Search Results (173)

Aspergillus can cause a spectrum of diseases depending on the immune status and predisposing conditions. Invasive pulmonary aspergillosis (IPA) is classically seen in patients with severe immunocompromise, such as patients with hematologic malignancies, transplant recipients, and chronic corticosteroid use at high doses. Recently, IPA cases in patients without these classic risk factors, including those associated with severe respiratory viral infections, chronic obstructive pulmonary disease, liver failure, and critical illness, are being increasingly recognized. Delayed recognition and missed diagnoses contribute to increased mortality in these patient populations. Maintaining a high index of suspicion and implementation of systematic screening protocols in high-risk patients may help reduce missed or delayed diagnoses and improve patient outcomes. This review describes the pathophysiology, incidence, risk factors, outcomes, and diagnostic and treatment considerations in IPA in patients with emerging risk factors. Full article

Objectives: Non-cystic fibrosis bronchiectasis (BE) is a chronic airway disease with increasing prevalence, reduced quality of life, and increased mortality. Inhaled corticosteroids (ICS) are used in BE despite limited evidence of effect on lung function parameters. ICS may increase the risk of Staphylococcus aureus (S. aureus) infections in patients with BE, but this is unexplored. We examined the association between ICS use prior to BE diagnosis at different doses and the risk of S. aureus isolation in patients with BE. Methods: We conducted a national register-based cohort study including Danish patients with a BE diagnosis code between 2001 and 2018 with a 1-year follow-up time from the date of diagnosis. ICS exposure was categorized based on accumulated prescriptions redeemed 365 days before BE diagnosis and divided into none, low, moderate, or high use based on clinically relevant doses. A cause-specific Cox proportional hazards regression model was used to estimate the risk of S. aureus isolation. A sensitivity analysis, an inverse probability of treatment weighted model (IPTW), was performed. Results: A total of 5093 patients were included in this study. S. aureus was isolated in 156 patients (3.1%). High-dose ICS was associated with an increased risk of S. aureus isolation, HR 3.81 (95% CI 2.51; 5.79). No association for low or moderate use was found, low-dose HR 1.22 (95% CI 0.77; 1.93), and moderate-dose HR 1.24 (95% CI 0.72; 2.16). IPTW analysis yielded similar results. Conclusions: High-dose ICS use in patients with BE was associated with an increased risk of S. aureus isolation. ICS should be used cautiously in patients with BE. Full article

Background: Inhaled corticosteroids (ICSs) are a cornerstone in asthma management, particularly during exacerbations, when high doses are often prescribed. However, patient concerns about potential side effects such as increased appetite, weight gain, and metabolic disturbances may reduce adherence, compromising treatment outcomes. While oral corticosteroids (OCSs) are well known to induce such effects, the metabolic impact of short-term high-dose ICSs remains poorly studied. Objective: This prospective pilot study aimed to assess whether a 14-day course of high-dose ICSs in adults with stable asthma induces changes in appetite, dietary intake, leptin levels, or body weight. Methods: Thirty-five adults (19 males, 16 females; mean age 48.7 ± 15.1 years) with stable mild asthma received ≥400 µg/day extrafine beclomethasone dipropionate/formoterol via pressurized metered-dose inhaler for 14 days. Participants underwent assessments at baseline and after 14 days, including body weight, BMI, fasting serum leptin levels, dietary intake (evaluated using 24 h dietary recalls), and appetite (measured via a visual analogue scale). Results: No significant changes were observed in body weight (mean change: −0.38 kg; 95% CI: −0.81 to 0.05; p = 0.083) or BMI (p = 0.912) following high-dose ICS use. Similarly, serum leptin levels (mean change: 0.13 ng/mL; 95% CI: −3.47 to 3.72; p = 0.945), subjective appetite scores (mean change: −4.93 mm; 95% CI: −13.64 to 3.79; p = 0.267), and dietary energy intake (mean change: +255 kJ/day; 95% CI: −380 to 891; p = 0.431) did not differ significantly post-intervention. Conclusions: Short-term high-dose ICS therapy in adults with mild asthma may not significantly affect appetite, dietary intake, leptin levels, or body weight. These findings support the metabolic safety of short-term high-dose ICSs and may help alleviate patient concerns, improving adherence during exacerbation management. Full article

Inhaled corticosteroids (ICSs) are widely used to manage chronic respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), and human immunodeficiency virus (HIV). However, prolonged use of ICS is associated with the development of oropharyngeal candidiasis, a fungal infection primarily caused by Candida albicans, due to local immunosuppression in the oral cavity. The incidence of oropharyngeal candidiasis varies depending on geographic region, patient age, and comorbidities, with immunocompromised individuals, those with diabetes, and the elderly being particularly vulnerable. Key risk factors include high ICS doses, poor oral hygiene, and improper use of inhalers. Prevention is the cornerstone of managing oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids. Patient education on proper inhaler technique and oral hygiene is essential to reduce the risk of fungal overgrowth in the oral cavity. Additional preventive strategies include the use of spacers, mouth rinsing after inhalation, and proper denture care. In cases where these measures fail to prevent the infection, prompt detection and early intervention are crucial to prevent progression or recurrence. This narrative review aims to analyze the most effective prophylactic measures to prevent oropharyngeal candidiasis associated with the chronic use of inhaled corticosteroids, emphasizing patient education, oral hygiene, and proper use of inhalation devices. Full article

Background and Clinical Significance: Neuromyelitis optica (NMO) is a chronic demyelinating inflammatory disease of the central nervous system (CNS), mediated by autoantibodies against aquaporin-4 (AQ4) receptors. In the spectrum of NMO, other autoimmune diseases also coexist, though their association with systemic lupus erythematosus (SLE) is rare. Case Presentation: We present two cases of patients in their 70s who were diagnosed with NMO in the context of SLE. The first case concerns a 78-year-old woman with drug-induced SLE and thoracic myelitis who developed T4-level incomplete paraplegia over three weeks. The second case involves a 71-year-old woman with a history of SLE and myasthenia gravis, presenting with cervical myelitis with progressive worsening of walking and C4-level paraparesis over two months. In both cases, elevated serum anti-AQ4 titers were detected, establishing the diagnosis of NMO and differentiation from an atypical manifestation of SLE-related myelitis. High doses of intravenous corticosteroids with gradual tapering, along with cyclophosphamide, followed by rituximab, were administered in both patients. The first patient showed a poor response, while the second showed improvement. Conclusions: The coexistence of NMO with SLE is rare, but the occurrence of myelitis in patients with connective tissue diseases should raise the suspicion of NMO, especially in elderly women and several years after the diagnosis of SLE. Time to treatment is critical, as delays in treating NMO can result in cumulative and disabling damage. Full article

The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, significantly improving patient outcomes across multiple malignancies. Nonetheless, these therapies are associated with immune-related adverse effects, including cardiotoxicity, which remains a critical concern. This review provides a comprehensive analysis of ICI-related cardiotoxicity, encompassing its pathophysiological mechanisms, risk factors, diagnostic modalities, and management strategies. The onset of cardiotoxicity varies widely, ranging from acute myocarditis to long-term cardiovascular complications. Early identification through clinical assessment, biomarkers, and advanced imaging techniques is crucial for timely intervention. Management strategies include high-dose corticosteroids, other immunosuppressive agents, and supportive therapies, with a focus on balancing oncologic efficacy and cardiovascular safety. Additionally, rechallenging patients with ICIs following cardiotoxic events remains a complex clinical decision requiring multidisciplinary evaluation. As immunotherapy indications expand to include high-risk populations in a curative setting too, optimizing screening, prevention, and treatment strategies is essential to mitigate cardiovascular risks. A deep understanding of the molecular and clinical aspects of ICI-related cardiotoxicity will enhance patient safety and therapeutic decision-making, underscoring the need for ongoing research in this rapidly evolving field. Full article

Background: Pneumocystis jirovecii pneumonia (PJP) remains a serious threat to non-HIV immunocompromised patients, who often experience rapid disease progression, delayed diagnosis, and higher mortality. Standard treatment with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) is based primarily on data from HIV-positive populations, despite differences in immune response and drug tolerability. Objective: This narrative review critically synthesizes the available evidence on lower-dose TMP-SMX strategies for PJP in non-HIV patients and explores the potential role of individualized dosing approaches to improve outcomes. Findings: Emerging retrospective data suggest that lower-dose regimens (<15 mg/kg/day) may provide similar survival outcomes with fewer adverse effects. The intense inflammatory response observed after treatment initiation in non-HIV patients, potentially exacerbated by high-dose therapy, may contribute to clinical deterioration. This raises the possibility that TMP-SMX dosing itself could influence immune-mediated lung injury. While adjunctive corticosteroids are frequently used to temper inflammation, their benefit remains uncertain. Conclusions: Existing data suggest that lower-dose TMP-SMX may be effective and better tolerated in some non-HIV patients with PJP. A personalized approach to dosing, informed by clinical and host-specific factors, represents a promising strategy to optimize outcomes and minimize harm. Future research should prioritize precision medicine frameworks and prospective evaluation of individualized dosing protocols. Full article

Background: Leprosy, caused by Mycobacterium leprae, presents on a spectrum ranging from tuberculoid to lepromatous disease. Borderline lepromatous leprosy represents an unstable immunological state that predisposes patients to immune-mediated reactions, including erythema nodosum leprosum (ENL), a severe inflammatory complication. Case Presentation: We report a case of a 62-year-old female with borderline lepromatous leprosy who presented with recurrent facial cellulitis and later developed disseminated ENL. She was initially diagnosed following a series of facial infections and confirmatory skin biopsy. Months later, she developed systemic inflammatory lesions consistent with ENL, requiring hospitalization. She was treated with high-dose corticosteroids for ENL and methotrexate to treat type 1 reaction and continued multidrug therapy (MDT) with minocycline, rifampin, and clarithromycin for leprosy, which led to significant clinical improvement. Conclusion: This case highlights the diagnostic challenges of leprosy in the United States and the importance of recognizing ENL as a severe immunologic complication requiring prompt intervention. A multidisciplinary approach is essential for optimal patient outcomes. Full article

Asthma is a highly heterogeneous respiratory disease that, in its severe forms, is characterized by persistent symptoms, frequent exacerbations, and a significant impact on patients’ quality of life. Despite high-dose inhaled corticosteroids and long-acting bronchodilators, a subset of patients remains uncontrolled, necessitating advanced therapeutic strategies. The advent of biologic therapies has revolutionized the management of severe asthma, offering targeted interventions based on the underlying inflammatory endotypes, primarily T2-high and T2-low. However, selecting the most appropriate biologic remains challenging due to overlapping phenotypic features and the limited availability of validated biomarkers. This narrative review explores the clinical utility of key biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), periostin, and total and specific IgE, in guiding biologic therapy. All the information provided is based on an extensive literature search conducted on PubMed. We also examine the clinical characteristics and comorbidities that influence therapeutic choices. Furthermore, we present a practical decision-making platform, including a clinical table matching phenotypes with biologic agents, such as omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab. By integrating biomarker analysis with clinical assessment, based on current guidelines and our extensive real-life experience, we aim to offer a logical framework to help clinicians select the most suitable biologic treatment for patients with uncontrolled severe asthma. Future research should focus on identifying novel biomarkers, refining patient stratification, and evaluating long-term outcomes to further advance precision medicine in the management of severe asthma. Full article

Background/Objectives: Autoimmune inner ear disease (AIED) causes sensorineural hearing loss that classically presents as fluctuating, asymmetric loss of hearing. Associated vestibular and other ear symptoms can be present in many patients. First-line treatment of AIED is high-dose corticosteroids. AIED can present either as a primary condition limited to ear involvement or secondary, as part of an underlying systemic autoimmune rheumatic disease, the most common of which include vasculitis and relapsing polychondritis. We described our cohort of primary AIED, including demographics, treatment, and outcomes. We excluded from this review sensorineural hearing loss in the context of vasculitis and relapsing polychondritis. Methods: We performed a chart review of patients with the diagnosis of AIED at Mayo Clinic and compared the cohort by sex. Results: Thirty-one patients met the inclusion criteria. The mean age was 48.5 years, and 17 were men. Patients were initially evaluated at the Department of Otorhinolaryngology or Internal Medicine, and 29 patients were subsequently referred to the Department of Rheumatology, with a mean of 12.2 weeks after the first evaluation. Treatment with corticosteroids showed improvement in hearing and vestibular symptoms during the first month but no further improvement by the end of the third month. Other immunosuppressive medications were used with various degrees of response. Methotrexate was the second most used therapy, with 11 of 17 patients reporting an improvement in symptoms. Conclusions: Corticosteroid therapy is an effective initial treatment for AIED and should be followed with corticosteroid-sparing agents to prevent further damage to the cochlea. Full article

Background: Immunomodulatory treatments targeting excessive host immune responses favorably shifting the course of COVID-19. High doses of calcifediol may reduce the mortality of this infection. Objective: To evaluate how a high dose of calcifediol modifies the risk of death in patients hospitalized with COVID-19 during the first outbreaks. Design: A retrospective, observational study to evaluate the relationship between treatment with calcifediol and the risk of death in patients hospitalized with COVID-19 at the “Complejo Hospitalario Universitario de Albacete” (CHUA), Spain, during the months of January to March 2021. Patients were treated with corticosteroids, and some patients also received baricitinib and/or high doses of calcifediol, according to CHUA’s therapeutic protocol 2021 for COVID-19. The primary outcome measure was mortality according to calcifediol treatment. Results: A total of 230 patients were included. 25(OH)D levels were measured on admission in 148 patients, showing a high prevalence of vitamin D deficiency [median 25(OH)D: 17.5 ng/mL]. Thirty-four (23%) had severe deficiency (25(OH)D ≤ 10 ng/mL). In the 119 patients (51.7%) who received in-hospital treatment with a high dose of calcifediol, the mortality rate was 12.6% (15 cases, 95% confidence interval [CI], 7.8–19.8%), while in 111 patients who did not receive treatment with calcifediol, the death rate was 23.4% (26 cases, 95% CI: 16.5–32.1%; p = 0.039). The odds ratio (OR) in treated vs. untreated patients was 0.47 (95% CI: 0.23–0.95). Among the patients admitted with severe deficiency, 16 received treatment with calcifediol, with a mortality rate of 0.0% (0 cases, 95% CI: 0.0–19.4%), while in the 18 not treated with calcifediol, a death rate of 38.9% was observed (7 cases, 95% CI: 20.3–61.4%; p = 0.008). The mortality rate was lower in patients treated with the combination of calcifediol and corticosteroids vs. those treated with corticosteroids alone (p = 0.038) and vs. those treated with corticosteroids and baricitinib (p = 0.033). Conclusions: In the ALBACOVIDIOL study, calcifediol treatment was associated with a lower observed mortality rate in hospitalized patients with COVID-19 treated with corticosteroids (with or without baricitinib), especially in those with severe vitamin D deficiency. Causality cannot be inferred due to the retrospective study design. (Public database: ClinicalTrials.gov, NCT05819918). Full article

IgA nephropathy (IgAN) is an inflammatory glomerular disease caused by the production of galactose-deficient IgA1 (Gd-IgA1), which induces the formation of autoantibodies and IgA immune complexes (IgAICs) that are ultimately deposited in the mesangium. This event triggers mesangial cell proliferation, cytokine release and complement activation, and both glomerular and interstitial damage, eventually leading to kidney function decline. Persisting proteinuria is the most relevant marker of disease progression. Systemic corticosteroids (CSs), a powerful anti-inflammatory approach, have shown kidney protective effects in early trials involving patients with IgAN at risk of progression with persistent proteinuria. However, later studies raised concerns regarding severe adverse events associated with high doses of methylprednisolone and questioned the long-term benefits. As a result, the KDIGO 2021 guidelines recommended limiting CS therapy to selected patients who accepted the high risk of adverse events. The treatment landscape shifted when reduced doses of methylprednisolone, combined with Pneumocystis pneumonia prophylaxis, demonstrated similar kidney protection compared to full methylprednisolone doses with fewer adverse events. An innovative approach involves a targeted budesonide formulation acting on Peyer’s patches, the main site of Gd-IgA1 production. This treatment showed benefits comparable to systemic CSs, with valuable limitations of adverse events. Several new drugs targeting key pathogenetic events of IgAN are under investigation, with promising results published in recent months. These new therapies target B cell activation (and subsequent Gd-IgA1 production), the complement cascade triggered by IgAIC deposition and the endothelin system, a key amplifier of kidney damage that contributes to the chronicity of IgAN. Full article

Background: Fluoroquinolones, available in topical and oral formulations, are used to manage bacterial skin and soft tissue infections, including Pseudomonas aeruginosa, atypical mycobacteria, and select multidrug-resistant Gram-negative organisms. Their excellent tissue penetration, bactericidal activity, and convenient dosing make them effective for certain skin and soft tissue infections. However, their use is limited by potential safety concerns, including tendinopathy (odds ratio up to 9.1 in corticosteroid users), QT interval prolongation with risk of torsades de pointes, phototoxicity, and rising antimicrobial resistance. Methods: A literature search of PubMed, Scopus, and Web of Science was conducted for articles from January 1985 to April 2025 with the search terms (quinolone OR fluoroquinolone) AND (dermatology OR “skin and soft tissue infection” OR “skin structure infection”). Abstracts and presentations were excluded. A Google search used the same terms for articles from government regulatory agencies. Results: This review provides practical guidance on the clinical use of topical and oral fluoroquinolones in dermatology. Delafloxacin demonstrated over 90% cure rates in trials for complicated skin infections. However, serious safety concerns remain, including a ninefold increase in tendinopathy risk among older adults on corticosteroids and corrected QT intervals exceeding 500 milliseconds in high-risk patients. Phototoxicity varies, with agents like sparfloxacin linked to heightened ultraviolet sensitivity. Resistance to ciprofloxacin exceeds 20 percent in Escherichia coli and P. aeruginosa in some populations. Culture-based prescribing, shorter treatment courses, and preference for topical treatments can reduce risk and preserve efficacy. Conclusions: Fluoroquinolones remain clinically useful in dermatology when prescribed selectively. Their appropriate use requires careful attention to patient risk factors along with their evolving resistance patterns and ongoing stewardship efforts. Full article

Effective multidisciplinary pain management involves an in-depth knowledge not only of diagnosis and treatment but of how interventional procedures affect patients across all health domains. One of the most common pharmacological tools utilized in patients suffering from chronic pain disorders is corticosteroids. Corticosteroids are leveraged for their anti-inflammatory properties across a wide range of disorders. This review examines the role of corticosteroids and pain management with a specific focus on their metabolic impact regarding glucose metabolism. Corticosteroids have been shown to increase gluconeogenesis, resulting in reduced insulin sensitivity and an impaired peripheral glucose uptake. These varied responses to corticosteroids are especially concerning given the high prevalence of diabetes mellitus in chronic pain patients. There is well-documented evidence of not only transient hyperglycemia but emerging literature on prolonged glycemic disturbances that may have a greater effect on patients than previously recognized. A review of the available literature reveals variations in hyperglycemia depending on corticosteroid type, dose, and various patient-specific factors. Some research does suggest that lower corticosteroid dosages can provide similar therapeutic benefits and potentially reduce glycemic aberrations. Given the current evidence, clinicians should closely monitor patients’ hemoglobin A1C levels when determining the risks and benefits of an interventional procedure and consider alternative pain management strategies when appropriate. Future research should focus on optimizing corticosteroid selection and dosing to balance the safety, particularly in diabetic or prediabetic patient populations. Full article

Diffuse alveolar hemorrhage (DAH), a catastrophic complication of connective tissue disorders (CTDs), manifests as rapid-onset hypoxemia, alveolar infiltrates, and progressive bleeding into the airways. While immune-mediated alveolar–endothelial injury primarily drives its pathophysiology, diagnosis is based on bronchoscopy and chest imaging. The clinical urgency lies in securing the compromised airway and stabilizing respiratory failure, a challenge increased by CTD-specific anatomical alterations such as cervical spine instability, cricoarytenoid arthritis, and subglottic stenosis. High-dose corticosteroids and immunosuppression are essential, while severe cases require extracorporeal membrane oxygenation or plasmapheresis. This comprehensive review introduces two novel approaches to address fundamental gaps in the management of CTD-induced DAH: a structured algorithm for a CTD-specific airway risk stratification tool, integrating anatomical screening and the application of lung ultrasounds (LUSs) for post-intubation CTD-induced DAH ventilation management. The need for a multidisciplinary team approach is also discussed. Despite aggressive care, mortality remains high (25–50%), underscoring the necessity for improved early recognition and intervention strategies for these high-risk patients. Full article