Platelet-Rich Plasma (PRP) and Adipose-Derived Stem Cell (ADSC) Therapy in the Treatment of Genital Lichen Sclerosus: A Comprehensive Review.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis mostly localized in the genital area, characterized by vulvar alterations that can severely impact a patient's quality of life. Current treatment modalities often provide incomplete relief, and there is a need for innovative approaches to manage this condition effectively. Platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) have emerged as potential regenerative therapies for LS, offering promising results in clinical practice. This comprehensive review explores the utilization of PRP and ADSC therapy in the treatment of genital LS, highlighting their mechanisms of action, safety profiles, and clinical outcomes. PRP is a blood product enriched in growth factors and cytokines, which promotes tissue regeneration, angiogenesis, and immune modulation. ADSC regenerative potential relies not only in their plasticity but also in the secretion of trophic factors, and modulation of the local immune response. Numerous studies have reported the safety of PRP and ADSC therapy for genital LS. Adverse events are minimal and typically involve mild, self-limiting symptoms, such as transient pain and swelling at the injection site. Long-term safety data are encouraging, with no significant concerns identified in the literature. PRP and ADSC therapy have demonstrated significant improvements in LS-related symptoms, including itching, burning, dyspareunia, and sexual function. Additionally, these therapies enable many patients to discontinue the routine use of topical corticosteroids. Several studies have explored the efficacy of combining PRP and ADSC therapy for LS. In combination, PRP and ADSCs seem to offer a synergistic approach to address the complex pathophysiology of LS, particularly in the early stages. The use of PRP and ADSC therapy for genital lichen sclerosus represents a promising and safe treatment modality. These regenerative approaches have shown significant improvements in LS-related symptoms, tissue trophism, and histological features. Combination therapy, which harnesses the synergistic effects of PRP and ADSCs, is emerging as a preferred option, especially in early-stage LS cases. Further research, including randomized controlled trials and long-term follow-up, is warranted to elucidate the full potential and mechanisms of PRP and ADSC therapy in the management of genital LS. These regenerative approaches hold great promise in enhancing the quality of life of individuals suffering from this challenging condition.

Case Report: Sequential postzygotic HRAS mutation and gains of the paternal chromosome 11 carrying the mutated allele in a patient with epidermal nevus and rhabdomyosarcoma: evidence of a multiple-hit mechanism involving HRAS in oncogenic transformation.

We report a 7-year-old boy born with epidermal nevi (EN) arranged according to Blaschko's lines involving the face and head, right upper limb, chest, and left lower limb, who developed a left paratesticular embryonal rhabdomyosarcoma at 18 months of age. Parallel sequencing identified a gain-of-function variant (c.37G>C, p.Gly13Arg) of HRAS in both epidermal nevus and tumor but not in leukocytes or buccal mucosal epithelial cells, indicating its postzygotic origin. The variant accounted for 33% and 92% of the total reads in the nevus and tumor DNA specimens, respectively, supporting additional somatic hits in the latter. DNA methylation (DNAm) profiling of the tumor documented a signature consistent with embryonal rhabdomyosarcoma and CNV array analysis inferred from the DNAm arrays and subsequent MLPA analysis demonstrated copy number gains of the entire paternal chromosome 11 carrying the mutated HRAS allele, likely as the result of paternal unidisomy followed by subsequent gain(s) of the paternal chromosome in the tumor. Other structural rearrangements were observed in the tumours, while no additional pathogenic variants affecting genes with role in the RAS-MAPK and PI3K-AKT-MTOR pathways were identified. Our findings provide further evidence of the contribution of "gene dosage" to the multistep process driving cell transformation associated with hyperactive HRAS function.

Therapeutic Management of a Case of Severe Psoriasis Coexistent with Bullous Pemphigoid in the Elderly.

A standardised therapeutic approach to coexistent psoriasis and bullous pemphigoid is lacking, although psoriasis is associated with an increased risk of developing bullous pemphigoid. Here, we report an elderly psoriatic patient who developed a refractory bullous pemphigoid and experienced clearance of both diseases following treatment with dymethylfumarate. Due to lymphopenia, this treatment was stopped and the patient was administered risankizumab without relapses. Dymethylfumarate may be able to inhibit the recruitment of neutrophils and monocytes into the skin. Therefore, thanks to pleiotropic effects, dymethylfumarate could be an effective treatment in psoriatic patients who develop bullous pemphigoid.

Effectiveness of etanercept in children with plaque psoriasis in real practice: a one-year multicenter retrospective study.

BACKGROUND: Etanercept is licensed for the treatment of moderate-to-severe plaque psoriasis in children. OBJECTIVES: The aim of this analysis was to investigate effectiveness, tolerability, and reasons for discontinuation of etanercept in a real-life cohort of children and adolescents with moderate to severe plaque psoriasis. METHODS: Data collected from a number of centers belonging to the 'Pediatric Dermatology Group' of the Italian Society of Dermatology (SIDeMaST) were examined in patients (age ≤17 years) who started treatment with etanercept from 2011 to 2015. A group of 23 patients were identified. Efficacy assessment was defined as the proportion of patients with a ≥50% and ≥75% improvement in Psoriasis Area Severity Index (PASI) at weeks 12, 24, and 52. Safety was evaluated on adverse event reporting. Reasons for discontinuation were classified as ineffectiveness, adverse events, remission, or other reasons. RESULTS: At week 12, 56.5% of patients achieved PASI 75, 86.9% achieved PASI 50. Efficacy was sustained through week 52. In 15 patients etanercept was still ongoing at the time of data collection. In three patients the therapy was suspended due to inefficacy. The medication was overall well tolerated. CONCLUSIONS: Etanercept was an effective and well-tolerated treatment in this real-life cohort of patients.

Ineffectiveness of tumor necrosis factor-α blockers and ustekinumab in a case of type IV pityriasis rubra pilaris.

Treatment of pityriasis rubra pilaris (PRP) may be difficult since no standardized therapeutic approach has been established. Recently, tumor necrosis factor-α (TNF-α) blockers have been demonstrated to be favorable in the management of recalcitrant PRP. The authors report a case of a patient who presented a type IV PRP or circumscribed, juvenile type. Such a condition follows an unpredictable course, presenting with diffuse, palmoplantar keratoderma and sharply-demarcated areas of follicular hyperkeratosis on the elbows and knees. Treatment with all available TNF-α inhibitors and ustekinumab did not prove to be helpful. The authors suggest that circumscribed variants of PRP could respond to therapy in ways different from classical PRP.

Current therapeutic approaches of psoriasis are affected by age at disease onset.

Psoriasis in patients with early onset follows an irregular course with tendency to become severe and extensive. The aim of this study was to look for an association between age at onset of psoriasis and use of biologic agents for its treatment. We reviewed the medical records of 350 patients with moderate to severe psoriasis treated with systemic therapies and compared differences in age at disease onset between patients who had received biologics and those who had not. The mean age of our patients was 54.9 ± 15.1 years; 100 of them (28.6%) were currently receiving or had previously received treatment with a biologic agent. For those with biologic use, average age at the time of diagnosis of psoriasis was 28.2 ± 14.7 years, compared with 40.4 ± 18.1 years for those who had not received biologics. A total of 139 patients had psoriasis diagnosed before or at age 30 years. Sixty out of them (43.1%) had used biologics. Forty-four patients had psoriasis diagnosed after age 60 years, but only three out of them (6.8%) had used biologics. Concomitant arthritis was significantly associated with use of biologics. In our patients with psoriasis disease, frequency of treatment with a biologic agent varied inversely with age at disease onset.

Clinical predictors of non-response to any tumor necrosis factor (TNF) blockers: a retrospective study.

BACKGROUND: Anti-tumor necrosis factor (TNF)-α therapies represent a significant innovation in therapy for psoriasis. However, a significant number of psoriasis patients do not respond well to TNF blockers or show an insufficient control of disease activity on a long-term basis. OBJECTIVE/AIM: The aim of this study was to recognize specific clinical factors that could be associated with a non-response to any available TNF blockers in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: The authors reviewed the medical records of all patients who had started etanercept, infliximab, adalimumab and had achieved a minimum of 24 months follow-up. The authors identified subjects who were not responsive to all available anti-TNF agents, whatever the chronology of their use. RESULTS: A total of 110 patients were retrospectively examined. Thirteen patients were identified as "non-responders" to all available TNF-α blockers. Current smoking at the start of anti-TNF therapy was associated with non-response to TNF blockers. The group of "non-responders" presented a high mean body mass index and a high baseline PASI score with respect to the group of responders. CONCLUSIONS: The data showed that the majority of non-responder patients were smokers, overweight or obese and had a high baseline PASI score. Concomitant arthritis was not significantly associated with non-response.

Platelet gel in the treatment of cutaneous ulcers: the experience of the Immunohaematology and Transfusion Centre of Parma.

BACKGROUND: Platelet gel is being ever more frequently used to promote healing of cutaneous ulcers. However, the factors that determine the often variable clinical outcome of this procedure are still incompletely understood. AIMS: The aims of this study were to demonstrate that platelet gel, even when obtained under strictly controlled conditions, produces highly variable outcomes in patients with cutaneous ulcers and to propose a method for in vitro standardisation of the biological properties of platelet gel. MATERIAL AND METHODS.: Patients were enrolled on the basis of a pre-defined protocol. Platelet concentrate was produced with standard methods, with a variability in platelet count among the different samples of less than 10%. The platelet gel for clinical use was obtained, under strictly standardized conditions, by adding thrombin and calcium gluconate to the concentrates. For in vitro studies, platelet gel, obtained from platelet-rich plasma from four donors, was frozen and thawed twice so as to increase gel contraction. The supernatant was used to modify cell proliferation, protein synthesis, and the expression of selected genes in cultures of human diploid fibroblasts. RESULTS: Seventeen patients (aged 44-78 years) with ulcers (4 diabetic, 11 vascular, 1 post-traumatic, 1 decubitus) were treated with platelet gel (4 autologous, 13 homologous). Complete re-epithelialisation of four ulcers (1 diabetic, 1 post-traumatic, 2 vascular) was obtained after applications of platelet gel (2 autologous, 2 homologous); in 11 other cases there was a greater than 50% reduction in the size of the ulcer. Two patients had no benefit. The supernatant of the platelet gel was able to promote dose-dependent proliferation and changes in gene expression as well as in metabolic activities related to protein synthesis. CONCLUSIONS: Although the use of platelet gel in the treatment of cutaneous ulcers is increasing, and conditions for its production are better standardised, very considerable variability of clinical outcomes is still observed, even within single centres, suggesting that there are differences in biological properties of platelet concentrates from individual patients which cannot be readily controlled with current techniques. The biological effects of the platelet gel supernatant described in this article may provide the basis for a simple biological validation of platelet preparations before their clinical use, so as to reduce this potentially important source of variability.

Treatment of chronic venous leg ulcers by platelet gel.

Chronic venous leg ulcers (CVLU) are chronic wounds, associated with long-standing venous hypertension, which have a poor prognosis for healing. In the process of wound healing the first step is represented by platelet aggregation and subsequent release of growth factors and other mediators, which play a key role in the repair response. Platelet gel (PG), a hemocomponent obtained by mixing platelets, thrombin, and calcium, is able, when applied topically, to release platelet mediators that likely favor CVLU healing. However, unstandardized protocols have been described in studies utilizing PG for the regeneration of a number of tissues, including CVLU; the relative clinical outcomes were hence highly variable. In our experience the topical use of PG, together with the strict adherence to the principles of good wound care, quickly promoted increased granulation tissue, followed by a complete CVLU epithelization. Although further studies and trials are needed to establish the major outcome affecting rules for optimal indications, preparation, and use of PG for CVLU treatment, PG can be undoubtedly considered a useful tool, able to improve the management of CVLU.

Therapeutic restoration of cytolytic and suicidal cell molecular machineries favours disease healing.

BACKGROUND/OBJECTIVE: Several drugs have recently been demonstrated to successfully treat diseases by activating cytolytic or suicidal cell molecular machineries. On the other hand, in healthy subjects cytolytic and suicidal machineries are able to maintain tissue homeostasis, thus preventing the onset of a number of diseases. These machineries include both the cytolysis, exerted by cytotoxic T lymphocytes, of cells 'altered' by infectious or neoplastic antigens (altered cell cytolysis [AlCC]), and the suicide of antigen-activated T cells when in antigen-excess (activated cell suicide [AcCS]). RESULTS/CONCLUSIONS: These drugs may therefore, in our opinion, restore AlCC or AcCS, and, as aconsequence, favour disease healing. Thus, such a restoration could prove helpful for treating disorders caused by failure of such machineries.