Search Results (108)

General pustular psoriasis (GPP) is a rare, potentially life-threatening neutrophilic dermatosis. Pediatric cases are uncommon and often misdiagnosed due to overlapping clinical and histopathological features with other pustular dermatoses. We present a case of an 11-year-old boy, initially diagnosed with Sneddon–Wilkinson syndrome, who presented with disseminated pustular eruptions, with no response to antibiotics, dapsone, and glucocorticosteroids. In histopathology, we observed subcorneal neutrophilic pustules. Due to atypical features and poor treatment response, the patient underwent genetic testing, which revealed a homozygous IL36RN gene c.338C>T (p.Ser113Leu) pathogenic variant, which enabled a definitive diagnosis of GPP. Treatment with acitretin led to clinical improvement. Pediatric GPP poses diagnostic and treatment challenges. Genetic testing for IL36RN pathogenic variants may aid in the diagnosis, especially in atypical cases. The presence of the biallelic IL36RN pathogenic variant supports the diagnosis of DITRA (Deficiency of the IL-36 Receptor Antagonist, ORPHA:404546)—a monogenic autoinflammatory form of GPP. Full article

Background: Acute radiation-induced skin injury (aRISI) is one of the most frequent adverse effects of radiotherapy (RT) in patients with head and neck cancer (HNC) and may compromise treatment delivery and quality of life. Topical glucocorticosteroids (GCS) are commonly used in clinical practice for aRISI management; however, evidence supporting their proactive use remains inconsistent. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of proactive topical GCS therapy during RT for HNC. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted from database inception to July 2025 in accordance with PRISMA 2020 guidelines. Randomized controlled trials comparing topical GCS with placebo or standard skin care in adult patients undergoing curative RT or RChT for HNC were included. The primary outcomes were incidence of clinically significant aRISI (grade ≥ 2) and severe aRISI (grade ≥ 3), assessed using validated grading systems (RTOG or CTCAE). Random-effects meta-analyses were performed to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Three randomized controlled trials comprising 459 patients were included. Proactive topical GCS did not significantly reduce the pooled incidence of grade ≥ 2 aRISI compared with placebo or standard skin care (RR 0.87, 95% CI 0.60–1.27). Similarly, no statistically significant reduction in grade ≥ 3 aRISI was observed in pooled analysis (RR 0.81, 95% CI 0.22–3.06). Qualitative synthesis of secondary outcomes reported in individual trials suggested potential benefits of topical GCS, including delayed onset or slower progression of aRISI, and, in one large double-blind study, a reduced risk of severe reactions. No increase in treatment-related adverse events was observed in any included trial. Conclusions: Proactive topical GCS do not significantly reduce the overall incidence of aRISI in pooled analysis. Individual studies showed trend towards delayed onset, slower progression, and reduced severe aRISI without compromising safety. These findings support the judicious use of topical GCS as part of proactive supportive care in HNC RT, while highlighting the need for larger, standardized trials to define optimal regimens and patient selection. Full article

Background and Objectives: Recurrence of lupus nephritis (LN) after kidney transplantation is a major clinical concern in patients with systemic lupus erythematosus (SLE) who progress to end-stage renal disease (ESRD). Reported rates of post-transplant LN recurrence vary widely and are influenced by patient characteristics, immunosuppressive regimens, and indications for allograft biopsy. Patients and Methods: Medical records of adult LN patients treated at the University Hospital in Kraków, Poland, during the years 2012–2022 were retrospectively reviewed to identify individuals who progressed to ESRD and received a kidney transplant. Data collected included patient demographics as well as clinical, laboratory, transplant-related, and dialysis-related information. Results: Among 1039 patients with SLE, LN was diagnosed in 351 (33.8%), and 28 (8.0%) progressed to ESRD, of whom n = 9 (32.1%) underwent kidney transplantation. All patients received deceased-donor grafts, with a median time from ESRD to transplantation of 3 years (range 1–8) and a median post-transplant follow-up of 6 years (3–20). Maintenance immunosuppression consisted predominantly of glucocorticosteroids, mycophenolate mofetil, and tacrolimus in 77.8% of patients, with basiliximab induction was used in 2 of 2 patients with available data. Biopsy-proven LN recurrence occurred in 22.2% (2/9) of recipients. Graft loss was observed in 22.2% (2/9), while overall mortality reached 33.3% (3/9), including one peri-transplant death and one death due to infectious complications. Hematological manifestations were present in 100% of patients, hypercholesterolemia in 100%, and arterial hypertension in 88.9%, while anti-dsDNA antibodies were detected in 77.8%. LN relapse occurred despite standard immunosuppressive therapy and in the absence of consistent clinical or immunological predictors. Conclusions: LN recurrence occurred in 2 of 9 patients (22.2%). Patients with LN after kidney transplantation require careful long-term monitoring and individualized immunosuppressive management, considering baseline risk profile and relevant clinical with immunological factors. Full article

Background/Objectives: Alopecia areata is an autoimmune disorder affecting approximately 2% of the global population and is associated with a substantial impairment in quality of life. Owing to the limited number of approved therapeutic options, off-label pharmacotherapy is frequently employed in clinical practice when managing this disease. Methods: This retrospective study analyzed electronic medical records of patients treated for alopecia areata at the University Clinical Centre in Gdańsk between 2014 and 2024 to characterize the epidemiological profile and real-world treatment patterns. Results: A total of 334 affected patients were identified, including 199 diagnosed exclusively with alopecia areata and others presenting with immune-mediated comorbidities, most commonly atopic dermatitis and psoriasis. Among patients with isolated disease, women were more frequently affected and were older at diagnosis than men. Most individuals were managed in the outpatient setting, and demographic characteristics remained stable throughout the study period. Off-label pharmacotherapy was used in 77.9% of all patients and in 99.4% of those receiving drug treatment, with no significant associations observed between off-label use and age, sex, place of residence, or calendar year. Glucocorticosteroids, administered both topically and systemically, were the most commonly prescribed off-label agents (65.3%), and monotherapy was the predominant treatment strategy. Conclusions: These findings highlight the extensive reliance on off-label therapies in routine management of alopecia areata in a real-world European clinical setting. Full article

Acute respiratory distress syndrome (ARDS) is a common condition among intensive care unit patients and is associated with high mortality. Currently, there are no unified therapeutic strategies, including for the use of systemic glucocorticosteroid (GCS) therapy, in the management of ARDS of various etiologies. Using our previously developed non-surgical and reproducible model of unilateral total diffuse alveolar damage (ARDS/DAD) in the left lung of ICR mice, we investigated the effects of GCS with different durations of action and administration regimens on lung function recovery. Our data show that repeated-course administration of dexamethasone promoted complete normalization of respiratory function, as well as restoration of aeration and perfusion of the left lung in mice following ARDS/DAD induction. In contrast, a single administration of the same drug or the use of a prolonged-release formulation, despite exhibiting anti-inflammatory effects, did not provide adequate lung tissue recovery and, in some cases, even exacerbated injury. These results underscore that in ARDS therapy, not just the use but the specific dosing regimen of glucocorticoids is critically important for driving complete functional and structural lung repair. Full article

Background/Objectives: Thyroid eye disease (TED) can lead to structural and microvascular changes in the orbit and retina. This study aimed to investigate the associations between Clinical Activity Score (CAS), orbital magnetic resonance imaging (MRI) measurements, and retinal microvascular changes in TED patients. Methods: This cross-sectional study included 38 patients (76 eyes) with TED. Each patient underwent a comprehensive ophthalmological evaluation, CAS assessment, and a detailed medical history. Optical coherence tomography angiography (OCTA) was performed to quantify vessel density (VD) in the superficial and deep capillary plexus (SCP and DCP). Exophthalmos, extraocular muscle thickness and orbital fat thickness were measured on MRI scans to evaluate structural changes. Laboratory analyses included thyroid hormone levels, thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase antibodies (anti-TPO), and lipid profile. Results: Active TED patients (CAS ≥ 3) had significantly higher TRAb levels (p < 0.001), while anti-TPO did not differ between groups. Active eyes showed significantly higher DCP VD in the whole image (p = 0.013), parafovea (p = 0.012), and perifovea (p = 0.009) across all quadrants, with no difference in SCP or the foveal avascular zone (FAZ). In linear mixed model regression analyses, after adjusting for previous glucocorticosteroid therapy, higher triglycerides, greater medial rectus thickness, and whole-image DCP VD independently predicted higher CAS values (R² = 42, p < 0.001). After adjusting for age and sex, CAS remained significantly positive predictor of DCP VD in the parafovea (R² = 0.22, p < 0.001). Conclusions: Changes in DCP VD reflect TED activity and structural orbital involvement. Full article

Background and Objectives: Pemphigus vulgaris (PV) is a rare autoimmune blistering disease caused by IgG au-toantibodies against desmoglein 1 and/or desmoglein 3, leading to flaccid blisters on the skin and mucous membranes. The course of PV during pregnancy represents a special clinical challenge due to immunological changes accompanying physiological immunosuppression and the need to protect the developing fetus. Materials and Methods: To analyze the current state of knowledge, a literature review was performed covering the years 2015–2025. Publications describing PV diagnosed during pregnancy or in neonates were screened, and nine case reports discussing ten patients meeting the inclusion criteria were selected for detailed analysis. In this study, we also present our own clinical case of PV in pregnancy to complement the literature review and provide practical insight into disease management. Results: In most cases, the disease was diagnosed in the first trimester of pregnancy, and the most common symptoms were flaccid blisters and erosions of the oral mucosa. The diagnosis was confirmed by direct immunofluorescence (DIF) and ELISA testing. The first-line treatment remained systemic glucocorticosteroids (GCS), mainly prednisolone, which is considered the safest. In resistant cases, intravenous immunoglobulins (IVIg) were used, which were considered effective and safe, though their use may limit the transplacental transfer of autoantibodies to the fetus. In newborns, the symptoms rarely occurred, were mild, and resolved spontaneously. Drugs with proven teratogenic effects, such as methotrexate, cyclophosphamide, and mycophenolate mofetil, are contraindicated during pregnancy. In the case of rituximab therapy, it is recommended to postpone pregnancy for at least 12 months after the completion of treatment to minimize the potential risk of immunosuppression in the newborn. Conclusions: The treatment of PV during pregnancy requires close interdisciplinary cooperation. Therapy should be carefully individualized, taking into account both therapeutic efficacy and fetal safety. Perhaps then, pregnancy-related pemphigus diseases, given their peculiarities, should be classified as a distinct variety within the desmosomal type of autoimmune blistering diseases. Full article

Background: Patients with rheumatic diseases (RMDs) are at increased risk of herpes zoster (HZ), particularly when receiving immunosuppressive treatment. While recombinant zoster vaccine (RZV) has shown high effectiveness in the general population, evidence in rheumatologic patients remain limited due to their exclusion from pivotal trials. Objectives: To evaluate the effectiveness of RZV and to collect additional safety data in a heterogeneous cohort of rheumatologic patients, compared with a control cohort from the general population. Methods: We conducted a retrospective study including 179 adults who received two intramuscular doses of RZV between January 2021 and June 2025. The cohort included 114 patients with RMDs and 65 individuals from the general population. Effectiveness was defined as the ability to prevent HZ reactivation while safety concerns were recorded as any adverse event temporally associated with the vaccination. Results: We observed a statistically significant reduction in terms of VZV relapses following vaccination (p < 0.001). Among patients diagnosed with RMDs, only one case of HZ recurrence was observed 14 weeks after vaccination, with no significant difference compared to general care patients. One patient experienced a disease flare requiring glucocorticosteroids. RZV demonstrated a favourable safety profile, with minor adverse events (fever, injection-site reactions, headache and myalgia) reported in 17.5% of patients after the first dose and 21.5% after the second. No significant association was observed between adverse events and advanced immunosuppressive therapy. Conclusions: RZV displayed an effective and reassuring safety profile in a heterogeneous cohort of patients affected by RMDs, irrespective of the diagnosis and the ongoing therapy. This supports the broader use of RZV as a safe and valuable preventive strategy in patients with RMDs. Full article

Background: Adverse reactions to tattoo pigments are increasingly recognized, yet severe systemic complications remain rare and poorly characterized. Red tattoo ink, in particular, is associated with delayed hypersensitivity reactions, but widespread manifestations affecting multiple organ systems have not been documented. This case report aims to describe an unusual constellation of erythroderma, alopecia universalis, anhidrosis, and vitiligo triggered by red tattoo ink and to highlight the diagnostic and therapeutic challenges associated with such reactions. Case presentation: This case report describes a 36-year-old Caucasian male who developed erythroderma, alopecia, anhidrosis, and vitiligo as complications of a red ink tattoo, marking a rare and previously unreported case of such extensive reactions. Four months after getting the tattoo, the patient began to develop itchy eczematous changes, which progressed to erythroderma over several months, along with alopecia universalis and anhidrosis. Results: After months of ineffective treatment with glucocorticosteroids, cyclosporine, methotrexate, and acitretin, patch tests confirmed hypersensitivity to possible components of the red tattoo ink, prompting surgical removal of the inflamed tattoo fragments. Unfortunately, aside from resolving the erythroderma, this did not improve the patient’s clinical condition, and he developed vitiligo. Only after the complete removal of the red tattoo ink from the same series that caused the sensitization and the use of immunosuppressive and immunomodulatory drugs, including JAK inhibitors, was hair growth restored and the progression of vitiligo halted, but with no effect on anhidrosis. Conclusions: This case highlights the challenges in managing systemic reactions to tattoo ink and the importance of thorough evaluation and treatment strategies. Full article

Cyclosporine is a selective calcineurin inhibitor used, among other areas, in pediatric gastroenterology as rescue therapy in the treatment of severe ulcerative colitis (ASUC—acute severe ulcerative colitis) in children. The introduction of systemic glucocorticosteroids (GCSs) has significantly reduced mortality in ASUC. However, it should be emphasized that long-term use of these drugs is limited due to the high risk of adverse effects observed during therapy and their limited efficacy. The role of cyclosporine as a second-line therapy is referred to as a ‘rescue therapy,’ which aims to alleviate the symptoms of ASUC, often avoiding life-threatening complications (including toxic megacolon) and postponing the need for urgent colectomy. If colectomy is necessary, this provides time to better prepare the patient nutritionally and psychologically for surgery and to await the effect of slower-acting thiopurine preparations or other chronic treatments; their effectiveness in achieving long-term clinical and endoscopic remission is limited. New therapeutic approaches include cyclosporine as an inducer, which acts as a bridge to new forms of therapy, such as biological drugs, which are used as maintenance preparations in patients. In pediatric patients, there is limited research in the literature on new strategies for the use of cyclosporine. The aim of this review is to assess current evidence on cyclosporine as induction or rescue therapy in pediatric ASUC and explore future integration with biologic and biosimilar strategies, emphasizing its evolving role as a bridging agent toward biologics and novel targeted therapies. Full article

Background: Swallowed topical corticosteroids (STCs) are used as the first-line therapy for eosinophilic esophagitis (EoE) and have been extensively studied in randomized controlled trials (RCTs); however, the presentation and doses varied widely among the studies. Aim: The goal of this study was to compare the safety and effectiveness of the different STC-based options in EoE patients. Methods: We performed a literature search for RCTs, spanning a time period from database inception to July 2024, in order to compare the efficacy and safety of all STCs used to induce or maintain EoE remission each other and also with placebo or proton pump inhibitors (PPIs) in a network meta-analysis. Outcomes are expressed as pooled risk ratios (RRs) of failure and 95% confidence intervals (CIs), and we aimed to evaluate histological remission at <15–20 eosinophils per high-power field (eos/hpf), <5–6 eos/hpf, and <1 eos/hpf. The effect sizes for symptomatic improvement and the mean differences for endoscopic EREFS improvement with 95% CIs were also measured. Adverse events were evaluated using RRs, and these included oropharyngeal and esophageal candidiasis and adrenal suppression. Results: Twenty studies involving 1455 patients with active EoE reported on STC effectiveness to induce remission; three additional studies on 232 patients assessed the maintenance of remission. Budesonide 1 mg orodispersible tablets ranked highest in SUCRA in terms of all histological remission endpoints. Budesonide from inhalation devices was the only option superior to placebo in improving symptoms. Budesonide viscous suspension was the only option superior to placebo in improving endoscopy. No therapy was significantly associated with the risk of any adverse event. Significant inconsistencies and small study effects were detected in multiple comparisons. Conclusions: Budesonide orodispersible tablets were the best option for achieving EoE histological remission, but not symptomatic or endoscopic improvement. STC formulations were as safe as placebo or PPI. Full article

Aim: Nephrotic syndrome (NS) represents a complex glomerular disorder with significant clinical heterogeneity across pediatric and adult populations. Although glucocorticosteroids have constituted the mainstay of therapeutic intervention for more than six decades, primary treatment resistance manifests in approximately 20% of pediatric patients and 50% of adult cohorts. Steroid-resistant nephrotic syndrome (SRNS) is associated with substantially greater morbidity compared to steroid-sensitive nephrotic syndrome (SSNS), characterized by both iatrogenic glucocorticoid toxicity and progressive nephron loss with attendant decline in renal function. Based on this, the current study aims to develop a robust machine learning (ML) model integrated with explainable artificial intelligence (XAI) to distinguish SRNS and identify important biomarker candidate metabolites. Methods: In the study, biomarker candidate compounds obtained from proton nuclear magnetic resonance (1 H NMR) metabolomics analyses on plasma samples taken from 41 patients with NS (27 SSNS and 14 SRNS) were used. We developed ML models to predict steroid resistance in pediatric NS using metabolomic data. After preprocessing with MICE-LightGBM imputation for missing values (<30%) and standardization, the dataset was randomly split into training (80%) and testing (20%) sets, repeated 100 times for robust evaluation. Four supervised algorithms (XGBoost, LightGBM, AdaBoost, and Random Forest) were trained and evaluated using AUC, sensitivity, specificity, F1-score, accuracy, and Brier score. XAI methods including SHAP (for global feature importance and model interpretability) and LIME (for individual patient-level explanations) were applied to identify key metabolomic biomarkers and ensure clinical transparency of predictions. Results: Among four ML algorithms evaluated, Random Forest demonstrated superior performance with the highest accuracy (0.87 ± 0.12), sensitivity (0.90 ± 0.18), AUC (0.92 ± 0.09), and lowest Brier score (0.20 ± 0.03), followed by LightGBM, AdaBoost, and XGBoost. The superiority of the Random Forest model was confirmed by paired t-tests, which revealed significantly higher AUC and lower Brier scores compared to all other algorithms (p < 0.05). SHAP analysis identified key metabolomic biomarkers consistently across all models, including glucose, creatine, 1-methylhistidine, homocysteine, and acetone. Low glucose and creatine levels were positively associated with steroid resistance risk, while higher propylene glycol and carnitine concentrations increased SRNS probability. LIME analysis provided patient-specific interpretability, confirming these metabolomic patterns at individual level. The XAI approach successfully identified clinically relevant metabolomic signatures for predicting steroid resistance with high accuracy and interpretability. Conclusions: The present study successfully identified candidate metabolomic biomarkers capable of predicting SRNS prior to treatment initiation and elucidating critical molecular mechanisms underlying steroid resistance regulation. Full article

Asthma and obesity are two common chronic diseases of growing clinical and social importance. One of the recognised phenotypes of asthma is obesity-related asthma, which is characterised by a more severe course, resistance to glucocorticosteroids, increased inflammation and poorer symptom control. This article discusses the complex pathophysiological mechanism of this phenotype, considering the role of chronic inflammation, immune dysregulation and metabolic disorders resulting from obesity. The potential role of glucagon-like peptide-1(GLP-1) receptor analogues as an innovative therapeutic option in the treatment of asthma in obese individuals, both with and without type 2 diabetes mellitus (T2DM), is also analysed. A literature review indicates that glucagon-like peptide-1 receptor analogue (GLP-1RA) drugs, in addition to their hypoglycaemic and weight-reducing effects, also exhibit anti-inflammatory activity in the respiratory system and may reduce the frequency of asthma exacerbations and improve asthma control. The article reviews current data from experimental and clinical studies, emphasising the need for further research on the use of GLP-1RA as an adjunct to conventional asthma therapy in the context of the obese asthma phenotype. Full article

Objective: Oral lichen planus (OLP) is a chronic immune-mediated condition of the oral mucosa, commonly associated with pain and burning sensations that impair quality of life. This study aimed to compare the efficacy of photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) and topical glucocorticosteroids (CT) in the treatment of OLP, considering lesion location on keratinized and non-keratinized mucosa. Materials and Methods: A randomized clinical trial was conducted on 90 patients with histologically confirmed OLP. Participants were allocated to receive either ALA-PDT in addition to novel oromucosal emulgel containing 5% ALA (five weekly sessions) or clobetasol propionate applied twice daily for two weeks. Lesion area, clinical severity (Reticulation, Erythema, Ulceration—REU index), and subjective symptoms (Visual Analog Scale—VAS) were evaluated before treatment, immediately after, and six months after therapy. Results: ALA-PDT achieved significantly greater and more durable reductions in lesion area, REU scores, and VAS values compared to CT, particularly on non-keratinized mucosa (mean lesion reduction from 2.64 to 0.56 cm² at six months; p < 0.0001). CT therapy showed initial improvement but was followed by relapse at six months. Both treatments were well tolerated, with only mild transient adverse effects reported. Conclusions: ALA-PDT, especially when applied to non-keratinized oral mucosa, provides superior and longer-lasting therapeutic outcomes than topical CT. The application of novel ALA-loaded emulgel enhances treatment efficacy and tolerability, supporting PDT as a promising alternative for OLP management. Full article

Background: Severe asthma is a chronic, difficult-to-treat disorder that significantly affects quality of life, and oral glucocorticosteroids are usually required. Many patients suffering from severe asthma exhibit T2 inflammation and may benefit from biological treatment. This study aims to evaluate changes in cytokine concentrations during therapy with benralizumab, dupilumab, and mepolizumab in severe eosinophilic asthma. Materials and Methods: In this prospective, single-center study, 39 patients with severe eosinophilic asthma received treatment with one of the above-mentioned biologics. Parameters, such as the cytokine profile (Human Th9/Th17/Th22 Luminex, Performance Assay 18-plex Fixed Panel, R&D Systems, Minneapolis, MN, USA) and additionally the Asthma Control Questionnaire (ACQ), mini-Asthma Quality of Life Questionnaire (mini-AQLQ), spirometry (FEV1, FEV/FVC), FeNO, and functional status, were assessed at baseline and after 3–4 months of therapy. Results: The biologic therapies demonstrated diverse effects on inflammatory biomarkers. Dupilumab showed the most pronounced decreases in CD40L, IL-6, and FeNO in comparison to other drugs. In turn, the greatest decrease in TNF-α concentration was observed in the group treated with mepolizumab. Conclusion: Changes in cytokine concentrations highlight the heterogenous immunomodulatory mechanisms of biologics and support personalized strategies based on inflammatory profiles. However, the results should be interpreted with prudence, as the concentrations of cytokines in blood serum fluctuate and the study sample size is small. Full article