[Cutaneous adverse events to systemic anticancer therapies : Hand-foot syndrome and nail changes]. / Kutane Nebenwirkungen onkologischer Systemtherapien : Hand-Fuß-Syndrom und Nagelveränderungen.

BACKGROUND: Hand-foot syndrome (HFS) and nail changes are frequent adverse events of anticancer therapies. OBJECTIVES: To provide a review of current evidence in HFS and nail disorders associated with medical tumor treatment. MATERIALS AND METHODS: Basis is the current German S3 guideline "Supportive therapy in oncologic patients" and literature on this topic published since the guideline was finalized. RESULTS: Two variants of HFS are distinguished: a chemotherapy-associated and a kinase-inhibitor-associated variant. In the first form, painful erythema, blisters and ulceration can occur, also in other areas with a high number of sweat glands such as axillary and inguinal regions. Thus, the secretion of toxic substances through sweat glands is a proposed pathogenetic mechanism. For the second form, which results in callus-like painful thickening of the horny layer on areas of mechanic pressure, a vascular mechanism is proposed. For prophylaxis of HFS, avoidance of mechanical stress, regular cleaning of predisposed areas, and also urea- and diclofenac-containing ointments are recommended; in case of infusions (taxanes, doxorubicine), cooling of hands and feet during infusion is recommended. In case of manifest HFS, dose reduction or prolongation of intervals of the associated treatment are recommended. Nail changes often develop under therapy with chemotherapeutic agents but also under treatment with agents such as checkpoint inhibitors or under targeted therapy. Different components of the nail unit may be involved such as the nail matrix, nail bed, nail plate, hyponychium, lunula and proximal and lateral nail folds. CONCLUSION: This work gives insight into the pathophysiology of HFS and nail disorders that develop under systemic oncologic treatments and gives recommendations for prophylaxis and treatment.

Natural Treatment Options for Nail Disorders.

The growing demand for natural treatments has raised concerns among clinicians due to limited scientific evidence supporting their use. This review article addresses the issue by assisting dermatologists and general practitioners in recommending natural treatments for the following common nail disorders: nail brittleness, onychomycosis, periungual verrucae, paronychia, chloronychia, nail psoriasis, nail lichen planus, onychocryptosis, onycholysis, and congenital malalignment of the great toenail. One limitation is the scarcity of existing reviews on natural treatment options for nail disorders in the literature. Through a comprehensive review of existing literature, this article consolidates the available evidence on natural treatment options for these conditions. Although some natural treatments for nail disorders are supported by scientific evidence, the indiscriminate use of such remedies may lead to severe poisoning and health problems. Given the widespread and increasing use of natural treatments, clinicians play a pivotal role in educating patients about evidence-based remedies and debunking misleading claims. By doing so, clinicians can enhance patient safety and improve treatment outcomes. It is essential for healthcare professionals to be well-informed and equipped with the knowledge to differentiate between effective natural treatments and unverified claims, ensuring that patients receive appropriate care.

Green Nails, Red Alert: An Unusual Exit site infection Presentation.

Green nail syndrome is an infectious nail disorder caused most commonly by Pseudomonas aeruginosa. We report a rare case of peritoneal dialysis (PD) exit site infection (ESI) accompanied by P. aeruginosa-associated green nail syndrome. The patient was treated with oral and topical antibiotics without the need for PD catheter removal. We aim to emphasise the importance of nail assessment for ESI in patients undergoing PD.

Nivolumab Safety in Renal Cell Carcinoma: A Case Report.

Nivolumab is used to treat several different types of cancers. Although it is generally considered to be effective and well-tolerated, it has been associated with adverse effects requiring discontinuation of treatment, like many other drugs used for cancer. A 70-year-old male was switched from sunitinib to nivolumab for renal cell carcinoma. The patient developed persistent hypothyroidism, onycholysis, and pneumonitis at nivolumab cycle 6, 10, and 11, respectively. Using the Naranjo causality method, the likelihood of causality was deemed "probable" for pneumonitis and hypothyroidism and "possible" for onycholysis. Nivolumab was eventually discontinued due to disease progression, rather than safety concerns. Eudravigilance, the European pharmacovigilance database, was searched for all nivolumab-related individual case safety reports from Malta, up to September 4, 2023. Six reports were identified in Malta, although the 3 events identified in this case report were not reported, suggesting under-reporting in Malta. This case report identified an uncommon nivolumab adverse drug reaction (ADR), onycholysis and showed how, despite the occurrence of 3 ADRs, it was its lack of efficacy rather than its safety which led to its discontinuation in this particular patient.

Cross-sectional study of the prevalence of hyperextension of the first metatarsophalangeal joint and its relationship to onycholysis in women with hallux valgus.

BACKGROUND: Hallux Valgus (HV) deformity is associated with misalignment in the sagittal plane that affects the first toe. However, the repercussions of the first toe hyperextension in HV have been scarcely considered. The purpose of this study was to provide evidence of the association between first-toe hyperextension and the risk of first toenail onycholysis in HV. METHODS: A total of 248 HV from 129 females were included. The extension of 1st MTP joint was measured while the patient was in the neutral position of the hallux using a two-branch goniometer. The classification of the HV severity stage was determined by the Manchester visual scale, and the height of the first toe in the standing position was measured using a digital meter. An interview and clinical examination were performed to collect information on the presence of onycholysis of the first toe. RESULTS: Of the 248 HV studied, 100 (40.3%) had onycholysis. A neutral extension > 30 degrees was noted in 110 (44.3%) HV. The incidence of onycholysis was higher in HV type C than in type B (p = 0.044). The probability of suffering onycholysis in the right foot was 2.3 times greater when the neutral position was higher than 30 degrees (OR = 2.3; p = 0.004). However, this was not observed in the left foot (p = 0.171). Onycholysis was more frequent in HV with more than 2 cm height of the first toe (p < 0.001). For both feet, the probability of suffering onycholysis was greater for each unit increase in hallux height (right foot OR = 9.0402, p = 0.005; left foot OR = 7.6633, p = 0.010). CONCLUSIONS: The incidence of onycholysis appears to be significantly associated with HV showing more than 30º extension, and more than 2 cm height of the first toe. Height and hyperextension of the first toe together with first toenail pathology should be mandatory in the evaluation of HV.

Paclitaxel-Induced Periarticular Thenar Erythema with Onycholysis Syndrome.

Introduction: Periarticular thenar erythema with onycholysis (PATEO) syndrome is a rare subtype of hand-foot syndrome seen in patients undergoing taxane-based chemotherapy. It presents as erythematous to violaceous plaques on the dorsum of hands, feet, and around the Achilles tendon along with nail changes, particularly onycholysis. Case Presentation: A 39-year-old female on paclitaxel chemotherapy for stage IIIA (T3N2aM0) invasive ductal breast carcinoma, presented with mildly tender erythematous to violaceous plaques involving the dorsa of bilateral hands and feet, in the periarticular areas of the Achilles tendon, with facial involvement. All fingernails showed shortening, orange-red chromonychia, Beau's lines, onychoschizia, and subungual debris. The toenail involvement was relatively less severe, with distal onycholysis being the predominant finding. The patient showed significant improvement in cutaneous lesions with topical steroid therapy and was advised cold water immersion during subsequent chemotherapy infusions. Discussion: A shorter interval between cycles and a higher cumulative number of cycles correlate with severity of dermatitis and nail involvement. Rarely, periocular and facial involvement can occur concurrently with PATEO syndrome. This case is being reported to increase awareness about this entity facilitating early diagnosis and treatment.

A case of rapid fingernail growth associated with nail psoriasis: A case report.

Overall, 80%-90% of patients with psoriasis will have nail involvement at some point during their lifetime, and nail changes, on average, are more common in patients with longer disease duration. Since there is accelerated keratinocyte proliferation and cell turnover in cutaneous psoriasis plaques compared to normal skin, it has been hypothesized that psoriasis increases nail growth rate. We describe a case of a 44-year-old male with a 10-year history of cutaneous and nail psoriasis, with acceleration in nail growth rate for 2 years prior to presentation. Clinical examination of the fingernails showed very long nails with onychorrhexis, onycholysis, and koilonychia and scattered erythematous plaques involving the chest and arms. We report a case of rapid fingernail growth in a patient with a 10-year history of psoriasis with skin and nail manifestations. Our case supports the hypothesis that increased cell turnover in psoriasis patients affects nail growth rate.

Eccrine Angiomatous Hamartoma Occurring on the Nail Bed.

A 71-year-old woman was referred to our clinic with a 2-month history of pain and exudate from her right first toe. Physical examination revealed a subungual nodule that elevated the nail plate and produced distal onycholysis. We performed onychectomy and removed the nodule. A histopathological specimen from the nodule showed hyperkeratosis and acanthosis in the epidermis, papillomatosis and dilated vessels in the superficial dermis, and aggregation of eccrine glands in the mid-dermis. Based on these findings, a diagnosis of eccrine angiomatous hamartoma (EAH) was made. EAH is a rare cutaneous hamartoma that is histologically characterized by proliferation of eccrine glands and vascular components. To our knowledge, EAH occurring in the subungual region has not been reported. The pathogenesis of acquired EAH has not been completely elucidated, but several cases have been reported to be caused by external stimuli. Although the subungual area generally has no sweat glands, our case suggests that a traumatic stimulus can induce EAH anywhere including regions where sweat glands are normally not found.

Two case studies of the treatment of simple onycholysis with disappearing nail bed caused by trauma by combined pharmacological, orthonyxia and taping methods.

BACKGROUND: Simple onycholysis is a common complaint after trauma and consists in separation of the nail plate from the nail bed. If untreated, prolonged onycholysis may cause a disappearing nail bed (DNB) that leads to the shortening or narrowing of the nail plate. OBJECTIVES: This study is aimed at discussing possible treatment of chronic simple onycholysis with DNB by combined conservative methods. METHODS: Simple onycholysis and DNB treatment consists of Onygen® cream application, nail bed massages, bracing procedures and nail folds taping with kinesio tape. RESULTS: Long-lasting simple onycholysis with DNB may be fully eliminated by applying the combined pharmacological, orthonyxia and taping treatment. CONCLUSION: Advanced simple onycholysis, which leads to the DNB and, in consequence, to the shortening or narrowing of the nail plate, causes cosmetic discomfort for patients. A damaged nail apparatus is also more susceptible to new traumas. Even long-standing onycholysis with DNB can be successfully treated with easy-to-apply conservative methods. The key point of therapy is the use of several methods of treatment with different effects on the nail apparatus. The effects of described therapy are highly satisfactory, the only drawback being its long term, which is caused by slow growth of the nails.

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.

Nail Loss in Mild to Moderate Pemphigus Vulgaris.

Introduction: Symptoms of pemphigus vulgaris (PV) rarely include nail findings. When ungual involvement does occur, the most common manifestations are paronychia and onychomadesis. Onycholysis is very uncommon, and complete nail loss has not been reported in the literature. Ungual involvement is thought to be closely correlated with disease severity, with only severe PV cases demonstrating nail symptoms. Case Presentation: We report a case of a 34-year-old female presenting with mild to moderate PV yet severe onycholysis of her first toe leading to secondary nail loss in conjunction with paronychia of her bilateral thumbs. Oral tofacitinib and rituximab infusions led to strikingly rapid improvement in her nail symptoms. Discussion/Conclusion: This case illustrates the importance of a thorough history and physical exam, as a primary complaint of nail symptoms in these patients may lead to unrecognized PV by even the most skilled practitioners. Tofacitinib and rituximab in combination may rapidly improve nail involvement.

Chronic Retronychia: Nonsurgical Treatment.

Introduction: Retronychia is a particular form of post-traumatic ingrown nail associated with repeated microtrauma of the underside of the proximal nail fold. It is caused by the nail embedding backward into the underside of the proximal nail fold, forming multiple generations of nail plate. Methods: The study aims to evaluate the results of a novel nonsurgical treatment of retronychia. A review was performed on 20 patients who underwent the treatment, 16 having suffered from a chronic form of the condition, with the remaining 4 being afflicted with retronychia for less than a year prior to treatment. Results: The treatment was a combination of eliminating the proximal sharp edge of the uppermost nail layer and thinning of the nail with fraises and drills of various sizes. This therapy was repeated every 7-14 days. The patients came for checkup every 6 weeks. Treatment duration varied from 2 to 14 months. The rate, at which the appearance of a healthy nail occurred depended on the length of the intact nail layer below the part of the nail affected by retronychia, the age of the patient, and cofactors such as obesity, diabetes, etc. The treatment result in our case study was completely healthy nail growth without relapse of retronychia in all the 20 patients for a follow-up period of 18 months. Conclusion: By combining a healthy nail growth and the simultaneous protection of the nail, we were able to achieve a normal nail in all cases. In order to maintain the achieved results, we recommended our patients to continue wearing protective tubes whenever they would wear closed shoes because recurrence of retronychia may occur even after minimal trauma.

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.

Reaching Treatment Goals in Psoriasis with Conventional Systemic Drugs: How Long Are We Willing to Wait?

OBJECTIVES: The purpose of this study was to investigate the attainment of treatment goals according to the European Consensus Programme (ECP-TGs) from 2011 in patients with moderate to severe psoriasis (Pso) treated with the first conventional systemic therapy and to identify factors that might compromise the attainment of these treatment goals. METHODS: In a multicenter, prospective observational study, patients with moderate to severe Pso, defined as either body surface area (BSA) >10% or psoriasis area severity index (PASI) >10 and dermatology life quality index (DLQI) >10, received a conventional systemic therapy that could be modified at each follow-up visit over the course of 18 months. All subjects signed an informed consent form, were ≥18 years of age as well as systemic therapy naïve, and had regular study visits at months 3, 6, 9, 12, and 18 after baseline. Among others and in addition to demographic and disease-related characteristics at baseline, we documented BSA, PASI, DLQI, and the physician-reported attainment of treatment goals at each follow-up visit. Factors related to a failure in achieving the ECP-TGs (i.e., either Δ PASI ≥75 or Δ PASI ≥50 and <75 with a DLQI ≤5) at month 18 were investigated by multiple logistic regression. Descriptive results are presented as the mean ± SD for interval data, and absolute as well as relative frequencies for nominal data. For this part of the analysis, data at baseline and months 6, 12, and 18 are presented. RESULTS: A total of 133 Pso patients with a mean age and disease duration of 49.5 ± 14.4 and 15.6 ± 12.8 years, respectively, were included in the analysis; 54.1% (n = 72) were male. The mean baseline disease-related outcomes were: BSA: 21.5 ± 15.8%, PASI: 13.7 ± 7.14, and DLQI: 12.0 ± 6.11. The most common conventional systemic therapies initiated at baseline were fumaric acid esters (n = 74, 55.6%), methotrexate (n = 46, 34,6%), and ciclosporin (n = 6, 4.5%). The ECP-TGs were achieved by 58 patients (43.6%) at month 6, 86 patients (64.7%) at month 12, and 97 patients (72.9%) at month 18. An optimized reduced logistic regression model identified the presence of onycholysis/nail dystrophy at two or more digits to be associated with failing to attain the ECP-TGs (OR 10.7, 95% CI 2.5-46.7, p = 0.002). CONCLUSION: Patients with onycholysis/nail dystrophy at two or more digits were identified as having a higher risk of not achieving ECP-TGs under conventional systemic therapy. The ECP-TGs from 2011 were attained by 43.6% of our patients 6 months after starting conventional systemic therapies. In the era of safe, fast, and efficacious Pso therapies, much higher treatment goals might be achieved during therapy. New treatment goals are only of use if patients and dermatologists strive to attain them.

A Case of Unexplained Long-Term Thumb Onycholysis Successfully Treated with Shimotsuto / 日本東洋医学雑誌

This report outlines the case of a 51-year-old female patient who had suffered from onycholysis of the thumbs for eight years. The patient complained of experiencing pain when she works in contact with water, affecting her quality of life. Before coming to our clinic, the patient was diagnosed and treated at three dermatology clinics. However, treatment proved ineffective and the cause was not elucidated. As the patient experienced symptoms of onycholysis and dry skin, we diagnosed her with ketsu deficiency and treated her with shimotsuto. The symptoms gradually improved with continuous oral administration, and were no longer present at eight months following the start of treatment. This case suggests that shimotsuto may be effective in treating instances of onycholysis where the cause is unknown.

Disappearing Nail Bed: Review of Etiology, Grading System, and Treatment Options.

Disappearing nail bed (DNB) is a condition characterized by irreversible epithelialization of the nail bed following long-standing onycholysis. This phenomenon can occur in fingernails and toenails. Factors implicated in the development of DNB include trauma, manicuring, and onychotillomania and dermatologic conditions like psoriasis and dermatitis. Specifically for the toenail, contributing factors also include increasing age, history of trauma, surgery, onychomycosis, and onychogryphosis. A grading system that stages the progression of onycholysis to DNB has been proposed to aid clinicians in the diagnosis and treatment of these conditions. Several methods have been designated for the treatment of DNB.