Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(4):e2024241 1 The Prevalence and Clinical Significance of Skin Manifestations in Parkinson’s Disease Patients Ayşegül Yalçınkaya Iyidal1, Funda Erduran1, Yıldız Hayran1, Yeşim Sücüllü Karadağ2 1 Department of Dermatology, Ankara Bilkent City Hospital, Çankaya/Ankara, Türkiye 2 Department of Neurology, University of Health Sciences, Ankara Bilkent City Hospital, Çankaya/Ankara, Türkiye Key words: Parkinson’s disease, Dermatological manifestations, Seborrheic dermatitis, Xerosis, Hyperhidrosis Citation: Yalçınkaya Iyidal A, Erduran F, Hayran Y, Karadağ Sücüllü Y. The Prevalence and Clinical Significance of Skin Manifestations in Parkinson’s Disease Patients. Dermatol Pract Concept. 2024;14(4):e2024241. DOI: https://doi.org/10.5826/dpc.1404a241 Accepted: May 13, 2024; Published: October 2024 Copyright: ©2024 Yalçınkaya Iyidal et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Ayşegül Yalçınkaya Iyidal, MD, Dermatologist, Department of Dermatology, Ankara Bilkent City Hospital, Üniversiteler, 1604. Cd No:9, 06800, Çankaya/Ankara; Phone: 05052720042; E-mail: draysegulyalcinkayaiyidal@gmail.com Background: Parkinson’s disease (PD) is primarily characterized by motor symptoms, but non-motor symptoms, including skin manifestations, are increasingly recognized. These remain underexplored despite their potential impact on quality of life. Objectives: This study aimed to evaluate the prevalence and clinical features of skin findings in PD patients, with a focus on identifying potential pathogenetic links between dermatological conditions and PD. Methods: A total of 215 PD patients were included. Comprehensive dermatological examinations were performed, and demographic and clinical data were collected. Statistical analysis was conducted using SPSS 23.0, with significance set at P < 0.05. Results: Skin conditions were found in 92.1% of PD patients. Xerosis, seborrheic dermatitis, and hyperhidrosis were the most common findings. Pre-PD xerosis was associated with an earlier stage of PD (P = 0.001). Use of PD medications, such as levodopa/carbidopa/entacapone, was linked to a lower incidence of seborrheic dermatitis (P = 0.040). A significant correlation was also noted between rosacea and cherry angioma (P = 0.01). Conclusion: Dermatological conditions are prevalent in PD and may precede its motor symptoms. Skin assessments could aid early diagnosis and management of PD, highlighting the need for further research on their pathogenetic mechanisms. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2024;14(4):e2024241 Introduction Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the triad of resting tremor, bra- dykinesia, and rigidity. In patients with PD, mainly motor disorders are observed; however, non-motor symptoms can also be seen at all stages of the disease. The most common non-motor symptoms are pain, sweating, insomnia, depres- sion, and skin manifestations [1-5]. These symptoms may occur before the onset or during the course of PD. Recent studies suggest a close relationship between neurological symptoms and skin findings in PD [1,2,6,7]. These studies have reported a higher incidence of seborrheic dermatitis (SD), rosacea, and sweating dysfunction in patients with PD [1–10]. In this context, there is a need for further studies on the relationship between skin diseases and PD in order to elucidate the pathogenesis of these diseases. Nevertheless, skin problems associated with PD that worsen the quality of life of PD patients go unnoticed or are underestimated by both the patient and the doctor who follows the patient. Objectives In view of the foregoing, the objective of this study was to in- vestigate the prevalence and clinical features of skin findings in PD in order to reveal the relationships, if any, between the skin and the nervous system. Materials and Methods Study Population The population of this cross-sectional observational study consisted of patients who were followed up with PD diag- nosis in the Hospital Neurology Outpatient Clinic and for whom the Dermatology Outpatient Clinic was consulted be- tween March 2022 and March 2023. Demographic and Clinical Characteristics Patients’ demographic and clinical characteristics, including age, sex, known dermatological diseases, PD duration, PD stage according to Hoehn & Yahr staging system (stage 1: Unilateral involvement only, usually with minimal or no func- tional disability; stage 2: Bilateral or midline involvement, without impairment of balance; stage 3: Bilateral disease, mild to moderate disability with impaired postural reflexes; physical independence, stage 4: Severely disabling disease, ability to walk or stand unassisted, stage 5: Confinement to bed or wheelchair unless aided), additional chronic diseases, regularly used PD medications and other regularly used med- ications were recorded. Physical Examinations Whole-body skin, scalp, nail, and oral mucosa examinations were performed on all patients, and the resulting skin find- ings were noted. Pathology Investigations It was investigated whether these pathologies started before, after, or simultaneously with PD and whether they pro- gressed with PD. Ethical Approval The study protocol was approved by the Hospital Ethics Committee (Approval No: E1-22-2404). Statistical Analysis Statistical analyses of the collected data were conducted using the SPSS 23.0 (Statistical Product and Service Solutions for Windows, Version 23.0, IBM Corp., Armonk, NY, US, 2015) software package. Percentages and proportions were used to express categorical variables, and mean (standard deviation, SD) or median (interquartile range, IQR) values were used to express numerical variables. Categorical variables were ana- lyzed using the chi-square test, and numerical variables were analyzed using the student’s t-test or Mann-Whitney U test. Probability (p) statistics of < 0.05 were deemed to indicate statistical significance. Results Demographic and Clinical Characteristics of Patients The study sample consisted of 215 PD patients: 143 (66.5%) male and 72 (33.5%) female. The mean age of the sample was 65.15 ± 9.8 years. Of the PD patients followed at the neurology polyclinic and for whom dermatology outpatient clinic was consulted, skin diseases were detected in 16.3%, scalp disease in 5.1%, nail disorders in 2.8%, and no derma- tological problem was detected in 75.8%. Additionally, sys- temic disease was detected in 43.3% of the patients. Patients’ demographic and clinical characteristics are summarized in Table 1. Findings from Dermatological Examination Skin, scalp, nail, and oral mucosa findings obtained in der- matological examination revealed at least one skin disease in 92.1% of the patients, at least one scalp disease in 39.1%, Original Article | Dermatol Pract Concept. 2024;14(4):e2024241 3 Table 1. Demographic and Clinical Characteristics of Patients Participating in the Study. Sex Frequency (%) Female 33.5 Male 66.5 Age, average (SD) 65.15 (±9.8) Reason for Attending the Dermatology Polyclinic Frequency (%) Skin disease 16.3 Scalp disease 5.1 Nail disease 2.8 No complaint 75.8 PD duration median, years (IQR) 4 (2-7) PD stage Frequency (%) 1 17.2 2 51.6 3 20.1 4 8.8 5 2.3 PD Treatment Frequency (%) Levodopa+DK inhibitor 73 MAO B inhibitor 83.3 Non-ergot dopamine agonist 81.4 Levodopa+DK inhibitor +COMT inhibitor 25.1 Amantadine 21.4 Levodopa/Carbidopa Intestinal Gel 5.6 Deep Brain Stimulation (DBS-Brain Stimulator) 0.9 PD Treatment Duration median, years (IQR) 3 (1-6) Previously Known Dermatological Disease in the Patient Frequency (%) Yes 5.2 Seborrheic Dermatitis 3.3 Rosacea 1.4 Vitiligo 0.5 Duration median, years (IQR) 7 (5-15) No 94.8 Systemic Disease Frequency (%) Yes 43.3 No 56.7 The Three Most Common Systemic Diseases Frequency (%) Hypertension 29.3 Diabetes mellitus type 2 19.5 Hypothyroidism 3.8 Abbreviations used in this table include SD for standard deviation, IQR for interquartile range, PD for Parkinson’s disease, DK inhibitor for decarboxylase inhibitor, MAO B inhibitor for monoamine oxidase B inhibitor, COMT inhibitor for Catechol-O-methyltransferase inhibitor, and DBS for Deep Brain Stimulation. The percentages indicate the proportion of patients with each characteristic or treatment, and the median years (with IQR) reflect the duration of PD and PD treatment as well as the duration of previously known dermatological diseases, where applicable. 4 Original Article | Dermatol Pract Concept. 2024;14(4):e2024241 Table 2. Summary of Dermatological Examination of Skin, Scalp, Nail, and Oral Mucosa. Duration, median months (IQR) Appearance of Skin, Scalp, and Nail Mucosa Findings Freq % Before PD, Freq % with PD, Freq % After PD, Freq % Skin Findings Xerosis 60.9 60 (36-60) 57.3 29.7 13.0 Cherry angioma 45.1 60 (36-60) 79.3 18.6 2.1 Hyperhidrosis 37.2 48 (24-60) 56.2 26.3 17.5 Seborrheic dermatitis 27.4 48 (24-60) 66.1 28.8 5.1 Rosacea 27.4 48 (36-60) 55.9 37.3 6.8 Erythema intertrigo 16.3 4 (2-5) Xerotic eczema 13 60 (36-60) Tinea pedis 14.4 4 (2-6) Actinic keratosis 9.8 60 (36-60) Hand eczema 4.1 60 (36-60) Stasis dermatitis 2.3 24 (24-36) P versicolor 1.9 2 (2-5) Scalp Disease Seborrheic dermatitis 31.6 48 (24-60) 50.8 44.4 4.8 Actinic keratosis 11.6 36 (30-60) Folliculitis 4.7 12 (12-15) Nail Disease Tinea ungium 14.9 Longitudinal ridges 9.3 Terry’s nail 1.4 Subungual Hyperkeratosis 1.4 Muehrcke’s nails 0.9 Oral Mucosa Atrophic glossitis 0.9 Black tongue 0.5 This table presents the findings from dermatological examinations focusing on skin, scalp, nail, and oral mucosa conditions in Parkinson’s disease (PD) patients. “Freq %” indicates the percentage of patients exhibiting each condition. “Duration, median months (IQR)” provides the median duration of each condition in months, along with the interquartile range (IQR), reflecting variability among patients. “Before PD”, “With PD”, and “After PD” percentages denote the timing of onset of each condition relative to the diagnosis of PD. Conditions with- out specified percentages for “Before PD”, “with PD”, and “After PD” did not have sufficient data for these categories. “Tinea ungium”, “Longitudinal ridges”, “Terry’s nail”, “Subungual hyperkeratosis”, and “Muehrcke’s nails” under Nail Disease as well as “Atrophic glossitis” and “Black tongue” under Oral Mucosa are reported without specific frequency or timing related to PD due to the nature of these findings. nail disease in 27.4%, and oral mucosa disease in 1.4%. Skin, scalp, nail, and oral mucosa findings obtained in der- matological examination are summarized in Table 2. Association between Pre-PD Dermatological Conditions and PD Stage In patients with pre-PD xerosis, the PD stage was earlier (stage 1: 22.8%, stage 2: 54.3%, stage 3: 17.4%, stage 4: 4.1%, and stage 5: 1.4%) than in patients without pre-PD xe- rosis (stage 1: 7.2%, stage 2: 44.7%, stage 3: 34,1%, stage 4: 12.5%, and stage 5: 1.5%) (p=0.001) (Table 3). Dopalevo use was significantly lower in patients with pre-PD xerosis than in those without pre-PD xerosis (14.7% vs. 39.3%, P = 0.028). The rate of PD patients with SD on the face and body was significantly higher among male patients than female patients (35% vs. 12.5%, P < 0.001). SD was significantly less common among those using levodopa/carbidopa/ entacapone (P = 0.040). SD was also significantly less com- mon in patients who had been using dopa agonists than in patients who had not been using dopa agonists (24.6% vs. 40%, P = 0.049). Pre-PD SD was significantly more common Original Article | Dermatol Pract Concept. 2024;14(4):e2024241 5 the patients noticed the findings in 62.6% of the cases and the neurologist in 4.5%. Conclusions PD, which affects approximately 0.3% of the general pop- ulation, is a disease that progresses with the loss of dopa- minergic neurons in the substantia nigra [1,3,5,11]. The incidence of PD, which is more common in men, increases after the fifth decade [2]. Although the pathogenesis of PD is not fully known, it has been suggested that factors such as mitochondrial dysfunction, oxidative stress, immune dysreg- ulation, and chronic inflammation may lead to PD [1]. Despite the general view that PD cases are sporadic, it has been reported that mutations detected in the Parkin (PARK2), PINK1 (PARK6), LRRK2, PARK7, and SNACA genes may be associated with PD [1,2,12]. PD is a hypokinetic motor disorder; however, non-motor symptoms can also be observed at all stages of the disease. Recent studies have suggested that the skin is an organ where non-motor symptoms are frequently observed [1,2]. PD is classified as a synucleinopathy due to the pathological accumulation of alpha-synuclein and the formation of Lewy bodies and Lewy neurites [1,4,6,11,13]. It has been shown that alpha-synuclein, a small protein consisting of 140 amino acids, plays a role in some cellular mechanisms, suggesting that its accumulation in peripheral tissues and the brain causes non- motor symptoms in PD, including in the skin [1,6,7,14]. In 2008, Ikemura et al. detected alpha-synuclein depos- its in the skin samples taken from the abdominal wall and upper extremities of 279 PD patients who had undergone autopsy. They also detected localized alpha-synuclein im- munoreactivity in the dermis in 23.5% of the patients with Lewy pathology in the central nervous system [15]. in male patients than in female patients (21% vs. 8.3%, P = 0.019). The PD stage at admission to our outpatient clinic was significantly lower in patients with pre-PD SD than in pa- tients without pre-PD SD (stage 1: 22.2% vs. 16.2%, stage 2: 66.7% vs. 48.6%, stage 3: 8.3% vs. 22.3, stage 4: 2.8% vs. 10.1%, and stage 5: 0% vs. 2.8%; P = 0.011) (Table 3). Specific Dermatological Conditions in PD Patients Cherry angioma (25 <) was significantly more common in PD patients with rosacea than in PD patients without rosa- cea (59.3% vs. 40.3%, P = 0.01). In parallel, rosacea was significantly more common in PD patients with cherry angi- oma than in PD patients without cherry angioma (36.1% vs. 20.3%, P = 0.01). Erythema intertrigo and tinea pedis were significantly more common in PD patients with hyperhidro- sis than in PD patients without hyperhidrosis (P < 0.001). The PD stage at admission to our outpatient clinic was sig- nificantly lower in patients with pre-PD SD on the scalp than in patients without pre-PD SD on the scalp (stage 1: 28.1% vs. 3.2%, stage 2: 59.4% vs. 41.9%, stage 3: 9.4% vs. 35.5%, stage 4: 3.1% vs. 12.9%, stage 5: 0% vs. 6.5%; P < 0.001) (Table3). Actinic keratosis was observed on the face of 9.8% of the PD patients and on the scalp of 4.7%. In patients with additional systemic diseases other than PD and drug use other than PD, there was no sta- tistically significant relationship between skin findings (P > 0.05) Improvement of Dermatological Findings After PD Diagnosis Of the patients with pre-PD dermatological findings, 92.4% described improvement in these findings after PD. In cases with skin findings detected after dermatological examination, Table 3. Comparative Analysis of Dermatological Conditions across Parkinson’s Disease Stages. PD Stage Xerosis, Freq % SD, Freq % SSD, Freq % Rosacea, Freq % Hyperhidrosis, Freq % pos neg P pos neg P pos neg P pos neg P pos neg P 1 22.8 7.2 0.001 22.2 16.2 0.011 28.1 3.2 <0.001 16.6 21.1 0.67 14.3 29.5 0.096 2 54.3 44.7 66.7 48.6 59.4 41.9 50.5 57.6 51.4 40.9 3 17.4 34,1 8.3 22.3 9.4 35.5 20.9 15.2 14.3 25 4 4.1 12.5 2.8 10.1 3.1 12.9 9.3 6.1 14.3 2.3 5 1.4 1.5 0 2.8 0 6.5 2.7 0 5.7 2.3 This table presents a comparative analysis of the frequency percentages of various dermatological conditions across different stages of Parkinson’s Disease (PD), ranging from stage 1 to stage 5 according to the Hoehn and Yahr scale. “Freq %” columns under each condition (Xerosis, Seborrheic dermatitis (SD), Scalp seborrheic dermatitis (SSD), Rosacea, and Hyperhidrosis) are divided into “pos” for positive (presence of the condition) and “neg” for negative (absence of the condition), indicating the proportion of patients at each PD stage. P-values indicate the statistical significance of the differences observed between the presence and absence of each condition at various PD stages, with values less than 0.05 considered statistically significant. The absence of a p-value indicates that statistical analysis data for those stages are not provided. This analysis aimed to identify potential correlations between the progression of PD and the prevalence of specific dermato- logical conditions. Chi-squared test. 6 Original Article | Dermatol Pract Concept. 2024;14(4):e2024241 alpha-synuclein aggregates have been found in the sebaceous glands in skin biopsies of patients with PD [14]. Alpha- synuclein deposits may affect sebum production and excre- tion in the sebaceous glands, causing skin oiliness or dryness. In our study, the frequency of SD in patients using levodopa/carbidopa/entacapone and dopa agonists was sta- tistically lower than in patients not using these drugs. Kohn et al. found a significant decrease in the sebum on the fore- heads of patients receiving L-dopa treatment. They did not find a relationship between dopa dose, treatment duration, and degree of sebaceous gland inhibition [19]. Martignoni et al. found no correlation between sebum excretion rates and duration of L-dopa treatment [17]. Tomic et al. found a positive correlation between age, motor symptom severity, and SD in PD [4]. In contrast, we did not find any signifi- cant relationship between PD stage, age, and SD. Tomic et al. found that 1/3 of the patients had symptoms of SD before PD diagnosis, and SD was 1.8 times more common in patients with moderate and severe symptoms than in patients with mild symptoms [4]. In our study, 61% of the PD patients had SD before they were diagnosed with PD. Unlike Tomic et al., we found the PD stage at admission to our outpatient clinic to be significantly lower in PD patients with SD than in those without SD. These findings suggest that PD may be less severe in patients with SD. Rosacea, whose prevalence in the population varies between 1% and 20% [1], was observed at a high rate in patients with PD in our study. A few studies suggested a relationship between rosacea and PD [8,20,21]. The relationship between PD and rosacea is not fully known. However, common mechanisms involving increased matrix metalloproteinase (MMP) activity have been suggested to play a role in the relationship between PD and rosacea. In addition, it has been stated that increased levels of MMP-3 and MMP-9 in the cerebrospinal fluid may lead to the death of dopaminergic neurons, and simultaneously, increased lev- els of MMP-1, MMP-3, and MMP-9 in the skin may lead to tissue damage [1,2,8]. Additionally, sensory nerve fiber dys- function is thought to cause immune destabilization and op- portunistic skin diseases in sensitive areas of the skin [1,8]. PD also affects the entire gastrointestinal system. Bac- terial overgrowth in the small intestine and H. Pylori may contribute to the pathogenesis of rosacea [1,2,22]. We found cherry angioma to be more common in patients with rosa- cea and rosacea to be more common in patients with cherry angioma. A thorough literature review did not reveal any study touching on that relationship. The fact that both dis- eases were seen more frequently together may be attributed to their similar pathogenesis. The prevalence of actinic keratosis (AK) varies from country to country, e.g., Italy: 1.4%, South Korea: 88% [23]. In a study conducted in Turkey, Yaldız et al. reported the prevalence of AK as 4.61% between the ages of 60 and 69, In comparison, in our study, 75.8% of the PD patients had no dermatological complaint. However, dermatological examination revealed at least one skin disease in 92.1% of the patients, at least one scalp disease in 39.1%, nail disease in 27.4%, and oral mucosa disease in 1.4%. The most common skin finding in our study was xerosis, common in the geriatric population. The frequent occurrence of xerosis in PD patients may be due to age or autonomic dysfunction. In our study, in most PD patients with xerosis, xerosis occurred before PD. Therefore, we think xerosis may be a non-motor precursor skin lesion associated with PD. Additionally, the PD stage at admission to our outpatient clinic was significantly lower in patients with xerosis than those without xerosis, suggesting that xerosis is a good prog- nostic factor. A thorough literature review did not reveal any study on xerosis in patients with PD. Dyshidrosis (hyperhidrosis and hypohidrosis), which is considered a part of orthostatic dysfunction, is a common finding in PD. In our study, hyperhidrosis was observed in 37.2% of the patients. Pont-Sunyer et al. reported that pa- tients with PD had excessive sweating for 2–10 years before the onset of typical motor symptoms [16]. Similarly, com- plaints of the majority of PD patients with hyperhidrosis in our study had started before the diagnosis of PD. Wamelan et al. reported that chronic hyperhidrosis may be associated with the dysautonomic dominant subtype of PD and can thus be used as a simple clinical screening tool. It has been suggested that sweating in PD patients occurs mainly in the head and trunk as part of a compensatory thermoregulation mechanism against the loss of sweating in the extremities [9]. In our study, we detected hyperhidrosis more frequently in female PD patients. In contrast, Wamelan et al. did not report any significant difference in the rate of hyperhidrosis according to sex [9]. In our study, we detected SD in 31.6% of patients with PD on the scalp and 27.4% in the skin on the face other than the scalp and the skin on the chest and/or other body parts. Our finding that the rate of SD, which is seen at 1-3% in the general population, was higher in PD patients is consis- tent with other studies conducted to date [1,2]. Krestin et al. reported seborrheic face as a skin finding in PD patients in 1927 [1,7]. In a retrospective study, Tanner et al. suggested that SD may be an early marker of PD [1]. In PD, dopamine deficiency causes a deficiency of melanocyte-stimulating hormone (MSH) inhibitory factor, causing an increase in alpha-MSH and sebum production. In addition, decreased facial mobility in PD contributes to a greater accumulation of sebum. Mortignoni et al. found SD to be more common in male PD patients [17]. Arsenijevic et al. found a positive correlation between SD, PD, Malas- sezia globosa incidence, high yeast density, and high skin phosphatase and lipase activity [18]. Additionally, numerous Original Article | Dermatol Pract Concept. 2024;14(4):e2024241 7 US patient population retrospective study. J Eur Acad Dermatol Venereol. 2018;32(4):e141-e144. DOI:10.1111/jdv.14638. 9. van Wamelen DJ, Leta V, Podlewska AM, et al. Exploring hyper- hidrosis and related thermoregulatory symptoms as a possible clinical identifier for the dysautonomic subtype of Parkinson’s disease. J Neurol. 2019;266(7):1736-1742. DOI:10.1007/s00415 -019-09325-w. 10. Scott GD, Lim MM, Drake MG, Woltjer R, Quinn JF. Onset of Skin, Gut, and Genitourinary Prodromal Parkinson’s Disease: A Study of 1.5 Million Veterans. Mov Disord. 2021;36(9): 2094-2103. DOI:10.1002/mds.28636.. 11. Jucevičiūtė N, Banaitytė I, Vaitkus A, Balnytė R. Preclinical signs of Parkinson’s disease: A possible association of Parkinson’s dis- ease with skin and hair features. Med Hypotheses. 2019;127: 100-104. DOI:10.1016/j.mehy.2019.04.013. 12. Zhang X, Guarin D, Mohammadzadehhonarvar N, Chen X, Gao X. Parkinson’s disease and cancer: a systematic review and meta-analysis of over 17 million participants. BMJ Open. 2021;11(7):e046329. DOI:10.1136/bmjopen-2020-046329. 13. Han Y, Wu D, Wang Y, Xie J, Zhang Z. Skin alpha-synuclein deposit patterns: A predictor of Parkinson’s disease subtypes. EBioMedicine. 2022;80:104076. DOI:10.1016/j.ebiom.2022 .104076. 14. Rodríguez-Leyva I, Calderón-Garcidueñas AL, Jiménez- Capdeville ME, et al. α-Synuclein inclusions in the skin of Par- kinson’s disease and parkinsonism. Ann Clin Transl Neurol. 2014;1(7):471-478. DOI:10.1002/acn3.78. 15. Wakabayashi K. Where and how alpha-synuclein pathology spreads in Parkinson’s disease. Neuropathology. 2020;40(5): 415-425. DOI:10.1111/neup.12691. 16. Pont-Sunyer C, Hotter A, Gaig C, et al. The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Mov Disord. 2015;30(2):229-237. DOI:10.1002/mds.26077. 17. Martignoni E, Godi L, Pacchetti C, et al. Is seborrhea a sign of autonomic impairment in Parkinson’s disease? J Neural Transm. 1997;104(11-12):1295-1304. DOI:10.1007/BF01294730. 18. Arsic Arsenijevic VS, Milobratovic D, Barac AM, Vekic B, Marinkovic J, Kostic VS. A laboratory-based study on patients with Parkinson’s disease and seborrheic dermatitis: the presence and den- sity of Malassezia yeasts, their different species and enzymes produc- tion. BMC Dermatol. 2014;14:5. DOI:10.1186/1471-5945-14-5. 19. Kohn SR, Pochi PE, Strauss JS, Sax DS, Feldman RG, Timberlake WH. Sebaceous gland secretion in Parkinson’s dis- ease during L-dopa treatment. J Invest Dermatol. 1973;60(3). DOI:10.1111/1523-1747.ep12682040.. 20. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Exploring the Association Between Rosacea and Parkinson Disease: A Danish Nationwide Cohort Study. JAMA Neurol. 2016;73(5):529-534. DOI:10.1001/jamaneurol.2016.0022 21. Fischer M, Gemende I, Marsch WC, Fischer PA. Skin function and skin disorders in Parkinson’s disease. J Neural Transm. 2001;108(2):205-213. DOI:10.1007/s007020170088. 22. Fasano A, Visanji NP, Liu LWC, Lang AE, Pfeiffer RF. Gastro- intestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015;14(6):625-639. DOI:10.1016/S1474-4422(15)00007-1. 23. Ferreira J, Silva JM, Freire R, et al. Skin cancers and precan- cerous lesions in Parkinson’s disease patients. Mov Disord. 2007;22(10):1471-1475. DOI:10.1002/mds.21575. 24. Yaldiz M. Prevalence of actinic keratosis in patients attend- ing the dermatology outpatient clinic. Medicine (Baltimore). 2019;98(28):e16465. DOI:10.1097/MD.0000000000016465. 9.38% between the ages of 70 and 79, and 14.5% above the age of 80 [24].We did not observe an increase in the in- cidence of AK in PD patients. There are conflicting results in the literature regarding the relationship between precancer- ous skin lesions and malignancies in PD [12,23]. Ferreria et al. reported an increase in the risk of skin cancer with PD [23]. In a meta-analysis study, Zhang et al. reported an inverse relationship between PD and total cancer risk, except for melanoma [12]. This finding may be explained by genes associated with PD. PARK2 is a tumor suppressor gene, while LRRK2 mutations are associated with an increased risk of cancer [12]. We did not detect skin cancer in patients with PD in our study. Similarly, we did not detect a significant increase in nail and oral mucosal diseases in patients with PD. The most com- mon nail disease in patients with PD was onychomycosis. The examining neurologist detected only 4.5% of the skin findings in PD patients, indicating that the skin findings of the PD patients were ignored by both the patient and the neurologist. This study investigated the skin findings in patients with PD. Consequently, xerosis, hyperhidrosis, seborrheic dermati- tis, rosacea, and cherry angioma were found to be common in patients with PD. On the other hand, premalignant skin le- sions were rarely observed in these patients. The PD stage was mostly lower in patients with xerosis and pre-PD SD. These findings suggest that xerosis and SD can be used as effective prognostic markers in PD. However, further large-scale stud- ies are needed to corroborate the findings of this study. References 1. Ravn A-H, Thyssen JP, Egeberg A. Skin disorders in Parkinson’s disease: potential biomarkers and risk factors. Clin Cosmet Investig Dermatol. 2017;10:87-92. DOI:10.2147/CCID.S130319. 2. Shah P, Sagar PR, Alhumaidi N, Bollampally VC, Malik BH. Parkinson’s Disease and Its Dermatological Associations: Is Your Skin Whispering You a Diagnosis? Cureus. 2020;12(8):e9933. DOI:10.7759/cureus.9933. 3. Shahid W, Satyjeet F, Kumari R, et al. Dermatological Manifestations of Parkinson’s Disease: Clues for Diagnosis. Cureus. 2020;12(10):e10836. DOI:10.7759/cureus.10836. 4. Tomic S, Kuric I, Kuric TG, et al. Seborrheic Dermatitis Is Related to Motor Symptoms in Parkinson’s Disease. J Clin Neurol. 2022;18(6):628-634. DOI:10.3988/jcn.2022.18.6.628. 5. Dinesh D, Lee JS, Gao X, Palacios N. Skin conditions in early Parkinson’s disease. Parkinsonism Relat Disord. 2021;84:40-46. DOI:10.1016/j.parkreldis.2021.01.018. 6. Skorvanek M, Bhatia KP. The Skin and Parkinson’s Disease: Review of Clinical, Diagnostic, and Therapeutic Issues. Mov Disord Clin Pract. 2017;4(1):21-31. DOI:10.1002/mdc3.12425. 7. Niemann N, Billnitzer A, Jankovic J. Parkinson’s disease and skin. Parkinsonism Relat Disord. 2021;82:61-76. DOI:10.1016 /j.parkreldis.2020.11.017. 8. Mathieu RJ, Guido N, Ibler E, et al. Rosacea and subsequent diagnosis for Parkinson’s disease: a large, urban, single center,