Exploring Remission Dynamics and Prognostic Factors in Lichen Planopilaris: a Retrospective Cohort Study.

INTRODUCTION: Lichen planopilaris (LPP) is a common type of primary cicatricial alopecia. Previous studies focused on the epidemiology, clinical characteristics, and treatment of LPP. A lack of knowledge regarding LPP outcomes and prognostic factors remained. METHODS: To delineate the rate and timing of remission in LPP, as well as the prognostic factors for achieving remission, a retrospective cohort study was conducted. The study included 126 patients, from a single tertiary center, diagnosed with LPP between January 2010 and December 2022, who were followed up for a minimum of 6 months. RESULTS: There were 89 (70.6%) women and 37 (29.4 %) men included in this study. The mean age of the patients was 47.92±14.2 years. The mean time from disease onset to diagnosis was 33.85 (±30) months, indicating significant diagnostic delays. The mean duration of follow-up was 34.13±22.7 months. Among the cohort, 43 patients achieved complete remission (CR) during the follow-up period, whereas 83 patients did not. Of the 83 patients who did not achieve CR, 35 partially improved and 48 did not improve or worsened. The median time for achieving CR was 46±18.8 months. Milder disease at presentation and comorbid lichen planus were associated with higher CR rates. CONCLUSION: This study demonstrates significant diagnostic delays that should be addressed as LPP causes irreversible alopecia, suggests disease severity and comorbid lichen planus as potential prognostic factors. Further, it emphasizes the limited efficacy of current treatments and the need for prolonged treatment in patients with LPP to achieve remission.

Tuftsin-phosphorylcholine (TPC) equally effective to methylprednisolone in ameliorating lupus nephritis in a mice model.

The role of helminth treatment in autoimmune diseases is growing constantly. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with challenging treatment options. Tuftsin-phosphorylcholine (TPC) is a novel helminth-based compound that modulates the host immune network. This study was conducted to evaluate the potential value of TPC in ameliorating lupus nephritis in a murine model and specifically to compare the efficacy of TPC to the existing first-line therapy for SLE: corticosteroids (methylprednisolone). Lupus-prone NZBxW/F1 mice were treated with TPC (5 µg/mouse), methylprednisolone (MP; 5 mg/body weight) or phosphate-buffered saline (PBS) (control) three times per week once glomerulonephritis, defined as proteinuria of grade > 100 mg/dl, was established. Levels of anti-dsDNA autoantibodies were evaluated by enzyme-linked immunosorbent assay (ELISA), splenic cytokines were measured in vitro and the kidney microscopy was analysed following staining. TPC and MP treatments improved lupus nephritis significantly and prolonged survival in NZBxW/F1 mice. TPC-treated mice showed a significantly decreased level of proteinuria (P < 0·001) and anti-dsDNA antibodies (P < 0·001) compared to PBS-treated mice. Moreover, TPC and MP inhibited the production of the proinflammatory cytokines interferon IFN-γ, interleukin IL-1ß and IL-6 (P < 0·001) and enhanced expression of the anti-inflammatory cytokine IL-10 (P < 0·001). Finally, microscopy analysis of the kidneys demonstrated that TPC-treated mice maintained normal structure equally to MP-treated mice. These data indicate that the small molecule named TPC hinders lupus development in genetically lupus-prone mice equally to methylprednisolone in most of the cases. Hence, TCP may be employed as a therapeutic potential for lupus nephritis.

Dust mite induces multiple polar T cell axes in human skin.

BACKGROUND: House dust mite/HDM atopy patch test/APT elicits positive reactions in a high fraction of atopic dermatitis/AD and healthy individuals. Experimental systems for new-onset/chronic AD are needed to support rapid therapeutic development, particularly since animal models representing human AD are lacking. While HDM APT has been considered to simulate AD, its suitability to model AD's emerging Th2/Th22 phenotype with Th1 and Th17 components is unknown. OBJECTIVE: To assess whether HDM APT reproduces AD. METHODS: Positive HDM APTs (n = 15) from patients with and without AD were evaluated, using genomic and immunohistochemistry studies, against intrapersonal control skin. RESULTS: APT lesions showed higher T cell and dendritic cell infiltrates vs. CONTROLS: Seven hundred and forty-three up- and 326 downregulated genes were differentially expressed in HDM APT (fold change >2 and false discovery rate < 0.05), with increased expression of Th2, Th9, Th17/Th22 polar cytokines (i.e. IL-5, IL-13, IL-9, IL-17, IL-22). CONCLUSION: While HDM caused significant Th2 skewing, it also illustrated differences in Th2 induction and barrier defects; thus, HDM APT does not fully simulate AD. Given its widespread availability and sensitization rates, HDM may potentially be a useful tool that represents select aspects of AD, psoriasis, or contact dermatitis.

When is onychomycosis onychomycosis? A cross-sectional study of fungi in normal-appearing nails.

BACKGROUND: The presence of fungal organisms in healthy-looking toenails has previously been reported in individuals with a known dermatophyte infection and in those with onycholysis, but has not been extensively studied in individuals who do not present with foot pathology. OBJECTIVES: To determine the prevalence of fungal organisms in the toenails and on the soles of normal-appearing feet. METHODS: Adults who visited a dermatology clinic between June 2012 and February 2013 for concerns unrelated to fungal infection of the nails and feet participated in this study. Participants' feet were clinically examined, and skin and nail samples were collected and sent for potassium hydroxide (KOH) light microscopy and culture. RESULTS: Five hundred and eighty-five individuals with normal-appearing feet and toenails participated in this study. Fungal organisms were detected in 9·2%, 3·9% and 3·1% of participants' toenails by KOH, culture, and a combination of KOH and culture, respectively, while fungal organisms were present on the soles of the feet of 7·0%, 2·9% and 1·4% of participants by KOH, culture and both these methods combined, respectively. A significant association between the presence of fungal organisms in toenails and on the soles of the feet was found (P < 0·01). CONCLUSIONS: The presence of fungal organisms in the nail, even in the absence of clinical signs, may be termed 'subclinical' onychomycosis. The normal-appearing nail plate may act as a reservoir for infectious dermatophyte and nondermatophyte organisms. When left unimpeded by the host's immune system, these organisms are inclined to proliferate to produce clinically apparent disease.

Clinical comparison and complete cure rates of Terbinafine efficacy in affected onychomycotic toenails.

BACKGROUND: Clinical studies regarding complete cure rate of onychomycosis using oral Terbinafine have a very broad range (14-90%) based solely on response to treatment on the big toenail. OBJECTIVE: To evaluate the efficacy of Terbinafine in all affected onychomycotic toenails and, furthermore, to evaluate differences in mycological, clinical and complete cure rate between affected onychomycotic toenails. PATIENTS AND METHODS: Inclusion criteria are as follows: distolateralsubungual onychomycotic involvement of the hallux and additional involvement of at least two more toenails of the same foot. Exclusion criteria are as follows: patients with nail traumata and hypersensitivity to Terbinafine. Patients were treated with oral Terbinafine 250 mg/day for 16 weeks. Mycological analysis was performed using direct microscopy and culture. Clinical improvement was assessed using digital photography. RESULTS: Statistically significant difference was found in clinical improvement between the great toenail and all other involved toenails. The rate of complete cure (100% clinical cure and mycological cure) of the big toenail was lower (23%) as compared to the second (65%), third (51%) and the fourth toenail (67%). LIMITATIONS: This is a case series study that was based on a single-centre cohort. CONCLUSIONS: Our results support findings that efficacy of Terbinafine should be based on all involved onychomycotic toenails; the big toenail is not superior in response compared to other affected toenails.

A rationale for systemic treatment in onychomycosis with negative results on fungal examination.

BACKGROUND: Fungal infection of the nail affects millions of people worldwide, and has an estimated prevalence of about 10% of the general population. Laboratory confirmation of fungal infection is currently accepted as a requirement before initiation of antifungal treatment in clinical practice. AIM: To examine the rationale for systemic treatment in cases of clinical onychomycosis with negative results on fungal examination (potassium hydroxide test and fungal culture). METHODS: In total, 147 patients with suspected clinical toenail onychomycosis but with negative results on fungal examination underwent up to three consecutive fungal examinations of the affected nails. Patients who were negative after these examinations underwent a fourth set of investigations, including PCR. RESULTS: Of the 147 cases initially thought to be negative, 138 (94%) were rated as positive after up to four consecutive sets of laboratory mycological investigations including PCR. Trichophyton rubrum was by far the commonest dermatophyte cultured from all samples. CONCLUSIONS: In the majority of cases of initially negative examinations, consecutive laboratory fungal tests will eventually produce positive results. These findings suggest that systemic antifungal treatment should be started in patients with suspected fungal infections, even if they have negative laboratory fungal examinations.

Iontophoretic delivery of terbinafine in onychomycosis: a preliminary study.

Background Onychomycosis is a common disease; topical treatment is usually poorly effective, while systemic treatment is more effective but may be associated with side-effects. Iontophoretic drug delivery may improve drug penetration through the nail and lead to better therapeutic results. Objectives To evaluate the efficacy, safety and tolerability of topical treatments with terbinafine HCl delivered with or without an iontophoretic patch in patients with onychomycosis of the toenails. Methods Patients enrolled into the study were divided randomly into two groups. Group A was treated with terbinafine and an iontophoretic patch (at a constant current density of 100 microA cm(-2)). Group B was treated with terbinafine without iontophoresis. Treatment was overnight wear, every day, 5 days per week, for 4 weeks. Follow-up period was 8 weeks from the end of treatment. Results A significant clinical response was recorded in patients of group A (active group). The percentage of patients having healthy toenail growth of more than 1.5 mm at the end of treatment was 40% compared with 11% in patients treated with terbinafine without current (passive group). The percentage of patients having fungal elements (KOH) in nail specimens decreased significantly at 8 weeks following the completion of treatment: 16% in the active group vs. 53% in the passive group. Patients in the active group reported a tingling sensation that is expected when using an iontophoretic drug delivery treatment. Conclusions The delivery of terbinafine under an electrical current of 100 microA cm(-2) appears to be efficacious and safe and is well tolerated for the treatment of nail onychomycosis.

A study of serial vertical sectioning of scalp biopsies to increase the histological diagnostic yield in alopecias.

BACKGROUND: This study was performed to determine whether serial vertical sectioning of scalp biopsies increases the histological diagnostic yield in alopecias. MATERIALS AND METHODS: The study group included 100 consecutively referred patients with scalp alopecias. The formalin-fixed paraffin-embedded specimens of the scalp alopecias were completely serially sectioned in a vertical orientation and stained with haematoxylin and eosin. The histological diagnosis rendered in the initial slide harbouring three to six sections was compared with the diagnosis in the following vertical serial sections (30-116 serial sections per specimen, mean 53). RESULTS: A total of 55 scalp biopsies were classified histologically as non-cicatricial alopecia, 35 as cicatricial alopecia and 10 as 'others'. Diagnostic histological findings were present in the initial sections of 50 (50%) cases of alopecia, and only in the following serial sections in 48 (48%) cases. Two cases (2%) lacked differentiating diagnostic histological features in all of the vertical sections. The diagnostic yield of the serial vertical sections compared with the initial sections was higher in the non-cicatricial alopecias (52.7%) than in the cicatricial alopecias (48.5%) and the 'others' category (10%). CONCLUSIONS: Serial vertical sectioning of scalp alopecias increases the histological diagnostic yield, substantially.

A novel two-step kit for topical treatment of tinea pedis--an open study.

BACKGROUND: Tinea pedis is a common skin disease affecting most of the population during their lifetime. Topical and systemic treatments give only temporary relief. OBJECTIVE: To evaluate the efficacy and safety of a new topical treatment for moderate-to-severe tinea pedis. METHODS: Fifty patients suffering from tinea pedis were treated in two stages: the active stage--single use of the novel topical solution for 45 min and novel cream twice weekly for 4 weeks; the preventive stage--cream application once weekly for 10 months. RESULTS: Forty-five patients completed the active stage and achieved 76% cure rate. The medication was well tolerated; one patient dropped from the study because of very mild irritation. No other topical or systemic side effects were noted. Another five patients were lost to follow-up during the preventive stage. The total cure rate after the preventive stage was 70%. CONCLUSIONS: This novel treatment was found to be effective, well tolerated and safe in the treatment of moderate and severe tinea pedis during the active and the preventive stages.

Fetal Exposure to MR Imaging: Long-Term Neurodevelopmental Outcome.

BACKGROUND AND PURPOSE: Very few studies have investigated long-term neurodevelopment of children exposed to MR imaging antenatally. Thus, the purpose of our study was to evaluate long-term neurodevelopmental outcomes of children exposed to MR imaging during pregnancy. MATERIALS AND METHODS: We conducted a historical prospective cohort study in a single tertiary medical center. Women exposed to 1.5T noncontrast MR imaging for maternal or fetal indications were matched to unexposed controls. Long-term neurodevelopmental outcomes were evaluated of their children, 2.5 to 6 years of age, according to the Vineland-II Adaptive Behavior Scale. The Vineland-II Adaptive Behavior Scale assesses communication, daily living skills, socialization, and motor skills. A composite score summarizes these 4 domains. RESULTS: A total of 131 exposed women matched our inclusion criteria and were included in the study group, and 771 unexposed women, in the control group. No difference was identified in the Vineland-II Adaptive Behavior Scale composite score between the children of the study and control groups (mean, 110.79 versus 108.18; P = .098). Differences were also not observed between the children of the 2 groups in 3 of the 4 questionnaire domains: communication (108.84 versus 109.10; P = .888), daily living skills (109.51 versus 108.28; P = .437), and motor skills (105.09 versus 104.42; P = .642). However, the socialization score was favorable for the study group (112.98 versus 106.47; P < .001). CONCLUSIONS: Exposure to 1.5T noncontrast MR imaging during pregnancy had no harmful effects on long-term neurodevelopmental outcomes. This study contributes to understanding the safety of MR imaging during pregnancy.

New criteria for the laboratory diagnosis of nondermatophyte moulds in onychomycosis.

BACKGROUND: Nondermatophyte moulds (NDM) may be found as aetiological agents or as contaminants in onychomycosis. The classic and most used criteria for the diagnosis of NDM are those established by English in 1976. OBJECTIVES: The aim of this article is to re-evaluate the laboratory criteria for the diagnosis of NDM in onychomycosis. PATIENTS AND METHODS: Patients with suspected NDM of the nail underwent five consecutive examinations by both KOH and mycological culture; at the first visit, three samples from the affected nail were taken and were examined separately. Later those patients underwent four consecutive examinations; during this stage only a single sample for both KOH and culture was taken. We compared the culture results obtained from the three nail samples obtained at the first visit with the results from the four consecutive visits. RESULTS: We noted a clear trend showing that as the number of positive cultures increases (one to three cultures) during the first examination, the percentage of subsequent positive cultures, taken during the four consecutive visits, also increased. CONCLUSIONS: We suggest that when NDM infection is found in the first culture, the patient should be re-examined in a subsequent visit in which three separate samples are taken from the affected nail. If NDM is confirmed in all three cultures, the diagnosis of NDM is established. Treatment should be recommended in patients who show positive results in all three cultures.

Toenail abnormalities and onychomycosis in chronic venous insufficiency of the legs: should we treat?

BACKGROUND: Toenail manifestations of chronic venous insufficiency (CVI) may often mimic the nail changes of onychomycosis. The current study aims to determine the frequency of toenails deformations in patients with CVI, onychomycosis prevalence among deformed toenails and the outcome of itraconazole treatment. METHODS: Patients with clinical evidence of (CVI) were enrolled. All patients with toenails deformations and proven onychomycosis were treated by itraconazole pulse therapy for 4 months and then followed-up for additional 5 to 6 months. RESULTS: Forty-four patients with CVI entered the study. Thirty-seven patients (84%) had nail deformations; 28 of 37 patients (75%) had onychomycosis; and 24 patients completed the follow-up period. Total cure was achieved in 6 of 24 patients (25%), and 14 patients (58%) had no improvement. Patients' age and CVI duration were significantly correlated to onychomycosis cure rate. CONCLUSIONS: Nail deformations are more prevalent in CVI patients (84%) then in the general elderly population, and 75% of affected nails had also onychomycosis. In these patients, itraconazole achieved only 25% total cure rate compared with the 60% to 70% cure rate commonly cited in the literature, probably due to irreversible nail deformity caused by the CVI and due to the thickened nail that prevented penetrance of itraconazole into the nail plate. Therefore, before antifungal treatment is started for onychomycosis in patients with CVI, especially in older patients, the caregiver must stress out that the final outcome might not be as desirable as in pure onychomycosis patients.

Collection of fungi samples from nails: comparative study of curettage and drilling techniques.

BACKGROUND: Onychomycosis is a common problem. Obtaining a positive laboratory test before treatment is important in clinical practice because the treatment of onychomycosis requires expensive oral antifungal therapy with potentially serious side-effects. OBJECTIVE: The purpose of this study was to compare curettage and subungual drilling techniques of nail sampling in the diagnosis of onychomycosis. METHODS: We evaluated 194 patients suffering from distal and lateral subungual onychomycosis and lateral subungual onychomycosis using curettage and subungual drilling sampling techniques. Nail samples were obtained in each case from proximal, medial and distal parts of the nail. KOH examination and fungal culture were used for detection and identification of fungal infection. RESULTS: With each technique, the culture sensitivity improved as the location of the sample was more proximal (drilling proximal vs. distal, chi(2) = 5.15, P = 0.023; curettage proximal vs. distal, chi(2) = 4.2, P = 0.041). In each sample location, the drilling technique has a better culture sensitivity (drilling vs. curettage proximal, chi(2) = 11.9, P = 0.001; drill vs. curettage distal, chi(2) = 13.7, P < 0.0001). Trichophyton rubrum was by far the most common pathogen detected by both techniques from all sampling sites. CONCLUSION: The drilling technique was found to be statistically better than curettage at each site of sampling. With each technique, we found that the culture sensitivity improved as the location of the sample was more proximal. More types of pathogens were detected in samples taken by both methods from proximal parts of the affected nails.

Onycomycosis due to artificial nails.

BACKGROUND: The use of artificial nails (ANs) as part of nail-care cosmetics is very popular. Several side effects and complications, such as contact dermatitis and bacterial and fungal infections, have been reported in patients using ANs. Objective The purpose of this study was to identify the fungal pathogens in nail abnormalities appearing in patients with ANs. METHODS: We evaluated 68 patients suffering from nail changes and paronychia, which appear after removal of ANs. Mycological samples were obtained from two sites: distal parts of the involved nail and the proximal nail fold. KOH examination and fungal culture were used for detection and identification of fungal infection. RESULTS: Mycological results from the distal part of the nail showed positive KOH test in 57 cases (83.8%), and culture was positive in 67 patients (98.5%). Mycological results obtained from the proximal nail fold showed positive KOH test in 36 patients (52.9%); in 36 of the cases, culture was positive. Candida spp. were the most common pathogen. Both KOH and culture results were significantly better while sampling from the distal part of the nail compared with sampling from the proximal nail fold (P = 0.0001). CONCLUSION: Onychomycosis was found to be very common in nail changes due to ANs, leading to an increased risk of transmitting microbial infections. Therefore, health care personnel and workers in the food industry should avoid using ANs.

An open comparative study of nail drilling as adjunctive treatment for toenail onychomycosis (.).

Introduction Novel treatment regimens are being developed to improve drug penetration through the nail plate. This study investigated the efficacy of nail drilling regimens for the treatment of onychomycosis. Methods Participants were assigned to holes with combination (oral plus topical terbinafine) therapy (Group 1), holes with topical terbinafine (Group 2) or topical terbinafine only (Group 3). Measurement of clear nail and mycology was performed at baseline and at weeks 4, 10, 16, 22 and 28. Mixed linear models were used to compare mean percent clear nail. Mycological cure rates were also tabulated for each group. Tolerability and adverse events were documented. Results Ninety-eight participants were enrolled (106 nails). Both groups with holes had significantly higher percentage of clear nail compared with topical terbinafine alone. Although no significant difference between the two groups where holes were drilled in the nail plate, Group 1 demonstrated improvement over Group 3 earlier than Group 2 (visit 2 versus visit 4). Group 1 also had the highest mycological cure rates. Conclusion Treatment with holes plus topical terbinafine produces significantly greater improvement in toenails' appearance and higher mycological cure rates compared to treating the dorsal aspect of the nail plate with topical terbinafine alone.

Enhanced low-density lipoprotein degradation and cholesterol synthesis in monocyte-derived macrophages of patients with adult xanthogranulomatosis.

Adult xanthogranulomatosis is an uncommon disorder in which dermal macrophages accumulate cholesterol intracellularly despite normal plasma cholesterol levels. In an attempt to elucidate an underlying biochemical abnormality in this disorder, we studied the rates of 125I-labeled low-density lipoprotein degradation, and intracellular cholesterol synthesis, in human monocyte-derived macrophages of three patients with adult xanthogranulomatosis. In all three patients, the rates of cellular 125I-low-density lipoprotein degradation and of cholesterol synthesis were 22-37% and 14-84% higher than those of the respective normal controls (p < 0.01). These findings suggest that in MDM of adult xanthogranulomatosis patients, the uptake and degradation of low-density lipoprotein-derived cholesterol and intracellular cholesterol biosynthesis are enhanced. Because dermal macrophages are derived from blood monocytes, it is possible that such an enhancement might play a role in the accumulation of cholesteryl esters in the macrophages that form the xanthogranulomatosis lesions.

5-HT1A agonists disrupt memory of fear conditioning in mice.

A series of experiments was carried out to analyze the effects of the 5-HT1A agonists tandospirone or buspirone on the retention of fear conditioning in mice. Fear was produced by pairing tone and shock in a conditioned emotional response (CER) paradigm and strength of conditioning was assessed by measuring suppression of drinking in presence of tone. Fear conditioning was disrupted if tandospirone and buspirone were administered before the conditioning session but not before the test trial. Diazepam disrupted conditioning at both times. Tandospirone did not disrupt performance if conditioning was tested 1 hr rather than 24 hr after training, suggesting that disrupted memory rather than impaired acquisition was responsible for the deficit. The effect of tandospirone on fear conditioning could be reversed by administration of d-amphetamine prior to the retention test, which suggests that information was stored but is inaccessible to normal retrieval cues. Tandospirone and buspirone also retarded extinction, a clear indication that the disruption caused by these drugs is unrelated to their anxiolytic action.