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Cureus Apr 2024is a first-generation anticonvulsant medicine that efficiently cures a wide range of seizures, including status epilepticus, complex partial seizures, and generalized...
is a first-generation anticonvulsant medicine that efficiently cures a wide range of seizures, including status epilepticus, complex partial seizures, and generalized tonic-clonic seizures (GCTS). The major advantage of phenytoin is that its neurological functions are preserved. Phenytoin works by inhibiting voltage-dependent membrane Na channels, which are essential to generate action potential. This function inhibits the positive feedback, leading to high-frequency repeated firing, reducing seizure spread in the focal region. A purple color rash on the chest, abdomen, and trunk developed in a 21-year-old female patient after being treated with phenytoin is being reported. The presentation, pathophysiology, and management are also reviewed.
PubMed: 38774164
DOI: 10.7759/cureus.58665 -
International Journal of Trichology 2023Graham-Little-Piccardi-Lasseur syndrome (GLPLS) is characterized by diffuse alopecia and a lichenoid follicular eruption affecting the scalp, eyebrows, and...
Graham-Little-Piccardi-Lasseur syndrome (GLPLS) is characterized by diffuse alopecia and a lichenoid follicular eruption affecting the scalp, eyebrows, and intertriginous regions. It is considered a variant of lichen planopilaris. The condition often begins as hyperkeratotic papules on the trunk and extremities followed by the development of alopecia. Several subtypes of lichen planus have been associated with a photodistriubuted eruption including lichenoid drug reactions, actinic lichen planus, and lichen planus pigmentosus; however, there are no reported cases associated with GLPLS. We herein report the first case of GLPLS displaying a photodistributed lichenoid eruption to expand upon the differential diagnosis of photoaggravated conditions. We also use this case to review the pathophysiology and therapeutic modalities to manage GLPLS.
PubMed: 38765727
DOI: 10.4103/ijt.ijt_47_22 -
Clinical Case Reports May 2024IgA pemphigus is usually treated by Dapsone. Recalcitrant cases may be treated by Colchicine, Sulfapyridine, or Acitretin. Some patients with recurrent severe disease...
KEY CLINICAL MESSAGE
IgA pemphigus is usually treated by Dapsone. Recalcitrant cases may be treated by Colchicine, Sulfapyridine, or Acitretin. Some patients with recurrent severe disease may not respond to the aforementioned medications. Our study highlights the role of TNFa inhibitor as an alternative modality in the treatment of recalcitrant IgA pemphigus.
ABSTRACT
IgA pemphigus is a rare autoimmune blistering disease characterized by a pruritic, annular, vesiculopustular eruption. In IgA pemphigus, there are IgA autoantibodies targeting the keratinocyte cell surface adhesion molecules, causing cell-to-cell dehiscence and a flaccid vesiculopustular eruption, mainly in the axilla and groin. Dapsone, despite being the drug of choice for treating IgA pemphigus, is not effective in clearing lesions in a minority of patients and such rare cases of recalcitrant IgA pemphigus need alternative modalities of treatment. Here, we report the successful treatment of a 50-year-old male patient with an adalimumab injection who had a poor response to dapsone.
PubMed: 38751960
DOI: 10.1002/ccr3.8807 -
Supportive Care in Cancer : Official... May 2024Hand-foot syndrome (HFS) significantly impacts quality of life in cancer patients undergoing capecitabine treatment. This study assessed capecitabine-associated HFS...
INTRODUCTION
Hand-foot syndrome (HFS) significantly impacts quality of life in cancer patients undergoing capecitabine treatment. This study assessed capecitabine-associated HFS prevalence, its impacts on chemotherapy treatment, and identified risk factors in multiracial Malaysian patients.
METHODS
We included adult cancer patients receiving capecitabine at Sarawak General Hospital for at least two cycles from April 1, 2021 to June 30, 2022. HFS rates, time to HFS, and proportions of HFS-related treatment modifications were determined. Characteristics between patients with and without HFS were compared and multivariable logistic regression was used to identify risk factors for all-grade HFS and grade ≥2.
RESULTS
Among 369 patients, 185 (50.1%) developed HFS, with 14.6% experiencing grade ≥2 and 21.6% (40/185) underwent treatment modifications. Risk factors for all-grade HFS include older age (OR 1.03 95%CI 1.01, 1.06), prior chemotherapy (OR 2.09 95%CI 1.22, 3.58), higher capecitabine dose (OR 2.96 95%CI 1.62, 5.38), prolonged treatment (OR 1.36 95%CI 1.21, 1.51), folic acid intake (OR 3.27 95%CI 1.45, 7.35) and lower neutrophil count (OR 0.77 95%CI 0.66, 0.89). For HFS grade ≥2, older age (OR 1.04 95%CI 1.01, 1.08), female sex (OR 2.10 95%CI 1.05, 4.18), Chinese race (OR 2.10 95%CI 1.06, 4.18), and higher capecitabine dose (OR 2.62 95%CI 1.28, 5.35) are significant risk factors. Use of calcium channel blockers were associated with reduced risks of all-grade HFS (OR 0.27, 95%CI 0.12, 0.60) and grade ≥2 (OR 0.21 95%CI 0.06, 0.78).
CONCLUSION
This study provides real-world data on capecitabine-induced HFS in Malaysian patients and identifies risk factors that may offer insights into its understanding and management.
Topics: Humans; Capecitabine; Malaysia; Male; Female; Middle Aged; Risk Factors; Prevalence; Hand-Foot Syndrome; Neoplasms; Aged; Antimetabolites, Antineoplastic; Adult; Quality of Life
PubMed: 38743316
DOI: 10.1007/s00520-024-08490-7 -
Frontiers in Immunology 2024Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized...
INTRODUCTION
Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions.
METHODS
In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR.
RESULTS
An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that expression could discriminate ENL from LL. Supernatants of blood cells stimulated with sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly and , were revealed.
DISCUSSION
In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.
Topics: Humans; Erythema Nodosum; Neutrophil Activation; Leprosy, Lepromatous; Adult; Male; Neutrophils; Female; Transcriptome; Middle Aged; Gene Expression Profiling; GPI-Linked Proteins; Thalidomide; Receptors, Cell Surface; Leprostatic Agents; Young Adult; Biomarkers; Isoantigens
PubMed: 38715615
DOI: 10.3389/fimmu.2024.1366125 -
BMC Ophthalmology May 2024To summarize the outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome (SJS).
PURPOSE
To summarize the outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome (SJS).
METHODS
This is a retrospective analysis of a consecutive case series. Twenty-four eyes of 18 SJS patients were included in this study. The ocular parameters, surgical procedures, postoperative complications, and additional treatments of the cases were reviewed.
RESULTS
A total of 29 corneal sight rehabilitating surgeries, which consists of 9 keratoplasties, 8 Keratolimbal allograft (KLAL) and 12 combined surgeries (keratoplasty and KLAL simultaneously) were performed on the 24 eyes. All patients were treated with glucocorticoid eyedrops and tacrolimus eyedrops for anti-rejection treatment without combining systemic immunosuppression, except two patients who were prescribed prednisone tablets for the management of systemic conditions. The mean follow-up period was 50.6 ± 28.1 months. The optimal visual acuity (VA) (0.74 ± 0.60 logarithm of the minimum angle of resolution [logMAR]) and endpoint VA (1.06 ± 0.82 logMAR) were both significantly better than the preoperative VA (1.96 ± 0.43 logMAR) (95% CI, p = 0.000). 57.1% patients (8/14) were no longer in the low vision spectrum, and 88.9% patients (8/9) were no longer blind. The mean epithelialization time was 7.1 ± 7.6 weeks. The success rate was 86.7%. Additional treatments for improving epithelialization included administration of serum eyedrops (n = 10), contact lens (n = 15), amniotic membrane transplantation (n = 6), and tarsorrhaphy (n = 8). Complications included delayed epithelialization (n = 4, over 12 weeks), glaucoma (n = 11), and severe allograft opacity (n = 4). Only one graft rejection was observed.
CONCLUSIONS
Keratoplasty and KLAL can remarkably enhance VA and improve low vision or even eliminate blindness for ocular complications of SJS. The outcome of the surgeries was correlated with the preoperative ocular situation and choice of operative methods.
Topics: Humans; Stevens-Johnson Syndrome; Retrospective Studies; Female; Male; Adult; Visual Acuity; Middle Aged; Young Adult; Adolescent; Corneal Diseases; Treatment Outcome; Child; Corneal Transplantation; Follow-Up Studies; Keratoplasty, Penetrating; Postoperative Complications; Limbus Corneae
PubMed: 38711013
DOI: 10.1186/s12886-024-03461-2 -
Skin Research and Technology : Official... May 2024Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have... (Review)
Review
INTRODUCTION
Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have turned to new biologic drugs known as DMARDs (disease-modifying anti-rheumatic drugs) in recent years.
AREAS COVERED
In this study, we evaluate the immune-mediated dermatological side effects of DMARDS by reviewing and analyzing previous peer-reviewed research on the effects of TNF-α inhibitors in the treatment of skin diseases, as well as adverse effects of these drugs and some of the main causes of these effects.
EXPERT OPINION
DMARDs are very effective in improving control of the above diseases. TNF-α inhibitors are an important group of DMARDs that are widely used. The paradoxical adverse events (PAEs) associated with the use of TNF-α inhibitors are divided into three categories: true paradoxical, borderline paradoxical, and non-paradoxical. True PAEs include conditions for which TNF-α inhibitors are approved for treatment. Borderline PAEs are considered to occur with this class of drugs for which there is no definite approval but for which there is sufficient evidence. Although these events are rare, early recognition of the accused drug and appropriate decision-making may prevent progression of complications and irreversible side effects.
Topics: Humans; Tumor Necrosis Factor-alpha; Antirheumatic Agents; Skin Diseases; Drug Eruptions
PubMed: 38700458
DOI: 10.1111/srt.13718 -
JNCI Cancer Spectrum Apr 2024Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose...
BACKGROUND
Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer.
METHODS
Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of .25.
RESULTS
Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks.
CONCLUSIONS
The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted.
CLINICALTRIALS.GOV IDENTIFIER
NCT02393755.
Topics: Humans; Capecitabine; Male; Female; Middle Aged; Indoles; Aged; Progression-Free Survival; Colorectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Adult; Fatigue; Hand-Foot Syndrome; Aged, 80 and over; Drug Resistance, Neoplasm; Bilirubin
PubMed: 38697618
DOI: 10.1093/jncics/pkae017 -
Frontiers in Immunology 2024Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is characterized by a widespread maculopapular rash, lymphadenopathy, fever, and multisystem involvement....
Sulfasalazine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) coinfected with COVID-19 complicated by hemophagocytic lymphohistiocytosis: a case report.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is characterized by a widespread maculopapular rash, lymphadenopathy, fever, and multisystem involvement. Conversely, hemophagocytic lymphohistiocytosis (HLH) is an infrequent yet critical condition presenting with fever, hepatosplenomegaly, cytopenias, coagulation abnormalities, and elevated inflammatory markers. The overlapping clinical and laboratory features between DRESS and HLH poses a significant diagnostic challenge. Secondary HLH (sHLH) typically occurs in adults triggered by viral infections, malignancies, rheumatologic diseases, or immune deficiencies. Recently, COVID-19 has also been identified as one of the triggers for sHLH. Herein, we present a case of Sulfasalazine-induced DRESS coinfected with COVID-19 that subsequently progressed into HLH. Our patient exhibited common hepatorenal and splenic involvement along with rare cholecystitis and appendicitis. However, a significant improvement was observed upon the addition of etoposide and azathioprine. We hypothesize that excessive activation of the immune system and cytokine storm due to DRESS combined with COVID-19 infection led to more extensive systemic damage resulting in HLH development. This highlights the potential for severe consequences when DRESS coincides with HLH during a COVID-19 infection.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; COVID-19; Drug Hypersensitivity Syndrome; Sulfasalazine; SARS-CoV-2; Coinfection; Male; Middle Aged; Female
PubMed: 38686382
DOI: 10.3389/fimmu.2024.1371490 -
The Pan African Medical Journal 2024
Topics: Humans; Anticonvulsants; Carbamazepine; Disease Progression; Stevens-Johnson Syndrome
PubMed: 38681105
DOI: 10.11604/pamj.2024.47.44.42577