Psoriasis and biological drugs at the time of SARS-CoV-2 infection: a mini review outlining risk of infection, seroprevalence, and safety and efficacy of the BNT162b2 vaccine.

Objective: The aim of this study is to review the life of patients with psoriasis on biologic therapy during the SARS-CoV-2 pandemic and the relevance of frailty within this context, reviewing studies that describe the course and severity of infection in patients with psoriasis on biologics, the seroprevalence of SARS-CoV-2, and the safety and efficacy of the BNT162b2 vaccine in these patients. Materials and methods: The keywords "Psoriasis," "Biologics," "SARS-CoV-2," "COVID-19," and "BNT162b2 Vaccine" were used in various combinations on database engines to find relevant articles on this topic. Results: A total of 36 articles were found, with 20 concerning the course, severity, and seroprevalence of SARS-CoV-2 in patients with psoriasis on biologic therapy and 16 concerning safety and efficacy of BNT162b2 in these patients. Discussion: Patients with psoriasis on biologic therapy did not have increased seroprevalence compared with the general population, indicating that they were not at an increased risk of SARS-CoV-2 infection compared with the general population. Furthermore, the immunosuppressive action of biologics may be protective, as patients on biologic therapy had better outcomes and less risk of severe infection. The seroconversion rate against SARS-CoV-2 from the BNT162b2 vaccine was similar in both patients with psoriasis on biologics and the general population, indicating that efficacy is not hindered by the biologic therapy. However, the cellular response in population with psoriasis was significantly less intense, and the humoral immune response was weaker than that in the general population, demonstrating that the possibility of tighter vaccination schedules and additional doses may be advantageous in these patients.

Lipschütz ulcers due to SARS-CoV-2 infection: a neglected diagnosis in emergency room.

Background: Primary acute genital ulcers, or Lipschütz ulcers (LU), are nonsexually transmitted, painful, self-limiting, nonrecurrent vulvar ulcers with unclear pathogenesis, representing a challenging diagnosis in emergency setting. LU have recently been described in association with severe acute respiratory syndrome coronaVirus 2 (SARS-CoV-2) infection and vaccination. Objective: The aim of this study is to describe 2 cases of LU due to SARS-CoV-2 infection, highlighting the diagnostic process, differential diagnosis, disease course, and management options. Methods: We describe 2 young females (12 and 9 years old) who presented to pediatric emergency room with the sudden onset of well-demarcated, painful, vulvar ulcers with fibrinous necrotic center. Results: Both patients tested positive to SARS-CoV-2 nasal swab, and, at physical examination, no other lesions were found in other cutaneous or mucosal sites. Sexual abuse was excluded in both cases, as well as infectious and autoimmune diseases. Supportive analgesic therapy was administered, and complete remission of lesions was observed at follow-up visits without evidence of scarring. Limitations: The main limitation of this work is represented by the small number of cases described. Conclusion: Even though extremely rare, LU related to COVID-19 are an emerging entity to be considered in the diagnosis of acute genital ulcerations. Multidisciplinary diagnostic workup of genital ulcers must be established in order to exclude sexual child abuse, to ensure patient safety, and to avoid unnecessary treatment and familial anxiety.

Circulating Mesenchymal Stromal Cells in Patients with Infantile Hemangioma: Evaluation of Their Functional Capacity and Gene Expression Profile.

We previously published that in patients with infantile hemangioma (IH) at the onset (T0) colony forming unit-fibroblasts (CFU-Fs) are present in in vitro cultures from PB. Herein, we characterize these CFU-Fs and investigate their potential role in IH pathogenesis, before and after propranolol therapy. The CFU-F phenotype (by flow cytometry), their differentiation capacity and ability to support angiogenesis (by in vitro cultures) and their gene expression (by RT-PCR) were evaluated. We found that CFU-Fs are actual circulating MSCs (cMSCs). In patients at T0, cMSCs had reduced adipogenic potential, supported the formation of tube-like structures in vitro and showed either inflammatory (IL1ß and ESM1) or angiogenic (F3) gene expression higher than that of cMSCs from CTRLs. In patients receiving one-year propranolol therapy, the cMSC differentiation in adipocytes improved, while their support in in vitro tube-like formation was lost; no difference was found between patient and CTRL cMSC gene expressions. In conclusion, in patients with IH at T0 the cMSC reduced adipogenic potential, their support in angiogenic activity and the inflammatory/angiogenic gene expression may fuel the tumor growth. One-year propranolol therapy modifies this picture, suggesting cMSCs as one of the drug targets.

Biological Therapies for Pediatric Atopic Dermatitis - A Review.

Atopic dermatitis (AD) is the most frequent chronic-recurrent inflammatory skin disease in the pediatric age. It has a complex and multifactorial pathogenesis: the two key actors are impaired skin barrier function and immune system dysregulation, which represent the main targets of AD therapy. Monoclonal antibodies have revolutionized the management of moderate-to-severe AD, by selective inhibition of key cytokines in the pathogenetic process. For this reason, there is great interest in exploring AD pathogenetic mechanisms to develop new therapeutic strategies. This review aims to summarize the most recent scientific evidence on available and future biological therapies for the treatment of pediatric AD, emphasizing the molecular mechanisms underlying their action.

A multidisciplinary dermatology-gastroenterology-rheumatology (DER.RE.GA) unit for the care of patients with immune-mediated inflammatory diseases: analysis of the first 5 years from the dermatologist's perspective.

Immune-mediated inflammatory diseases (IMIDs) constitute a heterogenous group of chronic and highly disabling conditions. The clinical challenges they often pose led to formation of numerous dermo-rheumatological interdisciplinary units around the world, which are reported to benefit their patients in various ways. The present paper describes our experience with a multidisciplinary dermatology-rheumatology-gastroenterology unit DERREGA at the IRCCS Foundation Policlinico San Matteo of Pavia over a period of 5 years of its activity (2017-2022). A digital database was created, containing the medical records of 146 patients referred to the dermatology unit only by rheumatologists or gastroenterologists belonging to the multidisciplinary unit DERREGA. Then, aspects such as demographics, initial basis of referral and final diagnosis among the patients were analyzed retrospectively. Patients were classified as either gastroenterological or rheumatological, and then categorized according to the specific basis of referral. Most of the gastroenterological patients (97%) were affected by inflammatory bowel diseases (IBDs). Rheumatological patients were divided in three subgroups, including patients referred with vasculitis, arthropathies (undifferentiated arthritis, psoriatic arthritis and other arthritis) and other rheumatological diseases. Then, final diagnoses were evaluated in each group. Almost a third of IBD patients received a diagnosis of paradoxical psoriasis. Dermatological examination allowed diagnosis of minimal psoriasis based on Caspar criteria in over 70% of the patients admitted with undifferentiated arthritis. A multidisciplinary approach is suggested to provide more effective management of IMIDs and, specifically, from a dermatological perspective, allows for the diagnosis of minimal manifestations of psoriasis in patients with a provisional diagnosis of undifferentiated arthritis.

Propranolol for the treatment of infantile hemangiomas: a nine-year monocentric experience from a tertiary hospital.

BACKGROUND: Propranolol is currently considered the first-line therapy for problematic infantile hemangiomas (IH), the most common benign vascular neoplasm of infancy. OBJECTIVES: We present a retrospective observational study aimed at assessing the efficacy of propranolol in 44 IH patients. MATERIALS & METHODS: A nine-year retrospective review considering clinicodemographical and therapy-related variables was performed on medical records of infants treated for IH with oral propranolol. Each lesion was assessed through a numeric severity score based on size and colour both at baseline and after treatment conclusion (p <0.05 was considered statistically significant). RESULTS: Complete remission was achieved in 90.7% cases of IH with a general mean improvement in severity of 94.94%. No severe adverse effects were reported. Preterm patients showed a superior response compared to term infants, even though the difference was not significant (p=0.185). CONCLUSION: Propranolol showed high efficacy in terms of safety profile and cosmetic results. Prematurity and precocious therapy could be linked to a superior response.

Eosinophilic dermatosis of hematologic malignancy in patients with chronic lymphocytic leukemia/non-Hodgkin's B lymphoma: a single center prospective clinico-pathological study.

Background: The pathogenesis of eosinophilic dermatosis of hematologic malignancy (EDHM) is poorly understood. Previously thought to be a hypersensitivity reaction to insect bites, immune dysregulation and cytokine imbalance are now thought to be responsible. Its prognostic significance is unclear. Objective: To describe the clinical, pathological and immunological findings in a series of oncohematological patients with EDHM. Methods: An observational prospective cohort study of oncohematological patients receiving a diagnosis of EDHM between April 2017 and December 2018. Results: A total of 15 patients with EDHM (10 females and 5 males) were identified among 422 oncohematological patients. Disease presentation varied from firm erythematous papules to more polymorphic presentations. The lesions were most prevalent on the exposed sites, 8/15 patients recalled an insect bite. Lesion seasonality was reported in 13/15 patients. IgE levels were elevated in six patients, circulating IL-4 and IL-5 were within a normal range. Twelve out of 15 patients developed skin manifestations after chemotherapy. The infiltrate could be eosinophil-rich or lymphocytic-rich. Interestingly, the histopathologic findings were in accordance with arthropod bites. Conclusion: A role for insect bites in EDHM is supported by our findings. EDHM may be related to aggressive hematologic disease.

Atypical exanthem with acral involvement in adult patients associated with human herpesvirus 7 active replication: A case series.

An "atypical exanthem" (AE) is an eruptive skin eruption that differs in morphology and etiology from classical exanthems and is often a reason for urgent medical evaluation. The most frequent cause of AEs is a viral infection, but an accurate etiology cannot be established basing on the sole clinical features. Human herpesviruses (HHV) have been often suspected as etiologic agents or cofactors in atypical rashes. We performed a retrospective analysis of adult patients presenting an atypical exanthem associated with HHV-7 active replication in our center. The charts of patients were reviewed and the demographic, clinical and laboratory data collected. Nine patients (six males and three females) were included in the study, with a mean age of 43 years for men and of 26 years for women. All patients presented active HHV-7 replication in plasma during the rash, which turned negative after the exanthem resolved. The exanthem displayed a maculopapular pattern involving the trunk, limbs and, notably, the acral regions, in six patients. In three cases the exanthem was confined to only the acral sites. In most cases, there was no fever and the inflammatory indices remained unchanged. Antihistamines, topical and systemic corticosteroids were used as treatment, with excellent symptom control. We propose adding skin manifestation associated with HHV-7 to the concept of atypical exanthems, in particular those localized to the acral regions.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Efficacy and Safety of Secukinumab in Elderly Patients with Moderate to Severe Plaque-Type Psoriasis: Post-Hoc Analysis of the SUPREME Study.

Purpose: Secukinumab is a fully human monoclonal antibody that inhibits interleukin (IL)-17A approved for the treatment of moderate to severe plaque psoriasis in adults and children. We compared the efficacy and safety of secukinumab in patients aged < 65 years (adult patients) versus patients aged ≥ 65 years (elderly patients) in a post-hoc analysis of the SUPREME study. Patients and Methods: Patients with moderate to severe plaque psoriasis received subcutaneous secukinumab 300 mg per week for the first 5 weeks, then 300 mg per month. We compared the following outcomes in patients aged ≥ 65 years vs < 65 years: baseline characteristics; PASI50/75/90/100 response rates (improvements ≥ 50%/75%/90%/100% in Psoriasis Area and Severity Index (PASI) from baseline); changes in Dermatology Life Quality Index (DLQI); Hospital Anxiety and Depression Scale (HAD-A, HAD-D) score changes; treatment-emergent adverse events (TEAEs). Results: Secukinumab was slightly less effective in elderly patients than in adult patients (response rates at week 16: PASI90, 69.4% vs 80.9%, p = 0.4528; PASI100, 44.4% vs 56.7%, p = 0.8973). Elderly and adult patients showed a similar time course of changes in absolute PASI scores. Patients aged ≥ 65 years had a statistically significantly lower improvement in quality of life (mean DLQI reduction) than patients aged < 65 years at week 16 [-5.4 (±4.3) vs -8.8 (±6.9), p = 0.0065] and at week 24 [-5.3 (±4.4) vs -9.2 (±7.1), p = 0.0038]. Secukinumab treatment resulted in comparable mean reductions in anxiety and depression scores in both cohorts at 24 weeks [HAD-A, -1.3 (±3.3) vs -2.1 (±3.8), p = 0.9004; HAD-D, -1.0 (±3.3) vs -1.5 (±3.1), p = 0.4598]. The frequency of TEAEs in the two cohorts was similar (16.7% vs 14.6%, p = 0.7391). Conclusion: Secukinumab is a valid option for the management of moderate to severe psoriasis in elderly patients.

Efficacy of Secukinumab in Psoriasis: Post Hoc Gender-Wise Analysis of the SUPREME Study.

Purpose: Psoriasis, a common systemic inflammatory disorder, presents with gender-related differences in the quality of life (QoL) and treatment outcomes. This post hoc analysis from the Phase 3b SUPREME study explored gender-related differences in patient characteristics and efficacy of secukinumab 300 mg on Psoriasis Area and Severity Index (PASI) 75/90/100 and impact on QoL using the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis through week 24. Patients and Methods: The proportion of patients achieving PASI 75/90/100 was computed using a nonresponder imputation approach. Differences between cohorts were analyzed using a logistic regression model. The mean change from baseline in DLQI was computed using the Wilcoxon test. Results: Among the 433 patients (males: 71.6%), females had a higher DLQI than males at baseline (13.1 vs 9.5; P<0.0001). Males had a slightly higher response for PASI 90 than females at week 16 (80.7% vs 78.1%; P=0.0779) and 24 (83.2% vs 79.7%; P=0.0319). No differences were observed between genders in PASI 100/75 responses at week 24. Both genders showed an improvement in DLQI with secukinumab at week 24 (-10.9 vs -8.1, respectively, in females vs males; P=0.0004). Conclusion: In summary, secukinumab was effective in the treatment of psoriasis, irrespective of gender.

Successful treatment with Omalizumab of a child affected by Systemic Mastocytosis: clinical and biological implications.

BACKGROUND: Pediatric Mastocytosis is a rare and heterogeneous disease, characterized by accumulation of mast cells in the skin (Cutaneous Mastocytosis) and/or, less frequently, in other organs, mainly liver, spleen, bone marrow, lymph nodes and gastrointestinal tract (Systemic Mastocytosis). Patients affected by Systemic Mastocytosis show symptoms caused by  a massive release of mast cell mediators: itching, flushing, abdominal pain, generalized weakness, fatigue and neuropsychiatric disorders. Moreover, children with Systemic Mastocytosis are at greater risk of anaphylactic/anaphylactoid reactions, often poorly controlled by the conventional therapy with antihistamines, mast cells stabilizers and steroids. As a result, children affected by Systemic Mastocytosis have a poor quality of life and suffer the consequence of prolonged steroidal treatment. CASE PRESENTATION: A child with Systemic Mastocytosis and severe symptoms, refractory to symptomatic and steroidal therapy, has been successfully treated with Omalizumab, an anti-IgE monoclonal antibody usually employed in allergic patients with severe asthma and orticaria. The onset of clinical benefit of Omalizumab therapy was extraordinarily rapid, but proved to be strictly dependent on drug administration. The child has become completely and steadily asymptomatic. No other anaphylactic episodes have been reported. Steroid treatment could be definitively withdrawn after the second dose of Omalizumab, and all the other medications were later reduced. Twenty months after beginning, Omalizumab therapy is still ongoing with good symptomatology control; no side effects have been observed so far. CONCLUSIONS: In our experience, Omalizumab is an effective treatment for children affected by Systemic Mastocytosis not responding to conventional medical treatments. The main strengths of this therapy are its rapid and extraordinary efficacy to control the severe mast cells mediator-related symptoms, the lack of side effects and its steroid-sparing effect. However, more extensive and controlled studies in pediatric patients affected by Systemic Mastocytosis are needed to substantiate these promising findings.

A monolateral pigmented lesion of the nipple.

Pigmented mammary Paget's disease is a very rare variant of mammary Paget's disease linked to an underlying carcinoma in almost all cases. We present the case of a 62-year-old female patient who came to our attention for the evaluation of a monolateral asymptomatic pigmented lesion of the right nipple, which turned out to be a pigmented mammary Paget's disease unassociated to an underlying malignancy - an extremely rare entity only anecdotally reported in literature. The two main peculiarities of our patient's lesion, the importance of immunohistochemistry in the differential diagnosis and the theories on its pathogenesis are discussed. Further studies are necessary to establish the best treatment options. Click here for the corresponding questions to this CME article.

Omalizumab as a corticosteroid-sparing agent in the treatment of bullous pemphigoid.

Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, characterized by the development of autoantibodies against hemidesmosomal components BP180 and BP230. The mainstay of therapy is topical and systemic corticosteroids (CS) and immunosuppressors. As this pathology mainly involves the elderly, subjects often have numerous comorbidities that influence the clinical management. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody which has recently emerged as a promising treatment for BP in patients for whom CS are contraindicated or conventional treatments have failed to control the disease. For this study, we selected five patients who presented with corticosteroid-dependent BP with a contraindication to the use of other immunosuppressive treatments. The objectives of our study were to evaluate the effectiveness of omalizumab in controlling BP and allowing to decrease the dosage of systemic CS, assessing the effects of omalizumab on the clinical manifestations and the titers of circulating anti-BP180 and BP230 antibodies, IgE and eosinophils. A reduction in the dose of systemic CS was possible in 100% of the patients and complete resolution of the clinical picture was seen in 100% for skin lesions and in 40% for pruritus. A reduction of circulating IgE was found in 40%, anti-BP180 and BP230 IgGs were decreased in 60% and eosinophils in 80%.