Corticosteroid Therapy in Combination with Antibiotics for Erysipelas.

BACKGROUND: Erysipelas, an acute infection of the dermal and subcutaneous tissue, is normally treated with antibiotics. Previous data indicated that treatment with prednisone in combination with antibiotics results in significant acceleration of the healing phase. OBJECTIVES: To investigate the effectiveness of corticosteroids combined with antibiotics for the treatment of erysipelas. METHODS: A retrospective study was conducted on hospitalized patients diagnosed with erysipelas between 2004 and 2011 at the Department of Dermatology at Sheba Medical Center, Israel. Data included epidemiology, medical background, and course of the disease as documented at admission and during hospitalization. RESULTS: Data were collected on 173 patients (66% males) who were divided into two groups: a control group treated with antibiotics only (97 patients) and a study group treated with antibiotics and prednisone (76 patients). The study group presented with a more severe form of erysipelas (bullous) and those patients were hospitalized for a longer period (8.5 vs. 7 days). Nevertheless, the study group exhibited a 71% clinical improvement shortly after being treated with prednisone, without significant side effects. Short-term follow-up revealed more edema in the study group; however, long-term follow-up revealed a higher incidence of erythema and recurrence of erysipelas in the control group. The return to full function was faster in the study group than in the control group. CONCLUSIONS: Combining prednisone with antibiotics for the treatment of erysipelas should be considered, especially in severe cases. In addition, a prospective double-blind study should be conducted to verify these conclusions.

The Histopathology of Urticaria Revisited-Clinical Pathological Study.

BACKGROUND: The classic histopathological findings of urticaria include dermal edema and a sparse perivascular infiltrate of neutrophils, eosinophils, macrophages, and lymphocytes. However, this pattern is inconsistently described. OBJECTIVE: To describe the histological and immunofluorescence characteristics of urticaria and to identify distinctive patterns. METHODS: A retrospective study was performed in which the medical files and biopsy specimens of 58 patients with acute and chronic classical urticaria were reviewed. Pathological parameters were quantified. RESULTS: We recognized 2 distinctive patterns of urticaria: lymphocyte and neutrophil predominant; the former was characterized by a perivascular location, whereas the latter was associated with an interstitial location and a denser infiltrate. Mast cells were relatively sparse, better demonstrated with special stains. Tryptase stain demonstrated more mast cells than Giemsa stain. Extravasated erythrocytes were present in 50% of the cases, but vasculitis was not observed. CONCLUSIONS: Histological findings in classical urticaria show a spectrum of findings from a sparse superficial perivascular to a deep perivascular and interstitial infiltrate. Distinctive groups based on the dominant cell type can be identified, accounting for the similarity to neutrophilic urticarial dermatosis. Lesions may have a purpuric appearance, but leukocytoclastic vasculitis is never present.

Efficacy of Dapsone in the Treatment of Pemphigus Vulgaris: A Single-Center Case Study.

BACKGROUND: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease. Most patients require long-term therapy with systemic steroids, and a steroid-sparing agent is usually also utilized. Dapsone is a chemotherapeutic agent with anti-inflammatory properties that is used as a steroid-sparing agent in PV. OBJECTIVE: The aim of the present study was to evaluate the efficacy of dapsone as an adjuvant therapy in patients with PV. METHODS: A retrospective analysis of patients' files was performed. All 26 patients included in the study group were treated with dapsone as an adjuvant to systemic steroids for at least 3 consecutive months and were followed up during their dapsone treatment period. RESULTS: After 3 months of treatment with dapsone, 13 patients were in the consolidation phase, 4 patients demonstrated partial remission on minimal therapy, 7 patients demonstrated complete remission on minimal therapy, and 2 patients were defined as treatment failures. The trend of clinical improvement continued after 6 months of treatment and at the study end point. CONCLUSION: This retrospective case series, one of the largest reported, indicates that dapsone is efficacious and safe for patients with PV in whom it is well tolerated soon after the initiation of treatment.

Epidemiological data of 290 pemphigus vulgaris patients: a 29-year retrospective study.

Pemphigus vulgaris (PV), an autoimmune blistering disease involving the skin and mucosa, is traditionally considered to be prevalent among Jews, particularly those of Ashkenazi origin. Israel, where the Ashkenazi and non-Ashkenazi Jewish population live alongside a large Arab minority, is a particularly interesting place for epidemiological studies of PV. To characterise the epidemiological and clinical parameters of PV patients from a single tertiary medical centre in Israel. Data was retrieved retrospectively from the medical records of newly diagnosed PV patients referred to the Sheba Medical Center between 1980 and 2009. A total of 290 PV patients were diagnosed during the study period. The mean age at diagnosis was 49.7 years (range: 10-92 years) and a female predominance was identified (1.54:1; p<0.001). Among the Jewish patients, the ratio of Ashkenazi to non-Ashkenazi was 1.23:1, which was not statistically significant in comparison to the ratio of the general Jewish population in Israel (p = 0.289). We describe the comorbidities found among the patients. Disease severity at diagnosis was not found to be related to the epidemiological parameters examined. Studies from different countries reveal variations in the clinical and epidemiological characteristics of the disease. The epidemiology of PV in Israel, a Middle-Eastern country with a Western lifestyle and a diverse ethnic population, shows some characteristics that represent an "admixture" between European and Middle-Eastern or Asian countries. The associated comorbidities of PV emphasize the need for dermatologists to keep a high index of suspicion and actively evaluate patients to determine their presence.

Diagnosis and classification of autoimmune blistering diseases.

Blistering skin diseases are a group of autoimmune disorders that are characterized by autoantibodies against structural proteins of the epidermis or the dermal-epidermal junction and clinically by blisters and erosions on skin and/or mucous membranes. Since clinical criteria and histopathological characteristics are not sufficient for diagnosis, direct immunofluorescence microscopy of a biopsy specimen or serological tests are needed for exact diagnosis. The differentiation between the various disorders became more important since prognosis as well as different treatment options are nowadays available for the various diseases. Moreover, some bullous diseases may indicate the presence of an underlying malignancy. The detection of serum autoantibodies have been shown to correlate with disease activity and thus may be helpful in deciding treatment options for these patients.

Adjuvant rituximab therapy in pemphigus: a single-center experience of 18 cases.

BACKGROUND: Pemphigus vulgaris (PV) follows a chronic relapsing course where the mainstay of therapy has been oral corticosteroids and second-line immunosuppressive and immunomodulating therapies. Successful responses have been reported with rituximab, a chimeric monoclonal anti-CD20 antibody targeting B lymphocytes, although its use in recalcitrant pemphigus is still being studied. METHODS: A retrospective analysis is presented of 18 patients with cutaneous and mucous membrane involvement after disease relapse following steroid and other adjuvant therapies who were treated with rituximab (4 intravenous infusions of 375 mg/m² once weekly for 4 consecutive weeks). RESULTS: At 3 months follow-up, 44% (8/18) of cases achieved complete disease remission with a further 44% (8/18) showing partial remission. Further follow-up showed 5/8 partial responders achieving a complete response with 4 cases experiencing disease relapse (72% response at 9 months). There were no adverse drug-related events and its use resulted in a significant reduction in steroid dosage during follow-up. CONCLUSION: Rituximab is beneficial in the management of refractory PV, resulting in clinical remission and a steroid-sparing effect. Further study needs to examine rituximab dosage and scheduling as well as its place within the treatment algorithm.

Population-specific association between a polymorphic variant in ST18, encoding a pro-apoptotic molecule, and pemphigus vulgaris.

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease caused by anti-epithelial antibodies, leading to disruption of cell-cell adhesion. Although the disease is exceedingly rare worldwide, it is known to be relatively prevalent in Jewish populations. The low prevalence of the disease represents a significant obstacle to a genome-wide approach to the mapping of susceptibility genes. We reasoned that the study of a genetically homogeneous cohort characterized by a high prevalence of PV may help exposing associated signals while reducing spurious results due to population sub-structure. We performed a genome-wide association study using 300K single-nucleotide polymorphisms (SNPs) in a case-control study of 100 PV patients of Jewish descent and 397 matched control individuals, followed by replication of significantly associated SNPs in three additional cohorts of Jewish, Egyptian, and German origin. In addition to the major histocompatibility complex locus, a genomic segment on 8q11.23 that spans the ST18 gene was also found to be significantly associated with PV. This association was confirmed in the Jewish and Egyptian replication sets but not in the German sample, suggesting that ST18-associated variants may predispose to PV in a population-specific manner. ST18 regulates apoptosis and inflammation, two processes of direct relevance to the pathogenesis of PV. Further supporting the relevance of ST18 to PV, we found this gene to be overexpressed in the skin of PV patients as compared with healthy individuals.

Methotrexate is an effective and safe adjuvant therapy for pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a chronic, autoimmune blistering disease. Most patients require long term therapy with systemic steroids as a first line of treatment. Immunosuppressive agents such as methotrexate (MTX) are administrated as second line therapy. Only a few reports have assessed MTX efficacy, with contradictory results. OBJECTIVE: The aim of this study was to evaluate MTX as an adjuvant therapy in patients with PV. METHODS: A retrospective study of 30 PV patients treated with MTX as an adjuvant therapy. Disease severity score and prednisone dosage served as assessing measures. RESULTS: All patients were treated with 15 mg MTX per week. Of the 25 patients defined as severe or moderate disease at the beginning of treatment, 21 (84%) improved and downgraded their severity status at 6 months of treatment. In 21 patients (76.6%) we were able to reduce the prednisone dose. There was a significant improvement in the severity score (p=0.00001) and in prednisone dose (p=0.0001). Four patients (13%) suffered from mild side effects. CONCLUSION: MTX treatment is safe and beneficial as a steroid-sparing agent in PV.

9-cis-rich ß-carotene powder of the alga Dunaliella reduces the severity of chronic plaque psoriasis: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Synthetic retinoids are one of the mainstay treatments of psoriasis. However, their use is occasionally limited by adverse effects, especially mucocutaneous, hepatic, and lipid profile toxicity. Thus, a search for retinoid metabolites that are both safe and active is essential. The alga Dunaliella bardawil is a natural source of the retinoid precursor 9-cis ß-carotene that has a good adverse effect profile. OBJECTIVE: To test the effect of the alga Dunaliella bardawil on psoriasis. METHODS: Thirty-four adult patients with mild, chronic, plaque-type psoriasis were included in this monocentric, prospective, randomized, double-blinded pilot study. Patients received either capsules of the alga D. bardawil or starch powder capsules, as the placebo, for 12 weeks. The response to treatment was evaluated by changes in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores. Safety of the treatment was evaluated. RESULTS: At the end of 6 weeks, the reduction in the mean PASI score was significantly higher in the Dunaliella group than in the placebo group (61.3% vs 34%, respectively, p = 0.002). The DLQI change did not reach significance (8.5% and 5.9% in the Dunaliella and in the control group, respectively, p = 0.9). We observed no significant change in the liver function tests or in the lipid profile. CONCLUSIONS: 9-cis ß-carotene, in the form of D. bardawil, is an effective and safe treatment for patients with mild, chronic, plaque-type psoriasis. A larger study is warranted.

[Rituximab (Mabthera) for treatment of rare autoimmune bullous skin disorders].

Autoimmune bullous skin disorders are characterized by a severe and potentially lethal course and may require aggressive long-term treatment with systemic corticosteroids and other immunosuppressive drugs, which can lead to serious adverse events. Recently, anti-CD20 antibody, Rituximab, was reported to be beneficial as an adjuvant therapy in these diseases. Herein, we present 2 case reports of patients suffering from resistant rare diseases from the aforementioned spectrum: linear IgA dermatosis and Pemphigoid gestationis. The patients were successfully treated with Rituximab (Mabthera). This is one of the first reports of this kind of treatment for these rare life-threatening diseases. These case reports emphasize the role of Rituximab as a crisis therapy in autoimmune blistering diseases.

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.

The impact of stratifying initial dose of corticosteroids by severity of pemphigus vulgaris on long-term disease severity.

BACKGROUND: Pemphigus vulgaris (PV) is a life-threatening disease affecting skin and mucous membranes. The "epitope spreading" theory posits that uncontrolled PV can gradually worsen because of exposure of cellular antigens to the immune system. To this end, high-dose systemic corticosteroids have been advocated as first-line treatment for patients with PV to achieve disease control. OBJECTIVE: To determine whether the initial dose of prednisone stratified by disease severity affects long-term disease severity. METHODS: A retrospective study was conducted on 58 patients with PV with at least five years of follow-up from diagnosis. Patients were categorized into three groups according to the initial dose of prednisone treatment. Parameters analyzed included age, gender, disease severity at baseline and follow-up, hospitalizations, prednisone doses and adjuvant therapy at follow-up, and remission rate. RESULTS: Ten patients received initial low-dose prednisone or were treated initially without systemic CS, 19 patients received intermediate-dose prednisone, and 29 received high-dose prednisone. Disease severity at presentation correlated directly with initial prednisone doses. The duration of the first hospitalization and number of hospitalization days during the five-year follow-up period were significantly lower in the group treated with initial low-dose prednisone and similar for the groups treated with intermediate and high doses. CONCLUSIONS: Disease severity of PV at presentation is a good predictor of the clinical course. Stratifying initial prednisone dose according to PV disease severity at presentation is appropriate.

Evidence for methotrexate as a useful treatment for steroid-dependent chronic urticaria.

Chronic urticaria is a relatively common disorder that can be severe and may impair quality of life. The management of recalcitrant chronic urticaria that is not responding to histamine antagonists includes short-term systemic corticosteroids, anti-inflammatory drugs (colchicine, dapsone and sulfasalazine) and immunomodulatory agents, such as cyclosporine, methotrexate, plasmapheresis and intravenous immunoglobulin. We report here our retrospective experience with the use of methotrexate in 8 patients (2 males and 6 females) with recalcitrant chronic urticaria who were not responding to high-dose first- and second-generation antihistamines. The mean duration of the disease prior to methotrexate treatment was 12 ± 8 months. Patients were treated for a mean duration of 4.5 months with a mean dose of 15 mg methotrexate/week. A complete response was achieved in 7 out of 8 patients (87%). Five out of the 7 patients were disease-free during a period of 1-10 months follow-up after discontinuing methotrexate and prednisone therapy. No serious adverse effects were reported. Methotrexate is an effective and safe treatment for chronic urticaria in patients who are not responsive to conventional therapy.

Autoimmune bullous diseases the spectrum of infectious agent antibodies and review of the literature.

Pemphigus and bullous pemphigoid are two autoimmune diseases that have a similar pathogenesis. Both have a genetic predisposition which promotes the production of auto-antibodies targeted against different components of the epidermal desmosome and hemidesmosome. Environmental factors play an important role in the pathogenesis of this autoimmune disease. Among these, the role of infectious agents was debated as a causative factor. We sought to determine a possible connection between various infectious agents and autoimmune bullous disease (ABD). A cohort of 148 serum samples of patients with pemphigus, bullous pemphigoid and controls was screened for evidence of a prior infection with HBV, HCV, EBV, CMV, Helicobacter pylori, Toxoplasma gondii and Treponema pallidum, utilizing the Bio-Rad BioPlex 2200 system as well as ELISA assays to complete the panel. HBV, HCV, H. pylori, T. gondii and CMV were demonstrated to have significantly higher prevalence of antibodies in patients with pemphigus and bullous pemphigoid in comparison to controls. Among them, we found a novel association between H. pylori and ABD. Our study suggests a contributing role for HBV, HCV, H. pylori, T. gondii and CMV in inducing ABD in the genetically susceptible host.

The Koebner phenomenon.

The Koebner phenomenon is one of the most well-known entities in dermatology. It was first described by Heinrich Koebner in 1876 as the formation of psoriatic lesions in uninvolved skin of psoriatic patients after cutaneous trauma. This isomorphic phenomenon is now known to involve numerous diseases, among them vitiligo, lichen planus, and Darier disease. The pathogenesis of the Koebner phenomenon is still obscure but may involve cytokines, stress proteins, adhesion molecules, and autoantigens. This contribution reviews the clinical manifestations of Koebner phenomenon, its provocative factors, suggested pathogenesis mechanisms, and the various skin conditions that exhibit this unique response.

Clinical application of static fluorescence-based cytometry, Cellscan, in cutaneous adverse drug reaction.

The aim of the present study was to evaluate the effectiveness of Cellscan in identifying culprit drugs causing cutaneous adverse drug reaction. It was a prospective study with 3 months follow up conducted at the Departments of Dermatology, Internal Medicine and Dermatology Outpatient Clinic, Chaim Sheba Medical Center, Tel Hashomer, Israel. The study included 36 patients with cutaneous reaction suspected to be secondary to drugs, treated with a total number of 148 drugs. All patients and drugs were classified to three probability groups according to accepted clinical criteria. The effectiveness of the Cellscan test in identifying the culprit drug was addressed according to the clinical probability for cutaneous drug reaction, the drug class and the type of rash. Data analysis according to the clinical probability for cutaneous drug reaction revealed that patients in the moderate and high probability groups had a high test sensitivity of 77.7% and 83.3% with specificity of 71% and 63%, respectively, in identifying the culprit drug. Classifying the data according to drug classes, revealed that for the antibiotic and cardiovascular drug classes the sensitivity of the test was 100% and 92% with specificity of 83.3% and 55.5%, respectively, in identifying the culprit drug. Finally, the classification of patients according to the type of rash revealed a high evaluating accuracy for culprit drugs in maculopapular rashes with sensitivity and specificity of 90% and 60.4%, respectively. The results of this study imply that the Cellscan test is it a good practical tool for identifying the culprit drug in cutaneous adverse drug reaction.

Ciclopirox nail lacquer for the treatment of onychomycosis: an open non-comparative study.

Onychomycosis is a relatively common disease accounting for up to 50% of all nail disorders. Topical treatment, although less effective than systemic, is usually preferred by patients. Topical antifungal nail lacquers have been formulated to provide better delivery of the antifungal agent to the nail unit. The purpose of this research is to evaluate the efficacy and safety of ciclopirox nail lacquer in the treatment of onychomycosis. Patients suffering from distal and lateral subungual toenail onychomycosis (DLSO) and lateral subungual onychomycosis (LSO) were treated by ciclopirox nail lacquer once daily for 9 months. Every week the nail lacquer was removed using acetone. Clinical nail status, KOH examination and mycological culture were recorded by the same investigator at 0, 3, 6 and 9 months. Thirty-six patients completed the 9-month regimen. Trichophyton rubrum was the most common pathogen. At the end of the study, good improvement to complete cure was observed in 13 patients (36%), 12 patients showed only mild to moderate improvement and 11 patients (31%) had no clinical improvement. No adverse effects were noted throughout the treatment period. Ciclopirox nail lacquer seems to be slightly more effective than other topical modalities and could be used in patients who cannot or do not want systemic treatment.

Onychomycosis in psoriatic patients - rationalization of systemic treatment.

Nail changes in patients with psoriasis have been reported with varying prevalence. Onychomycosis has been reported in up to 47% of the psoriasis patients. The purpose of this study was to determine the prevalence of nail abnormalities, onychomycosis in psoriasis and response to itraconazole treatment. We evaluated 312 patients suffering from psoriasis for nail changes and onychomycosis. Patients having laboratory confirmation of onychomycosis were treated with three courses of itraconazole (400 mg day(-1) for 1 week). Of 312 patients with psoriasis, 67 (21.5%) patients had nail changes, 23 (34%) of them suffered from onychomycosis. Complete cure (clinical and mycological) was achieved in 30% of the patients with onychomycosis. The response to treatment of onychomycosis with itraconazole in psoriasis patients was found to be lower than in the general population. Considering the low response to onychomycosis systemic therapy in psoriatic patients and the potential side-effects of the treatment, the rationality of this treatment is questionable.

Iontophoretic terbinafine HCL 1.0% delivery across porcine and human nails.

BACKGROUND: Onychomycosis is a common disease. Topical treatment is usually not effective due to limitation of trans-nail delivery of antifungal drugs. Successful treatment of deep-seated nail infections remains elusive as the delivery of efficacious levels of antifungal drug to the site of action is very difficult. OBJECTIVES: To evaluate the influence of several parameters including; the effect of low electrical current, incubation time and the presence of electrolyte (NaCl or KCl) on the penetration of terbinafine through the nail plate into the nail bed, using various formulations and concentrations of terbinafine HCl. METHODS: Iontophoresis was applied across porcine and human nail in vitro to assess its efficiency in enhancing delivery of terbinafine HCl. RESULTS: In this study, we have demonstrated that an optimal electrolyte concentration (1% NaCl or KCl) is required for an effective delivery. There is a significant increase in drug delivery into the nail and into the receiving compartment in the presence of 3% DMSO. CONCLUSIONS: This study demonstrates the efficacy of iontophoresis in enhancing the trans-nail delivery of terbinafine. Clinical studies are needed to evaluate the feasibility, efficacy and safety of iontophoresis of terbinafine in onychomycosis in human.