Examining treatment strategies for xanthelasma palpebrarum: a comprehensive literature review of contemporary modalities.

Xanthelasma palpebrarum (XP) is the predominant form of cutaneous xanthoma, as it accounts for greater than 95% of cases. It is characterized by the presence of foam cell clusters containing a large amount of low-density lipoprotein (LDL), which are located in the connective tissue of skin, tendons, and fascia. XP lesions commonly present as distinctive yellow-orange macules, papules, or nodules, and are primarily on the upper eyelids as well as the inner canthus. Women are affected twice as often as men, with lesions typically emerging between the ages of 35 and 55. The pathophysiology of XP involves abnormal lipid metabolism and is often associated with hyperlipidemic states like Type II and IV hyperlipidemia, hypothyroidism, weight gain, and fatty diet. Despite the availability of various treatment methods, current XP management lacks standardization, particularly due to limited comparative research. To address this gap, we conducted an extensive literature review of 45 studies published between 2012 to 2023, which provides an updated overview of current XP treatment modalities. This comprehensive analysis will inform researchers and clinicians on the evolving landscape of XP management.

A Clinical and Dermatoscopic Perspective of the Efficacy and Safety of Erbium: YAG Laser Ablation Versus 50% Trichloroacetic Acid for the Management of Xanthelasma Palpebrarum.

Xanthelasma palpebrarum (XP) is a benign cosmetic condition. Although the role of CO2 laser is well described, there are only a few studies on Erbium: YAG in XP. Similarly, trichloroacetic acid (TCA) is commonly used in XP. However, there are only a few studies comparing these modalities in the treatment of XP. Aim: To evaluate the effectiveness and safety of Erbium: YAG laser and 50% TCA in the treatment of XP with the role of dermoscope in the evaluation of lesions. Materials and Methods: A total of 20 subjects were randomly allocated into two groups: group A (TCA) and group B (laser). All patients were subcategorized into three grades viz. I (mild), II (moderate), and III (severe) using a self-devised scoring system. Results: About 25% and 70% of patients achieved complete clearance in groups A and B, respectively (P = 0.017). The rate of recurrence was 40% and 15% in groups A and B. Dyspigmentation and erythema were the most common side effects. Pretreatment dermoscopic evaluation of the lesion showed a network of brown streaks on a background of a yellowish structureless area and was used to assess the area and margins of the lesion where the adipose tissue was found during the procedure and serial assessment of the lesion.

Genetic insight into putative causes of xanthelasma palpebrarum: a Mendelian randomization study.

Xanthelasma palpebrarum (XP) is the most common form of cutaneous xanthoma, with a prevalence of 1.1%~4.4% in the population. However, the cause of XP remains largely unknown. In the present study, we used Mendelian randomization to assess the genetic association between plasma lipids, metabolic traits, and circulating protein with XP, leveraging summary statistics from large genome-wide association studies (GWAS). Genetically predicted plasma cholesterol and LDL-C, but not HDL-C or triglyceride, were significantly associated with XP. Metabolic traits, including BMI, fasting glucose, type 2 diabetes, systolic and diastolic blood pressure, were not significantly associated with XP. Furthermore, we found genetically predicted 12 circulating proteins were associated with XP, including FN1, NTM, FCN2, GOLM1, ICAM5, PDE5A, C5, CLEC11A, CXCL1, CCL2, CCL11, CCL13. In conclusion, this study identified plasma cholesterol, LDL-C, and 12 circulating proteins to be putative causal factors for XP, highlighting the role of plasma cholesterol and inflammatory response in XP development.

Complete Blood Cell Count-Derived Inflammation Biomarkers in Patients with Xanthelasma Palpebrarum.

Objectives: Xanthelasma palpebrarum (XP) is the most common type of cutaneous xanthoma, characterized by yellowish cutaneous plaques commonly located near the medial canthus of the eyelid. Although dyslipidemia significantly contributes to its development, inflammation is also believed to be another element in the pathogenesis, especially in normolipidemic patients. Recently, cell counts derived from complete blood counts have been identified as indicators of systemic inflammatory conditions and have also been under discussion concerning their relevance to ocular diseases. This study aimed to assess inflammation indices derived from complete blood cell counts (CBC) in XP patients with normal lipid levels. Methods: Patients who had been referred to the oculoplasty department with the diagnosis of XP between January 2020 and January 2023 and age-matched control subjects were retrospectively reviewed. Patients who had abnormal lipid profiles and systemic diseases such as diabetes mellitus, hypertension, malignancy, cardiovascular diseases, systemic infections, and inflammatory diseases were not included in the study. CBC parameters were analyzed and compared between the groups. Results: The study comprised 27 normolipidemic patients with XP and 27 age-matched healthy individuals as the control group. There were no statistically significant differences between the two groups in terms of age (p=0.143). The mean hemoglobin, neutrophil, monocyte, lymphocyte, platelet, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, and aggregate index of systemic inflammation values were higher in the patient group, but the differences were not statistically significant (p>0.05). The mean red cell distribution width and platelet-to-lymphocyte ratio appeared to be lower in the patient group compared to the control group; however, no significant differences were observed between the two groups (p=0.272, p=0.387, respectively). Conclusion: This study might offer insights into the pathogenesis of XP, yet numerous questions remain unanswered, awaiting further investigation in future studies.

Widespread xanthomas regression by personalized lipid lowering therapy in heterozygous familial hypercholesterolemia / Regresión generalizada de xantomas mediante terapia hipolipemiante personalizada en hipercolesterolemia familiar heterocigótica

“The lower, the better” is the recommended approach in the management of high LDL cholesterol. Unfortunately, this does not always achieve as in the case of a 69-year-old woman referred to our Institute for her lipid profile (LDL cholesterol 412mg/dl), bilateral xanthelasma and cutaneous xanthomas. With a maximized and personalized lipid-lowering therapies (rosuvastatin, ezetimibe, PCSK9i and lipoprotein apheresis), after only six months, the patient showed an impressive regression in her cutaneous xanthomas. (AU)

«Cuanto más bajo, mejor» es el enfoque recomendado en el tratamiento del colesterol LDL alto. Lamentablemente esto no siempre se logra como en el caso de una mujer de 69 años remitida a nuestro Instituto por su perfil lipídico (colesterol LDL 412 mg/dL), xantelasma bilateral y xantomas cutáneos. Con terapias hipolipemiantes maximizadas y personalizadas (rosuvastatina, ezetimiba, iPCSK9 y aféresis de lipoproteínas), después de solo seis meses, la paciente mostró una regresión impresionante en sus xantomas cutáneos. (AU)

Widespread xanthomas regression by personalized lipid lowering therapy in heterozygous familial hypercholesterolemia.

"The lower, the better" is the recommended approach in the management of high LDL cholesterol. Unfortunately, this does not always achieve as in the case of a 69-year-old woman referred to our Institute for her lipid profile (LDL cholesterol 412mg/dl), bilateral xanthelasma and cutaneous xanthomas. With a maximized and personalized lipid-lowering therapies (rosuvastatin, ezetimibe, PCSK9i and lipoprotein apheresis), after only six months, the patient showed an impressive regression in her cutaneous xanthomas.

Efficacy and Safety of Erbium-YAG Laser Ablation Therapy in Superficial Dermatoses: The Workhorse of Dermatology.

Background: Erbium-YAG laser has been the working horse in dermatology for years. Surprisingly, data on the efficacy and adverse effects of this novel resurfacing and ablative technique of erbium-YAG laser for superficial dermatoses in Indian skin is limited. Aim and Objective: To evaluate the efficacy and safety profile of erbium-YAG laser ablation in superficial cutaneous lesions. Materials and Methods: Two hundred and fifty patients of various superficial dermatoses, treatable by erbium-YAG laser, were recruited in the study. All the patients were subjected to erbium-YAG laser sessions. The number of laser sessions, fluence, frequency and other parameters were individualized as per the respective dermatosis. The clinical response was evaluated as grade 4 (100% lesion clearance), grade 3 (75-99%), grade 2 (50-75%) or grade 1 (<50%). Results: The overall mean age of our study group was 37.70 years. In our study, 52.38% cases of verruca plana, 36.84% cases of seborrheic keratosis, 56.4% cases of xanthelasma palpebrarum, 22% cases of acquired melanocytic nevus, 23.8% cases of plantar wart and 40% cases of sebaceous hyperplasia showed complete clearance. The most common adverse effect was post-laser erythema in 50.4% of cases, followed by pain in 36.8%. Besides this, scarring and dyspigmentation were observed in 11.6% and 12% of cases, respectively. The rate of recurrence on 3 months follow-up was 9 (23.07%) cases in xanthelasma palpebrarum, 11 (28.9%) cases in seborrheic keratosis, 10 (23.8%) cases in verruca plana and 9 (42.8%) cases in plantar warts. Conclusion: This study suggested that erbium-YAG ablation achieved good results for superficial lesions like verruca plana, seborrheic keratosis, xanthelasma palpebrarum, plantar wart, sebaceous hyperplasia and acquired melanocytic nevus. Thus, Er: YAG laser can offer a one-step procedure with better cosmetic results and a lesser rate of recurrence.

Digital Patient Education on Xanthelasma Palpebrarum: A Content Analysis.

Patient education has been transformed using digital media and online repositories which disseminate information with greater efficiency. In dermatology, this transformation has allowed for patients to gain education on common cutaneous conditions and improve health literacy. Xanthelasma palpebrarum is one of the most common cutaneous conditions, yet there is a poor understanding of how digital materials affect health literacy on this condition. Our study aimed to address this paucity of literature utilizing Brief DISCERN, Rothwell's Classification of Questions, and six readability calculations. The findings of this study indicate a poor-quality profile (Brief DISCERN < 16) regarding digital materials and readability scores which do not meet grade-level recommendations in the United States. This indicates a need to improve the current body of educational materials used by clinicians for diagnosing and managing xanthelasma palpebrarum.

Clinical and dermoscopic assessment of ablative carbon dioxide laser versus intradermal heparin sodium in xanthelasma.

BACKGROUND: Ablative carbon dioxide (CO2 ) laser is still a cornerstone in the management of xanthelasma. However, post-laser complications such as post-inflammatory hyperpigmentation or scarring have to be considered. Heparin sodium was recently suggested as an effective therapeutic modality for xanthelasma. OBJECTIVE: The aim of this work was to compare the therapeutic value of ablative CO2 laser versus intradermal heparin sodium in xanthelasma. METHODS: This study was piloted on 30 xanthelasma patients, whose lesions were randomly categorized into two groups. Group A was managed with CO2 laser ablation (2 sessions scheduled every 4 weeks), whereas Group B was managed with intradermal heparin sodium injections (10 sessions scheduled every week). Pre- and post-treatments evaluations were done both clinically and dermoscopically. RESULTS: Significant reduction of xanthelasma lesions was reported in response to both therapeutic interventions. However, the ablative CO2 laser was more significantly effective than intradermal heparin sodium. Interestingly, intradermal injection of heparin sodium was nearly as effective as ablative CO2 laser in early (<2 years duration) grade I and II xanthelasma, with a lower incidence of post-therapy side effects. CONCLUSIONS: Intradermal injection of heparin sodium could be suggested as a safe and cost-effective therapeutic technique for early mild grade I and II xanthelasma. Moreover, it could be recommended as a pre-operative management of grade III and IV xanthelasma to reduce the lesions to be easily ablated with CO2 laser.

Gastric xanthelasma is a warning sign for Helicobacter pylori infection, atrophic gastritis, and intestinal metaplasia.

Background: Contradictory evidence suggested gastric xanthelasma (GX) was associated with some upper gastrointestinal (GI) diseases. Additionally, no research has been performed on the relationship between esophageal/duodenal xanthelasma and upper GI diseases. Methods: Individuals who underwent esophagogastroduodenoscopy at Tongji Hospital, Tongji Medical College, participated in this retrospective study. This study evaluated whether the risk of GX or esophageal/duodenal xanthelasma was influenced by the following gastroesophageal diseases: superficial gastritis, gastric polyp, bile reflux, peptic ulcer, reflux esophagitis, Barrett's esophagus, esophageal cancer, atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia, gastric cancer, and Helicobacter pylori (H. pylori) infection. Furthermore, subgroup analysis was conducted to establish the relationship between the number of GX and upper GI diseases. Results: Of the 69,071 subjects reviewed, 1,220 (1.77%) had GX, and 54 (0.08%) had esophageal/duodenal xanthelasma. There was no difference in the prevalence of upper GI diseases between patients with and without esophageal/duodenal xanthelasma. Nevertheless, compared with non-xanthelasma patients, GX patients had a greater proportion of AG, IM, dysplasia, gastric cancer, and H. pylori infection and a lower incidence of superficial gastritis (p < 0.05). The multivariate logistic regression analysis indicated AG (OR = 1.83, 95%CI: 1.56-2.16), IM (OR = 2.42, 95%CI: 2.41-2.85), and H. pylori infection (OR = 1.32, 95%CI: 1.17-1.50) were independent risk factors for GX. In addition, patients with multiple GXs had a higher rate of AG and IM than those with single GX. Conclusion: Esophageal/duodenal xanthelasma may not be associated with upper GI diseases, and further research is needed to support this hypothesis. Notably, GX, especially multiple GXs, may be a more easily detected warning sign of AG, IM, or H. pylori infection.

Possible roles of human mast cells in the formation of xanthelasma palpebrarum.

Cutaneous xanthoma consist of foam cells that originate from monocytes or macrophages and accumulate in perivascular areas of the skin. The main component of these cells is oxidized low-density lipoprotein (oxLDL). In this study, we show that mast cells surround the accumulated foam cells, suggesting their involvement in xanthoma formation. Coculture of THP-1 or U937 monocytes with the human mast cell line LUVA upregulated their uptake of oxLDL. Positive staining for intracellular cell adhesion molecule-1 (ICAM-1) at the borders between mast cells and foam cells was seen in pathological specimens of the most common cutaneous xanthoma, xanthelasma palpebrarum, and in cocultures. In the latter, ICAM1 messenger RNA levels were upregulated. The administration of anti-ICAM-1 blocking antibody inhibited the increase in oxLDL uptake by THP-1 or U937 monocytes cocultured with LUVA. Taken together, these results suggest a role for mast cells in the formation of xanthelasma palpebrarum and the involvement of ICAM-1 in this process.

[Diagnosis and treatment of benign eyelid tumors]. / Diagnose und Therapie der benignen Lidtumoren.

BACKGROUND: Benign tumors of the eyelids are frequent entities. They are often cause for cosmetic concern or can lead to irritation of the ocular surface. The differentiation from premalignant or malignant eyelid tumors is particularly important. In most cases this can be done clinically; however, in some cases histological evaluation is warranted. OBJECTIVE: The aim of this article is to characterize the most important benign tumors of the eyelid and to ascertain when a histological examination is necessary. Furthermore, fundamental treatment procedures are discussed. METHODS: This narrative review was prepared based on a selective literature search. The characteristics of some eyelid tumors are underlined with illustrations from clinical cases. RESULTS: Most benign eyelid tumors are treated because of cosmetic or functional concerns. Some of them, including actinic keratosis, keratoacanthoma, cutaneous horn, trichofolliculoma, resemble malignant lid tumors or precancerous lesions and are thus excised in oder to obtain a diagnosis. Dermoid cysts can cause complications and congenital melanocytic naevi can exhibit malignant transformation and may need treatment. Inflammatory tumors can be treated conservatively in most cases but might require surgery in certain cases. Systemic associations exist with some of the benign lid tumors and should not be overlooked as they can be crucial for overall patient morbidity. CONCLUSION: Benign tumors of the eyelids are frequent and can be found at any age depending on the diagnosis. This article describes the lesions most commonly encountered in the clinical routine and helps at making a plan for further management.

Study on the correlation between xanthelasma palpebrarum and the genetic factor of hypercholesterolemia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the correlation between xanthelasma palpebrarum(XP)and the genetic factor of hypercholesterolemia and provide a basis for the elucidation of the pathogenesis of xanthelasma palpebrarum.METHODS: A total of 29 patients with XP who treated in the ophthalmology department of Foshan Sanshui District People's Hospital from November 2019 to January 2021 were selected. Peripheral blood was drawn, and the Next Generation Sequencing(NGS)technology was used to detect the genetic mutations of patients, while blood lipids of XP patients were analyzed.RESULTS: Gene mutations were detected in 21 patients with XP, among which 13 cases had hypercholesterolemia and 8 cases had normal cholesterol levels. Genes including STAP1, APOB, LDLRAP1, LDLR, PCSK9 and APOE mutated, and the types of gene mutation included 3-UTR mutation, in-frame deletion, missense mutation, 5-UTR mutation, synonymous mutation, intronic mutation, alternative splice variant, non coding transcript exon variant, and non coding transcript variant.CONCLUSION: There is a correlation between genetic factors of hypercholesterolemia and XP.

Effects of repair for defect after xanthelasma removal with a orbicularis oculi myocutaneous flap by converse shift grafting / 中华医学美学美容杂志

Objective:To explore the method and effect of blepharoplasty of upper eyelid combined with orbicularis oculi myocutaneous flap in repair of the canthus defect after excision of xanthelasma.Methods:According to the relaxation of the upper eyelid skin and the width of the xanthoma to be removed, the double eyelid line and the peeling line were designed individually, and the myocutaneous flap was removed to repair the inner canthus defect. After resection of the xanthelasma, the orbicularis oculi myocutaneous flap was transferred retrogradely to repair the defect, and then the upper eyelid plasty was performed.Results:During the follow-up of 3-12 months after operation, 13 cases (24 eyes) of the transferred flaps in the inner canthus survived well, the incision scars were hidden, and the double eyelids on both sides were naturally symmetrical.Conclusions:The method of upper eyelid plasty combined with the reverse transfer of orbicularis oculi myocutaneous flap provides more options for the treatment of defects after resection of xanthoma of the inner canthus. The flap survives well, improves the shape of the upper eyelid while completely removing the focus, and avoids complications such as postoperative deformation and obvious scars.

Metabolic syndrome and dyslipidemia in xanthelasma palpebrarum and associated risk-2 factors-A case-control study.

BACKGROUND: Xanthelasma palpebrarum (XP) primarily causes cosmetic disfigurement. However, systemic associations like metabolic syndrome (MetS) and dyslipidemia need consideration. OBJECTIVE: Determining the prevalence of MetS and dyslipidemia in XP patients and explore risk factors. METHODS: Our case-control study included 106 XP patients(cases) and 106 age-and-sex matched healthy controls. All subjects underwent detailed history taking, physical examination, and biochemical investigations. MetS and obesity were diagnosed by NCEP-ATP III criteria and modified BMI classification for Asian-Indians, respectively. RESULTS: The odds ratio (OR) and 95% CI for XP patients vs. non-XP controls were 1.6 (95% CI 0.8-3.2, p = 0.1) for MetS, 1.4 (95% CI 0.6-3.1, p = 0.4) for dyslipidemia and 0.2 (95% CI 0.07-0.4, p < 0.0001) for overweight/obesity. Extensive disease, DM, and low serum HDL-C were significantly associated with MetS in XP patients (vs. controls). Normal waist circumference (AOR 21.3, 95% CI 3.5-127.6, p = 0.0008), normal blood glucose (AOR 21.4, 95% CI 3.1-145.1, p = 0.002), and normal blood pressure (AOR 22.3, 95% CI 3.9-124.9, p = 0.0004) significantly reduced the risk of MetS, while bilateral ocular involvement (AOR 4.3, 95% CI 1.1-18.7, p = 0.04) significantly increased the risk of dyslipidemia in XP patients. CONCLUSION: Xanthelasma palpebrarum patients are more prone to develop MetS and dyslipidemia and need evaluation, despite being a primarily cosmetic concern. Extensive disease and bilateral ocular involvement are significant risk factors. Adequate counseling and healthy life-style measures are crucial to minimize systemic complications.

Esophageal xanthoma with nearby coexistent squamous cell carcinoma observed using magnifying endoscopy with narrow-band imaging.

We report the case of a 63-year-old man who underwent annual surveillance esophagogastroduodenoscopy, during which a small squamous cell carcinoma and a tiny yellowish granular lesion were found in the middle esophagus, slightly apart from each other. Magnifying endoscopy with narrow-band imaging of the yellowish granular lesion showed yellowish spots and blots scattered within an approximately 2-mm area. The larger spots appeared nodular and were overlaid with tortuous microvessels. Subsequently, both the lesions were excised en masse via endoscopic submucosal dissection, and the yellowish lesion was determined to be xanthoma. Histologically, an aggregated nest of foam cells surrounded by intrapapillary capillary vessels filled the intraepithelial papillae; the foam cells also extended inferiorly, below the rete ridges, and were sparsely distributed through the lamina propria mucosae. To our knowledge, the latter finding is the first to be described in literature, which leads us to postulate that the number of foam cells in the lamina propria mucosae may affect how thick and yellow a xanthoma appears on endoscopy. We believe that this case that presents a highly detailed comparison between endoscopic and histologic findings improves our understanding of the endoscopic appearance of esophageal xanthomas and may facilitate a precise diagnosis of this rare disease.

Ultrapulsed CO2 ablation in the treatment of xanthelasma palpebrarum: high satisfaction treatment with low recurrence.

Xanthelasma are localized accumulation of lipid deposits on the eyelids. Lesions are typically asymptomatic and treatment is often sought for cosmetic purposes. Unfortunately, there is paucity of strong evidence in the literature for the effective treatment of normolipidaemic xanthelasmas. Lasers have been used in the management of xanthelasma and in this article the experience with ultrapulsed CO2 laser is discussed with efficacy, complications and risk of recurrence explained.

Animal experimental research of intralesional bleomycin and pingyangmycin in the treatment of xanthoma.

BACKGROUND: Xanthelasma palpebrarum is a type of human xanthoma that occurs on the skin of human eyelids and is a benign skin lesion. Pingyangmycin (also known as bleomycin A5) is one of the 13 components of bleomycin. The aim of this study was to explore the efficacy of intralesional bleomycin and pingyangmycin in the treatment of xanthoma based on histopathological observations in animal experimental research. METHODS: An animal model of xanthoma was established by feeding rabbits with a high-cholesterol diet. Pingyangmycin and bleomycin interfered with the skin xanthoma of the animal model. Skin tissue specimens were stained with hematoxylin-eosin and oil red O to evaluate the effect of the intervention. RESULTS: A xanthoma animal model was established. Pingyangmycin and bleomycin could reduce the abnormal lipid deposition in the lesion area of the skin xanthoma of the animal, via a local injection. In addition, pingyangmycin was more effective than bleomycin in eliminating lipid deposition in rabbit skin xanthoma.

Disease modifying drugs in idiopathic sclerosing orbital inflammatory syndrome.

PURPOSE: Idiopathic sclerosing orbital inflammatory syndrome (ISOIS) is a rare, progressive and hard to control disease. There is a deep gap of evidence regarding application of disease-modifying drugs (DMD) regimen as a potentially effective treatment for orbital inflammatory diseases. We aimed to report the results of using DMDs and discuss the concept of applying this modality of treatment in patients with ISOIS. METHODS: This was a prospective interventional case series conducted in a tertiary university-based hospital. Biopsy proven patients with active ISOIS were included. Systematic criteria were developed to define and measure disease activity and monitor response to treatment. A DMD regimen including an anti-tumor necrosis factor alpha (anti-TNF alpha) agent plus azathioprine and low-dose corticosteroids were used. Comprehensive ophthalmic, orbital and systemic assessments were performed during each visit. RESULTS: Five eligible patients with primary ISOIS were included. Mean age was 34.20 (SD = 13.33, range 19-53) years. Three had unilateral and two had bilateral involvement. Four had diffuse orbital involvement pattern and progressive worsening of visual functions, reduced extraocular motility and proptosis. In one patient the disease was localized to extraocular muscle and lacrimal gland. Disease activity was decreased and stabilized after DMDs regimen in all patients. Mean follow up was 32.80 (SD = 30.80, range: 12-86) months. CONCLUSION: Biologic DMD (b-DMD) including anti-TNF alpha, corticosteroid and azathioprine were effective in decreasing disease activity and could change course of the disease. This study supports the concept of using b-DMD regimen in treatment of ISOIS.