Disease burden, clinical management and unmet treatment need of patients with moderate to severe alopecia areata; consensus statements, insights, and practices from CERTAAE (Central/Eastern EU, Russia, Türkiye AA experts) Delphi panel.

Objectives: This study aims to update the understanding of Alopecia Areata (AA) in Poland, Czechia, Russia, and Türkiye, focusing on the disease burden, clinical management, and patient journey. It seeks to establish a consensus on optimal management strategies for AA in these regions. Methods: A modified 2-round Delphi panel was conveyed with 23 Dermatologists (Russia; 4, Türkiye; 7, Poland; 6, and Czechia; 6). The Delphi questionnaire consisted of 61 statements and 43 questions designed to obtain an overall understanding of the perception and acceptance of available information regarding the care of patients with alopecia areata. Results: The study revealed that moderate-to-severe AA significantly impacts patients' and their families' QoL, consistent with previous studies. AA was found to cause more substantial impairment when additional lesions appeared in visible areas besides the scalp. Work and productivity impairment were notably higher in adults with moderate-to-severe AA. Diagnostic consensus highlighted the importance of skin biopsies and trichoscopy, while the need for more practical severity scoring systems was emphasized. Current treatments, including topical therapies, corticosteroids, and systemic immune modifiers, were deemed insufficient, highlighting the unmet medical need. Conclusion: The Delphi study underscores a significant disease burden and unmet medical needs in patients with moderate-to-severe AA. It highlights the necessity of access to novel treatments and further research to develop more effective therapies with a tolerable safety profile. The findings align with global research, emphasizing the psychosocial impact of AA and the need for standardized, effective treatment protocols.

Analysis of clinical characteristics and factors affecting treatment responses in patients with pyoderma gangrenosum: a multicenter study of 239 patients☆.

BACKGROUND: Pyoderma Gangrenosum (PG) is a chronic disease characterized by recalcitrant skin ulcers. OBJECTIVE: We aimed to evaluate the demographic, clinical characteristics, treatments and factors affecting the treatment responses of patients with PG. METHODS: We performed a multicenter study of 12 tertiary care centers. We analyzed the data of the patients who were followed up with a diagnosis of PG between the years 2012‒2022 retrospectively. RESULTS: We included a total of 239 patients of whom 143 were female and 96 were male, with an average age of 54.2 ±â€¯17.4 years. The most common treatment was systemic steroids (n = 181, 75.7%). Among these patients, 50.8% (n = 92) used systemic steroids as the sole systemic agent, while 49.2% (n = 89) used at least one adjuvant immunosuppressive agent. The independent factors determined in regression analysis to influence response to systemic steroids positively were disease onset age ≥ 30-years, negative pathergy, absence of leukocytosis, negative wound culture, presence of a single lesion, and absence of upper extremity involvement. Biological agents were used in 18.4% (n = 44) of the patients in the present study. We also analyzed pathergy positive PG and early onset (onset age < 30) PG separately due to their distinct clinical features which were revealed during statistical analysis. STUDY LIMITATIONS: Retrospective nature of the present study. CONCLUSIONS: Analyses of the factors influencing treatment responses are addressed in this study. Also, we concluded that investigation for accompanying autoinflammatory diseases of pathergy positive PG and early onset PG is necessary and the patients in these two groups are more resistant to treatment, necessitating more complicated treatments.

Evaluation of the Factors Influencing Mortality in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Multicenter Study of 166 Patients.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening acute mucocutaneous disorders usually triggered by drugs. In this study, we aimed to evaluate the factors affecting mortality in patients with SJS-TEN. METHODS: Our study is a retrospective cohort study, analyzing data collected from a total of 12 tertiary care centers between April 2012 and April 2022. RESULTS: The study included 59 males and 107 females, a total of 166 patients, with an average age of 50.91 ± 21.25 years. Disease classification was TEN in 50% of cases, SJS in 33.1%, and SJS-TEN overlap in 16.9%. The average SCORTEN within the first 24 h was 2.44 ± 1.42. Supportive care was provided to 99.4% of patients. The most commonly used systemic immunomodulatory treatments were systemic steroids (84.3%), IVIG (intravenous immunoglobulin) (49.3%), and cyclosporine (38.6%). Plasmapheresis was administered to five patients. While 66.3% of patients were discharged, 24.1% resulted in exitus. Our comparative analysis of survivors and deceased patients found no effect of systemic steroids, IVIG, and cyclosporine treatments on mortality. Univariate analysis revealed that the SCORTEN scores on days 1 and 3 as well as the rates of detachment at the onset and during follow-up were significantly higher in deceased patients compared to survivors. The rates of fever, positive blood cultures, and systemic antibiotic use were higher in deceased patients compared to survivors. The presence of comorbidities, diabetes, and malignancy were significantly more common in deceased patients. Multivariate regression analysis indicated that over SCORTEN 2, the mortality risk exponentially rose with each SCORTEN increment, culminating in an 84-fold increase in mortality at SCORTEN 5-6 (odds ratio [95% confidence interval]: 13.902-507.537, p < 0.001) compared to SCORTEN 0-1. Additionally, the utilization of plasmapheresis was associated with a 22-fold increase in mortality (odds ratio [95% confidence interval]: 1.96-247.2, p = 0.012). CONCLUSION: Our study found that a high SCORTEN score within the first 24 h and the use of plasmapheresis were related to increased mortality, while systemic steroids, IVIG, and cyclosporine treatments had no impact on mortality. We believe that data gathered from one of the most comprehensive studies which we conducted on SJS-TEN will enrich the literature, although additional research is warranted.

Evaluation of Arterial Stiffness Parameters and the Growth Differentiation Factor-15 Level in Patients with Premature Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI) is increasing at a younger age. Growth differentiation factor-15 (GDF-15) has been implicated in several key mechanisms of atherogenesis. Arterial stiffness parameters, including pulse wave velocity (PWV) and the augmentation index (AIx), can indicate the presence or progression of atherosclerosis. The aim of this study is to evaluate the GDF-15 level and arterial stiffness parameters in patients with premature MI. METHOD: Thirty patients aged ≤45 years (mean age: 39 ± 5 years, 23 male) who recovered from a MI and 15 age and sex-matched subjects were consecutively included. The serum GDF-15 concentration levels and arterial stiffness parameters of the patients and controls were measured. RESULTS: GDF-15 levels were significantly higher in patients with premature MI, while there were no significant differences in PWV and AIx between the groups. The GDF-15 level was correlated negatively with high-density lipoprotein (HDL) cholesterol and positively with uric acid levels. Both GDF-15 (p = 0.046, odds ratio: 1.092, 95% confidence interval: 1.003-1.196) and HDL cholesterol (p = 0.037, odds ratio: 0.925, 95% confidence interval: 0.859-0.995) were found as independent factors associated with premature MI. CONCLUSIONS: GDF-15 could be a risk factor for premature MI. Further studies are needed to elucidate the central role of GDF-15 in the pathophysiology of early atherosclerosis and MI in the young population.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

Immunogenicity, efficacy, and safety of CoronaVac and Pfizer/BioNTech mRNA vaccines in patients with psoriasis receiving systemic therapies: A prospective cohort study.

BACKGROUND AND OBJECTIVES: Evidence of immune response to COVID-19 vaccine in psoriasis patients on biological agents is lacking. This study aimed to evaluate SARS-CoV-2 antibody levels following vaccination with CoronaVac or Pfizer/BioNTech mRNA in patients using biological agents or methotrexate, high-titer antibody levels achievement rate, and impact of medications on immunogenicity. METHODS: This noninterventional, prospective cohort study included 89 patients and 40 controls vaccinated with two doses of inactivated (CoronaVac) or Pfizer/BioNTech mRNA vaccines. Anti-spike and neutralising antibodies were analysed before and three to six weeks after the second dose. Adverse effects and symptomatic COVID-19 were assessed. RESULTS: Median anti-spike and neutralising antibody titers after CoronaVac were significantly lower in patients than controls (57.92 U/mL vs 125.4 U/mL, and 1/6 vs 1/32, respectively, p < 0.05). Patients were less likely to achieve high-titer anti-spike antibody levels (25.6 % vs 50 %). Infliximab was associated with attenuated vaccine response. Pfizer/BioNTech vaccine induced comparable median anti-spike (2,080 U/mL vs 2,976.5 U/mL,) and neutralising antibody levels (1/96 vs 1/160) in patients and controls, respectively (p > 0.05). High-titer anti-spike and neutralising antibodies development rates were comparable among patients and controls (95.2 % vs 100 %, and 30.4 % vs 50.0 %, respectively, p > 0.05). Nine (10.1 %) COVID-19 cases- all mild - were identified. Psoriasis flare was seen in 6.74 %, mostly after Pfizer/BioNTech vaccine. CONCLUSION: Psoriasis patients treated with biological agents and methotrexate developed similar response to mRNA vaccine but weaker response to inactivated vaccine. Infliximab reduced response to the inactivated vaccine. Adverse effects were more frequent with mRNA vaccine, but none was severe.

Earlier and more aggressive treatment with biologics may prevent relapses and further new organ involvement in Behçet's disease.

OBJECTIVE: Immunosuppressives (IS) are the choice of treatment for major organ involvement in Behçet's disease (BD). In this study, we aimed to investigate the relapse rate and new major organ development in BD under ISs during long-term follow-up. METHODS: The files of 1114 BD patients followed in Marmara University Behçet's Clinic were analyzed retrospectively. Patients with a follow-up less than 6 months were excluded. Conventional IS and biologic treatment courses were compared. 'Events under IS' were defined as a relapse of the same organ and/or new major organ development in patients receiving ISs. RESULTS: Among 806 patients included in the final analysis (male: 56%, age at diagnosis: 29 (23-35) years, median follow-up time: 68 (33-106) months). Major organ involvement was present in 232 (50.5%) patients at diagnosis, and 227 (49.5%) developed new major organ involvement during follow-up. Major organ involvement developed earlier in males (p = 0.012) and in patients with a first-degree relative history of BD (p = 0.066). ISs were given mostly for major organ involvement (86.8%, n = 440). Overall, 36% of the patients had a relapse or new major organ involvement under ISs (relapse: 30.9%, new major organ involvement: 11.6%.) 'Events under IS' (35.5% vs 20.8%, p = 0.004), and relapses (29.3% vs 13.9%, p = 0.001) were more common with conventional ISs compared to biologics. CONCLUSION: Any major event under ISs was less common with biologics compared to conventional ISs in patients with BD. These results suggest that earlier and more aggressive treatment may be an option in BD patients who had the highest risk for severe disease course.

Biologic Therapy Carries a Very Low Risk of Reactivation in Hepatitis B Surface Antigen-Negative Phase of Hepatitis B.

BACKGROUND: The risk of hepatitis B reactivation in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients exposed to biologic agents is not clear. We aimed to investigate the reactivation rate in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients after biologic therapy. METHODS: Patients followed at gastroenterology, rheumatology, and dermatology clinics with a diagnosis of immune-mediated inflam matory diseases were screened. Immune-mediated inflammatory diseases patients exposed to biologic agents with a negative hepatitis B surface antigen and positive hepatitis B core immunoglobulin G antibody were included in the study. RESULTS: We screened 8266 immune-mediated inflammatory disease patients, and 2484 patients were identified as exposed to biologic agents. Two hundred twenty-one patients were included in the study. The mean age was 54.08 ± 11.69 years, and 115 (52.0%) patients were female. The median number of different biologic subtype use was 1 (range: 1-6). The mean biologic agent exposure time was 55 (range: 2-179) months. One hundred and fifty-two (68.8%) patients used a concomitant immunomodulatory agent, and 84 (38.0%) patients were exposed to corticosteroids during biologic use. No hepatitis B reactivation with a reverse seroconversion of hepatitis B surface antigen positivity was seen. Antiviral prophylaxis for hepatitis B was applied to 48 (21.7%) patients. Hepatitis B virus-DNA was screened in 56 (25.3%) patients prior to the biologic exposure. Two patients without antiviral prophylaxis had hepatitis B virus-DNA reactivation with a negative hepatitis B surface antigen during exposure to the biologic agent. CONCLUSION: We found 2 reactivations and no hepatitis B surface antigen seroconversion in our cohort. Antiviral prophylaxis for patients exposed to biologic agents may need to be discussed in more detail.

The assessment of presenteeism and activity impairment in Behçet's syndrome and recurrent aphthous stomatitis: a multicentre study.

OBJECTIVE: To evaluate key factors for presenteeism and activity impairment in multinational patients with Behçet's syndrome (BS) and recurrent aphthous stomatitis (RAS). METHODS: In this cross-sectional study, 364 BS patients from Jordan, Brazil, the United Kingdom and Turkey and 143 RAS patients from the United Kingdom and Turkey were included. The Work Productivity Activity Impairment (WPAI) scale was used for presenteeism and activity impairment. Mediation analyses were performed to evaluate both direct and indirect causal effects. RESULTS: Presenteeism score was higher in active patients with genital ulcers and eye involvement as well as patients with comorbidities and current smokers than the others in BS (P < 0.05). In RAS, presenteeism score was elevated by oral ulcer activity in the direct path (P = 0.0073) and long disease duration as a mediator in the indirect path (P = 0.0191). Patients with active joint involvement had poor scores in absenteeism, presenteeism, overall impairment and activity impairment compared with those of inactive patients (P < 0.05). Using mediation analysis, the activity impairment score was directly mediated by joint activity (P = 0.0001) and indirectly mediated through oral ulcer-related pain in BS (P = 0.0309). CONCLUSION: In BS, presenteeism was associated with disease activity, presence of comorbidities and being a current smoker, whereas in RAS, presenteeism was associated with oral ulcer activity and increased length of the disease. Moreover, activity impairment was adversely affected by joint activity and oral ulcer related pain in BS. Patients need to be empowered by using appropriate treatment strategies in their working environment and daily life.

Pathergy Phenomenon.

Skin pathergy reaction (SPR) is a hyperreactivity response to needle induced trauma which is characterized by a papule or pustule formation, 24-48 h after sterile-needle prick. It is affected by a wide array of factors, including the physical properties of the needles being used, number of pricks and disease related factors such as male gender, active disease. There is a great variation in reactivity among different populations with very low positivity rate in regions of low prevalence like Northern Europe, and higher prevalance mainly in communities living along the historical Silk Road, like Turkey, China and Middle Eastern countries. SPR is not constant during the disease course, has lost its sensitivity over decades and can be positive in various disorders including Sweet's syndrome, pyoderma gangrenosum, Crohn's diesease, A20 haploinsufficiency, deficiency of IL-1-receptor antagonist and few others. Nevertheless, it is a criteria included into many currently used diagnostic or classification criteria for Behçet's disease. Although, not being fully uncovered yet, available data points to the activation of both innate and adaptive immune system with an inflammatory response mediated by polymorphonuclears and T-cells. In addition to its utility in diagnosis of Behçet's Disease, SPR may serve as a model for investigating the inflammatory pathways involved in the etiopathogenesis of this complex disease.

Mesenchymal stem cells derived from human dental follicle modulate the aberrant immune response in atopic dermatitis.

Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder. The advancements in the understanding of AD immunological pathogenesis have caused the development of therapies that suppress the dysregulated immune response. We aimed to evaluate the immunomodulatory effect of dental stem cells (dental follicle-mesenchymal stem cells [DF-MSCs]) on AD patients. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on T cell response in AD and compared them with psoriasis and healthy individuals and the underlying mechanisms. Results: DF-MSCs significantly reduced Fas, FasL and TNFR II frequency in T cells, increased naive T cell population while reducing memory T cell, decreased inflammatory cytokine levels and promoted Tregs frequency in the AD population. Conclusion: These results imply that DF-MSCs are modulating inflammation through decreasing T cell apoptosis, inducing Treg expansion and stabilizing cytokine levels.

Lay abstract Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. There is no definite solution for the treatment of AD. We aimed to evaluate the immunomodulatory and immunosuppressive effect of dental stem cells (dental follicle-mesenchymal stem cell [DF-MSCs]) on AD. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on inflammatory response in AD and compared them with psoriasis and healthy individuals and the mechanism underlying it. Results: DF-MSCs significantly reduced apoptosis-related markers in immune cells, decreased inflammatory cytokine levels and promoted Treg frequency in the AD. Conclusion: Our findings provide basic evidence for the potential role of DF-MSCs as a cellular therapy option in the treatment of AD and shed light on future clinical studies.

Serum high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin (IL)-1ß, IL-17A and IL-23 levels in patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease that leads to scar formation. The immune pathogenesis of HS is not fully understood and inhibitors of tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-1, IL-23 can be used for treating HS. Identification of serum biomarkers may help understanding individual differences in HS pathogenesis, evaluating disease severity and developing more effective treatment methods. OBJECTIVES: To assess the serum levels of proinflammatory cytokines TNF-α, IL-1ß, IL-17A, IL-23 and high-sensitivity C-reactive protein (hs-CRP) in patients with HS and to evaluate the impact of treatment on cytokine levels. METHODS: Serum proinflammatory cytokine and hs-CRP levels were measured using enzyme-linked immunosorbent assay kits in 24 healthy controls and in 26 HS patients at baseline and after a 3-month treatment. Patients were treated with clindamycin, adalimumab, dapsone, doxycycline and acitretin, based on HS condition and laboratory results. Control, pre-treatment and post-treatment values were compared. RESULTS: HS patients had significantly higher hs-CRP levels than controls which decreased following treatment (p = 0,010, p = 0,007). No significant difference was found in serum levels of TNF-α, IL-1ß, IL-17A, IL-23 compared to controls and post-treatment levels. CONCLUSIONS: There is insufficient data to suggest TNF-α, IL-1ß, IL-17A and IL-23 as serum biomarkers in HS. hs-CRP can be used as an indicator of treatment response and systemic inflammation.

The impact of antipsoriatic treatment on serum pro-BDNF, BDNF levels, depression, anxiety scores, and quality of life.

Depression is a comorbidity of psoriasis. Suppression of neurotrophins has been proposed to cause depression. Peripheral brain-derived neurotrophic factor (BDNF) and its precursor, pro-BDNF have been shown to be altered in depression. To compare serum pro-BDNF and BDNF levels, depression, anxiety, and quality of life (QoL) in psoriasis patients, diseased, and healthy controls, to assess impact of 12-week antipsoriatic treatment on abovementioned markers. At baseline, all groups completed Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Inventory-II (STAI-II) and DLQI; serum BDNF, proBDNF levels were measured. These were repeated after 3-months of treatment in psoriasis patients. Depression and anxiety were significantly higher, QoL was poorer in psoriasis. ProBDNF and proBDNF/BDNF ratios were not different among groups at baseline but significantly decreased after treatment in psoriasis. Depression and QoL improved significantly, BDNF and anxiety scores did not change. Altered pro-BDNF and proBDNF/BDNF ratios may have a role in depression pathogenesis in psoriasis. Antipsoriatic treatment causes improvement in depression, QoL, and reduction of proBDNF and proBDNF/BDNF ratios. Effective disease control may reverse dysregulated neurotrophin pathways and its consequences like depression.

Femoral vein wall thickness measurement: A new diagnostic tool for Behçet's disease.

OBJECTIVES: Diagnosing Behçet's disease (BD) is a challenge, especially in countries with a low prevalence. Recently, venous wall thickness (VWT) in lower extremities has been shown to be increased in BD patients. In this study, we aimed to investigate the diagnostic performance of common femoral vein (CFV) thickness measurement in BD and whether it can be used as a diagnostic tool. METHODS: . Patients with BD (n = 152), ankylosing spondylitis (n = 27), systemic vasculitides (n = 23), venous insufficiency (n = 29), antiphospholipid syndrome (APS; n = 43), deep vein thrombosis due to non-inflammatory causes (n = 25) and healthy controls (n = 51) were included in the study. Bilateral CFV thickness was measured with ultrasonography by a radiologist blinded to cases. RESULTS: Bilateral CFV thickness was significantly increased in BD compared with all control groups (P < 0.001 for all). The area under the receiver operating characteristic curve for bilateral CFV thicknesses in all comparator groups was >0.95 for the cut-off value (0.5 mm). This cut-off value also performed well against all control groups with sensitivity rates >90%. The specificity rate was also >80% in all comparator groups except APS (positive predictive value: 79.2-76.5%, negative predictive value: 92-91.8% for right and left CFV, respectively). CONCLUSION: Increased CFV thickness is a distinctive feature of BD and is rarely present in healthy and diseased controls, except APS. Our results suggest that CFV thickness measurement with ultrasonography, a non-invasive radiological modality, can be a diagnostic tool for BD with sensitivity and the specificity rates higher than 80% for the cut-off value ≥0.5 mm.