Melanoma brain metastases represents a significant clinical challenge, frequently associated with high morbidity and mortality. Recent advancements in neuroimaging, radiation therapy, and targeted systemic therapies, specifically BRAF and MEK inhibitors, have improved the management of this condition. Nevertheless, the optimal therapeutic approach for melanoma brain metastases remains a subject of ongoing debate, with no universally accepted treatment protocol. The combination of stereotactic radiosurgery with targeted therapy using encorafenib and binimetinib in patients harboring BRAF V600E mutation holds therapeutic promise but requires careful toxicity management to ensure both safety and efficacy.
The use of hyaluronic acid (HA) fillers in oncology patients undergoing PET-CT scans is a topic of debate due to potential interference with imaging accuracy. A 54-year-old female, postmelanoma metastasectomy in the parotid region with subsequent facial nerve palsy (FNP), received HA filler injections for facial symmetry and functional restoration. Follow-up PET-CT scans showed no interference or artifacts attributable to HA injection, allowing for accurate imaging results. This case suggests that HA fillers administered in oncology patients may not universally pose challenges or disrupt PET-CT imaging interpretation. Due to the possible false positives induced by fillers, the inclusion of aesthetic treatments in patients’ anamnesis is a crucial step to accurately interpret PET-CT images. Although maintaining high level of caution in interpreting PET-CT results after filler injection is essential, our case emphasizes the safety of this procedure in oncology patients undergoing follow-up PET-CT scans.
Thyroid Eye Disease (TED), also known as Grave's Ophthalmopathy, is an autoimmune disorder characterized by inflammation of orbital and periorbital tissues, leading to ocular symptoms like proptosis, eyelid retraction with corneal exposure and diplopia. About 50% of Graves' disease patients develop TED, with increased risk in women, smokers, and those undergoing radioactive iodine therapy.1 TED usually emerges concurrently with hyperthyroidism, with an initial inflammatory phase lasting up to 2 years followed by a quiescent phase, during which symptoms may plateau or improve. While mild TED is usually self-limiting, moderate-to-severe cases often persist, with proptosis being the least likely to resolve. Treatment varies based on disease activity and severity, emphasizing achieving euthyroidism and smoking cessation. Mild cases may require symptomatic relief and selenium supplements, while moderate-to-severe active TED may necessitate glucocorticoids, orbital radiotherapy, or immunomodulatory agents. In stable phases, surgical interventions may restore function and aesthetics.2 Minimally invasive options such as Hyaluronic acid (HA) and Botulinum toxin type A (BTX-A) offer alternatives for ineligible or surgery-averse patients, providing fine-tuning postoperatively. We present a case of a 42-year-old woman who was referred to our dermatology ambulatory with a history of bilateral TED. The patient reported a diagnosis of Graves' disease at the age of 38, associated with significant ocular symptoms. She underwent antithyroid therapy for 18 months, experiencing an improvement, but the ophthalmic condition persisted. Upon clinical evaluation, the patient reported weight loss in the past few months, accompanied by tachycardia. Significant eyelid retraction and proptosis were observed with aesthetic and functional discomfort, indeed the patient reported dryness and irritation. We decided to start treatment utilizing Vycross® HA filler. All injections were performed bilaterally, and the procedure was repeated over three separate sessions, spaced 1 month apart, for a total treatment period of 2 months. The following injection sites and volumes were used: three needle injections of 0.1 mL each were administered into the zygomatic arch (malar region). An additional injection of 0.2 mL was placed into the mid-cheek area at the bone level. In the lower cheek, one needle injection of 0.5 mL was performed at the bone level, followed by two more injections of 0.5 mL each using a 22-gauge cannula (70 mm length) at the deep muscular facial plane (DMFP) and the suborbicularis oculi fat (SOOF) levels, respectively. Two injections of 0.5 mL each, using a 22-gauge cannula (70 mm length), were conducted at the subcutaneous level in the lower cheek region. Two subcutaneous needle injections of 0.7 mL and 0.3 mL were administered in the labiomental angle and chin apex areas, respectively. Finally, a 0.3 mL needle injection at the bone level of the right temple, and a 0.7 mL injection on the left temple were administered, followed by one needle injection of 0.2 mL in central and lateral infraorbital area and 0.1 mL in the medial infraorbital area. There were no reported adverse effects and the result was extremely pleasing and remained stable at the 6 and 12-month follow-up visit (Figures 1 and 2). Managing TED is challenging. Surgical options, such as orbital decompression, strabismus correction, and eyelid surgery carry risks and uncertain outcomes, especially in acute cases, as well as prolonged recovery.2 Recently, noninvasive technique like HA fillers and BTX-A are emerging. BTX-A injections can be associated with ptosis and ecchymosis, requiring careful administration and monitoring.3 Additionally, its effects have a relatively short duration, necessitating repeated administrations.4 In contrast, HA fillers addresses both aesthetic and functional challenges with minimal invasiveness and reversibility thanks to the possible use of hyaluronidase and adjustability through repeat treatments.5 Vycross® fillers provide durable volume and structural support for correcting proptosis and eyelid retraction, with reduced inflammation and side effects compared to other fillers, ensuring natural results and better tissue integration.6 The patient was in the stable phase of TED, which is ideal for interventions as inflammation had subsided. Specific injection sites were carefully chosen to restore facial symmetry and volume, particularly in the cheek and temple areas, commonly affected in TED patients. Precise targeting across various anatomical planes offered a more balanced correction compared to singular injections. A combination of cannulas and needles was chosen to reduce the risk of bruising and swelling and ensure even filler distribution. This technique is particularly important for TED patients, who may have sensitive and inflamed tissues. The treatment involved three sessions spaced a month apart to allow gradual improvement and manage complications, with carefully calculated volumes at each site to ensure balanced, natural results and avoid overcorrection. Our study underscores the efficacy and safety of nonsurgical approaches such as HA fillers, as a versatile alternative for patients ineligible or averse to surgical interventions. Aesthetic interventions must consider the disease's activity and timing, ensuring treatments are administered after the inflammation has subsided to prevent complications like granulomas or nodules. In this particular case, we employed Vycross® technology to demonstrate promising outcomes, stability and favorable results over a 12-month follow-up. However, to make definitive claims about the safety, effectiveness, and favorable outcomes of HA fillers in the treatment of TED, larger and more comprehensive studies need to be conducted. Future research with a larger sample size will be necessary to confirm these preliminary findings and to establish standardized treatment protocols. All authors were responsible for the concept and design of the study, collection and collation of data, analysis, and interpretation of data, write an article, reviewing this article, final reviewing this article and graphics performance. All authors declare that they have no conflicts of interest. This study was reviewed by local institutional review board (Ethics Committee of the Medical University Sapienza: Approval number US2345). Written consent is given by patient. The data that support the findings of this study are available from the corresponding author upon reasonable request.
To the editor, facial deformities can result from traumatic events, surgical interventions, or congenital conditions. They have a significant impact on patients, affecting various aspects of daily life and social interactions. The treatment of these conditions has undergone significant evolution over the years, employing increasingly advanced and personalized techniques. Despite the progress in current craniofacial plastic surgery methods, aesthetic imperfections can persist. To achieve facial harmony, it is crucial to consider the application of minimally invasive techniques in addition to surgery or as an alternative approach.1 Fat injections and hyaluronic acid (HA) fillers have proven to be an excellent option, thanks to their biocompatibility, versatility, and low immunogenicity.1-3 In this report, we describe a successful correction of facial deformity achieved exclusively with HA injections, with a long-lasting response. We present the case of a 40-year-old man who, following a road accident in 2008, experienced a traumatic brain injury with infarction of the optic chiasm and subsequent total blindness, followed by stabilization of the cranial vault with a titanium plate. After 15 years from the event, he referred to our dermatology ambulatory. Clinical examination revealed a loss of structure in the superolateral area of the left orbit and in the frontal region, leading to challenges in using eyeglasses and noticeable deformity (Figure 1A,C). The patient underwent treatment using Vycross® HA filler with a density of 20 mg/mL of HA (VYC-20) following the MD CodesTM system4 (Figure 2). In T1 and T2, two injections of HA filler, each of 1 mL, were administered into the supraperiosteal plane using a 27-gauge needle (12 mm length) with the bolus technique. Additionally, needle injections of three boli of 0.2 mL each were performed into the supraperiosteal plane along the zygomatic arch (Ck1), and another of 0.4 mL in Ck2. In Ck3, one bolus of 1 mL was performed into the supraperiosteal plane with needle and two injection of 1 mL each were administrated into the deep malar fat pad and suborbicularis oculi fat levels, with a 22-gauge cannula (70 mm length). Lastly, a 1 mL needle injection of HA filler was conducted at the inner canthus in the supraorbital region of the left eye and 2 mL was administered in the left frontal region using a fanning technique with cannula. These last two areas were treated without following the MD CodesTM system. There were no reported adverse effects, and the volumes were almost fully restored allowing the patient to wear hat and sunglasses. After 4 months from the treatment, an additional HA filler injection of 2 mL with cannula was performed in the frontal region (Figure 1B,D). The result was extremely pleasing and remained stable at the 8 month follow up visit. The use of HA fillers has experienced rapid diffusion in the last few decades quickly becoming the standard intradermal injection material for facial recontouring and rejuvenation.2 Despite its primary application in aesthetic procedures, in recent years, there has been an opportunity to propose HA injections as an alternative approach or in conjunction with surgery, in patients with facial deformities.1, 3, 5 Even though fat injections have demonstrated efficacy in patients experiencing significant volume loss, the primary hurdle in structural fat grafting lies in preserving its viability. Moreover, fat may not be reabsorbed uniformly and could lead to asymmetries, requiring a reintervention.1, 3 On the other hand, HA fillers have the advantage of a low incidence of adverse events, attributed to the availability of an antidote, hyaluronidase, making its action reversible.1, 5 The fluidity of HA fillers ensures precision during injection and the ability to perform the procedure both in superficial and deep levels. The use of fillers featuring a medium density, as presented in our case, allows for good versatility and adaptability to the characteristics of the treated area. Furthermore, the development of cross-linking technology, like Vycross®, has allowed enhancing his durability and longevity.1, 6, 7 Several cases of patients with facial deformities treated with surgery in conjunction with fat or HA fillers are reported in literature.1, 5 Our study stands out as a distinctive example of exclusive HA injection treatment in the reconstruction of facial deformities. In conclusion, HA filler emerges as a reliable non-surgical option for facial deformities. It offers versatility in addressing aesthetic concerns with lower risks and quicker recovery times than traditional surgery. Additionally, its non-permanent nature allows for personalized results without committing to irreversible interventions, highlighting its promising role supported by sustained responses over time. All authors were responsible for the concept and design of the study, collection and collation of data, analysis, and interpretation of data, write an article, reviewing this article, final reviewing this article and graphics performance. All authors declare that they have no conflicts of interest. This study was reviewed by local institutional review board (Ethics Committee of the Medical University Sapineza: Approval number US2345). Written consent is given by patient. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Localized scleroderma (LS), commonly known as morphea, presents a significant clinical challenge due to its chronic, inflammatory nature affecting the skin and potentially underlying tissues. This systematic review explores the innovative approach of combining laser therapy and injectable fillers, specifically hyaluronic acid, for the treatment of LS. We conducted a comprehensive literature review following PRISMA guidelines, examining articles from MEDLINE/PubMed to assess the combined efficacy of these treatments in improving both esthetic and functional outcomes for LS patients. The search yielded 64 articles, with six selected for in-depth analysis for a total of nine patients, covering a range of patient demographics and treatment types. Our review highlights cases where fractional CO
Melasma is a challenging skin condition which involves both structural and functional skin alterations. Despite the availability of various treatment options, the management remains complex. This is the first study to investigate topical application of Rosa Damascena stem cell exosomes when used concomitantly with microneedling in women and men with facial melasma. We recruited 20 subjects with Fitzpatrick skin types I-III, exhibiting melasma of varying severity. The modified Melasma Area and Severity Index (mMASI) and Global Aesthetic Improvement Scale (GAIS) were utilized to evaluate treatment response. The treatment protocol involved microneedling followed by exosome application over four or five sessions, at 4-week intervals. Ninety percent of subjects demonstrated a significant improvement in mMASI scores, while only 10% showed no change. GAIS assessment further supports overall improvement, with just 10% categorized as "not changed". Tolerability was favorable, with mild, transient side effects. Our findings suggest promising outcomes with this combined therapy, underscoring its potential as a safe and effective approach for treating melasma, particularly in severe and moderate cases. However, further research with larger sample sizes and control arms is warranted to validate these findings and explore long-term efficacy.
IgE-mediated food allergy is characterized immunologically by a type 1 immune response triggered upon exposure to specific foods and clinically by a broad range of manifestations and variable severity. Our understanding of food allergy within the allergic march of atopic dermatitis (AD) is still incomplete despite the related risk of unpredictable and potentially severe associated reactions such as anaphylactic shock. The aim of this pilot study was to investigate the effects of dupilumab, an IL-4/IL-13 monoclonal antibody approved for AD, on the allergic sensitization profile of patients with AD and type 1 hypersensitivity-related comorbidities, including oral allergy syndrome, anaphylaxis, and gastrointestinal disorders. We conducted an observational pilot study with a longitudinal prospective design, enrolling 20 patients eligible for treatment with dupilumab. Laboratory exams for total serum IgE, specific IgE, and molecular allergen components were performed at baseline and after 16 weeks of therapy. Our results demonstrate a statistically significant decrease in molecular components, specific IgE for trophoallergens, and specific IgE for aeroallergens following treatment with dupilumab. We suggest that modulating type 2 immunity may decrease IgE-mediated responses assessed with laboratory exams and therefore could minimize allergic symptoms in polysensitized patients. Upcoming results of randomized controlled trials investigating dupilumab in food allergy are highly anticipated to confirm its potential effect in the treatment of IgE-mediated food allergies.
Melasma is a challenging skin condition which involves both structural and functional skin alterations. Despite the availability of various treatment options, the management remains complex. This is the first study to investigate topical application of Rosa Damascena stem cell exosomes when used concomitantly with microneedling in women and men with facial melasma. We recruited 20 subjects with Fitzpatrick skin types I-III, exhibiting melasma of varying severity. The modified Melasma Area and Severity Index (mMASI) and Global Aesthetic Improvement Scale (GAIS) were utilized to evaluate treatment response. The treatment protocol involved microneedling followed by exosome application over four or five sessions, at 4-week intervals. Ninety percent of subjects demonstrated a significant improvement in mMASI scores, while only 10% showed no change. GAIS assessment further supports overall improvement, with just 10% categorized as “not changed”. Tolerability was favorable, with mild, transient side effects. Our findings suggest promising outcomes with this combined therapy, underscoring its potential as a safe and effective approach for treating melasma, particularly in severe and moderate cases. However, further research with larger sample sizes and control arms is warranted to validate these findings and explore long-term efficacy.
Clear Cell Sarcoma (CCS) of soft tissue is a rare and highly malignant neoplasm primarily affecting young adults, often presenting in the deep soft tissues of the extremities. Despite morphological and immunophenotypic similarities to melanoma, CCS arises from connective tissues and is characterized by a distinct genetic hallmark: the EWSR1-ATF1 fusion resulting from t(12;22)(q13;q12) translocation. This genetic signature is absent in melanoma, making molecular diagnosis essential for accurate differentiation. Additionally, recent evidence highlights the utility of PRAME as an immunohistochemical marker to distinguish CCS from melanoma and other neoplasms. Clinically, CCS commonly involves tendons and aponeuroses, with metastatic potential leading to poor prognoses despite optimal local disease management. Histologically, CCS features lobular growth, spindle-to-epithelioid cells with clear cytoplasm, and low mitotic activity, often necessitating a multimodal diagnostic approach incorporating histopathology, immunohistochemistry, and molecular testing. Therapeutically, wide surgical excision remains the cornerstone for localized disease, with sentinel lymph node biopsy aiding in staging. Adjuvant radiotherapy is considered in select cases, while chemotherapy has limited efficacy in metastatic settings. Emerging treatments, including targeted therapies focusing on EWSR1-ATF1-driven pathways and immune checkpoint inhibitors, offer hope for improved outcomes. This review synthesizes current knowledge on CCS, emphasizing diagnostic challenges, the role of PRAME, and advancements in therapeutic strategies to enhance patient care.
Rosacea is a chronic inflammatory skin condition with a multifactorial etiology, characterized by various signs and symptoms such as flushing, erythema, telangiectasia, and papules. In the erythematous clinical form, patients' skin appears thin, sensitive, and dehydrated.1 Although primary treatments often involve oral antibiotics and topical therapies, there remains a need for alternative approaches for optimal long-term cosmetic and therapeutic management. Hyaluronic acid (HA) holds promise in managing this skin condition. HA, in its high molecular weight form (HMWHA), is a ubiquitous component of the stratum corneum, which is depolymerized into fragments of low molecular weight hyaluronic acid (LMWHA) in the presence of inflammation or tissue injuries. LMWHA fragments penetrate the skin more easily than HMWHA and activate innate immune defense mechanisms, promoting the production of anti-inflammatory cytokines.2, 3 In 2013, Schlesinger et al. published a study evaluating the efficacy and safety of a topical device containing LMW-HA at a concentration of 0.2% in the treatment of rosacea, showing clinically observable improvements after 12 weeks.4 Hyal-system ACP (Auto-Crosslinked Polymer) is an internal ester of HA, available as an injectable device. With its slow-release system of LMWHA (approximately 200 kDa), represents an innovative technology in the fields of cosmetics and aesthetic medicine, providing a prolonged effect in the dermis.5 Two female patients, aged 41 and 62 years, with Fitzpatrick skin type II, presented to our clinic with erythematous rosacea. Upon clinical evaluation, they exhibited diffuse redness on the face, visible dilated blood vessels, along with sensations of burning or stinging, skin sensitivity, and cosmetic intolerance. Both patients had not received any prior treatment. We initiated treatment with Hyal-system ACP (one vial per side of the face) in addition to HA and sodium salt 0.2% cream twice daily at home for 30 days. After 1 month, improvement in skin quality and reduction in red areas, assessed using the Vectra H1 imaging system (Canfield Scientific, NJ, USA), were observed (Figures 1 and 2). The release mechanism of Hyal-system ACP occurs through the action of enzymes called esterases, naturally present in the skin. They slowly degrade HA, allowing the gradual release of LMWHA into the surrounding environment and ensuring a constant effective concentration in the skin for a prolonged period. Once released, HA can interact with skin cells, promoting hydration, regeneration, and production of collagen and elastin, thereby improving overall skin appearance and reducing signs of aging and cutaneous xerosis.5 In particular, 200 kDa HA has shown activation of fibroblasts and basal keratinocytes. Fibroblasts are responsible for the production of collagen, elastin, and other components of the extracellular matrix (ECM), crucial for maintaining skin elasticity, strength, and firmness by improving the skin structure. Stimulation of basal keratinocytes leads to improved texture, brightness, and ability to respond to environmental stressors, which is diminished in patients with rosacea. Moreover, LMW-HA has the ability to normalize cutaneous inflammatory response.5, 6 The results of this study on a small sample of patients suggest that Hyal-system ACP infiltration and in addition to HA and sodium salt 0.2% cream at home may have a promising role in managing patients with rosacea, in particular, in its erythematous form. The ability to activate HA release through esterase action offers a more targeted and controlled approach compared to traditional release systems, allowing personalized adaptation to specific skin needs and increased efficacy in treating skin conditions such as dryness, loss of tone, and cutaneous thinning. Finally, the injectable formulation, compared to the topical ones, ensures direct absorption of the product, deeper penetration, greater precision, and longer duration of action. Further research with larger samples and longer follow-up periods is needed to confirm these results and establish the long-term efficacy and safety profile in managing patients with sensitive skin affected by rosacea. All authors were responsible for the concept and design of the study, collection and collation of data, analysis, and interpretation of data, write an article, reviewing this article, final reviewing this article and graphics performance. All authors declare that they have no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. This study was reviewed by local institutional review board (Ethics Committee of the Medical University Sapienza: Approval number US2345). Written consent is given by patient.
