Apremilast for the treatment of palmo-plantar non-pustular psoriasis: A real-life single-center retrospective study.

Palmoplantar psoriasis (PP) is a type of psoriasis that involves the skin of the palms and soles and can present as hyperkeratotic, similar to the vulgaris psoriasis of the body. Apremilast, as an oral inhibitor of phosphodiesterase 4 (PDE4), is currently approved for the treatment of psoriatic arthritis and for moderate-to-severe psoriasis in adult patients who have not responded or have contraindications or do not tolerate other systemic treatments. We evaluated the efficacy and safety of apremilast in the treatment of non-pustular palmo-plantar psoriasis in a cohort of 12 patients. We found a clinical response of clear/almost clear palmoplantar psoriasis (PPPGA score 0/1) in 83.33% of our patients, at week 16. No significant safety issues were reported and none of our patients had to discontinue the drug.

Real-life Effectiveness and Safety of Risankizumab in Moderate-to-severe Plaque Psoriasis: A 40-week Multicentric Retrospective Study.

Risankizumab is a humanized monoclonal antibody that binds the p19 subunit of interleukin-23. It is approved for treatment of moderate-severe chronic plaque psoriasis. This retrospective study included 66 consecutive adults with moderate-to-severe psoriasis vulgaris treated with risankizumab in monotherapy up to week 40 in a "real-life" setting. At week 40, 98.7%, 85.7% and 62.3% of patients achieved a Psoriasis Area and Severity Index (PASI) reduction ≥ 75% (PASI 75), PASI 90 and PASI 100, respectively. Patients who had not responded to 2 or more previous biologic treatments were significantly less likely to achieve PASI 75/90 at week 16 and PASI 90/100 at week 40 compared with those who had been previously treated with only 1 biologic, and compared with those treated with risankizumab as a first-line biologic. Increasing body mass index decreased the chances of reaching PASI 90 at week 40. No significant safety findings were recorded throughout the study, and none of the patients had to interrupt the treatment. These data suggest that the efficacy of risankizumab for plaque psoriasis in "real-life" clinical practice could differ from pivotal clinical trials data.

Specific infiltrate of Hodgkin lymphoma at site of cellulitis mimicking secondary cutaneous involvement.

Hodgkin lymphoma (HL) usually involves the lymph nodes, but concomitant cutaneous manifestations can also occur. The diagnosis of cutaneous involvement by HL must be supported by specific clinical and histopathological findings. We describe the case of a 56-year-old man recently diagnosed with HL of the left axillary nodes who developed cellulitis of the left trunk. Histopathological examination of a skin biopsy specimen revealed the presence of large atypical lymphoid cells with the same immunophenotype of those located in the lymph node affected by HL. Our case adds to the many cutaneous infiltrations by neoplastic cells during the course of an inflammatory skin disease, namely cellulitis.

Brodalumab: A new way to inhibit IL-17 in psoriasis.

Psoriasis is a chronic inflammatory disease that affects 2% to 4% of the population; about 20% of the patients present a moderate-to-severe form. The IL-23/Th17/IL-17 molecular axis is considered crucial in the pathogenesis of psoriasis and IL-17 is fundamental in the maintenance of the immune and inflammatory alterations causing psoriasis. Expression of IL-17A, IL-17F, and IL-17C is strongly increased in psoriatic plaques. Effective therapy leads to restoration of the expression of a wide range of genes (including effector cytokines and chemokines downstream of IL-17) to near normal levels. Brodalumab is the first biologic drug targeting specifically the subunit A of the IL-17 receptor (IL-17RA) and thus inhibiting not only IL-17A but also other members of the IL-17 family. Brodalumab is very effective and safe in treating moderate-to severe psoriasis.

Red grape (Vitis vinifera L.) flavonoids down-regulate collagen type III expression after UV-A in primary human dermal blood endothelial cells.

Red grape (Vitis vinifera L.) flavonoids including flavan-3-ols (eg, catechin and epicatechin), flavonols (eg, quercetin) and anthocyanins (eg, malvidin) exert anti-inflammatory and antioxidant activities. In the skin they also have a photoprotective action, and their effects have been extensively investigated in keratinocytes, melanocytes and fibroblasts. Despite their known effects also on blood vasculature, little is known on their activities on human dermal blood endothelial cells (HDBECs), which are critically involved in skin homeostasis as well as in the pathogenesis of neoplastic and inflammatory skin diseases. We sought to study the biological effects of selected red grape flavonoids in preventing the consequences of ultraviolet (UV)-A irradiation in vitro. Our results show that red grape flavonoids prevent UV-A-induced sICAM-1 release in HDBECs, suggesting that this cell type could represent an additional target of the anti-inflammatory activity of flavonoids. In addition, flavonoids effectively inhibited UV-A-induced synthesis of collagen type III at both RNA and protein level, indicating that dermal blood microvasculature could be actively involved in ECM remodelling as a consequence of skin photo-ageing, and that this can be prevented by red grape flavonoids.

Hypoxia-Inducible Factor-1α and CD271 inversely correlate with melanoma invasiveness.

Melanoma is characterized, among other features, by microenvironmental factors and by an altered apoptotic machinery. Melanoma cell response to a hypoxic environment is transcriptionally regulated by the Hypoxia-Inducible Factor (HIF)-1α. p75 neurotrophin receptor (p75(NTR) ), also called CD271, mediates apoptosis in several cell systems. The purpose of this study was to analyze the expression of HIF-1α and CD271 in melanomas at different phases of progression, as evaluated by histology and reflectance confocal microscopy (RCM). By RCM, 41.67% tumors were characterized by the presence of a population of dendritic and pleomorphic cells (D+P), corresponding to in situ melanoma; 25% exhibited a predominantly round-cell (RN) proliferation with histologic features of superficial melanoma, and 33.33% showed the presence of cells aggregated in nests (DN), typical of invasive melanoma. HIF-1α was scarcely detected in D+P and in RN melanomas, while it was highly expressed in DN tumors. By contrast, CD271 positive cells were mostly detected in D+P population, and barely observed in the other subtypes. This work demonstrates that CD271 expression inversely correlates with hypoxia in melanoma, and that the two markers may be used in the future as diagnostic/prognostic tools for this neoplasm.

Usefulness of in vivo photodiagnosis for the identification of tumor margins in recurrent basal cell carcinoma of the face.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent malignant tumor of the skin. The high prevalence of BCC, the risk of local recurrence, and the difficult clinical identification of the excision margins emphasize the importance of studying new approaches, ensuring complete surgical excision that allows preservation of normal tissue, especially for BCCs located on cosmetically important areas such as the mid face. Photodiagnosis (PD) is a pre-operative technique that allows a more accurate distinction of neoplastic lesions from surrounding healthy skin in vivo. PURPOSE: The aim of this study is to assess the usefulness of PD for the evaluation of tumor margins in 10 patients with recurrent BCC of the face. METHODS: We study the red fluorescence emitted by neoplastic tissue under a Wood's lamp irradiation, after accumulation of methyl amino levulinate (MAL) cream in 10 patients with recurrent BCC. RESULTS: Our histologic analysis of perilesional skin by PD allowed to delineate more precise tumor margins, thus achieving radical excision in 90% of patients. CONCLUSION: PD represents a diagnostic method that helps to distinguish between tumor tissue and surrounding healthy tissue especially in case of recurrent BCC of the face when the clinical delimitation is not clear.

Adult-onset tufted angiomas associated with an arteriovenous malformation in a renal transplant recipient: case report and review of the literature.

Tufted angioma (TA) is a rare benign vascular neoplasm characterized histopathologically by the proliferation of endothelial cells arranged in lobules in the dermis and subcutaneous fat. To date, about 200 cases have been reported, most of which are of Japanese ethnicity. TA predominantly affects children and young adults, developing in 80% of patients younger than 10 years. A white 72-year-old renal transplant recipient presented with 2 asymptomatic dusky red papules on his right leg. The lesions appeared 5 years after the start of immunosuppressive treatment. Histopathologic examination showed a proliferation of poorly canalized capillary-sized vascular structures with typical "cannonball" pattern in the dermis and subcutaneous fat. Eccrine glands were also evident focally in the stroma of capillary lobules. On immunohistochemistry, endothelial cells in the vascular tufts stained positive for CD31 and CD34 but were negative for factor VIII-related antigen, human herpes virus 8, and podoplanin (clone D2-40); α-smooth muscle actin stained pericytes disposed in a single layer in capillary-sized vessels and in 2-3 or more layers in vessels of larger size, respectively. The microscopic findings were suggestive of TA. In the deep dermis, venules with smooth muscle wall and arterioles, as shown by Van Gieson staining, normally not found at that level, were present and appeared surrounded by capillary lobules. Onset of TA in adulthood is rare and may be associated with pregnancy, varicella zoster virus infection, and pharmacological immunosuppression. A case of acquired adult-onset TA associated with an arteriovenous malformation in an elderly transplanted patient is described.

Glomuvenous malformations with smooth muscle and eccrine glands: unusual histopathologic features in a familial setting.

Glomuvenous malformations (OMIM 138000) are hamartomas presenting in childhood as multiple, bluish papules and nodules in the skin, which are characterized histopathologically by irregular vascular spaces surrounded by typical glomus cells. Glomuvenous malformations are caused by autosomal dominant mutations of the GLMN gene. A 34-year-old woman and her 16-year-old son presented with bluish papules and nodules since childhood. Biopsy specimens from both patients showed histopathologic features of glomuvenous malformations, unusually in consistent and close association with smooth muscle, hair follicles and eccrine glands. Sequencing of the GLMN gene revealed the p.C36X (c.108C>A) mutation in germline DNA from both patients. This is probably the first report describing the hamartomatous features of familial glomuvenous malformations consistently associated with a prominent smooth muscle component and eccrine glands.

Risk of acute postoperative hypertension after topical photodynamic therapy for non-melanoma skin cancer.

BACKGROUND: Topical photodynamic therapy with methyl aminolevulinate (MAL-PDT) is a non-surgical treatment for actinic keratoses, Bowen's disease and basal cell carcinoma. MAL-PDT is particularly useful in elderly patients, who often present co-morbidities and/or in whom surgical excision could be contraindicated. MAL-PDT is generally well tolerated; the most frequent acute adverse events include pain and burning sensation localized to the treatment area. We describe our observation of the occurrence of acute postoperative hypertension (APH) and hypertensive crisis, after a MAL-PDT. METHODS: BP measurement was taken twice at 2-min intervals, both before and shortly after the MAL-PDT session. APH was defined as an increase in systolic BP by more than 20% or an increase in diastolic BP to above 110 mmHg. Hypertensive crisis was defined as a systolic BP ≥ 180 mmHg or a diastolic BP ≥ 110 mmHg, with or without acute target organ involvement. RESULTS: Prevalence of post-MAL-PDT APH was 22%; 11% of patients developed hypertensive crisis after MAL-PDT, requiring immediate treatment. CONCLUSION: We highlight the importance of blood pressure measurement both before and after MAL-PDT session to identify high-risk patients and to prevent potentially severe organ involvement subsequent to hypertensive crisis.

Efficacy of acitretin for porokeratosis in a child with chronic cutaneous graft versus host disease.

Porokeratosis is a rare disorder of epidermal keratinization that is regarded as a precancerous. Recipients of hematopoietic stem cell transplantation (HSCT) have a greater risk of skin cancer; chronic graft versus host disease (GVHD) is an additional risk factor. A 16-year-old boy who had received HSCT for acute myelogenous leukemia was referred to us for sclerodermoid chronic cutaneous GVHD. Two years later, he developed disseminated porokeratosis with a few atypical lesions. Despite cryotherapy, numerous lesions of porokeratosis recurred rapidly. Acitretin resulted in good clinical response and reduced the rate of onset of new lesions.

Long-Term Sequential Digital Dermoscopy of Low-Risk Patients May Not Improve Early Diagnosis of Melanoma Compared to Periodical Handheld Dermoscopy.

Sequential digital dermoscopy (SDD) enables the diagnosis of a subgroup of slow-growing melanomas that lack suspicious features at baseline examination but exhibit detectable change on follow-up. The combined use of total-body photography and SDD is recommended in high-risk subjects by current guidelines. To establish the usefulness of SDD for low-risk individuals, we conducted a retrospective study using electronic medical records of low-risk patients with a histopathological diagnosis of cutaneous melanoma between 1 January 2016 and 31 December 2019, who had been referred and monitored for long-term follow-up of clinically suspicious melanocytic nevi. We sought to compare the distribution of "early" cutaneous melanoma, defined as melanoma in situ and pT1a melanoma, between SDD and periodical handheld dermoscopy in low-risk patients. A total of 621 melanomas were diagnosed in a four-year timespan; 471 melanomas were diagnosed by handheld dermoscopy and 150 by digital dermoscopy. Breslow tumor thickness was significantly higher for melanomas diagnosed by handheld compared to digital dermoscopy (0.56 ± 1.53 vs. 0.26 ± 0.84, p = 0.030, with a significantly different distribution of pT stages between the two dermoscopic techniques. However, no significant difference was found with respect to the distribution of pT stages, mean Breslow tumor thickness, ulceration, and prevalence of associated melanocytic nevus in tumors diagnosed on periodical handheld dermoscopy compared to SDD. Our results confirm that periodical dermoscopic examination enables the diagnosis of cutaneous melanoma at an earlier stage compared to first-time examination as this was associated in our patients with better prognostic features. However, in our long-term monitoring of low-risk subjects, Breslow tumor thickness and pT stage distribution did not differ between handheld periodical dermoscopy and SDD.

Understanding Barriers Impacting upon Patient Wellbeing: A Nationwide Italian Survey and Expert Opinion of Dermatologists Treating Patients with Moderate-to-Severe Psoriasis.

A nationwide cross-sectional online survey was administered to dermatologists managing patients with moderate-to-severe plaque psoriasis across Italy to obtain real-world dermatologists' perspectives on the impact of psoriasis and its treatment on patients' daily lives and quality of life (QoL). A total of 91 dermatologists (aged 39.1 ± 11.2 years) completed a 31-question survey and workshop sessions were undertaken in order to identify the best management approach to achieve patient wellbeing. Social (4.2 ± 0.1), physical (4.26 ± 0.2) and mental components (4.1 ± 0.3) were rated by dermatologists as contributing to patient wellbeing to similar extents. While a high proportion (85.4%; rating of 4.3 out of 5) of dermatologists felt that they considered the QoL of patients, a lower proportion (69.6%; rating of 3.7 out of 5) felt that patients were satisfied in this regard. The psoriasis area and severity index and body surface area were the instruments most frequently used to assess the physical domain, while interviews/questions and the dermatology life quality index were used to assess social and mental domains, with only 60% of dermatologists following up on these aspects. The importance of investigating the presence of comorbidities was recognized but not always carried out by many dermatologists, (>70%), particularly for obesity and anxiety/depression. This survey identified key components contributing to barriers impacting on the QoL of patients with moderate-to-severe psoriasis from the perspective of the dermatologist.

Sharing Patient and Clinician Experiences of Moderate-to-Severe Psoriasis: A Nationwide Italian Survey and Expert Opinion to Explore Barriers Impacting upon Patient Wellbeing.

A nationwide survey was conducted in adult patients with psoriasis (PsO) across Italy to obtain their real-world perspective of the impact of PsO on their wellbeing. Patients completed a 26-question survey (based on the patient benefit index; PBI, The Dermatology Life Quality Index; DLQI and the World Health Organization-five; WHO-5 wellbeing index) and workshop discussion sessions were undertaken by dermatologists to interpret results from the survey. 392 patients with PsO completed the survey. Analysis of results was restricted to patients who had moderate-to-severe plaque psoriasis (assessed by patients; n = 252; 64.3%). Dermatologists (n = 32) completed one question from the survey related to wellbeing and rated social, physical and mental domains as contributing to a similar extent, with comparable scores also observed by patients. For treatment, biologics yielded higher scores on average, whereas little difference was observed between topical and conventional systemic treatments. Only 23.8% of patients felt that their dermatologist was taking into consideration their wellbeing and 32.6% of the patients considered their therapy as inadequate in improving signs and symptoms of the disease. This survey identified key factors contributing to barriers impacting on patient wellbeing. Simple, but comprehensive questionnaires can provide important insight to patients' needs that may significantly increase clinician awareness during visits leading to tailored treatment.

A novel mutation of the glomulin gene in an Italian family with autosomal dominant cutaneous glomuvenous malformations.

Glomuvenous malformations (GVM) are hamartomas characterized histologically by glomus cells, which should be distinguished from glomus tumors. Familial GVM are rare, often present as multiple lesions, and exhibit familial aggregation, with autosomal dominant transmission. GVM are caused by mutations of the glomulin (GLMN) gene on chromosome 1p21-p22. Their development is thought to follow the 'two-hit' hypothesis, with a somatic mutation required in addition to the inherited germline mutation. We describe a novel GLMN mutation in an Italian family with GVM in which some members present with the less commonly observed phenotype of solitary lesions. A second somatic 'hit' mutation in GLMN was not discovered in our family. We further provide histological, immunohistochemical and electron microscopic data exhibiting the classic features of GVM. The diagnosis of GVM is critical because of distinction from venous malformations and blue rubber bleb nevus syndrome, which may demonstrate clinical similarities but require different treatment.

The IL23-IL17 Immune Axis in the Treatment of Ulcerative Colitis: Successes, Defeats, and Ongoing Challenges.

Ulcerative colitis (UC) is a chronic relapsing disorder of the colonic tract, characterized by a dysregulated innate and adaptive immune response to gut microbiota that contributes to the perpetuation of intestinal inflammatory processes. The Interleukin (IL) 23/IL17 axis has been reported to play a key role in UC pathogenesis promoting Th17 cells and cytokines-related immune response. Recently, the blockade of IL23/IL17 pathways has been raised enormous interest in the treatment o several chronic inflammatory disorders. In this review, we summarize the emerging results from clinical trials that evoked both promise and discouragement in IL23/IL17 axis in the treatment of UC. Targeting IL23 p40 through Ustekinumab results safe and effective to induce and maintain clinical remission, low inflammatory indexes, mucosal healing, and a better quality of life. Studies targeting IL23 p19 through Mirikizumab, Risankizumab, Brazikumab and Guselkumab are still ongoing. To date, no clinical studies targeting IL17 pathway are ongoing in UC. IL-17 targeting is thought to have a context-dependent biological effect, based on whether cytokine is selectively targeted or if its function is dampened by the upstream block of IL23.