BACKGROUNDaAlthough rare, bullous pemphigoid (BP) is the most common autoimmune blistering disease. Recent studies have shown that patients with bullous pemphigoid are more likely to have neurological and psychiatric diseases, particularly prior to the diagnosis of bullous pemphigoid.OBJECTIVEThe aims were: (i) to evaluate the demographic and clinical features of bullous pemphigoid from a database of patients at a Portuguese university hospital and (ii) to compare the prevalence of comorbid conditions before the diagnosis of bullous pemphigoid with a control group.METHODSSeventy-seven patients with bullous pemphigoid were enrolled in the study. They were compared with 176 age- and gender-matched controls, which also had the same inpatient to outpatient ratio, but no history of bullous or cutaneous malignant disease. Univariate and multivariate analyses were used to calculate odds ratios for specific comorbid diseases.RESULTSAt least one neurologic diagnosis was present in 55.8% of BP patients compared with 20.5% controls (p<0.001). Comparing cases to controls, stroke was seen in 35.1 vs. 6.8%, OR 8.10 (3.80-17.25); dementia in 37.7 vs. 11.9%, OR 5.25 (2.71-10.16); and Parkinson's disease in 5.2 vs. 1.1%, OR 4.91 (0.88-27.44). Using multivariate analysis, all diseases except Parkinson's retained their association with BP. Patients under systemic treatment were eight times more likely to have complications than those treated with topical steroids (p< 0.017).CONCLUSIONSThe results of this study substantiate the association between BP and neurological diseases. In addition, they highlight the potential complications associated with the treatment of BP.

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Glioblastoma is the most common and aggressive brain tumor, with a subpopulation of stem-like cells thought to mediate its recurring behavior and therapeutic resistance. The epithelial-mesenchymal transition (EMT) inducing factor Zeb1 was linked to tumor initiation, invasion, and resistance to therapy in glioblastoma, but how Zeb1 functions at molecular level and what genes it regulates remain poorly understood. Contrary to the common view that EMT factors act as transcriptional repressors, here we show that genome-wide binding of Zeb1 associates with both activation and repression of gene expression in glioblastoma stem-like cells. Transcriptional repression requires direct DNA binding of Zeb1, while indirect recruitment to regulatory regions by the Wnt pathway effector Lef1 results in gene activation, independently of Wnt signaling. Amongst glioblastoma genes activated by Zeb1 are predicted mediators of tumor cell migration and invasion, including the guanine nucleotide exchange factor Prex1, whose elevated expression is predictive of shorter glioblastoma patient survival. Prex1 promotes invasiveness of glioblastoma cells highlighting the importance of Zeb1/Lef1 gene regulatory mechanisms in gliomagenesis.

Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction.

During mitosis, chromatin condensation is accompanied by a global arrest of transcription. Recent studies suggest transcriptional reactivation upon mitotic exit occurs in temporally coordinated waves, but the underlying regulatory principles have yet to be elucidated. In particular, the contribution of sequence-specific transcription factors (TFs) remains poorly understood. Here we report that Brn2, an important regulator of neural stem cell identity, associates with condensed chromatin throughout cell division, as assessed by live-cell imaging of proliferating neural stem cells. In contrast, the neuronal fate determinant Ascl1 dissociates from mitotic chromosomes. ChIP-seq analysis reveals that Brn2 mitotic chromosome binding does not result in sequence-specific interactions prior to mitotic exit, relying mostly on electrostatic forces. Nevertheless, surveying active transcription using single-molecule RNA-FISH against immature transcripts reveals differential reactivation kinetics for key targets of Brn2 and Ascl1, with transcription onset detected in early (anaphase) versus late (early G1) phases, respectively. Moreover, by using a mitotic-specific dominant-negative approach, we show that competing with Brn2 binding during mitotic exit reduces the transcription of its target gene Nestin. Our study shows an important role for differential binding of TFs to mitotic chromosomes, governed by their electrostatic properties, in defining the temporal order of transcriptional reactivation during mitosis-to-G1 transition.

Pyoderma gangrenosum (PG) is a rare, chronic neutrophilic dermatosis of unknown aetiology that usually presents with necrotising ulcers, although the evolution of the disease can be variable and is not always progressive. Its pathogenesis is poorly understood but an underlying immunological abnormality seems to be implicated in the genesis of the lesions. This hypothesis is supported by its frequent association with inflammatory bowel disease, malignancies, and rheumatological disorders. The diagnosis is challenging even for dermatologists as there are no specific tests or histological features. There are no clinical trials evaluating the efficacy of the different drugs used to treat the disease due to its rarity, and therefore there is no ’gold standard’ therapy. In this mini-review we describe the main clinical aspects of PG, its pathophysiology, association with underlying diseases, diagnosis, treatment options, and prognosis.

Background. Sentinel lymph node biopsy (SLNB) is a standard procedure for patients with localized cutaneous melanoma. The National Comprehensive Cancer Network (NCCN) Melanoma Panel has reinforced the status of the sentinel lymph node (SLN) as an important prognostic factor for melanoma survival. We sought to identify predictive factors associated with a positive SLNB and overall survival in our population. Methods. We performed a retrospective chart review of 221 patients who have done a successful SLNB for melanoma between 2004 and 2010 at our department. Univariate and multivariate analyses were done. Results. The SLNB was positive in 48 patients (21.7%). Univariate analysis showed that male gender, increasing Breslow thickness, tumor type, and absence of tumor-infiltrating lymphocytes were significantly associated with a positive SLNB. Multivariate analysis confirmed that Breslow thickness and the absence of tumor-infiltrating lymphocytes are independently predictive of SLN metastasis. The 5-year survival rates were 53.1% for SLN positive patients and 88.2% for SLN negative patients. Breslow thickness and the SLN status independently predict overall survival. Conclusions. The risk factors for a positive SLNB are consistent with those found in the previous literature. In addition, the SLN status is a major determinant of survival, which highlights its importance in melanoma management.

[Cr]) along the last 20 years, particularly considering age, sex and its relation with occupational activity. Results: Out of 5 250 consecutively patch-tested patients, 1 626 (31%) were reactive to at least one metal (26.5% to Ni; 10.0% to Co and 7.9% to Cr). Women had a higher prevalence of sensitization to Ni (34.4% vs 8.9%) whereas men were more reactive to Cr (11.5% vs 5.0%). Nickel sensitization did not decrease significantly over the years, although in recent years among women sensitized to nickel the percentage of younger patients (16-30 years-old) is significantly lower (p < 0.001). Chromium sensitization significantly decreased, particularly in men (r = -0.535), and mainly in the construction workers (r = -0.639). Chromium reactivity associated with the shoe dermatitis has remained stable. Discussion: We emphasize the higher and stable percentage of nickel sensitized individuals suggesting, so far, a low impact from the EU Ni directive, although a decreasing percentage in the the younger group among Ni sensitized women may suggest a beneficial effect is becoming evident is this age group. On the contrary, the impact of the directive regarding the modification of Cr in cement seems to be effective. There is now a need to regulate chromium content in leather products, namely in shoes. Conclusions:The regulation of interventional measures related either to the manufacture and trade of adornments or professional use will better protect the population of allergy to metals.