ONYCHOLYSIS AS A COMPLICATION OF TAXANE-BASED CHEMOTHERAPY WITH CONCOMITANT CRYOTHERAPY IN BREAST CANCER PATIENTS: TWO CASE REPORTS.

Nail changes are a common side effect of taxane chemotherapy, although onycholysis is quite a rare complication the correct management of which is poorly standardized. These case reports provide a description and analysis of onycholysis, a rare but noteworthy complication observed during taxane-based chemotherapy with concomitant cryotherapy in two patients with breast cancer. Despite prophylactic measures, both cases experienced nail complications during Paclitaxel treatment, underlining the complex nature of onycholysis during taxane therapy and highlighting the critical role of nail assessment and infection screening.

Mild Cryotherapy for Prevention of Paclitaxel-Induced Nail Toxicity in Breast Cancer Patients: A Phase II Single-Arm Clinical Trial.

BACKGROUND: Nail changes are among the most common dermatological adverse events in paclitaxel-receiving patients. Although effective, low-temperature prophylactic cryotherapy is discomforting and a potential cause of side effects, resulting in low patients' adherence. PATIENTS AND METHODS: A phase II single-arm study evaluating mild cryotherapy for the reduction of 12-week, grade 2 nail toxicity was conducted on 67 taxane-naïve breast cancer patients (age 18-74 years) undergoing weekly adjuvant chemotherapy with paclitaxel. Instant-ice packs were fixed over the fingers and toes for a total of 70 minutes during paclitaxel infusion at a temperature between -5 °C and +5 °C. Nail toxicity was evaluated weekly (CTCAE vs 4.03), including grade 2 (ie, onycholysis, subungual hematoma, onychomadesis) and grade 1 nail toxicities. RESULTS: Twelve patients experienced grade 2 nail toxicities (17.9%, 95% confidence interval [CI] 9.6%-29.2%; median time to onset: 56 days): onycholysis was the most frequent grade 2 toxicity (13.4%), followed by subungual hematoma (9.0%) and onychomadesis (1.5%). Grade 1 toxicity occurred in 33 patients (63.5%, 95% CI 49.0%-76.4%) with nail discoloration representing by far the most frequent toxicity (59.6%). Seventeen patients (25.4%) reported no nail toxicity. 62.7% of patients reported no pain and 22.4% suffered moderate pain. No patient experienced severe pain or others adverse effects. CONCLUSIONS: Instant-ice pack is a feasible prophylactic intervention for nail toxicity, well tolerated by patients and with limited impact on routine workload. It could be considered for patients refusing (or interrupting) cryotherapy, and it can be implemented when frozen gloves management is not feasible.

[Peripheral neuropathy, onycholysis and health-related quality of life in womens with breast cancer treated with taxanes. Prospective longitudinal study.] / Neuropatía periférica, onicólisis y calidad de vida en mujeres con cáncer de mama en tratamiento con taxanos. Estudio longitudinal prospectivo.

OBJECTIVE: Peripheral neuropathy and onycholysis are adverse events produced by taxanes in breast cancer that persist even after the end of treatment and negatively influence quality of life. The objectives of the study were to describe these side effects and the degree of involvement and relating them to the drug doses received. METHODS: Prospective, cross-sectional study of in 50 womens dignosed of breast cancer, treated with docetaxel and paclitaxel in Hospital Universitario Miguel Servet in Zaragoza (Aragón, Spain). CTCAE v.5.0 scale and Semes Weinsten test were used to evaluate peripheral neuropathy and onycholysis. ECOG scale was performed to measure the health-related quality of life. Study variables were evaluated before-during treatment and 1 and 6 months after finish treatment. Statistical analysis was performed using Jamovi 1.2®. For the relationship of the qualitative variables, the chi-square, Fisher's exact test, Mc's test were used. Nemar and the Odds Ratio test. Effects were considered significant if p<0.05. RESULTS: 43 subjects were included. During treatment the 9.8 presented motor neuropathy and 12.2% sensitive neuropathy, 37.2% onycholisis in upper extremities and 39.5% in lower extremities (χ2=11.3; p<0.001 / χ2=13.0; p<0.001) and 38.1% a health related quality of live limited in excessive activities (χ2=10.3; p=0.001). Post-treatment evaluation the 20.9% presented motor neuropathy and 32.6% sensitive neuropathy (χ2=3.57; p=0.059 / χ2=6.23; p=0.013), the 86% onycholisis in upper extremities and lower extremities (χ2=6.07; p=0.048 / χ2=10.1; p=0.006) and 58.5% a health related quality of live limited in excessive activities (χ2=8.47; p=0.014). 6 month later, the initials parameters were not recuperated. CONCLUSIONS: Taxanes have a negative impact on the health-related quality of life in patients, even 6 months after finishing treatment due to the peripheral neuropathy and onycholysis that they cause.

OBJETIVO: La neuropatía periférica y la onicólisis son eventos adversos producidos por los taxanos en el cáncer de mama, que perduran incluso habiendo finalizado el tratamiento e influyendo negativamente en la calidad de vida. Los objetivos del estudio fueron describir estos efectos secundarios, midiendo el grado de afectación, y relacionarlos con las dosis de fármaco recibidas. METODOS: Se realizó un estudio observacional, longitudinal prospectivo con muestreo consecutivo inicial de concuenta mujeres con cáncer de mama en tratamiento con docetaxel y/o paclitaxel en el Hospital Universitario Miguel Servet de Zaragoza (Aragón, España). Para la valoración de la neuropatía periférica (motora y sensitiva) se utilizó la escala CTCAE v.5.0 y el test de Semmes Weinsten. La valoración de la calidad de vida relacionada con la salud se midió mediante la escala ECOG. Se realizaron valoraciones previo-durante-post y a los 6 meses de haber finalizado el tratamiento. El análisis estadístico se realizó mediante Jamovi 1.2®. Para la relación de las variables cualitativas se utilizó la chi-cuadrado, el test exacto de Fisher, el test de Mc.Nemar y el test de Odds Ratio. Los efectos se consideraron significativos si p<0,05. RESULTADOS: Se incluyeron finalmente 43 mujeres. Durante el tratamiento, el 9,8% presentó neuropatía motora y el 12,2% neuropatía sensitiva, el 37,2% onicólisis en extremidades superiores y el 39,5% en inferiores (χ2=11,3; p<0,001 / χ2=13,0; p<0,001), y el 38,1% una calidad de vida restringida a actividad exagerada (χ2=10,3; p=0,001). En la valoración postratamiento, el 20,9% presentó neuropatía motora y el 32,6% neuropatía sensitiva (χ2=3,57; p=0,059 / χ2=6,23; p=0,013), el 86% onicólisis en extremidades superiores y el 90,7% en inferiores (χ2=6,07; p=0,048 / χ2=10,1; p=0,006) y el 58,5% al menos una calidad de vida restringida a actividad exagerada (χ2=8,47; p=0,014). A los seis meses no se recuperaron los valores iniciales de evaluación. CONCLUSIONES: Los taxanos repercuten negativamente en la calidad de vida de las mujeres incluso a los seis meses tras finalizar el tratamiento debido a la neuropatía periférica y la onicólisis que provocan.

A randomised controlled trial of interventions for taxane-induced nail toxicity in women with early breast cancer.

Onycholysis and paronychia has been associated with chemotherapy treatment for women with breast cancer. Our primary aim was to investigate the effectiveness of different topical interventions to ameliorate nail toxicity. Secondary aims were to explore the full range and severity of possible nail changes associated with taxane-based chemotherapy and the specific impact this had on quality of life, using two novel measures. This was an exploratory randomised controlled trial of three topical interventions (standard care, nail polish or specialist nail drops) for the prevention or reduction of nail changes induced by taxane-based chemotherapy. Outcomes included nail toxicity assessed at three time points (baseline, 3 weeks and 3 months post completion of chemotherapy) using two novel clinical tools (NToX-G12, NToX-QoL) and the Common Terminology Criteria for Adverse Events (CTCAE v3) and EQ-5D-5L. A total of 105 women were recruited (35 in each arm) and monitored up to three months post completion of chemotherapy. Almost 20% of patients were over the age of 60 years. There were 26 withdrawals, the majority from the nail polish arm. Residual Maximum Likelihood REML analysis indicated a significant arm, time and interaction effect for each intervention (p < 0.001). Less nail toxicity was observed in patients receiving specialist nail drops or standard care arms in comparison to those using nail polish. This study provides evidence to support clinicians' suggestions on nail care recommendations based on the patients' needs and preferences. Future investigations into comparing or combining cryotherapy and topical solutions that can support patient's decisions are warranted.

Application of Topical Lidocaine for Pain Relief in the Setting of Targeted Therapy-Induced Onycholysis: A Case Report.

Selective pan fibroblast growth factor receptor (FGFR) inhibitors have been linked to severe onycholysis, the uncomfortable separation of the nail plate from the nail bed. Recommendations to assist with FGFR inhibitor onycholysis vary based on the severity. We hypothesized that the application of topical lidocaine to mimic a digital nerve block would be beneficial in addition to traditional supportive care interventions and subsequently report its immediate and continued efficacy for targeted therapy-induced onycholysis.

Prophylactic management for taxane-induced nail toxicity: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. RESULTS: We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. CONCLUSIONS: Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.

Sparfloxacin-induced photo-onycholysis and photosensitivity characteristically sparing lepromatous skin lesions: an interesting observation.

Sparfloxacin is an antibiotic in the quinolone group of antibacterial agents, which often induce photosensitive skin reactions, more often phototoxic reactions than photoallergic ones, and sometimes associated photo-onycholysis. We present a case of phototoxic dermatitis with photo-onycholysis in a 38-year-old man probably induced by sparfloxacin, which was prescribed to him along with rifampicin and clofazimine because he was suffering from borderline lepromatous leprosy. He developed exaggerated sunburn-like eruptions mainly on sun-exposed sites along with painful onycholysis of the fingernails. Interestingly, the hypopigmented patches of leprosy were spared, which is a very rare phenomenon. Withdrawal of sparfloxacin along with administration of systemic steroids and other supportive measures helped heal the skin eruptions with hyperpigmentation, but the photo-onycholysis was slow to resolve.

[Integrated podiatrist care for prostate cancer patients treated with docetaxel: Feasibility and results]. / Soins podologiques intégrés chez les patients atteints de cancer de prostate traités par docétaxel : faisabilité et résultats.

BACKGROUND: Docetaxel is frequently used for the treatment of metastatic prostate cancer patients. Nail toxicity is a commonly described side effect, but no precise recommendation exists concerning its management. We experimented the integration of a podiatrist in routine cancer care. METHODS: Patients having received docetaxel for a metastatic prostate cancer since the arrival of the podiatrist were studied. RESULTS: Fifty-six patients were included, half had docetaxel-induced nail toxicity and 18 were referred to the podiatrist. The integration of the podiatrist in routine care was feasible and allowed characterizing nail toxicity. The main lesions observed were non-coagulated nail hematomas, coagulated nail hematomas and onycholysis. This experience led to propose an integrated care for docetaxel-induced nail toxicity. CONCLUSION: The integration of podiatrist care is feasible in routine cancer care and can help improving the management of docetaxel-induced nail toxicity in metastatic prostate cancer patients.

Investigation of a correlation between taxane-based chemotherapy and the ultrasonic time-of-flight of human fingernails.

BACKGROUND: Medical practitioners have long associated the physical appearance of human fingernails with certain underlying health conditions due to their direct connection to the vascular system. The objective of this study was to demonstrate how human fingernails can potentially be used as a biomarker to determine the severity of a patient's reaction to chemotherapy. METHODS: Quantitative investigation of fingernails in patients undergoing taxane-based chemotherapy was conducted using a high-frequency 50 MHz ultrasound device in B-mode in the form of a pilot study. Time-of-Flight (TOF) ultrasonic signal measurements were recorded longitudinally across fingernails over three time intervals; (before treatment, in the middle of treatment, and on the last day of treatment); a neuropathy assessment and photographs were also taken for comparison. RESULTS: A total of 17 patients were examined in this study with ages ranging from 35-69 years old with both weekly and biweekly chemotherapy regimens. Onycholysis and fingernail discoloration were observed in 8 of the 17 patients. White transverse lines and white lunula were observed on 4 of the 17 patients. Quantitative assessment revealed a TOF median decrease in fingernails during the first half of chemotherapy treatment; conversely, TOF median was found to have increased during the second half. Median TOF measurements at the end of treatment were found to return to approximately that of the baseline value. CONCLUSION: This was a novel application of ultrasound in fingernails as chemotherapy biomarkers and further studies should be considered to verify and expand on the results obtained in this study.

A prospective randomized controlled trial of hydrating nail solution for prevention or treatment of onycholysis in breast cancer patients who received neoadjuvant/adjuvant docetaxel chemotherapy.

PURPOSE: Onycholysis and other nail toxicities occur in approximately 20-30% of breast cancer (BC) patients receiving docetaxel chemotherapy. Onycholysis is often associated with painful paronychia, decreasing patients' quality of life. In this study, we aimed to evaluate the efficacy of hydrating nail solution (HNS) (EVONAIL® solution, Evaux Laboratories, France) for the prevention and treatment of docetaxel-induced onycholysis and nail toxicities. METHODS: This study was a prospective, randomized, controlled study of HNS for the prevention or treatment of onycholysis in patients with docetaxel after doxorubicin plus cyclophosphamide. In the experimental arm, patients painted HNS on nails and periungual areas once a day till developing onycholysis grade 2. After grade 2 onycholysis development, patients applied HNS twice a day regardless of treatment arm. The primary endpoints were the incidence of onycholysis grade 2 and recovery rate from grade 2 onycholysis. RESULTS: From August 2015 to May 2016, 103 patients were enrolled and completed this study. Of these, 25 cases of grade 1 and 22 of grade 2 onycholysis were observed. Prophylactic application of HNS resulted in a statistically significant reduction of grade 2 onycholysis compared to controls (P = 0.001) and all grade onycholysis was also significantly lower in the experimental arm (P = 0.034). Multivariate analysis showed that HNS decreased grade 2 onycholysis (Hazard ratio (HR) 0.366, 95% confidence interval (CI) 0.148, 0.902; P = 0.029) and all grade onycholysis (HR 0.372, 95% CI 0.201-0.687, P = 0.002). CONCLUSIONS: Hydrating nail solution significantly reduced the incidence of docetaxel-induced onycholysis in BC patients (NCT02670603).

Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention.

BACKGROUND: One of the most important dermatologic side effects of doxycycline is photosensitivity. As doxycycline is important for malaria prophylaxis and malaria is mainly spread in countries with high sun radiation, special attention should be paid to this adverse effect. While there are many publications on the phototoxicity of tetracyclines in general, only a few exist focusing on doxycycline. The objective of this systematic review was to summarize all available reports on clinical manifestations, influencing factors like UV dose or dose of medication, and the possibilities of prevention by sun protection. METHODS: This review is based on a systematic search in PubMed for articles in English and German and a manual search between 1990 and 2015. RESULTS: The number of publications is low. Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis. Also, onycholysis is possible. The triggering UV spectrum seems to consist mainly of UVA1 (340-400 nm), so UV-protective products should be used that cover this range. Travelers to tropical countries taking doxycycline for malaria prophylaxis need thorough medical counseling to avoid possibly severe phototoxic reactions. CONCLUSION: Evidence base must be improved for giving advice on appropriate prevention measures to travelers taking doxycycline and having a risk of significant sun exposure.