Psoriasis with Leg Involvement as the New Difficult-To-Treat Area: A Cohort Study of Patients Treated With Risankizumab.

INTRODUCTION: Historically, difficult-to-treat areas in psoriasis included face, scalp, folds, genitalia, nails, and palmoplantar region. Recent studies have found that lower limbs behave like a "new" difficult-to-treat area as they can be the only site of residual disease even in patients undergoing biologic therapies. OBJECTIVES: We aimed to evaluate whether legs had different response rates and response times to treatment with a new biologic drug, risankizumab, compared to other body sites. METHODS: We conducted a real-life, observational, retrospective, multicenter study including patients affected by moderate-to-severe psoriasis with leg involvement and undergoing biological therapy with risankizumab for more than 16 weeks. The Psoriasis Area Severity Index (PASI) and Leg-PASI were collected at T0 and at weeks 16, 28, 40, 52, 64, and 76. Statistical analysis using Student's t test and linear regression analysis were performed. RESULTS: A total of 124 patients were included. The difference between the improvement percentage compared to baseline was statistically significant at weeks 16 and 28, demonstrating that Leg-PASI improved less than PASI. From the linear regression it was deduced that the slope is statistically less steep for Leg-PASI than for overall PASI, confirming that this site responds more slowly to the therapy. CONCLUSIONS: Leg response to risankizumab appears to differ significantly from other body sites in the first weeks of treatment, even if after 28 weeks, statistical significance is lost. Our preliminary finding suggests that risankizumab can be considered an effective treatment for leg psoriasis but with longer response times than other areas, demonstrating the relative nature of resistance to treatment of this district.

A Case of Noonan Syndrome and Kyrle's Disease: Coincidence or Causality?

A 39-year-old Caucasian woman affected by Noonan Syndrome (NS) mutated in RAF1 was referred to us with itchy lesions on her limbs that had appeared two months earlier. Clinically, there were multiple umbilicated papules with a hyperkeratotic central plug, localized on the upper and lower limbs (Figure 1, a-b). The patient had no personal history of diabetes mellitus and no chronic renal failure, but suffered from hypertrophic cardiomyopathy. Blood tests showed no abnormalities. On histological examination of a skin lesion, an ectatic hair follicle with hyperkeratotic ostium was observed with fragments of hair, inflammatory cells, and epidermal perforation. A final diagnosis of Kyrle's disease (KD) was established. The patient underwent narrowband UVB (NB-UVB) phototherapy with residual atrophic scars (Figure 1, c-d) but with complete and long-lasting resolution of symptoms as well. KD belongs to perforating dermatoses (PD), a heterogeneous group of skin diseases characterized by the transepidermal elimination of dermal components. Despite the classification of PD being debated, four primary forms are traditionally recognized: reactive perforating collagenosis, elastosis perforans serpiginosum, perforating folliculitis, and KD (1). The typical skin manifestation of KD is an eruption of dome-shaped papules and nodules with a whitish central keratotic plug, mainly localized on the extremities and the buttocks. Described by Kyrle in 1916, KD is frequently associated with systemic diseases, especially chronic renal failure and diabetes mellitus. Other associated conditions include chronic hepatic disease, internal malignancies, and congestive heart disease (1). Despite the absence of a consensus, the control of the underlying disease remains the first therapeutic target. Both topical (keratolytics, retinoids, and corticosteroids) and systemic treatments (corticosteroid, retinoids, antibiotics, and phototherapy) have been reported to control skin manifestations (2). In our experience, NB-UVB is an effective option as first-line therapy in case of diffuse lesions, both in KD and in other PDs (3). NS is a relatively common RASopathy, an heterogenous group of genetic disease characterized by a defect of the Ras-mitogen-activated protein kinase (Ras-MAPK) pathway, with an estimated prevalence of 1/1000-2500. PTPN11 is the most frequent mutated gene, accounting for 50% of cases, but more than ten genes were identified as causing NS (4). Classical features include a distinctive facial dysmorphism, short stature, pulmonic stenosis, and other anomalies of different organs. The skin is commonly involved. Keratinization disorders and hair abnormalities such as keratosis pilaris, ulerythema ophryogenes, wavy or curly hair, and scarce scalp hair are often described. Other cutaneous signs include easy bruising, skin hyperlaxity, multiple lentigines, and café-au-lait spots (5). To the best of our knowledge, no cases of KD in patients with NS have been previously reported to date. The exact etiopathogenesis of KD is not clear, but it was hypothesized that systemic diseases, such as diabetes and chronic renal failure, can cause a deposit of substances or dermis alterations, which triggers the inflammatory process with subsequent transepidermal extrusion (1). In our patient, we ruled out all the causes commonly associated with KD. It is however possible that this manifestation could be a direct result of our patient's illness. Our patient suffered from diffuse keratosis pilaris, and one of the possible pathogenetic mechanisms of KD was theorized to be an abnormal epidermal keratinization with a secondary inflammatory dermic response (1). On the other hand, the hyperlaxity and fragility of the skin typical of NS suggest the presence of altered connective tissue, which could trigger an abnormal keratinization and, subsequently, the transepidermal extrusion, as well as perforating elastosis, and is associated with genetic connective tissue diseases (1). Moreover, our patient suffered from a cardiac disease, another condition associated with KD (5). Although these explanations have their appeal, there is currently insufficient evidence of a link between KD and NS, and it will be necessary to collect additional data to confirm this hypothesis.

Comparative effectiveness of tildrakizumab 200 mg versus tildrakizumab 100 mg in psoriatic patients with high disease burden or above 90 kg of body weight: a 16-week multicenter retrospective study - IL PSO (Italian landscape psoriasis).

PURPOSE: Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight. MATERIALS AND METHODS: Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2. RESULTS: After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively. CONCLUSIONS: Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden.

Characteristics of Patients Experiencing a Flare of Generalized Pustular Psoriasis: A Multicenter Observational Study.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, severe inflammatory skin disease characterized by recurrent episodes of flares. Characteristics of patients experiencing a flare are hardly described in a real-life setting. The aim of the study is to investigate the clinical characteristics of patients experiencing a flare of GPP. METHODS: Multicenter retrospective observational study on consecutive patients experiencing a flare of GPP between 2018 and 2022. Disease severity and quality of life were assessed by Generalized Pustular Psoriasis Area, Body Surface Area (BSA), and Severity Index (GPPASI), and Dermatology life quality index (DLQI) questionnaire, respectively. Visual analogue scale (VAS) of itch and pain, triggers, complications, comorbidities, pharmacological therapies, and outcome were collected. RESULTS: A total of 66 patients, 45 (68.2%) females, mean age 58.1 ± 14.9 years, were included. The GPPASI, BSA, and DLQI were 22.9 ± 13.5 (mean ± standard deviation), 47.9 ± 29.1, and 21.0 ± 5.0, respectively. The VAS of itch and pain were 6.2 ± 3.3 and 6.2 ± 3.0, respectively. Fever (>38 °C) and leukocytosis (WBC > 12 × 109/L) were found in 26 (39.4%) and 39 (59.1%) patients, respectively. Precipitating triggers were identified in 24 (36.3%) and included infections (15.9%), drugs (10.6%), stressful life events (7.6%), and corticosteroids withdrawal (3.0%). Fourteen (21.2%) patients were hospitalized because of complications including infections in 9 (13.6%) leading to death in one case and hepatitis in 3 (4.5%). CONCLUSIONS: GPP flares can be severe and cause severe pain and itch with significant impact on the quality of life. In about one-third of patients the flare may have a persistent course and, with complications, lead to hospitalization.

A Case of Noonan Syndrome and Kyrle Disease: Casualty or Causality?

A 39-year-old Caucasian woman affected by Noonan Syndrome (NS) mutated in RAF1 was referred to us with itchy lesions on her limbs that had appeared two months earlier. Clinically, there were multiple umbilicated papules with a hyperkeratotic central plug, localized on the upper and lower limbs (Figure 1, a-b). The patient had no personal history of diabetes mellitus or chronic renal failure, but suffered from hypertrophic cardiomyopathy. Blood tests showed no abnormalities. On histological examination of a skin lesion, an ectatic hair follicle with a hyperkeratotic ostium was observed with fragments of hair, inflammatory cells, and epidermal perforation. A final diagnosis of Kyrle disease (KD) was established. The patient underwent narrowband UVB (NB-UVB) phototherapy with residual atrophic scars (Figure 1, c-d), but with a complete and long-lasting resolution of symptoms. KD belongs to perforating dermatoses (PD), a heterogeneous group of skin diseases characterized by the transepidermal elimination of dermal components. Despite the classification of PD still being under debate, four primary forms are traditionally recognized: reactive perforating collagenosis, elastosis perforans serpiginosum, perforating folliculitis, and KD (1). The typical skin manifestation of KD is an eruption of dome-shaped papules and nodules, with a whitish central keratotic plug, mainly localized on the extremities and the buttocks. Described by Kyrle in 1916, KD is frequently associated with systemic diseases, especially chronic renal failure and diabetes mellitus. Other associated conditions include chronic hepatic disease, internal malignancies, and congestive heart disease (1). Despite the absence of a consensus, the control of the underlying disease remains the first therapeutic target. Both topical (keratolytics, retinoids, and corticosteroids) and systemic treatments (corticosteroids, retinoids, antibiotics, and phototherapy) have been reported to control skin manifestations (2). In our experience, NB-UVB is an effective option as first-line therapy in case of diffuse lesions, both in KD and in other PD (3). NS is a relatively common RASopathy, a heterogenous group of genetic diseases characterized by a defect of the Ras-mitogen-activated protein kinase (Ras-MAPK) pathway, with an estimated prevalence of 1/1000-2500. PTPN11 is the most frequent mutated gene, accounting for 50% of cases, but more than ten genes have been identified as causing NS (4). Classical features include a distinctive facial dysmorphism, short stature, pulmonic stenosis, and other anomalies of different organs. The skin is commonly involved. Keratinization disorders and hair abnormalities such as keratosis pilaris, ulerythema ophryogenes, wavy or curly hair, and scarce scalp hair, are often described. Other cutaneous signs include easy bruising, skin hyperlaxity, multiple lentigines, and café-au-lait spots (5). To the best of our knowledge, no cases of KD in patients with NS have been previously reported to date. The exact etiopathogenesis of KD is not clear, but it has been hypothesized that systemic diseases, such as diabetes and chronic renal failure, can cause a deposit of substances or dermis alterations, which triggers the inflammatory process with subsequent transepidermal extrusion (1). In our patient, we ruled out all the causes commonly associated with KD. It is however possible that this manifestation could be a direct result of the patient's illness. Our patient suffered from diffuse keratosis pilaris, and an abnormal epidermal keratinization with a secondary inflammatory dermic response is among the suggested possible pathogenetic mechanisms of KD (1). On the other hand, the hyperlaxity and fragility of the skin typical of NS suggest the presence of altered connective tissue, which could trigger an abnormal keratinization and, subsequently, the transepidermal extrusion, as well as perforating elastosis, which is associated with genetic connective tissue diseases (1). Moreover, our patient suffered from a cardiac disease, another condition associated with KD (5). Although these explanations have their appeal, there is currently insufficient evidence of a link between KD and NS, and it will be necessary to collect additional data to confirm this hypothesis.

Skin reaction to COVID-19 vaccine: A report of 4 cases.

Since the beginning of the covid-vaccine campaign, a lot of local and systemic dermatologic reactions happening after the administration of Coronavirus disease 2019 (COVID-19) vaccines have been described, even if their exact biological mechanism is still debated. In this paper we report 4 cases of cutaneous manifestations arose within ten days after the first dose of messenger RNA (mRNA)-based COVID-19 vaccination: one case of giant urticaria, one case of head and neck redness and two cases of Erythema Multiforme (EM). In our experience these reactions were mild, transient and all of them resolved, not recurring after the second dose, so these manifestations shouldn't be considered as an absolute contraindication to the second dose of vaccine, that to date is fundamental.

Development and single laboratory validation of a targeted liquid chromatography-triple quadrupole mass spectrometry-based method for the determination of insulin like growth factor-1 in different types of milk samples.

A simple and reliable targeted liquid chromatography-electrospray-tandem mass spectrometry (LC-MS/MS) method was developed and validated through the selection of two biomarker peptides for the identification and determination of bovine insulin like growth factor-1 (IGF-1) in milk samples. Two urea-based sample extraction procedures were tested. The validation results provided detection limits at the 1-5 ng IGF-1/mL level as a function of the milk matrix, precision ranged from 3 to 8% and the method accuracy in the different milk matrices was assured. Finally, IGF-1 was measured in milk samples obtained by treatment with eleven different technological processes: IGF-1 concentrations were spread over a wide range from 11.2 ± 0.3 ng/mL to 346 ± 8 ng/mL with a median of 57.0 ± 0.2 ng/mL. The highest amount of IGF-1 was found in fresh whole milk samples and no significant correlation was found between the total milk protein content and the IGF-1 concentration level.

The influence of Mediterranean diet in acne pathogenesis and the correlation with insulin-like growth factor-1 serum levels: Implications and results.

Acne is a chronic inflammatory disease of the pilosebaceous unit, and its etiology is complex and multifactorial. The role of the diet in its pathogenesis is still debated. The purpose of this study was to assess the association between MD and IGF-1 in acne patients and, as secondary objective, the role of systemic treatment on IGF-1 serum levels, in accordance with the patients' diet. This study included 35 patients aged 14-30 years affected by acne and treated in line with the EDF guidelines. Patients were divided into 2 groups based on a questionnaire score assessing the adherence to the Mediterranean diet: the Mediterranean Group (score ≥6) and the Western Group (score< 5). IGF-1 serum levels were measured in all patients before and after treatment and then compared to healthy population. IGF-1 levels were higher in patients than in controls and in the Western group than in the Mediterranean group. We speculate that the Mediterranean diet can have a protective role in the pathogenesis of acne by acting on the systemic route of IGF-1.

Vitiligo: What's old, what's new.

Vitiligo is an acquired pigmentary disorder afflicting 0.5-2% of the world population for both sexes and all races with a capricious and unpredictable course. It has a complex etiology and varies in its manifestation, progression and response to treatment. Even if the precise aetiology and pathobiology of the disease are complex and still debated, recent evidence supports that vitiligo is a T CD8+ cell-mediated autoimmune disease triggered by oxidative stress. To date no clinical, biological and histological criteria allow us to establish the prognosis with certainty. The choice of the best therapy for adult and childhood vitiligo is based on various factors, such as the patient's age, psychological condition and expectations, distribution and extension of skin lesions, type of vitiligo (stable or not) and availability and cost of therapeutic options. Since vitiligo has a deep psychological impact on patients and their quality of life, treating the disease is very important. As dermatologists, we have important goals in the treatment of vitiligo patients: stabilization of the disease progression, repigmentation of the lesions and especially the persistence of the aforementioned repigmentation. Although several medical and surgical therapeutic options have been proposed, no definite cure has yet been developed and the long-term persistence of repigmentation is unpredictable. We review the different therapeutic options with particular attention on the recurrence rate.

Case of large lentigo maligna melanoma of the scalp treated with 5% and 3. 75% Imiquimod

Abstract The paper presents a case of lentigo maligna melanoma of the scalp in an elderly patient treated for the nodular part with surgery and the residual melanoma in situ with 5% Imiquimod and subsequently with 3.75% Imiquimod (each concentration for 4 months, 5 times per week), with complete regression of the lesion. 3.75% Imiquimod, which is already used for the treatment of actinic keratosis, could be a useful weapon with the same effectiveness and fewer side effects compared to 5% Imiquimod.

Case of large lentigo maligna melanoma of the scalp treated with 5% and 3.75% Imiquimod.

The paper presents a case of lentigo maligna melanoma of the scalp in an elderly patient treated for the nodular part with surgery and the residual melanoma in situ with 5% Imiquimod and subsequently with 3.75% Imiquimod (each concentration for 4 months, 5 times per week), with complete regression of the lesion. 3.75% Imiquimod, which is already used for the treatment of actinic keratosis, could be a useful weapon with the same effectiveness and fewer side effects compared to 5% Imiquimod.