Interrated for human Not Animals hospitols

For Human

1. Integrated Care Approach in Nurturing Sensitive Skin NEMCON 2024, RSPAD Gatot Subroto June 9 th DR med. Dr. Maya Surjadjaja, M Gz , SpGK , FAAM

2. Short CV

3. OUTLINES Definition International Forum for the Study of Itch (IFSI) Sensitive skin is a syndrome. Affect the Quality of Life Gut Skin Axis Management

4. WHAT’S IN A NAME Cosmetic intolerance syndrome (Maybach 2017), Cosmetic intolerance state, delicate skin, and skin sensory irritation response. Sensitive skin, hyper-reactive skin, reactive skin, highly reactive skin, intolerant skin, easily irritated skin Among these terms, sensitive skin is the most commonly used G.  Honari , R. Andersen, H.  Maibach Sensitive Skin Syndrome (2nd Ed.), CRC Press, Boca Raton, United States (2017)   Sensitive skin was reported as a syndrome in 2006 Berardesca E, Fluhr JW, Maib ach HI. Sensitive Skin Syndrome. New York, NY: Taylor & Francis; (2006)

5. CLINICAL DEFINITION Characteristic sensory perceptions Tightness, abnormal stinging, burning, tingling, pain and pruritus. Other unpleasant skin sensations Can’t be diagnosed as common neuropathies 2016 International Forum for the Study of Itch Facial erythema Other body areas can be involved. Wollenberg A, Giménez-Arnau A. Sensitive skin: A relevant syndrome, be aware. J Eur Acad Dermatol Venereol . 2022 Apr;36 Suppl 5:3-5. Unpleasant sensations In response to stimuli normally not provoke sensations. CAN’T be explained by any skin disease. Functional disorders without any precise diagnosis. Misery L, et al.. Neuropathic pruritus.  Nat Rev Neurol.  (2014) 10:408–16.

6. A consensus Definition IFSI (The International Forum for the Study of Itch) Sub classification primary sensitive skin (without any underlying skin disease) to secondary sensitive skin (with an underlying skin disease)  Guerra- Tapiaa A, et al   Diagnóstico y tratamiento del síndrome de piel sensible: un algoritmo para la práctica clínica habitual.  Actas Dermosifiliogr . (2019)

7. CLINICAL PRESENTATION Subjects with sensitive skin Minimally visible skin lesions or no lesions at all Erythema is often observed. Spontaneously, induced by exogenous triggers Cosmetics, environmental conditions [e.g., UV light, temperature, or wind] and psychological (e.g., stress) and hormonal factors (e.g., menstrual cycle) In most patients, symptoms occur within 1 h following exposure to trigger factors Persist for minutes or even hours NO proven relationship between sensitive skin and psychological symptoms 

8. Pathophysiology NOT an immunological disorder Alterations of skin nervous system. Frequent Association with Skin barrier abnormalities NO cause and direct relationship The International Forum for the Study of Itch (ISFI). Pathophysiology and management of sensitive skin: position paper from the special interest group on sensitive skin of the International Forum for the Study of Itch (IFSI). J Eur Acad Dermatol Venereol . 2020 Feb;34(2):222-229 . Do LHD, Azizi N, Maibach H. Sensitive Skin Syndrome: An Update. Am J Clin Dermatol. 2020 Jun;21(3):401-409. Prevalence of sensitive skin 60-70% among women 50-60% among men.

9. Pathophysiology of Sensitive Skin ? Disorder of cutaneous small nerve fibers ?  ( A)  Role of extrinsic and intrinsic factors Extrinsic factors (radiations, climate, irritants, or cosmetics) as well as intrinsic factors ( gender, hormones, or psychological factors can trigger a small-fiber neuropathy Associated with an impaired epidermal barrier function. An innate immunity disorder remains discussed   (B)  Induction of inflammation and abnormal perceptions by nerve fiber (and keratinocyte) activation. Extrinsic and intrinsic factors induce an inflammation after an excessive nerve fiber activation (activation of TRPV1, TRPV4, and other channels followed by the release of neuropeptides in the skin) and a keratinocyte activation (inducing cytokines release ) Misery L, et al Sensitive Skin Syndrome: A Low-Noise Small-Fiber Neuropathy Related to Environmental Factors? Front Pain Res (Lausanne). 2022 Mar 25;3:853491

10. OUTLINES Definition Gut Skin Axis Gut-Skin communication through immuno -cross-linking. Eczema, atopic dermatitis, and rosacea Acne Management

11. Several dermatologic conditions Acne, atopic dermatitis, psoriasis, and rosacea are linked with intestinal dysbiosis

12. Unbalanced bacterial composition or aberrant immune reactions to commensal flora Linked to metabolic, neurodegenerative, and neoplastic diseases. Altered gut flora favor the production of effector over regulatory T cells Development of autoimmune disorders. Segmented filamentous bacteria in the gut Associated with a variety of Th17-mediated diseases. Intestinal Dysbiosis Kosiewicz M. M., et al (2014). Relationship between gut microbiota and development of T cell associated disease. FEBS Lett . 588 4195–4206. 10.1016/j.febslet.2014.03.019  2005 discovery of T-helper 17 (Th17) cells, a unique CD4 +  T-cell subset characterized by production of interleukin-17 (IL-17). IL-17 is a highly inflammatory cytokine

13. The Gut-Skin Axis Mahmud MR,et al . Impact of gut microbiome on skin health: gut-skin axis observed through the lenses of therapeutics and skin diseases. Gut Microbes. 2022 Jan-Dec;14(1):2096995 A . The alteration lead to dysbiosis B . Dysbiotic gut microbes, toxic products, neurotransmitters, and altered immune cells pass through the circulatory system Turning skin condition from healthy ( left ) to dysbiotic ( right ).   C . Dysbiotic skin microbes trigger skin inflammation and can be involved in the onset of a variety of skin illnesses. 

14. Gut Microbiome influences Skin Microbiome Affects skin differentiation and keratinization Modulating the cutaneous immune response in various diseases SCFAs resulting from fiber fermentation in the gut – propionate, acetate, and butyrate Determining predominance of certain skin microbiomic profiles influence cutaneous immune defense mechanisms.  Salem I, et al   The Gut Microbiome as a Major Regulator of the Gut-skin Axis . Front Microbiol . 2018;9:1459. Gut microbiome major regulator of gut-skin axis Skin commensal microbiome can be affected by bioactive compounds End-products of gut microbial metabolism Neurotransmitters, hormones, and SCFAs, Schwarz, A., et al (2017). The short-chain fatty acid sodium butyrate functions as a regulator of the skin immune system. J. Investig . Dermatol . 1, 855–864.

15. ACNE CROSS talk between intestinal commensal bacteria and mTOR pathway (Noureldein and Eid, 2018 ) Important role of mTORC1 in the pathogenesis of acne Gut microbiome influences acne pathophysiology. Metabolites of gut microbiota regulate Cell proliferation, lipid metabolism, other metabolic functions mediated by the mTOR pathway. MTOR pathway Affect intestinal microbiota COMPOSITION through regulation of the intestinal barrier. Intestinal dysbiosis and disrupted gut barrier integrity BIDIRECTIONAL relationship Positive feedback cycle of metabolic inflammation.

16. ACNE Hypochlorhydria is frequently associated with acne. Low levels of acidity Migration of colonic bacteria to distal parts of small intestine Intestinal dysbiosis and small intestinal bacterial overgrowth (SIBO). Increase intestinal permeability Promote skin inflammation Lee YB, Byun EJ, Kim HS. Potential role of the microbiome in acne: a comprehensive review. J clini med. 2019;8(7):987 SIBO Production of toxic metabolites, injured enterocytes, increase intestinal permeability Systemic inflammation Bures et al., 2010 , Bowe and Logan, 2011, Bowe et al.,2014

17. Atopic dermatitis (AD)  Two metagenomic studies South Korea Fecal samples of patients with AD when compared with healthy controls Decrease abundance in  Faecalibacterium prausnitzii  along with Significant reduction in SCFA production Song H, et al   Faecalibacterium prausnitzii  subspecies–level dysbiosis in the human gut microbiome underlying atopic dermatitis. J Allergy Clin Immunol . 2016;137(3):852–860 Hrestak D, et al Skin Microbiota in Atopic Dermatitis. Int J Mol Sci. 2022 Mar 23;23(7):3503 Lower abundance of  Bifidobacterium  in the gut in AD compared to healthy control

18. ROSACEA IBD patients experience lesions and other skin disorders BOTH IBD and rosacea genetic overlap on histocompatibility complex class II gene HLA DRB1 One potential pathogenic mechanism Activation of transient receptor potential cation channels  Neurogenic vasodilatation. Huang BL, Chandra S, Shih DQ.  Skin Manifestations of Inflammatory Bowel Disease . Front Physiol. 2012;3:13. H. pylori  infection, IBD, and small intestinal bacterial overgrowth (SIBO) are potentially associated with rosacea pathogenesis Holmes AD. Potential role of microorganisms in the pathogenesis of rosacea. J Am Acad Dermatol . 2013;69(6):1025–1032 Combination of immune system dysregulation, abnormal neurological and vascular signaling, and dysbiosis LEADING TO skin sensitivity and inflammation Individuals with rosacea HIGHER incidence of gastrointestinal disease,

19. OUTLINES Definition Gut Skin Axis Management How to Nurture Sensitive Skin

20. GENERAL APPROACH in SKIN CARE Avoidance of possible triggering factors USE well-tolerated cosmetics Hair dyes should be avoided, particularly those containing ammonia. Published data NOT SUFFICIENT to reach a consensus on sensitive skin management NO CLINICAL TRIAL supporting the use of topical or systemic drugs in sensitive skin. NO DRUG STUDY such as gabapentin, pregabalin or duloxetine. Lev-Tov H, Maibach HI. The sensitive skin syndrome. Indian J Dermatol . 2012 Nov;57(6):419-23 NO STUDY providing data to reach a consensus on the management of sensitive skin.

21. MANAGEMENT Patients with sensitive skin require a personalized approach Various biomedical, neural and psychosocial factors affecting sensitive skin. The role of psychosocial factors Stress or negative expectations relevant for subgroups of patients Enough sleep Lev-Tov H, Maibach HI. The sensitive skin syndrome. Indian J Dermatol . 2012 Nov;57(6):419-23

22. DIET Weiss E, Katta R.  Diet and Rosacea: The Role of Dietary Change in the Management of Rosacea .  Dermatol Pract Concept. 2017;7(4):31-37 MTOR PATHWAY Activated by high glycemic load. High glycemic load sole contributor to increased insulin/insulin-like growth factor (IGF-1) signaling Enhancing cytoplasmic expression of FoxO1 ( Forkhead box transcription factor O1). FoxO1 stimulates mammalian target of rapamycin complex 1 (mTORC1) ACNE DEVELOPMENT Salem I, et al The gut microbiome as a major regulator of the gut-skin axis. Front Microbiol . 2018;9:1459 High-collagen peptide diet, W hey and pea protein extracts Increase SCFA levels in intestinal mucosa keeping mucosal barrier intact Singh RK, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15(1)

23. The Right Microbiome Mix BIO fermented whole foods Probiotic Supplementation Topical probiotic Mahmud MR, et al Impact of gut microbiome on skin health: gut-skin axis observed through the lenses of therapeutics and skin diseases. Gut Microbes. 2022 Jan-Dec;14(1):2096995 Anti Aging Effect 110 middle-aged Korean subjects 12 weeks double-blind, placebo-controlled study, oral supplementation of  L. plantarum  HY7714 Improve cutaneous elasticity Increase skin hydration

24. PREBIOTIC High fiber foods Legumes black beans and chickpeas whole grains oats and quinoa Vegetables broccoli and asparagus Nuts almonds and pistachios Fruits apples and peaches garlic Fermented foods Great dietary sources of probiotics. K imchi, sauerkraut, yogurt, kefir Ried K, et al The Effect of Kyolic Aged Garlic Extract on Gut Microbiota, Inflammation, and Cardiovascular Markers in Hypertensives: The GarGIC Trial. Front Nutr . 2018 Dec 11;5:122

25. Probiotic NO ONE SIZE FIS ALL Wang X, et al Probiotics Regulate Gut Microbiota: An Effective Method to Improve Immunity. Molecules. 2021 Oct 8;26(19):6076. Lee, D. E., et al. (2015). Clinical evidence of effects of Lactobacillus plantarum  HY7714 on skin aging: a randomized, double blind, placebo-controlled study. J. Microbiol . Biotechnol . 25, 2160–2168

26. Acne Lactobacillus acidophilus  and  Lactobacillus bulgaricus  probiotic tablets by 300 acne patients Acne improvement in 80% of subjects in subjects with inflammatory lesions Bowe, W., et al (2014). Acne vulgaris, probiotics and the gut-brain-skin axis: from anecdote to translational medicine.  Benef . Microbes 5, 185–199 Lactobacillus rhamnosus  SP1 for 12 weeks Reduce expression of IGF-1 and oxidative stress markers  Fabbrocini, et al (2016). Supplementation with Lactobacillus rhamnosus  SP1 normalises skin expression of genes implicated in insulin signaling and improves adult acne.  Benef . Microbes 7, 625–630 Probiotics reduce acne inflammation Reducing levels of inflammatory cytokines Increasing CD8 cell recruitment Suppressing IL−1α Activating Tregs . Baquerizo et al Probiotics and prebiotics in dermatology.  J Am Acad Dermatol . 2014;71(4):814–821

27. ACNE Noureldein & Eid INHIBITION of mTORC1 together with changes in gut microbiome Improve glucose tolerance level Reduce hyperinsulinemia. Reduced level of acne lesion was found in patients supplied with a low glycemic load diet for 12 weeks Noureldein MH, Eid AA. Gut microbiota and mTOR signaling: insight on a new pathophysiological interaction.  Microb Pathog . 2018;118:98–104

28. AD/ eczema short-term (2-week) use of corticosteroids stop the inflammatory process. Synbiotics for at least eight weeks had a significant effect on a measure of AD severity Chang Y-S, et al . Synbiotics for prevention and treatment of atopic dermatitis JAMA Pediatr.2016;170(3):236. The risk of atopic d e rmatitis development was also found considerably lower in children who took probiotic supplements in the post-neonatal period of life. Polkowska‐Pruszyńska B, et al The gut microbiome alterations in allergic and inflammatory skin diseases – an update. J EurAcad Dermatol Venereol . 2019;34(3):455–464

29. ROSACEA Increase Prevalence of small intestinal bacterial overgrowth (SIBO) E limination of SIBO Si gnificant reduction in cutaneous lesions Rosacea exacerbations linked to dietary factors H eat-related, alcohol-related, capsaicin-related, and cinnamaldehyde-related Survey by the National Rosacea Society of over 400 patients 78% change the diet Of this group, 95% reported a subsequent reduction in flares MOA A ctivation of TRP ( transient receptor potential) channels G ut–skin connection Weiss E., Katta R. Diet and rosacea: The role of dietary change in the management of rosacea. Dermatol. Pract . Concept. 2017;7:31.

30. THANK YOU To heal the skin, it’s essential that you first heal the gut @mayasurjadjaja @anti-aging-corner-drmaya