Allergic Contact Dermatitis to Topical Preparations Containing Minoxidil: A Systematic Review and Individual Participant Data Meta-Analysis.

Topical minoxidil is generally well tolerated, yet there have been a few reports of allergic contact dermatitis (ACD) confirmed through patch testing. This systematic review and individual participant data meta-analysis sought to elucidate the primary allergens in patients exhibiting ACD in response to topical minoxidil formulations and to ascertain the appropriate testing concentrations and vehicles of minoxidil itself. A comprehensive search was conducted across the PubMed, Scopus, and Embase databases utilizing the keywords "minoxidil" and "contact dermatitis," or "contact allergy," or "contact eczema." Studies documenting ACD in patients using topical minoxidil confirmed by patch testing were deemed eligible. Our analysis included 46 studies encompassing 99 patients with patch-test-confirmed ACD to minoxidil-based topical treatments. The majority of these patients (93.9%) were exposed to minoxidil without additional active components. Minoxidil itself was identified as the primary allergen in 74.7% of the patients, with propylene glycol being the next most common allergen at 17.1%. Other allergens identified included estradiol, butylene glycol, methylchloroisothiazolinone/methylisothiazolinone, canrenone, and latanoprost. The most effective concentration was found to be 2% minoxidil in propylene glycol, which yielded a 100% positivity rate. The findings indicate that minoxidil is the predominant allergen in ACD reactions to its topical formulations, followed by propylene glycol. For the accurate diagnosis of ACD related to minoxidil, patch testing with 2% minoxidil in propylene glycol is recommended, as are separate tests for propylene glycol and other potential allergenic ingredients.

In Vitro Antifungal Activity of Plain Socks and Zinc Oxide Nanoparticle-Coated Socks.

BACKGROUND: Fungal foot infection is a common superficial fungal infection and is recognized as an important public health problem. Related to the wearing of occlusive footwear, foot infection is usually caused by dermatophytes and nondermatophyte molds. Previous in vitro studies have demonstrated that zinc oxide nanoparticles (ZnO-NPs) have antimicrobial activity against fungi. This study, therefore, evaluated the ability of socks coated with ZnO-NPs to inhibit fungal growth in an in vitro model mimicking real-life situations. METHODS: Scale from patients with fungal foot infections was equally divided into three groups: control, plain socks, and ZnO-NP socks. The specimens in the control group were routinely fungal cultured, whereas in the plain sock and ZnO-NP sock groups, scale was incubated with plain socks and ZnO-NP socks, respectively, for 24 hours. After incubation, each piece of sock was cultured. The fungal culture results of the three groups were progressively evaluated for 4 weeks. RESULTS: From 31 specimens, the positive fungal culture results of the control, plain sock, and ZnO-NP sock groups were 100%, 64.5%, and 54.8%, respectively. Specimens incubated with plain socks (P = .001) or with ZnO-NP socks (P < .001) had a significant reduction in the number of positive fungal cultures compared with the control. CONCLUSIONS: Plain socks and ZnO-NP socks significantly inhibited fungal growth relative to the control. The wearing of either plain socks or ZnO-NP socks can prevent fungal foot infection because these socks act as a barrier to the insoles of shoes.

Onychomycosis in older adults: The age and associated factors affecting the complete cure rate.

BACKGROUND: Limited studies exist on the factors associated with a complete cure of onychomycosis in older adults. OBJECTIVES: To determine the age and factors associated with a complete cure among older adults diagnosed with toenail onychomycosis. METHODS: A retrospective cohort study was conducted of 95 older adult patients (aged ≥ 60 years) diagnosed with toenail onychomycosis between January 2016 and December 2017. Demographic data, mycological findings, treatments and durations to a complete cure were reviewed. RESULTS: The complete cure rates of the patients aged < 70 years and ≥70 years were 67.4% and 44.9%, respectively (P = 0.027). Patients aged ≥ 70 years were significantly higher in male gender, had higher history of smoking, peripheral arterial disease, impaired renal function, antihypertensive drug and amorolfine nail lacquer usage, and polypharmacy. A multivariate analysis revealed that being aged ≥70 years and having a nail thickness >2 mm were associated with failure to achieve a complete cure. The median times to a complete cure for older adults aged <70 years and ≥70 years were 20 months and 47 months, respectively (P = 0.007). CONCLUSIONS: An age ≥ 70 years was related to a lower cure rate and delays in achieving a complete cure. A nail thickness > 2 mm was a poor prognostic factor for a complete cure. Moreover, very old adults were more likely to suffer side effects arising from the use of systemic antifungal medications.

Effectiveness and safety of topical amphotericin B in 30% dimethyl sulfoxide cream versus 30% dimethyl sulfoxide cream for nondermatophyte onychomycosis treatment: A pilot study.

Background Although topical amphotericin B cream is effective for the treatment of nondermatophyte mold onychomycosis in vitro, studies of its effectiveness and safety in vivo are limited. Objectives We studied the effectiveness and safety of topical 0.3% amphotericin B in 30% dimethyl sulfoxide cream (amphotericin B cream) in nondermatophyte mold onychomycosis using the vehicle cream 30% dimethyl sulfoxide cream as control. Methods This randomized controlled study was conducted between January 2019 and November 2020. Patients diagnosed with nondermatophyte mold onychomycosis were randomly divided into two groups of ten patients each: one treated with amphotericin B cream and the other with the vehicle cream. Clinical and mycological cure as well as safety were evaluated. Results Ten patients each treated with amphotericin B cream and the vehicle cream were included in the study, but only nine patients in the vehicle cream group were available for follow up. All the 19 evaluable patients had distal lateral subungual onychomycosis and the great toenails were affected in 18 (94.7%) of these. Mycological cure was achieved in 8 (80%) patients treated with amphotericin B cream and in 4 (44.4%) patients using the control (vehicle) cream. Clinical cure was achieved in 7 (70%) patients treated with amphotericin B cream, but only in 2 (22.2%) patients on the control cream. No adverse events were observed. Limitations The small sample size and the fact that PCR fungal identification that provides accurate identification of fungal species was not performed are limitations of our study. Conclusion Topical amphotericin B cream was both very effective and safe in the treatment nondermatophyte mold onychomycosis. The control (vehicle) cream containing 30% dimethyl sulfoxide also demonstrated some antifungal activity.

Sulphur Nuggets.

BACKGROUND: Dermoscopy is a new method to diagnose and manage nail disorders. The definite dermoscopic finding for onychomycosis, however, is still debatable. OBJECTIVE: To identify the dermoscopic features that help differentiate between onychomycosis (OM) and traumatic onychodystrophy (TOD). METHODS: A prospective study of 65 patients with toenail abnormalities was conducted. The patients were classified into OM and TOD groups using mycological tests (potassium hydroxide test, fungal culture, and histological examination). OM was diagnosed from positive results for all tests, while TOD was decided based on negative results for all tests and evidence of foot trauma. Dermoscopic features were recorded and compared between the two groups. RESULTS: Most patients of the 65 patients were female (72.3%), and had a mean age of 67.9 years. Twenty-seven patients (41.5%) were diagnosed with OM, all of which were distal and lateral subungual onychomycosis. TOD, on the other hand, was determined in 38 patients. Dermoscopic findings revealed that the yellow, clumping, sulphur-nugget-like debris in the ruin appearance was significantly associated with onychomycosis (p = 0.002), while ruin appearance without sulphur nugget was not statistically correlated with onychomycosis (p = 0.068). CONCLUSION: The presence of sulphur nuggets in the ruin appearance is a new and helpful dermoscopic feature for onychomycosis diagnosis.

Effectiveness and safety of zinc oxide nanoparticle-coated socks compared to uncoated socks for the prevention of pitted keratolysis: a double-blinded, randomized, controlled trial study.

BACKGROUND: Pitted keratolysis (PK) and bromodosis have negative impacts on the quality of life especially for military personnel. The antibacterial efficacy and safety of zinc oxide nanoparticles (ZnO-NPs) make them a suitable additive for textiles. We aim to establish the ability of ZnO-NP-coated socks to prevent PK and bromodosis in a real-life setting. MATERIALS AND METHODS: A double-blinded, randomized, controlled trial was conducted in January 2019. Naval cadets assigned to a 14-day field training course were randomly allocated to either a ZnO-NP-coated or an uncoated-sock group. They completed questionnaires evaluating behavioral risk factors and self-assessed foot odor levels using a visual analogue scale (VAS); intervention-blinded dermatologists also performed foot examinations. They reassessed their odor levels and had their feet re-examined upon completion of the training course. RESULTS: The 148 cadets enrolled for the study were allocated to two groups of 74 each. The ZnO-NP-coated sock participants demonstrated significantly less PK development than uncoated socks (P = 0.05). There was a reduction of the foot odor levels in both groups, as measured by the VAS, without statistical difference. However, the uncoated sock group experienced more foot odor with a significantly greater negative effect on their daily lives (P = 0.04) than the ZnO-NP-coated sock group. CONCLUSIONS: ZnO-NP-coated socks proved their efficacy in inhibiting the development of PK for military personnel.

Randomized, controlled trial testing the effectiveness and safety of 2.5% and 5% benzoyl peroxide for the treatment of pitted keratolysis.

BACKGROUND: The appropriate dosage and duration of topical benzoyl peroxide gel (BP) treatment of pitted keratolysis (PK) is controversial. OBJECTIVE: To compare the effectiveness and safety of topical 2.5% and 5% BP for the treatment of PK. MATERIALS AND METHODS: This randomized, controlled trial was conducted at Chumpol Naval Rating School, Chonburi, Thailand. Naval rating cadets with PK were randomly assigned to either a 2.5% or a 5% BP group and were requested to apply the related medication on each sole once daily, for 2 weeks. RESULTS: All 42 and 47 participants who were treated with 2.5% and 5% BP, respectively, were included in the later analysis. Self-evaluation of the foot odor level using a visual analog scale (VAS) showed significant decreases for both groups (p<.001). The pitted lesions were evaluated by dermatologists and found to have improved in the 2.5% and 5% BP groups (69.0% versus 63.8%, respectively; p=.457). Side effects did not statistically differ between the two groups (p>.05). CONCLUSIONS: Either 2.5% or 5% BP can be used for the treatment of PK and foot malodor. Due to the similarities in their efficacies and side effects, the use of 2.5% BP may be preferable.

Vibratory Angioedema Subgroups, Features, and Treatment: Results of a Systematic Review.

BACKGROUND: Vibratory angioedema (VA) is a subtype of chronic inducible urticaria that manifests with erythematous wheals or angioedema after skin exposure to vibration. Because the condition is rare, the available information is limited. OBJECTIVE: To systematically review the clinical manifestations and treatment options of VA. METHODS: Relevant literature published until August 2020 was searched using the terms "vibratory urticaria," "vibratory angioedema," "vibratory-induced angioedema," and "vibratory-induced urticaria." Preferred Reporting Items for Systematic Reviews and Meta-analysis recommendations were applied to this systematic review. RESULTS: On the basis of review of 22 studies (16 case reports, 4 case series, and 2 cohort studies) that had a combined total of 83 patients, we propose that VA be classified as hereditary VA (33.7%) and acquired VA (66.3%). Vibration-induced itching was frequent in both subgroups. Patients with hereditary VA more commonly had wheals and systemic symptoms, whereas patients with acquired VA more frequently had angioedema, burning, pain, or tingling. Although many VA treatments are used, there is little information on their efficacy. Most patients do not achieve complete control. CONCLUSIONS: The novel VA classification proposed could help clinicians with the diagnostic workup of patients with VA. Because of the paucity of reported cases, firm recommendations for the treatment of VA are currently not possible. For patients with acquired VA, we suggest second-generation H1-antihistamines as the first-line treatment. Controlled therapeutic trials are needed and should be performed.

Symptomatic Dermographism: A Systematic Review of Treatment Options.

BACKGROUND: Symptomatic dermographism (SD), the most common form of chronic inducible urticaria, presents with transient wheals accompanied by itching in response to scratching. Little is known about available treatment options and their efficacy in SD. OBJECTIVE: To systematically review the efficacy of treatment options for patients with SD. METHODS: Using predefined search terms, we searched for relevant literature published until September 2019. The systematic review process was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. RESULTS: The 23 studies identified included 15 randomized controlled trials; 22 and 17 assessed treatment responses in patients with SD by provocation/threshold testing and patient/physician clinical assessment, respectively. Thirteen different treatments were investigated in a total of 430 adult patients. The most frequently studied therapy, first-generation H1-antihistamines, showed variable efficacy and significant side effects. In contrast, second-generation H1-antihistamines (2ndAH1), in all studies, were effective and well tolerated. Monotherapy with an H2-antihistamine (AH2) was not effective, whereas adding an AH2 increased the efficacy of treatment with an H1-antihistamine (AH1). SD improved with omalizumab. All other treatments were only investigated in small, unrepeated, and/or uncontrolled studies. There are no studies on updosing of 2ndAH1. CONCLUSIONS: The available SD studies are heterogeneous, mostly monocentric, old, small, and unrepeated, pointing to a high need for more and better studies. We suggest that 2ndAH1 should be the first-line treatment. In uncontrolled cases, the combination of AH1 and AH2 may be tried. Even though there is no evidence of its efficacy over standard dosage, updosing of 2ndAH1 may be considered based on the extrapolation of evidence from chronic spontaneous urticaria; omalizumab should be added in recalcitrant patients.

Randomized controlled trial comparing long-pulsed 1064-Nm neodymium: Yttrium-aluminum-garnet laser alone, topical amorolfine nail lacquer alone, and a combination for nondermatophyte onychomycosis treatment.

BACKGROUND: Studies of the laser treatment of nondermatophyte mold (NDM) onychomycosis are limited. Long-pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) 1064-nm laser has been introduced as an adjuvant dermatophyte onychomycosis treatment. AIMS: To investigate the efficacy and safety of long-pulsed Nd:YAG 1064-nm laser for NDM onychomycosis treatment, compared with topical amorolfine nail lacquer alone and a combination treatment. PATIENTS/METHODS: This randomized controlled trial was conducted at the Nail Clinic, Siriraj Hospital. Patients diagnosed with NDM were included and randomly assigned to three treatment groups: laser at 1 month interval (1064-nm Nd:YAG at a fluence of 35 J/cm2 , pulse width 30 ms, and pulse rate 1.0 Hz); topical amorolfine nail lacquer alone; and a combination treatment. RESULTS: Sixty patients completed the study. The patients treated with the laser, amorolfine, and the combination achieved mycological cure rates of 35%, 60%, and 65%, respectively (P = .05), while 10%, 30%, and 30% of the patients in the respective groups were clinically cured. The mean durations to the mycological cures in the patients treated with laser, amorolfine, and the combination were 5.9, 4.8, and 5.2 months, respectively. By comparison, the corresponding mean durations to the clinical cures were 6.9, 6.5, and 5.9 months. Both the times to the mycological cures and the clinical cures did not differ significantly between the groups (P = .290 and P = .309, respectively). There were no serious complications with the laser treatment. CONCLUSIONS: Laser alone achieved only a 30% mycological cure rate for NDM onychomycosis. The combination treatment yielded similar outcomes to the topical treatment alone.

Cold Urticaria: Clinical Features and Natural Course in a Tropical Country.

PURPOSE: To review the clinical features and natural courses of cold urticaria (ColdU) in a tropical country. METHODS: A retrospective chart review was performed of patients who visited Siriraj Urticaria Clinic, Siriraj Hospital, Bangkok, Thailand, and were diagnosed with ColdU between 2007 and 2018. Data on provocation and threshold tests, clinical courses, and laboratory work-up were analyzed and compared with data reported by studies in temperate countries. RESULTS: Of 1,063 chronic urticaria patients, 27 (2.5%) were diagnosed with ColdU, with a mean age of symptom onset of 34.8 years. Half of the patients had a history of atopy, and 1 (3.7%) had a history of anaphylaxis. All patients were positive to 1 of 3 provocation tests: an ice cube test; TempTest 4.0; or a tray filled with ice, salt and water. Thirteen patients underwent the ice cube test, and all had positive results. TempTest was performed on 15 patients, 8 of whom had positive results, with a mean critical temperature threshold (CTT) of 21.0°C. All of the 7 patients who had a negative TempTest result later produced positive results to the immersion of their hand and forearm in a tray filled with ice, salt, and water. All patients were treated with H1-antihistamines, the vast majority (96.3%) being non-sedating H1-antihistamines. Some (14.8%) needed to be administered oral corticosteroids, ciclosporin, or omalizumab. Six patients (22.2%) were in remission. A Kaplan-Meier survival curve demonstrated 5-year and 10-year remission rates of 13.8% and 42.6%, respectively. CONCLUSIONS: The rate of anaphylaxis in patients with ColdU in a tropical country was lower than those reported by other studies conducted intemperate climates. On the other hand, the number of female patients, mean age at symptom onset, atopy rate, rate of concomitant chronic spontaneous urticaria and mean CTT were higher.