Acute localized exanthematous pustulosis caused by enoxaparin.

Notably, enoxaparin has not been described to cause acute localized exanthematous pustulosis (ALEP). Herein, we present a case of a woman with a cutaneous drug reaction consistent with ALEP that occurred after enoxaparin. This case highlights enoxaprin as a novel causative agent for this type of drug reaction.

Cultured allogeneic fibroblast injection vs. fibroblasts cultured on amniotic membrane scaffold for dystrophic epidermolysis bullosa treatment.

BACKGROUND: Different methods of fibroblast application have been examined to treat recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVES: To compare the effects of intradermal injection of cultured allogeneic fibroblasts in healing RDEB wounds with those of fibroblasts seeded on amniotic membrane scaffolds (FAMS) or standard wound care (SWC) with Vaseline® gauze as controls. METHODS: Seven patients were recruited, and seven wounds were assessed in each patient: three wounds were treated with injection of intradermal fibroblasts, three were treated with FAMS and one was dressed with SWC. Changes in wound size were assessed after 2 and 12 weeks of treatment. Qualitative wound scores (QWS) were used to assess wound severity. Additionally, biopsies and antigen mapping were performed to detect type VII collagen in the dermoepidermal junction. RESULTS: In both treated areas, the QWS and wound size were significantly decreased (P < 0·001), whereas there were no changes in the control group (P = 0·29). After 2 and 12 weeks of treatment, the wound size was significantly decreased in wounds that were treated with fibroblast injection compared with those treated with FAMS (P < 0·001); but no significant changes were found in the control group. CONCLUSIONS: Fibroblast injection has been shown to promote healing of RDEB wounds and is superior to FAMS or the control treatment.

Serum 25-hydroxy vitamin D level in patients with pemphigus and its association with disease severity.

BACKGROUND: There is a growing number of studies suggesting a key role for vitamin D in the pathogenesis and progression of autoimmune disorders. AIM: To determine the serum levels of 25-hydroxy vitamin D [25(OH)D] in patients with pemphigus and association of 25(OH)D with clinical features. METHODS: We enrolled 52 patients with pemphigus and 56 age- and sex-matched healthy controls (HCs). Only patients newly diagnosed with pemphigus or patients who had relapsed after discontinuing their treatment for > 6 months were included. Serum 25(OH)D and parathyroid hormone (PTH) levels were measured. Data on demographics, body mass index (BMI), disease severity (based on Pemphigus Area and Activity Score; PAAS) and involved surface body area (BSA) were obtained. RESULTS: Suboptimal levels of vitamin D (< 30 ng/mL) were observed in 78.8% and 91.0% of patients and HCs, respectively (P = 0.13). Univariate and multivariate ordinal logistic regression models showed that low vitamin D status was more likely to occur in patients with higher BSA (OR = 1.07, 95% CI 1.01-1.13) and those with higher cutaneous (OR = 1.36, 95% CI 1.11-1.66) and total (OR = 1.24, 95% CI 1.08-1.41) PAAS. However, there was no significant association between vitamin D levels and presence of pemphigus, season of sampling, age, BMI or smoking habit. CONCLUSION: Vitamin D deficiency is common both in patients with pemphigus and in HCs. Patients with more severe disease (higher PAAS) are likely to have lower vitamin D levels.

A new homozygous nonsense mutation in LAMA3A underlying laryngo-onycho-cutaneous syndrome.

Laryngo-onycho-cutaneous (LOC) syndrome is a subtype of autosomal recessive junctional epidermolysis bullosa in which there is prominent skin and mucosal granulation tissue that can lead to delayed wound healing, laryngeal obstruction and blindness. Thus far, all cases are of Punjabi ancestry and have been shown to result from a founder mutation in the LAMA3 gene, notably involving a single nucleotide insertion mutation in exon 39, which is specific to the LAMA3A (designated exon 1 of LAMA3A) and not the LAMA3B1 or LAMA3B2 isoforms. Here, we describe a new pedigree with LOC syndrome. Affected individuals (from Iran) have the characteristic clinicopathological and molecular features of LOC syndrome: prominent granulation tissue (especially affecting the eyes), normal intensity laminin-332 immunostaining at the dermal-epidermal junction, and autosomal recessive mutations in the LAMA3A-specific exon. The pathogenic mutation is a homozygous nonsense mutation, designated p.Gln57X, which just affects the laminin-α3a transcript. These findings therefore expand the molecular basis of LOC syndrome.

Differences in faecal microbiome composition between adult patients with UCD and PKU and healthy control subjects.

Urea cycle disorders (UCDs) are a group of rare inherited metabolic diseases causing hyperammonemic encephalopathy. Despite intensive dietary and pharmacological therapy, outcome is poor in a subset of UCD patients. Reducing ammonia production by changing faecal microbiome in UCD is an attractive treatment approach. We compared faecal microbiome composition of 10 UCD patients, 10 healthy control subjects and 10 phenylketonuria (PKU) patients. PKU patients on a low protein diet were included to differentiate between the effect of a low protein diet and the UCD itself on microbial composition. Participants were asked to collect a faecal sample and to fill out a 24 h dietary journal. DNA was extracted from faecal material, taxonomy was assigned and microbiome data was analyzed, with a focus on microbiota involved in ammonia metabolism.In this study we show an altered faecal microbiome in UCD patients, different from both PKU and healthy controls. UCD patients on dietary and pharmacological treatment had a less diverse faecal microbiome, and the faecal microbiome of PKU patients on a protein restricted diet with amino acid supplementation showed reduced richness compared to healthy adults without a specific diet. The differences in the microbiome composition of UCD patients compared to healthy controls were in part related to lactulose use. Other genomic process encodings involved in ammonia metabolism, did not seem to differ. Since manipulation of the microbiome is possible, this could be a potential treatment modality. We propose as a first next step, to study the impact of these faecal microbiome alterations on metabolic stability. TAKE HOME MESSAGE: The faecal microbiome of UCD patients was less diverse compared to PKU patients and even more compared to healthy controls.

Chronic non-healing ulcers as presenting sign of acquired immunodeficiency syndrome.

Atypical forms of herpes simplex virus (HSV) infections, which indicate severe impairment of cellular immunity can be challenging to diagnose. In this paper, we report the case of an atypical HSV infection presenting as chronic nonhealing wounds, which are the first sign of HIV, in a 50-year-old female patient. The lesions had emerged as two large, chronic, and painful ulcerations on the left buttock and labia major 8 months prior. The skin biopsy revealed multinucleated keratinocytes with ground glass nuclei and intranuclear Cowdry type A viral inclusions. A serologic test for HIV-1 was positive. Her CD4+ T-cell count was 42/mm3. Clinicians should be familiar with the dermatologic manifestations of HIV, as they are occasionally key to correctly suspecting an underlying HIV infection, allowing for early diagnosis and treatment.

Immunization with HIV-1 envelope T20-encoding DNA vaccines elicits cross-clade neutralizing antibody responses.

BACKGROUND: Genetic immunization is expected to induce the expression of antigens in a native form. The encoded peptide epitopes are presented on endogenous MHC molecules, mimicking antigen presentation during a viral infection. We have explored the potential of enfuvirtide (T20), a short HIV peptide with antiviral properties, to enhance immune response to HIV antigens. To generate an expression vector, the T20 sequence was cloned into a conventional plasmid, the novel minicircle construct, and a replicon plasmid. In addition, 3 conventional plasmids that express the envelope of HIV-1 subtypes A, B and C and contain T20 in their gp41 sequences were also tested. RESULTS: All combinations induced HIV-specific antibodies and cellular responses. The addition of T20 as a peptide and as an expression cassette in the 3 DNA vectors enhanced antibody responses. The highest anti-HIV-1 Env titers were obtained by the replicon T20 construct. This demonstrates that besides its known antiviral activity, T20 promotes immune responses. We also confirm that the combination of slightly divergent antigens improves immune responses. CONCLUSIONS: The antiretroviral T20 HIV-1 sequence can be used as an immunogen to elicit binding and neutralizing antibodies against HIV-1. These, or similarly modified gp41 genes/peptides, can be used as priming or boosting components for induction of broadly neutralizing anti-HIV antibodies. Future comparative studies will reveal the optimal mode of T20 administration.

Terbinafine susceptibility and genotypic heterogeneity in clinical isolates of Trichophyton mentagrophytes by random amplified polymorphic DNA (RAPD).

OBJECTIVE OF THE STUDY: The four RAPD systems tested in the present study have aimed at investigating DNA fingerprinting of Trichophyton mentagrophytes strains and the correlation between genotyping and antifungal susceptibility to terbinafine. PATIENTS: Twenty-nine clinical isolates of T. mentagrophytes were recovered from patients suspected of having active dermatophytosis who were referred to the laboratory of medical mycology department in Tehran university. Then, they were subjected to conventional examination by performing direct microscopic examination, culture on primary media, physiological tests. MATERIALS AND METHODS: The in vitro antifungal susceptibility of twenty-nine T. mentagrophytes isolates against terbinafine was evaluated by modified agar dilution method to determine the minimum inhibitory concentration (MIC). Twenty-one sensitive and eight resistant to terbinafine, were submitted to RAPD using 4 decamer primers (A, B, C, D) with the purpose of encountering a genetic marker to terbinafine sensibility and resistance. The UPGMA-Jaccard's correlation coefficient was used to build up dendogram that could represent clusters of similarity. According to their correlation coefficient, the samples were classified as much related (100%), moderately related (80%) and unrelated (<70%). RESULTS: All amplifications revealed distinct polymorphic bands and a total of 34 band positions was scored (0/1) for the 4 primers tested. Genetic distances between each of the isolates were calculated and cluster analysis was used to generate a dendrogram showing relationships between them. The combined dendrogram at an average similarity value of 65% grouped all strains into 2 (A, B) groups corresponding to their susceptibility reactions to terbinafine. All susceptible samples were properly grouped, but a few numbers of resistant isolates were also included. Nevertheless, further biochemical and molecular biological studies will be required to fully elucidate the point that resistance might be the result of a mutation in the gene encoding squalene epoxidase in T. mentagrophytes. CONCLUSION: This study proved efficacy of applying RAPD molecular technique to complement traditional mycological culture and drug susceptibility tests for accurate and appropriate management of recurrent dermatophytosis and highlights the need for newer antifungals that can combat the emergence of terbinafine-resistant T. mentagrophytes strains.