OBJECTIVES:Bullous pemphigoid (BP) is a rare, autoimmune, blistering disease in elderly patients that can be triggered by external factors including drugs. Drug-induced bullous pemphigoid (DIBP) does not always follow a self-limiting course after the withdrawal of the offending drug. Dipeptidyl peptidase-4 (DPP-4) inhibitors or gliptins seem to be associated with a significant risk of inducing BP.CASE PRESENTATION:We report 2 cases of BP attributed to the DPP-4 inhibitor linagliptin. In both cases, the clinical manifestation was strongly suggestive of BP. The diagnosis was verified by histology and direct immunofluorescence (DIF). Linagliptin and all other possible drug triggers of BP were discontinued after consultation with an endocrinologist and a cardiologist. Systemic treatment of BP consisted of methylprednisolone and tetracycline. During the follow-up period, one of the patients suffered a fatal brain stroke while the other was managed with reduced doses of corticosteroids.CONCLUSION:The proper management of autoimmune bullous skin disorders in elderly patients includes a scrupulous assessment of plausible drug triggers. Systemic corticosteroids for treating severe cases of DIBP can worsen concomitant diseases which often necessitates multidisciplinary care.

AIMS:The present study aimed to assess vitamin D status and serum concentrations of pro-inflammatory cytokines IL-17, Il-23, and IL-18 in patients with chronic plaque psoriasis and their association with various demographic and clinical characteristics.METHODS:The study was conducted during the autumn/winter period on 48 patients with chronic plaque psoriasis and 48 controls. Total serum 25(OH)D level was determined with Roche Elecsys® 2010 Vitamin D total assay. Commercial ELISA kits were used for quantifying the serum levels of IL-17A, IL-18, and IL-23.RESULTS:Serum 25(OH)D had a median value of 16.95 ng/mL (IQR 10.8-23.50) for patients with psoriasis and 18.80 ng/mL (IQR 15.45-25.85) for the control group (P=0.09). A moderate negative correlation was found between PASI score and 25(OH)D levels (rs=-0.34; P=0.02). The serum levels of IL-17 (P=0.001), IL-23 (P=0.01) and IL-18 (P=0.02) were significantly higher in the patient group compared to controls. IL-17 concentrations were higher in patients with moderate to severe psoriasis compared to patients with mild psoriasis (P=0.003). No significant correlations were detected between the serum concentrations of 25(ОH)D and IL-17, IL-23, and IL-18.CONCLUSION:It was confirmed that IL-17 serum level is associated with psoriasis severity. Measurement of 25(OH)D serum concentration can be useful in patients with moderate to severe psoriasis with or without comorbidities. A direct association between 25(OH)D serum concentration and the serum concentrations of IL-17, IL-23, or IL-18 was not identified in this study.

Purpose: The study aims to examine the use of dietary supplements (DSs) in patients with chronic dermatological diseases, as well as, the patients' views of the safety and benefit of DSs. Methods: A crosssectional study of patients hospitalized in the Clinic of Dermatology and Venereology at the University Нospital "Prof. Dr Stoyan Kirkovich" - Stara Zagora from March 2019 to March 2020 was performed. A specially designed and validated questionnaire was used to collect data. Descriptive statistics was performed to analyze the results. Results: Overall 250 patients were involved in the study. The intake of DSs was established in 174 (69.6%) of the participants. Commonly used DSs were vitamins/minerals (41.2%) and herbal supplements (8.2%). Most of the respondents (59.2%) were ignorant about adverse reactions to DSs and 44.4% perceived DSs as completely safe. The majority of DSs consumers (59%) declared satisfaction with the effect of DSs and were convinced (62.4%) of their benefits. Conclusions: DSs are widely used in patients with chronic skin diseases. Most of the patients are ignorant about the risk associated with DSs intake. Physicians' awareness of DSs use in hospitalized patients is important for the rational use of DSs and their safe combination with drugs.

Objectives: The aim of this research is to examine the effects of fructose-drinking on the plasma levels of appetite-regulating hormones insulin, leptin and ghrelin in male and female rats. Methods: Mature Wistar rats were divided as follows: two control groups - male (CM) and female (CF); two fructose-drinking groups - male (FDM) and female (FDF), received 15% fructose solution. The experiment lasted 11 weeks. At the end, insulin, leptin and ghrelin levels as well as lipid and glucose profile were assessed. Results: Plasma concentrations of the examined hormones were elevated in fructose-drinking groups. However, in the FDM group only the leptin levels were significantly increased compared to the control. In the FDF group, all three appetite-regulating hormones showed the highest concentrations in comparison to the other groups. Conclusion: Sex hormones may affect the appetite-regulation signals and could be a factor contributing to degree of metabolic changes caused by long-term fructose overconsumption.

Хроничната злоупотреба с райски газ сред юношите се превръща в сериозен проблем, тъй като води до функционален дефицит на витамин В12 с последващи миелоневропатии. Представяме кохорта от 5 пациента на възраст от 15 до 18 г. с анамнестични данни за хронична злоупотреба на райски газ до 10-12 пълнителя на ден – един до два пъти седмично за период между 3 месeца и 2 г. При всички пациенти се установяват парестезии по дистален тип, сензорна атаксия, а при една болна и силно смутена походка. Електроневрографското изследване е с данни да смесен тип полиневропатия, по-изразена в долните крайници. Серумните нива на витамин В12 са намалени при 4/5, докато нивата на хомоцистеин и метилмалонова киселина са увеличени над 7 пъти над нормата при всички. Магнотнорезонансната томография е с данни за хиперинтензни лезии, засягащи задните стълбци на гръбначния мозък при една болна. Пациентите са лекувани с витамин В12 с различна степен на подобрение. Хроничната злоупотреба с райски газ води до обратима подост ро прогресираща миелоневропатия. Преустановяването на приема и приложението на витамин В12 е с добър ефект.

Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are oral antidiabetic agents commonly used for the treatment of type 2 diabetes mellitus. More than ten years of clinical experience with this group of drugs provides evidence of their efficacy and good tolerability especially in patients at risk of hypoglycemia. DPP-4 inhibitors act by increasing the levels of the incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) and thus augmenting glucose-induced insulin secretion. The enzyme DPP-4 degrades plenty of substrates including chemokines, cytokines, and neuropeptides. Thus the inhibition of DPP-4 may affect many biological and pathological processes. Although rarely DPP-4 inhibitors have been reported to induce the development of infections, heart failure, liver injury and pancreatitis. The long-term effects of DPP-4 inhibition on the immune function are still not clarified. The close monitoring of polymorbid patients using DPP-4 inhibitors, and the reporting of possible adverse reactions associated with these drugs is warranted.

PURPOSE. To evaluate the incidence of urticarial adverse drug reactions (ADRs) to ACE inhibitors and beta-blockers, patient demographics, drug causality, and treatment outcome. METHODS. An epidemiological study including 154 patients with urticarial ADRs, out of a total of 3554 hospitalized patients in the Clinic of Dermatology and Venereology, for a 7-year period. ADRs were defined according to the WHO and the Naranjo algorithm was used for case drug causality assessment. RESULTS. Urticarial ADRs were found in 4,1% of the study population (≥ 18 years), the average age was 50,2 years, and female prevalence was established. Concomitant cardiovascular diseases were found in 45,2% of the patients and 30,1% declared using ACE inhibitors and/or beta-blockers. The suspected drug was withdrawn, and alternative therapy was recommended by a cardiologist. The Naranjo algorithm showed 4.5% “definitive”, 45,5% “possible”, and 50% “probable” urticarial ADRs. Systemic antihistamines were administered to all patients and single short corticosteroid courses were added in 81,8%. Clinical recovery was achieved in 59% of the patients and improvement in 41%. CONCLUSIONS. The need for drug therapy and hospitalization in severe cases of urticarial ADRs to ACE inhibitors and beta-blockers are factors contributing to the overall socio-economic burden of ADRs.

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Ganeva M, Gancheva T, Deliyska R, Gancheva D, Hristakieva E. Drug-related psoriasis. Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. 2023. doi:10.5114/ada.2022.124418. APA Ganeva, M., Gancheva, T., Deliyska, R., Gancheva, D., & Hristakieva, E. (2023). Drug-related psoriasis. Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. https://doi.org/10.5114/ada.2022.124418 Chicago Ganeva, Maria, Tanya Gancheva, Radostina Deliyska, Desislava Gancheva, and Evgenya Hristakieva. 2023. "Drug-related psoriasis". Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. doi:10.5114/ada.2022.124418. Harvard Ganeva, M., Gancheva, T., Deliyska, R., Gancheva, D., and Hristakieva, E. (2023). Drug-related psoriasis. Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. https://doi.org/10.5114/ada.2022.124418 MLA Ganeva, Maria et al. "Drug-related psoriasis." Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology, 2023. doi:10.5114/ada.2022.124418. Vancouver Ganeva M, Gancheva T, Deliyska R, Gancheva D, Hristakieva E. Drug-related psoriasis. Postępy Dermatologii i Alergologii/Advances in Dermatology and Allergology. 2023. doi:10.5114/ada.2022.124418.

Macrophage activation syndrome (MAS) is a rare, life-threatening condition, characterized by excessive inflammation due to uncontrolled and dysfunctional immune response -a continuous activation of T-lymphocytes and macrophages, leading to hypersecretion of proinflammatory cytokines.It is most commonly reported to occur in rheumatic diseases.However, development of MAS can be triggered by numerous infectious agents.We present the clinical case of a 12-year old girl with congenital bilateral optic nerve hypoplasia, in whom based on fever, cough, chest X-ray findings of right-sided pneumonia and positive IgM antibodies to Mycoplasma pneumoniae, a diagnosis of mycoplasma pneumonia was made.In addition, rash, hepatomegaly, lymphadenopathy and laboratory changes -thrombocytopenia (PLT 89x109/l), elevated transaminases (Aspartate aminotransferase 228 U/L), hyperferritinemia (1844 ng/ml), hypofibrinogenemia (3.2 g/l), positive D-dimers, were found.Based on the described findings, a diagnosis of macrophage activation syndrome, triggered by Mycoplasma pneumoniae was made.The initiated treatment with intravenous Methylprednisolone pulse therapy and Cyclosporine in combination with definitive antibiotic therapy resulted in clinical improvement and normalization of lab parameters, except ferritin value and platelet count.Addition of a recombinant IL1R antagonist resulted in continuously stable ferritin levels and cessation of cyclosporine therapy.

INTRODUCTION:The high-fructose diet in rats has been reported to cause metabolic disorders such as impaired fasting glucose levels, in-sulin resistance, dyslipidemia, and dysregulation of the renin-angiotensin system. This could lead to further complications, for instance, to the smooth muscle dysfunction.AIM:The present study aimed at developing fructose-induced metabolic perturbations in rats and the investigation of their impact on angiotensin II-induced smooth muscle intestinal motility.MATERIALS AND METHODS:Mature Wistar rats were randomly divided into two groups (9 rats per group): control group (drinking tap water) and fructose-drinking group (15% fructose, dissolved in tap water). At the end of the experimental period (11 weeks), the plasma levels of insulin, renin, angiotensin II and creatinine, as well as the lipid profile were assessed. Morphometric analysis and lipid index calculation were also performed. The contractile properties of ileum, colon and rectum were studied using stimulation with angiotensin II in the isolated tissue bath system.RESULTS:Our experiment showed that drinking 15% fructose solution induced dyslipidaemia accompanied by elevated lipid indexes as well as an increase in creatinine and renin plasma levels in the rats.CONCLUSIONS:Fructose drinking and consequently the developed metabolic disorders modified the Ang II-induced intestinal activity causing a gradual alteration in the distal direction with the rectum being the most strongly affected organ.

OBJECTIVES:Evidence suggests that the use of dietary supplements in patients with various disorders is growing. The study aims to examine the use of drug supplements in patients with dermatological disorders, regarding their type, the reasons and predictors of their use, and the safety beliefs and communication attitude of users.MATERIALS AND METHODS:A cross-sectional study of patients hospitalized in the Clinic of Dermatology and Venereology at the University Нospital in Stara Zagora, Bulgaria, was carried out from October 2018 to December 2019. Data were collected using a specially designed and validated questionnaire. Statistical analysis included the χ2-test, the Mann-Whitney U test, and logistic regression.RESULTS:Overall 348 patients (204 females and 144 males) were involved in the study. The patients who reported having used dietary supplements were 67% of the study population. Various combinations ranked first among the dietary supplement types, and vitamins/minerals presented a substantial part (75.9%). The majority of the patients (61.6%) used dietary supplements for more than one reason, mainly for organ-related disorders. Most of the respondents (76.4%) considered them to be completely safe. Higher education (OR = 1.91; CI: 1.14 - 3.19), being a non-smoker (OR = 1.81; CI:1.14 - 2.88), and sporting activities (OR = 1.71; CI: 1.03 - 2.83) increased the odds of using dietary supplements.CONCLUSION:The examined cohort of dermatology patients presented a dietary supplement user profile similar to the general population. The study confirmed that these products are considered to be safe by the majority of participants. Factors indicative of a healthy lifestyle and higher education were predictive for their use.

The increasing use of food supplements (FS), including plant-based food supplement (PBFS), raises questions about their safe use. The risk of adverse reactions (ARs) and interactions associated with FS implies the need for active communication between physicians and patients. The practice and knowledge of outpatient care physicians (OCPs) towards PBFS and its association with physicians' characteristics was examined in a cross-sectional study conducted in Stara Zagora, Bulgaria. Primary data were collected using directly administered questionnaire. More than two-thirds (89.8%) of the respondents recommended PBFS. A substantial part inquired about patient use of PBFS (76.8%) and discussed issues related to PBFS (65.7%). A moderate positive correlation was found between the personal use of PBFS and their recommendation to patients (p<0,001). More than half of the OCRs (58.10%) claimed to have poor or no knowledge of PBFS. The majority emphasized the need for additional education concerning the efficacy and safety of PBFS.

Various algorithms have been used for establishing causality of adverse drug reactions (ADRs) in everyday clinical practice. Due to shortcomings and discrepancies between them there is still no universally accepted algorithm. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, severe, multiorgan ADR characterized by the presence of fever, cutaneous eruption, lymphadenopathy, internal organ involvement (hepatitis, carditis, interstitial nephritis, pneumonitis, etc) and hematological abnormalities, mainly leucocytosis, eosinophilia and sometimes atypical lymphocytosis. DRESS syndrome is considered to be a hypersensitivity reaction but factors like defective drug detoxification and accumulation of toxic metabolites, as well as reactivation of different human herpes viruses have been proposed to be involved in its pathogenesis. The aim of the study was to compare the results from evaluation of cases with DRESS syndrome performed with the Naranjo probability scale and the RegiSCAR scoring system. Patients hospitalized in the Clinic of Dermatology and Venereology in Stara Zagora, Bulgaria are prospectively monitored for the development of ADRs. Causality is assessed with the Naranjo probability scale. Cases with DRESS syndrome are additionally evaluated with the RegiSCAR scoring tool. DRESS syndrome was detected in 6 patients and was attributed to carbamazepine (5 cases) and sulfasalazine (1 case). Using the Naranjo scale, drug causality was scored as "probable" in half of the cases and as "possible" in the rest. The RegiSCAR scoring system confirmed 5 "definite" and 1 "probable" case of DRESS syndrome. The concordance between the two scales was low (kappa=0.091). Regarding some characteristic features of DRESS e.g. concomitant viral reactivation, tendency to relapse, high risks in performing rechallenge, the Naranjo scale compared to RegiSCAR does not provide a precise assessment of this severe hypersensitivity ADR. However, differentiation between different culprit drugs can be made only with the Naranjo probability scale.

Dysregulation of cytokine production or action is thought to have a central role in the development of autoimmunity and autoimmune disease. The aim of this study was to analyze serum TNF-alpha, IL-18, IL-12p40, IL-17 and IL-23 in patients with ankylosing spondylitis (AS) and their relation to disease activity and treatment regimens. Cytokines in the serum of 77 AS patients and 48 age- and sex-matched healthy controls were measured by ELISA assay. Disease activity was assessed by the ASDAS-CRP, ESR and CRP. Serum levels of most of the studied pro-inflammatory cytokines were elevated in AS patients compared to healthy subjects; 1L23, IL-17 and IL-18 were significantly higher (p<0.001), whereas TNF-alpha, was higher but not significantly elevated. The cytokine concentrations between subgroups upon TNF - specific blockade and non-anti-TNF therapy were comparable and not statistically different for all cytokines, but, notably, TNF-alpha was numerically higher in patients upon treatment with anti-TNF. No association was calculated between TNF-alpha, IL-17 14 IL-23 with the ASDAS-CRP and both inflammatory biomarkers, Only a weak correlation between IL-18 and ASDAS-CRP and between 1L-12p40 and CRP was found, because of which we consider that the investigated cytokines are poor indicators of activity in this disease and do not reflect it accurately.