Real-Life Effectiveness and Safety of Guselkumab in Patients with Psoriasis Who Have an Inadequate Response to Ustekinumab: A 3-Year Multicenter Study.

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment.

Efficacy and tolerability of tirbanibulin 1% ointment in the treatment of cancerization field: a real-life Italian multicenter observational study of 250 patients.

BACKGROUND: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp. METHODS: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs. RESULTS: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded. CONCLUSION: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas.

Keratolytics can replace curettage in daylight photodynamic therapy for actinic keratosis on the face/scalp: A randomized clinical trial.

BACKGROUND: Methyl aminolevulinate (MAL) photodynamic therapy (PDT) is commonly used for field treatment of actinic keratoses (AKs). In standard natural daylight PDT (n-DL-PDT) the first step, after the application of chemical solar filter, is removal of crusts and scales by curettage, followed by the application of MAL cream. Some patients experience intense pain during curettage and stinging after application of the photosensitizer to just curettaged skin. OBJECTIVES: To evaluate whether n-DL-PDT without curettage, but preceded by application of keratolytics, would maintain a similar efficacy, based on clinical, dermoscopic, reflectance confocal microscopy (RCM) assessments, safety and patient satisfaction as standard n-DL-PDT with curettage. METHODS: Forty patients with multiple AKs on the face and/or scalp were enrolled in this study. Patients were randomized into two groups of treatment as follows: (i) MAL n-DL-PDT without previous curettage, preceded by skin preparation at home with keratolytics (30% urea cream, twice a day for 7 days; -Cur group) and (ii) MAL n-DL-PDT preceded by skin preparation at the hospital with curettage (+Cur group). RESULTS: Thirty-nine participants completed the study. Four hundred and twenty-one AKs in -Cur group and 337 AKs in +Cur group were treated. The mean reduction in the number of AK lesions 3 months after the treatment was 10.7 (-54.7%) in the -Cur and 10.4 (-58.7%) in the +Cur group. We found that the differences in terms of efficacy and patient satisfaction comparing the two treatment regimens were not statistically significant. The pain score reported during and after daylight exposure was similar and low in both groups. Moreover, no unexpected adverse events occurred during the trial period. CONCLUSIONS: According to our results, curettage is not necessary to obtain the full treatment effect of n-DL-PDT. We experienced in a real-life setting that n-DL-PDT protocol could be changed by replacing curettage with keratolytics.

Primary Cutaneous B-Cell Lymphomas with Large Cell Morphology: A Practical Review.

Most primary cutaneous lymphomas consist of T-cell lymphomas or small cell lymphomas; however, the skin may also be affected by lymphomas with large cell morphology, as a primary or secondary localization. A minority of cases consist of primary cutaneous B-cell lymphomas (PCBCLs). PCBCLs are a heterogeneous group of rare neoplasms with an overlapping morphological and immunohistochemical picture of the different subtypes. Nevertheless, differential diagnosis in the setting of this group of neoplasms is mandatory to identify the correct therapy and prognosis, but it may be challenging since, due to the rarity of these neoplasms, they may not always be familiar to pathologists. Indeed, immunohistochemistry may not be enough to distinguish the different histotypes, which overlap in immunohistochemical features. Furthermore, the ever-increasing knowledge of the molecular features of systemic B-cell lymphomas, such as gene rearrangements with clinical significance, has led in recent years to further investigation into the molecular landscape of PCBCLs with large cell morphology. This work aimed to provide a practical diagnostic guide for pathologists dealing with primary cutaneous large B-cell lymphomas.

Real-World Experience With Topical 5-Fluorouracil 4% (40 mg/g) Cream for the Treatment of Actinic Keratosis.

INTRODUCTION: 5-fluorouracil (5-FU) is one of the most effective topical treatments for actinic keratosis (AK). A new 4% formulation of 5-FU was recently approved in Europe. OBJECTIVES: This study aimed at evaluating 4% 5-FU cream safety and effectiveness in a real-world setting. METHODS: Adult AK patients were retrospectively selected from the University of Campania Dermatology Unit database. Selection criteria included a diagnosis of non-hyperkeratotic, non-hypertrophic AK (Olsen grade I and II) of the face, ears, and/or scalp, treatment with 4% 5-FU once daily for 4 weeks, and at least 3 follow-up visits (4 and 8 weeks after treatment initiation, and 6 months after treatment end). The primary objectives were to evaluate AK lesions improvement at 8 weeks and relapse rate at 6 months. Patient-reported erythema and burning sensation intensity were also assessed at 4 weeks. RESULTS: Ninety-eight patients were included in this analysis (male/female 80/18, mean age 74.7 years). AK lesions improvement at 8 weeks resulted complete or significant in 74.5% and 20.4% of the patients, respectively. At 6 months, 65.3% of the patients did not show AK relapses. Burning sensation at 4 weeks was reported as light, moderate, or absent by 44.9%, 22.4%, and 31.6% of the patients, respectively. Erythema was reported as light, moderate, or absent by 37.8%, 51%, and 10% of the patients, respectively. Burning sensation and erythema disappeared gradually during follow-up. No other side effects were reported. CONCLUSIONS: In this real-world study 4% 5-FU proved to be highly effective for AK lesions clearance with a favorable safety profile.

Multidisciplinary Approach to the Diagnosis and Therapy of Mycosis Fungoides.

Mycosis fungoides is the most common primary cutaneous T-cell lymphoma, characterized by skin-homing CD4+ T cells derivation, indolent course, and low-grade of malignancy. Mycosis fungoides's classic type typically onsets with cutaneous erythematous patches, plaque, and tumor. In WHO-EORTC classification, folliculotropic mycosis fungoides, pagetoid reticulosis, and granulomatous slack skin are recognized as distinct variants of mycosis fungoides, because of their clinical and histological features, behavior, and /or prognosis. Mycosis fungoides often shows diagnostic difficulties, due to its absence of specific features and lesional polymorphism. A patient's treatment requires staging. In about 10% of cases, mycosis fungoides can progress to lymph nodes and internal organs. Prognosis is poor at advanced stage and management needs a multidisciplinary team approach. Advanced stage disease including tumors, erythroderma, and nodal, visceral, or blood involvement needs skin directed therapy associated with systemic drugs. Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated.

Hidradenitis Suppurativa Burdens on Mental Health: A Literature Review of Associated Psychiatric Disorders and Their Pathogenesis.

Skin, mental health and the central nervous system (CNS) are connected by a deep link. It is not only the aesthetic and sometimes the disfiguring aspects of dermatological conditions that can cause a severe psychological burden; also, different studies have shown how chronic skin-inflammatory diseases may influence the activity of the CNS and vice versa. Moreover, the skin and brain share a common embryogenic origin. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting the hair follicles of the apocrine regions. The main clinical features are nodules, abscesses, cysts, fistulae and disfiguring scars. Pain and stinking discharge from fistulae are often present. It is not surprising that the psychological burden associated with HS is frequently a challenge in dermatologists' daily routines. Patients often suffer from depression and anxiety, but also from substance abuse, psychotic and bipolar disorders and an increased suicide risk. The aim of this article is to review the main psychiatric disorders associated with HS and their pathophysiology. Research on Pubmed was conducted with the key words Hidradenitis suppurativa, psychiatric, depression, anxiety, bipolar, schizophrenia, abuse, suicidal. A high incidence of psychiatric disorders has been described in HS compared to controls. Hidradenitis suppurativa is not a rare disease, and acknowledging the HS psychological burden, psychiatric-associated diseases and associated biomolecular pathways will help dermatologists to better care for their patients.

Photodynamic Therapy as an Effective Treatment for Cutaneous Lymphomas.

Topical photodynamic therapy (PDT) is a non-invasive treatment modality frequently used in dermatology to treat superficial skin cancers but also some inflammatory or infectious dermatoses. PDT appears a more and more promising therapeutic option also for cutaneous lymphomas, either of T- or B-cell origin. It is a well-tolerated treatment and has excellent cosmetic outcomes, less side effects compared to other therapies (steroids, surgery, radiotherapy, and so on), no particular contraindications, and is easily repeatable in case of relapses. However, how PDT works in the treatment of cutaneous lymphoproliferative diseases is poorly understood and the literature data are still controversial. Further randomized, controlled clinical trials involving a greater number of patients and centers with a long follow-up are necessary to assess the efficacy of PDT and establish a unique standardized treatment protocol in relation to the lymphomatous disease and the type, thickness, and location of the lesions.

Body Mass Index and Melanoma Prognosis.

INTRODUCTION: Obesity has been suggested as a risk factor in the progression of malignancies, including melanoma. Most studies defined obesity using body mass index (BMI), although the index is considered an imperfect measure of body composition. OBJECTIVE: The aim of this article is to examine whether BMI can impact on the prognosis of cutaneous melanoma, regardless of anti-tumor therapy. The relationship between BMI and specific prognostic factors in melanoma patients has been reviewed. METHODS: Literature search was conducted on PubMed using the terms "melanoma" and "body mass index" or "obesity". We selected articles, published up to 30 November 2020, examining the prognostic aspects of melanoma. Articles evaluating the risk and incidence of melanoma were excluded as well as studies regarding morbidity and complications following surgical procedures, or those performed in metastatic melanoma patients treated with anti-tumor therapies. RESULTS: Mixed results have emerged from studies assessing the clinical outcomes in melanoma patients in relation to BMI. More consistent data seem to support the relationship between BMI and Breslow thickness. CONCLUSIONS: Studies that focus specifically on the link between obesity and melanoma prognosis are limited; further research is needed to deepen our knowledge on this link.

A Randomized Double-Blind Parallel-Group Study to Evaluate the Long-Term Effects of a Medical Device Containing 0.3% Octatrienoic Acid in the Treatment of Grade III Actinic Keratosis.

INTRODUCTION: Actinic keratosis (AK) consists of skin lesions with a milder degree of keratinocytic atypia. It can be also referred to as "field of cancerization," which can potentially evolve to cutaneous squamous cell carcinoma (SCC). Several therapeutic options are currently available, but not all are indicated on hyperkeratotic lesions. This study aimed to test the efficacy and tolerability of a medical device containing 2,4,6-octatrienoic acid and urea for the treatment of hyperkeratotic AK lesions. METHODS: Seventy male and female subjects with grade III AK were enrolled in this randomized double-blind parallel-group study. The product was applied once daily for three consecutive months. The primary efficacy endpoint was the reduction in the mean number of AK lesions per subject from baseline (T0) to the end of the trial (T1) and 3 months after the end of the treatment period (T2). Therefore, clearance of target AK lesions at the end of the treatment period and local skin reaction score (LSR) versus baseline were evaluated. RESULTS: There was a decrease of mean values from baseline to visit T2 in both treatment groups, but the decrease (versus baseline values) was more evident in the Kerà K2 group than in the placebo group (-42.78, SD 26.53, versus -6.20, SD 31.57), and the difference was statistically significant (p < 0.001). For 70 subjects (56.7%) in the Kerà K2 group and 3 (11.54%) in the placebo group, a significant (p < 0.005) partial clearance was evidenced. The product was well tolerated, and no serious adverse events were reported during the duration of the trial. Subject self-assessment of acceptability, local tolerability, and the cosmetic result was good at both T1 and T2 for both groups. CONCLUSIONS: The medical device has demonstrated good efficacy in the reduction of visible AKs, encouraging its use.

Chronic Chest Pain Control after Trans-Thoracic Biopsy in Mediastinal Lymphomas.

Chest pain following a trans-thoracic biopsy often has multiple etiologies, especially in patients with lymphomas. Pathological neuronal mechanisms integrate with an overproduction of IL-6, TNF-α, IL1-ß by macrophages and monocytes, which amplifies inflammation and pain. In consideration of this complex pathogenesis, international guidelines recommend diversified analgesia protocols: thoracic epidural, paravertebral block, and systemic administration of opioids. This study reports an attempt to reduce chest pain and prevent chronic pain in 51 patients undergoing trans-thoracic biopsy for mediastinal lymphoma. The entity of pain, measured 72nd hour after biopsy by the Numerical Rating Scale (NRS), was compared with that seen at a 6th month checkpoint in 46 patients. The pain decreased in all cases. At the 6th month checkpoint, among 31 opioid-treated patients, none of the 16 patients with NRS < 6 within the 72nd hour post biopsy had developed chronic chest pain, while 8 of the 15 with higher values did (p < 0.01). Of 10 patients undergoing thoracotomy and treated with opioids, eight had a NRS of no more than 2, of which six had no chronic pain. Of the twenty-one patients who underwent VATS biopsy and were treated with opioids, fifteen had NRS no greater than 2, of which ten had no chronic pain. Subgroups of patients biopsied under mediastinotomy or video-assisted thoracoscopic surgery (VATS) and treated with thoracic epidural analgesia (TEA) or PVB were too small for such analysis.

Primary Extra-Nodal DLBCL of Glands: Our Experiences outside Guidelines of Treatment.

Lymphomas usually involve lymph nodes and other lymphoid tissues, but sometimes occur in non-lymphoid organs, called extra-nodal sites. Primary diffuse extra-lymph node large B-cell lymphoma (DLBCL) of the thyroid and parotid gland have been observed rarely. According to the most accredited guidelines, primary extra-nodal DLBCL of the parotid and thyroid glands should be treated with three cycles of R-CHOP followed by radiotherapy of the involved site (ISRT). Surgery alone is not enough to treat DLBCL. We describe two unusual cases of primary extra-nodal DLBCL in elderly patients treated exclusively with surgical resection, given the inability to apply chemotherapy. Both patients achieved clinical recovery, which was maintained after a follow-up of more than 18 months, despite not having performed the indicated chemotherapy protocol. The two cases presented here, and a few others reported in the literature, should be considered exceptions to the rule, and do not allow the conclusion that surgery alone might be sufficient for complete remission.