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The Cochrane Database of Systematic... Jan 2020Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in 2007; a substantial amount of new research warrants a review exclusively on toenails.
OBJECTIVES
To assess the clinical and mycological effects of topical drugs and device-based therapies for toenail onychomycosis.
SEARCH METHODS
We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers, and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical and device-based therapies for onychomycosis in participants with toenail onychomycosis, confirmed by positive cultures, direct microscopy, or histological nail examination. Eligible comparators were placebo, vehicle, no treatment, or an active topical or device-based treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete cure rate (normal-looking nail plus fungus elimination, determined with laboratory methods) and number of participants reporting treatment-related adverse events.
MAIN RESULTS
We included 56 studies (12,501 participants, average age: 27 to 68 years), with mainly mild-to-moderate onychomycosis without matrix involvement (where reported). Participants had more than one toenail affected. Most studies lasted 48 to 52 weeks; 23% reported disease duration (variable). Thirty-five studies specifically examined dermatophyte-caused onychomycosis. Forty-three studies were carried out in outpatient settings. Most studies assessed topical treatments, 9% devices, and 11% both. We rated three studies at low risk of bias across all domains. The most common high-risk domain was performance bias. We present results for key comparisons, where treatment duration was 36 or 48 weeks, and clinical outcomes were measured at 40 to 52 weeks. Based on two studies (460 participants), compared with vehicle, ciclopirox 8% lacquer may be more effective in achieving complete cure (risk ratio (RR) 9.29, 95% confidence interval (CI) 1.72 to 50.14; low-quality evidence) and is probably more effective in achieving mycological cure (RR 3.15, 95% CI 1.93 to 5.12; moderate-quality evidence). Ciclopirox lacquer may lead to increased adverse events, commonly application reactions, rashes, and nail alteration (e.g. colour, shape). However, the 95% CI indicates that ciclopirox lacquer may actually make little or no difference (RR 1.61, 95% CI 0.89 to 2.92; low-quality evidence). Efinaconazole 10% solution is more effective than vehicle in achieving complete cure (RR 3.54, 95% CI 2.24 to 5.60; 3 studies, 1716 participants) and clinical cure (RR 3.07, 95% CI 2.08 to 4.53; 2 studies, 1655 participants) (both high-quality evidence) and is probably more effective in achieving mycological cure (RR 2.31, 95% CI 1.08 to 4.94; 3 studies, 1716 participants; moderate-quality evidence). Risk of adverse events (such as dermatitis and vesicles) was slightly higher with efinaconazole (RR 1.10, 95% CI 1.01 to 1.20; 3 studies, 1701 participants; high-quality evidence). No other key comparison measured clinical cure. Based on two studies, compared with vehicle, tavaborole 5% solution is probably more effective in achieving complete cure (RR 7.40, 95% CI 2.71 to 20.24; 1198 participants), but probably has a higher risk of adverse events (application site reactions were most commonly reported) (RR 3.82, 95% CI 1.65 to 8.85; 1186 participants (both moderate-quality evidence)). Tavaborole improves mycological cure (RR 3.40, 95% CI 2.34 to 4.93; 1198 participants; high-quality evidence). Moderate-quality evidence from two studies (490 participants) indicates that P-3051 (ciclopirox 8% hydrolacquer) is probably more effective than the comparators ciclopirox 8% lacquer or amorolfine 5% in achieving complete cure (RR 2.43, 95% CI 1.32 to 4.48), but there is probably little or no difference between the treatments in achieving mycological cure (RR 1.08, 95% CI 0.85 to 1.37). We found no difference in the risk of adverse events (RR 0.60, 95% CI 0.19 to 1.92; 2 studies, 487 participants; low-quality evidence). The most common events were erythema, rash, and burning. Three studies (112 participants) compared 1064-nm Nd:YAG laser to no treatment or sham treatment. We are uncertain if there is a difference in adverse events (very low-quality evidence) (two studies; 85 participants). There may be little or no difference in mycological cure at 52 weeks (RR 1.04, 95% CI 0.59 to 1.85; 2 studies, 85 participants; low-quality evidence). Complete cure was not measured. One study (293 participants) compared luliconazole 5% solution to vehicle. We are uncertain whether luliconazole leads to higher rates of complete cure (very low-quality evidence). Low-quality evidence indicates there may be little or no difference in adverse events (RR 1.02, 95% CI 0.90 to 1.16) and there may be increased mycological cure with luliconazole; however, the 95% CI indicates that luliconazole may make little or no difference to mycological cure (RR 1.39, 95% CI 0.98 to 1.97). Commonly-reported adverse events were dry skin, paronychia, eczema, and hyperkeratosis, which improved or resolved post-treatment.
AUTHORS' CONCLUSIONS
Assessing complete cure, high-quality evidence supports the effectiveness of efinaconazole, moderate-quality evidence supports P-3051 (ciclopirox 8% hydrolacquer) and tavaborole, and low-quality evidence supports ciclopirox 8% lacquer. We are uncertain whether luliconazole 5% solution leads to complete cure (very low-quality evidence); this outcome was not measured by the 1064-nm Nd:YAG laser comparison. Although evidence supports topical treatments, complete cure rates with topical treatments are relatively low. We are uncertain if 1064-nm Nd:YAG laser increases adverse events compared with no treatment or sham treatment (very low-quality evidence). Low-quality evidence indicates that there is no difference in adverse events between P-3051 (ciclopirox hydrolacquer), luliconazole 5% solution, and their comparators. Ciclopirox 8% lacquer may increase adverse events (low-quality evidence). High- to moderate-quality evidence suggests increased adverse events with efinaconazole 10% solution or tavaborole 5% solution. We downgraded evidence for heterogeneity, lack of blinding, and small sample sizes. There is uncertainty about the effectiveness of device-based treatments, which were under-represented; 80% of studies assessed topical treatments, but we were unable to evaluate all of the currently relevant topical treatments. Future studies of topical and device-based therapies should be blinded, with patient-centred outcomes and an adequate sample size. They should specify the causative organism and directly compare treatments.
Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Female; Humans; Male; Middle Aged; Onychomycosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31978269
DOI: 10.1002/14651858.CD012093.pub2 -
JTO Clinical and Research Reports Dec 2023Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The...
A Phase 2 Single-Arm Study of Osimertinib for Radiotherapy-Naive Central Nervous System Metastasis NSCLC: Results for the First-Line Cohort of the OCEAN Study (LOGIK 1603/WJOG 9116L).
INTRODUCTION
Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The OCEAN study assessed the efficacy of osimertinib against RT-naive CNS metastasis in patients previously treated (T790M cohort) and untreated patients (first-line cohort) with mutation. Here, we report the results of the first-line cohort.
METHODS
Previously untreated patients with RT-naive CNS metastasis and mutation-positive NSCLC were treated with osimertinib. The brain metastasis response rate (BMRR), progression-free survival (PFS), and overall survival in the first-line cohort were secondary end points.
RESULTS
A total of 26 patients were enrolled in the study between September 2019 and July 2020. The median age was 72.0 years with 80.8% female. There were 20 patients who had multiple CNS metastases. BMRR assessed by PAREXEL criteria was 76.9% (90% confidence interval [CI]: 63.3%-90.5%), BMRR assessed by Response Evaluation Criteria in Solid Tumors was 76.9% (95% CI: 54.0%-99.8%), and median PFS of CNS metastasis was 22.0 months (95% CI: 9.7 mo-not reached). The overall response rate was 64.0% (95% CI: 45.2%-82.8%), median PFS was 11.5 months (95% CI: 6.9 mo-not reached), and median survival time was 23.7 months (95% CI: 16.5 mo-not reached). Paronychia and increased creatinine level were the most frequent nonhematological toxicities observed in 13 patients (50%). Grade three and higher adverse events were less than 10%, and there were no treatment-related deaths. Pneumonitis was observed in five patients (19.2%).
CONCLUSIONS
These results suggest that osimertinib is effective in untreated patients with RT-naive asymptomatic CNS metastasis in a clinical practice first-line setting.
TRIAL REGISTRATION
UMIN identifier: UMIN000024218. jRCT identifier: jRCTs071180017.
PubMed: 38046380
DOI: 10.1016/j.jtocrr.2023.100587 -
Frontiers in Medicine 2022Common autoimmune bullous diseases (AIBDs) include pemphigus and bullous pemphigoid (BP), which are primarily caused by IgG autoantibodies against the structural...
Common autoimmune bullous diseases (AIBDs) include pemphigus and bullous pemphigoid (BP), which are primarily caused by IgG autoantibodies against the structural proteins of desmosomes at the cell-cell junction and hemidesmosomes at the epidermal-dermal junction. Few studies have assessed nail changes in patients with pemphigus or BP. In the present study, we collected the clinical data of 191 patients with AIBDs (108 patients with pemphigus and 83 patients with BP) and 200 control subjects. Nail changes were observed in 77.0% (147/191), 77.8% (84/108), and 75.9% (63/83) of patients with AIBDs, pemphigus, and BP, respectively, and 14.5% (29/200) of control subjects. Beau's lines and paronychia were the most common nail involvement, observed in 22.5% (43/191) and 22.5% (43/191) of patients with AIBDs, 25.0% (27/108) and 25.9% (28/108) of patients with pemphigus, 19.3% (16/83) and 18.1% (15/83) of patients with BP, respectively. The autoimmune bullous skin disorder intensity score (ABSIS) and the onset time of patients with pemphigus or BP with nail changes were different. Onychomycosis accounted for 21.5% (41/191) of all patients with AIBDs. The ABSIS was correlated with nail involvement in patients with BP ( = 0.46, < 0.001), and weakly correlated with nail involvement in patients with AIBDs ( = 0.37, < 0.001), pemphigus ( = 0.29, = 0.009), and pemphigus vulgaris (PV; = 0.35, = 0.008). No correlation was observed between nail involvement and disease antibody titers. In conclusion, nail changes are frequently observed in patients with pemphigus and BP. The type and onset time of nail changes may indicate the severity of pemphigus and BP, which warrants the attention of dermatologists.
PubMed: 36203762
DOI: 10.3389/fmed.2022.933608 -
Cureus Dec 2021Cutaneous metastases occur in approximately 10% of oncology patients as a feature of a persistent solid tumor or the harbinger of recurrent neoplastic disease. However,...
Cutaneous metastases occur in approximately 10% of oncology patients as a feature of a persistent solid tumor or the harbinger of recurrent neoplastic disease. However, they can be the presenting manifestation of an unsuspected visceral malignancy in one percent of previously cancer-free individuals. Metastatic skin lesions from breast carcinoma are diverse in their appearance. The clinical presentation of cutaneous metastases in three women with breast cancer is described and both the morphology of skin metastases caused by breast carcinoma and the conditions that are mimicked by breast cancer cutaneous metastases are reviewed. Skin metastases from breast carcinoma commonly appear as firm, flesh-colored to red, smooth or ulcerated or crusted, nodules, papules, and plaques on the ipsilateral chest wall and breast. However, unique sites of breast cancer cutaneous metastases are the eyelids, inframammary folds, ipsilateral lymphedematous arm, scalp, subungual nail bed, and umbilicus; in addition, skin metastases can occur in mastectomy scars and radiation therapy ports. Carcinoma erysipelatoides, carcinoma telangiectoides, and carcinoma en cuirasse are classic patterns of skin metastases that can be observed in breast cancer patients; carcinoma hemorrhagiectoides is a recently observed skin metastases pattern that has also been noted in oncology patients with breast carcinoma. The pleomorphic skin lesions of breast cancer metastases can masquerade as benign cutaneous lesions and tumors (such as a collision tumor, cyst, dermatofibroma, and milia-en-plaque), cutaneous malignancies (such as melanoma and non-melanoma skin cancers), infections (such as cellulitis, folliculitis, herpes zoster, and paronychia), reactive erythema (such as erythema annulare centrifugum, and urticaria), skin conditions (such as alopecia areata, dermatitis, hidradenitis suppurativa, and scleroderma), and vascular lesions (such as angiokeratoma, angiosarcoma, lymphangioma circumscriptum, purpura, and pyogenic granuloma). In addition, breast carcinoma cutaneous metastases can not only mimic other miscellaneous conditions such as erosions and ulcers, Paget's disease, and papillomatosis cutis lymphostatica but also have unusual morphology such as targetoid lesions or a sharply demarcated red infiltration of the nasal tip similar to a clown's nose. The possibility of a breast cancer cutaneous metastasis should be considered in the evaluation of a patient with breast cancer--and although less likely, in a cancer-free individual--who develops a new and/or a treatment-unresponsive cutaneous lesion. A biopsy of the skin lesion is necessary to confirm the diagnosis of breast cancer cutaneous metastasis.
PubMed: 35028206
DOI: 10.7759/cureus.20301 -
Indian Journal of Dermatology 2020Nail toxicity is a relatively uncommon cutaneous adverse effect of chemotherapeutic agents. Rapidly dividing cells of the nail matrix are perturbed by the antimitotic...
INTRODUCTION
Nail toxicity is a relatively uncommon cutaneous adverse effect of chemotherapeutic agents. Rapidly dividing cells of the nail matrix are perturbed by the antimitotic activity of these agents. Although most of these changes are cosmetic and regress once the therapy is completed, a few of these adverse effects are challenging to manage and require temporary or permanent suspension of chemotherapeutic agents.
MATERIALS AND METHODS
A total of 205 patients with various malignancies and under chemotherapy in oncology ward of the hospital over a period of 3 months were screened for nail involvement postchemotherapy. Relevant details, protocol of chemotherapeutic agents were assessed. Nail examination was carried out in daylight and the changes were analyzed.
RESULTS
A total of 124 (60.4%) patients had nail changes due to chemotherapeutic agents. The most common change was diffuse hyperpigmentation in 101 (81.4%) patients commonly due to a combination of cyclophosphamide and adriamycin in 43 (42.5%) patients. Longitudinal melanonychia was seen in 36 (29%), Beau's lines in 31 (25%), onychomadesis in 17 (13.7%), Mees' lines in 15 (12%), paronychia in 12 (9.6%), subungual hyperkeratosis in 10 (8%), and Muehrcke's lines in 4 (3.2%) patients. All the patients who developed Muehrcke's lines were on a combination of cyclophosphamide/doxorubicin/5 FU. Exudative onycholysis was observed in 2 (1.6%) patients; both these patients were on paclitaxel therapy. A total 2 (1.6%) patients who developed exudative onycholysis were advised discontinuation and another substitute chemotherapy was advised. Therapy for 2 (1.6%) patients who developed acute paronychia due to gefitinib was temporarily suspended. Unfortunately, most of the patients were on multiple chemotherapeutic agents hence, we could not pinpoint one drug as a cause. Therefore, a combination of agents was implicated in most cases.
CONCLUSION
Nail toxicities are common with chemotherapeutic agents, however less importance is given to nail involvement. Apart from being cosmetically significant, a few adverse effects may warrant modification of the chemotherapy.
PubMed: 32565559
DOI: 10.4103/ijd.IJD_37_19 -
Journal of Cutaneous and Aesthetic... 2023Retronychia refers to the embedding of the nail into the proximal nail fold. Patients present with chronic paronychia in the setting of disrupted nail growth. Nail...
Retronychia refers to the embedding of the nail into the proximal nail fold. Patients present with chronic paronychia in the setting of disrupted nail growth. Nail avulsion is curative and unlike other forms of ingrown nails, it does not tend to recur. We report a case of retronychia who presented with pain and swelling around bilateral great toes. Further examination showed growth of overlapping nail plates, which led to the diagnosis of retronychia. This article emphasizes the clinical features and treatment options available for retronychia, thereby avoiding misdiagnosis.
PubMed: 38314366
DOI: 10.4103/JCAS.JCAS_71_21 -
Dermatology and Therapy May 2022Erlotinib (Tarceva) is a drug used for the treatment of non-small cell lung cancer in patients with epidermal growth factor receptor (EGFR) mutations. Since EGFR is...
Erlotinib (Tarceva) is a drug used for the treatment of non-small cell lung cancer in patients with epidermal growth factor receptor (EGFR) mutations. Since EGFR is expressed in the skin, EGFR inhibitors commonly develop cutaneous side effects such as acneiform eruption, paronychia, telangiectasias, and abnormal eyelash growth. A 56-year-old man and a 46-year-old man visited the dermatology clinic complaining of yellowish papuloplaques and acneiform eruption on the face. They had been treated with erlotinib for lung cancer. Since patients using EGFR inhibitors are increasing, physicians should be aware that xanthomatous change can occur in severe acneiform eruptions after erlotinib treatment.
PubMed: 35508798
DOI: 10.1007/s13555-022-00739-5 -
Revista Medica de Chile May 2021Taxanes are a class of chemotherapeutic agents with common associated dermatologic adverse events, such as skin hyperpigmentation, hand-foot skin syndrome, paronychia...
Taxanes are a class of chemotherapeutic agents with common associated dermatologic adverse events, such as skin hyperpigmentation, hand-foot skin syndrome, paronychia and onycholysis. Taxane-induced scleroderma is rare. Few cases with skin findings resembling systemic sclerosis, have been reported after the administration of these agents. We report two cases with stage IV breast cancer, aged 66 and 71 years, who developed sclerodermic skin lesions in their extremities after starting treatment with placlitaxel and nabplaclitaxel respectively.
Topics: Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Female; Humans; Scleroderma, Systemic; Taxoids
PubMed: 34751336
DOI: 10.4067/s0034-98872021000500807 -
Targeted Oncology Jul 2023In RELAY, a randomized, double-blind, phase III trial investigating the efficacy and safety of ramucirumab+erlotinib (RAM+ERL) or ERL+placebo (PBO) in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Tolerability of Ramucirumab Plus Erlotinib in Taiwanese Patients with Untreated, Epidermal Growth Factor Receptor-Mutated, Stage IV Non-small Cell Lung Cancer in the RELAY Study.
BACKGROUND
In RELAY, a randomized, double-blind, phase III trial investigating the efficacy and safety of ramucirumab+erlotinib (RAM+ERL) or ERL+placebo (PBO) in patients with untreated, stage IV, epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), RAM+ERL demonstrated superior progression-free survival (PFS) versus PBO+ERL, with no new safety signals.
OBJECTIVE
The aim of this paper was to report efficacy and tolerability findings for the Taiwanese participants of RELAY.
PATIENTS AND METHODS
Patients were randomized 1:1 to RAM+ERL or ERL+PBO. Primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate (ORR), duration of response (DoR) and tolerability. Data for the current analysis are reported descriptively.
RESULTS
In RELAY, 56 Taiwanese patients were enrolled; 26 received RAM+ERL, 30 received ERL+PBO. The demographic profile of the Taiwanese subgroup was consistent with that of the overall RELAY population. Median PFS for RAM+ERL/ERL+PBO, respectively, was 22.05 months/13.40 months (unstratified hazard ratio 0.4; 95% confidence interval 0.2-0.9); ORR was 92%/60%; median DoR was 18.2 months/12.7 months. All patients experienced one or more treatment-emergent adverse events (TEAEs); those most commonly reported were diarrhea and dermatitis acneiform (58% each) for RAM+ERL and diarrhea (70%) and paronychia (63%) for PBO+ERL. Grade ≥ 3 TEAEs were experienced by 62%/30% of RAM+ERL/PBO+ERL patients, respectively, and included dermatitis acneiform (19%/7%), hypertension (12%/7%), and pneumonia (12%/0%).
CONCLUSIONS
PFS for the Taiwanese participants of RELAY receiving RAM+ERL versus ERL+PBO was consistent with that in the overall RELAY population. These results, together with no new safety signals and a manageable safety profile, may support first-line use of RAM+ERL in Taiwanese patients with untreated EGFR-mutant stage IV NSCLC.
TRIAL REGISTRATION
www.
CLINICALTRIALS
gov , NCT02411448.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; Lung Neoplasms; Antineoplastic Combined Chemotherapy Protocols; ErbB Receptors; Diarrhea; Dermatitis; Mutation; Ramucirumab
PubMed: 37329423
DOI: 10.1007/s11523-023-00975-5 -
Journal of Traditional and... Sep 2020Cancer is a major public health problem worldwide, and there has been a sustained rise in its incidence in both developing and developed countries. Although there are... (Review)
Review
Cancer is a major public health problem worldwide, and there has been a sustained rise in its incidence in both developing and developed countries. Although there are currently numerous effective therapeutic options for cancer, they sometimes exhibit resistance and obvious side effects. Traditional Chinese medicine (TCM) currently plays a major role in cancer therapy by downregulating the growth of cancer cells through various pathways and by relieving side effects. Studies in cultured human malignant cell lines have demonstrated that can control cancer cell proliferation and cancer progression by inducing autophagic and apoptotic cell death. Case-control studies have indicated that TCM can relieve the side effects of cancer therapy. This review provides brief insights into the anticancer effects of TCM, the side effects relieved by TCM, and the role of TCM doctors in cancer treatment.
PubMed: 32953557
DOI: 10.1016/j.jtcme.2019.07.001