Search Results (304)

Background: In solid-organ transplant recipients, hypomagnesemia is a frequent and persistent complication, predominantly related to long-term use of calcineurin inhibitors. Oral magnesium supplementation is often ineffective due to poor adherence, gastrointestinal adverse effects, and high treatment costs. Objectives: This pilot study aimed to (i) develop a topical magnesium formulation for use in renal transplant recipients with persistent hypomagnesemia; (ii) evaluate the influence of formulation excipients on magnesium release from pharmaceutical preparations; and (iii) preliminarily assess the clinical outcomes, functional parameters, patient satisfaction, and tolerability associated with topical magnesium lipogel use in renal transplant recipients with persistent hypomagnesemia. Materials and Methods: Three lipogel formulations containing magnesium orotate, citrate, or sulfate were prepared and characterized in terms of organoleptic properties, pH, colloidal stability, and rheological behavior. In vitro magnesium release was evaluated using Franz diffusion cells. The formulation demonstrating the most favorable release profile, magnesium orotate lipogel, was administered twice daily for two months to 21 renal transplant recipients with persistent hypomagnesemia who had shown inadequate response, intolerance, or non-adherence to oral magnesium supplementation. Laboratory parameters were assessed at baseline and after treatment. Patient satisfaction was evaluated using the Lübeck questionnaire, while physical activity and exercise capacity were assessed using the International Physical Activity Questionnaire (IPAQ) and metabolic equivalent task (MET) calculations. Results: Franz cell studies demonstrated superior magnesium release from the magnesium orotate lipogel compared with the other formulations. After two months, serum magnesium levels were higher than baseline (1.554 ± 0.124 vs. 1.448 ± 0.111 mg/dL, p < 0.001), although they remained below the normal reference range. No significant changes were observed in eGFR or hsCRP. Moderate-intensity physical activity increased significantly (310.475 ± 92.505 vs. 279.286 ± 89.907 MET-min/week, p < 0.001), while vigorous-intensity activity did not change significantly. No relevant adverse effects were reported. Patient satisfaction was high across all evaluated domains, including practicability (86.6%), efficacy (96.4%), tolerability (97.1%), and trust in medical professionals (97.6%). Conclusions: In this pilot study, topical magnesium orotate lipogel was well tolerated and accepted by renal transplant recipients with persistent hypomagnesemia. Serum magnesium levels and moderate physical activity improved over the two-month observation period, although magnesium levels remained below the normal range. These preliminary findings warrant confirmation in larger, randomized, placebo-controlled studies. Full article

Background/Objectives: Kidney graft dysfunction remains a major challenge limiting long-term transplant survival despite advances in immunosuppressive therapy. Cytokine signaling pathways have been implicated in the regulation of alloimmune responses and chronic inflammation, but their contribution to long-term graft function and immunosuppressant pharmacokinetics remains incompletely understood. This study investigated associations among selected cytokine gene polymorphisms (IL-2 −330T>G, IL-6 −174G>C, and IL-10 −1082A>G), biochemical and hematological parameters, and calcineurin inhibitor (tacrolimus and cyclosporine) dosing in kidney transplant recipients. Methods: A total of 394 kidney transplant recipients receiving tacrolimus or cyclosporine were enrolled. Genotyping of IL-2 rs2069762, IL-6 rs1800795 and IL-10 rs1800896 was performed using real-time PCR. Clinical, biochemical, and pharmacokinetic data were analyzed using univariate and multivariate statistical models adjusted for relevant demographic and clinical covariates. Results: IL-2 rs2069762 and IL-6 rs1800795 polymorphisms were not associated with clinically relevant differences in biochemical parameters, calcineurin inhibitor dosing, or transplant outcomes. For IL-10 rs1800896, no statistically significant associations were observed with cyclosporine A blood levels, dose, or C/D ratio. Among tacrolimus-treated patients, the regression model for the C/D ratio was borderline significant (F(2,207) = 3.048, p = 0.050, R² = 0.029). However, the genotype-specific association for the heterozygous GA genotype versus AA was not statistically significant in the unadjusted model (B = −0.462, 95% CI: −0.97 to 0.04, p = 0.072) or after adjustment for age, sex, and time since transplantation (B = −0.450, 95% CI: −0.95 to 0.05, p = 0.078). Although univariate analyses identified associations between IL-10 rs1800896 and selected biochemical parameters, these findings were not confirmed in multivariable models. No significant associations were observed between the analyzed cytokine polymorphisms and graft rejection, graft survival, patient survival, or clinically relevant markers of kidney graft function. Conclusions: The results suggest a possible, although not statistically significant, association between IL-10 rs1800896 and tacrolimus exposure, as assessed by the C/D ratio. This observation should be considered preliminary and interpreted with caution. The lack of CYP3A5 genotyping and functional assessment of IL-10 activity, inflammation, and CYP3A-dependent metabolism further limits the interpretation of this potential association. Larger prospective studies with comprehensive pharmacogenetic and functional characterization are needed to determine whether IL-10 rs1800896 contributes to interindividual variability in tacrolimus exposure and whether it may have potential applications in individualized immunosuppressive therapy. Full article

Background: Pregnancy after solid organ transplantation carries increased maternal and fetal risks, compounded by the teratogenicity, nephrotoxicity, and metabolic effects of available immunosuppressive agents. Belatacept, a calcineurin inhibitor-sparing T-cell costimulation blocker with favorable renal and metabolic profiles, has emerged as an alternative; however, evidence regarding its safety during pregnancy remains scarce. Methods: A scoping review was conducted per PRISMA-ScR recommendations. PubMed, Google Scholar, Web of Science, Scopus, and the Cochrane Library were searched (January 2015–March 2025), supplemented by citation searching, for studies reporting pregnancy outcomes in solid organ transplant recipients receiving belatacept. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools. Results: Three studies (one case series and two case reports) encompassing 21 pregnancies among 15 recipients were included, predominantly in kidney transplant recipients; several recipients contributed more than one pregnancy, so pregnancy-level outcomes are not statistically independent. Sixteen pregnancies resulted in live birth and five ended in miscarriage, at least four of which occurred in pregnancies with periconception mycophenolate exposure. No congenital malformations were reported among live-born infants, although the number of exposures is far too small to characterize teratogenic risk. Stable allograft function was reported in 14 of 19 pregnancies with available follow-up, with no rejection episodes during belatacept exposure. Maternal complications included preeclampsia (8 of 16 in the case series), gestational diabetes, cytomegalovirus reactivation, and acute kidney injury. Low birth weight (<2500 g) was reported in all live births, predominantly in the context of preterm delivery. Conclusions: The published cases have not identified congenital malformations to date, but the number of documented exposures is far too small to characterize teratogenic risk, and the overall certainty of evidence is very low. Because no comparative studies were available, maternal and neonatal outcomes cannot be assumed equivalent to those of conventional immunosuppression. Belatacept cannot be recommended for routine use during pregnancy; clinical decisions must remain individualized, and preconception counseling and prospective multicenter registries are urgently needed. Full article

Kidney transplant recipients (KTRs) face a significantly elevated risk of persistent high-risk human papillomavirus (HR-HPV) infection and subsequent anal squamous cell carcinoma (ASCC) due to chronic immunosuppressive therapy impairing immunosurveillance. Despite the markedly increased risk of ASCC in this vulnerable cohort, standardized screening protocols and optimal clinical management guidelines are not exhaustive. Chronically compromised immunosurveillance permits prolonged HR-HPV carriage and viral genome integration, driving oncogenesis via the E6 and E7 oncoproteins. While calcineurin inhibitors exert pro-oncogenic effects, transitioning to mTOR inhibitors offers distinct antiproliferative and antiviral advantages. Early detection relies on risk-stratified screening utilizing digital anorectal examination, anal cytology, and high-resolution anoscopy. For managing anal intraepithelial neoplasia, traditional topical agents and minimally invasive ablative procedures are widely used, although high recurrence rates present a major clinical challenge. This review analyzes HPV pathogenesis and clinical management in KTRs, evaluating the impact of immunosuppressive regimens and exploring innovative diagnostic and therapeutic strategies. To address viral persistence without compromising the allograft, integrating novel non-invasive, target-specific nutraceuticals may represent an interesting complementary approach. Ultimately, mitigating post-transplant ASCC requires a multidisciplinary strategy that couples early localized screening with tailored systemic immunosuppression. Full article

Thromboembolism is a life-threatening complication of nephrotic syndrome, which is treated with oral anticoagulants (warfarin and direct oral anticoagulants [DOACs]) that possess a variety of pharmacokinetic characteristics. This narrative review focused on drug–drug interactions between oral anticoagulants and calcineurin inhibitors (CNIs) (e.g., tacrolimus, cyclosporine, and voclosporin) for the management of thromboembolism in nephrotic syndrome. While warfarin has less potential for interacting with CNIs, DOACs carry a risk of drug–drug interactions with CNIs owing to the inhibition of drug-metabolizing enzymes and transporters, including cytochrome P450 3A4 (CYP3A4) and P-glycoprotein. Specifically, a significant increase in DOAC exposure was observed when DOACs were co-administered with cyclosporine, a more potent P-glycoprotein inhibitor than tacrolimus. Limited evidence suggests that more pronounced drug interactions occur in specific cases: (1) apixaban and CNIs in patients with renal impairment, (2) edoxaban combined with cyclosporine in patients with renal impairment, and (3) a combination of rivaroxaban with dual inhibitors of P-glycoprotein and CYP3A4 (e.g., cyclosporine and fluconazole). From a pharmacological viewpoint, CNI-induced nephrotoxicity and hypertension may increase the risk of critical bleeding in patients receiving DOACs. In addition, the variation factors of pharmacokinetic parameters, such as renal function, pharmacogenomic profiles, and pathophysiological changes directly caused by nephrotic syndrome, may vary between patients, which could potentially augment the magnitude of drug–drug interactions between oral anticoagulants and CNIs. Further studies are required to understand the clinical significance of drug interactions in patients with nephrotic syndrome. Full article

The gut microbiome has emerged as a critical determinant of health and disease across virtually all organ systems. In the context of chronic kidney disease (CKD) and renal transplantation, mounting evidence reveals a complex bidirectional relationship between the intestinal microbiota and kidney function—commonly referred to as the gut–kidney axis. Patients with CKD harbor a profoundly altered gut microbial ecosystem characterized by reduced diversity, depletion of beneficial commensal organisms, and expansion of pathobiont taxa capable of generating uremic toxins and pro-inflammatory mediators. These perturbations are further compounded by the uremic milieu itself, dietary restrictions, frequent antibiotic exposure, and the use of immunosuppressive agents following transplantation. The gut–liver–kidney axis adds an additional layer of complexity, linking hepatic metabolism, bile acid signaling, endotoxemia, and systemic immune activation to the progression of renal disease. Gut-derived metabolites—including short-chain fatty acids (SCFAs), bile acids, trimethylamine N-oxide (TMAO), and tryptophan-derived uremic solutes such as indoxyl sulfate and p-cresyl sulfate—serve as molecular mediators of inter-organ crosstalk and have been identified as both biomarkers and therapeutic targets. A growing body of literature supports the diagnostic and prognostic utility of microbiome composition and its metabolic signatures in patients with CKD and those undergoing renal replacement therapy. Therapeutic strategies aimed at restoring microbial homeostasis—encompassing dietary interventions, prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), bile acid–based therapies, and novel pharmacological approaches—hold considerable promise for improving outcomes in CKD and transplant recipients. Importantly, the bidirectional relationship between immunosuppressive drugs and the gut microbiota has emerged as a clinically significant determinant of both microbial ecology and drug pharmacokinetics: each major immunosuppressive agent class—corticosteroids, calcineurin inhibitors, mycophenolate mofetil, and mTOR inhibitors—induces characteristic dysbiotic patterns, while in turn, the microbiota modulates drug bioavailability through enzymatic biotransformation (notably bacterial beta-glucuronidase activity affecting mycophenolic acid enterohepatic recirculation) and modulation of host drug-metabolizing enzymes. This narrative review provides a comprehensive overview of the current understanding of microbiome dysbiosis in the setting of renal disease and transplantation, examines the mechanistic underpinnings of the gut–liver–kidney axis, details the multifaceted impact of dysbiosis on transplant outcomes—including allograft function and rejection, infection, post-transplant diabetes, and cardiovascular complications—and critically appraises the translational potential of microbiome-targeted interventions. We conclude by highlighting ongoing challenges and future directions toward personalized, microbiome-informed clinical care. Full article

Vitiligo is a chronic autoimmune disease characterized by the loss of melanocytes, resulting in the appearance of depigmented patches on the skin. The aim of the present review is to discuss current therapeutic methods and to outline promising directions for the treatment of this dermatosis. The review describes pathogenetic mechanisms, including the role of oxidative stress, immune dysregulation, and the JAK/STAT pathways, which constitute the foundation of contemporary therapeutic interventions. The efficacy and safety of topical treatments (corticosteroids, calcineurin inhibitors, JAK inhibitors), phototherapy (NB-UVB, PUVA, excimer laser), combination therapies, and surgical methods such as cellular and tissue grafts are discussed. Data indicate that the combination of phototherapy with topical agents enhances repigmentation efficacy, and JAK inhibitors represent promising drugs in targeted therapy. Particular value is attributed to preparations modulating the immune response and to melanocyte transplantation techniques, which emerge as highly effective and forward-looking treatment options for vitiligo. Nevertheless, effective management of vitiligo requires a multidirectional approach combining pharmacological, immunomodulatory, and regenerative interventions. Full article

Childhood-onset lupus nephritis (cLN) should no longer be framed as a smaller version of adult lupus nephritis. It is a high-stakes pediatric kidney disease in which immune injury, treatment toxicity, growth, puberty, fertility, adherence, and transition to adult care intersect over decades. Approximately 10–20% of systemic lupus erythematosus begins in childhood, and 40–60% of affected children develop lupus nephritis. Regional cohorts report even higher renal involvement in some populations, including 65–73% among Saudi children with SLE. Contemporary guidance has moved from prolonged high-dose glucocorticoids and cyclophosphamide-dominant treatment toward biopsy-driven, treat-to-target care built around mycophenolic acid analogues, hydroxychloroquine, nephroprotection, rapid steroid tapering, and selected belimumab- or calcineurin-inhibitor-based triple therapy. This Viewpoint argues that the central question in cLN is no longer simply how to induce remission, but how to produce a durable kidney response early enough, with sufficiently low cumulative toxicity, to preserve kidney function and childhood development. Pediatric practice must therefore combine adult trial evidence with child-specific caution, explicit adherence strategies, fertility and growth protection, and structured transition planning. The aim should be efficacy without toxicity: not undertreatment, but intelligent, sustainable, developmentally informed treatment. Full article

Background: Acute rejection (AR) is an established risk factor for kidney allograft loss, but whether the timing of the first AR episode adds prognostic information independent of secular changes in immunosuppression remains incompletely defined. We re-examined this question in a cohort restricted to the contemporary calcineurin-inhibitor (CNI) era and explicitly accounted for the maintenance CNI (tacrolimus vs. cyclosporine). Methods: We studied 2470 recipients of an isolated kidney transplant performed between 2000 and 2018 at a single academic center. Recipients were classified by the timing of the first AR episode as AR-free, Early AR (≤6 months), Intermediate AR (6–12 months), or Late AR (>12 months). Co-primary outcomes were estimated glomerular filtration rate (eGFR) and death-censored graft survival. Multivariable Cox regression adjusted for recipient and donor age, recipient sex, HLA mismatch, donor type, ABO incompatibility, diabetes, retransplantation, transplant year, and maintenance CNI. A pre-specified secondary analysis evaluated whether the observed AR-timing association was explained by the maintenance CNI. Results: AR occurred in 294 of 2470 recipients (11.9%): 253 Early, 10 Intermediate, and 31 Late. Median follow-up was 105 months. Mean 5-year eGFR was 67.1 (AR-free), 56.5 (Early), 47.5 (Intermediate), and 47.2 mL/min/1.73 m² (Late) (p < 0.001). Kaplan–Meier 10-year death-censored graft survival was 90.5%, 80.7%, 77.8%, and 52.2%, respectively (log-rank p < 0.001). After adjustment, the hazard of graft failure relative to AR-free recipients was 2.25 (95% CI 1.68–3.01) for Early AR and 7.03 (4.28–11.54) for Late AR (both p < 0.001). The Intermediate AR estimate was directionally consistent but imprecise because of the small number of cases. Tacrolimus use was associated with a lower observed incidence of AR (8.5% vs. 20.0%, p < 0.001), but the observational CNI comparison was confounded by era and follow-up duration and did not explain the AR-timing gradient. Conclusions: Within a contemporary CNI-era cohort and after adjustment for maintenance immunosuppression and transplant year, late-onset AR—particularly onset beyond the first post-transplant year—provided strong prognostic information for long-term graft dysfunction and graft failure. Full article

Lichen planus (LP) is a chronic T-cell-mediated interface dermatitis. Genital involvement is frequently refractory to topical corticosteroids and calcineurin inhibitors and may lead to fibrosis, architectural distortion, and substantial impairment in quality of life. We report the case of a 39-year-old male with a 15-year history of biopsy-confirmed genital LP unresponsive to high-potency topical corticosteroids and tacrolimus 0.1%, who received topical Rosa damascena stem cell-derived exosomes (RSCEs) at biweekly sessions for four months. Each session combined 2 mL of in-office application with superficial microneedling in hyperkeratotic areas, followed by 3 mL of the same-day home application. No concomitant topical corticosteroid or calcineurin inhibitor was used during the treatment period. Paired pre- and post-treatment 4 mm punch biopsies were obtained from the same anatomical region, processed using identical protocols, stained with hematoxylin and eosin, and reviewed by a board-certified dermatopathologist. After four months, we observed clinical resolution of pruritus and fissuring, progressive desquamation of hyperkeratotic plaques, and improved tissue elasticity. The post-treatment biopsy showed reduced hyperkeratosis and hypergranulosis, attenuation of the band-like lymphohistiocytic infiltrate, partial restoration of the dermoepidermal interface, and reduced basal vacuolar degeneration relative to baseline. No dysplastic changes or treatment-related adverse events were observed. These observations are based on a single uncontrolled case and cannot establish causality, isolate the contribution of microneedling, or demonstrate disease modification beyond the descriptive level. Histological assessment was qualitative; no semi-quantitative or immunohistochemical analysis was performed. The exosome preparation was used as a standardized commercial product and was not independently characterized in our laboratory. The findings are intended solely as hypothesis-generating. Independent characterization of the exosome preparation, immunohistochemical and ideally transcriptomic profiling of paired tissue, and prospective controlled studies are required before any therapeutic claim can be supported. Full article

Background/Objectives Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family of amine oxidases involved in collagen cross-linking, has emerged as a key mediator of pathological extracellular matrix remodeling and tissue fibrosis. Dysregulated LOXL2 activity has been implicated in various fibrotic diseases; however, its role in fibrosis-driven chronic kidney injury, particularly in the context of calcineurin inhibitor-induced kidney toxicity, remains incompletely defined. Methods To investigate the contribution of LOXL2 inhibitor to cyclosporine A (CsA)-induced nephropathy, a well-established model of progressive tubulointerstitial fibrosis, male CD-1 mice were administered either saline or CsA (15 mg/kg/day, intraperitoneally) for 8 weeks. After 4 weeks of CsA exposure, CsA-treated mice were further divided into two groups and received either vehicle or a LOXL2 inhibitor (10 mg/kg/day, oral gavage) for an additional 4 weeks. Kidney function, albuminuria, histological fibrosis, inflammatory cell infiltration, and profibrotic gene expression were assessed. Results In a murine model of CsA-induced nephropathy, pharmacological inhibition of LOXL2 markedly improved kidney outcomes. LOXL2 inhibition significantly reduced albuminuria and ameliorated kidney dysfunction. In parallel, tubulointerstitial fibrosis was substantially attenuated, accompanied by reduced myofibroblast activation and extracellular matrix accumulation. These protective effects were associated with downregulation of profibrotic and inflammatory mediators and inhibition of TGF-β-related downstream signaling pathways activated by CsA. Conclusions The present preclinical findings suggest that Compound #765-mediated LOXL2 inhibition may offer a potential therapeutic benefit in CsA-induced fibrosis, though further validation is warranted. Full article

Cardiovascular disease remains the leading cause of mortality in kidney transplant recipients (KTRs). Arterial hypertension is present in a vast majority of patients after kidney transplantation, constituting the most prevalent cardiovascular comorbidity, and is a significant modifiable risk factor for other cardiovascular complications and graft loss. The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines do not address blood pressure control strategies in KTRs, and the prior 2021 KDIGO recommendations targeting values below 130/80 mmHg rely primarily on data extrapolated from non-KTR populations. This represents an existing evidence gap in the management of post-transplant hypertension. Dihydropyridine calcium channel blockers and angiotensin receptor blockers remain first-line antihypertensive medications, although most studies assessing their effectiveness in KTRs date back more than 15 years. The current treatment guidelines are based largely on limited and outdated data. Optimal selection and individualization of immunosuppressive therapy and—when feasible—its modification in some KTRs may be important in improving blood pressure control. This includes, for example, a reduction in the calcineurin inhibitor or steroid dose, as well as the use of mTOR inhibitors or belatacept. The lack of large, up-to-date randomized trials in the KTR population underscores the pressing need for further extensive research focused on this patient group. Full article

Atopic dermatitis (AD) is a common chronic inflammatory condition of the skin that has increased dramatically over the past decade and significantly impacts individual quality of life. Corticosteroids are still the primary therapy for AD, but there are limitations to their continued use due to potential adverse effects, particularly when used in sensitive areas. Topical calcineurin inhibitors (CNIs), such as tacrolimus and pimecrolimus, are available as a safe, steroid-sparing alternative that directly inhibit calcineurin-mediated activation of T cells and have been shown to be efficacious according to varying clinical study designs including randomized controlled trials, registry studies and meta-analyses. Although there was controversy regarding the safety of CNIs subsequent to the FDA’s black-box warning in 2006, the preponderance of evidence supports their continued safety when used as directed. In contrast to biologics and JAK inhibitors, CNIs occupy an inherently unique therapeutic niche for use in pediatric patients, have demonstrated historical efficacy, and can provide localized affordable treatment in sensitive areas including the face, eyelids and intertriginous surfaces. Furthermore, the role of CNIs in the context of precision dermatology continues to be defined through new innovations including barrier-repair strategies used in combination with topical medications, microneedle systems, and nanocarrier formulations. Hence, the role of CNIs in the current AD treatment paradigm is crucial and lies at the interface between topical corticosteroids and systemic immunomodulatory agents. The narrative review discusses recent advances in formulation strategies, combination approaches, and targeted delivery systems, underscoring how CNIs continue to bridge established practice and emerging therapeutic innovation in AD. Full article

Introduction: Steroid-resistant nephrotic syndrome (SRNS) represents a severe and challenging form of pediatric nephrotic syndrome and is associated with a high risk of progression to end-stage kidney disease. Calcineurin inhibitors (CNIs) are the standard second-line therapy; however, their use is limited by frequent relapses and long-term nephrotoxicity. Mycophenolate mofetil (MMF) offers a more favorable safety profile and a complementary mechanism of action; however, the clinical utility of combining MMF with CNIs remains largely under-explored in this population. Case Presentation: We describe a series of nine pediatric patients with steroid-resistant or steroid-dependent nephrotic syndrome who were refractory to cyclosporine monotherapy. These patients were treated with a combination regimen of cyclosporine (4–5 mg/kg/day; target trough levels of 75–150 ng/mL) and MMF (600 mg/m²/day). This therapeutic approach was associated with a reduction in corticosteroid dosage and a decrease in the annual number of relapses in most patients. Conclusions: In this small case series of pediatric patients with corticosteroid-dependent or steroid-resistant nephrotic syndrome refractory to cyclosporine monotherapy, the addition of mycophenolate mofetil was associated with a reduction in relapse frequency and corticosteroid requirements. Despite the limited sample size, these findings suggest that combination therapy may be a therapeutic option in difficult-to-treat pediatric nephrotic syndrome and warrant further evaluation in controlled studies. Full article

Background: Lichen planus (LP) is a chronic inflammatory dermatosis with multiple clinical variants involving the skin, mucous membranes, nails, and hair follicles. Methods: We conducted a retrospective, descriptive study of patients diagnosed with LP at a tertiary referral center from January 2011 to December 2024. Inclusion required concordance between clinical presentation and histopathologic findings. Demographic characteristics, LP subtypes, anatomical involvement, comorbidities, therapeutic approaches, and treatment outcomes were extracted from electronic health records. In addition, an exploratory sensitivity analysis restricted to patients with a single LP subtype was performed to allow for independent subgroup comparisons, and a modified Charlson Comorbidity Index (CCI) based on available comorbidity domains was calculated. Pairwise multivariable logistic regression models adjusted for age, sex, and outcome-specific modified CCI were performed for selected comorbidities. Results: A total of 754 patients were included (mean age 53.1 years), with cutaneous LP (cLP), oral LP (oLP), genital LP (gLP), and lichen planopilaris (LPP) being the most frequent subtypes; a total of 620 had a single major LP subtype and were included in the mutually exclusive analysis. In these groups, modified CCI, age-adjusted modified CCI, and overall comorbidity count differed significantly across subtypes (Kruskal–Wallis p < 0.001). After adjustment in pairwise models, cLP-only showed higher odds of malignancy compared with oLP-only, gLP-only, and LPP-only and higher odds of diabetes mellitus compared with all other pure subtypes. Most other comorbidity comparisons were non-significant or imprecise because of low event numbers. Topical glucocorticoids were the most frequently used treatment, and treatment responses varied by subtype, being more effective in cLP and gLP compared to LPP. Topical calcineurin inhibitors demonstrated the highest response rates in gLP. Acitretin was most effective in cLP, whereas isotretinoin showed favorable responses in oLP. Conclusions: This large, histopathologically confirmed cohort highlights distinct differences in comorbidity patterns, anatomical involvement, and therapeutic response across LP subtypes. Treatment outcomes vary substantially by subtype, underscoring the need for individualized management strategies. Prospective studies are warranted to further elucidate subtype-specific disease associations and optimize treatment approaches. Full article