Effect of the Intralesional Forms of Methylprednisolone Acetate and Methotrexate on Psoriatic Nails.

Individuals with psoriatic nails often have a lower quality of life relative to their counterparts with healthy nails. Methotrexate (MTX), an anti-neoplastic agent, is a longstanding treatment option for nail psoriasis. In the current study, we compared the effects of MTX to that of a corticosteroid, namely, methylprednisolone acetate (i.e., Depo-Medrol®) across individuals with nail psoriasis. We used a cohort study design, and both agents were administered intralesionally. Outcome variables were based on the Nail Psoriasis Severity Index (NAPSI). We quantified the effect in terms of change in NAPSI, complete cure at week 16, and cure between 32 and 36 weeks. Our regressions demonstrated that reduced NAPSI scores with Depo-Medrol were, on average, greater than that with MTX by 2.27 (n = 48, P = 0.000255) at week 16. Similarly, the odds of complete cure at week 16 was greater with Depo-Medrol® than with MTX (odds ratio = 18.6, P < 0.0001). In terms of both complete cure and change in NAPSI, Depo-Medrol® was significantly more effective than MTX at a follow-up period of 32-36 weeks. Our study established that intralesional Depo-Medrol® is more effective than intralesional methotrexate for treating nail psoriasis.

A role of BPTF in viral oncogenicity delineated through studies of heritable Kaposi sarcoma.

Kaposi sarcoma (KS), caused by Herpesvirus-8 (HHV-8; KSHV), shows sporadic, endemic, and epidemic forms. While familial clustering of KS was previously recorded, the molecular basis of hereditary predilection to KS remains largely unknown. We demonstrate through genetic studies that a dominantly inherited missense mutation in BPTF segregates with a phenotype of classical KS in multiple immunocompetent individuals in two families. Using an rKSHV.219-infected CRISPR/cas9-model, we show that BPTFI2012T mutant cells exhibit higher latent-to-lytic ratio, decreased virion production, increased LANA staining, and latent phenotype in viral transcriptomics. RNA-sequencing demonstrated that KSHV infection dysregulated oncogenic-like response and P53 pathways, MAPK cascade, and blood vessel development pathways, consistent with KS. BPTFI2012T also enriched pathways of viral genome regulation and replication, immune response, and chemotaxis, including downregulation of IFI16, SHFL HLAs, TGFB1, and HSPA5, all previously associated with KSHV infection and tumorigenesis. Many of the differentially expressed genes are regulated by Rel-NF-κB, which regulates immune processes, cell survival, and proliferation and is pivotal to oncogenesis. We thus demonstrate BPTF mutation-mediated monogenic hereditary predilection of KSHV virus-induced oncogenesis, and suggest BPTF as a drug target.

Medication-Related Osteonecrosis of the Jaw: A Cross-Sectional Study on the Prevalence of Cutaneous Manifestations and the Primary Care Physician's Role in its Early Diagnosis.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a side effect in patients undergoing treatment with bone-modifying agents (BMA) for cancer or osteoporosis. Although most cases are treated by oral medicine specialists, some cases may present extraorally as a fistula in the skin or erythematous swelling localized to the jaw area, causing these patients to consult a primary care physician. This study examined the prevalence and clinical characteristics of extraoral manifestations of MRONJ in a large cohort to raise awareness among primary care physicians of this entity, enabling prompt diagnosis and treatment. METHODS: Medical records were retrieved of patients diagnosed with MRONJ between 2003 and June 2020 in the Oral Medicine Unit of The Sheba Medical Center, Israel. Data relating to demographics, medical background, type of BMA, and clinical presentation were collected. RESULTS: In total, 515 patients (378 women [73%] and 137 men [27%]; mean age: 65 years, range: 32-94 years) met the inclusion criteria, among whom 84 (16.5%) presented with extraoral manifestations of MRONJ. Of these 84 patients, 21 (24.7%) presented with extraoral fistulas. Extraoral manifestations were strongly correlated with MRONJ of the mandible (n = 67; P = .0006). CONCLUSIONS: MRONJ is a significant side effect of BMA therapy. Although MRONJ mostly presents intraorally, some patients may initially present with extraoral manifestations of erythematous swelling or fistulas localized to the jaw area. Primary care physicians should consider MRONJ as a differential diagnosis in such patients.

Bath psoralen plus ultraviolet-A photochemotherapy for chronic graft-versus-host disease: a retrospective cohort study.

BACKGROUND: Chronic graft-versus-host disease is a severe complication of allogeneic stem cell and bone marrow transplantation. First-line immunosuppressive agents, such as steroids, are used to prevent this disease; however, they have multiple side effects. Therefore, bath psoralen plus ultraviolet-A (PUVA) is an alternative second-line treatment. This study aimed to evaluate the clinical efficacy of bath PUVA for managing chronic graft-versus-host disease. METHODS: This retrospective, case-control study included 14 patients with extensive cutaneous chronic graft-versus-host disease, resistant to systemic corticosteroid, treated with bath PUVA. Major and partial responses were defined as clinical improvements of >70% and 50-70%, respectively. We analyzed the graft-versus-host disease clinical presentation and timing after allogeneic stem cell and bone marrow transplantation, bath PUVA doses, background diseases, additional treatments, and adverse effects. RESULTS: We observed eight major (three lichenoid and five sclerodermatoid) and six partial (three lichenoid and three sclerodermatoid) responses after a mean of 28 treatment sessions. After 6 to 25 months, four of the eight patients with sclerodermatoid lesions and all those with lichenoid lesions experienced relapse but responded to additional treatment cycles. CONCLUSIONS: Bath PUVA is well-tolerated and effective for extensive cutaneous chronic graft-versus-host disease. It allows rapid tapering of adjuvant immunosuppressants; however, most patients require prolonged maintenance phototherapy.

Diagnostic approach to tinea capitis with kerion: A retrospective study.

BACKGROUND: Kerion is an inflammatory type of tinea capitis manifesting as boggy crusted nodules. Diagnosis of kerion is often challenging due to high rates of false-negative mycological samples. METHODS: A retrospective study among children with kerion, prior to antifungal treatment, was conducted to assess rates of false-negative mycological samples. Specimens for direct microscopy and fungal culture were collected at baseline and after administration of an oral antibiotic course, with or without an oral steroid course. Kerion was categorized as highly inflammatory when a painful, moist scalp nodule with spontaneous purulent discharge or exuberant crust was present, or mildly inflammatory when an erythematous, dry scalp nodule was seen. RESULTS: Twenty-three children (mean age 7.9 ± 3.0 years) were included in the study. Trichophyton tonsurans was the most common species isolated (69.6%). Highly inflammatory kerions were significantly more likely to be culture negative before treatment than mildly inflammatory kerions (80% vs. 16.7%, p < .01). Non-inflammatory tinea capitis lesions (n = 13) were culture positive in all cases. Following a combined oral antibiotic and steroid course given to most highly inflammatory kerions (n = 11/13), higher rates of positive fungal cultures were found compared to baseline (90.9% vs. 18.2%, p < .01). CONCLUSION: High rates of negative fungal cultures were found only in highly inflammatory kerion. Sampling a highly inflammatory kerion after a combined oral antibiotic and steroid course improved rates of positive fungal cultures. In addition, sampling of non-inflammatory tinea capitis lesions (when present in addition to the kerion) had the highest culture sensitivity.

Efficacy of Fluocinonide\Bifonazole Cream for the Treatment of Trachyonychia: A Retrospective Case Series.

Background: Trachyonychia is a benign nail condition, most commonly seen in children. Trachyonychia manifests as excessive longitudinal ridging, nail roughness, and nail brittleness. Treatment is sought mainly for esthetic reasons as well as functional reasons. A number of therapeutic approaches exist, mainly based on case reports or small non-comparative case series. Aims: To report treatment outcome among patients with trachyonychia. Methods: A retrospective case-series study was conducted among patients who were treated trachyonychia between years 2017 and 2020. Patients were prescribed fluocinonide 0.05% with bifonazole 1% cream, applied with or without occlusion, and methylprednisolone 1-2 mg/nail, injected into the involved nail matrix, or oral cyclosporine 3 mg/kg. Complete response (over 90% improvement) and partial response (over 50% improvement) were assessed. Results: A total of 43 patients with trachyonychia were included [mean age 10.0 years (±5.7), 69.8% males, mean disease duration 4.7 years (±3.0)]. In 90.7% of the cases, topical fluocinonide\bifonazole cream was prescribed. Under-occlusion topical application was found to be highly effective, achieving complete response in 35.3% and partial response in an additional 52.9% of the patients. Occluded application was also found to be significantly more effective than non-occluded application. Treatment efficacy was not affected by the severity of nail roughness, trachyonychia morphology, or whether trachyonychia was idiopathic or coexisted with other dermatological conditions. Conclusion: Occluded application of fluocinonide plus bifonazole cream is efficient for the treatment of trachyonychia and should be considered a first line of treatment.

Tinea capitis in an immigrant pediatric community; a clinical signs-based treatment approach.

BACKGROUND: Tinea capitis is a common cutaneous infection of the scalp and hair follicles, typically diagnosed by direct examination and culture. Treatment with oral antifungals is usually withheld until mycology results are available. In Israel, African refugee children demonstrate higher susceptibility to Tinea capitis and generally fail to undergo follow-up evaluations. METHODS: This study aimed to identify the clinical characteristics and treatment responses of refugee children in Israel with Tinea capitis, in order to formulate a treatment plan for primary care physicians. To this end, demographic, clinical and laboratory data were extracted from the electronic medical records of 76 refugee children presenting with Tinea capitis during 2016-2017. All measured variables and derived parameters are presented using descriptive statistics. The correlation between background clinical and demographic data and Tinea capitis diagnosis was assessed using the chi-squared and Wilcoxon tests. Correlations between demographic/clinical/laboratory characteristics and other types of fungi or other important findings were assessed using a T-test. RESULTS: Scaling was the most common clinical finding. Cultures were positive in 64 (84%) and direct examination in 65 (85%) cases, with a positive correlation between the methods in 75% of cases. The most common fungal strain was T. violaceum. Fluconazole treatment failed in 27% of cases. Griseofulvin 50 mg/kg/day was administered to 74 (97%) children, and induced clinical responses. No side effects were reported. CONCLUSIONS: The key aim of this study was to emphasize the importance of diagnosis and treatment of these immigrant children by their primary pediatric doctor since it takes, an average of 4.3 months until they visit a dermatologist. During this critical time period, the scalp can become severely and permanently damaged, and the infection can become systemic or cause an outbreak within the entire community. In conclusion, we recommend to relate to scaly scalp in high-risk populations as Tinea capitis, and to treat with griseofulvin at a dosage of up to 50 mg/kg/day, starting from the first presentation to the pediatrician.

H3K27Ac modification and gene expression in psoriasis.

BACKGROUND: Numerous alterations in gene expression have been described in psoriatic lesions compared to uninvolved or healthy skin. However, the mechanisms which induce this altered expression remain unclear. Epigenetic modifications play a key role in regulating genes' expression. Only three studies compared the whole-genome DNA methylation of psoriasis versus healthy skin. The present is the first study of genome-wide comparison of histone modifications between psoriatic to healthy skins. OBJECTIVE: Our objective was to explore the pattern of H3K27Ac modifications in psoriatic lesions compared to uninvolved psoriatic and healthy skin, in order to identify new genes involved in the pathogenesis of psoriasis. METHOD: Using ChIP-seq with anti H3K27Ac we compared the acetylation of lysine 27 on histone 3 (H3K27Ac) modification between psoriatic to healthy skins, combined with mRNA array. RESULTS: We found a differential H3K27Ac pattern between psoriatic compared to uninvolved or healthy skins. We found that many of the overexpressed and H3K27Ac enriched genes in psoriasis, harbor a putative GRHL transcription factor-binding site. CONCLUSIONS: In the most overexpressed genes in psoriasis, there is an enrichment of H3K27Ac. However, the loss of H3K27 acetylation modification does not correlate with decreased gene expression. GRHL appears to play an important role in the pathogenesis of psoriasis and therefore, might be a new target for psoriasis therapeutics.

Management of tinea capitis in Israel: A comparative study.

BACKGROUND: Tinea capitis is a common fungal infection in Israel, most commonly caused by the dermatophyte Trichophyton tonsurans. OBJECTIVES: To investigate the effectiveness of oral antifungal monotherapy in producing clinical or complete cure. We also evaluated the impact of topical therapy (bifonazole 1% shampoo and/or betamethasone valerate 0.1% solution), prior to oral treatment, on patients' likelihood of clinical or complete cure. METHODS: A retrospective chart review was conducted. Patients with mycologically confirmed tinea capitis were treated with one of four regimens: (1) terbinafine (greater than 40 kg: 250 mg/day, 20 to 40 kg: 125 mg/day, less than 20 kg: 62.5 mg/day), (2) itraconazole 5 mg/kg daily, (3) fluconazole 6 mg/kg daily, or (4) griseofulvin 20 mg/kg daily. We used generalized linear models (GLM) to determine whether there was a significant association between the odds of cure and choice of treatment. RESULTS: The causative species was Trichophyton tonsurans in all but 6 cases that grew T violaceum. For pediatric patients, the odds of having complete or clinical cure within 6 weeks was greater if they used terbinafine compared to itraconazole, fluconazole, or griseofulvin (odds ratio [OR] = 9.06, P = .047). The likelihood of complete or clinical cure within 8 weeks of oral therapy was lower if topical steroids were previously used compared to if topical antifungals were used prior to systemic treatment (OR = 0.29, P = .046). CONCLUSIONS: Our findings substantiate prior literature demonstrating that terbinafine is non-inferior to griseofulvin, itraconazole, and fluconazole in the therapy of pediatric tinea capitis caused by T tonsurans.

Low-dose isotretinoin versus minocycline in the treatment of rosacea.

Rosacea is a common inflammatory facial skin condition affecting the adult population. Its papulopustular subtype is mainly treated pharmacologically by topical and oral antibiotics. For severe or antibiotics-recalcitrant disease, daily low-dose isotretinoin has also been reported to be effective. However, no previous study has assessed the efficacy of once-weekly administered isotretinoin for papulopustular rosacea. For this purpose, a retrospective comparative study was conducted. For severe rosacea, 40 mg/week isotretinoin (24 patients) was administered. For mild to moderate rosacea, once-weekly 20 mg/week isotretinoin (28 patients) was compared with 100 mg/day minocycline (24 patients). Treatment courses lasted 4 to 7 months. Forty milligrams per week isotretinoin was highly effective for severe rosacea, achieving complete response (over 90% improvement) in 62.5% of patients and partial response (50%-90% improvement) in additional 29.2% of patients. Twenty milligrams per week isotretinoin and hundred milligrams per day minocycline showed comparable efficacy for mild to moderate rosacea (complete response of 10.7% vs 8.3% and partial response of 28.6% vs 33.3%, respectively). This study demonstrates that that the use of a weekly low-dose isotretinoin is an effective treatment for papulopustular rosacea, including among patients with severe disease.

IL6R is a target of miR-197 in human keratinocytes.

Psoriasis is a chronic inflammatory disorder with cutaneous and systemic manifestations and substantial negative effects on patients' quality of life. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play a role in the pathogenesis of psoriasis. Previously studies, from others and by us, highlighted specific miRNAs that are dysregulated in psoriatic lesions. MicroRNA-197-3p (miR-197) expression is downregulated in psoriatic lesions compared to normal or uninvolved skin in patients with psoriasis. We have previously reported that miR-197 could modulate IL-22 and IL-17 signalling in psoriasis. Herein, we identify additional biochemical targets of miR-197 in psoriasis. We applied a transcriptome-wide biochemical approach, Protein argonaute-2 photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (Ago2 PAR-CLIP), to search for new targets of miR-197 in live keratinocytes, and validated its results using reporter assay and analysing by Western blot protein levels in cells overexpressing miR-197. Ago2 PAR-CLIP identified biochemical targets of miR-197, including the alpha subunit of the IL-6 receptor (IL6R). This work provides evidence that IL6R in bona-fide biochemical target of miR-197. IL6R is known to be up-regulated in psoriasis and even was considered as a possible therapeutic target. From the present data and our previous studies, it appears that miR-197 is a major regulator of the interaction between immune system cells and keratinocytes.

Custom-made trays for targeted treatment of oral vesiculobullous diseases: A proposed protocol.

Topical and intralesional corticosteroids (CS) are effective treatments for oral manifestations of autoimmune vesiculobullous diseases (VBD); however, may cause unnecessary absorption in the adjacent healthy mucosal surfaces, local infections, atrophy, and injection pain. To propose a protocol using a unique modality for targeted administration of CS for the treatment of local manifestations of oral VBD. The medical records of nine patients with systemic CS-resistant VBD oral lesions, were reviewed following 3 weeks of treatment and 3 months of tapering using a custom-made tray designed for precise application of topical CS targeted to the involved mucosa. Following treatment, lesions have healed in 8/9 patients. Involvement of surrounding mucosa was minimal, and no systemic adverse effects were recorded. The proposed protocol using custom-made trays for targeted CS treatment could be an effective alternative treatment for oral VBD.

Cold sub-atmospheric and atmospheric pressure plasma for the treatment of Trichophyton rubrum onychomycosis: An in-vitro study.

Previous studies have suggested the applicability of cold atmospheric pressure plasma for the treatment of onychomycosis. Whether delivering cold plasma in sub-atmospheric pressure would be beneficial for this purpose is yet to be established. The current study aimed to evaluate efficacy of cold sub-atmospheric and atmospheric pressure plasma in Trichophyton rubrum growth inhibition. Bovine nails infected with T. rubrum were treated by a cold air plasma device, which enables utilizing plasma in sub-atmospheric pressures (Low = 100 millibar; High = 300 millibar) or atmospheric pressure. The infected foci were exposed to the plasma source directly or indirectly. Treatment with high sub-atmospheric pressure setting achieved T. rubrum growth reduction of 94.0% and 73.0%, for direct and indirect exposure to the plasma source, respectively (P < .001). Low sub-atmospheric pressure setting achieved similar T. rubrum growth reduction of 86.2% for direct exposure to the plasma source (P < .001), but only marginally significant 58.8% reduction rate for indirect exposure to the plasma source (P = .056). None statistically significant fungal growth reduction was attained with the use of atmospheric pressure setting. Cold plasma was shown to effectively inhibit T. rubrum nail growth, with sub-atmospheric pressure setting achieving better outcome than atmospheric pressure.

Clinical significance of Candida isolation from dystrophic fingernails.

BACKGROUND: Candida onychomycosis mostly involves fingernails. Yet, in contrast to dermatophytes, Candida isolation from dystrophic fingernails does not prove casualty, as sample contamination and non-pathogenic Candida growth occur. Characterising treatment outcome of Candida-positive dystrophic nails is crucial to avoid unnecessary treatment. OBJECTIVE: To investigate predicators associated with treatment outcome among Candida-positive dystrophic fingernails. PATIENTS AND METHODS: A retrospective cohort study was carried out among 108 adults with Candida-positive dystrophic fingernails not cured with adequate systemic anti-fungal course. Diagnosis was based on a single mycological culture. Patients with treatment failure (n = 85; 78.7% of the cases) were compared to patients with partial response (mild to almost cure; n = 23; 21.3% of the cases) at 9 to 12 months following treatment initiation. RESULTS: Treatment failure was significantly associated with primary onycholysis (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.1-7.4) and prolonged dystrophy (12.8 vs. 3.7 years in average), compared to partial treatment response. Non-responders had lower odds to present with distal lateral subungual onychomycosis, compared to partial responders (OR 0.3; 95% CI 0.1-0.7). Demographic and mycological characteristics, as well as number of nails affected, co-presence of paronychia, and treatment regime were not found to be associated with treatment response. CONCLUSION: Candida-positive primary onycholysis was shown to be non-responsive to systemic anti-fungal treatment, suggesting that anti-fungal treatment is not indicated. For other clinical scenarios, high proportions of treatment non-response suggest that determining causality of Candida should not be based on a single positive mycological culture.

Tinea capitis-like infection caused by Rhodotorula mucilaginosa in a shelter for African Refugee Children in Northern Israel.

Rhodotorula is a genus of unicellular pigmented yeasts, part of the division Basidiomycota. In this article, we report three cases of refugee children in a day care shelter in northern Israel who were clinically diagnosed and treated empirically as with ringworm infection but with clean and exclusive growth of Rhodotorula mucilaginosa in repeated cultures of several skin samples. Skin infections caused by this yeast are rare and there are few reports in the literature, mainly in patients who are immunocompromised. Here we report an infectious process of the scalp in immunocompetent children, caused by Rhodotorula mucilaginosa mimicking tinea capitis.

The Possible Role of Infertility Drugs in Later Malignancy: A Review.

BACKGROUND: Some 15% of all couples in the industrialized world suffer from infertility. Accordingly, any possible life-long morbidity that may result from treatments for infertility presents a significant concern to public health. The use of medications for infertility is specifically relevant to their possible effects on the classical target tissues for hormones involved in the sex axes, i.e., uterus, ovaries, and breast, but may have an effect on other organs, which harbor receptors for some of the hormones involved in reproduction. When one deals with the effect of treatment for infertility on the occurrence of malignant conditions, there is no doubt that certain malignancies tend to occur more frequently in women who suffered from and/or were treated for infertility. OBJECTIVE: To review the accumulated data on the association of treatments for infertility with subsequent malignancies both in the classical target organs of sex steroids and in non-target organs. METHODS: Systematic compilation of the relevant literature. RESULTS & CONCLUSION: Contrary to popular believes, treatment for infertility is associated with very little increase in malignacies.

Treatment of erosive oral lichen planus with local ultraviolet B phototherapy.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease that can significantly affect the patient's quality of life. OBJECTIVE: We sought to demonstrate the therapeutic efficacy of local ultraviolet (UV) B phototherapy in OLP. METHODS: Patients with biopsy-confirmed erosive OLP recalcitrant to previous medical therapy were treated with the TheraLight UV 120-2 system (TheraLight Inc, Carlsbad, CA). Lesions were accessed directly using a flexible fiber guide. Local phototherapy was delivered 3 times a week, with gradual increase in UVB dose every other session. Affected oral mucosa was defined as the area showing erosions or symptomatic reticular lesions. Complete response was defined as reduction of at least 80% in the affected mucosal area, and partial response was defined as a reduction of 50% to 80% in the affected mucosal area. The primary end point was efficacy after 8 weeks of treatment. RESULTS: Fourteen patients were included in the study. Nine achieved complete response and 5 partial response after 8 weeks. Ten patients were continued on maintenance therapy and were able to maintain their response for another 29 weeks. None of the patients showed any serious side effects from local UVB therapy. LIMITATIONS: The study was performed in a small series of patients at a single medical center. Further studies with larger patient samples are required to validate our findings. CONCLUSION: Local UVB phototherapy may be a promising treatment modality for erosive OLP.

Religious sensitivity pitted against the need to know: autopsy of Jewish children in Israel.

BACKGROUND: The aim of the study was to compare autopsy findings with antemortem findings in children who died in a pediatric intensive care unit. MATERIAL/METHODS: Consecutive series of patients who died in the pediatric intensive care unit during 2-year period were used. The study was conducted as a retrospective chart review at community, regional-referral, university-affiliated tertiary medical center of 1200 bed in Israel. RESULTS: Permission was given to perform autopsies on only 10 children (23.8%, mean age 85.7 months) out of the 42 who died during the study period. The mean length of stay in the pediatric intensive care unit prior to death was 13.3 days. Cardiac or hemato-oncologic diseases comprised the major pre-admission diagnoses. The autopsy revealed a major finding that, if known before death, would have altered clinical management in 50% of the patients: pneumonia, pneumonitis as well as intestinal perforation or necrosis. No correlation was found between patient length of stay in the intensive care unit and the autopsy disclosed information. CONCLUSIONS: Our findings support the importance of autopsy assessment in the pediatric intensive care setup. We believe that postmortem examination is also essential for improving the quality of pediatric patient care.