Survival and prognostic factors in bullous pemphigoid: A retrospective cohort study.

Background Bullous pemphigoid is the most common subepidermal autoimmune blistering disease. Till now, the reported prognostic factors in bullous pemphigoid vary considerably. Aims The purpose of this study was to determine the overall survival rate and prognostic factors in bullous pemphigoid. Methods We conducted a retrospective cohort study on newly diagnosed bullous pemphigoid patients between July 2001 and November 2019 in a referral unit for autoimmune blistering skin diseases in Romania. Results One hundred forty-eight patients were included in the study. The Kaplan-Meier overall survival rates at 1, 3, 5 and 10 years were respectively 74.2% (95% confidence interval, 67.5-81.6%), 53.4% (45.7-62.2%), 43.6% (35.9-53%) and 31.3% (23.5-41.7%). The median follow-up among survivors was 48 months (interquartile range: 11-150). Ninety (60.8%) patients died during the follow-up period; of them, 38 (42.2%) had active disease at the time of death. Advanced age, neurological diseases, valvular heart disease, malignancies, use of statins, skin infections and extensive cutaneous involvement were linked to poorer outcomes, while the use of topical corticosteroids was associated with increased overall survival. Limitations This study lacks a control cohort to validate the obtained results. It was conducted in a retrospective manner in a single centre. In addition, indirect immunofluorescence microscopy was not performed in all patients. Conclusion Beyond ageing and neurological comorbidities, the prognosis of bullous pemphigoid patients was significantly influenced by the presence of skin infections, valvular heart disease, use of statins and extensive cutaneous involvement. Topical corticosteroid treatment was associated with increased survival in these patients.

Risk factors for positive sentinel lymph node, lymphatic or hematogenous dissemination over time in patients with cutaneous melanoma.

The aim of the present study was to assess the influence of localization, age or sex and histopathological characteristics upon the chance of developing lymphatic or hematogenous metastatic spread over time, or a positive sentinel lymph node in cutaneous melanoma patients. Patients from the Department of Dermatology, County Emergency Hospital Cluj-Napoca (Cluj-Napoca, Romania), presenting with cutaneous melanoma confirmed histopathologically and a SPECT/CT or lymphoscintigraphic examination to detect the sentinel lymph node, were included in the present study. Our results revealed that Breslow index >2 mm [odds ratio (OR)=4.22, 95% confidence interval (CI) (1.12; 15.93)], presence of ulceration [OR=6.01, 95% CI (1.87; 19.35)], and positive sentinel lymph node [for at least one sentinel lymph node OR=3.58, 95% CI (1.06; 12.04)] were risk factors for hematogenous metastases. All these, except for the Breslow index >2 mm, were demonstrated to be a risk factor for lymphatic spread metastases over time. Ulceration and male sex also represented risk factors for a positive sentinel lymph node, men having a higher risk of developing sentinel lymph nodes than women [adjusted OR=2.27, 95% CI (1.00; 5.13)]. In conclusion, the predictors that influence the occurrence of lymphatic or hematogenous metastases may differ, ulceration and positive sentinel lymph node being common for both types of metastatic spread, while Breslow index being a significant predictor only for hematogenous metastases. Male sex and the presence of ulceration were demonstrated to be significant risk factors for positive sentinel lymph nodes.

Assessment of sun-related behavior and serum vitamin D in basal cell carcinoma: Preliminary results.

Ultraviolet radiation (UV), mainly from sunlight, is the main risk factor of the most common human skin cancer, basal cell carcinoma (BCC). A positive effect of UV on the skin is its contribution to the synthesis of vitamin D, which is important in sustaining general health, but having high levels of vitamin D is considered a risk factor for BCC. However, vitamin D receptor has antagonistic effects to UV radiation in regulating Sonic Hedgehog pathway. This is a pilot study aimed at characterizing the sun-related behavior and vitamin D status of 52 BCC patients and 59 controls from our geographical area. Patients were included in 4 subgroups: Single, multiple, recurrent, and both multiple and recurrent BCCs. Patients, more than controls, had at least one sunburn in childhood and lentigines (P<0.001). Also, they spent daily, on average, more time in the sun than controls (P<0.001) (3.00-8.00 and 1.50-4.00 h respectively). Outdoor work was similar in both groups. Participants had lower vitamin D serum levels than expected. Due to the small number of cases, no statistically significant differences were found between the subgroups but some tendencies were noted. Patients with only one recurrent BCC had less sunburns than the ones who also developed tumors at multiple sites (P=0.2). Patients with multiple and recurrent tumors had slightly lower vitamin D levels compared with single BCC patients (P=0.1) although they used more vitamin D supplements after the BCC diagnosis (P=0.2). Having a diagnosis of BCC, made patients more compliant to the use of sunscreen cream, but even so, half of them still did not use it. In conclusion, more effort should be invested in sun-related education and public health actions should focus on vitamin D deficiencies.

A novel IKBKG mutation in a patient with incontinentia pigmenti and features of hepatic ciliopathy.

We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor-kappa B in a patient with incontinentia pigmenti. The patient had a severe cholestatic liver disease with features of a ciliopathy and underwent liver transplantation. We cannot establish a link between incontinentia pigmenti, a very rare disease, and hepatic ciliopathy, but we suggest that hepatic evaluation should be considered in patients with incontinentia pigmenti.

Clinico-pathologic, dermoscopic and ultrasound examination of a rare acral tumour involving the nail - case report and review of the literature.

There is a large spectrum of tumors presenting as nodular lesions that may affect the subungual space. We report the case of a 62-year-old woman presenting with a rapidly growing nodular lesion under the nail of the first left toe. Non-invasive examinations using dermoscopy, ultrasonography and elastography were performed for the preoperative assessment of the lesion. The biopsy of the lesion revealed superficial acral fibromyxoma, a benign tumor with predisposition for acral sites. The patient underwent radical surgery with wide resection margins. This is the first case report of a superficial acral fibromyxoma affecting the subungual region characterized by dermoscopic, ultrasonographic and elastographic features. We also performed a short review of the literature.

Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study.

BACKGROUND: Factors associated with survival in pemphigus have not yet been thoroughly addressed. Therefore, in the present study, risk factors for overall mortality in a large group of patients with pemphigus vulgaris and foliaceus were investigated. METHODS: A retrospective hospital-based cohort study was carried out, between October 1998 and November 2012, in the Department of Dermatology of the University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania. The investigated prognostic endpoint was the overall survival of the patients. RESULTS: A total of 130 patients were studied (108 with pemphigus vulgaris and 22 with pemphigus foliaceus). In pemphigus vulgaris group, univariate analysis found a statistically significant association between the age of onset ≥ 65 years (p < 0.001), presence of coronary heart disease (p = 0.006), presence of cardiac arrhythmia (p = 0.004), level of anti-desmoglein1 autoantibodies ≥ 100 U/mL (p = 0.047) at diagnosis and the survival of the patients. An age-adjusted analysis showed significant results for coronary heart disease. Multivariate analysis identified the age of onset ≥ 65 years and the presence of coronary heart disease at diagnosis as independent risk factors associated with overall mortality. In patients with pemphigus foliaceus, age of onset ≥ 65 years (p = 0.021) was associated with poor survival. CONCLUSIONS: In addition to common prognostic factors, including older age and cardiovascular comorbidities, level of autoantibodies was found to be a disease-specific factor associated with overall mortality in pemphigus vulgaris. The newly identified factors have major implications for the stratification of patients and should greatly facilitate further epidemiological studies in pemphigus. In addition, they provide useful information for the design of personalized therapeutic plans in the clinical setting.

An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice.

Uncontrolled macrophage activation is now considered to be a critical event in the pathogenesis of chronic inflammatory diseases such as atherosclerosis, multiple sclerosis, and chronic venous leg ulcers. However, it is still unclear which environmental cues induce persistent activation of macrophages in vivo and how macrophage-derived effector molecules maintain chronic inflammation and affect resident fibroblasts essential for tissue homeostasis and repair. We used a complementary approach studying human subjects with chronic venous leg ulcers, a model disease for macrophage-driven chronic inflammation, while establishing a mouse model closely reflecting its pathogenesis. Here, we have shown that iron overloading of macrophages--as was found to occur in human chronic venous leg ulcers and the mouse model--induced a macrophage population in situ with an unrestrained proinflammatory M1 activation state. Via enhanced TNF-α and hydroxyl radical release, this macrophage population perpetuated inflammation and induced a p16(INK4a)-dependent senescence program in resident fibroblasts, eventually leading to impaired wound healing. This study provides insight into the role of what we believe to be a previously undescribed iron-induced macrophage population in vivo. Targeting this population may hold promise for the development of novel therapies for chronic inflammatory diseases such as chronic venous leg ulcers.

Pemphigus vulgaris is the most common autoimmune bullous disease in Northwestern Romania.

BACKGROUND: Autoimmune bullous diseases are organ-specific diseases characterized by autoreactive T and B cells specific for structural proteins of the skin. The incidence and prevalence of autoimmune blistering diseases vary in different countries and their epidemiology has not yet been addressed in Romania. METHODS: In this study between 2001 and 2007, we prospectively investigated a total of 116 patients with autoimmune blistering diseases from the Northwestern region of Romania. The diagnosis was based on the clinical, histo- and immunohistological as well as serological findings. RESULTS: Pemphigus was the most common disease representing 58.6% of the case (68 cases); 40 cases (34.5%) were diagnosed with bullous pemphigoid (BP) and eight cases (6.9%) with other autoimmune sub-epidermal diseases. The incidence and prevalence of pemphigus diseases were four patients/1,000,000 inhabitants/year and 0.00248%, respectively. BP occurred in 2.5/1,000,000 inhabitants/year and its prevalence was 0.00146%. While the average onset age for pemphigus vulgaris was 53 years, BP patients were first diagnosed at a mean age of 73.6 years. CONCLUSION: The genetic background of the local population may explain why pemphigus occurs more commonly than BP in Northwestern Romania compared with the population of Western Europe. In addition, the shorter life expectancy in Romania (71.3 years) compared with Western Europe (>80 years) may contribute to this phenomenon.

Hyperimmunoglobulin E syndrome (Job's syndrome).

Hyperimmunoglobulin E (Hyper IgE) syndrome, also described as Job's syndrome, is a rare primary immunodeficiency disease characterized by recurrent skin and respiratory tract infections, chronic eczematous dermatitis, skeletal abnormalities associated with markedly elevated serum IgE levels. Variable impaired T cell function is described in this disease, but no direct association between IgE levels or clinical manifestations with these abnormalities does exist. We report a case of a patient with recurrent staphylococcal cold abscesses, eczematous dermatitis and high serum IgE levels in which the treatment with Cyclosporine A seems to have a favorable effect.