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Atopic dermatitis (AD) is a chronic inflammatory disease that may involve any cutaneous site; involvement of the genital area may greatly impair patients' quality of life but, as the inspection of genitals is not usually conducted during the routine physical examination of patients with AD, the genital presentation of AD is frequently neglected and under-reported. We decided to evaluate the incidence of genital AD in patients with moderate-severe AD and the relative response to anti-interleukin (IL)-4/IL-13 dupilumab. In our study, a high incidence of genital AD emerged but the use of dupilumab allowed a generalized improvement.

Neurofibromatosis type 1 still lacks established treatment options aimed at controlling the progression of neurofibromas as well as effective therapy for the neurogenic itch associated with the disease. We report the case of a 30-year-old Caucasian woman with type 1 neurofibromatosis coexisting with severe refractory atopic dermatitis. Dupilumab, a novel anti-IL-4 receptor alpha monoclonal antibody, the first biologic agent approved for atopic dermatitis, was the drug of choice in this case. We observed remission of atopic dermatitis and a remarkable reduction in the size and swelling of neurofibromas and in the related pruritus, that became evident after one month of treatment. After 18 months of therapy, no new neurofibromas were detected and preexistent lesions showed no increase in size. These findings are consistent with the hypothesis that dupilumab, a potent anti-inflammatory drug, may have a positive effect on type 1 neurofibromatosis by stopping the progression of preexisting neurofibromas and the onset of new lesions.

The current global healthcare response to the COVID-19 pandemic is focused on a widespread vaccination campaign, which started with the authorization of Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines in December 2020. Local injection site reactions have been described during the clinical trials of both the abovementioned mRNA vaccines; skin rashes were additionally reported in the trial of Moderna. Despite this, cutaneous adverse reactions to the vaccines and their timing remain to date poorly characterized (1,2).

Background Recent studies highlight that high levels of cytokines may precede the onset of many systemic autoimmune disorders and may also be related to chronic spontaneous urticaria (CSU) activity. Methods Eight patients with CSU candidate to omalizumab therapy were enrolled. Four healthy controls were included with the purpose of comparing baseline cytokine levels. We evaluated serum levels of IFN-γ, IL-2, 4, 6, 8, and 10, TNF-α, and GM-CSF. For the patient group, venous blood samples were drawn at T0, T1 (1 week after first drug administration), T2 (after 3 months), T3 (after 6 months), and in case of relapse. Cytokine levels were measured using the human cytokines 8-plex kit. Disease activity and effect of therapy were calculated by means of Urticaria Activity Score 7. Results Higher levels of IL-6 and IFN-γ were found in patients with CSU compared to those observed in the control group. Moreover, a common trend between these cytokines and the clinical history of disease could be hypothesized, with a decrease in levels of IFN-γ and IL-6 following remission of CSU with omalizumab treatment. Levels of other tested cytokines were similar between patients and healthy subjects. Conclusion IFN-γ and IL-6 are proinflammatory cytokines that are strongly related to autoimmunity. Despite being limited by the small sample size, our data offer new insight into a better understanding of the pathogenesis of CSU and support the need for further investigations.

Background: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. Methods: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. Results: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection, 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. Conclusions: Most AD patients continued systemic treatments during COVID pandemicand lockdown period, without high impact on disease control, particularly dupilumab-treatedpatients.

BACKGROUND: Chronic spontaneous urticaria might affect elderly patients, causing a serious impairment of their quality of life. The therapeutic management of the elderly patient is challenging; in fact, the first-line recommended therapy for symptom control are antihistamines, that may have interactions or increased risk of side effects in patients with comorbidities and poly-pharmacological regimen. Omalizumab is the first biological drug approved for chronic spontaneous urticaria resistant to antihistamines. Real-life data focusing on patients > 65 years old (yoa) treated with omalizumab are rare. METHODS: In our retrospective study, we evaluated the efficacy and safety of this biologic therapy in patients over 65yoa. We performed Urticaria Activity Score-7 (UAS-7) in order to evaluate the efficacy of omalizumab and the time of remission. We collected any adverse event related to the treatment. Moreover, we investigated the presence of comorbidities and their impact on the efficacy of omalizumab. RESULTS: 63 patients, with a mean age of 72.3 ± 5.6 years, range: 65-89) were enrolled. Of 63 subjects, 23 (36.5%) had an "early complete response" profile, which means the achievement of a UAS7 score of "0" within the first 7 days of therapy. The most frequent comorbidity was hypertension, which affected 26/63 (41.3%) patients; no adverse events were reported. No significant correlations were found between treatment effectiveness and comorbidities. CONCLUSIONS: omalizumab is a safe and effective therapy also in elderly patients with multiple comorbidities. This article is protected by copyright. All rights reserved.

It is Leonard F. Hoenig, MD Data on the tolerability and response to biologic therapies for type 2 immune disorders in the context of coronavirus disease 2019 (COVID-19) are currently lacking. Our survey aimed at assessing the adherence of patients to dupilumab therapy and the risk of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 80 patients with atopic dermatitis treated with dupilumab completed a web-based survey. Of the 80 patients, 7 discontinued dupilumab owing to concerns and difficulties related to COVID-19. Our sample was highly susceptible to viral infection owing to the frequency of risk factors including living in high SARS-CoV-2 burden areas, such as in Northern Italy; having comorbidities, such as asthma, diabetes, and cardiovascular disease; and being of advanced age. Older patients in our sample are particularly exposed to the risk of COVID-19–related cytokine storm, triggered by excessive interleukin-4 production and type 2 immune response. One patient contracted SARS-CoV-2 infection without the progression of COVID-19 despite continuing scheduled dupilumab treatment. Because evidence on the appropriate management of biologic therapy in the setting of COVID-19 is lacking, the collection of clinical data from patients in treatment with dupilumab is a valuable addition to current clinical practice. Our survey provides a contribution to the understanding of the tolerability and response to dupilumab during COVID-19 and suggests a feasible and effective approach to patients being treated with biologics even when social distancing is required.

Dupilumab showed significant improvement of adolescent atopic dermatitis (AD) signs and symptoms in clinical trials, with a good safety profile. Herein we report the real-word effectiveness and safety of dupilumab in adolescents with moderate to severe AD from January to October 2020, during the COVID-19 pandemic in Italy. All patients had a diagnosis of AD for a mean [SD] 12.8 [3.1] years. Baseline demographics, AD characteristics (EASI, cDLQI, NRS itch score, NRS sleep loss score) at baseline and week 16, and safety data were collected. Nineteen patients (52.6% men; mean [SD] age, 15.6 [1.4] years [range, 13-17 years]) were included in the analysis. All patients reached EASI-50 and 78.9% EASI-75, especially in those with EASI≥30 and BMI

An in‐depth characterization of the incidence, morphology, and onset of COVID‐19‐vaccines cutaneous adverse reactions is currently lacking. The existing literature on COVID‐19 vaccination‐related cutaneous adverse reactions largely focused on messenger RNA vaccines and mainly included type 1 hypersensitivity reactions, such as urticaria and angioedema. Other cutaneous manifestations are still poorly characterized and have been classified as delayed hypersensitivity rash. Our prospective observational study on a sample of 2740 subjects who underwent the COVID‐19 vaccination aimed at defining the prevalence of cutaneous adverse reactions and at identifying their timing of onset and their correlation with the administered dose. Vaccine‐related cutaneous adverse reactions occurred in 50 subjects. Patients were asked to complete a questionnaire on the type of COVID‐19 vaccine received, the time of onset of cutaneous reactions, and the dates of administration. Out of 2740 individuals who received the COVID‐19 vaccination, 50 were diagnosed with cutaneous adverse reactions to vaccine, after the first dose in 28 patients, after the second in 20, and after both in two. We reported localized injection site erythema in 12 patients and generalized cutaneous reactions in 38 patients. Our study shows that cutaneous adverse reactions to COVID‐19 vaccination are not common and most often occur after the first dose, recurring infrequently after the second dose. These reactions are usually easily manageable and, even in severe generalized cases, oral antihistamines and corticosteroids were sufficient for resolution. Therefore, except for immediate hypersensitivity reactions, cutaneous adverse reactions do not represent a contraindication to the completion of the vaccination cycle.

Introduction: Physicians have largely studied the cutaneous involvement of coronavirus disease 2019 (COVID-19), but only few reports have focused on telogen effluvium (TE) as a possible sequela of COVID-19. We assessed 14 cases of hair loss occurring after SARS-CoV-2 infection using trichoscopy and trichogram to investigate patterns related to COVID-19. Furthermore, we discussed possible mechanisms involved in COVID-19 TE. Case Presentation: Fourteen individuals were referred to our post-COVID-19 dermatology office complaining acute hair loss after SARS-CoV-2 infection. Clinical evaluation included pull test, trichoscopy, and trichogram. CO­VID-19 TE occurred after a median of 2 months (range 1–3 months) following SARS-CoV-2 infection. The median duration of hair loss was 5 months (range 1–6 months). Trichoscopy showed variable but typical TE patterns. Trichogram showed different telogen/anagen ratio depending on the interval between onset of hair loss and trichological visit. Discussion/Conclusion: Our cases showed TE between 1 and 3 months after the onset of SARS-CoV-2 infection, thus earlier than classic TE. Trichoscopic features and trichogram showed no variations from classic TE. Different pathogenetic mechanisms including pro-inflammatory cytokines and direct viral damage on the hair follicle can be hypothesized; further studies on a larger sample are needed to better understand this condition.

Background: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. Methods: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. Results: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection, 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. Conclusions: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.

Background: Omalizumab is not considered a disease-modifying drug and, accordingly, a large proportion of patients experience a relapse following withdrawal from treatment. Patients & methods: A total of 42 patients who underwent at least one cycle of treatment with omalizumab were enrolled. Two groups of relapsed and not-relapsed subjects were compared. Then, patients were divided into subgroups. Results: Female patients relapse more frequently than male subjects. Patients who relapsed complained a long duration of disease, while patients who did not relapse had short a history of disease. Very early responders are thought to have a high recurrence rate. Basal IgE levels were increased in early responders and cholesterol levels were high in very early responders, who relapse following withdrawal from omalizumab. High D-dimer levels were observed in late responders. Conclusion: The identification of clinical and serological predictors will play a pivotal role in the future management of patients treated with omalizumab.

Since the new fatal pneumonia was identified in December 2019 in Wuhan, China, the WHO declared the infection a health emergency of international concern. The novel ss‐RNA ß‐coronavirus (SARS‐CoV‐2) spreads through airborne and direct contagion; virulence is high in the elderly and in patients with diabetes, chronic pulmonary, cardiovascular and neoplastic diseases. SARS‐CoV‐2 ssRNA is recognized by intracellular Pattern Recognition Receptors (PRRs), which trigger NF‐kB – the master regulator of inflammation – and Interferon Regulatory Factors (IRFs)1.

The case of a woman who suffered from CSU and prurigo Besnier, with a history of chronic hyper-eosinophilia, ulcerative colitis and thyroiditis, unresponsive to anti-histamines and steroids is reported. The patient received omalizumab treatment, and obtained resolution of urticaria along with improvement of cutaneous symptoms of prurigo.

Background Atopic dermatitis (AD) is a chronic relapsing eczematous dermatitis typically affecting young patients in a percentage from 15 to 20%; although it typically affects young people and adults, recent papers highlighted the emerging of the disease in the elderly population. Methods The aim of the study was to identify the clinical criteria and allergic sensitization that may be able to support physicians and dermatologists in making a correct diagnosis of AD in the elderly. The second aim of this study was to investigate the incidence, the main features, the gender prevalence, the immunological profile, and comorbidities characterizing patients older than 65 years affected by AD. Results Based on clinical and serological patterns, different phenotypes of AD were identified: generalized AD (55%) characterized by eczematous lesions involving typical areas of the body or prurigo nodularis-like AD; chronic eczematous hand dermatitis (23%); face and neck involvement (9%); and nummular eczema (13%). Skin prick tests revealed a positivity for aeroallergens in 49.6% of patients, most of them being polysensitized (55%). Additionally, food skin prick tests were positive in 25% of patients. Most of the patients reported comorbidities, particularly IgE-mediated diseases, such as seasonal rhino-conjunctivitis, asthma, and chronic obstructive pulmonary disease. Gastrointestinal symptoms such as meteorism, dyspepsia, cramps/abdominal pain, and diarrhea/constipation, were observed in 35% of patients consequent to food allergy. Conclusion In our study, we suggest clinical and serological criteria that may be able to guide in the diagnosis of AD in Caucasian elderly, and to design an appropriate treatment according to the current standard protocol.

The long-term efficacy and safety of dupilumab has been demonstrated in clinical trials and only in few real-world studies. We conducted an extension analysis from a previous 16-week study on 109 adult patients affected by moderate-to-severe atopic dermatitis treated with dupilumab. Eczema-Area-and-Severity-Index (EASI), itch numerical-rating-score (itch-NRS), Dermatology-Life-Quality-Index (DLQI) scores, drug survival rate and occurrence of adverse events after 24 and 48 weeks of dupilumab treatment were retrospectively collected. Dupilumab demonstrated sustained improvement of disease severity, pruritus, and quality of life in our series with an increasing percentage of patients gaining EASI75 and EASI90 response during the study period. Few patients interrupted treatment resulting in a very high drug survival rate. We also confirmed the favorable safety profile of the drug with absence of serious adverse events and serious infections throughout the 48-week period. The prevalence of conjunctivitis was low and mainly occurred in the mid-term with resolution of the majority of cases at 48 weeks.

Chronic spontaneous urticaria (CSU) is perceived as a difficult to manage disease with negative impact on quality of life. The aim of this study was to highlight how to improve the care of people with CSU, using the methodology of narrative medicine. From June 2014 to March 2015, CSU-diagnosed patients and their physicians were asked to record their experiences of the condition in writing. Fourteen healthcare teams participated: 41% considered CSU as a challenge to overcome, while 22% experienced CSU as a big commitment. The number of professional involved was evaluated as insufficient in 11 hospitals. Seventy-five percent of the 190 Italian patients had visited 3 or more physicians before receiving a final diagnosis, with a perceived waste of time and resources. The therapeutic pathways were described as unsatisfactory in 83% of cases. As a result, anger and frustration were life-dominant emotions in 92% of patients. The critical points of the care pathway are related to organizational issues and lack of awareness.

Background The prevalence of latex allergy varies according to the population studied from 3% to 64%. No data exist in the present literature about elderly people because they were not considered among populations at risk. We report a retrospective observational study of 88 elderly patients of our centre of Dermatology and Allergology at Policlinico Umberto I, University of Rome, Sapienza. Results First and second level diagnostic tests showed latex positivity in 11,4% of patients studied for latex allergy in the elderly population. Conclusions Our study demonstrates a prevalence of elderly-latex sensitization of 11,4%, showing that allergy to latex is a growing disease that can occur at any age. So, we propose these patients as an additional risk category for latex allergy.

Promethazine hydrochloride is a first-generation H1 receptor antagonist, antihistamine, and antiemetic medication that can also have strong sedative effects. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r was translated into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function.

Topical ketoprofen (KP) is widely used because of its anti-inflammatory effect. Parallel with its popular usage, the number of reported cases of ketoprofen-induced photoallergic contact dermatitis has increased. A review of the literature was made to evaluate the spectrum of cross sensitization in patients with ketoprofen-induced photoallergic contact dermatitis using ketoprofen and other structurally similar chemicals and sunscreens, fragrance components, as well as the presence of prolonged photosensitivity related to it. Furthermore, the distinction between true cross-reactivity and concomitant sensitization may be difficult. Therefore, further investigations are needed to gain a more complete understanding of this important topic. This article also reviews some patents related to alternative treatment of musculoskeletal diseases and/or treatment of allergic reactions due to NSAIDs use.

Sir, the appearance of new elements similar to blue naevus or cavernous hemangioma. Dermal melanocyte hamartoma (DMH) is a rare clinico-pathological entity characterized by the persistSkin biopsies from the large grey-blue patches on his back showed basal hyperpigmentation and slight orthoence of ectopic melanocytes in the dermis after birth (1–6). Related entities are the pilar neurocristic hamarkeratotic hyperkeratosis of the epidermis with normal number of intraepidermal melanocytes. In the upper toma (7) and phakomatosi s pigmentovasculari s type IVa (8, 9), in which the blue-coloured spots are associdermis, a mild perivascular inŽ ltrate was present with many melanophagic histiocytes. In the middle and lower ated with naevus  ammeus. Here, we report a rare case of DMH associated with dermis there were scattered spindle and elongated cells with dusty melanin cytoplasmatic granules disposed along hereditary motor and sensory neuropathy type 2A (HMSN 2A), also known as Charcot Marie Tooth collagen Ž bres (Fig. 2) or focally arranged in perineural and perivascular localization. An immunological test for disease, a neurological disorder with recessive autosomal inheritance, characterized by a demyelinizing peripheral S-100 protein performed with Avidin–Biotin–Complex (DAKO) and Diamino-Benzidine chromogen counneuropathy and progressive myopathy (10). terstained with Giemsa showed the nuclear and cytoplasmic positivity typical of neuro-ectodermal cells with CASE REPORT the green dusty appearance of melanin. The nerve bundles appeared only slightly hypertrophic, with minimal signs A 54-year-old man presented with several congenital pigmented lesions, mottled with small, well-demarcated of onion bulb appearance. This histological picture was consistent with the diagnosis of dermal melanocytosis. macular-papules of a dark-blue colour on the upper trunk and extensor region of the limbs, including hands, According to clinical and histological features we diagnosed a case of DMH. The patient was also aVected by with characteristic mantle distribution (Fig. 1). During childhood the macules had increased in number with a muscle hypotrophy in the forearms and hands, resulting in a claw-like appearance. The distal muscle atrophy of the lower limbs was notable too. There was no family history of neurological symptoms of this disease. The neurological motor disturbance manifested in the eighth year of life with a limp in the left leg. Symptoms worsened progressively, involving the other limbs. An electromyography and electroneurography showed a sensory-motor neuropathy associated with severe axonopathy. It has not been possible to perform the motor evoked potential because of severe muscular

Rivastigmine is a cholinesterase inhibitor which improves cognitive function and is currently being used in patients with mild to moderate Parkinson's and Alzheimer's dementia. This drug can be given orally or topically, as transdermal patch. The latter form is currently used for most excellent compliance and few side effects. The most common cutaneous side effects are irritative dermatitis. We report the second case of active sensitization by the rivastigmine-patch in a patient suffering from Alzheimer's dementia.