Search Results (172)

Background/Objectives: Primary steroid-resistant nephrotic syndrome (SRNS) in children is an ominous diagnosis due to limited therapeutic options and poor prognosis. The younger the child, the greater the probability of a genetic etiology which is typically resistant to immunosuppressive therapy. International guidelines recommend genetic testing and a search for rare infectious causes in the youngest age group. When no identifiable etiology is found, an immunologic cause of SRNS is suspected, with few therapeutic options available, which lately have included anti-CD20 therapy for children > 7 years of age. This is the first report on the successful use of obinutuzumab in a very young child with primary SRNS. Methods: Two consecutive doses of obinutuzumab, a humanized anti-CD20 antibody (300 mg/m² BSA), were administered two weeks apart to a 24-month-old boy with severe, complicated SRNS which had been refractory to cyclosporin A and rituximab and in whom previous genetic testing and a search for multiple infectious causes had been negative. Results: Complete remission of severe nephrotic syndrome was achieved 2 months after the last infusion with, to date, sustained resolution of proteinuria and normal serum albumin levels without further use of IMS drugs and no severe adverse effects noted. Conclusions: Obinutuzumab may be a rescue option for severe, multidrug-resistant ISN, even in young children, when no other therapeutic options are available. Full article

Background and Clinical Significance: Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by acute or subacute bilateral central vision loss, typically in young males. Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are immune-mediated demyelinating diseases that may present with optic neuritis and myelitis. Although distinct in etiology, recent evidence suggests that mitochondrial dysfunction and neuroinflammation can overlap, giving rise to combined phenotypes such as LHON-MS (also known as Harding’s disease). Case Presentation: We report a 42-year-old man who initially presented in 2018 with right-eye pain and severe visual loss diagnosed as idiopathic optic neuritis. Despite corticosteroid and plasma-exchange therapy, visual recovery was poor, and he was maintained on azathioprine. One year later, he developed visual flashes and left-eye visual loss with bilateral optic nerve thinning on OCT. Genetic testing revealed a pathogenic MT-ND4 (m.11778G>A) mutation, confirming LHON. In 2021, he presented with ascending lower-limb numbness and bladder urgency. MRI demonstrated a central thoracic cord lesion at T11, consistent with acute transverse myelitis, while serum AQP4 and MOG antibodies were negative. CSF showed five unique oligoclonal bands. The diagnosis of LHON-MS overlap was established, and he was treated with corticosteroids followed by rituximab with clinical stability thereafter. Conclusions: This case highlights the diagnostic challenges of LHON with atypical optic neuritis initially followed by the development of demyelinating disease. Red flags such as poor visual recovery, bilateral or sequential optic neuropathy, and steroid-refractory episodes should prompt genetic testing to rule out LHON. Recognition of the mitochondrial–immune overlap is essential for accurate diagnosis, counseling, and an appropriate therapeutic strategy. Full article

Background/Objectives: Vogt–Koyanagi–Harada (VKH) disease is a bilateral granulomatous panuveitis that can progress to a chronic, relapsing phase. Patients refractory or intolerant to systemic corticosteroids and conventional immunomodulatory therapy pose a major therapeutic challenge, as persistent inflammation can lead to cumulative ocular damage and permanent vision loss. This study assessed the efficacy of tumor necrosis factor-α (TNF-α) inhibitor adalimumab in chronic recurrent VKH disease. Methods: We retrospectively reviewed 16 eyes from 8 patients with chronic recurrent VKH disease who had persistent inflammation despite treatment with corticosteroids and conventional immunomodulatory therapy, and subsequently received adalimumab. Primary outcomes were changes in subfoveal choroidal thickness (SFCT) and systemic corticosteroid dose reduction. Secondary outcomes included visual acuity, inflammatory parameters (anterior chamber cell, flare, and vitreous haze), and central macular thickness (CMT). All outcomes were compared between baseline and 6 months after adalimumab initiation using the Wilcoxon signed-rank test. Results: Mean patient age was 47.6 years and mean follow-up was 31.8 months. SFCT decreased from 326.7 ± 129.1 µm to 231.6 ± 72.9 µm at 6 months (p < 0.001). Systemic steroid dose decreased from 14.7 ± 14.0 mg to 4.1 ± 3.8 mg (p = 0.027). Mean annualized relapse rate decreased from 3.61 to 0.08 episodes/year (p = 0.012). Anterior chamber cell grade decreased from 0.81 ± 0.66 to 0.09 ± 0.20 (p < 0.001). Visual acuity, flare, vitreous haze, and CMT showed no significant change. No serious adverse events occurred. Conclusions: TNF-α inhibition with adalimumab appears effective as steroid-sparing therapy for controlling recurrent inflammation and reducing steroid dependence in patients with chronic recurrent VKH disease refractory to conventional treatment. Full article

Dermatomyositis (DM) is a prototypic idiopathic inflammatory myopathy in which characteristic skin disease frequently precedes or parallels muscle involvement and signals risks such as interstitial lung disease (ILD) and malignancy. This literature review integrates recent advances across dermatology, neuromuscular medicine, and immunology to refine diagnosis and management. We surveyed the literature from 2000 to 2025, prioritizing randomized trials, large cohorts, and translational studies that spanned classic and juvenile DM, amyopathic/hypomyopathic variants, and overlap phenotypes. Key insights include the diagnostic weight of pathognomonic cutaneous lesions with nailfold microangiopathy; the utility of myositis-specific autoantibodies for endotyping and risk (e.g., anti-TIF1-γ/anti-NXP2 and cancer, anti-MDA5 and rapidly progressive ILD); and the value of myxovirus-resistance protein A (MxA) immunohistochemistry and muscle MRI patterning (including distinctions from immune-mediated necrotizing myopathy) when enzymes are normal, or biopsies are treatment-modified. Management is anchored in early steroid-sparing immunosuppression tailored to phenotype, with evidence for IVIG in active DM and growing support for JAK inhibition, particularly in interferon-high or anti-MDA5 ILD, alongside selective use of calcineurin inhibitors and rituximab, with plasma exchange considered for refractory, rapidly progressive ILD. We highlight risk-stratified malignancy screening (IMACS 2023) and complications, including calcinosis, lipodystrophy, and chronic cutaneous damage. Skin-led recognition coupled with antibody-guided, phenotype-directed therapy and interdisciplinary care offers a pragmatic precision framework to improve outcomes and reduce long-term disability. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies, but they may cause a wide range of immune-related adverse events (irAEs). Hepatic toxicity occurs in approximately 1–6% of patients treated with nivolumab and usually presents with a hepatocellular pattern responsive to corticosteroids. The cholestatic-predominant immune-mediated hepatitis seems to respond poorly to immunosuppression. We describe an 87-year-old man with metastatic melanoma treated with nivolumab who developed steroid-refractory, cholestatic-predominant immune-mediated hepatitis after 18 cycles of therapy. Laboratory tests revealed a mixed but predominantly cholestatic pattern (ALT 585 U/L, GGT 2261 U/L, total bilirubin 2.0 mg/dL). Imaging excluded biliary obstruction or hepatic metastases. Liver biopsy showed acute lobular hepatitis with intracanalicular cholestasis and mild bile duct injury, consistent with immune-mediated, drug-induced injury (Ishak score 5). Mycophenolate mofetil produced only partial biochemical improvement. The patient died one month later from influenza A pneumonia in the context of combined immunosuppressive therapy. This case illustrates a cholestatic-predominant phenotype of nivolumab-induced hepatitis, characterized by poor corticosteroid response and incomplete recovery despite second-line immunosuppression. Recognition of this entity is essential, as early introduction of agents such as mycophenolate may improve outcomes. In elderly and frail patients, however, the risks of intensified immunosuppression must be carefully balanced against infection risk, highlighting the need for individualized management and vigilant monitoring. Full article

Background and Clinical Significance: Targeted biologic therapies, especially monoclonal antibodies (mAbs) such as nivolumab and alemtuzumab, have revolutionized treatment for malignancies and autoimmune conditions but can cause rare immune-related adverse events (IRAEs), including orbitopathy. To date, only a handful of cases have described the treatment of thyroid eye disease secondary to mAbs, and even fewer have described how to treat refractory disease. Case Presentation: We are illustrating two cases in this report: a 73-year-old woman who developed thyroid eye disease (TED) after nivolumab therapy for melanoma, and a 36-year-old man who presented with TED following alemtuzumab treatment for multiple sclerosis. Both patients failed corticosteroid therapy but showed a significant improvement with teprotumumab, an anti-insulin-like growth factor (IGF)-1 receptor mAb. Conclusions: These cases highlight underrecognized orbital IRAEs linked to mAb therapy and demonstrate teprotumumab’s potential as an effective option for steroid-refractory thyroid orbitopathy. Clinicians should maintain an awareness of orbital complications in patients receiving mAbs to enable prompt diagnosis and intervention, minimizing visual morbidity. Further studies are needed to clarify the pathogenesis of mAb-associated orbitopathy and to establish evidence-based treatment protocols for these rare but impactful complications. Full article

Background/Objectives: Wells’ syndrome (WS) is an uncommon cutaneous disease with unknown etiology. Itchy bullous lesions and erythematous plaques characterize the bullous WS (BWS), a rare subtype of the syndrome. We describe the case of a woman affected by chronic lymphocytic leukemia who developed BWS and responded to the classic corticosteroid treatment. We also systematically reviewed the literature, analyzing the clinical, laboratory, and histological features and treatments of this rare disease. Methods: We used the databases Ovid MEDLINE, PubMed, and EMBASE with the following search terms: ((bullous Wells’ syndrome [MeSH Terms]) OR (eosinophilic cellulitis)) OR (bullous eosinophilic dermatitis) to identify and compare case reports of BWS. Results: We analyzed 28 patients, including our case. They were primarily female adults with a median age of 44.92 years. Blood eosinophilia was common, and histologically, the tissue samples showed an eosinophilic-neutrophilic dermal infiltrate. From a clinical perspective, the bullae were typically associated with or preceded by other lesions, primarily urticarial plaques, and mainly involved the extremities. Possible triggering agents of BWS include medications, insect bites, malignancies, and autoimmune/infectious diseases. Systemic steroids constituted the first-line treatment. Recent studies described the efficacy of the anti-interleukin-5 monoclonal antibody Mepolizumab in refractory cases of WS. Conclusions: Diagnosis of BWS is often challenging due to the rarity of the disease, clinical polymorphism, and multiple differential diagnoses. Integrating clinical features with laboratory and histopathological findings is essential for achieving a definitive diagnosis. Although the causal link between WS and underlying neoplastic/autoimmune/infective conditions is not always present, this possibility should be taken into account and investigated for the best patient management. Full article

Background: Lichen planus (LP) is a common inflammatory disease affecting skin, mucous membranes, hairs, and nails, with an unpredictable course involving remissions and relapses. LP is a Type-I-Inflammation disease involving IFN-γ and IL-17 as key inflammatory mediators. Materials and Methods: We searched PubMed/MEDLINE and Google Scholar search engines for studies on the esophageal manifestation of lichen planus over an unlimited time frame. Articles were searched with combinations of Medical Subject Heading (MeSH) terms. Given the limited number of publications, no exclusion criteria were applied. Results: Esophageal lichen planus (ELP) is an underreported manifestation of LP that primarily affects middle-aged women. Its prevalence among LP patients remains to be defined. Though potentially clinically silent, ELP can significantly impact patient wellbeing and serve as a precursor to esophageal squamous cell carcinoma. While dysphagia is the primary symptom, the condition may also remain subclinical. The endoscopic hallmarks of ELP are mucosal denudation and tearing, trachealization, and hyperkeratosis. Chronic disease progression may lead to scarring esophageal stenosis. Histologically, ELP shows mucosal detachment, T-lymphocytic infiltrations, epithelial cell apoptosis (Civatte bodies), dyskeratosis, and hyperkeratosis. Fibrinogen deposits along the basement membrane zone distinguish ELP from various immunological esophageal diseases. There is currently no standardized therapy available. Topical steroids lead to symptomatic and histologic improvements in two-thirds of patients. Severe or refractory cases require immunosuppressive therapy, whereas JAK-inhibitors represent a promising emerging option. Endoscopic dilation helps symptomatic stenosis. Considering ELP’s precancerous potential, timely diagnosis and treatment are crucial in preventing complications, such as stenosis or invasive esophageal squamous cell carcinoma. Conclusions: ELP is an underdiagnosed and underreported manifestation of LP. While it may remain clinically silent, it can nevertheless significantly affect patients’ wellbeing and life expectancy. This narrative review aims to initiate multidisciplinary cooperation among gastroenterologists, dermatologists, oral health professionals, and histopathologists to support clinical diagnosis and management. Full article

Acute severe ulcerative colitis (ASUC) is a medical emergency affecting up to 25% of patients with ulcerative colitis (UC), with colectomy required in approximately 25–30% of cases during the initial admission. Intravenous corticosteroids remain the first-line therapy, though one-third of patients do not respond, necessitating rescue with infliximab or calcineurin inhibitors, which are both supported by randomized trials and guideline recommendations. Comparative studies and meta-analyses have shown similar efficacy between these agents, while sequential use is associated with higher adverse event rates and should be restricted to specialized centers. Recent data have refined infliximab use, with the PREDICT-UC trial showing no superiority of intensified dosing over standard regimens. Emerging therapies are under investigation: vedolizumab has been used as maintenance following calcineurin induction; ustekinumab has shown benefits in retrospective UC cohorts, particularly after cyclosporine; and Janus kinase (JAK) inhibitors represent the most recent addition. The randomized TACOS trial and the prospective TRIUMPH study demonstrated an improved short-term response with tofacitinib in steroid-refractory ASUC, and real-world reports suggest promising outcomes with upadacitinib. While infliximab and cyclosporine remain as standard rescue therapies, ongoing trials with novel agents are likely to broaden treatment options. This review summarizes the clinical features, initial management, and the role of advanced therapies in ASUC. Full article

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease of the esophagus within the type 2 inflammatory spectrum, characterized by progressive tissue remodeling driven by uncontrolled inflammation. Its incidence and prevalence are rising sharply, likely reflecting environmental triggers acting on genetic and epigenetic susceptibility. Therapeutic options have expanded rapidly, with recent approvals of new topical steroidal formulations together with biologic compounds. Proton pump inhibitors (PPIs), older swallowed topical corticosteroid (STC), and dietary interventions remain in use but are limited by suboptimal adherence and treatment discontinuation. This has driven a shift toward advanced orally dispersible STCs formulations—most notably budesonide orally dispersible tablets (BOT), budesonide oral suspension (BOS), and fluticasone orally dispersible tablets (FOT). BOT, the most extensively studied, achieves high rates of histologic and clinical remission, with favorable safety and superior adherence compared to earlier STCs formulations. This comprehensive overview focuses on following key research findings and novelty aspects of new treatments: (a) optimized esophageal targeting through orally dispersible or viscous formulations of STC, enhancing mucosal contact time and improving drug delivery to affected tissues compared to older formulations; (b) robust evidence for both induction and maintenance rates of remission, with data extending up to nearly 2 years and showing stable efficacy across clinical, histologic, and endoscopic endpoints; (c) effectiveness in STC-refractory patients, with BOT showing benefit even in those previously unresponsive to older STC formulations. This review synthesizes evidence of steroid therapy in EoE, from pharmacological aspects to clinical efficacy from randomized trials and emerging real-world studies, highlighting its impact on EoE management and outlining future therapeutic directions. Full article

Steroid-induced osteonecrosis of the femoral head (SONFH) is a common and refractory orthopedic disorder, often resulting from prolonged or high-dose glucocorticoid use that impairs bone repair and vascularization. The critical impact of exosomes derived from bone mesenchymal stem cells (BMSCs) in bone regeneration has drawn increasing attention. In this study, we developed a novel type of exosomes derived from Magnesium-preconditioned BMSCs (Mg-Exos) and evaluated their therapeutic potential. In vitro experiments demonstrated that Mg-Exos effectively counteracted Dex-induced impairment in the angiogenic function of human umbilical vein endothelial cells (HUVECs) and the osteogenic differentiation of BMSCs. These findings highlight the promise of Mg-Exos as a potential cell-free therapeutic strategy for SONFH, acting through the concurrent enhancement of vascularization and bone formation. Consequently, this work lays a solid foundation for the future application of Mg-Exos in treating SONFH. Full article

Chronic pelvic neuropathies involving the pudendal, ilioinguinal, and genitofemoral nerves are a major source of refractory pain and disability, yet conventional steroid injections typically provide only short-lived benefit. We retrospectively analyzed 78 patients: 49 with pudendal neuralgia treated by pulsed radiofrequency and 29 with ilioinguinal (n = 15) or genitofemoral (n = 14) neuropathies treated by continuous radiofrequency ablation. For pudendal neuropathy, pRF provided a mean pain relief of 9.48 ± 9.52 weeks versus 3.98 ± 3.56 weeks after the first steroid injection and 3.32 ± 3.21 weeks after the most recent (p < 0.0001 for both). Quality-of-life scores improved significantly through 3 months, and analgesic use declined during this period. No correlation was found between symptom duration and treatment response. For ilioinguinal and genitofemoral neuropathies, cRFA extended pain relief to 21.76 and 17.68 weeks, respectively. Mean VAS scores improved from 6.87 to 1.73 for ilioinguinal (p < 0.0001) and from 6.36 to 2.36 for genitofemoral (p = 0.0007) neuropathies. Quality-of-life scores improved through 3 months, with trends toward baseline by 6 months, while analgesic use decreased initially before returning to baseline. Across all nerves, no major complications occurred. Radiofrequency treatment offers safe, longer-lasting relief than steroid injections for refractory pelvic neuropathies. Full article

Sarcoidosis is a chronic inflammatory disease of unknown etiology that can involve virtually any organ, with pulmonary involvement seen in over 90% of cases. Although many patients experience spontaneous remission, approximately 10–30% develop progressive pulmonary disease, which may lead to fibrocystic changes, respiratory failure, and death. Oral glucocorticoids remain the cornerstone of treatment for symptomatic patients with pulmonary infiltrates and abnormal pulmonary function tests, with typical starting doses ranging from 20 to 40 mg/day followed by a slow taper over 6–18 months based on clinical and radiographic response. However, prolonged glucocorticoid therapy is associated with significant toxicity, and many patients require additional immunosuppressive agents for disease control or steroid-sparing purposes. Antimetabolites such as methotrexate, azathioprine, mycophenolate mofetil, and leflunomide are commonly used second-line therapies. For refractory disease, particularly in those with metabolically active lesions on FDG-PET, anti-tumor necrosis factor (TNF) agents like infliximab may be effective but carry risks of serious adverse effects. In select cases, newer strategies—including RCI, rituximab, JAKi or investigational regimens—are being explored. Management must also account for non-inflammatory complications such as sarcoidosis-associated pulmonary hypertension and bronchiectasis, which can mimic disease progression and require distinct therapeutic approaches. Given the heterogeneity of sarcoidosis and lack of robust clinical trial data, a stepwise and individualized approach to immunosuppression remains essential in optimizing outcomes while minimizing treatment-related harm. Full article

Background and Clinical Significance: Common Variable Immunodeficiency (CVID) is a prevalent manifestation of primary immunodeficiency disorder. The current mainstay of treatment is immunoglobulin replacement therapy; however, in patients with severe complications or refractory disease, hematopoietic stem cell transplant (HSCT) is indicated. Despite this, there has been little research regarding HSCT as a treatment for CVID, with few case reports demonstrating clinical benefit. Case presentation: We present a unique case of common variable immunodeficiency Type XII (CVID12) with rare NFKB mutation and its management. A 20-year-old female with autoimmune alopecia, eczema, and a congenital atrophic right kidney presented to the emergency department with a three-month history of intermittent fever, malaise, lymphadenopathy, mouth sores, diarrhea, and odynophagia, accompanied by a 5 lb. unintentional weight loss and night sweats. Previously, she received multiple steroid prescriptions for these symptoms, providing only temporary relief with each course. Lab findings revealed severe neutropenia and imaging demonstrated hepatosplenomegaly and lymphadenopathy. Flow cytometry revealed a slightly atypical CD8-positive T-cell population and bone marrow biopsy revealed variable cellular marrow with trilineage hematopoiesis. Genetic testing confirmed the diagnosis of Autosomal Dominant Common Variable Immunodeficiency Type XII with an NFKB1 mutation. Pre-transplant treatments included monthly IVIG, weekly rituximab, and daily filgrastim, all of which failed to improve her autoimmune neutropenia and hypogammaglobulinemia and failed to reduce her symptomatic burden. Given the patient’s young age and refractory autoimmune neutropenia, it was decided to manage them definitively with hematopoietic stem cell transplantation (HSCT). She ultimately underwent allogenic stem cell transplantation (haploidentical, donor was the mother) with 3.96 × 10⁸/kg TNC without immediate post-transplant complications. Conclusions: This article demonstrates a rare case of NFKB1-positive CVID that was successfully treated with HSCT and highlights the importance of considering transplant therapy in younger patients with clinically significant, refractory autoimmune cytopenia. Full article

Background/Objectives: Recent studies have investigated the effectiveness of second-line agents in patients with ulcerative colitis (UC) who have experienced failure with first-line biologics. Although cytapheresis (CAP) is an effective therapeutic strategy for refractory UC, the efficacy of second-line agents in patients with UC with previous CAP failure remains unexplored. Herein, we examined the efficacy of biologics in patients with refractory UC who experienced non-response or insufficient response to previous CAP. Methods: We retrospectively assessed the efficacy of biologics administered between January 2013 and June 2024 in patients with refractory UC who experienced non-response or insufficient response to previous CAP. Rates of clinical remission, steroid-free remission, and endoscopic improvement were also determined. Clinical remission was evaluated using Lichtiger’s clinical activity index. Results: Eighty-one patients with refractory UC underwent CAP, thirty of whom were eligible for study inclusion. The use of biologics was associated with clinical and steroid-free remission rates of 75.9% and 44.8%, respectively. Clinical and steroid-free remission rates of biologics did not differ significantly between patients with an insufficient response to previous CAP and those with non-response to previous CAP. There were no significant differences in clinical or steroid-free remission rates of biologics between patients with steroid-dependent and steroid-refractory UC. Endoscopic improvement was observed in 54.5% of patients. Conclusions: Despite the limited number of patients, biologic therapy was effective in patients with refractory UC who had experienced a non-response or insufficient response to previous CAP. Accordingly, biologics may be a useful second-line therapy for patients with refractory UC who have failed CAP. Full article