Insights into Early Systemic Treatment in Atopic Dermatitis: Scientific Facts and Practical Considerations.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized clinically by pruritus, and pathophysiologically by immune dysregulation, and compromised skin barrier function. While topical therapies are currently the cornerstone of AD management, especially in mild disease, recent advancements in systemic treatments and a deeper understanding of similar skin diseases, such as psoriasis, have highlighted the importance of early intervention. In this commentary, we explore the potential benefits of early systemic intervention in AD, with pruritus determining such a decision. Building on this concept, we assume that, through the timely systemic treatment that targets the immune dysregulation present in AD, the progression of the disease could be modified, improving overall patient outcomes. Early systemic intervention may minimize systemic inflammation, halting the "atopic march" and disrupting the "itch-scratch" cycle. Managing pruritus at its root could prevent secondary complications and reduce the psychosocial burden of the disease. This paradigm shift fosters a collaborative healthcare approach that empowers patients with long-term disease control strategies. In conclusion, the safety and efficacy of novel systemic treatments offer a compelling scenario for early intervention in atopic dermatitis care.

Photodynamic Therapy for Field Cancerization in the Skin: Where Do We Stand?

INTRODUCTION: Photodynamic therapy (PDT) with a photosensitizer is available for the treatment of multiple actinic keratoses (AKs) in a restricted skin area or, as it is established, for the field-cancerized skin. OBJECTIVES: Our review aims to present the up-to-date literature on skin field cancerization using PDT employing different topical photosensitizers, modified light delivery protocols and combination treatments to obtain excellent efficacy and safety in everyday clinical practice. METHODS: We sought PubMed, MEDLINE, Scopus, OVID, Embase, Science Direct, Cochrane Library, Research Gate and Google Scholar for [(aminolevulinic acid OR aminolevulinate) AND photodynamic therapy] with (field-directed OR field cancerization, (actinic keratosis), and (efficacy OR effectiveness OR pain OR tolerability) for studies published until February 2023. RESULTS: Advantages of PDT compared to the other field treatments, including imiquimod, 5-fluorouracil, ingenol mebutate gel and diclofenac, reported better cosmetic outcomes and greater patient satisfaction. On the other hand, some drawbacks of field PDT include pain and treatment duration. Alternate illumination methods have also been investigated, including daylight as a light source. Pretreating the affected area may enhance photosensitizer absorption leading to better therapeutic results, while combinational treatments have also been tested. Patients prefer daylight PDT to traditional light sources since it is more well-tolerated and equally effective. Even as a preventive treatment, field PDT yields promising outcomes, especially for high-risk individuals, including organ transplant recipients. CONCLUSIONS: This review provides a thorough display of the field of PDT on cancerized skin, which will facilitate physicians in applying PDT more efficiently and intuitively.

Topical immunotherapy treatment of alopecia areata with diphenylcyclopropenone: Regulatory T cells as biomarkers for treatment response.

Treatment of alopecia areata is often challenging, especially for patients with extended disease. Contact immunotherapy with diphenylcyclopropenone (DPCP) has been reported as an effective topical treatment but the exact immunologic mechanism of diverting the immune response is still unknown. We investigated the efficacy of topical immunotherapy with DPCD in acute, intermediate, and chronic lesions of AA and the response rate was associated with perifollicular infiltrate of T regulatory cells. Approximately two-thirds of our patients (67.5%) had a response rate > 50% after 6 months of DPCP therapy. Patients with acute and intermediate onset of the disease were more likely to respond to the therapy. Although responders demonstrated FOXP3+ positive lymphocytes in immunohistochemistry, this association could not be confirmed by statistical significance (p = 0.052). In patients with multiple lesions, that had different chronological onset, the lesions with more recent onset responded faster than lesions of longer duration.

Dermoscopic Predictors of Benignity and Malignancy in Equivocal Lesions Predominated by Blue Color.

BACKGROUND: Blue color in dermoscopy can be seen in a wide range of benign and malignant lesions, melanocytic or not. Some blue-colored dermoscopic criteria have been associated with specific tumors, such as blue-white veil with melanoma and homogeneous blue with blue nevi. However, when blue color occupies a large part of the lesion's surface, the dermoscopic assessment might be particularly challenging. OBJECTIVE: To identify dermoscopic predictors associated with benignity and malignancy in tumors characterized by a predominant dermoscopic presence of blue color. METHODS: We retrospectively screened our institutional database for tumors exhibiting blue color in at least 50% of their surface with available histopathologic diagnosis. Lesions with blue color covering less than 50% of their extent and lesions not histopathologically assessed were excluded. The dermoscopic images were evaluated for the presence of predefined criteria, including the characteristics of the blue color, coexisting colors, and the vascular structures. RESULTS: Of 91 included tumors, 53 were benign (35 blue nevi, 10 angiomas, and 8 seborrheic keratoses) and 38 malignant (12 melanomas and 26 basal cell carcinomas). Our analysis revealed 3 potent dermoscopic predictors of benignity: extension of blue color in more than 75% of the surface, diffuse distribution of blue color, and absence of vessels, posing a 2.3-fold, 5.6-fold, and 6.7-fold increased probability of benignity, respectively. In contrast, asymmetric distribution of blue color, blue clods, coexistence of gray color and linear vessels were significantly predictive of malignancy, posing a 8.9-fold, 2.8-fold, 13.5-fold, and 10.4-fold increased probability, respectively. CONCLUSION: In predominantly blue tumors, the probability of malignancy is high when blue color is seen in clods or is asymmetrically distributed and when gray color or linear vessels coexist. In contrast, a diffuse distribution of blue color, its expansion in more than 75% of the surface, and the absence of vessels are highly suggestive of a benign tumor.

The role of prostaglandins in androgenetic alopecia.

BACKGROUND: Though androgenetic alopecia (AGA) is one of the most common diseases affecting both sexes and all races, its pathogenesis is not completely clarified. The aim of this study was to investigate the role of the four major prostaglandins (PGs) (PGE2 , PGD2 , PGF2α , and PI2 or prostacyclin) in the pathogenesis of AGA in males and females. METHODS: Human scalp biopsies were obtained from 30 adults (17 males and 13 females) suffering from AGA and from 30 healthy adults (18 males and 12 females). In each subject, two skin biopsies were performed, one from the frontal bald area and another one from the occipital area with normal hair growth. In the healthy group, biopsies were taken from both areas too. In each sample, all four PGs were measured. RESULTS: In the patient group, PGD2 and prostacyclin or PGI2 levels were increased in bald compared to haired scalp. On the contrary, measurements of PGE2 and PGF2α showed that they were diminished in bald areas compared to haired areas. PG levels in healthy samples were comparable to the haired areas. CONCLUSION: These results support that there is a fine balance between these four proteins in scalp hair follicles, and its maintenance may be crucial for hair growth. Furthermore, their receptors could be potential targets for treatment of AGA.

Dermoscopy of pagetoid reticulosis, with dermoscopic-pathologic correlation.

Pagetoid reticulosis (PR), also known as Woringer-Kolopp disease, is a rare variant of mycosis fungoides with distinctive clinicopathologic features. It clinically manifests as a solitary, erythematous, gradually enlarging, scaly, or verrucous plaque on the lower extremities, and due to its indolent course and nonspecific clinical features, may remain undiagnosed for years. In the current study, we describe the clinical and dermoscopic characteristics of a rare case of PR disease and correlate them with the corresponding histopathologic findings. Dermoscopy may prove beneficial in early diagnosis of this rare entity.

Targeting IL-23 in psoriasis: current perspectives.

The recent advances in the understanding of psoriasis pathogenesis have clarified the pivotal role of interleukin (IL)-23. It is a heterodimeric cytokine consisting of two subunits, the unique p19 and the p40, which are shared with IL-12. The basic role of IL-23 in psoriasis is the activation and maintenance of the T-helper 17 pathway. New research findings indicate that IL-23 is more important than IL-12 in the pathogenesis of psoriasis. Based on that background, the selective targeting of the IL-23p19 subunit emerged as an attractive therapeutic option and led to the development of a new category of biologic agents. Three monoclonal antibodies that selectively inhibit the IL-23p19 subunit, guselkumab, tildrakizumab, and risankizumab, are in the pipeline for the treatment of moderate-to-severe psoriasis. In this article, we review the most recent efficacy and safety data regarding these IL-23p19 inhibitors.

Basal Cell Carcinoma in a Childhood Cancer Survivor: What Neurosurgeons Should Avoid.

Among childhood cancer survivors (CCSs), non-melanoma skin cancer (NMSC) is the most common type of second malignancy. Morbidity related to the development of NMSC in this group of patients may be sometimes unpredictable and difficult to manage. We present the case of a 49-year-old female who was a CCS and developed giant superficial basal cell carcinomas (sBCCs) over the previously irradiated field of the scalp. BCC involved the atrophic skin overlying the catheter of the peritoneal cerebral shunt that was set there for the management of hydrocephalus. Topical treatment with imiquimod 5% resulted in local skin reaction that was further complicated with catheter exposure. The patient underwent an emergency neurosurgery for reposition of the cerebral shunt. Subsequent treatment with imiquimod resulted in complete resolution of sBCC. Given the increased risk for the development of BCCs in CCSs, awareness of neurosurgeons is crucial. Avoidance of setting the catheter of the cerebral shunt within the radiotherapy field is highly recommended, in order to avoid unnecessary future surgeries and subsequent morbidity, as in our case.

IL-17A, IL-22, and IL-23 as Markers of Psoriasis Activity: A Cross-sectional, Hospital-based Study.

INTRODUCTION: T-helper 1 (Th1), Th17 cells, and their related cytokines are implicated in psoriasis pathogenesis although the contribution of each group of cytokines in psoriasis activity has not been fully clarified. OBJECTIVES: To investigate whether Th17-related cytokines are associated with psoriasis activity. METHODS: The serum levels of interleukin (IL)-1ß, 6, 8, 17Α, 22, 23, and tumor necrosis factor-α (TNFα) were measured with flow cytometry in 35 patients with plaque psoriasis (21 with stable and 14 with active disease) and in 20 healthy controls. RESULTS: Interleukin-6, 8, 17A, 22, 23, and TNFα were significantly elevated in psoriasis patients compared with controls. In the sensitivity analyses, patients with active disease showed significantly increased levels of IL-17A, IL-23, and IL-22 as compared to the group of patients with stable psoriasis. CONCLUSIONS: Our study highlights a possible crucial role of IL-17A, IL-22, and IL-23 in the activity of psoriasis and the early stages of the disease.

Onychomadesis after hand-foot-and-mouth disease outbreak in northern Greece: case series and brief review of the literature.

BACKGROUND: Nail abnormalities in childhood are generally uncommon. Recently, onychomadesis was described as a late complication of hand-foot-and-mouth disease (HFMD). Onychomadesis outbreaks following HFMD have been reported in many countries worldwide. AIM: To present a case series of onychomadesis in children, following HFMD outbreak in Northern Greece, and review literature data. METHODS: Children with evident onychomadesis attending the outpatient clinic between November 2012 and January 2013 were included in the study. A questionnaire including demographic personal and family history information of the children was completed by the parents. Patients were clinically examined, and their pediatric and dermatological records were studied to confirm precedent HFMD. Direct microscopic examination and cultures for fungi were performed. Exposure of participants to coxsackievirus, based on serology testing during infection, was also recorded. RESULTS: Sixty-eight children with onychomadesis were included. The mean number of affected nails was 8.82. Fingernails were more often involved. Previous clinical diagnosis of HFMD was confirmed in 67/68 cases. The mean time from HFMD diagnosis to onychomadesis development was 39.6 days (range: 28-56 days, STD: 7.33). Direct microscopic examination, as well as cultures for fungal species, was negative for the whole sample size. All the nail changes were transient with spontaneous regrowth after 1-4 months. CONCLUSION: Our data indicate that onychomadesis outbreak in the region of Thessaloniki during fall-winter 2012-13 was highly related to the outbreak of HFMD. Our study reinforces existing evidence for the association between onychomadesis and HFMD.

Dermoscopic pattern of psoriatic lesions on specific body sites.

BACKGROUND: Scarce evidence exists on the dermoscopic pattern of psoriasis on specific body sites. OBJECTIVE: To describe the dermoscopic characteristics of psoriatic plaques located on the scalp, face, folds, palms, soles and genitalia. METHODS: Dermoscopic images of psoriatic lesions located on the aforementioned body sites were retrospectively evaluated for the presence of predefined criteria. RESULTS: A total of 139 lesions from 85 patients were included in the study. Dotted vessels were the commonest dermoscopic criterion (97.1%) followed by white scales (64.7%), while vessel distribution was regular in 87.7% of cases. Regularly distributed dotted vessels represented a constant finding in all locations, while the frequency of white scales varied significantly among different body sites. CONCLUSION: The well-known dermoscopic criteria of psoriasis can also be seen in lesions located on the scalp, face, palms, soles, folds and genitalia, with the frequency of white scales varying among different body sites.

Spontaneous abortion during ustekinumab therapy.

BACKGROUND: Psoriasis affects a considerable proportion of women in their reproductive years. Limited published data exist about the possible negative impact of the disease itself in the prognosis of pregnancy. On this background, the emergence of newer biologic agents for psoriasis treatment - such as ustekinumab - raises safety issues concerning the exposure to the drug during pregnancy. To our knowledge this is the first report in the literature describing a pregnancy outcome under ustekinumab treatment. OBSERVATION: We report a 35-year-old female psoriasis patient who was under treatment with ustekinumab for a year when she inadvertedly became pregnant. The drug was discontinued immediately and the patient did not opt for termination. During the 12th week of gestation she experienced a spontaneous abortion. CONCLUSION: Although the patient's profile fulfilled 2 general risk factors for spontaneous abortion - she was a smoker and this was her third pregnancy - one could not underestimate the possible role of the drug and of psoriasis per se in this adverse pregnancy outcome. Pregnancy registries and large prospective studies are needed in order to determine whether poorer pregnancies outcomes in psoriatic women are due to the disease itself, associated comorbidities or side-effects of new therapies such as ustekinumab.

The impact of different fluence rates on pain and clinical outcome in patients with actinic keratoses treated with photodynamic therapy.

BACKGROUND/PURPOSE: Literature data suggest that lower fluence rates are preferable in terms of clinical response and tolerability for treating patients with actinic keratoses (AKs). We aimed to clarify the impact of different fluence rates on pain during photodynamic therapy (PDT) for AKs, as well as on treatment outcome. METHODS: Individuals with at least three discrete AKs were recruited. Each lesion was randomly allocated to 25, 50 or 75 mW/cm2 of topical 5-aminolevulinic acid (5-ALA) PDT, using non-coherent light source. Primary end point was pain during illumination, evaluated using a visual analogue scale (VAS). Secondary end points were clinical outcome and adverse events. RESULTS: Fifty adults, with 150 AKs lesions were recruited in the study. Mean VAS score did not significantly differ between the groups of 25 and 50 mW/cm2 (P=0.714). However, mean VAS was significantly higher at the group of 75 mW/cm2 in comparison to the former ones (P=0.000). With respect to the clinical outcome and adverse events during the first year of follow-up, no differences were observed between the three groups. Comparison between the 25 and the 50 mW/cm2 (P=0.749), as well as between the former and the 75 mW/cm2, did not show a dependence of complete response rate on fluence (P=0.749 and P=1.000, respectively). CONCLUSIONS: According to our observations a fluence rate between 25 and 50 mW/cm2 is effective and better tolerated by patients treated with topical 5-ALA PDT for AKs.

Treatment of giant Bowen's disease with sequential use of photodynamic therapy and imiquimod cream.

We present a 79-year-old man with a 2-year history of Bowen's disease. The 10 × 10 plaque was located on the right frontotemporal area. The patient was treated with two photodynamic therapy (PDT) sessions, performed 1 week apart, followed by five times per week application of imiquimod 5% cream for 6 consecutive weeks. Complete clinical and histological response was achieved 3 months after treatment was completed. The patient remains recurrence free 12 months after treatment. Cosmetic outcome was evaluated as fair because of residual erythema. Long-term follow-up is mandatory for assessment of recurrences. Further studies are needed in order to confirm the improved outcome using the combination of PDT and imiquimod cream.