Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2022;12(3):e2022144 1 Dermatology Practical & Conceptual Comparison of Early and Late Onset Psoriasis (EOP and LOP) Regarding Systemic Inflammatory Comorbidities: LOP is a More Rapid Subtype of Psoriasis Leyla Huseynova Terzi1, Sibel Dogan Gunaydin1,2 1 Hacettepe University, Faculty of Medicine, Department of Dermatology and Venereology, Ankara, Turkey 2 Hacettepe University, Graduate School of Medical Sciences, Department of Pediatric Basic Sciences, Immunology, Ankara, Turkey Key words: psoriasis, comorbidity, early onset psoriasis, late onset psoriasis, inflammation Citation: Huseynova Terzi L, Dogan Gunaydin. Comparison of early (EOP) and late onset psoriasis (LOP) regarding systemic inflammatory comorbidities: LOP is a more rapid subtype of psoriasis. Dermatol Pract Concept. 2022;12(3):e2022144. DOI: https://doi.org/10.5826/ dpc.1203a144 Accepted: November 28, 2021; Published: July 2022 Copyright: ©2022 Tognetti 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: Leyla Huseynova Terzi, MD, Hacettepe University, Faculty of Medicine, Department of Dermatology and Venereology 9. entrance, 06100 Sıhhiye, Ankara, Turkey, +90 312 305 17 04- 17 06, Fax: +90 312 880 58 08, E-mail: leyla.huseynova@ymail.com Introduction: Early onset psoriasis (EOP) and late onset psoriasis (LOP) differ regarding genetic background, clinical presentation and course of disease. Objectives: In this study, comparison of EOP and LOP regarding systemic inflammatory comorbidi- ties which are frequently seen in psoriasis and determination of possible differences is aimed. Methods: A total of 160 plaque psoriasis patients (121 with EOP and 39 with LOP) were enrolled for the study. Data was collected with face-to-face questionnaire and patients medical chart evaluation. Collected data included medical and family history, clinical features and parameters indicating severity of psoriasis, results of laboratory work-up, physical and dermatological examination findings, presence of joint and nail involvement and associated inflammatory systemic comorbidities such as cardiovas- cular diseases (CVD), diabetes mellitus (DM), hypertension (HT), metabolic syndrome (MS), obesity. Results: Nail involvement and PsA occurred more rapidly in LOP compared to EOP (P < 0.01, P < 0.01). Compared frequencies in LOP and EOP were 7.7% versus 0.8% for CVD, 38.5% versus 14% for HT, 33.3% versus 9.9% for DM and 44.7% versus 24.8% for MS, respectively. CVD, HT, DM and MS were significantly more frequent in LOP compared to EOP (P = 0.045, P = 0.001, P < 0.01, P = 0.022). Results of multivariate analysis performed taking into account the age, gender, severity parameters of disease, alcohol consumption, smoking habits and other concurrent systemic comorbidities revealed LOP to be an independent risk factor for CVD and DM (P < 0.01, R2: 0.036, P < 0.01, R2: 0.077). Conclusions: LOP seems to interact with systemic comorbidities hence generates more severe inflam- matory burden and shows a more rapid course. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2022;12(3):e2022144 Introduction Psoriasis is a chronic, multifactorial inflammatory skin disease with a polygenic background and variable clinical presentations. Nowadays, it is more frequently referred as “psoriatic disease” due to its association with systemic co- morbidities such as psoriatic arthritis (PsA), obesity (OB), cardiovascular diseases (CVD), diabetes mellitus (DM), hy- pertension (HT), metabolic syndrome (MS) and inflamma- tory bowel diseases (IBD). Psoriasis is classified based upon phenotypic presentation, association with human leukocyte antigen (HLA) and age at onset [1]. Henseler and Christophers have observed that clinical characteristics of psoriasis differ according to the age of onset [2]. In patients who developed psoriasis before age 40, psoriasis tends to be more severe, recurrent and resistant to treatment. Thus, they offered new classification of psoriasis based upon the age of onset; psoriasis which developed before 40 years was accepted as early onset psoriasis (EOP) and psoriasis which developed after 40 years as late onset pso- riasis (LOP). Although this cut-off point have been used by several authors, others have used a wide range of cut-off point (30-50 years), thus limiting comparisons between studies [1,3–6]. Differences in the clinical characteristics and course of the disease, response to treatment, genetic predisposition and psychosocial effects in EOP and LOP have been reported in previous studies. EOP have been shown to be more severe and pose recurrent flares, positive family history, Koebner phe- nomenon and association with HLA-C [3–5,7–9]. EOP was also claimed to have more prominent psychosocial effect and requirement for systemic treatment is usually more frequent [1,7,10]. Epidemiologic studies have demonstrated association of psoriasis with systemic inflammatory diseases, but to our knowledge there is only one report comparing EOP and LOP regarding concomitant systemic inflammatory comorbidities, which found OB to be more frequent in LOP than EOP [1]. Objectives Based on previous literature and lack of data in this aspect, we aimed to compare inflammatory comorbidities along with clinical characteristics and severity of psoriatic dis- ease and possibly determine differences in EOP and LOP in this study. Methods Patients Data was collected by a face-to-face questionnaire and medi- cal chart evaluation. Patients older than 18 years of age with plaque psoriasis who were on follow-up at our department of dermatology between 1st October 2018 and 1st March 2019 were enrolled for the study. Patients with disease onset before age of 40 years were accepted as EOP and patients with disease onset equal or after 40 years were considered to have LOP. The study was approved by the ethic commit- tee of non-invasive clinical studies of Hacettepe University (ID GO 18/1057-30). Methods Questionnaire The face-to-face questionnaire consisted of 5 main sec- tions: (1) patient demographics; (2) psoriasis characteristics; (3) concurrent comorbidities; (4) physical and dermatologi- cal examination; (5) laboratory studies. Patient demographics Age, gender, place of birth, place of residence was recorded. Psoriasis characteristics Age of onset of the disease, existence of nail involvement, age at the onset of nail involvement, type of nail involvement, existence of concomitant PsA, age at the onset of PsA, family history of psoriasis and PsA and age at the onset of psoriasis and PsA of the family member, received treatment regimens and duration of the treatment were recorded. Duration of active psoriatic disease was also required to be evaluated. To make this assessment; active psoriatic disease was defined as existence of cutaneous psoriatic lesions affecting more than 3% of body surface area with or without given treatments and was calculated for each patient. Hospitalizations due to psoriasis and any existed erythroderma attacks were also recorded. Existent or previous psoriatic nail involvement in- cluding onycholysis, pitting, subungual hyperkeratosis and oil-drop sign were questioned in detail and recorded. Joint involvement was questioned based on the previous diagno- sis of PsA established by a rheumatologist. All patients were also filled out rheumatologic screening questionnaire (RSQ) regarding existence of PsA. RSQ included 5 items: (I) exis- tence of joint and muscle pain at rest, (II) existence of neck, waist or back pain awakening at nights, (III) existence of pain, edema and tenderness in hands or feet joint, (IV) his- tory of morning stiffness lasting for more than 20 minutes, and (V) existence of tenderness while stepping on heels in the mornings [11]. Patients were also consulted to rheumatol- ogy department based on the suspicion of PsA according to RSQ (patients with one or more positive answers to 5 items were consulted) and consultation results were added to the study data. Concurrent comorbidities Any previous diagnosis of concurrent systemic inflammatory comorbidities comprising HT, DM, NASH, CVD, DLP, MS, Original Article | Dermatol Pract Concept. 2022;12(3):e2022144 3 OB was noted. Patients who had physical examination and/ or laboratory findings indicative of definite disease according to below mentioned criteria despite lack of previous diagnosis, they were referred to concordant specialist for further evalu- ation, the results of this consultations were also added to this study data. HT was accepted as having systolic blood pressure ≥ 150 mmHg and diastolic blood pressure ≥ 90 mmHg in pa- tients ≥ 60 years and systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg in patients < 60 years [12]. Fasting blood glucose ≥ 126 mg/dl and random blood glucose ≥ 200 mg/dl was accepted as DM [13]. DLP was defined as total cholesterol levels > 200 mg/dl, LDL cholesterol > 100 mg/ dl, HDL cholesterol < 40 mg/dl, TG >150 mg/dl and non-HDL cholesterol > 130 mg/dl, as proposed by American Endocri- nology Association [14]. MS was accepted as having any three of the following five criteria: 1. obesity: waist circumference ≥ 102 cm in men and ≥ 88 cm in women; 2. dyslipidemia: TG > 150 mg/dl or having pharmacologic treatment (Rx); 3. dyslip- idemia (second, separate criteria): HDL cholesterol < 40 mg/dl in men and HDL cholesterol < 35 mg/dl in women or Rx; 4. HT: systolic blood pressure ≥ 130 mmHg and diastolic blood pressure ≥ 85, or Rx; 5.hyperglycemia fasting blood glucose ≥ 100 mg/dl or Rx [15]. CVD included history of MI, coronary artery by-pass surgery, balloon angioplasty or coronary artery stent, cerebrovascular accident or peripheral atherosclerotic vascular disease. OB was defined BMI ≥ 30 [16]. Physical and dermatologic examination Physical and dermatological examination findings ob- tained during examination in the last 6 months were noted. Physical examination findings included blood pres- sure, height, weight and waist circumference. Obtained dermatologic examination results comprised PASI score and affected body surface area (BSA). The severity of psoriasis was classified as mild (BSA ≤ 10; PASI ≤ 10) or moderate-to-severe (BSA > 10 and PASI > 10). Systemic treatment regimen, duration of systemic treatment, dura- tion of active disease (both under treatment and without any treatment), number of erythroderma attacks and hos- pitalization due to psoriasis were also collected to assess the severity of psoriasis. Laboratory studies Obtained laboratory test results conducted during the last 6 months including complete blood count, fasting blood glu- cose, C-reactive protein (CRP), total cholesterol (TC), high density lipoprotein cholesterol (HDL), low density lipopro- tein cholesterol (LDL), triglycerides (TG), blood urea nitro- gen (BUN) were recorded. Statistical Analysis Statistical analysis was performed using Statistical Package for the Social Science (SPSS) version 20.0. Patient group data were presented as mean ± standard deviation (SD) or median (range), as appropriate and compared with adjustments us- ing Fisher exact tests (for categorical variables) and Student two-sample t tests or Wilcoxon rank-sum tests (for contin- uous variables), subject to normality assumptions being sat- isfied. Associations between the age at the time of diagnosis and binary comorbidity outcomes were evaluated using mul- tiple logistic regression adjusted for age and other relevant confounders. Results Demographic Data and Disease Characteristics in EOP and LOP Data of 160 patients; 75.62% (N = 121) with EOP and 24.38% (N = 39) with LOP was analyzed and shown in Table 1. Family history of psoriasis was more frequent in EOP significantly. Family history of psoriasis was most fre- quently positive in the first-degree relatives in EOP and LOP: 23.1%, N = 28 and 10.3%, N = 4, respectively. Assessment of Severity of Psoriasis in EOP and LOP Severity of psoriasis was accessed depending on BSA per- centage, PASI score, active duration of the disease without any treatment and under treatment, history of hospitaliza- tions due to psoriasis and number of erythroderma attacks and no statistically significant difference was found in any parameters between EOP and LOP (Table 2). Physical Examination Findings in EOP and LOP Physical examination findings in EOP and LOP are shown in Table 3. Indicative findings of comorbidities such as HT and OB, eg systolic and diastolic blood pressure and BMI were significantly higher in LOP than EOP statistically (P = 0.005, P = 0.047 and P = 0.020). Laboratory Studies in EOP and LOP Laboratory work-up findings of the patients are shown in Table 4. Parameters indicating increased systemic inflam- mation, eg Red Cell Distribution Width (RDW), C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) were statistically higher in LOP than in EOP respectively (P = 0.017, P = 0.006, P = 0.001). Fasting blood glucose was also higher in LOP (P = 0.002). Systemic Treatments in EOP and LOP Duration of systemic treatment was 42.09 ± 44.41 months in all patients, 44.41 ± 45.76 in EOP and 34.91 ± 39.65 months in LOP showing no significant difference (P = 0.158). 4 Original Article | Dermatol Pract Concept. 2022;12(3):e2022144 Table 1. Demographics and family history of psoriasis in EOP and LOP Variables Total patients (N = 160) EOP (N = 121) LOP (N = 39) P Gender 0.144male, N (%) 90 (56.3) 72 (59.5) 18 (46.2) female, N (%) 70 (43.8) 40 (40.5) 21 (53.8) Age, years, 44.73 ± 13.66 40.46 ±12.24 57.95±8.40 <0.01 mean±SD (range) (18-75) (18-65) (41-75) Age at onset of psoriasis, years, 27.24±15.06 20.07±8.45 49.49±7.20 <0.01 mean±SD (range) (4-67) (4-38) (41-67) Family history of psoriasis, N (%) 64 (40) 57 (47.1) 7 (17.9) 0.001 EOP = early onset psoriasis; LOP = late onset psoriasis; SD = standard deviation. Table 2. Comparison of disease severity in EOP and LOP Variables Total patients (N = 160) EOP (N = 121) LOP (N = 39) P BSA, % 3.50 ± 8.65 3.34 ± 8.58 3.99 ± 8.96 mean±SD (range) (0-74.5) (0.1-74.7) (0-37.8) 0.636 PASI 3.46 ± 6.42 3.16 ± 6.07 4.37 ± 7.43 mean±SD (range) (0-53.10) (0.2-53.10) (0-36) 0.460 Active disease without Rx, months 24.46 ± 49.59 28.62 ± 55.26 11.54 ± 20.57 mean±SD (range) (0-360) (0-360) (0-96) 0.083 Active disease with Rx, months 28.29 ± 68.68 33.78 ± 77.57 11.26 ± 18.32 mean±SD (range) (0-492) (0-492) (0-72) 0.334 History of hospitalization Number of positive history, N (%) 28 (17.5) 24 (19.8) 4 (10.3) 0.171 Number of hospitalizations 0.38 ± 1.25 0.35 ± 0.90 0.49 ± 1.99 mean±SD (range) (0-12) (0-5) (0-12) 0.380 History of erythroderma number of positive history, N (%) 12 (7.5) 11 (9.1) 1 (2.6) 0.296 Number of erythroderma 0.13 ± 0.55 0.16 ± 0.61 0.05 ± 0.32 mean±SD (range) (0-5) (0-5) (0-2) 0.187 BSA = body surface area; EOP = early onset psoriasis; LOP = late onset psoriasis; PASI = psoriasis area and severity index; Rx = systemic treatment; SD = standard deviation. Table 3. Physical examination findings in EOP and LOP Variables Total patients (N = 160) EOP (N = 121) LOP (N = 39) P Systolic BP, mm/Hg 118.17 ± 13.39 116.24 ± 12.46 124.18 ± 14.55 mean±SD (range) (90-160) (90-150) (100-160) 0.005 Diastolic BP, mm/Hg 79.31 ± 10.94 78.14 ± 10.02 82.95 ± 12.86 mean±SD (range) (50-120) (50-100) (60-120) 0.047 BMI, kg/m2 28.02 ± 4.93 27.62 ± 5.16 29.27 ± 3.94 mean±SD (range) (16.67-46.90) (16.67-46.90) (21.39-39.40) 0.020 Waist circumference/men, cm 102.07 ±13.55 101.13 ±13.97 105.83 ±11.31 mean±SD (range) (76-143) (76-143) (79-129) 0.190 Waist circumference/women, cm 99.80 ± 13.29 98.67 ±14.62 102.42 ± 9.29 mean±SD (range) (76-149) (76-149) (84-127) 0.282 BMI = body mass index; BP = blood pressure; EOP = early onset psoriasis; LOP = late onset psoriasis; SD = standard deviation. Original Article | Dermatol Pract Concept. 2022;12(3):e2022144 5 Nail Involvement in EOP and LOP Psoriatic nail involvement was compared in EOP and LOP, and results are shown in Table 5. The duration of disease between onset of psoriasis and nail involvement was sta- tistically significantly shorter in LOP than EOP (P < 0.01). Duration of active psoriatic disease in patients with nail in- volvement was also significantly shorter in LOP than in EOP (P < 0.01, P < 0.01). The most frequent psoriatic nail involvement was seen as pitting, observed in 14% (N = 17) of EOP and 12.8% (N = 5) in LOP. Subungual hyperkeratosis was only observed in 5% (N = 6) of EOP, distal onycholysis was observed in 5% (N = 6) and 10.3% (N = 4), oil-drop sign was observed in 5% (N = 6) and 2.3 % (N = 1) of EOP and LOP, respectively. PsA in EOP and LOP Data regarding prevalence of PsA, age at onset of PsA, dura- tion between onset of psoriasis and PsA, and active disease duration of patients with PsA with and without treatment are shown in Table 6. Duration between onset of psori- asis and PsA was significantly shorter in LOP than EOP (P < 0.01). Duration of active disease in PsA patients with or without systemic treatments was also significantly shorter in LOP than EOP respectively (P = 0.002, P < 0.01). RSQ revealed morning stiffness in 10.7% (N = 13) of EOP and 5.1 % (N = 2) of LOP. Muscle-joint complaints was observed in 9.1% (N = 11) and 10.3% (N = 4), small joints complaints were found in 9.1% (N = 11) and 5.1% (N = 2), enthesis complaints were found in 14% (N = 17) and 12.8% (N = 5) and axial complaints were noted in 14.9 % (N = 18) and 20.5% (N = 8) of EOP and LOP patients respectively. None of the patients referred to rheumatologic consultations were diagnosed with PsA. Concurrent Systemic Inflammatory Comorbidities in EOP and LOP Prevalence and age at onset of systemic inflammatory co- morbidities in EOP and LOP are shown in Table 7. CVD, HT, DM and MS were found significantly more frequent in LOP compared to EOP (P = 0.045, P = 0.001, P < 0.01, P = 0.022). In order to evaluate the effect of psoriasis subtype to the development of concurrent systemic inflammatory comor- bidities, multivariate regression analysis was performed; age, gender, severity parameters of disease, alcohol consumption, smoking habits and other concurrent systemic comorbidities were taken into account (Table 8). Based on this analysis, LOP was found as an independent risk factor for CVD and DM (P < 0.01, R2: 0.036; P < 0.01, R2: 0.077). Risk of CVD, DM, HT and MS were increased accordingly with decades of psoriasis onset (P = 0.036, P = 0.007, P = 0.001, P = 0.003). NASH, DLP and OB development risk was not found to be showing this relationship with psoriasis onset (P = 0.194, P = 0.158, P = 0.644). Conclusions As it was aimed, comparison of disease characteristics and concurrent inflammatory comorbidities enabled us to spot the peculiar differences in EOP and LOP; we were also able Table 4. Laboratory findings in EOP and LOP Variables Total patients (N = 160) EOP (N = 121) LOP (N = 39) P Hemoglobin, gr/dL 14.71 ± 1.46 14.85 ± 1.43 14.28 ± 1.48 mean±SD (range) (9.6-17.6) (9.6-17.6) (11.0-17.2) 0.035 WBC, x103/µL 7069 ± 1716.37 6973 ±1701.75 7364 ± 1750.11 mean±SD (range) (3800-13400) (3900-11800) (3800-13400) 0.222 Platelets, x103/µL 230597±60028.87 227699 ±58982.59 239589 ± 63101.30 mean±SD (range) (24600-424000) (24600-381000) (137000-424000) 0.283 RDW, % 13.99±1.64 13.84 ± 1.33 14.46 ± 2.34 mean±SD (range) (12-27) (12-20.1) (12.5-27.1) 0.017 Fasting blood glucose, mg/dL 97.75 ± 25.77 94.84 ± 22.37 106.65 ± 32.92 mean±SD (range) (68-260) (68-203) (77-260) 0.002 CRP, mg/L 0.52 ± 0.81 0.45 ± 0.59 0.76 ± 1.28 mean±SD (range) (0.02-7.90) (0.02-5.59) (0.15-7.99) 0.006 ESR, mm/hour 11.61 ± 9.52 10.30 ± 8.58 16.56 ± 11.30 mean±SD (range) (2-54) (2-37) (2-54) 0.001 CRP = C-reactive protein; EOP = early onset psoriasis; ESR = erythrocyte sedimentation rate; LOP = late onset psoriasis; MCV = mean corpuscular volume; MPV = mean platelet volume; NLR = neutrophil lymphocyte ratio; RDW = red cell distribution width; SD = standard deviation; WBC = white blood cells. 6 Original Article | Dermatol Pract Concept. 2022;12(3):e2022144 Table 6. PsA characteristics in EOP and LOP Variables Total patients (N = 160) EOP (N = 121) LOP (N = 39) P PsA, N (%) 41 (25.6) 33 (27.3) 8 (20.5) 0.057 Age at PsA onset, years 38.98 ± 11.64 37.0 ± 11.49 47.13 ± 8.77 mean±SD (range) (10-71) (10-63) (37-71) 0.025 Duration between Ps and PsA, years 12.80 ± 11.46 15.72 ± 10.36 0.75 ± 7.36 -a, < 0,01b mean±SD (range) (15-34) (1-34) (1-15) Active Ps duration in PsA patients with Rx, months 28.34 ± 9.2 34 ± 20.1 6 ± 8.3 0.761 a, 0.002 b mean±SD Active Ps duration in PsA patients without Rx, months 27.98 ± 10.3 33 ± 15.1 9 ± 18.1 0.803 a, < 0.0 b mean±SD EOP = early onset psoriasis; LOP = late onset psoriasis; Ps = psoriasis; PsA = psoriatic arthritis; Rx = systemic treatment; SD = standard deviation. Pa: patients with psoriasis; Pb: between EOP and LOP Table 5. Psoriatic nail involvement in EOP and LOP Variables Total patients (N = 160) EOP (N = 121) LOP (n = 39) P Nail involvement, n (%) 87 (54.3) 68 (56.1) 19 (48.7) 0.415 Age at nail involvement onset, years 34.29 ± 12.93 29.51 ± 10.23 49.85 ± 7.33 mean±SD (range) (10-70) (10-62) (37-70) < 0.01 Disease duration between Ps and nail involvement, years 7.4 ± 8.1 9.06 ± 8.5 2.1 ± 3.0 - a, < 0.01b mean±SD (range) (4-37) (0-37) (4-9) Concurrent nail involvement and PsA, N (%) 28 (17.5) 8 (6.6) 5 (12.8) 0.072 a, 0.041 b Active disease duration in patients with nail involvement and Rx, months 30.63 ± 9.1 35 ± 48.32 16 ± 19.3 0.639 a, < 0.01 b mean±SD Active disease duration in patients with nail involvement without Rx, months 30.22 ± 9.8 34 ± 50.1 17 ± 18.2 0.027a, < 0.01 b mean±SD EOP = early onset psoriasis; LOP = late onset psoriasis; Ps = psoriasis; PsA = psoriatic arthritis; Rx = systemic treatment; SD = standard deviation. P a: patients with psoriasis; Pb: between EOP and LOP to evaluate the sole contribution of psoriasis subtype (LOP) to the developmental risk of certain comorbidities deter- mined as CVD and DM. Psoriasis is proven to cause serious systemic inflammation however the exact tools to monitor the inflammatory bur- den is yet to be discovered. Reports in literature concerning the severity of psoriasis subtypes comparing EOP and LOP are few and contradictory. In these data, authors mostly used PASI score, BSA and duration of systemic treatment to evaluate severity of psoriasis. Although some researches did not find significant difference in the severity of psoria- sis between EOP and LOP , others found EOP to be more severe than LOP [1,3,4,7,17]. In this study, evaluation of psoriatic inflammation was assessed by severity parameters along with calculations made for active disease duration and duration of time between onset of psoriasis and concurrent inflammatory comorbidities. Although traditional markers of psoriasis severity such as PASI scores and BSA did not show any difference between EOP and LOP, we found that LOP was associated with rapid development of psoriatic nail involvement and PsA in statistically significantly shorter periods of time despite shorter active disease durations with and without treatment. LOP was also found to associate with higher levels of inflammatory serum markers like CRP, ESR and RDW. As a whole, our results strongly support that LOP poses heavier and rapid inflammatory burden. Accordingly, we prioritize the determination of the disease subtype as EOP or LOP and suggest exploring the duration of time between Original Article | Dermatol Pract Concept. 2022;12(3):e2022144 7 Table 7. Prevalence and age at onset of psoriatic comorbidities in EOP and LOP Variables Total patients (N = 160) EOP (N = 121) LOP (N = 39) P CVD, N (%) 4 (2.5) 1 (0.8) 3 (7.7) 0.045 Age at CVD onset, years 50.75 ± 2.36 51 50.67 ± 1.67 0.929 mean±SD (range) (49-54) 51 (49 -54) HT, n (%) 32 (20) 17 (14) 15 (38.5) 0.001 Age at HT onset, years 44.28 ± 8.23 41.53 ± 5.37 47.40 ± 9.87 mean±SD (range) (33-70) (33-53) (39-70) 0.165 DM, N (%) 25 (15.6) 12 (9.9) 13 (33.3) < 0.01 Age at DM onset, years 42.68 ± 9.79 37.75 ± 7.70 47.23 ± 9.53 0.004 mean±SD (range) (28-65) (28-57) (38-65) NASH, N (%) 29 (18.1) 22 (18.2) 7 (17.9) 0.974 Age at NASH onset, years 39.21 ± 8.20 37.48 ± 8.34 44.43 ± 5.38 0.045 mean±SD (range) (20-59) (20-59) (38-53) DLP, N (%) 99 (61.9) 72 (59.5) 27 (69.2) 0.392 MS, N (%) 47 (29.6) 30 (24.8) 17 (44.7) 0.022 OB, N (%) 46 (28.7) 36 (29.8) 10 (25.6) 0.622 CVD = cardiovascular disease; DLP = dyslipidemia; DM = diabetes mellitus; EOP: early onset psoriasis; HT = hypertension; LOP = late onset psoriasis; MS = metabolic syndrome; NASH = non-alcoholic steatohepatitis; OB = obesity; SD = standard deviation. Table 8. Multivariate regression analysis of impact of psoriasis subtype on concurrent systemic inflammatory comorbidities HT DM IBD NASH CVD DLP MS OB Rx duration Disease duration HT - 0.158 - - - -0.249 0.225 0.177 - - DM - - - 0.167 - - 0.235 - - - IBD - - - - - - - - 0.217 - NASH - - - - - - - 0.219 0.249 - CVD - - - - - - - - - - DLP -0.231 - - - - - 0.557 - -0.194 - MS 0.402 0.309 - - - 0.632 - - - - OB - - - 0.220 - - - - - - PASI - - - - - - - - - - BSA - - - - - - - - - - Ps subtype - 0.168 - - 0.248 - - - - -0.747 Gender - - - -0.265 -0.163 - - 0.182 - 0.101 Duration of Rx - - 0.236 0.250 - - - - - - Age 0.403 - - - - 0.224  - - 1.009 0.663 Disease duration - - - - - -  - - -0.516 - Duration of active disease without Rx. - - - - - -  - - - 0.156 Duration of active disease with Rx - - - - - - 0.123 - - 0.188 Smoking - - - - - - - - - - R2 Value 0.288 0.237 0.056 0.200 0.133 0.451 0.538 0.115 0.325 0.620 P Value 0.000 0.000 0.003 0.000 0.000 0.000 0.000 0.000 0.000 0.000 BSA = body surface area; CVD = cardiovascular disease; DLP = dyslipidemia; DM = diabetes mellitus; HT = hypertension; IBD = inflamma- tory bowel disease; MS = metabolic syndrome; NASH = nonalcoholic steatohepatitis; OB = obesity; PASI = psoriasis area and severity index; Ps = psoriasis; Rx = systemic treatment. 8 Original Article | Dermatol Pract Concept. 2022;12(3):e2022144 onset of psoriatic involvements and comorbidities (psoriatic nail, PsA, CVD, DM, HT, MS) and active disease duration for evaluating inflammation and its consequences in psoriasis. We believe that the all- together analysis of these parameters with the traditional clinical severity scores may create a new concept of approach for psoriasis follow-up. Nail involvement is observed in 13%-50% of psoriasis patients and this rate increases to 80%-90% by age [18]. Reports on nail involvement in EOP and LOP differ; some report more frequent nail involvement in EOP, others found that LOP more frequently affect nails [3,5,10,17]. There are also studies showing no difference in nail involvement between EOP and LOP [1,4,7]. We did not observe statis- tically significant difference in both nail involvement and type of nail involvement, neither. But interestingly, nails were found to be affected in significantly shorter duration in LOP in comparison with EOP. Similar to the findings observed in psoriatic nail involvement, PsA was found to develop in significant shorter periods of time in EOP. Generally, PsA is observed in 5-30% of patients with psoriasis [19]. Most researches did not find difference in concurrent PsA between EOP and LOP [3,4,7]. Heredi et al have demonstrated that the PsA was more frequent in EOP and risk of development of PsA decreases by increasing age and this risk completely disappears after age 75 [1]. In this study, there was no differ- ence between EOP and LOP for associating PsA prevalence. RSQ responses were also similar in two disease subtypes. As it leads to PsA faster than EOP, LOP can be accepted to generate a rapid inflammatory course and cause damage target organs such as nails, ligaments, tendons and joints. Increased frequencies of systemic comorbidities such as CVD, DM, HT and MS in LOP compared to EOP were detected in this study. BMI, systolic and diastolic blood pressure values, fasting blood glucose, BUN, CRP, ESR, RDW levels were also higher in LOP. These findings suggest that concomitant inflammatory comorbidities may increase the amount and speed of psoriatic inflammation. To our knowledge there are no reports comparing the laboratory indicatives of systemic inflammation in EOP and LOP, but these parameters have been shown to be higher in psoriasis patients in comparison to general population [20,21]. RDW and CRP levels have also been suggested as reliable markers of inflammation in psoriasis [20,21]. Besides, elevated levels of CRP have been shown to be an independent risk factor for development of CVD in psoriasis and may be associated with increased risk of MS [21]. However, there is again few data of psoriasis subtype and its contribution to these concurrent comorbidities. Heredi et al did not found difference in the risk of development of CVD between EOP and LOP [1]. Despite our low number of cases in the study, LOP was able to be shown as an independent risk factor for CVD and DM. This risk must be kept in mind in LOP and on time referral and adequate anti-psoriatic treatment choice is mandatory and is lately recommended in psoriasis guidelines [22]. EOP and LOP are two different types of psoriasis with different etiologies, clinical characteristics, laboratory indic- atives and concurrent systemic comorbidities. Despite similar treatment regimens and shorter duration of active disease, LOP causes faster nail and joint involvement in a shorter period of time and is more frequently associated with sys- temic inflammatory comorbidities such as CVD, DM, HT and MS. LOP was also found to be independent risk factor for development of CVD and DM. From this aspect, we prioritize the determination of the disease subtype as EOP or LOP and suggest LOP to be closely monitored for potential develop- ment of end-organ inflammatory comorbidities. 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