Differentiating pagetoid Bowen disease from Paget disease on the nipple-areola complex: Two unique, challenging cases.

Pagetoid Bowen disease is a subtype of Bowen disease that accounts for 5% of Bowen disease. It is extremely rare for Bowen disease to appear on the nipple-areola complex, with only seven cases described in the previous literature. Of those seven cases, only one was of the pagetoid subtype. We report two cases of pagetoid Bowen disease on this location, one of them being the first case of pagetoid Bowen disease affecting the nipple reported to date. On this location, it is crucial to perform a meticulous differential diagnosis to rule out Paget disease, because of its contrasting therapeutic and prognostic implications. In order to do this, clinical and histopathological aspects must be considered. From a clinical point of view, previous literature has stated that nipple involvement can be a clue that points to Paget disease. However, one of our cases shows that this is not always true. Regarding histopathological analysis, a complete excision of the tumor might be necessary to observe clear features of Bowen disease, such as full-thickness atypia of the epidermis and intercellular bridges. An immunohistochemical panel comprising carcinoembryonic antigen, gross cystic disease fluid protein, epithelial membrane antigen, p63, CK34betaE12, periodic acid-Schiff, estrogen receptor, and progesterone receptor can be decisive in complicated cases.

Vulvar edema: diagnostic clue to Crohn disease.

Vulvar lesions are clinically challenging for physicians because the differential diagnosis may include many entities. Vulvar edema is one of the most frequent symptoms and is normally attributed to a local cause. Herein, we present a case report of vulvar Crohn disease (VCD) in a 9-year-old girl, in which skin lesions preceded the systemic gastrointestinal symptoms. Both clinical features and histopathological findings guided us to an early Crohn disease (CD) diagnosis. Dermatologists often have the opportunity to detect systemic diseases at early stages. A good knowledge of the CD skin manifestations could lead to an early CD diagnosis, especially in children. The suspicion of CD in those cases in which cutaneous involvement precedes digestive symptoms is crucial to prevent future psychological and physical consequences.

Vascular obliteration because of endothelial and myointimal growth in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a systemic multi-organ viral illness. Previous studies have found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the damage to vascular tissues are not well-elucidated yet. Histological data in COVID-19 patients are still limited and are mainly focused on post-mortem analysis. Given that the skin is affected by COVID-19 and the relative ease of its histological examination, we aimed to examine the histology of skin lesions in COVID-19 patients to better understand the disease's pathology. METHODS: Five skin lesions from COVID-19 adult patients were selected for a deep histological tissue examination. RESULTS: A strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cell growth was identified. Endothelial cell distortion generated vascular lumen obliteration and striking erythrocyte and serum extravasation. Significant deposition of C4d and C3 throughout the vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was also observed. CONCLUSIONS: COVID-19 could comprise an obliterative microangiopathy consisting on endothelial and myointimal growth with complement activation. This mechanism, together with the increased vascular permeability identified, could contribute to obliteration of the vascular lumen and hemorrhage in COVID-19. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent increased risk of hemorrhage. Findings of this study could contribute to a better understanding of physiopathological mechanisms underlying COVID-19 on living patients and could help further studies find potential targets for specific therapeutic interventions in severe cases.

Use of permethrin in the treatment of rosacea fulminans during pregnancy: One case report.

Rosacea fulminans (RF) is a rare dermatological condition which occurs exclusively in women and it is characterized by a sudden onset of painful papules, pustules, cysts, and nodules on the face. A 28-year-old woman was referred to our clinic due to a painful facial eruption within the 13th week of her second pregnancy. After physical examination, the diagnosis of RF during pregnancy was established. Several treatments were used: mupirocin ointment, topical zinc oxide, topical erythromycin, oral erythromycin, metronidazole gel, oral metronidazole, oral amoxiciline, and oral prednisone. Finally, the patient was started on 5% permethrin cream with complete clearing of the lesions. Nowadays, a wide range of treatments for rosacea is available: topical metronidazole, oral metronidazole, topical ivermectin, oral tetracyclines, oral isotretinoin, systemic steroids, photodynamic therapy, or pulsed dye laser. However, in pregnant patients, the treatment alternatives are limited. We consider that 5% permethrin cream could be an effective, cheap, and safe treatment not only in regular patients with rosacea but also in pregnant women, representing an important alternative in the context of pregnancy when therapeutic options are limited. To our knowledge, this is the first case of rosacea treated with 5% permethrin cream in monotherapy during pregnancy.

Use of low-dose naltrexone in the treatment of severe Hailey-Hailey disease: One case report.

Hailey-Hailey disease (HHD) or chronic benign familial pemphigus is an autosomal dominant genodermatosis with complete penetrance characterized by painful vesicles, erosions, and macerated intertriginous skin. We present a 66-year-old woman with a personal 35-year history of pruritic recurrent vesicles and erosions in both axillae and inguinal folds. HHD was confirmed by cutaneous biopsy. Past treatments had failed, including topical corticosteroids, antibiotics and oral doxycycline, minocycline, dapsone, and acitretin. Phototherapy and intralesional injection of toxin botulinum A was performed in the axillae. The patient was started on naltrexone 6.25 mg nightly. Six weeks later, complete clearing was observed. At typical doses, naltrexone blocks µ and δ opiod receptors, thereby blocking the union of ß-endorphins at those sites. Paradoxically, at low doses, the partial binding to those receptors leads to a homeostatic increase of opioid receptors and an upregulation of endogenous opioids. Low-dose naltrexone (LDN) may also exert an anti-inflammatory action through its antagonist effect on toll-like receptor 4 found on macrophages. We consider that LDN is an effective and safe alternative for the HHD, representing an important progress in the management of this disease with limited therapeutic options.

Comparative Study of Different Classification Models in Renal-Cell Carcinoma.

The aim of this study was to compare the Memorial Sloan-Kettering Cancer Center (MSKCC) and the Cleveland Clinic Foundation (CCF) models of classification of aRCC patients. In addition, the model developed from the pivotal trial of temsirolimus and those proposed by Motzer et al. in 2004, Escudier et al., Heng et al., Choueiri et al. and Bamias et al. were examined. An observational, retrospective study of patients starting first-line systemic therapy was conducted between 2008 and 2011. The variables used to evaluate the classification models were median overall survival (mOS) and median progression-free survival (mPFS). The comparison of different classification models was performed by comparing the area under the ROC (Receiver Operating Characteristic) curve (AUC) for time-dependent variables proposed by Heagerty. Eighty-eight patients were included. When the different models were compared, it was found that although based on the mOS, the Escudier model had better short-term (1-year) prognostic value, followed by the Heng model; in the long term, the models that presented a higher prognosis capacity were the Hudes and CCF models, closely followed by the Heng model. In addition, the Heng model had a slightly higher predictive ability than the other models. Based on the results, and in line with the European society for medical oncology (ESMO) guidelines, it appears that the model of Heng could be the best model to classify patients with aRCC and combines good short- and long-term prognostics while possessing better predictive ability and a more equal distribution of patients.

Cost-effectiveness analysis of the bevacizumab-irinotecan regimen in the treatment of primary glioblastoma multiforme recurrences.

The purpose of the present study was to calculate the cost-effectiveness of the inclusion of the bevacizumab (BVZ) + irinotecan (CPT-11) regimen in the second-line of treatment for primary glioblastoma multiforme. A retrospective cohort study with a control group was performed in which the cost-effectiveness of a course of chemotherapy was calculated based on survival time and the incremental cost between the two lines of treatment. A total of 77 patients were included, 36 of who formed the BVZ/CPT-11 cohort. The median survival time for the non-BVZ control cohort was 13.23 months [95% confidence interval (CI), 11.79-14.68], while for the BVZ/CPT-11 treatment cohort, the median survival time was 17.63 months (95% CI, 15.38-19.89). Overall, each year of life gained for each patient treated with BVZ/CPT-11 would cost €46,401.99. These results demonstrate the effectiveness of the BVZ/CPT-11 combination, but its incremental cost compared with other lines of treatment or the best care available does not appear to be acceptable for public health systems in the current situation of budgetary adjustments.

Study of the effectiveness of first-line treatment in renal cell carcinoma.

The emergence of novel drugs corresponds with the determination of the effectiveness of the current treatments used in clinical practice. A retrospective observational study was conducted to evaluate the effectiveness of first-line treatments and to test the influence of the prognostic factors established using the Memorial Sloan-Kettering Cancer Center (MSKCC) and the analysis of Mekhail's study for two or more metastatic sites. The primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS) times. A total of 65 patients were enrolled and the mPFS and mOS of the patients treated with sunitinib (n=51) were 9.0 and 20.1 months, respectively, and for the patients treated with temsirolimus (n=14) these were 3.0 and 6.2 months, respectively. In the poor-prognosis (PP) group, a difference of 1.2 months (P=0.049) was found in mPFS depending on the first-line treatment. A difference of 4.1 months (P=0.023) was also found in mPFS when classified by histology (clear verses non-clear cell) in the sunitinib-treatment group. When stratified by the prognostic group, differences of >7 months (P<0.001) were found between the groups. Therefore, it was concluded that the effectiveness of the treatments was reduced compared to previous studies and differences were found in the PP group when classified by first-line drug and histology. Additionally, the influence of prognostic factors on OS and the value of stratifying patients using these factors have been confirmed.

Effectiveness of the bevacizumab-irinotecan regimen in the treatment of recurrent glioblastoma multiforme: Comparison with other second-line treatments without this regimen.

A retrospective cohort study was conducted to analyse the effectiveness of bevacizumab and irinotecan (BVZ/CPT-11) as a second-line treatment in patients with primary glioblastoma multiforme (GBM) in comparison with a control group that were not administered BVZ/CPT-11 at the first recurrence. The difference in overall survival (OS) between the two groups was used as a predictor of effectiveness. OS was calculated according to prognostic factors and gender. A total of 28 and 32 patients were enrolled in the BVZ/CPT-11 cohort and control group, respectively. The median OS was 17.94 months (95% CI, 14.91-20.96) in the BVZ/CPT-11 treatment cohort and 10.97 months (95% CI, 7.65-14.30) in the control cohort. The results obtained on the effectiveness of BVZ/CPT-11 treatment in patients with primary GBM are consistent with data from previous studies. No significant differences were identified in OS based on prognostic factors; therefore, the latter cannot be used to select patients who would incur the greatest benefits from BVZ/CPT-11 treatment.