Search Results (40)

Background: Drug reaction with eosinophilia and systemic symptoms is a severe cutaneous reaction with a high mortality rate. It is challenging to diagnose due to its similar presentation to infectious disease syndromes, variation with the culprit drug, and lack of awareness. Methods: We searched PubMed, and Embase, for RegiSCAR-scored observational studies, the FDA Adverse Events Reporting System (FAERS) for adverse event reports, and the Allele Frequency Net Database (AFND) for HLA allele frequency. In our meta-analysis, we employed a random effects model to subgroup patients by ethnicity to determine the proportion of DRESS cases compared with various associated medications. Additionally, we identified a correlation between the proportion of cases and the presence of the HLA*A-32:01allele, which is suspected to predispose individuals to DRESS. Results: Twenty-one studies on 1949 DRESS cases in vancomycin and 2558 antimicrobial DRESS reports in the FAERS database were analyzed. Meta-analysis showed a 27% incidence of vancomycin-DRESS, with Caucasians having the highest proportion at 36%. The median latency for symptom onset was 21 days, with no female predisposition. The proportional incidence of vancomycin-DRESS did not correlate with the HLA-A*32:01 allele. The adjusted ROR for vancomycin was 2.40 compared to other antimicrobials, and the risk increased by 77% with concurrent antimicrobials. Piperacillin/tazobactam had a similar DRESS reporting risk at 0.95 (95%CI: 0.88–1.02). Conclusions: Vancomycin significantly contributes to the incidence of DRESS and is more closely related to ethnicity than to allele frequency, indicating that the HLA-A*32:01 allele may not be directly involved. Furthermore, the use of other antimicrobials can influence the reaction, underscoring the need to minimize antimicrobial use for better coverage. Full article

Type 2 diabetes (T2DM) is a chronic metabolic disease with a steadily increasing prevalence worldwide. Diabetes affects the function of many organs, including the skin. Pharmacotherapy for T2DM is mainly based on oral hypoglycemic drugs. The therapeutic strategy is chosen taking into account the individual patient’s characteristics, among other comorbidities. Antidiabetic drugs can induce cutaneous adverse reactions (CADRs) ranging in severity from mild erythema to serious disorders such as DRESS or Stevens–Johnson syndrome. CADRs can result from hypersensitivity to the drug but can also be related to the mechanism of action of the drug or cross-reactivity with drugs of similar structure. This paper reviews CADRs induced by oral antidiabetic drugs, considering their dermatological manifestations and possible pathomechanisms. Particular attention was paid to specific dermatological conditions such as dipeptidylpeptidase 4 inhibitor-associated bullous pemphigoid or Fournier’s gangrene associated with sodium-glucose cotransporter 2 inhibitor therapy. Knowledge of the dermatological manifestations of CADRs is important in clinical practice. Recognition of a skin lesion resulting from an adverse drug reaction allows for appropriate management, which in this case is primarily related to drug discontinuation. This is particularly important in the treatment of T2DM since this disease has a high prevalence in the elderly, who are at higher risk of adverse drug reactions. Full article

Background: CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. Methods and Results: We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. Conclusions: The present study highlights the importance of considering the investigation of the CACNA1C gene in children’s neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder. Full article

Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe form of drug hypersensitivity reaction characterized by significant morbidity, mortality, and long-term sequelae, coupled with limited therapeutic avenues. Accurate identification of the causative drug(s) is paramount for acute management, exploration of safe therapeutic alternatives, and prevention of future occurrences. However, the absence of a standardized diagnostic test and a specific causality algorithm tailored to DRESS poses a significant challenge in its clinical management. Methods: We conducted a retrospective case–control study involving 37 DRESS patients to validate a novel causality algorithm, the ALDRESS, designed explicitly for this syndrome, comparing it against the current standard algorithm, SEFV. Results: The ALDRESS algorithm showcased superior performance, exhibiting an 85.7% sensitivity and 93% specificity with comparable negative predictive values (80.6% vs. 97%). Notably, the ALDRESS algorithm yielded a substantially higher positive predictive value (75%) compared to SEFV (51.40%), achieving an overall accuracy rate of 92%. Conclusions: Our findings underscore the efficacy of the ALDRESS algorithm in accurately attributing causality to drugs implicated in DRESS syndrome. However, further validation studies involving larger, diverse cohorts are warranted to consolidate its clinical utility and broaden its applicability. This study lays the groundwork for a refined causality assessment tool, promising advancements in the diagnosis and management of DRESS syndrome. Full article

Nursing home (NH) residents commonly face limitations in basic activities of daily living (BADLs), following a hierarchical decline. Understanding this hierarchy is crucial for personalized care. This study explores factors associated with early, middle, and late loss in BADLs among NH residents. A multicenter cross-sectional study was conducted in 30 NHs in Catalonia, Spain. Dependent variables were related to limitations in BADLs: early loss (self-care-related BADLs: personal hygiene, dressing, or bathing), middle loss (mobility-related BADLs: walking or wheelchair handling, toileting, and transferring), and late loss (eating). Independent variables were based on a comprehensive geriatric assessment and institutional factors. Logistic regression was used for the multivariate analyses. The study included 671 older adults. Early loss in BADLs was significantly associated with urinary incontinence, cognitive impairment, and falls. Middle loss in BADLs was linked to fecal incontinence, urinary incontinence, ulcers, and cognitive impairment. Late loss in BADLs was associated with fecal incontinence, the NH not owning a kitchen, neurological disease, cognitive impairment, dysphagia, polypharmacy, and weight loss. These findings highlight the need to address geriatric syndromes, especially cognitive impairment and bladder/bowel incontinence. Monitoring these syndromes could effectively anticipate care dependency. The presence of kitchens in NHs may help to address limitations to eating, allowing for potential personalized meal adaptation. Full article

Lamotrigine, widely used for managing epilepsy and bipolar disorder, carries potential side effects, including severe anticonvulsant hypersensitivity syndrome (AHS) or drug rash with eosinophilia and systemic symptoms (DRESS), which may lead to hepatotoxicity. Patients with Type 2 Diabetes (TD2) and Non-Alcoholic Fatty Liver Disease (NAFLD) are identified as more susceptible to these adverse reactions. This exploratory analysis aims to identify clinical parameters influencing lamotrigine pharmacokinetics across diverse populations, shedding light on toxicity and therapeutic drug monitoring (TDM) considerations. Starting with a retrospective analysis of 41 lamotrigine-treated patients at Hospital Santo António reveals changes or deviations from normal levels in various blood parameters and significant correlations between these parameters. Serum level changes, including creatinine, albumin, gamma-glutamyl transferase, total bilirubin, and Vitamin B12, are observed, with strong negative correlations between Vitamin B12 and creatinine. Then, we used GastroPlus and DILIsym to explore the impact of clinical parameters on lamotrigine for different patient populations. We constructed a Physiologically Based Pharmacokinetic (PBPK) model for lamotrigine in GastroPlus, based on ADMET predictions and data from the literature, to simulate the pharmacokinetic variability of lamotrigine in different populations, and we visualized the impact of increasing lamotrigine dose on its plasma concentration–time profiles (200 mg, 400 mg, 600 mg, 1200 mg) and reduced bioavailability. At higher doses, it is possible that the saturation of metabolic pathways leads to the formation of toxic metabolites or intermediates. These metabolites may exert inhibitory effects on drug-metabolizing enzymes or disrupt normal physiological processes, thereby impeding the drug’s clearance and potentially lowering its bioavailability. In DILIsym, we investigated lamotrigine’s DILI potential for individuals with diabetes and NAFLD. The results demonstrated an increased risk, emphasizing the need for careful monitoring. This study underscores the importance of understanding lamotrigine’s pharmacokinetics for tailored treatment decisions, improved outcomes, and minimized adverse reactions. Full article

The complexity of autoimmunity initiation has been the subject of many studies. Both genetic and environmental factors are essential in autoimmunity development. Among others, environmental factors include infectious agents. HHV-6 is a ubiquitous human pathogen with a high global prevalence. It has several properties suggestive of its contribution to autoimmunity development. HHV-6 has a broad cell tropism, the ability to establish latency with subsequent reactivation and persistence, and a range of immunomodulation capabilities. Studies have implicated HHV-6 in a plethora of autoimmune diseases—endocrine, neurological, connective tissue, and others—with some studies even proposing possible autoimmunity induction mechanisms. HHV-6 can be frequently found in autoimmunity-affected tissues and lesions; it has been found to infect autoimmune-pathology-relevant cells and influence immune responses and signaling. This review highlights some of the most well-known autoimmune conditions to which HHV-6 has been linked, like multiple sclerosis and autoimmune thyroiditis, and summarizes the data on HHV-6 involvement in autoimmunity development. Full article

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a drug reaction commonly related to eosinophilia, from uncertain epidemiology, and without consensus for diagnosis and treatment globally. It presents a great challenge in its management and is characterized by fever, lymphadenopathy, skin rash, and multisystemic involvement. An aggressive and difficult-to-manage clinical case is presented in a 50-year-old man with chronic kidney disease due to diabetes mellitus type 2 and systemic arterial hypertension, who developed an unusual variant similar to DRESS and Stevens–Johnson syndrome (SJS) overlap secondary to allopurinol, with skin manifestations without eosinophilia, but fulfilling clinical and laboratory criteria for DRESS and SJS syndrome. Full article

Unlike other adverse drug reactions, visceral organ involvement is a prominent feature of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and correlates with mortality. The aim of this study was to systematically review cases published in PubMed-indexed, peer-reviewed journals in which patients had renal injury during the episode of DRESS syndrome (DS). We found 71 cases, of which 67 were adults and 56% were males. Female sex was associated with higher mortality. Chronic kidney disease (CKD) was present in 14% of patients who developed acute kidney injury (AKI) during DS. In 21% of cases, the kidneys were the only visceral organ involved, while 54% of patients had both liver and kidney involvement. Eosinophilia was absent in 24% of patients. The most common classes of medication associated with renal injury in DS were antibiotics in 34%, xanthine oxidase inhibitors in 15%, and anticonvulsants in 11%. Among antibiotics, vancomycin was the most common culprit in 68% of patients. AKI was the most common renal manifestation reported in 96% of cases, while isolated proteinuria or hematuria was present in only 4% of cases. In cases with AKI, 88% had isolated increase in creatinine and decrease in glomerular filtration (GFR), 27% had AKI concomitantly with proteinuria, 18% had oliguria, and 13% had concomitant AKI with hematuria. Anuria was the rarest manifestation, occurring in only 4% of patients with DS. Temporary renal replacement therapy was needed in 30% of cases, and all but one patient fully recovered renal function. Mortality of DS in this cohort was 13%, which is higher than previously reported. Medication class, latency period, or pre-existing CKD were not found to be associated with higher mortality. More research, particularly prospective studies, is needed to better recognize the risks associated with renal injury in patients with DS. The development of disease-specific biomarkers would also be useful so DS with renal involvement can be easier distinguished from other eosinophilic diseases that might affect the kidney. Full article

Introduction: The differential diagnoses of lumbar spinal stenosis (LSS) and adult spinal deformity (ASD) have been demonstrated primarily using sagittal radiographic spinopelvic parameters. However, it is more important to know the differences in the characteristic clinical symptoms to make accurate treatment decisions. Recently, the relationship between spinal disease and Locomotive Syndrome (LS) has been reported. Additionally, the Geriatric Locomotive Function Scale-25 (GLFS-25) was reported to be a useful scale to evaluate disease severity and characteristic clinical symptoms in spinal disease. Methods: Sixty-nine consecutive patients with ASD and 196 patients with LSS who underwent spinal surgery were included. Locomotive dysfunction was evaluated using the GLFS-25 questionnaire and physical performance tests including the two-step test and the stand-up test, measured preoperatively. The correlations between sagittal spinopelvic parameters of ASD and LS were examined. Results: All subjects with lumbar degenerative disease in the present study were diagnosed with LS preoperatively. The severity of LS in patients with LSS and ASD were statistically similar. GLFS-25 scores in the mobility and community domain were similarly poor in both groups. Several scores in the domestic life and self-care domains were significantly worse in the ASD group. Question 20 of the GLFS-25, related to load-bearing tasks and housework, was significantly associated with a large pelvic incidence in ASD patients. Conclusions: Lumbar degenerative disease requiring surgery severely affects the LS of older people. ASD patients had more difficulty with load-bearing tasks and housework such as cleaning the yard, carrying heavy bedding, dressing, and bathing compared to LSS patients. Full article

Background and Objectives: Systemic juvenile idiopathic arthritis (sJIA) is a distinctive JIA subtype with mostly nonspecific systemic clinical features, which can be a diagnostic challenge. This study aimed to analyze our experience with sJIA in Latvia for twelve years: assessing clinical and epidemiological characteristics, the efficacy of therapy, and disease outcomes, including the development of macrophage activation syndrome (MAS). Materials and methods: This is a descriptive study in which we conducted a retrospective case review of all patients with sJIA diagnosis admitted to the only pediatric tertiary centre in Latvia during the period 2009–2020. Results: sJIA was diagnosed in 35 patients with a mean annual incidence rate of 0.85 patients per 100,000 children. Major clinical signs at the first visit were: fever, rash, arthritis, and lymphadenopathy. Almost half of the patients, 48.5%, had a monocyclic disease course, and only 20% of patients had persistent disease. MAS developed in 28.6% of patients. Biological therapy was administered to 48.6% of patients, mostly by tocilizumab, which induced remission in 75% after one year, and in 81.2% after two years without any serious therapy-related complications. In our study, none of the patients had interstitial lung disease, drug reaction with eosinophilia and systemic symptoms (DRESS)-like syndrome, or fatal disease. Conclusions: The incidence and clinical characteristics of sJIA correlate with the literature findings, although MAS was more common than described in other studies. There is a tendency for the persistent disease to decrease with the use of biological therapy. Tocilizumab is an efficient choice of treatment with a good safety profile. Full article

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a heterogeneous, multiorgan and potentially life-threatening drug-hypersensitivity reaction (DHR) that occurs several days or weeks after drug initiation or discontinuation. DHRs constitute an emerging issue for public health, due to population aging, growing multi-organ morbidity, and subsequent enhanced drug prescriptions. DRESS has more consistently been associated with anticonvulsants, allopurinol and antibiotics, such as sulphonamides and vancomycin, although new drugs are increasingly reported as culprit agents. Reactivation of latent infectious agents such as viruses (especially Herpesviridae) plays a key role in prompting and sustaining aberrant T-cell and eosinophil responses to drugs and pathogens, ultimately causing organ damage. However, the boundaries of the impact of viral agents in the pathophysiology of DRESS are still ill-defined. Along with growing awareness of the multifaceted aspects of immune perturbation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the ongoing SARS-CoV-2-related disease (COVID-19) pandemic, novel interest has been sparked towards DRESS and the potential interactions among antiviral and anti-drug inflammatory responses. In this review, we summarised the most recent evidence on pathophysiological mechanisms, diagnostic approaches, and clinical management of DRESS with the aim of increasing awareness on this syndrome and possibly suggesting clues for future research in this field. Full article

Toxic epidermal necrolysis, Leyll’s syndrome (TEN), is a rare mucocutaneous blistering disease burdened with high mortality rates. The diagnosis of TEN is based on clinical symptoms and histopathological findings. In approximately 90% of cases, it is a severe adverse reaction to drugs. In TEN, not only is the skin affected, but also mucosa and organs’ epithelium. There are no unequivocal recommendations in regard to systemic and topical treatment of the patients. The aim of this paper is to review available literature and propose unified protocols to be discussed. Early management and multidisciplinary treatment are necessary to improve patients’ outcome. Treatment of patients with TEN suspicions should be initiated with early drug withdrawal. TEN patients, like patients with burns, require intensive care and multidisciplinary management. Each patient with TEN should be provided with adequate fluid resuscitation, respiratory support, nutritional treatment, pain control, infection prophylaxis, anticoagulant therapy, and gastric ulcer prophylaxis. The key to local treatment of patients with TEN is the use of nonadherent dressings that do not damage the epidermis during the change. The aim of the systemic treatment is purification of the blood stream from the causative agent. The most efficient way to clarify serum of TEN patients’ is the combination of plasmapheresis and IVIG. Immunomodulatory therapy can reduce the mortality five times in comparison with the patients with immunosuppression or lack of full protocol. Full article

The functional sequelae grouped under the name “long COVID” most often bring the patient in front of a team of specialists in pulmonary rehabilitation. The aim of this study was to evaluate clinical features and paraclinical findings in patients with SARS CoV-2 (Severe Acute Respiratory Syndrome-Corona Virus-2) pneumonia and to also evaluate the impact of rehabilitation in this category of patients. This study included 106 patients diagnosed with SARS CoV-2. The division of the patients into two groups was performed based on the presence of SAR-CoV-2 pneumonia. Clinical symptoms, biochemical parameters, and pulmonary functional and radiological examinations were recorded and analyzed. The Lawton Instrumental Activities of Daily Living (IADL) scale was applied to all patients. Patients in group I were included in the pulmonary rehabilitation program. Among demographic characteristics, age over 50 years (50.9%; p = 0.027) and the female sex (66%; p = 0.042) were risk factors for pneumonia in patients with SARS CoV-2. Over 90% of the 26 patients included in the rehabilitation program were less able to feed, bathe, dress, and walk. After 2 weeks, approximately 50% of patients were able to eat, wash, and dress. It is important to provide longer rehabilitation programs in cases of moderate, severe, and very severe COVID-19 patients, in order to significantly improve patients’ participation in daily activities and their quality of life. Full article

Drug hypersensitivity reactions are classified into immediate and delayed types, according to the onset time. In contrast to the immediate type, delayed drug hypersensitivity mainly involves T lymphocyte recognition of the drug antigens and cell activation. The clinical presentations of such hypersensitivity are various and range from mild reactions (e.g., maculopapular exanthema (MPE) and fixed drug eruption (FDE)), to drug-induced liver injury (DILI) and severe cutaneous adverse reactions (SCARs) (e.g., Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP)). The common culprits of delayed drug hypersensitivity include anti-epileptics, antibiotics, anti-gout agents, anti-viral drugs, etc. Delayed drug hypersensitivity is proposed to be initiated by different models of molecular recognition, composed of drug/metabolite antigen and endogenous peptide, HLA presentation, and T cell receptor (TCR) interaction. Increasing the genetic variants of HLA loci and drug metabolic enzymes has been identified to be responsible for delayed drug hypersensitivity. Furthermore, preferential TCR clonotypes, and the activation of cytotoxic proteins/cytokines/chemokines, are also involved in the pathogenesis of delayed drug hypersensitivity. This review provides a summary of the current understanding of the molecular recognition, genetic susceptibility, and immune mediators of delayed drug hypersensitivity. Full article