the column positioned between the patient’s legs. Pneumoperitoneum to 20 mmHg was established with closed Veress needle insertion just above the umbilicus. A 12-mm port was placed above the umbilicus, two 8-mm robotic ports were placed just lateral to the medial umbilical ligaments 14–16 cm from the pubic symphysis and 10 cm from the midline. A third 8-mm robotic port was placed for robotic arm on the left side 10 cm lateral to the left-sided 8-mm robotic port. A 12-mm assistant port was placed in the right lower quadrant. After the intestinal bundle is replaced from the pelvis and adhesiolysis is performed, we first open the lateral leaf of the broad ligament. In the retroperitoneum, the first structure to be identified is the psoas muscle, and then ureter and iliac bifurcation are detected. The obturator nerve, the obturator muscle, and the whole course proximal to the internal iliac artery must be visualized. Lymphadenectomy then begins from the proximal side of the lateral external iliac nodes. The lymph node packet between the external iliac artery and the vein was dissected up to the bifurcation of the common iliac artery. After, excision of superficial and deep obturator lymph node chains and retro crural lymph nodes was performed. The packets were placed in 10-mm Endobags and the specimens were removed through the midline port site. The first patient was a 48-year-old woman, who initially underwent a wide local excision of a 1.3-cm melanoma over the right fibular head. Pathology revealed a nodulartype malignant pigmented melanoma (Clark IV, Breslow 2.75 mm; pT3b) with epithelioid cells (MART1-), with negative margins (no-brisk tumor). One month later, the patient was underwent radicalization of the previous excision and a biopsy of the sentinel lymph node. Two of three sentinel lymph nodes were positive for micrometastatic disease. Two months later a RDPL (ileo-crural inguinal/obturator) with deep inguinal groin lymph node dissection was performed, with removal of 18 negative lymph nodes. The second case concerned a pigmented melanoma of the right thigh with spindles cells (Clark IV, Breslow 1.93 mm; pT2a; no-brisk tumor; MART-1) in a 40 year-old patient. At radicalization and biopsy, micrometastatic disease was A. Pellegrino G. R. Damiani (&) Operative Unit of Gynecology and Obstetrics, Alessandro Manzoni Hospital, Lecco, Italy e-mail: damiani14@alice.it

We present an original method for the preparation of "stable" dialysate containing 35 mEq/l of bicarbonate. The dialysate was utilized with 4 patients for periods ranging from 4 months to 1 year according to a short-term recirculated dialysis schedule in closed circuit (20-40L) (2-2 1/2 hrs) on alternate days. Preliminary results are reported here with respect to the tollerance of the dialytic run and correction of the acid-base balance equilibrium. The clinical tollerance is excellent despite high dehydration rates even in patients particularly sensitive to ultrafiltration. The acidosis correction would seem to be much better with bicarbonate than with traditional dialysis. The difference is even higher if we consider the brevity of the dialysis. During the bicarbonate dialysis we do not observe any fall of the PCO2 or significant difference in PO2 in the patient's blood. The correction of acidosis probably causes the normalization of pre-dialytic potassiemia in spite the "net" removal of K with short dialysis is considerably less.