A survey of carboplatin desensitization therapy in Japan: A multicenter retrospective study.

INTRODUCTION: Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. METHODS: Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. RESULTS: This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre-existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620-18,282) mg, and the mean number of doses was 14 (4-63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. CONCLUSION: Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

Skin Manifestations of Micafungin Breakthrough Disseminated Trichosporonosis in Acute Megakaryoblastic Leukemia.

Disseminated trichosporonosis is a rare fungal infection whose risk factors are hematological malignancies and neutropenia. Recently, breakthrough Trichosporon infections after administration of micafungin, the first-line systemic antifungal agent in compromised hosts, have been widely recognized. A man in his seventies about 1 month into chemotherapy for acute megakaryoblastic leukemia presented with a worsening fever and dyspnea. The patient was being administered with empirical micafungin therapy for suspected candidiasis. As the symptoms progressed, scattered erythema appeared on the trunk, some with a dark red vesicle at the center. Blood cultures identified Trichosporon asahii, as did the specimen of the skin biopsy. On the basis also of the presence of pneumonia on chest computed tomography, we confirmed the diagnosis of disseminated trichosporonosis and changed the antifungal agent from micafungin to voriconazole. Blood culture turned out to be negative 1 month after administrating voriconazole. However, the patient died of the leukemia. Our review of previous reports on cutaneous manifestations of disseminated trichosporonosis revealed that despite their morphological diversity, erythema with a red papule or vesicle at the center, implying necrosis, was also observed in previous cases. Our case report suggests that dermatologists should be aware of skin manifestations of disseminated trichosporonosis after micafungin administration, especially in cases of hematological malignancies.

Effects of Curcumin on the treatment of oral lichen planus symptoms: a systematic review and meta-analysis study.

BACKGROUND AND OBJECTIVES: Oral lichen planus (OLP) is a relatively common chronic T-cell-mediated disease that can cause significant pain, particularly in its erosive or ulcerative forms. This study aimed to examine the therapeutic impact of curcumin on symptoms of OLP. MATERIALS AND METHODS: This meta-analysis was performed according to the PRISMA guidelines. All related English documents indexed in electronic databases (including PubMed, Web of Science, Scopus, Embase, Wiley, Cochrane, and ProQuest databases [updated to August 15, 2023]) were retrieved. Data were double-extracted into a predefined worksheet, and quality analysis was performed using the Joanna Briggs Institute (JBI) scale. We carried out meta-analyses, and the random effects model was used to estimate the differences in erythema, lesion size, and pain between the curcumin control groups. RESULTS: The search identified 289 studies, of which 10 were found to meet the inclusion criteria. The overall findings of the meta-analysis revealed that curcumin did not have a significant effect on erythema of OLP (standardized mean difference [SMD] = -0.14; 95% CI, -0.68 to 0.40; P = 0.61; I2 = 57.50%), lesion size of OLP (SMD = -0.15; 95% CI, -0.45 to 0.15; P = 0.33; I2 = 28.42%), and pain of OLP (SMD = -0.38; 95% CI, -0.97 to 0.22; P = 0.22; I2 = 86.60%). However, subgroup analysis based on treatment duration indicated that 2-week treatment duration was significantly associated with a reduction in OLP pain (n = 3; SMD = -1.21; 95% CI, -2.19 to -0.23; P = 0.01). CONCLUSIONS: Curcumin had no significant effect on erythema, lesion size, and pain of OLP compared to the control groups. However, subgroup analysis revealed that curcumin was more effective in reducing pain in non-randomized trials and in trials with a treatment duration of 2 weeks.

Clinical characteristics of the well-defined upper eyelid vascular network pattern in patients with rosacea.

BACKGROUND: Rosacea is a chronic inflammatory skin disease. The diagnosis is based on the symptoms and physical signs, which still lacks objective laboratory tests or imaging tests. OBJECTIVES: To propose and evaluate the upper eyelid network pattern in rosacea. METHODS: Participants included patients diagnosed with rosacea, other facial erythematous skin diseases, and normal controls, all of whom underwent full-face imaging utilizing the VISIA® system software. According to these images, researchers evaluated the condition of the upper eyelid vascular network, developed the grading scale and then compared the difference of distribution in the three groups. RESULTS: The occurrence rate of upper eyelid vascular network in rosacea was significantly higher than that in other facial erythematous skin diseases (84.3 vs. 32.0%, P < 0.001) and normal controls (84.3 vs. 28.0%, P < 0.001). The upper eyelid vascular network pattern was proposed (none [no clearly reticular vessels], mild [10-50% area of reticular vessels], moderate-to-severe [>50% area of reticular vessels]). Moderate-to-severe grade was defined as well-defined upper eyelid vascular network pattern, which was specific to patients with rosacea (rosacea vs. other facial erythematous skin diseases, adjusted odds ratio [aOR] = 5.814, 95% confidence interval [CI]: 3.899-8.670) (rosacea vs. heathy controls, aOR = 12.628, 95% CI: 8.334-19.112). The severity of the well-defined pattern had no significant association with age, duration, and phenotypes of rosacea (P > 0.05). CONCLUSION: The well-defined upper eyelid vascular network pattern specifically appeared in patients with rosacea, which could be a possible clue to the diagnosis of rosacea.

[Systemic lupus erythematosus associated macrophage activation syndrome with neuropsychiatric symptoms: A report of 2 cases].

Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.

Lotilaner Ophthalmic Solution 0.25% for Demodex Blepharitis: Randomized, Vehicle-Controlled, Multicenter, Phase 3 Trial (Saturn-2).

PURPOSE: To evaluate the safety and efficacy of lotilaner ophthalmic solution 0.25% compared with vehicle for the treatment of Demodex blepharitis. DESIGN: Prospective, randomized, double-masked, vehicle-controlled, multicenter, phase 3 clinical trial. PARTICIPANTS: Four hundred twelve patients with Demodex blepharitis were assigned randomly in a 1:1 ratio to receive either lotilaner ophthalmic solution 0.25% (study group) or vehicle without lotilaner (control group). METHODS: Patients with Demodex blepharitis treated at 21 United States clinical sites were assigned either to the study group (n = 203) to receive lotilaner ophthalmic solution 0.25% or to the control group (n = 209) to receive vehicle without lotilaner bilaterally twice daily for 6 weeks. Collarettes and erythema were graded for each eyelid at screening and at all visits after baseline. At screening and on days 15, 22, and 43, 4 or more eyelashes were epilated from each eye, and the number of Demodex mites present on the lashes was counted with a microscope. Mite density was calculated as the number of mites per lash. MAIN OUTCOME MEASURES: Outcome measures included collarette cure (collarette grade 0), clinically meaningful collarette reduction to 10 collarettes or fewer (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes as well as erythema), compliance with the drop regimen, drop comfort, and adverse events. RESULTS: At day 43, the study group achieved a statistically significant (P < 0.0001) higher proportion of patients with collarette cure (56.0% vs. 12.5%), clinically meaningful collarette reduction to 10 collarettes or fewer (89.1% vs. 33.0%), mite eradication (51.8% vs. 14.6%), erythema cure (31.1% vs. 9.0%), and composite cure (19.2% vs. 4.0%) than the control group. High compliance with the drop regimen (mean ± standard deviation, 98.7 ± 5.3%) in the study group was observed, and 90.7% of patients found the drops to be neutral to very comfortable. CONCLUSIONS: Twice-daily treatment with lotilaner ophthalmic solution 0.25% for 6 weeks generally was safe and well tolerated and met the primary end point and all secondary end points for the treatment of Demodex blepharitis compared with vehicle control. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Epidemiological profile of rosacea in dermatology outpatient clinics in Brazil: an observational report from the Brazilian study group on rosacea.

BACKGROUND: Rosacea prevalence varies worldwide and there is a lack of information in Brazil. OBJECTIVES: To describe the epidemiological profile of rosacea in subjects who consulted in dermatological outpatient clinics in Brazil. MATERIALS & METHODS: A cross-sectional study was conducted in 13 dermatological outpatient clinics across the country. Patients with rosacea diagnosis were eligible for the study according to the investigator's clinical assessment. Clinical, social and demographic data were collected. The overall and regional rosacea prevalence was calculated, and association with baseline characteristics was analysed. RESULTS: A total of 3,184 subjects were enrolled, and rosacea prevalence was 12.7%. The southern region of Brazil presented a higher prevalence, followed by the southeast. The subjects in the rosacea group were older than those without rosacea (52.5 ±14.9 vs. 47.5 ±17.5; p<0.001). Moreover, the rosacea group was associated with Fitzpatrick's phototypes I and II, Caucasian ethnicity, a family history of rosacea, and facial erythema, however, no association with gender was found. The most prevalent clinical sign and clinical subtype in rosacea patients were erythema and erythematotelangiectatic, respectively. CONCLUSION: Rosacea is highly prevalent in Brazil, mostly in the southern region, associated with phototypes I and II and a family history.

Treatment of Periorbital Vascularity, Erythema, and Hyperpigmentation.

Periorbital hyperpigmentation (POH) is a common aesthetic concern that impacts patients' emotional well-being and quality of life. POH can be difficult to manage as the etiology is often multifactorial or difficult to elucidate. An understanding of different contributing factors and ability to classify hyperpigmentation can aid in the management of POH. Classification of POH is divided into pigmented, vascular, structural, and mixed subtypes. A wide array of treatment options has been proposed belying the challenges inherent to improving POH. Modalities vary from topical therapies, chemical peels, dermal fillers, and lasers, to surgical intervention. Because POH can be multifactorial, successful management of POH will depend on elucidating the etiology and often requires a combination of therapies.

The safety of intravenous peripheral administration of 3% hypertonic saline: A systematic review and meta-analysis.

BACKGROUND: Three percent hypertonic saline (3% HTS) is used to treat several critical conditions such as severe and symptomatic hyponatremia and increased intracranial pressure. It has been traditionally administered through a central venous catheter (CVC). The avoidance of peripheral intravenous infusion of 3% HTS stems theoretically from the concern about the ability of the peripheral veins to tolerate hyperosmolar infusions. The aim of this systematic review and meta-analysis is to assess the rate of complications associated with the infusion of 3% HTS using peripheral intravenous access. METHODS: We conducted a systematic review and meta-analysis to assess the rate of complications related to the peripheral infusion of 3% HTS. We searched several databases for available studies that met the criteria until February 24th, 2022. We included ten studies conducted across three countries examining the incidence of infiltration, phlebitis, venous thrombosis, erythema, and edema. The overall event rate was calculated and transformed using the Freeman-Tukey arcsine method and pooled using the DerSimonian and Laird random-effects model. I2 was used to evaluate heterogeneity. Selected items from Newcastle-Ottawa Scale2 were used to assess the risk of bias in each included study. RESULTS: A total of 1200 patients were reported to have received peripheral infusion of 3% HTS. The analysis showed that peripherally administered 3% HTS has a low rate of complications. The overall incidence of each of the complications was as follows: infiltration 3.3%, (95% C.I. = 1.8-5.1%), phlebitis 6.2% (95% C.I. = 1.1-14.3%), erythema 2.3% (95% C.I. = 0.3-5.4%), edema 1.8% (95% C.I. = 0.0-6.2%), and venous thrombosis 1% (95% C.I. = 0.0-4.8%). There was one incident of venous thrombosis preceded by infiltration resulting from peripheral infusion of 3% HTS. CONCLUSIONS: Peripheral administration of 3% HTS is considered a safe and possibly preferred option as it carries a low risk of complications and is a less invasive procedure compared to CVC.

Erythromelalgia in a patient with feet erythema and cyanosis.

Erythromelalgia is a rare disease characterised by a triad of a clinical syndrome of redness, warmth and painful extremities. We present the case of a male adolescent with no prior medical history who presents to our family medicine clinic with a 3-month history of bilateral feet erythema followed by episodes of cyanosis in bilateral toes. Given his history, the findings on clinical examination, and the lack of any pathology on the diagnostic testing, the patient is diagnosed with erythromelalgia. He is then counselled on both pharmacological and non-pharmacological treatments for his condition and is discharged on non-pharmacological treatment options such as leg elevation, cooling with a fan and limiting exposure to heat. The patient is also advised to perform an annual complete blood count given the association of erythromelalgia with myeloproliferative disorders.

Dual role of basophils in the pathogenesis of bullous pemphigoid elucidated by pathological and ultrastructural studies

Background: Bullous pemphigoid (BP), one of the most common autoimmune blistering disorders, is characterized by early erythematous and bullous lesions. Histopathologically, eosinophilia in the dermal tissue is a common finding in BP. In addition, basophils infiltrate the BP skin lesion. Although basophils are involved in the induction of type 2 immunity along with eosinophils, their role in both the erythema and blister, as well as the chronology of their involvement, have not been investigated. Objectives: To elucidate the role of basophils in BP development and resolution by performing early- and late-phase histopathological analysis of BP. Materials & Methods: A total of 25 patients with BP who underwent biopsy for both erythema and bullous lesions and were not taking oral steroids at the time of biopsy, were selected. Biopsy specimens of the erythematous (inflammatory) and bullous (resolution) phases were compared by histopathology, immunohistochemistry and electron microscopy. Results: During the early phase of BP, the number of basophils positively correlated with the number of eosinophils compared with other immune cells. In the late phase (bullous phase) of BP, the number of basophils significantly increased and more cell-cell contact between the basophils and M2 macrophages was noted, compared to the early phase Conclusions: Basophils are involved in the development of BP and its resolution, in part, via cell-cell contact with eosinophils or M2 macrophages, as demonstrated by pathological analysis.

Paclitaxel-induced diffuse scleroderma with possible scleroderma-renal crisis: a case report and literature review of taxanes-induced scleroderma.

INTRODUCTION/OBJECTIVES: Scleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and treatment outcomes were reviewed and summarized rarely. This study reported a patient who developed diffuse scleroderma and possible scleroderma renal crisis after paclitaxel therapy for ureter cancer. METHOD: A PubMed literature review on published cases of taxanes-induced scleroderma up until April 2022 was included for analysis. RESULTS: The search identified 27 patients with adequate information for analysis. Of the 28 patients, including the one presented here, 22 were female. Peripheral edema was the most common symptom in all but one patient, and often accompanied by erythema in 11. Symptoms usually occurred in half of the patients within the 4th course of treatment. Skin lesions gradually progressed to skin fibrosis, and extended proximally. Internal organ involvements were uncommon. Antinuclear antibody tests were positive occasionally, but anti-Scl70 and anti-centromere usually were negative. Taxanes therapy was discontinued, continued and unavailable in 21, 3, and 4 patients, respectively. Corticosteroids for skin lesions with or without immunosuppressive drugs were given to 15 patients. Of 25 patients with available skin outcomes, 19 improved. There was no significant skin improvement between those who did or did not receive skin treatment (62.5% vs. 75.0%, p = 0.37). Skin usually improved after discontinuing taxanes. CONCLUSION: Taxanes-induced scleroderma is different from idiopathic scleroderma. Physicians should be aware of this condition in order to provide early diagnosis and apply appropriate management in order to avoid serious complications from severe skin sclerosis. Key Points • Scleroderma is a rare but unique and serious complication of taxanes therapy • Skin manifestations and distribution are similar to idiopathic scleroderma, but vascular phenomenon, internal organ involvement and scleroderma-associated auto-antibodies are presented rarely. Skin improvement usually occurs shortly after discontinuing taxanes • The role of immunosuppressive therapy in treating taxanes-induced scleroderma is not clear.

Three cases of symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by proton-pump inhibitors.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), previously termed drug-related baboon syndrome, is an uncommon drug eruption. It is characterized by symmetrical erythema involving the gluteal and/or inguinal area in association with one other intertriginous area in the absence of systemic involvement. It typically develops a few hours to days after drug exposure. The diagnosis is based on clinical presentation and drug history. The treatment consists mainly of withdrawal of the causative agent; corticosteroids (topical or systemic) are prescribed to accelerate the resolution. We present three cases that appeared after proton-pump inhibitors (PPIs) intake.

Flagellate dermatitis in bleomycin chemotherapy: a causality?

Flagellate dermatitis is a relatively rare reaction to toxicity. It appears as skin lesions with erythematous patches or papules of linear, multiple, flagellate structures. Flagellate dermatitis can be triggered by several causes, which are most commonly associated with bleomycin. This paper reports two cases of flagellate dermatitis, one in a patient with germ cell carcinoma and another in a patient with osteosarcoma who were both diagnosed with flagellate dermatitis after the administration of bleomycin.

The factors related to recovery time of diaper dermatitis in infants: A prospective observational study.

AIM: Prolonged diaper dermatitis may increase the risk of atopic dermatitis or infections. This prospective observational study aimed to investigate the prevalence, symptoms, areas, and recovery time of diaper dermatitis in infants aged 1 month and identify the factors related to recovery time. METHODS: Diaper dermatitis was defined as the presence of erythema, papules, dryness, erosion, or ulceration in the diapered area. Recovery time was days between infant's 1-month medical check-up and disappearance of symptoms. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to identify the factors related to recovery time. RESULTS: Among 113 infants, 66 (58.4%) had diaper dermatitis, with erythema at the perianal area being the most common symptom. The median recovery time was 10 days. Four infants (6.1%) had diaper dermatitis for >5 weeks. Severity was not related to recovery time. CONCLUSIONS: A frequency of diaper changing of ≤10 times per day was a risk factor for recovery time. Our data showed recovery in approximately 10 days, regardless of severity at study enrollment. Health care professionals could inform parents of recovery time and recommended diaper changing frequency.