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.

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.

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.

First Confirmed Description of Acremonium egyptiacum from Greece and Molecular Identification of Acremonium and Acremonium-like Clinical Isolates.

Acremonium and the recently separated acremonium-like genera, such as Sarocladium, are emerging causes of opportunistic disease in humans, mainly post-traumatic infections in immunocompetent hosts, but also invasive infections in immunocompromised patients, such as those undergoing transplantation. Acremonium egyptiacum has emerged as the major pathogenic Acremonium species in humans, implicated mainly in nail but also in disseminated and organ specific infections. In this first study of acremonium-like clinical isolates in Greece, 34 isolates were identified and typed by sequencing the internal transcribed spacer, and their antifungal susceptibility was determined by a modified CLSI standard M38 3rd Edition method for filamentous fungi. A. egyptiacum was the primary species (18 isolates) followed by Sarocladium kiliense (8), Acremonium charticola, Gliomastix polychroma, Proxiovicillium blochii, Sarocladium terricola, Sarocladium zeae, and Stanjemonium dichromosporum (all with one isolate). Two isolates, each with a novel ITS sequence, possibly represent undescribed species with an affinity to Emericellopsis. All three A. egyptiacum ITS barcode types described to date were identified, with 3 being the major type. Flutrimazole, lanoconazole, and luliconazole presented the lower minimum inhibitory concentration (MIC) values against A. egyptiacum, with a geometric mean (GM) MIC of 2.50, 1.92, and 1.57 µg/mL, respectively. Amphotericin B, itraconazole, posaconazole, voriconazole, terbinafine, amorolfine, and griseofulvin MICs were overall high (GM 12.79-29.49 µg/mL). An analysis of variance performed on absolute values showed that flutrimazole, lanoconazole, and luliconazole were equivalent and notably lower than those of all the other drugs tested against A. egyptiacum. Antifungal susceptibility of the three different A. egyptiacum genotypes was homogeneous. Overall, the high MICs recorded for all systemically administered drugs, and for some topical antifungals against the tested A. egyptiacum and other acremonium-like clinical isolates, justify the routine susceptibility testing of clinical isolates.

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.

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.

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.

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.

Complete resolution of a squamous cell carcinoma of the skin using intralesional 5-aminolevulinic acid photodynamic therapy intralesional PDT for SCC.

We present an 82-year-old female patient with a 2-year history of an infiltrative squamous cell carcinoma (SCC) on her right cheek. The patient was treated with one intralesional photodynamic therapy (PDT) session using 10% 5-aminolevulinic acid solution. We used red light by a non-coherent light source at a light dose of 100 J/cm² and a fluency rate of 100 mW/cm². Complete clinical and histological response was achieved 3 months after the treatment procedure. Cosmetic outcome was evaluated as fair. The patient remains disease free with the absence of any clinical sign of recurrence 16 months after PDT. Long-term follow-up is needed for assessment of recurrences. Optimization of the therapeutic protocol, as well as justification of our results in larger studies are needed in order to elicit safe conclusions.

Telangiectasia macularis eruptive perstans successfully treated with PUVA therapy.

We present the case of a 58-year-old woman who was diagnosed as having telangiectasia macularis eruptiva perstans (TMEP) and was successfully treated with PUVA photochemotherapy. During the 6-month follow-up, no recurrence of pruritus or skin lesions was observed. TMEP represents a rare form of cutaneous mastocytosis, which is clinically characterized by reddish-brown telangiectatic macules symmetrically distributed over the trunk and extremities. Although in the majority of cases the disease is limited to the skin, systemic involvement may occur. The treatment of TMEP is challenging and several therapeutic modalities have been proposed in the past.

Multiple nevoid hypertrichosis as an isolated developmental defect.

A 3-year-old girl presented with longer hair on the left side of her scalp, coarse hair of abnormal length on her extremities, and a tuft of hair in the lumbosacral region, with all hair distributed on normally pigmented skin. Neither similar or relevant family history nor associated extracutaneous abnormalities was detected after a thorough examination. Clinical diagnosis of patchy nevoid hypetrichosis was confirmed by histology. Nevoid hypertrichosis is a rare hair growth disorder that usually presents at or soon after birth. It is characterized by patches of hypertrichosis distributed in a segmental pattern. It may be accompanied by mental, ocular, or myoskeletal abnormalities. Cases of nevoid hypertrichosis with multiple patches presenting as a solitary developmental defect have been rarely described in the literature.

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.