Dystrophic Epidermolysis Bullosa (DEB): How Can Pregnancy Alter the Course of This Rare Disease? An Updated Literature Review on Obstetrical Management with an Additional Italian Experience.

Epidermolysis Bullosa (EB) is an extremely rare and disabling inherited genetic skin disease with a predisposition to develop bullous lesions on the skin and inner mucous membranes, occurring after mild friction or trauma, or even spontaneously. Within the spectrum of EB forms, dystrophic EB (DEB) represents the most intriguing and challenging in terms of clinical management, especially with regard to pregnancy, due to the highly disabling and life-threatening phenotype. Disappointingly, in the literature little focus has been directed towards pregnancy and childbirth in DEB patients, resulting in a lack of sound evidence and guidance for patients themselves and clinicians. The current study aims to contribute to the DEB literature with an updated summary of the existing evidence regarding the obstetrical and anesthesiological management of this rare disease. Furthermore, this literature review sought to answer the question of whether, and if so, in which way, the pregnancy condition may alter the course of the underlying dermatologic skin disease. Having all this information is indispensable when counseling a patient with DEB who desires a child or is expecting one. Finally, we reported own experience with a pregnant woman with a recessive DEB whom we recently managed, with a favorable outcome.

Congenital Cutis Verticis Gyrata in a Newborn with Turner Syndrome: A Rare Clinical Manifestation of This Chromosomal Disease with Trichoscopic Evaluation.

Cutis verticis gyrata (CVG) is a rare disorder of the scalp that entails the development of ridges and furrows, which mimic the anatomical conformation of the brain. This skin condition has been classified in primary essential, primary non-essential, and secondary CVG, depending on the presence or absence of other associated disorders. We present the case report of a one-month-old female newborn affected by congenital CVG (CCVG), who also received a diagnosis of Turner syndrome (TS). Skin folding was present at birth and located at the left frontal region of the scalp in the sagittal plane. Our purpose was to make this pathology clinically and tricoscopically better known, since it can be related to different genetic, inflammatory, and neoplastic conditions, etc. Non-invasive investigations, such as ultrasonography (U/S) of the brain and scalp and trichoscopy, were also used to obtain the important clues necessary to help in the CVG classification. The clinical diagnosis and trichoscopical investigation of CVG may also be useful for those patients who may have a genetic disease that is not screened for during prenatal examinations.

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.

Photodynamic Therapy Used to Treat an HIV Patient with an Efflorescence of Viral Warts after HAART Therapy.

Healing from viral warts lesions can be hard to achieve in immunocompromised subjects like HIV-positive patients. The therapeutic target in immunocompetent subjects can be reached using different methods, including topical ointments, cryotherapy, laser therapy, imiquimod, and photodynamic therapy (PDT). We present a case of a male HIV-positive patient who came to the Dermatology department with multifocal wart lesions on his face, auricular, and retro-auricular areas after treatment with highly active antiretroviral therapy (HAART). In our case, surprisingly, only one session of PDT proved to induce complete regression of lesions which, despite their thickness, had a much more robust response to treatment than we could have possibly expected. After a brief review of the literature, it is possible to state that PDT revealed itself to be a valid option in immunocompromised patients who have a major risk of relapse.

PRAME Immuno-Expression in Cutaneous Sebaceous Carcinoma: A Single Institutional Experience.

Background: In recent years, great research interest has been directed to the diagnostic, therapeutic and marker role of Preferentially expressed Antigen in Melanoma (PRAME) in the setting of various human neoplasms. Although it has been extensively studied mainly in the differential diagnosis setting of melanocytic pigmented lesions, still very few papers have analyzed the usefulness or otherwise of PRAME in the context of other non-melanoma skin cancers (NMSC). (2) Methods: In this paper, we report the data of our experience of 21 cases of sebaceous carcinoma (SC) classified in the three WHO grade and collected in the period between January 2005 and 31 October 2022, on which immunostaining for PRAME was performed; Non-parametric Mann−Whitney test for non-normally distributed values was performed. A comparison was made of the means between the three study groups (grade I, II and III). A value of p ≤ 0.05 was set as statistically significant (3) Results: Only seven cases (33.3%) were positive with an immunoscore of 2+/3+ for intensity and 1+/2+ for percentage cells positivity, while 14 cases (66.6%) were totally or nearly totally negative for PRAME with a few of sebaceous-like cells positive with an immunoscore of 1+. Eight cases of SC grade I were immunostaining for PRAME, a level of the cytoplasm of foci of sebaceous differentiation with a significant statical value (p < 0.0001) with respect to ten cases of SC grade II; furthermore, the eight cases of grade I were positive for PRAME in the same areas respect the 3 cases of SC grade III (p = 0.0303). There were no statistical significance between the 10 cases of grade II and 3 cases of grade III (p = 0.2028); (4) Conclusions: PRAME not seems to add particular information in the case of histopathological diagnostics of SC where other markers, including adipophylline, can be quite indicative. It seems, on the other hand, that PRAME can be useful in the subclassification setting of sebaceous carcinoma in grades I−II−III according to the directives of the latest WHO 2018, highlighting the foci of mature sebaceous differentiation most present in grades 1−2 and almost completely absent in grade 3 of the SC.

A Case of Purpura Annularis Telangiectodes of Majocchi after Anti-SARS-CoV-2 Pfizer-BioNTech Vaccine: Is There an Association?

The advent of vaccines has drastically reduced the incidence, morbidity, and mortality related to COVID-19, and with the increase in the number of vaccinated subjects, there have been reports of some adverse events, including skin reactions. In this paper, we report a clinical case of Purpura Annularis Telangiectodes of Majocchi following a third-dose administration of the Pfizer-BioNTech COVID-19 vaccine. Almost 30 days after the third dose, the patient presented erythematous annular patches on the lower limbs with purpuric peripheral areas and a central clearing with no other symptoms. A dermoscopic examination showed capillaritis, reddish-brown dot-clods on a coppery-red background caused by leaky capillaries. To date, the causes of Majocchi's disease are not well-defined; in the literature, three vaccination-related cases have been reported: one after a flu vaccination and two after an anti-SARS-CoV-2 one. Dermatologists should be trained to promptly recognize these clinical manifestations after vaccination, which will likely become a common finding in daily clinical practice, especially given the large diffusion of SARS-CoV-2 vaccinations.

Self-inflicted pathological cutaneous disorders. Part II.

Self-inflicted skin disorders are artefact diseases inflicted by the use of multiple different means, for various different purposes. They account for about 2% of dermatology patient visits, and include disorders with a denied or hidden pathological behavior (factitious disorders) and disorders with a non-denied and non-hidden pathological behavior (compulsive disorders). In turn, factitious skin disorders are subdivided into 2 groups: factitious disorders without an external incentive (considered in a preceding work) and factitious disorders with external incentives. In the second eventuality, the simulator is motivated by illicit intent, wishing to evade civil duties or a prison sentence, for instance, or to exploit situations of an occupational nature, and is fully aware of his action and his intention. Apart of the two groups of pathomimic artefacts and malingering, some self-inflicted dermatoses are due to behavioral disorders involving compulsive habits (tics, psychological excoriations). The great majority of subjects suffering from the latter disturbances are quick to confess their urge to self-inflict lesions. The management, including both psychiatric and dermatological assessment, concludes this second part of the work regarding the self-inflicted cutaneous diseases.

Self-inflicted pathological cutaneous disorders. Part I.

Self-inflicted skin disorders are artefact diseases inflicted by the use of multiple different means, for various different purposes. They account for about 2% of dermatology patient visits and include disorders with a denied or hidden pathological behavior (factitious disorders) and disorders with a non-denied and non-hidden pathological behavior (compulsive disorders). In turn, factitious skin disorders are subdivided into two groups: factitious disorders without an external incentive and factitious disorders with external incentives. In addition to the general diagnostic criteria, the present work examines the clinical forms of diseases of the first group (including dermatitis artefacta, Munchausen Syndrome, Munchausen Syndrome by proxy, and Morgellons Syndrome). In this case, the subject suffers from psychological problems and generally aims to attract the attention of the people around him, and in particular of his general practitioner, or else is reacting to difficult or unfavorable environmental conditions by means of an involuntary somatization at the level of the skin. The second part of the work on self-inflicted skin disorders will comprise the factitious disorders with external incentives and the compulsive disorders.

Update on the Management of Pediatric Psoriasis: An Italian Consensus.

INTRODUCTION: Psoriasis affects children with a considerable burden in early life. Treating pediatric psoriasis is challenging also because of the lack of updated specific guidelines. With the recent approval of several biologics for pediatric psoriasis and the ongoing COVID-19 pandemic, the management of young psoriatic patients is facing major changes. A revision of treatment recommendations is therefore needed. METHODS: In September 2021, a board of six Italian dermatologists convened to update treatment recommendations. The board issued evidence- and consensus-based statements covering relevant areas of pediatric psoriasis, namely: assessment of psoriasis severity, management of children with psoriasis, and treatment of pediatric psoriasis. To reach consensus, the statements were submitted to a panel of 24 experts in a Delphi process performed entirely via videoconference. A treatment algorithm was produced. RESULTS: There was full consensus that psoriasis severity is determined by the extension/severity of skin lesions, site of lesions, and impact on patient quality of life. Agreement was reached on the need for a multidisciplinary approach to pediatric psoriasis and the importance of patient/parents education. The relevance of vaccinations, including COVID-19 vaccination, for psoriatic children was acknowledged by all participants. Management issues that initially failed to reach consensus included the screening for psoriasis comorbidities and early treatment with biologics to prevent them and the use of telemedicine to facilitate patient follow-up. There was full consensus that topical corticosteroids are the first choice for the treatment of mild pediatric psoriasis, while phototherapy and systemic therapy are used in children with moderate-severe psoriasis. According to the proposed treatment algorithm, biologics are the first line of systemic therapy. CONCLUSIONS: Targeted systemic therapies are changing the treatment of moderate-severe pediatric psoriasis, while topical corticosteroids continue to be the first choice for mild disease. Children-centered research is needed to further improve the treatment of pediatric psoriasis.

Narrative review on the management of moderate-severe atopic dermatitis in pediatric age of the Italian Society of Pediatric Allergology and Immunology (SIAIP), of the Italian Society of Pediatric Dermatology (SIDerP) and of the Italian Society of Pediatrics (SIP).

Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ​​is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.

Contact allergy in children with and without atopic dermatitis: An Italian multicentre study.

BACKGROUND: Contact allergy and atopic dermatitis (AD) are both common inflammatory T cell-mediated diseases and many factors may influence the prevalence of contact allergy in AD patients. In children, their possible correlation was debated with conflicting results. OBJECTIVES: The present study aimed to assess the prevalence of contact sensitivity in children and to investigate the association with AD. MATERIALS AND METHODS: A retrospective multicentre study on children aged from 0 to 14 years patch tested between January 2017 and December 2018 was performed. Children were consecutively patch tested with the SIDAPA (Società Italiana Dermatologia Allergologica Professionale Ambientale) baseline series. RESULTS: Among the 432 children investigated for contact allergy, 125 (28.9%) showed a positive reaction to at least one of the allergens tested, with a higher prevalence of positive patch test reactions in girls (32.3%) than in boys (25.0%). The most frequent contact allergens were nickel sulphate (10.2%), cobalt chloride (6.7%), methylisothiazolinone (3.7%), fragrance mix-2 (3.2%), potassium dichromate (2.8%), fragrance mix-1 (2.1%) and methylchloroisothiazolinone/methylisothiazolinone (2.1%). One-hundred-three children (23.8%) suffered from AD showing a higher prevalence of positive patch test (36.9%) compared to children without AD (26.4%). CONCLUSIONS: Despite the topic being still controversial, the present study suggests a consistent prevalence of contact allergy among children with higher sensitivity rate among children with AD than without AD.

Squamous Cell Carcinoma in Patients with Inherited Epidermolysis Bullosa: Review of Current Literature.

Epidermolysis bullosa (EB) is a group of rare congenital diseases caused by mutations in structural proteins of the dermal/epidermal junction that are characterized by extreme epithelial fragility, which determines the formation of bullae and erosions either spontaneously or after local mechanical traumas. In EB patients, skin fragility leads to many possible complications and comorbidities. One of the most feared complications is the development of cutaneous squamous cell carcinomas (SCCs) that particularly in the dystrophic recessive EB subtype can be extremely aggressive and often metastatic. SCCs in EB patients generally arise more often in the extremities, where chronic blisters and scars are generally located. SCCs represent a big therapeutic challenge in the EB population. No standard of care exists for the treatment of SCC in these patients, and therapy is based on small case studies. Moreover, the pathogenesis of cSCC in EB patients is still unclear. Many theories have been indeed postulated in order to explain why cSCC behaves so much more aggressively in EB patients compared to the general population. cSCC in EB seems to be the result of many complex interactions among cancer cells, skin microenvironment, susceptibility to DNA mutations and host immune response. In this review, we analyze the different pathogenetic mechanisms of cSCC in EB patients, as well as new therapies for this condition.

Nutritional impairment of neonates with epidermolysis bullosa: a retrospective study.

BACKGROUND: Epidermolysis bullosa (EB) is a highly invalidating genodermatosis characterized by skin and mucosa fragility and blister-formation caused by mutations of genes encoding components of the cutaneous basement membrane zone. Nutritional impairment is one of the main complications of all forms of EB, having a huge impact on growth, pubertal development, wound healing, resistance to infections and quality of life. METHODS: In our study we have retrospectively evaluated 17 children with EB to define whether nutritional impairment in those patients is already present in the neonatal period. As secondary outcomes we considered nutritional status differences among EB subtypes and relative percentages of underweight infants at birth, first and third month. Moreover, information concerning feeding modality, possible complications were also collected, as well as cutaneous or systemic infections and duration of hospital stay. RESULTS: Our study demonstrated that nutritional impairment of neonates with EB has an early onset since as at first month 35% of patients were below 5th centile for weight-for-age, and 94% were below the 50th percentile. Moreover, the number of infants at one month of life <5th centile for weight-for-age was significantly higher compared to birth. The nutritional status is also heavily related to the occurrence of complications, in particular infections; therefore, the prevention of these complications must play a central role in the treatment of these infants, also to avoid any nutritional impairment. CONCLUSIONS: Nutritional status of neonates with EB seems to be compromised already during the first month of life and it is heavily related to the occurrence of infections; therefore, the prevention of these complications must play a central role in the treatment of these infants, also to avoid any nutritional impairment.

Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications of recessive dystrophic epidermolysis bullosa (RDEB). We recently demonstrated a reduction in immune cell peritumoral infiltration in RDEB patients with cSCC, together with a reduction in CD3+, CD4+, CD68+ and CD20 lymphocytes as compared to primary and secondary cSCC in patients without RDEB. Recently, new molecules, such as high mobility group box 1 (HMGB1), T cell immunoglobulin, mucin domain 3 (TIM-3) and Heme oxygenase-1 (HO-1), have been shown to play a role in antitumoral immunity. OBJECTIVE: Patients with RDEB are known to be at increased risk of developing skin cancers, including the dreaded squamous cell carcinoma of the. Tendentially, cSCCs that arise in the context of EBDR are more aggressive and lead to statistically significant bad outcomes compared to cSCCs developed on the skin of patients without EBDR. In an attempt to study the microenvironment of these lesions, we conducted an immunohistochemical analysis study of proteins that could be actively involved in the genesis of this type of malignant neoplasms. METHODS: In this retrospective study, the OH1-HMGB1-TIM3 activation axis, as correlated to the T lymphocytes cell count, was assessed in biopsy samples from 31 consecutive cases consisting of 12 RDEB patients with cSCC, 12 patients with primary cSCC and 7 RDEB patients with pseudoepitheliomatous cutaneous hyperplasia. Parametric Student's t-test was applied for normally distributed values, such as CD4+ and CD8+, and non-parametric Mann-Whitney test for non-normally distributed values, such as HMGB-1, TIM-3 and HO-1. RESULTS: In RDEB patients with cSCC and with pseudoepitheliomatous hyperplasia, the expression of CD4 T helper lymphocytes was lower than in the peritumoral infiltrate found in primary cSCC. CD8 cytotoxic T lymphocytes were increased in primary cSCC compared to the other two groups. An increased HMGB1 expression was evident in both primary and RDEB cSCC. TIM3 expression was higher in RDEB patients with cSCC compared to the other two groups. A significantly reduced immunohistochemical expression of HO-1 was evident in the tumoral microenvironment of cSCC-RDEB as compared to primary cSCC. CONCLUSIONS: These data suggest that a reduced immune cell peritumoral infiltration in RDEB patients could be responsible, in the complexity of the mechanisms of carcinogenesis and host response, of the particular aggressiveness of the cSCC of RDEB patients, creating a substrate for greater local immunosuppression, which, potentially, can "open the doors" to development and eventual metastasis by this malignant neoplasm.