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Farmacia Hospitalaria : Organo Oficial... Jun 2024Topical rapamycin is the pharmacological treatment of choice for facial angiofibromas in rare tuberous sclerosis disease. A new, more advanced, and complex formula was...
AIM
Topical rapamycin is the pharmacological treatment of choice for facial angiofibromas in rare tuberous sclerosis disease. A new, more advanced, and complex formula was developed in our pharmacy service: rapamycin 0.4% liposomal formulation, with better organoleptic characteristics and a more favorable release profile of the active ingredient. The purpose of this study is to evaluate the effectiveness and safety of liposomal topical rapamycin for the treatment of facial injuries in this rare disease.
METHOD
This was an observational, prospective, and multicenter study. Effectiveness was evaluated mainly through facial angiofibromas severity index (FASI), investigator's global assessment (IGA) scores, and dermatology life quality index (DLQI) questionnaire. To assess the safety profile of rapamycin, adverse reactions were reported, and blood tests and blood rapamycin levels were performed during treatment.
RESULTS
Eleven patients were included, of which 8/11 (73%) patients obtained successful treatment according to FASI and IGA scores after 24 weeks of treatment. Statistical analysis demonstrated a significant improvement (p<.05) in FASI and IGA scores, erythema, and FA size after treatment with rapamycin liposomal formulation (FASI before treatment, median (interquartile range): 6.0 (2.0), FASI after treatment: 3.5 (2.0), p=.0063). Five patients also improved their quality of life after treatment. Regarding safety profile of rapamycin, the most common adverse reaction was mild pruritus and 2 patients reported erythema, who discontinued treatment prematurely. All hematological tests were normal, and blood rapamycin levels were undetectable.
CONCLUSIONS
After galenic improvements and clinical evaluations, the rapamycin liposomal formulation proved to be effective and safe for this therapeutic indication. This new formulation was included as a magistral formula in our hospital pharmacy service, now accessible for prescribing by dermatologists. Drug development in hospital pharmacy is often the only pharmacological alternative available to treat the symptoms of rare diseases, when treatment options are limited or inadequate.
PubMed: 38851908
DOI: 10.1016/j.farma.2024.04.023 -
Skin Health and Disease Jun 2024Excoriated pruritus can be an intolerable symptom in patients with cancer where Type 2 inflammation and its associated cytokines IL-4 and IL-13 play major roles in the...
Excoriated pruritus can be an intolerable symptom in patients with cancer where Type 2 inflammation and its associated cytokines IL-4 and IL-13 play major roles in the pruritus. Dupilumab, an antibody blocking IL-4 and IL-13, is approved for treating moderate to severe atopic dermatitis (AD) where itching is a significant symptom. We present a case report of intractable malignancy-associated AD and pruritus with eosinophilia in a patient with stage IV malignant melanoma who was treated with dupilumab. Biweekly treatment with dupilumab led to an immediate improvement in itching and resolution of the AD, which subsided after a few doses and without significant adverse effects. Routine radiologic monitoring of the malignant melanoma showed concomitant resolution of secondary nodules in the lung, liver, and pleura. It was concluded that dupilumab may be a safe and effective treatment for intractable malignancy-associated AD with pruritus and may have potential for moderating metastatic malignant melanoma.
PubMed: 38846700
DOI: 10.1002/ski2.362 -
JAMA Dermatology Jun 2024Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are...
IMPORTANCE
Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising therapy for both conditions.
OBJECTIVE
To assess the efficacy and safety of 200-mg oral abrocitinib administered once daily in adults with moderate to severe PN or CPUO.
DESIGN, SETTING, AND PARTICIPANTS
This phase 2, open-label, nonrandomized controlled trial conducted between September 2021 and July 2022 took place at a single center in the US. A total of 25 adult patients with moderate to severe PN or CPUO were screened. Ten patients with PN and 10 patients with CPUO were enrolled. All 20 patients completed the 12-week treatment period, 18 of whom completed the 4-week follow-up period.
INTERVENTION
Abrocitinib, 200 mg, by mouth once daily for 12 weeks.
MAIN OUTCOMES AND MEASURES
The primary efficacy end point was the percent change in weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from baseline to week 12. Key secondary end points included the percentage of patients achieving at least a 4-point reduction in weekly PP-NRS score from baseline to week 12 and the percent change in Dermatology Life Quality Index (DLQI) scores.
RESULTS
A total of 10 patients with PN (mean [SD] age, 58.6 [13.1] years; all were female) and 10 patients with CPUO (mean [SD] age, 70.7 [5.6] years; 2 were female) enrolled in the study. The mean (SD) baseline PP-NRS score was 9.2 (1.0) for PN and 8.2 (1.2) for CPUO. PP-NRS scores decreased by 78.3% in PN (95% CI, -118.5 to -38.1; P < .001) and 53.7% in CPUO (95% CI, -98.8 to -8.6; P = .01) by week 12. From baseline to week 12, 8 of 10 patients with PN and 6 of 10 patients with CPUO achieved at least a 4-point improvement on the PP-NRS. Both groups experienced significant improvement in quality of life as demonstrated by percent change in DLQI scores (PN: -53.2% [95% CI, -75.3% to -31.1%]; P = .002; CPUO: -49.0% [95% CI, -89.6% to -8.0%]; P = .02). The most common adverse event among patients was acneiform eruption in 2 of 20 patients (10%). No serious adverse events occurred.
CONCLUSIONS AND RELEVANCE
The results of this nonrandomized controlled trial suggest that abrocitinib monotherapy may be effective and tolerated well in adults with PN or CPUO. Randomized, double-blind, placebo-controlled trials are warranted to validate these findings.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05038982.
PubMed: 38837144
DOI: 10.1001/jamadermatol.2024.1464 -
Pain Reports Aug 2024Notalgia paresthetica (NP) is a chronic condition characterized by pruritus and other unpleasant dysesthetic sensations unilaterally on the subscapular back. Its...
INTRODUCTION
Notalgia paresthetica (NP) is a chronic condition characterized by pruritus and other unpleasant dysesthetic sensations unilaterally on the subscapular back. Its specific underlying mechanisms are largely unknown, though hypothesized to be neuropathic. Determination of possible somatosensory contributors to the condition could pave the way for novel treatments.
OBJECTIVES
Given the potential involvement of non-pruritic mechanisms in NP, our objective was to broadly characterize the somatosensory function in NP-affected and unaffected skin using methods that have been standardized in pain-free controls and painful neuropathic disorders. We hypothesized that if NP is caused by neuropathic mechanisms not targeted directly to pruritoceptors in the skin, somatosensory abnormalities would not be itchspecific. Second, given the lack of symptoms on the contralateral side of the back, we hypothesized that this region would be normally sensitive.
METHODS
In this study, quantitative sensory testing (QST) was used to comprehensively assess the somatosensory function in 15 adult patients with NP. Standardized QST metrics were performed in the NP-affected region and compared with the contralateral asymptomatic skin and itch-free individuals using an age, gender, and site-matched reference data set.
RESULTS
There were no significant differences in sensitivity between symptomatic and asymptomatic skin, except for increased mechanical-evoked itch on the itchy side. However, reference data set comparisons revealed bilateral hyposensitivity to innocuous cold and noxious pinprick and higher temporal summation of pain in patients with NP. In addition, compared with reference data, patients with NP demonstrated decreased sensitivity to cold and pinprick, presence of paradoxical heat sensations, and increased wind-up of pain.
CONCLUSION
These results suggest a role for Aδ fiber pathways and central sensitization in NP-associated itch. More research is needed to determine whether sensory differences extend beyond the NP-affected dermatomal level and what might cause neuropathy specifically targeting Aδ fibers.
PubMed: 38835743
DOI: 10.1097/PR9.0000000000001162 -
Clinical Liver Disease 2024
PubMed: 38831766
DOI: 10.1097/CLD.0000000000000216 -
Cureus May 2024Kimura disease (KD) is a rare chronic inflammatory disorder characterized by the development of painless subcutaneous nodules, predominantly in the head and neck region....
Kimura disease (KD) is a rare chronic inflammatory disorder characterized by the development of painless subcutaneous nodules, predominantly in the head and neck region. Diagnosis relies on a high index of clinical suspicion and clinicopathological correlation, with core biopsy serving as the gold standard for a definitive diagnosis. While the disease itself is benign, it can cause significant morbidity if left untreated. This case report describes a 48-year-old male who presented with bilateral infraauricular swellings, pruritus, and elevated serum IgE levels along with eosinophilia. Imaging and histopathological correlation confirmed the diagnosis of KD. Combination therapy of corticosteroids and cyclosporine resulted in significant clinical improvement, highlighting the efficacy of the approach while avoiding surgical resection. This case emphasizes the importance of radiologic-pathologic correlation along with the use of serology to effectively diagnose KD, even in atypical presentations.
PubMed: 38826922
DOI: 10.7759/cureus.59570 -
Cureus May 2024The antibiotic cefepime is a fourth-generation cephalosporin with extended-spectrum coverage against both gram-positive and negative bacteria. It is commonly used in...
The antibiotic cefepime is a fourth-generation cephalosporin with extended-spectrum coverage against both gram-positive and negative bacteria. It is commonly used in the inpatient setting to treat community-acquired pneumonia or urinary tract infection and has side effects, including diarrhea, nausea, vomiting, pruritus, headache, and, more rarely, hypersensitivity reactions or neurotoxicity. The current report is about an 88-year-old female patient who was brought to the hospital by her daughter due to an acute change in mental status resulting from a urinary tract infection. The patient received intravenous cefepime and subsequently developed a low-frequency tremor after one day of treatment. Cefepime was discontinued with a resolution of tremor in three days. Though neurotoxicity has been documented as a serious adverse event with cefepime, tremor is not one of the known neurotoxic manifestations. This patient is the first reported to develop a tremor as a neurotoxic side effect from taking cefepime. Healthcare providers should be aware of this potential side effect and may consider discontinuing treatment with cefepime if their patient develops a new tremor within days of initiating treatment.
PubMed: 38826906
DOI: 10.7759/cureus.59518 -
Frontiers in Oncology 2024This study comprehensively assesses the incidence and profiles of treatment-related adverse events (trAEs) of immune checkpoint inhibitor (ICI)-based therapies across...
AIM
This study comprehensively assesses the incidence and profiles of treatment-related adverse events (trAEs) of immune checkpoint inhibitor (ICI)-based therapies across cancer at various sites.
METHODS
We systematically searched the PubMed, Embase, and Cochrane databases for trials investigating ICI-based therapies published between their inception and August 2023.
RESULTS
In total, 147 studies involving 45,855 patients met the inclusion criteria. Among them, patients treated with ICIs reported 39.8% and 14.9% of all-grade and grade ≥3 immune-related adverse events (irAEs), respectively. The most common all-grade irAEs were dermatological and gastrointestinal issues, diarrhea, and pruritus, whereas patients who received ICIs showed most common grade ≥3 irAEs, including gastrointestinal events, diarrhea, increased aspartate aminotransferase and alanine transaminase levels, and hepatic and dermatological events. The overall trAE incidence in patients treated with ICIs was 83.2% for all-grade trAEs and 38.2% for grade ≥3 trAEs. TrAE incidence was highest for patients treated with cytotoxic T lymphocyte antigen-4 inhibitors for all-grade and grade ≥3 trAEs, with incidences of 86.4% and 39.2%, respectively. ICIs combined with targeted therapy showed the highest all-grade and grade ≥3 trAEs, with incidences of 96.3% and 59.4%, respectively. The most common all-grade trAEs were anemia, decrease in white blood cell count, decrease in neutrophil count, nausea, fatigue, diarrhea, and alopecia; patients who received ICIs presented relatively high incidences of grade ≥3 trAEs.
CONCLUSION
This study provided comprehensive data regarding irAEs and trAEs in patients receiving ICIs. These results should be applied in clinical practice to provide an essential reference for safety profiles of ICIs.
SYSTEMATIC REVIEW REGISTRATION
INPLASY platform, identifier INPLASY202380119.
PubMed: 38826783
DOI: 10.3389/fonc.2024.1391724 -
Case Reports in Hepatology 2024Drug-induced liver injury resulting from herbal and dietary supplement use is increasingly common and underrecognized. We report a case of a 34-year-old male...
Drug-induced liver injury resulting from herbal and dietary supplement use is increasingly common and underrecognized. We report a case of a 34-year-old male recreational bodybuilder who presented with muscle cramping, fatigue, and diffuse itching in the setting of bodybuilding supplement use. Labs showed cholestatic liver injury, and liver biopsy revealed bland cholestasis and sinusoidal dilation. He was diagnosed with anabolic-androgenic steroid-induced liver injury. He was symptomatically managed with plasmapheresis for debilitating pruritus. This case highlights drug-induced liver injury as a complication of bodybuilding supplement use containing unlabeled anabolic-androgenic steroids. Sports medicine providers should inquire on herbal and dietary supplement use and be aware of potential contaminants.
PubMed: 38826497
DOI: 10.1155/2024/5112461