Hedgehog Inhibitors Beyond Clinical Complete Response in Basal Cell Carcinoma: Should I Stop or Should I Go?

INTRODUCTION: In advanced basal cell carcinoma (BCC), the issue of whether Hedgehog inhibitors (HHIs) should be stopped or not after clinical complete response (cCR) achievement remains an unmet clinical need. MATERIALS AND METHODS: We conducted a retrospective, multicenter study across 7 Italian dermato-oncology units including patients with BCC who continued vismodegib after cCR between 2012 and 2019. We assessed the relationship between the duration of vismodegib intake (days to cCR [DTCR], days to stop after cCR [DTS], total treatment days [TTD]), and disease-free survival (DFS). Reasons to stop vismodegib were (R1) toxicity and (R2) disease recurrence. The relationship between DTCR, DTS, TTD, and DFS in the whole population and in R1 subgroup was assessed by Pearson's correlation coefficient (P < .05) and Bayesian statistics (BF10). RESULTS: Sixty-eight BCC patients with a median (m) age of 75.5 years (39-100) were included. Most patients were male (N = 43, 63%), without Gorlin syndrome (N = 56, 82%) and with head and neck area as primary site (N = 51, 75%). After cCR, out of 68 patients, 90% (N = 61/68) discontinued vismodegib: 82% (N = 50/61) due to toxicity (R1), and 18% (N = 11/61) due to recurrence (R2). Conversely, 10% (N = 7/68) continued vismodegib until last follow-up. In the whole population (N = 68), cCR was achieved with a mDTCR of 180.50 days. DFS showed a significant correlation with DTS (P < .01, BF10 = 39.2) and TTD (P < .01, BF10 = 35566), while it was not correlated to DTCR (BF10 < 0.1). The analysis of R1 subgroup (N = 50) confirmed these results. DFS correlated with DTS in all recurrent patients (N = 38, r = 0.44, P < .01) and in the recurrent patients who stopped vismodegib for toxicity (N = 26, r = 0.665, P < .01). DFS was longer when vismodegib was maintained for >2 months after cCR (mDFS > 2 months, N = 54 vs. ≤ 2 months, N = 14: 470 vs. 175 d, P < .01). CONCLUSIONS: Our retrospective results suggest that HHIs should be continued after cCR to improve DFS in BCC.

Prurigo-like atopic dermatitis in a child with CARD11-associated severe combined immunodeficiency successfully treated with dupilumab.

A 12-year-old boy affected by severe combined immunodeficiency due to a heterozygous variant in the CARD domain of CARD11, c.169G>A; p.Glu57Lys, developed severe atopic dermatitis and alopecia areata. After failure of conventional systemic therapy, dupilumab was administered at a dose of 400 mg subcutaneously, followed by 200 mg every 14 days. The patient had an excellent clinical response after 1 month and complete remission after a year, with the absence of side effects, demonstrating good efficacy and safety profile.

The Diagnostic Role of Skin Manifestations in Rheumatic Diseases in Children: A Critical Review of Paediatric Vasculitis.

Skin lesions are frequently observed in children with rheumatic diseases, particularly in conditions such as IgA vasculitis (IgAV) and Kawasaki disease (KD). In paediatric vasculitis, the presence of skin lesions serves as an early indicator, emphasising the importance of timely diagnosis to prevent complications, such as cardiac or renal involvement. Conversely, autoinflammatory disorders like juvenile systemic lupus erythematosus (SLE) and juvenile dermatomyositis (DM) may manifest with cutaneous manifestations either at the onset of disease or during its progression. Identifying these skin lesions prior to the appearance of systemic symptoms offers an opportunity for early diagnosis and treatment, which has a positive influence on the outcomes. Additionally, it is noteworthy that specific rheumatological conditions, such as acute rheumatic fever (ARF) or oligoarticular or polyarticular forms of juvenile idiopathic arthritis (JIA), may exhibit occasional, but significant skin involvement, which is strongly correlated with an unfavourable prognosis. The assessment of skin is important in the holist approach to assessing patients for potentially systemic/multisystem disorder and helps distinguish discrete conditions.

Sequential treatments of Hailey-Hailey disease with photodynamic therapy, botulinum toxin type A and dapsone: A case report.

Hailey-Hailey disease is a rare autosomal dominant chronic recalcitrant blistering genodermatosis involving the intertriginous areas. Therapeutic options are various, depending on the type and size of the lesion, and include topical and systemic corticosteroids, topical and systemic retinoids, and DMARDs, but the only true curative approach is represented by the destruction of the affected areas through different techniques like carbon dioxide laser, photodynamic therapy, electron beam radiotherapy, botulinum toxin type A. We report a case of Hailey-Hailey disease successfully treated with a consequential regimen of PDT, botulinum toxin type A and dapsone.

Characterization of Basosquamous Cell Carcinoma: A Distinct Type of Keratinizing Tumour.

Basosquamous carcinoma is a rare clinical entity, which comprises 1.7-2.7% of all skin carcinomas. It is described as a basal cell carcinoma with features of squamous differentiation. To date, studies of the epidemiology of basosquamous carcinoma have been few and small in size. We report here the most extensive series of basosquamous carcinomas published to date, highlighting the differences between basosquamous carcinoma and other keratinizing tumours. Patients undergoing surgical excision for keratinizing tumours were enrolled in this study. Age, sex and tumour characteristics were recorded. A total of 1,519 squamous cell carcinomas, 288 basosquamous carcinomas and 4,235 basal cell carcinomas were collected. Basosquamous features were compared with those of basal cell and squamous cell carcinomas. For basosquamous carcinomas, 70.5% were located on the head and neck, particularly on the nose, forehead and cheeks, and represented almost 10% of the keratinizing tumours on the ears. Significant differences were found between basosquamous carcinoma and basal cell or squamous cell carcinomas. Basosquamous carcinoma should be considered a distinct type of keratinizing tumour with different anatomical, sex and age distributions.

Allergic contact versus irritant contact dermatitis in patients with hard-to-heal leg ulcer: clinical and diagnostic approach.

BACKGROUND: Dermatitis of surrounding skin may complicate hard-to-heal leg ulcers, delaying wound healing. The coexistence of hard-to-heal leg ulcers and irritant or allergic contact dermatitis may create difficulties for both diagnostic and therapeutic management. OBJECTIVE: The aim of our study was to evaluate the incidence of dermatitis occurring in the surrounding skin in a population affected by hard-to-heal leg ulcers during treatment, and to differentiate between allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) with the use of a patch test. Furthermore, we investigated which medications were most probably related to these conditions. METHOD: We conducted an observational study from 21 February to 21 July 2017, enlisting all patients affected by hard-to-heal leg ulcers who attended the Wound Care Service of the Dermatologic Department of ASST, Spedali Civili, Brescia, Italy. RESULTS: We enrolled 95 patients; 81 patients did not develop dermatitis, while 14 patients developed dermatitis of the surrounding skin. These patients underwent a patch test which gave a positive result in seven patients, permitting the diagnosis of ACD. CONCLUSION: Our study confirmed the incidence of dermatitis of the surrounding skin reported in the literature but reassessed the incidence of ACD as opposed to ICD.

Wound Repair and Extremely Low Frequency-Electromagnetic Field: Insight from In Vitro Study and Potential Clinical Application.

Wound healing is a complex, staged process. It involves extensive communication between the different cellular constituents of various compartments of the skin and its extracellular matrix (ECM). Different signaling pathways are determined by a mutual influence on each other, resulting in a dynamic and complex crosstalk. It consists of various dynamic processes including a series of overlapping phases: hemostasis, inflammation response, new tissue formation, and tissue remodeling. Interruption or deregulation of one or more of these phases may lead to non-healing (chronic) wounds. The most important factor among local and systemic exogenous factors leading to a chronic wound is infection with a biofilm presence. In the last few years, an increasing number of reports have evaluated the effects of extremely low frequency (ELF) electromagnetic fields (EMFs) on tissue repair. Each experimental result comes from a single element of this complex process. An interaction between ELF-EMFs and healing has shown to effectively modulate inflammation, protease matrix rearrangement, neo-angiogenesis, senescence, stem-cell proliferation, and epithelialization. These effects are strictly related to the time of exposure, waveform, frequency, and amplitude. In this review, we focus on the effect of ELF-EMFs on different wound healing phases.

Nested graft for chronic ulcer in scar tissue after heroin extravasation in a drug addict.

INTRODUCTION: Nested graft is a surgical technique that allows to manage difficult-to-treat medical conditions such as chronic cutaneous ulcers, thanks to the high efficacy it has in reverting the fibroblasts senescence. Because of its peculiar regenerative property, nested graft is a surgical technique suitable also for the treatment of cutaneous ulcers developing on fibrotic scar tissue. CASE REPORT: We reported the case of a 45-year-old man, drug-addict, with a large ulcer on the back of the right forearm in the context of scar fibrotic tissue. This lesion resulted from a previous heroin extravasation treated with a dermo-epidermal skin graft, that was accidentally scratched away by mechanical trauma. After several therapeutic failures with topical medications, we decided to treat the ulcer performing a skin graft using the nested graft technique. No adverse events were reported by the patient during or after the surgery. At the clinical evaluation performed three years later the wound was completely healed. CONCLUSIONS: Nested graft represents a safe and easy-to-use technique that can be successfully used to treat ulcers on scar tissue, ensuring the achievement and the long-term maintenance of optimal resistance and aesthetic results.

Effect of immunosuppressive drugs in immune-mediated inflammatory disease during the coronavirus pandemic.

The safety of immunosuppressive treatment in patients with Immune-Mediated Inflammatory Diseases (IMIDs) during the Coronavirus pandemic is questioned and it is utmost important for public health. We searched studies trough MEDLINE/EMBASE database, including patient with IMID, undergoing immunosuppressive treatment with a positive diagnosis for SARS-CoV 2. We included 11 studies for the descriptive analysis and 10 studies for the pooled analysis, with a total population of 57 and 53 IMID-affected SARS-CoV-positive patients respectively. Overall no death was reported; 16 patients were hospitalized (30.2%) and only two cases were admitted to Intensive Care Unit (ICU) (3.8%). We found a significant association between the risk of hospitalization and older age (P .03), obesity (P .02), and presence of multi-comorbidity (P .03). No significant association was found between the risk of hospitalization and the use of biological or conventional DMARDs (respectively P .32 and .26), neither when they are used combined (P .85). We found consistent results in the sub-analysis of Psoriasis: 10 patients were hospitalized (31.3%) and only one case was admitted to Intensive Care Unit (ICU) (3.1%) Particular attention should be placed for patients with older age, obesity and multi-comorbidity that are at higher risk of hospitalization.

COVID-19 and psoriasis: Should we fear for patients treated with biologics?

The new coronavirus pandemic poses question and challenges for dermatologists. One of question is if psoriasis patients treated with immunomodulating and immunosuppressive drugs have to discontinue their treatment in the midst of fears for the infection and its consequences. One of the challenges is how can we support our patients in this critical time. Previous coronaviruses outbreaks reports, current published evidences on pathogenesis and on clinical reports of COVID infection in immunosuppressed patients are used to make a scientifically based decision.

Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study.

PURPOSE: Selective IgA deficiency (SIgAD) is the most common humoral primary immunodeficiency. Long-term follow-up data in large cohort of pediatric patients are scarce. METHODS: We report on a single-center cohort of 184 pediatric patients affected with selective IgA deficiency and describe the characteristics at diagnosis and during follow-up. RESULTS: Respiratory infections were the most common clinical finding leading to the initial diagnosis (62%). Positive family history for antibody deficiencies (selective IgA deficiency, common variable immunodeficiency) led to SIgAD diagnosis in 16% of cases. During follow-up, while the incidence of respiratory infections was not particularly high, gastrointestinal symptoms were reported in 27% of patients. Allergic manifestations were found in 23% at diagnosis and an additional 16% of patients during follow-up, leading to a prevalence of atopy of 39% among SIgAD patients. Autoimmune manifestations, excluding celiac disease, were found in 9% of affected patients during follow-up. Celiac disease was found in a high prevalence (14%). Increase of serum IgA levels to partial deficiency (9%) and normal serum levels for age (4%) was observed during follow-up. A small percentage of patients (2%) progressed to common variable immunodeficiency (CVID). CONCLUSIONS: In conclusion, this is the first study to describe a large single-center pediatric cohort of patients affected with SIgAD, revealing that overall most patients do well with regard to infections. Many develop CD, at a rate much higher than the general population. A few normalize their IgA levels. A few progress to CVID. Thus, careful follow-up is suggested to diagnose and treat potential complications earlier for avoiding potential morbidities.

Epidemiology of pyoderma gangrenosum: Results from an Italian prospective multicentre study.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterised by painful, necrotic ulcerations. PG is described as a rare disease: the world-wide incidence is estimated to be around 3 to 10 cases per million population per year. These estimations are based mostly on case reports and retrospective case series; there are no prospective, multicentre studies on the matter. The apparent rarity of PG is in contrast with our clinical perception as dermatologists: in our opinion, PG is not so uncommon. Therefore, we decide to investigate the epidemiology of PG in the Italian population and confirm our clinical suspicions that it is not an orphan disease. We enrolled all patients diagnosed with PG in 8 Italian Dermatological Departments from 1st October 2014 to 1st November 2015, and we recorded their features. Our data, collected from 64 patients, are in accordance with those of the published literature regarding the epidemiology and features of PG. In an Italian population of roughly 8 million inhabitants of 7 provinces, we found an incidence of 5.17 new cases per million population per year. Unlike our predictions before the study, we confirmed the world-wide incidence of PG. To our knowledge, this is the first observational, multicentre study on PG. We hope that it provides a stimulus for further researches on PG and for the creation of an Italian register.

Validation and Field Performance of the Italian Version of the Psoriatic Arthritis Screening and Evaluation (PASE) Questionnaire.

Psoriatic arthritis (PsA) is a potentially severe inflammatory condition (entheso-arthro-osteopathy), and early diagnosis is important to guide treatment choices in patients with psoriasis. The objective of this study is to further validate the PsA Screening and Evaluation (PASE) questionnaire, and to assess its field performance. Data were collected in 10 Italian centres, and the PASE was administered at baseline, after 3 days and after 3 months. The Skindex-29 was also administered. To determine the best cut-off value to identify patients with PsA we produced receiver operating characteristic (ROC) curves using the rheumatologist's diagnosis as outcome. Of the 298 patients that were enrolled, 28% were classified as having PsA according to the CASPAR criteria, while 19% had received a diagnosis of PsA from a rheumatologist. PASE score were always significantly different in patients with or without PsA, while Skindex-29 scores never were. The internal consistency of the PASE was very good (Cronbach's α of 0.90-0.95), the test-retest reliability was also very high (intraclass correlation coefficients 0.91-0.93), and the PASE scores showed good responsiveness to clinical change over time. The optimal cut-off identified through the ROC curves was ≥ 48 on the total PASE score, which was able to distinguish PsA from non-PsA patients with a 73.2% sensitivity and a 76.1% specificity. Our results confirm the good psychometric properties of the PASE, and indicate that it may be a useful tool for the dermatologists, both to screen for PsA and to obtain a standardized patient-reported measure to monitor and evaluate the health status of the patients with PsA.

The nested graft acts by inducing the process of de-senescence of the fibroblasts in chronic venous ulcers.

Senescent fibroblasts, which are present in chronic ulcers, are the reason for the wound becoming chronic. In this study, we introduce full-thickness micro skin grafts in the ulcer, a surgical technique known as a 'nested graft', which gave encouraging results leading to complete wound healing in all patients. The assessment of fibroblast cultures taken from the wound before and after treatment and comparison with fibroblasts from healthy skin showed that the fibroblasts taken from the ulcer after the nested graft treatment acquire morpho-functional characteristics overlapping those of fibroblasts from healthy skin. This surgical approach is, therefore, able to lead to the healing of chronic ulcers through the de-senescence of the fibroblasts.