Impurities in Hyaluronic Acid Dermal Fillers? A Narrative Review on Nonanimal Cross-Linked Fillers.

Importance: Nonanimal cross-linked hyaluronic acid (HA) dermal fillers are among the most versatile tools in minimal invasive esthetic medicine. Filler injections aim to volumize, provide contour, and reduce wrinkles and skinfolds. In the hand of the experienced user, HA fillers have an excellent safety profile. Nevertheless, adverse events have been reported related to poor injection techniques, infection, and immune reactions. Observations: In this review, the focus is on filler impurities. Impurities can originate from the fermentation process, crosslinking, packaging, and contamination. Impurities consist of particular and nonparticular matter. We discuss possible risks for the patient to be treated with HA fillers. Conclusions and Relevance: Impurities of dermal fillers bear a potential risk for patients, such as delayed autoimmune and inflammatory reactions, biofilm formation, and exposure to leachable Endocrine Disrupting Chemicals. Amount and quality of impurities can be considered as one of the quality parameters of commercially fillers. Considering patient safety, filler impurities should be further reduced.

Kerion Celsi in infants and children-A narrative review 2010-2023.

Kerion Celsi is an inflammatory, deep fungal infection of the scalp. It is rare in neonates but gets more common in children about 3 years and older. It represents with swelling, boggy lesions, pain, alopecia and purulent secretions. Secondary bacterial infection is not unusual after maceration. Extracutaneous manifestations include regional lymphadenopathy, fever and very rare fungemia. Id-reactions can occur. Diagnosis is based on clinical suspicion, clinical examination and medical history. Diagnosis should be confirmed by microscopy, fungal culture and molecular procedures. The most common isolated fungal species are anthropophilic Trichophyton (T.) tonsurans and zoophilic Microsporum (M.) canis, while geophilic species and moulds rarely cause Kerion Celsi. Treatment is medical with systemic and topical antifungals supplemented by systemic antibiotics when necessary, while surgery needs to be avoided. Early and sufficient treatment prevents scarring alopecia. The most important differential diagnosis is bacterial skin and soft tissue infections.

Cavernous hemangioma of the lip: combined treatment with intralesional laser and surgery.

Infantile cavernous hemangioma is a benign vascular tumor in childhood. Cavernous hemangiomas have a tendency of slow enlargement with subsequent complications such as ulceration and bleeding. We report a case of a large cavernous hemangioma affecting the median upper lip in an 11-year-old girl. The lesion was growing and painful on pressure. The patient felt stigmatized. Treatment was wished for by patient and parents. After careful examination including Doppler ultrasound, we suggested a combined approach. In the first step the lesion was coagulated with an intralesional neodymium-YAG laser using a blunt tip. In the second step, immediately after the action of the laser, the lesion was removed completely by surgery. Defect closure was realized with bilateral tissue-expanding vermillion myocutaneous flaps. The patient was followed-up to 5 months. Disfigurement and functional impairment were eliminated. The result was satisfying for both patient and parents. Vascular lesions of the upper lip-particularly when close to Cupid's bow-can become disfiguring and cause functional impairment. We propose a combined approach with intralesional neodymium-YAG laser photocoagulation to avoid bleeding and to shrink the lesion before complete surgical removal. For defect closure, bilateral tissue-expanding vermillion myocutaneous flaps (Goldstein technique modified by Sawada) were used.

Morphea after Silicone Implants.

Dear Editor, Silicone is a hydrophobic polymer containing silicon. Silicon is an essential compound of soft tissue proteoglycans. Reports about morphea and other autoimmune connective tissue disorders in association with silicone implants have stimulated the discussion of a possible link between the two, such as immunological cross-reactivity of silicone and connective tissue components (1). A number of case reports suggested a possible link to adjuvant autoimmune syndrome (2), morphea of the breast (3-5), and systemic scleroderma (6-8), among others. One study measured tissue silicon levels in women with silicone breast implants with and without symptoms or signs and compared these data with women who had either a saline breast implant or no augmentation at all. The authors detected higher levels of silicon in capsular tissue of patients with silicone implants, independent of the presence of any symptoms or signs (9,10). The conclusion was that there is no evidence of an association between silicone implants and autoimmune connective tissue disorders. Three other clinical trials investigating the role of silicone implants and induction of autoimmune connective tissue disorders also failed to find an association between the two (11-13). We report the case of a 32-year-old female patient who developed morphea of the breasts after silicone implants for augmentation after risk-reducing mastectomy for Cowden syndrome. She presented with pronounced capsule fibrosis of the implants. With a delay of several years, an ill-defined slightly hyperpigmented area developed on the breasts and ventral chest (Figure 1). The lesion was analyzed by dermoscopy (Figure 2), which found mild erythema, reduced vessels, and white areas (ill-defined dull white globules, fibrotic beams). A skin biopsy was taken. Histopathological analysis showed a normal epidermal layer, minor papillary edema, and some vascular ectasias in the papillary dermis and upper corium (Figure 3). There was mild perivascular inflammatory infiltrate of the deep dermal vascular plexus, composed of lymphocytes and monocytes with some plasma cells (Figure 4). Elastic fibers seemed unaffected (Figure 5). The diagnosis of an early morphea of the edematous-inflammatory stage was established. Treatment with topical corticosteroids and UVB-311 nm irradiation was recommended. Morphea of the breasts is an uncommon disorder. It may occur after radiotherapy of breast cancer, after silicone augmentation, or without any known cause (14-16). A meta-analysis found an increased risk for morphea/scleroderma, with a relative risk between 1.30 to 2.13 and an odds ratio for case control studies of 1.68 (17). The US FDA Breast Implant Approval Study evaluated almost 100,000 female patients with breast implants. An increased risk of Sjögren's syndrome, scleroderma, and rheumatoid arthritis was reported (18). We could not find any reference of an association between capsular fibrosis and morphea of the breast, although both represent fibrotic disorders. In conclusion, it seems possible that there is a link between morphea of the breast and chest as described herein and silicone breast implants, which is supported by epidemiological studies. However, a direct causal relationship is hard to demonstrate with a single case.

Rosacea in children: a review.

Rosacea is a facial inflammatory disorder that shows an increasing incidence with age. While rosacea is common > 60 years of age, pediatric rosacea is uncommon. Diagnostic criteria are based on clinical symptoms. Laboratory investigations and histopathology are only needed to exclude other differential diagnoses. There are several subtypes such as erythemato-telangiectatic, papulo-pustular, periorificial, and granulomatous variants. In contrast to adult rosacea, phymatous subtypes do not belong to pediatric rosacea. A special subtype seen in infants and children is an idiopathic facial aseptic granuloma. Genetic and environmental factors contribute to its pathogenesis. Treatment options are in analogy to adult rosacea classified into topical and systemic drugs. In the case of oral tetracyclines, discoloration of teeth and impairment of enamel are possible adverse events. CONCLUSION: Pediatric rosacea belongs to the rosacea spectrum but has peculiarities compared to the adult subtype. WHAT IS KNOWN: • Rosacea is a chronic inflammatory disorder different from acne. • Rosacea gets more common with advanced age. WHAT IS NEW: • Pediatric rosacea is an uncommon subtype with peculiar clinical presentation. • Demodicosis is very rare in immunocompetent children.

Adult acne versus adolescent acne: a narrative review with a focus on epidemiology to treatment

Abstract Acne vulgaris is one of the most common chronic inflammatory diseases and is characterized by papules, pustules, comedones, and nodules. Although adolescence is the preferential age group, acne may affect various age groups. Acne shares different properties in adults and adolescents. These differences extend from epidemiology to treatments. Increased awareness of these two subtypes will allow for better management of the disease. In this review, the authors examined all aspects of acne in adults and adolescents under the light of current literature.

Melanoma surgery-An update.

Cutaneous melanoma is the major cause of mortality from all skin cancers. The treatment has been revolutionized in recent years by introduction of immunotherapy and targeted therapy for melanoma patients Stages III and IV. Therefore, the role of surgery in melanoma treatment needs to be redefined. In this narrative review, we will focus on surgery for diagnosis, treatment of primary tumor, and metastases in the era of new and effective medical treatment options. Neoadjuvant therapy is currently investigated in several trials. Surgery for treatment-resistant metastases is another field of interest. In conclusion, surgery remains a cornerstone for diagnosis and treatment of primary melanoma. Therapeutic lymphadenectomy has lost importance while surgery in sentinel lymph node diagnostics and metastasectomy are useful in a tailored individual approach of combined treatments. There is a trend to less invasive surgical procedures.

Prognosis of Patients With Primary Melanoma Stage I and II According to American Joint Committee on Cancer Version 8 Validated in Two Independent Cohorts: Implications for Adjuvant Treatment.

PURPOSE: The first randomized trial of adjuvant treatment with checkpoint inhibitor in stage II melanoma reported a significant reduction in risk of tumor recurrence. This study evaluates two independent data sets to further document survival probabilities for patients with primary stage I and II melanoma. PATIENTS AND METHODS: The Central Malignant Melanoma Registry (CMMR) in Germany evaluated 17,544 patients with a primary diagnosis of stage I and II melanoma from 2000 to 2015. The exploratory cohort consisted of 6,725 patients from the Center for Dermato-Oncology at the University of Tübingen, and the confirmatory cohort consisted of 10,819 patients from 11 other German centers. Survival outcomes were compared with published American Joint Committee on Cancer version 8 (AJCCv8) stage I and II survival data. RESULTS: For the two CMMR cohorts in stage IA compared with the AJCCv8 cohort, melanoma-specific survival rates at 10 years were 95.1%-95.6% versus 98%; 89.7%-90.9% versus 94% in stage IB; 80.7%-83.1% versus 88% in stage IIA; 72.0%-79.9% versus 82% in stage IIB; and 57.6%-64.7% versus 75% in stage IIC, respectively. Recurrence rates were approximately twice as high as melanoma-specific mortality rates in stages IA-IIA. CONCLUSION: The melanoma-specific survival rates in the two CMMR cohorts across stages I and II are less favorable than published in AJCCv8. This has important implications for the consideration of adjuvant treatment in this population.

SARS-CoV-2 vaccination-induced cutaneous vasculitis: Report of two new cases and literature review.

Currently the most powerful tool in combating the COVID-19 pandemic is vaccination against SARS-CoV-2. A growing percentage of the world's population is being vaccinated. Various vaccines are worldwide on the market. Several adverse reactions have been reported as a part of post-marketing surveillance of COVID-19 vaccines. Among the possible adverse events, cutaneous vasculitis has occasionally been reported. We present a narrative review on cutaneous vasculitis related to COVID-19-vaccination to summarize clinical findings, histopathology, treatment and outcome. We searched for "COVID vaccine", "COVID vaccination" AND "cutaneous vasculitis" in PUBMED. Articles in English have been selected, from inception to December 2021, and analyzed for patient's characteristics, type of vaccine, time of appearance of cutaneous vasculitis and clinico-histopathologic type. Treatment and outcome have also been considered in this narrative review. Two new unpublished cases of ours were added. Cutaneous vasculitis is a rare adverse event to COVID-19 vaccination. It has been observed with mRNA and adenovirus-vector vaccines. IgA vasculitis, lymphocytic and ANCA-associated vasculitis, leukocytoclastic and urticarial vasculitis have been reported. This adverse event can occur after first or second shot. Most cases run a mild to moderate course. Cornerstone of medical treatment are systemic corticosteroids. Complete remission could be achieved in most patients. Vasculitis may not be considered as a contraindication of vaccination, being uncommonly reported and shows a favorable prognosis. The benefit of the vaccination remains high especially for immunocompromised patients. COVID-vaccine induced vasculitis is important in the differential diagnosis of purpuric and vasculitis disorders.

Herpes zoster: A Review of Clinical Manifestations and Management.

The Varicella-zoster virus (VZV) or human herpes virus 3 is a neurotropic human alpha herpes virus responsible for chickenpox/varicella and shingles/Herpes zoster (HZ). This review will focus on HZ. Since HZ is secondary to varicella, its incidence increases with age. In children and youngsters, HZ is rare and associated to metabolic and neoplastic disorders. In adults, advanced age, distress, other infections (such as AIDS or COVID-19), and immunosuppression are the most common risk factors. HZ reactivation has recently been observed after COVID-19 vaccination. The disease shows different clinical stages of variable clinical manifestations. Some of the manifestations bear a higher risk of complications. Among the possible complications, postherpetic neuralgia, a chronic pain disease, is one of the most frequent. HZ vasculitis is associated with morbidity and mortality. Renal and gastrointestinal complications have been reported. The cornerstone of treatment is early intervention with acyclovir or brivudine. Second-line treatments are available. Pain management is essential. For (secondary) prophylaxis, currently two HZV vaccines are available for healthy older adults, a live attenuated VZV vaccine and a recombinant adjuvanted VZV glycoprotein E subunit vaccine. The latter allows vaccination also in severely immunosuppressed patients. This review focuses on manifestations of HZ and its management. Although several articles have been published on HZ, the literature continues to evolve, especially in regard to patients with comorbidities and immunocompromised patients. VZV reactivation has also emerged as an important point of discussion during the COVID-19 pandemic, especially after vaccination. The objective of this review is to discuss current updates related to clinical presentations, complications, and management of HZ.

Cutaneous and hypersensitivity reactions associated with COVID-19 vaccination-a narrative review.

Vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV­2) has become a major tool in the battle against the coronavirus disease 2019 (COVID-19) pandemic. Numerous products have been developed and more are to come. Vaccination success varies greatly between different countries. There are a number of different vaccine types, such as mRNA, DNA vaccines, adenovirus vector vaccines, and full-length spike protein nanoparticles with a special matrix. The different types may also cause a different spectrum of adverse events. With mass vaccination, post-marketing surveillance for product safety becomes increasingly important. In this review, we discuss possible hypersensitivity and cutaneous adverse events related to SARS-CoV­2 vaccination-from local reactions like COVID arm to systemic and severe reactions like anaphylaxis. Vaccination may also induce or exacerbate preexisting disorders such as herpes zoster infection. This review should provide information to tailor, whenever possible, vaccination to patients' needs. It is a contribution to patient safety as well. There is general consensus that the benefits of SARS-CoV­2 vaccination currently outweigh the risks of possible adverse events.

Histopathological progression of hidradenitis suppurativa/acne inversa : A morphological study with a closer look on the early changes of the folliculosebaceous apocrine apparatus.

BACKGROUND: It is generally acknowledged that the first morphological change of hidradenitis suppurativa/acne inversa (HS/AI) consists of infundibular plugging of the folliculosebaceous apocrine apparatus, which is followed by acute and chronic inflammation, cysts with sinus formation, and fibrosis. Alternatively, it has been hypothesized that HS/AI is primarily a neutrophilic autoinflammatory disease and that the follicular plugging typical of this disease is secondary to inflammation. OBJECTIVE: To review the sequence of the changes that mark the disease development, we have performed a histopathologic study on the surgical material from a series of axillary and inguinal/perineal cases. METHODS: The histologic material from surgery on Hurley's second and third stage HS/AI was retrieved and collected with the patients' clinical images. The virtually uninvolved skin peripheral to the lesions was studied together with the main inflammatory foci on vertical sections stained with hematoxylin-eosin and immunohistochemistry for the follicle sheaths. RESULTS: The fully developed lesions showed acute and chronic, suppurative and granulomatous inflammation overlapping fibrosis, cysts, and sinuses. Instead, the skin adjacent to florid inflammation showed plugging and dysmorphic alterations of the hair follicles associated with immunopathological changes of the inner root sheath keratin expression. CONCLUSION: Our observations coincide with the classical pathological studies on the progressive changes of HS/AI; however, in our specimens, the virtually normal skin peripheral to the fully developed lesions show seemingly initial follicular changes that suggest development error. This finding would support the hypothesis of combined mutation-induced epithelial differentiative defects and immunological derangement in HS/AI pathogenesis.

Laser in the Treatment of Granulomas on the Nose Produced by Polymethylmethacrylate: A Case Series.

BACKGROUND: The search for aesthetic non-surgical procedures is growing. The use of polymethylmethacrylate (PMMA) as a filling material in the nose represents one of the many options among these aesthetic procedures. Its use, however, can lead to complications. The treatment of these complications is often challenging. METHODS: We performed a retrospective clinical analysis of the medical records of patients undergoing treatment of PMMA granulomas of the nose at a private clinic from January, 2015, to January, 2021. A short-pulsed neodymium-YAG (Nd:YAG) laser was applied intranasally or directly by cutaneous incision in the granulomas. Laser-tissue interaction heats the alloplastic material, fragments the product and creates cleavage paths, thereby facilitating the removal of PMMA, either by intercartilaginous removal or aspiration. RESULTS: Twenty-seven patients were included in the study. All had a history of PMMA injection in the nose. All patients were treated with an intralesional pulsed 1064nm Nd:YAG laser. The material removed after laser-tissue interaction was sent for histopathological examination; this showed the presence of microparticles of exogenous material compatible with PMMA. The partial removal of the alloplastic material was shown to be effective in all cases. One patient developed a small blister in the nasal dorsum. Follow-up ranged from six to 47 months. CONCLUSIONS: The use of intralesional Nd:YAG laser for the treatment of PMMA granulomas on the nose proved to be an effective and safe procedure with improvement of nasal shape, without compromising respiratory function. This technical option represents yet another alternative in the treatment of PMMA granuloma complications. J Drugs Dermatol. 2021;20(11): 1161-1166. doi:10.36849/JDD.6550.

Deoxycholic Acid (ATX-101) for Fat Reduction.

Excess, unwanted fat in submental and other body areas has been a focus of new modalities in aesthetics. Invasive and, more recently, non-invasive modalities for removal of unwanted fat have been on an increase. ATX-101 (deoxycholic acid injection) is the only injectable drug approved in the United States and Canada for reduction of moderate or severe submental fat in adults, with ongoing trials testing its efficacy in body contouring and lipomas. It has proven efficacy in submental fat reduction with a good safety profile. This article reviews the pharmacology, mechanism of action, clinical effects and adverse effects of ATX-101. It emphasizes on careful patient selection and advises on appropriate volume administration, number of treatments, and injection technique. The literature research includes peer-reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) till December 2019 and reference lists of respective articles. Only articles published in English language were included. J Drugs Dermatol. 2021;20(11):1169-1173. doi:10.36849/JDD.3936.

Immune Checkpoint Inhibitor-Related Adverse Effects and 18F-FDG PET/CT Findings.

Immune checkpoint inhibitor (ICI) treatments activate T cells against tumors. Activated T cells attack not only the tumor but also healthy cells, causing an autoimmune reaction in various tissues. These immune-related adverse effects (IRAEs) cause 18F-FDG uptake in various tissues due to inflammation. It is important to recognize and report these findings on 18F-FDG PET/CT studies. 18F-FDG PET helps to determine the presence, location, and severity of IRAEs. In severe cases, ICI treatments are interrupted or suspended and antiinflammatory treatments are started. 18F-FDG uptake due to IRAEs may mimic metastases or disease progression. Their presence may also help in predicting response to treatment and have prognostic implications. In this review article, we provide basic information about ICI treatments, IRAEs, and 18F-FDG PET/CT findings.

Correction of tear trough deformity by hyaluronic acid soft tissue filler placement inferior to the lateral orbital thickening.

Tear trough deformities can be a sign of facial aging and exert a negative impact in facial attractiveness. Surgical techniques and adipose tissue transfer have been used to improve tear trough deformity. In recent years, minimal invasive procedures such as soft tissue filler injections became more popular. We report a retrospective evaluation of 45 Caucasian female patients ≥40 years (mean age of [58.8 ± 8.9] years). Severity of tear trough was classified according to Hirmand: 3 as grade I, 28 as grade II, and 14 grade III tear trough deformities. We used a monophasic hyaluronic acid, low G prime filler placed inferior to the lateral orbital thickening. On average, 0.4 ml of hyaluronic acid (HA) filler were injected per side. The improvement was I grade 29 patients and II grades in 16 patients. The improvement lasted (10.8 ± 2.3) months. No severe adverse events were noted. Vascular danger zones can be avoided.

Cutaneous squamous cell carcinoma of head and neck region: A single center analysis of 1296 tumors with clinical characteristics, comorbidities, treatment, and sun-protection behavior.

Cutaneous squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer among Caucasians. We analyzed our data on tumors been treated between 2006 and 2016 at the Skin Cancer Center of an academic teaching hospital. Thousand hundred and ninety-four patients with 1296 SCC have been identified including 804 males (67.3%) and 390 females (32.7%). The mean age among females was significantly higher with (83.9 ± 7.9) years compared with males ([79.3 ± 8.1] years; P < .001). The most common tumor localizations were outer ears (n = 227, 17.5%), scalp (216, 16.7%), and forehead (215, 16.6%). The majority of tumors was stage I. 31.9% of patients had previous SCC or Bowen's cancer, 29.1% had actinic keratoses. Major non-dermatological comorbidities were cardiovascular diseases and diabetes. SCC were treated by delayed Mohs surgery. First Mohs procedure resulted in R0 status in 83.9%. Most cases with R1 resection were located on nose and eyelids. For a subpopulation of patients (n = 105), a structured questionnaire study evaluated changes in sun protection behavior after skin cancer. After the confirmed diagnosis of a cutaneous SCC concerns about harm to the skin by intense sunlight was reported by 78.4% (76) of participants, with 92.0% among females versus 73.6% among males. Eighty percent of females and 76.8% of males wanted to care more about sun-protection in the future, spend less time 84.0% (females) and 72.5% (males) in the sun, and adapt their leisure activities for a better sun protection in 92.0% (females) and 81.9% (males). Secondary prevention in males needs improvement.

Treatment Update of Port-Wine Stain: A Narrative Review.

BACKGROUND: Port-wine stain (PWS) is a congenital vascular malformation affecting 0.3–0.5% of normal population. These characteristic lesions arise due to the interplay of vascular, neural, and genetic factors. Treatment options include lasers, cosmetic tattooing, electrotherapy, cryosurgery, derma-abrasion, and skin grafting; however, none of these treatment alternatives appears to be satisfactory and is unable to provide consistent, satisfactory responses or even complete cures. Currently, laser is the treatment of choice, as it is comparatively safe and more effective than other procedures. The most commonly used modality is pulsed dye laser (PDL). The literature research includes peer-reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) to January 2020 and reference lists of respective articles. Only articles published in English language were included. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5005.

Time to Change Theory; Medical Leech from a Molecular Medicine Perspective Leech Salivary Proteins Playing a Potential Role in Medicine.

Followed by developing modern medicine, leeches did not have extensive use as before; however, in the late 19th century, they were still used in most countries all over the world. Thus far, leeches were utilized in treating various diseases like skin disorders, arthritis, and cancer. In Egypt, using leeches for treatment dates back to early 1500 BC. A medical leech's salivary glands involve over 100 bioactive proteins and the salivary gland secretion contains bacteriostatic, analgesic, and anticoagulation influences; with resolving activity, it causes microcirculation disorders elimination, restoring the hurt vascular permeability of organs and tissues, removing hypoxia, decreasing blood pressure and detoxifying the organism by antioxidant paths. The current work reviews the innovative treatment with medical leech, especially proteins in leech saliva extraction (LSE) with high potential in medicine. The virtue of salivary gland secretions which are proteinaceous enzymes, leech acts on various diseases such as venous congestion in reconstructive and plastic surgery, osteoarthritis, cardiovascular diseases caused by blood coagulation disorders, pain management, priapism, macroglossia, cancer complications, wounds and many other. To confirm the potential therapeutic impacts of leech treatment, more studies are required in more extensive areas with more exact methodologies.