Abstract
Introduction
Minimal erythema dose (MED) remains a parameter of paramount importance to orient narrow-band (NB)-UVB phototherapy in psoriatic (PsO) patients. Recently, circadian rhythm and diet were recognized as potential MED modulators, but their mutual interaction remains understudied. Thus, we aimed to evaluate the potential diet modulation of MED circadian oscillations.
Methods
In the first phase, a cohort study was performed comparing potential MED oscillations (morning, afternoon, and evening) among omnivorous psoriatic patients before and after a phototherapy cycle and omnivorous healthy controls. The two groups were age-, gender-, skin-type-, MED-, and diet-matched. Then, in the second phase, another cohort study was carried out comparing MED oscillations 24 h after the last phototherapeutic session only in psoriatic patients cleared with NB-UVB and undergoing different diets (vegan, vegetarian, paleo , ketogenic, intermittent circadian fasting, and omnivore). Patients with different diets were age-, gender-, and skin-type matched.
Results
In the first phase, we enrolled only omnivores, specifically 54 PsO patients and 54 healthy individuals. Their MED before and after NB-UVB therapy changed significantly among the three different time-points (morning, afternoon, and evening) (p < 0.001). The time effect was statistically significant in both groups before and after phototherapy. In the second phase, we enrolled 144 PsO patients (vegan, vegetarian, paleo, ketogenic, intermittent circadian fasting, and omnivore). MED circadian oscillations preserved a significant difference also after clearance and were influenced by diet type and time of day (p < 0.001). In particular, vegans displayed the lowest MED values, whilst Ramadan fasting showed the highest values in morning, afternoon, and evening.
Conclusions
Diet, like other ongoing therapies, should be reported in the medical records of patients with psoriasis undergoing NB-UVB and patients with lower MEDs should be preferentially treated in the morning when the MED is higher.
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Avoid common mistakes on your manuscript.
Post-phototherapy erythema occurrence is influenced also by diet in patients with psoriasis. |
Circadian oscillations of minimal erythema dose (MED) are clinically relevant only in untreated PsO patients. |
Phototherapy treatment normalized circadian oscillations of MED in treated psoriasis (PsO) patients. |
After clearance MED circadian oscillations are still influenced by diet type. |
Diet anamnesis should be carefully recorded in PsO patients undergoing phototherapy. |
Introduction
Psoriasis (PsO) is a chronic autoimmune disease that affects approximatively 40.8 million people worldwide [1], and also deeply influences patients’ quality of life. A PsO patient’s history may also be influenced by the great burden of comorbidities (i.e., gastrointestinal [2, 3], neurological [4, 5], respiratory [6,7,8], and even psychological [9, 10]). From a clinical point of view, PsO often presents a typical relapsing–remitting behavior mitigated by seasonality (in summer, PsO improves, whilst in winter it worsens) [11, 12], whilst little is known regarding the influence of circadian rhythm [13].
However, perturbation of the circadian rhythm such as night shift work [14, 15], sleep disorders [16, 17], jet-lag effect [5, 18], or even feeding time-shifts (i.e., intermittent circadian fasting) [19, 20] influence PsO severity and anti-psoriatic drug response.
Furthermore, by orienting therapeutic delivery following chronomedicine principles, psoriatic patients can maximize the anti-psoriatic effects of drugs: for example, topical corticosteroids have higher efficacy if applied in the evening when keratinocytes preferentially differentiate and proliferate [21] and the pruritus peaks [22,23,24,25,26,27].
The circadian rhythm differentially regulates both the biology of skin layers [28] and the immune system [29,30,31]. In fact, neutrophils infiltrate more and Langerhans cells are more active during the day; conversely, macrophages and Th 17 are more functional at night when the inflammation rises up in psoriatic skin.
Immune system activation, together with vessel permeability, are the two main modulators of minimal erythema dose (MED), a measure of UVB cutaneous sensitivity, which is fundamental to orient NB-UVB therapy in PsO patients. In fact, NB-UVB remains an effective first line treatment in patients with moderate to severe psoriasis [32,33,34], in patients with contraindications, or in those who refuse biologics due to personal motivation, or even COVID-phobia [35, 36]. Recently, together with circadian rhythm, diet was suggested to be an important MED modulator [37,38,39], but their mutual interaction remains understudied. Furthermore, diet behavior is increasingly variable among PsO patients. Consequently, we encounter patients with different diet regimens (i.e., paleo, ketogenic diet, vegan, and vegetarian diets) more often in the psoriasis ambulatory clinic. We would like to know the potential influence of diet or foods on PsO, but scarce evidence is present in the literature [40].
Thus, we decided to investigate the circadian oscillation (at different times of the day) of MED in PsO patients undergoing phototherapy and characterized by different dietary habits.
Materials and Methods
Study Design
This study was conducted in two Italian primary referral dermatological departments (IRCCS Istituto Ortopedico Galeazzi and IRCCS San Gallicano) with an experienced (> 15 years activity and > 150 patients treated per year) photobiological unit and expert photobiologists and dermatologists (> 10 years of experience in phototherapy and research). It was divided in two phases (Fig. 1):
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A.
The first phase was a cohort study comparing circadian oscillations of MED in morning, afternoon, and evening of the same day in patients with psoriasis, before and after clearance, and in healthy controls. The two groups were age-, gender-, skin-type-, MED-, and diet-matched. Both patients and controls were omnivores.
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B.
The second phase was a cohort study comparing MED circadian oscillations 24 h after NB-UVB therapy in patients whose psoriasis was already cleared, and who had different dietary habits. Patients with different diets were age-, gender-, and skin-type matched.
All subjects provided informed consent for inclusion before they participated in the study. The entire study was performed in accordance with the Declaration of Helsinki of 1975 (https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/), revised in 2013, and the protocol was approved by the Ethics Committee of Saint Rafael Hospital (OSR) (Project 176/int/2020).
Inclusion and Exclusion Criteria
In this clinical study different inclusion and exclusion criteria were adopted in the two phases.
Phase 1
The inclusion criteria were: adult patients (≥ 18 years) with a diagnosis of plaque psoriasis (> 6 months), undergoing on-label treatment with NB-UVB monotherapy, compliant with medical prescriptions (< 2 therapy auto-modification/discontinuation in the previous year), and who had signed an informed consent form.
The exclusion criteria were: patients with a concurrent type of psoriasis (i.e., pustular, erythrodermic or sebopsoriasis); those with other autoimmune/inflammatory conditions [41]; those who were obese (body mass index ≥ 30 [42]); those with addictions (i.e., alcohol [Alcohol Use Disorders Identification Test > 7] [43], smokers, and marijuana/other illegal drugs users [44]); those with chronic metabolic diseases (i.e., diabetes) [45]; those who were infectious (hepatitis B and C [3, 46], HIV [47], or tuberculosis [48]) or had neoplastic diseases [49]; and any who refused to sign the informed consent form.
Parallel control individuals were otherwise healthy and were recruited from patients undergoing the annual nevi control and without concurrent dermatological/rheumatological, or gastroenterological immune disorders.
In addition, controls with concomitant dermatoses were also excluded.
Phase 2
In phase 2 of the study, all the phase 1 criteria of inclusion and exclusion were still valid, plus PsO patients also had to adhere to their habitual diet and complete a nutritional diary daily during the previous month. MED was measured in the morning, afternoon, and evening to evaluate the potential circadian oscillations post-phototherapy, a well-known modulator of the cutaneous peripheric clock.
Clinical Evaluation
Medical history and drug history were collected for every patient screened in the study, with or without psoriasis.
Patients with psoriasis were characterized using the Psoriasis Area Severity Index (PASI) [50] to quantify disease severity, and underwent the Psoriasis Epidemiology Screening Tool (PEST) [51] to exclude the occurrence of psoriatic arthritis (PsA) (a contraindication for NB-UVB in monotherapy).
Before and after each phototherapy session, patients were carefully evaluated to detect cutaneous sign of burns (i.e., erythema, vesicles) or photosensitivities/photoallergies.
Diet Evaluation
Patients and controls completed detailed dietary diaries, recording foods and beverages consumed daily, and time of consumption, during the preceding month.
Based on the dietary diary, the following diets were derived:
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Vegan diet: “the practice of dispensing with all products derived wholly or partly from animals” [52]. We also included fruitarians (eating only fruits) and crudists (eating only uncooked fruits and vegetables) in this category;
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Vegetarian diet: a diet in which patients “never ate meat, poultry and fish, or ate these foods less than once a month” [53]. In this category we included lacto-vegetarians (also eating dairy foods), ovo-vegetarians (also eating eggs), lacto-ovo vegetarians (eating both eggs and dairy foods), but we excluded pescatarians (eating fish);
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Ketogenic diet or standard ketogenic diet (SKD): a fat-rich (70% of the intake), moderate protein (20% of the intake) and low-carbohydrate (10% of the intake, < 50 g/day) diet [54]. We excluded ketogenic diets other than SKD, such as the cyclical ketogenic diet (CKD) (cycle = 5 ketogenic days + 2 high-carbohydrate days), targeted ketogenic diet (TKD) (added carbs during intensive workout), and also the high-protein ketogenic diet (HPKD) (food intake = 60% fats, 35% proteins, and 5% carbohydrates) [55];
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Paleo diet: a diet inspired by the one consumed in the Paleolithic era and characterized by a scarce dairy intake and the absence of processed foods; conversely, it is rich in fruits, nuts, vegetables, fish, eggs, and meats, as suggested in the newly proposed paleo diet score [56];
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Omnivore diet: a daily various diet that does not avoid certain food categories. A flexitarian or semi-vegetarian diet, in which patients observe “primarily a plant-based diet but includes meat, dairy, eggs, poultry and fish on occasion or in small quantities,” was included into the omnivore diet.
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Intermittent circadian fasting (Ramadan fasting): one month strict (food and beverages) fasting from dawn to sunset in line with the Islamic calendar, adjusted for location (https://www.islamicfinder.org/world/italy/). We enrolled patients following the 2021 Ramadan from April 13th to May 12th 2021.
Minimal Erythema Dose (MED) Calculation
MED was measured with a Multiport UV Solar Simulator 601 (Solar Light CO.INC: Philadelphia, PA, USA). Measures were performed in winter on covered areas (buttocks), to avoid socio-cultural and seasonal confounders, at least after 2 h after the meal in the morning (between 8 and 11 a.m.), in the afternoon (between 2 and 5 p.m.), and in the evening (between 6 and 9 p.m.) to evaluate circadian oscillations of MED. Notably, before collecting MED measurements, patients had to use a daily sensitive skin shampoo and shower gel (Ceramol Shampoo 200 ml and Ceramol Face-Body Cleansing Base 400 ml, Unifarco S.p.a., Via Cal Longa, 62, 32,035 Santa Giustina, Belluno, Italy) for 1 week, and the same emollient (Ceramol body crema, Unifarco S.p.a., Via Cal Longa, 62, 32035 Santa Giustina, Belluno, Italy) twice a day without perfumes to avoid potential photosensitizations and/or allergies [57, 58].
Sunscreens, perfumes, and emollients had to be avoided at least 4 h before MED measurement.
Narrow-Band UVB Therapy
Patients were treated with NB-UVB delivered by a PUVA Combi Light PCL 8000 phototherapy booth (Heverlee, Belgium), with 48 Phillips® TL100 W/01 tubes and a Waldmann Variocontrol dosimeter (Waldmann Medizintechnik GmbH, Villingen-Schwenningen, Germany).
In the first phototherapy session, 70% of the MED was delivered and in each subsequent session we increased the dose by 20%, halved in case of erythema, 3 times a week for 8 weeks [59,60,61]. This protocol was performed to avoid photoadaptation, as previously described [62].
Statistical Analysis
Descriptive statistical analysis was carried out, computing means and standard deviations or medians for continuous variables and percentages for categorical parameters. In particular, given the longitudinal study design at different time-points, besides means, grand and marginal means (adjusted for covariates and repeated measures) were computed.
Student’s t-test, or alternatively one-way ANOVA, was then performed to compare means between psoriatic subjects against healthy subjects and between different diet groups. The χ2 test, or alternatively Fisher’s exact test (for an expected frequency lower than five), was used to address differences in the distribution of the categorical variables between the same groups. A mixed ANOVA was performed to quantify the group effect, both by psoriasis presence and by diet, together with the circadian oscillation effect on MED. Similarly, a MANOVA was conducted to adjust for other characteristics of the sample, such as age, gender, and skin type. For all the continuous dependent variables, non-significant departures from the normal distribution and homogeneity of variances were checked (with the Shapiro–Wilk and Levene tests, respectively) prior to proceeding with parametric analysis.
RStudio software was used for the analysis.
Results
Circadian MED Oscillations in Psoriatic Patients Before and After NB-UVB Therapy (Phase 1)
Patient Characteristics
We recruited 108 subjects: 54 PsO patients and 54 healthy individuals. PsO patients displayed a PASI of 4.69 ± 1.37 (median 5) and 27 (50%) also had PsO family history. The most common Fitzpatrick skin-type (phototype) was III (n = 42, 38.9%), followed by II (n = 24, 22.2%), IV (n = 20, 18.5%), I (n = 12, 11.1%), and V/VI were the least common (n = 10, 9.3%) (Table 1). In line with matching criteria, no differences were present for age-, gender-, skin-type-, MED- or diet.
MED Values Before Clearance
Comparing MED oscillations in morning, afternoon and evening between psoriasis patients and healthy controls no statistical difference was found (Fig. 2A), conversely comparing circadian oscillations of MED in the whole day only psoriasis patients had stitistically significant oscillations (Table 2).
Despite intergroup differences in MED not being significant, intragroup differences in psoriatic untreated patients resulted highly significant differences (p < 0.001) (Fig. 2B).
There was a statistically significant (p < 0.001) difference in MED values before and after NB-UVB only in psoriatic patients.
Diet-Related Modifications of MED Circadian Oscillation in Remitted Psoriatic Patients Treated with Phototherapy (Phase 2)
Patient Characteristics
One hundred forty-four PsO patients were recruited (mean age 40.29 ± 7.39 years, 66 females, 45.8%, 78 males, 54.2%). The majority of the subjects [95 (66.0%)] had skin-type III, while only 49 (34.0%) had skin-type IV. Patients were also categorized according to their type of diet: vegans, vegetarians, following paleo or ketogenic diets, or observing Ramadan fasting (n = 24 for each group). In line with matching criteria, no statistically significant differences were detected for age-, gender-, or skin-type in the six considered groups (Table 3).
Diet and Time of the Day are the Main Determinants of MED Circadian Oscillations
After NB-UVB treatment and complete clinical resolution, psoriatic patients still maintain circadian oscillations of MED that are influenced by time effect and diet (p < 0.001), as reported by both two-way mixed ANOVA and mixed MANOVA (Table 4).
Remarkably, MED results in the Ramadan fasting group were statistically different in the morning, afternoon, and evening from MED results of patients practicing other diets. Ramadan patients displayed both globally, and at the considered timepoints, the highest MED, while vegans displayed the lowest MED (Table 4).
In the morning, MED values for the ketogenic diet were statistically different from omnivores, Ramadan and vegans, while the paleo diet differed in terms of MED from Ramadan and vegan. Then, vegans differed from all other diets except omnivores. Vegetarians differed only from vegans and Ramadan fasting.
In the afternoon, MED values of Ramadan fasting patients and vegans were statistically significantly different to all the other considered groups. Omnivores differed from paleo diet patients. Ketogenic, paleo and omnivore diets did not differ.
Likewise, in the evening, Ramadan fasting patients and vegans exhibited MED values statistically significantly different to all the other considered groups (Fig. 3A).
Interestingly, when we evaluated the different diets separately, we did not find a statistically significant difference in MED measured in the morning, afternoon, or evening, except for vegan and vegetarian diets. Furthermore, vegan patients still showed differences in MED measured in the morning and in the afternoon (Fig. 3B).
Discussion
In the present study, we found that circadian oscillations of MED exist in both healthy and PsO patients: MED decreases from the morning to the evening. In the past decade, several clinical determinants of MED have been found to have conflicting results, from skin color (assessed with colorimetric methods) [63, 64] to skin phototype [65,66,67], gender [65, 66], age [66], and meteorological factors [64, 67,68,69].
All these potential modulators act on three main biological mechanisms: melanin production, skin thickness, and vessels. Melanin and hemoglobin are the main chromophores of human skin; in particular, melanin increases UVB reflection, thus increasing MED. Conversely, vessel vasodilatation decreases refraction (thinner skin) and increases hemoglobin-dependent UVB absorption, thereby decreasing MED. Thus, MED is mainly determined by the interaction of melanin and hemoglobin, and external exposure (exposome) [70] (i.e., drugs or temperature) [64, 71] or internal factors (i.e., fever) can alter MED [72].
Physiological internal factors are mainly controlled by the circadian rhythm, a well-known peripheral clock in the skin controlling and regulating keratinocyte proliferation and differentiation, melanocyte metabolism, trans-epidermal water loss (TEWL), gland function, and even vessel tone [13]. Likewise, we demonstrated, for the first time, MED circadian oscillations in both patients with psoriasis and healthy controls, finding that MED is higher in the morning and tends to decrease in the evening. This aspect has a practical implication because patients with low MED (20–25 mJ/cm2) should be preferentially treated in the morning to minimize the possibility of burns and increase the session implementation, especially if the patient is vegan.
Remarkably, psoriasis represents a pathological internal condition characterized by both cutaneous and systemic inflammation capable of creating circadian dysfunction both in peripheral and in central clocks [28, 73]. The central clock dysfunction in psoriatic patients manifests with sleep disorders such as obstructive sleep apnea and insomnia, two factors negatively influencing quality of life [74,75,76]. Furthermore, keratinocyte hyperplasia, neutrophil chemoattraction in the skin, Th1/Th17 dysregulation, and neoangiogenesis represent the clinical hallmarks of psoriasis but are also related to circadian rhythm de-regulation in the cutaneous peripheral clock [38] and to MED [64].
Focusing on the external factors capable of modulating MED, our team has previously shown that diet modulates cutaneous severity in both PsO [19] and PsA [20] patients, and that vegan/vegetarian diets modify cutaneous photosensitivity to UVB [77]. In the present study, we found that diets can impact MED values at different daily time-points, with MED values significantly lower in vegan patients, confirming and expanding our previous study [77], and MED values higher in those following Ramadan fasting. In fact, different dietary compounds modify microRNA expression [78], gut microbiome [79], and clinical severity of psoriasis [78]: three well-known modulators of MED. Similarly, the content, quality, and dietary sources of macronutrients, including fats, carbohydrates, and proteins, may modulate cell/tissue inflammation, oxidative stress, proliferation/differentiation, and clinical severity of psoriasis [80]. Interestingly, the afternoon MED differences in patients following omnivore, ketogenic or paleo diets disappeared. The ketogenic diet [81], characterized by a low carbohydrate intake along with a high intake of protein and fat, has been demonstrated to improve clinical symptoms and biochemical and inflammatory markers in PsO patients. Similarly, Ramadan fasting, with the corresponding changes in sleep–wake cycles, has been shown to be beneficial in terms of PsO severity [19]. Data on paleo diet in psoriasis are very scarce, but recently a US survey in PsO patients has found self-reported symptom improvement with the paleo diet [39]. Further research is, however, warranted to confirm and mechanistically investigate the effects of diets and their components on psoriasis management.
Furthermore, some dietary compounds, including polyphenols, vitamins, fatty acids, or the macronutrient content of the diet, have been shown to affect the expression and/or function of the circadian clock machinery in different peripheral tissues, with the ability to also function as circadian clock drivers (zeitgebers) of biological processes, either impairing or restoring circadian rhythmicity [82, 83]. Further investigation is needed to assess the specific effects of dietary compounds on the skin circadian clock system in relation to psoriasis-linked circadian dysfunction.
Interestingly, after NB-UVB treatment, MED circadian oscillations are modified and increase from morning to evening only in vegan psoriatic patients. In fact, NB-UVB treatment modifies the cutaneous reactivity to external exposures via (a) the migration of Langerhans cells to lymph nodes [84] and (b) regularizing the skin microbiome dysregulation due to psoriatic inflammation [36, 85], and these effects are magnified by quantities of furocumarins ingested, as seen in the vegan diet. Circadian re-set of MED after treatment also suggests that cutaneous psoriasis should always be treated with the principal of chronomedicine to avoid immunological dysfunction.
Skin exposure to NB-UVB also modulates the human gut microbiome and increases vitamin D serum levels linearly with Lachnospiraceae prevalence [86]. Thus, a proper diet may act synergically with anti-psoriatic drugs to re-establish cutaneous homeostasis and to extinguish peripheral clock dysregulation.
In this study, we focused on circadian oscillations and diet in psoriatic non-obese patients that had no addictions (i.e., smoking or alcohol), so future studies should further investigate these patient subsets that display contraindication to first line systemic treatments (i.e., methotrexate). NB-UVB was also evaluated as a single therapy, while in real life, phototherapy is commonly used as a combination therapy to achieve PASI 100 or even to counteract a gradual loss of response to a biologic drug. Further studies should also evaluate the knowledge of, attitude to, and practice of sun-exposure in patients undergoing NB-UVB.
Thus, detailed knowledge of MED determinants is of paramount importance in order to increase NB-UVB efficacy while decreasing the frequency of burns.
Conclusions
The present study further strengthens the concept of both chronomedicine and precision medicine, showing that NB-UVB should be preferentially delivered in the morning, and phototherapy protocols should account for a patient’s diet. In contrast with Rodriguez et al. [87], MED should always be calculated before starting NB-UVB because (a) internal and external factors may alter MED, (b) MED is not directly derived from the skin type, and (c) circadian rhythm can modify cutaneous UVB susceptibility.
References
Damiani G, Bragazzi NL, Karimkhani CA, Wu D, Alicandro G, McGonagle D, et al. The global, regional, and national burden of psoriasis: results and insights from the global burden of disease 2019 study. Front Med. 2021. https://doi.org/10.3389/fmed.2021.743180.
Buja A, Miatton A, Cozzolino C, Brazzale AR, Lo Bue R, Mercuri SR, Proft FN, Kridin K, Cohen AD, Damiani G. The prevalent comorbidome at the onset of psoriasis diagnosis. Dermatol Ther (Heidelb). 2023. https://doi.org/10.1007/s13555-023-00986-0.
Damiani G, Franchi C, Pigatto P, Altomare A, Pacifico A, Petrou S, et al. Outcomes assessment of hepatitis C virus-positive psoriatic patients treated using pegylated interferon in combination with ribavirin compared to new direct-acting antiviral agents. World J Hepatol. 2018;10(2):329–36.
Yen H, Yen H, Chi CC. Is psoriasis associated with dementia or cognitive impairment? A critically appraised topic. Br J Dermatol. 2021;184(1):34–42.
Damiani G, Bragazzi NL, Garbarino S, Chattu VK, Shapiro CM, Pacifico A, et al. Psoriatic and psoriatic arthritis patients with and without jet-lag: does it matter for disease severity scores? Insights and implications from a pilot, prospective study. Chronobiol Int. 2019;36(12):1733–40.
Papadavid E, Dalamaga M, Vlami K, Koumaki D, Gyftopoulos S, Christodoulatos GS, et al. Psoriasis is associated with risk of obstructive sleep apnea independently from metabolic parameters and other comorbidities: a large hospital-based case-control study. Sleep Breath. 2017;21(4):949–58.
Damiani G, Pacifico A, Rizzi M, Santus P, Bridgewood C, Bragazzi NL, et al. Patients with psoriatic arthritis have higher levels of FeNO than those with only psoriasis, which may reflect a higher prevalence of a subclinical respiratory involvement. Clin Rheumatol. 2020;39(10):2981–8.
Santus P, Rizzi M, Radovanovic D, Airoldi A, Cristiano A, Conic R, et al. Psoriasis and respiratory comorbidities: the added value of fraction of exhaled nitric oxide as a new method to detect, evaluate, and monitor psoriatic systemic involvement and therapeutic efficacy. Biomed Res Int. 2018;2018:3140682.
Soliman MM. Depressive, anxiety, stress, and insomnia symptoms in patients with psoriasis: a cross-sectional study. Postepy Dermatol Alergol. 2021;38(3):510–9.
Aguayo-Carreras P, Ruiz-Carrascosa JC, Ruiz-Villaverde R, Molina-Leyva A. Four years stability of type D personality in patients with moderate to severe psoriasis and its implications for psychological impairment. An Bras Dermatol. 2021;96(5):558–64.
Jensen KK, Serup J, Alsing KK. Psoriasis and seasonal variation: a systematic review on reports from Northern and Central Europe—Little overall variation but distinctive subsets with improvement in summer or wintertime. Skin Res Technol. 2021. https://doi.org/10.1111/srt.13102.
Zheng X, Wang Q, Luo Y, Lu W, Jin L, Chen M, et al. Seasonal variation of psoriasis and its impact in the therapeutic management: a retrospective study on Chinese patients. Clin Cosmet Investig Dermatol. 2021;14:459–65.
Addison R, Weatherhead SC, Pawitri A, Smith GR, Rider A, Grantham HJ, et al. Therapeutic wavelengths of ultraviolet B radiation activate apoptotic, circadian rhythm, redox signalling and key canonical pathways in psoriatic epidermis. Redox Biol. 2021;41: 101924.
Li WQ, Qureshi AA, Schernhammer ES, Han J. Rotating night-shift work and risk of psoriasis in US women. J Invest Dermatol. 2013;133(2):565–7.
Kecklund G, Axelsson J. Health consequences of shift work and insufficient sleep. BMJ. 2016;355: i5210.
Cohen JM, Jackson CL, Li TY, Wu S, Qureshi AA. Sleep disordered breathing and the risk of psoriasis among US women. Arch Dermatol Res. 2015;307(5):433–8.
Garbarino S, Lanteri P, Feeling NR, Jarczok MN, Quintana DS, Koenig J, et al. Circadian rhythms, sleep, and the autonomic nervous system: a position paper. J Psychophysiol. 2020;34(1):1–9.
Herxheimer A. Jet lag. BMJ Clin Evid. 2014;2014:2303.
Damiani G, Watad A, Bridgewood C, Pigatto PDM, Pacifico A, Malagoli P, et al. The impact of Ramadan fasting on the reduction of PASI Score, in moderate-to-severe psoriatic patients: a real-life multicenter study. Nutrients. 2019;11(2):277.
Adawi M, Damiani G, Bragazzi NL, Bridgewood C, Pacifico A, Conic RRZ, et al. The impact of intermittent fasting (Ramadan fasting) on psoriatic arthritis disease activity, enthesitis, and dactylitis: a multicentre study. Nutrients. 2019;11(3):601.
Nguyen S, Bahakeem H, Alkhalifah A, Cavalié M, Boukari F, Montaudié H, et al. Topical corticosteroids application in the evening is more effective than in the morning in psoriasis: results of a prospective comparative study. J Eur Acad Dermatol Venereol. 2017;31(5):e263–4.
Taliercio VL, Snyder AM, Webber LB, Langner AU, Rich BE, Beshay AP, et al. The disruptiveness of itchiness from psoriasis: a qualitative study of the impact of a single symptom on quality of life. J Clin Aesthet Dermatol. 2021;14(6):42–8.
Podder I, Mondal H, Kroumpouzos G. Nocturnal pruritus and sleep disturbance associated with dermatologic disorders in adult patients. Int J Womens Dermatol. 2021;7(4):403–10.
Damiani G, Cazzaniga S, Conic RR, Naldi L. Psocare registry network. Pruritus characteristics in a large Italian cohort of psoriatic patients. J Eur Acad Dermatol Venereol. 2019;33(7):1316–24.
Damiani G, Kridin K, Pacifico A, Malagoli P, Pigatto PDM, Finelli R, et al. Antihistamines-refractory chronic pruritus in psoriatic patients undergoing biologics: aprepitant vs antihistamine double dosage, a real-world data. J Dermatolog Treat. 2020. https://doi.org/10.1080/09546634.2020.1840502.
Sommer R, Augustin M, Hilbring C, Ständer S, Hubo M, Hutt HJ, et al. Significance of chronic pruritus for intrapersonal burden and interpersonal experiences of stigmatization and sexuality in patients with psoriasis. J Eur Acad Dermatol Venereol. 2021;35(7):1553–61.
Geyfman M, Kumar V, Liu Q, Ruiz R, Gordon W, Espitia F, et al. Brain and muscle arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis. Proc Natl Acad Sci. 2012;109:11758–63.
Ando N, Nakamura Y, Aoki R, Ishimaru K, Ogawa H, Okumura K, et al. Circadian gene clock regulates psoriasis-like skin inflammation in mice. J Invest Dermatol. 2015;135:3001–8.
Labrecque N, Cermakian N. Circadian clocks in the immune system. J Biol Rhythms. 2015;30:277–90.
Torres AE, Lyons AB, Hamzavi IH, Lim HW. Role of phototherapy in the era of biologics. J Am Acad Dermatol. 2021;84(2):479–85.
Garbarino S, Lanteri P, Bragazzi NL, Magnavita N, Scoditti E. Role of sleep deprivation in immune-related disease risk and outcomes. Commun Biol. 2021;4(1):1304.
Kostović K, Žužul K, Čeović R, Bukvić Mokos Z. Psoriasis in the mature patient: therapeutic approach in the era of biologics. Clin Dermatol. 2018;36(2):222–30.
Benáková N. Phototherapy of psoriasis in the era of biologics: still in. Acta Dermatovenerol Croat. 2011;19(3):195–205.
Conti A, Damiani G, Ruggeri R, Odorici G, Farnetani F, Pigatto PDM, et al. Switching infliximab in psoriatic patients during COVID-19 pandemics: a real-life retrospective study comparing intra-versus interclass switching strategies. Dermatol Ther. 2021;34(5): e15088.
Gisondi P, Piaserico S, Naldi L, Dapavo P, Conti A, Malagoli P, et al. Incidence rates of hospitalization and death from COVID-19 in patients with psoriasis receiving biological treatment: a Northern Italy experience. J Allergy Clin Immunol. 2021;147(2):558-560.e1.
Assarsson M, Duvetorp A, Dienus O, Söderman J, Seifert O. Significant changes in the skin microbiome in patients with chronic plaque psoriasis after treatment with narrowband ultraviolet B. Acta Derm Venereol. 2018;98(4):428–36.
Patra V, Gallais Sérézal I, Wolf P. Potential of skin microbiome, pro- and/or pre-biotics to affect local cutaneous responses to UV exposure. Nutrients. 2020;12(6):1795.
Pacifico A, Conic RRZ, Cristaudo A, Garbarino S, Ardigò M, Morrone A, et al. Diet-related phototoxic reactions in psoriatic patients undergoing phototherapy: results from a multicenter prospective study. Nutrients. 2021;13(9):2934.
Afifi L, Danesh MJ, Lee KM, et al. Dietary behaviors in psoriasis: patient-reported outcomes from a U.S. national survey. Dermatol Ther (Heidelb). 2017;7(2):227–42.
Kridin K, Ludwig RJ, Damiani G, Cohen AD. Increased risk of pemphigus among patients with psoriasis: a large-scale cohort study. Acta Derm Venereol. 2020;100(17):adv00293.
Rui W, Xiangyu D, Fang X, Long G, Yi Y, Wenjuan W, et al. Metabolic syndrome affects narrow-band UVB phototherapy response in patients with psoriasis. Medicine (Baltimore). 2017;96(50): e8677.
www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption. Accessed 10 Aug 2023.
Damiani G, Pacifico A, Russo F, Pigatto PDM, Bragazzi NL, Bonifati C, et al. Use of secukinumab in a cohort of erythrodermic psoriatic patients: a pilot study. J Clin Med. 2019;8(6):770.
Chi CC, Lee CY, Liu CY, Wang SH, Tien O’Donnell F, Tung TH. Effects of antidiabetic drugs on psoriasis: a meta-analysis. Eur J Clin Invest. 2021;51(2): e13377.
Fiore M, Leone S, Maraolo AE, Berti E, Damiani G. Liver illness and psoriatic patients. Biomed Res Int. 2018;2018:3140983.
Arisi M, Gelmetti A, Focà E, Rossi M, Rovati C, Calzavara-Pinton P, et al. UVA1 phototherapy as a treatment option for plaque psoriasis in HIV-positive patients. Photodermatol Photoimmunol Photomed. 2020;36(6):478–80.
Gisondi P, Cazzaniga S, Chimenti S, Maccarone M, Picardo M, Girolomoni G, et al. Latent tuberculosis infection in patients with chronic plaque psoriasis: evidence from the Italian Psocare Registry. Br J Dermatol. 2015;172(6):1613–20.
Karaosmanoglu N, Ozdemir Cetinkaya P, Kutlu O, Karaaslan E, Imren IG, Kiratli Nalbant E, et al. A cross-sectional analysis of skin cancer risk in patients receiving narrow-band ultraviolet B phototherapy: an evaluation of 100 patients. Arch Dermatol Res. 2020;312(4):249–53.
Fredriksson T, Pettersson U. Severe psoriasis—oral therapy with a new retinoid. Dermatologica. 1978;157(4):238–44.
Ibrahim GH, Buch MH, Lawson C, Waxman R, Helliwell PS. Evaluation of an existing screening tool for psoriatic arthritis in people with psoriasis and the development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire. Clin Exp Rheumatol. 2009;27:469–74.
https://www.vegansociety.com/go-vegan/definition-veganism. Accessed 10 Aug 2023.
Jaacks LM, Kapoor D, Singh K, Narayan KV, Ali MK, Kadir MM, Mohan V, Tandon N, Prabhakaran D. Vegetarianism and cardio-metabolic disease risk factors: differences between South Asian and US adults. Nutrition. 2016;32:975–84.
Sremanakova J, Sowerbutts AM, Burden S. A systematic review of the use of ketogenic diets in adult patients with cancer. J Hum Nutr Diet. 2018;31(6):793–802.
Shilpa J, Mohan V. Ketogenic diets: boon or bane? Indian J Med Res. 2018;148(3):251–3.
de la Víctor O, Zazpe I, Martínez JA, Santiago S, Carlos S, Zulet MÁ, et al. Scoping review of Paleolithic dietary patterns: a definition proposal. Nutr Res Rev. 2021;34(1):78–106.
Stingeni L, Bianchi L, Hansel K, Corazza M, Gallo R, Guarneri F, et al. Italian guidelines in patch testing—adapted from the European society of contact dermatitis (ESCD). G Ital Dermatol Venereol. 2019;154(3):227–53.
Damiani G, Calzavara-Pinton P, Stingeni L, Hansel K, Cusano F, et al. Italian guidelines for therapy of atopic dermatitis—adapted from consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis). Dermatol Ther. 2019;32(6): e13121.
Russo F, Vispi M, Sirna R, Mancini V, Bagnoni G, Bartoli L, et al. Tuscan consensus on the use of UVBnb phototherapy in the treatment of psoriasis. G Ital Dermatol Venereol. 2019;154(2):99–105.
Damiani G, Pacifico A, Chu S, Chi CC, Young Dermatologists Italian Network (YDIN). Frequency of phototherapy for treating psoriasis: a systematic review. Ital J Dermatol Venerol. 2021. https://doi.org/10.23736/S2784-8671.21.06975-3.
Pacifico A, Ardigò M, Frascione P, Damiani G, Morrone A. Phototherapeutic approach to dermatology patients during the 2019 coronavirus pandemic: real-life data from the Italian red zone. Br J Dermatol. 2020;183(2):375–6.
Pacifico A, Damiani G, Iacovelli P, Conic RRZ, Scarabello A, Filoni A, et al. Photoadaptation to ultraviolet B TL01 in psoriatic patients. J Eur Acad Dermatol Venereol. 2020;34(8):1750–4.
Lee Y. What repeated measures analysis of variances really tells us. Korean J Anesthesiol. 2015;68(4):340–5.
Tan Y, Wang F, Fan G, Zheng Y, Li B, Li N, et al. Identification of factors associated with minimal erythema dose variations in a large-scale population study of 22 146 subjects. J Eur Acad Dermatol Venereol. 2020;34(7):1595–600.
Li YW, Chu CY. The minimal erythema dose of broadband ultraviolet B in Taiwanese. J Formos Med Assoc. 2007;106(11):975–8.
Rodríguez-Granados MT, Estany-Gestal A, Pousa-Martínez M, Labandeira J, Gato Otero R, Fernández-Redondo V. Is it useful to calculate minimal erythema dose before narrowband UV-B phototherapy? Actas Dermosifiliogr. 2017;108(9):852–8.
Ettler K. Determination of the minimal erythema dosage and natural photoprotection of the skin in the population. Acta Medica (Hradec Kralove). 1998;41:81–104.
Gniadecka M, Lock-Andersen J, de Fine Olivarius F. Skin temperature and phototest evaluation. Photodermatol Photoimmunol Photomed. 1996;12:189–93.
Sayre RM, Desrochers DL, Wilson CJ. Skin type, minimal erythema dose (MED), and sunlight acclimatization. J Am Acad Dermatol. 1981;5:439–43.
Cameron H, Dawe RS. Photosensitizing drugs may lower the narrow-band ultraviolet B (TL-01) minimal erythema dose. Br J Dermatol. 2000;142(2):389–90.
DeBord DG, Carreón T, Lentz TJ, Middendorf PJ, Hoover MD, Schulte PA. Use of the “exposome” in the practice of epidemiology: a primer on -omic technologies. Am J Epidemiol. 2016;184(4):302–14.
Fujii N, Amano T, Kenny GP, Honda Y, Kondo N, Nishiyasu T. Nicotinic receptors modulate skin perfusion during normothermia, and have a limited role in skin vasodilatation and sweating during hyperthermia. Exp Physiol. 2019;104(12):1808–18.
Lyons AB, Moy L, Moy R, Tung R. Circadian rhythm and the skin: a review of the literature. J Clin Aesthet Dermatol. 2019;12(9):42–5.
Nowowiejska J, Baran A, Flisiak I. Mutual relationship between sleep disorders, quality of life and psychosocial aspects in patients with psoriasis. Front Psychiatry. 2021;12: 674460.
Tas B, Kabeloglu V. Prevalence of metabolic syndrome and its parameters and their correlations with psoriasis duration, severity, and sleep quality in psoriasis patients: a cross-sectional study. Dermatol Pract Concept. 2021;11(3): e2021049.
Kelly A, Meurling J, Kirthi Jeyarajah S, Ryan C, Hughes R, et al. Obstructive sleep apnoea in psoriasis and hidradenitis suppurativa. Br J Dermatol. 2021;184(6):1183–5.
Zheng D, Ratiner K, Elinav E. Circadian influences of diet on the microbiome and immunity. Trends Immunol. 2020;41(6):512–30.
Kocic H, Damiani G, Stamenkovic B, Tirant M, Jovic A, Tiodorovic D, et al. Dietary compounds as potential modulators of microRNA expression in psoriasis. Ther Adv Chronic Dis. 2019;10:2040622319864805.
Damiani G, Bragazzi NL, McCormick TS, Pigatto PDM, Leone S, Pacifico A, et al. Gut microbiota and nutrient interactions with skin in psoriasis: a comprehensive review of animal and human studies. World J Clin Cases. 2020;8(6):1002–12.
Keaney TC, Kirsner RS. New insights into the mechanism of narrow-band UVB therapy for psoriasis. J Invest Dermatol. 2010;130(11):2534.
Katsimbri P, Korakas E, Kountouri A, Ikonomidis I, Tsougos E, Vlachos D, et al. The effect of antioxidant and anti-inflammatory capacity of diet on psoriasis and psoriatic arthritis phenotype: nutrition as therapeutic tool? Antioxidants (Basel). 2021;10(2):157.
Castaldo G, Pagano I, Grimaldi M, Marino C, Molettieri P, Santoro A, et al. Effect of very-low-calorie ketogenic diet on psoriasis patients: a nuclear magnetic resonance-based metabolomic study. J Proteome Res. 2021;20(3):1509–21.
Pickel L, Sung HK. Feeding rhythms and the circadian regulation of metabolism. Front Nutr. 2020;7:39.
Ribas-Latre A, Eckel-Mahan K. Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health. Mol Metab. 2016;5(3):133–52.
Ron-Doitch S, Frušić-Zlotkin M, Soroka Y, Duanis-Assaf D, Amar D, Kohen R, Steinberg D. eDNA-mediated cutaneous protection against UVB damage conferred by staphylococcal epidermal colonization. Microorganisms. 2021;9(4):788.
Burns EM, Ahmed H, Isedeh PN, Kohli I, Van Der Pol W, Shaheen A, et al. Ultraviolet radiation, both UVA and UVB, influences the composition of the skin microbiome. Exp Dermatol. 2019;28(2):136–41.
Bosman ES, Albert AY, Lui H, Dutz JP, Vallance BA. Skin exposure to narrow band ultraviolet (UVB) light modulates the human intestinal microbiome. Front Microbiol. 2019;10:2410.
Lakens D. Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front Psychol. 2013;4:863.
Acknowledgments
Funding
No funding or sponsorship was received for this study or publication of this article.
Medical Writing
Authors entirely wrote the manuscript without external support.
Author Contributions
Conceptualization, Giovanni Damiani, Alessia Pacifico and Sergio Garbarino; methodology, Giovanni Damiani, Alessia Pacifico, Egeria Scoditti, and Christopher G. Bunick; software, Claudia Cozzolino and Santo R. Mercuri; validation, Sara di Gregorio, Claudia Cozzolino, and Alessandra Buja; formal analysis, Claudia Cozzolino, Vittoria G. Bianchi and Ayman Grada; investigation, Giovanni Damiani; resources, Giovanni Damiani, Santo R. Mercuri and Sergio Garbarino; data curation, Alessia Pacifico and Egeria Scoditti; writing—original draft preparation, Giovanni Damiani and Vittoria G. Bianchi; writing—review and editing, Giovanni Damiani, Alessia Pacifico, Egeria Scoditti, Sara di Gregorio, Massimo Del Fabbro, Claudia Cozzolino, Alessandra Buja, Santo R. Mercuri, Vittoria G. Bianchi, Ayman Grada, Sergio Garbarino and Christopher G. Bunick; visualization, Giovanni Damiani; supervision, Giovanni Damiani and Sergio Garbarino; project administration, Giovanni Damiani, Alessia Pacifico, Sara di Gregorio, Santo R. Mercuri and Vittoria G. Bianchi; funding acquisition, Giovanni Damiani and Sergio Garbarino. All authors have read and agreed to the published version of the manuscript.
Disclosures
The authors declare no conflict of interest.
Compliance with Ethics Guidelines
Saint Rafael Hospital (OSR) local ethical committee approved in 28.05.2021 the study protocol 176/int/2020 and the current study represents a post-hoc analysis. The study fulfilled all the prin-ciples of Helsinki Declaration. Informed consent was obtained from all subjects involved in the study.
Data Availability
The data presented in this study are available on request from the corresponding author (dr.giovanni.damiani@gmail.com). The data are not publicly available due to privacy issues.
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Damiani, G., Pacifico, A., Scoditti, E. et al. Circadian Oscillations of Minimal Erythema Dose (MED) are Also Influenced by Diet in Patients with Psoriasis: A Chronomedical Study. Dermatol Ther (Heidelb) 13, 2229–2246 (2023). https://doi.org/10.1007/s13555-023-00987-z
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DOI: https://doi.org/10.1007/s13555-023-00987-z