Brain MRI findings in patients with bullous pemphigoid: A case-control study.

Evidence suggests that bullous pemphigoid (BP) is associated with multiple neurological disorders. We aimed to compare brain magnetic resonance (MRI) findings between BP patients and a control group. This case-control study included patients with BP referred to two dermatology clinics during a two-year period. A group of individuals attending the same clinics for cosmetic procedures were selected as controls. First, participants' general information including age, gender, education, weight and underlying disease was recorded. For BP patients, the drugs and the BP Disease Area Index (BPDAI) were recorded as well. Then, all participants underwent brain MRI without contrast. The Fazekas scale, the general cerebral atrophy (GCA) score, and the Medial Temporal lobe Atrophy (MTA) score were used to assess MRI images. Overall, 24 BP patients and 24 controls were evaluated in this study. Both groups were comparable regarding age, gender and education. However, diabetes and hypertension were more frequent in the control group. The mean BPDAI total score was 51.39 ± 68.92 in BP patients and most of them used rituximab (41.7%). None of the participants had MS or Alzheimer MRI patterns. There was no difference between groups in terms of GCA and MTA scores. Furthermore, the frequency of partially empty sella did not differ significantly between BP patients and controls (p = 0.461); nevertheless, grade-3 Fazekas was significantly higher in BP patients compared to controls (25% vs. 0%, p = 0.019). Of note, one BP patient had an epidermoid cyst and another had moderate enlargement of three ventricles. Also, new infarcts were observed in two and old infarcts in four BP patients. Although the majority of abnormal brain MRI findings were more frequent in BP patients compared to controls, only grade-3 Fazekas was significantly higher and acute infarcts were exclusively observed in BP patients.

The diagnostic value of p63, p16, and p53 immunohistochemistry in distinguishing seborrheic keratosis, actinic keratosis, and Bowen's disease.

Seborrheic keratosis (SK), actinic keratosis (AK), and Bowen's disease (BD) are squamoproliferative disorders of the skin. Histologically, they may mimic each other and therefore, they might be misinterpreted, especially in small samples. The aim of this study is to clarify the expression of p63, p16, and p53 proteins in SK, AK, and BD and evaluate the efficacy of these markers in order to distinguish between the aforementioned lesions. A total of 46 cases were collected (15 SK, 16 AK, and 15 BD) and stained for p63, p16, and p53. The stain intensity and the cell distribution labeling were scored and then analyzed by SPSS software. All cases of BD which became positive for p53 revealed basal keratinocytes sparing. Instead, all or nearly all basal keratinocytes in AK cases were positive for this marker. These were also seen in p16 staining results and they were between AK and BD (P = .024). Our study demonstrates p16 and p53 are useful markers in separating AK and BD according to basal keratinocytes involvement and sparing, respectively.

Measurement of melatonin, indole-dioxygenase, IL-6, IL-18, ferritin, CRP, and total homocysteine levels during herpes zoster.

The risk of herpes zoster (HZ) increases with age and declining immune function. Increased oxidative stress and inflammatory conditions may cause a negative impact on the immune responses. The present study aimed to assess the levels of oxidative/inflammatory stress biomarkers in HZ patients compared with the controls. This case-control study included 43 HZ patients and 47 age-matched controls. Melatonin (MLT), Indole-dioxygenase (IDO), Interleukin-18 (IL-18), Interleukin-6 (IL-6), ferritin, C-reactive protein (hsCRP), and total homocysteine (tHcy) levels were measured and compared in both groups. The significant high levels of IDO, IL-18, IL-6, ferritin, hsCRP, and tHcy, as well as low levels of MLT were found in HZ patients compared with the controls (P < 0.001); these significant differences were also associated with rash and pain severity (P < 0.001). The final logistic regression model with the area under the curve (0.99; 95% confidence interval [CI], 0.98-1.00) showed the association of HZ with decreased level of MLT (odds ratio [OR], 0.95; 95% CI, 0.92-0.98; P = 0.007) and increased levels of tHcy (OR, 1.53; 95% CI, 1.06-2.19; P = 0.02). The findings showed increased inflammation-associated oxidative stress in HZ patients. Elevated tHcy levels and reduced MLT levels may be associated with the manifestation of HZ. More investigations are required to confirm the results.

Neutrophil/platelet to lymphocyte ratio in monitoring of response to TNF-α inhibitors in psoriatic patients.

Neutrophil or platelet to lymphocyte ratio (NLR and PLR) has been proposed to be used as prognostic purposes in a variety of diseases. The aim of this study was to evaluate the usefulness of these ratios in monitoring of response to TNF-α-inhibitors in psoriatic patients. Eighty psoriatic patients were included and treated with TNF-α-inhibitors for 12 months based on drug protocol. Hematologic indices, including NLR and PLR values were assessed before and after treatment. Data on psoriasis area and severity index (PASI), smoking behavior, alcohol intake habit, nail abnormality, body mass index (BMI), joint involvement, and disease duration were also recorded. PASI scores were improved significantly after one-year treatment (P = .000). Furthermore, this type of treatment significantly reduced the NLR and PLR (P = .000). These changes were in accordance with PASI scores. Patients with BMI greater than 24.9 had higher, but non-significant NLR and PLR than normal or lean individuals. Cigarette smokers and alcohol consumers had lower NLR and PLR values than other individuals (P < .05). There was no significant association between NLR and PLR and joint or nail involvement. Although NLR and PLR will not be helpful in primary diagnosis of inflammatory diseases, they could be accounted as monitoring tools in management of psoriasis or globally indicators of inflammation.

Evaluation of serum level of sex hormones in women with frontal fibrosing alopecia in comparison to healthy controls.

The pathogenesis of frontal fibrosing alopecia (FFA) is still unknown while hormonal factors have been postulated to play a role. There is scarce evidence with divergent results on the role of sex hormones in FFA. To evaluate the possible association between sex hormone levels and FFA, this study included 30 female cases of FFA and 34 healthy controls. Serum free testosterone, dehydroepiandrosterone sulfate (DHEAS), Luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17-OH progesterone, androstenedione, and prolactin levels were measured in all subjects. Median and interquartile ranges of DHEAS and androstenedione were 79.26 (52.91-195.50) and 1.41 (0.90-2.29) in patients and 152.34 (81.72-218.63) and 2.31 (1.54-2.84) in healthy controls, respectively. The serum levels of DHEAS and androstenedione were significantly lower in FFA patients in comparison with healthy controls (P-value = .038 and .012, respectively). There were no significant differences in serum levels of free testosterone, LH, FSH, 17-OH progesterone, and prolactin between the FFA group and the control group The lower serum levels of DHEAS and androstenedione in FFA patients compared to controls is supporting a new growing concept of the low androgen level theory in the pathogenesis FFA, while the exact mechanism, clinical significance, and also the potential therapeutic effects of these hormones in FFA remain to be determined in future studies.

Anti-Staphylococcal and cytotoxic activities of the short anti-microbial peptide PVP.

Over the past years, short anti-microbial peptides have drawn growing attention in the research and trade literature because they are usually capable of killing a broad spectrum of pathogens by employing unique mechanisms of action. This study aimed to evaluate the anti-bacterial effects of a previously designed peptide named PVP towards the clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) in vitro. Secondary structure, cytotoxicity, and membrane-permeabilizing effects of the peptide were also assessed. PVP had a tendency to adopt alpha-helical conformation based upon structural predictions and circular dichroism spectroscopy (in 50% trifluoroethanol). The peptide showed MIC values ranging from 1 to 16 µg/mL against 10 strains of MRSA. In contrast to ciprofloxacin and gentamicin, PVP at sub-lethal concentration (1 µg/mL) did not provoke the development of peptide resistance after 14 serial passages. Remarkably, 1 h of exposure to 4 × MBC of PVP (8 µg/mL) was sufficient for total bacterial clearance, whereas 4 × MBC of vancomycin (8 µg/mL) failed to totally eradicate bacterial cells, even after 8 h. PVP showed negligible cytotoxicity against human dermal fibroblasts at concentrations required to kill the MRSA strains. The results of flow cytometric analysis and fluorescence microscopy revealed that PVP caused bacterial membrane permeabilization, eventually culminating in cell death. Owing to the potent anti-bacterial activity, fast bactericidal kinetics, and negligible cytotoxicity, PVP has the potential to be used as a candidate antibiotic for the topical treatment of MRSA infections.

The elevated level of osteopontin in patients with pemphigus vulgaris: A cytokine-like protein with a therapeutic potential.

BACKGROUND: Pemphigus vulgaris (PV) is a life-threatening autoimmune disease with no certain treatment. Anticytokine therapy is being increasingly discussed in multiple autoimmune diseases. Osteopontin (OPN) is a glycoprotein produced by a variety of immune cells. Increased OPN serum levels have been reported in several autoimmune diseases, with targeting OPN considered as a promising therapy in these diseases. However, the role of OPN in PV has not been well studied so far. OBJECTIVE: To investigate whether OPN level is elevated in PV patients in the active stage of the disease and to examine its possible relationship with disease severity and anti-desmoglein (anti-Dsg) antibodies levels. MATERIALS AND METHODS: This study included 53 consecutive subjects affected by PV and 38 age- and sex-matched healthy controls. Clinical characteristics and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) were assessed. Serum OPN levels (pg/mL) and anti-Dsg antibodies were also measured. RESULTS: The serum OPN level of the patient group proved to be statistically higher than that of the control group (11.08 ± 5.24 vs 8.47 ± 5.68; p = .02). No significant relationship were detected between the serum OPN level and anti-Dsg1 or anti-Dsg3 antibodies (r = 0.1, p = .2 and r = 0.1, p = .4), respectively. In addition, no correlation was found between serum OPN levels and severity of PV as measured by ABSIS (r = 0.08 and p = .5). CONCLUSION: The growth observed in OPN levels in pemphigus patients suggests the role of OPN in pemphigus pathogenesis, but there is a need for more extensive studies to show how OPN can be associated with the PV pathogenesis and whether OPN could be used as an important therapeutic target in pemphigus disease.

Methylprednisolone pulse therapy plus adjuvant therapy for pemphigus vulgaris: an analysis of 10 years' experience on 312 patients.

Steroid pulse therapy has shown satisfactory efficacy and safety in treating pemphigus vulgaris (PV). However, there is a paucity of data about the efficacy and safety of methylprednisolone, despite its frequent administration. The aim of this study is to evaluate the efficacy and safety of steroid pulse therapy in treating PV. In this 10-year retrospective cohort study, 312 patients with PV, who had received methylprednisolone pulse therapy, were included. Data of pulse therapy sessions, adjuvant medications, dosages, remission rates, complications, and mortalities were collected from all patients. A total of 276 patients out of 312 underwent the final follow-up at least 6 months after the last session of pulse therapy. Complete remission off therapy was achieved in 83 patients (30%), and 152 patients (55%) had complete remission on therapy. About 29 (10.5%) patients had lesions of pemphigus at the time of the study follow-up, and 26.8% of remained patients were on the minimal therapy. Methylprednisolone pulse therapy could be considered as an option for proper control of PV in severe cases. It might lead to shorter periods of hospitalization and reduce the need to take long-term high-dose oral steroid therapy.

Melittin: from honeybees to superbugs.

The emergence of antibiotic-resistant bacteria, dubbed superbugs, together with relative stagnation in developing efficient antibiotics has led to enormous health and economic problems, necessitating the need for discovering and developing novel antimicrobial agents. In this respect, animal venoms represent a rich repertoire of pharmacologically active components. As a major component in the venom of European honeybee Apis mellifera, melittin has a great potential in medical applications. In this mini-review, we summarize a multitude of studies on anti-bacterial effects of melittin against planktonic and biofilm-embedded bacteria. Several investigations regarding synergistic effects between melittin and antibiotics were also described. On the whole, the properties of melittin can open up new horizons in a range of biomedical areas, from agriculture to veterinary and clinical microbiology.

Impaired oxidative status as a potential predictor in clinical manifestations of herpes zoster.

Oxidative stress, caused by an imbalance between reactive oxygen species and antioxidants, is related to many dermatologic diseases. Increased reactive oxygen species is also associated with various decreased T-cell immune responses. The incidence and severity of herpes zoster (HZ), which is caused by the reactivation of varicella-zoster virus, increase with age because of declining cell-mediated immunity. The main purpose of this study was to assess the levels of oxidative stress biomarkers in patients with HZ compared with control subjects. In this case-control study, the serum levels of total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index, glutathione, superoxide dismutase, and total polyphenol content (TPC) in 43 patients with HZ and 47 age-matched controls were determined, and their biomarker patterns were compared. TAC and TPC levels were significantly lower in patients with HZ; however, TOS and oxidative stress index levels were significantly higher in comparison with the control (P < .001). In addition, a significantly strong negative correlation was found between TAC and TPC with TOS levels in patients with HZ (r = -.79, P < .001; r = -.81, P < .001, respectively). Our findings showed an oxidative stress imbalance in HZ. Whether this change correlates with HZ pathogenesis or is a consequence of the inflammatory response to HZ needs more investigation.

Risk factors in patients with oral pemphigus vulgaris: a case-control study.

Pemphigus vulgaris (PV) is considered a chronic disease with a potentially fatal outcome. Studies have suggested that environmental factors and personal habits play an important role in the pathogenesis of PV, but more studies are required to elaborate their connection to the disease. The goal of this multicenter case-control study was to determine some of the environmental factors related to PV. Cases (n = 99) were patients with PV, and controls (n = 198) were individuals who did not have PV. Data about demographics, history, clinical findings, occupational exposures to pesticides, smoking status, number of births (parity), herpes simplex virus (HSV) infection, and fast food consumption were collected using a structured questionnaire. Chi-square and logistic regression analyses were used for data analysis. Univariate logistic regression analysis indicated that the statistically significant factors related to PV were infection with HSV in recent weeks (odds ratio [OR], 3.35; 95% confidence interval [CI], 1.75-6.43), parity (OR, 0.50; 95% CI, 0.39-0.63), and lack of occupational exposure to pesticides (OR, 0.36; 95% CI, 0.21-0.60). Multivariate analysis revealed that significant factors were cessation of smoking (adjusted odds ratio [AOR], 4.36; 95% CI, 1.50-12.66), HSV infection (AOR, 2.91; 95% CI, 1.47-5.75), and lack of occupational exposure to pesticides (AOR, 0.35; 95% CI, 0.20-0.63). The findings indicated that cessation of smoking and HSV infection in recent weeks are risk factors for PV, while lack of occupational exposure to pesticides and increasing parity (a greater number of births) are protective factors against PV.

Rituximab-induced psoriasis in a patient with pemphigus vulgaris: A case report and literature review.

Key Clinical Message: Rituximab which is established as a main treatment for pemphigus vulgaris can be a potential causative factor for development of psoriasis in some patients. It is preferred to avoid using rituximab in patients who had a history of psoriasis. Acquainting medical doctors about rituximab-related cutaneous complications will help them in detection and management. Abstract: Rituximab is a human/murine monoclonal antibody targeting the CD20 antigen on B-lymphocytes surface. Although it is used as promising treatment for pemphigus, nowadays it is also a new therapy for other autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, and others like non-Hodgkin's lymphoma. Although there is increasing evidence regarding the safety and effectiveness of rituximab in these diseases, many cutaneous adverse effects have been reported. Here, we describe a 48-years-old patient affected with pemphigus vulgaris who developed psoriatic lesions on her on scalp, trunk, and extremities, 4 months after the second course of rituximab.

Mild cognitive impairment in pemphigus.

BACKGROUND: Pemphigus is a group of autoimmune blistering disorders that have been associated with dementia in previous studies. Mild cognitive impairment (MCI) can be the first stage of progression into dementia. The objective of the present study was to evaluate the frequency of MCI in pemphigus patients compared to a control group. METHODS: This case-control study included 80 patients with pemphigus referred to the dermatology clinics of Shohadaye Tajrish and Loghman Hakim hospitals, Tehran, Iran, in 2021. A group of 80 individuals without pemphigus who visited the same clinics for cosmetic consultation or interventions were regarded as controls. Age, sex, marital status, and education were recorded for all participants. Disease duration, medications, and severity were noted for pemphigus patients. The Persian version of the Montreal Cognitive Assessment (MoCA) test was used to assess cognitive function. RESULTS: MCI was significantly more frequent in pemphigus patients than in controls (55% vs. 37.5%, P = 0.026). Furthermore, the total MoCA score was significantly lower in pemphigus patients compared to controls (23.98 ± 3.77 vs. 25.21 ± 3.45, P = 0.032); however, among MoCA's different domains, only the executive functions score was significantly lower in pemphigus patients (P = 0.010). After adjustment, multivariable logistic regression analysis revealed that every 1-year higher education in patients decreased the odds of MCI by 52% (adjusted odds ratio = 0.483, 95% confidence interval 0.326; 0.715, P < 0.001). CONCLUSIONS: The frequency of MCI was found to be significantly higher, and overall scores of the MoCA test, as well as its executive function domain, were significantly lower among pemphigus patients in this study compared to the control group. Additionally, a higher level of education was associated with decreased odds of MCI in pemphigus patients. Identifying pemphigus patients with MCI through the use of the MoCA test can facilitate early intervention, enabling them to seek help and support.

Iranian psoriasis registry: Research protocol and preliminary results of a pilot study.

BACKGROUND: Psoriasis as a common cutaneous inflammatory disease affect many aspects of patients' life. Disease registries render it possible to collect valuable data regarding a disease prevalence and burden as well as long-term observations concerning possible therapeutic regimens. METHODS: This registry was designed for the ongoing systematic data collection on patients with psoriasis at two referral dermatology centers in Iran. The pilot phase of the registry was used to identify possible obstacles in the application and execution of systematic registration. RESULTS: A total of 281 patients were registered with the mean age of 42.02 years. The disease duration was 12.06 ± 10.90 years with the variety of clinical presentations. There was no significant difference between males and females in the age of disease onset (p = 0.53). Notably, 167 patients had children. Among them, 13 had children with psoriasis. The gender of the affected parent did not affect the possibility of psoriasis transmission to the child, and no significant difference was seen between the two sexes (P = 0.569). Regarding treatment, 99.4% of patients (n = 280) had used topical agents, 52.3% (n = 147) biologics, and 60.9% (n = 171) nonbiologic medications. CONCLUSION: Clinical trials report the efficacy and safety data regarding limited study populations in a restricted time window, and the results may differ from the general population. This highlights the importance of registry-based studies for collecting and analyzing longitudinal information. In terms of long-term disease complications such as malignancies, cardiovascular events, and serious adverse events, registry-based studies will help clinicians better recognize and manage each disease.

Variation in the Care of Children with Inflammatory Bowel Disease Within and Across Canadian Provinces: A Multi-Province Population-Based Cohort Study.

Purpose: The incidence of childhood-onset inflammatory bowel disease (IBD) is rising. We described variation in health services utilization and need for surgery among children with IBD between six and 60 months following IBD diagnosis across Canadian pediatric centers and evaluated the associations between care provided at diagnosis at each center and the variation in these outcomes. Patients and Methods: Using population-based deterministically-linked health administrative data from four Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario) we identified children diagnosed with IBD <16 years of age using validated algorithms. Children were assigned to a pediatric center of care using a hierarchical approach based on where they received their initial care. Outcomes included IBD-related hospitalizations, emergency department (ED) visits, and IBD-related abdominal surgery occurring between 6 and sixty months after diagnosis. Mixed-effects meta-analysis was used to pool results and examine the association between center-level care provision and outcomes. Results: We identified 3784 incident cases of pediatric IBD, of whom 2937 (77.6%) were treated at pediatric centers. Almost a third (31.4%) of children had ≥1 IBD-related hospitalization and there were 0.66 hospitalizations per person during follow-up. More than half (55.8%) of children had ≥1 ED visit and there were 1.64 ED visits per person. Between-center heterogeneity was high for both outcomes; centers where more children visited the ED at diagnosis had more IBD-related hospitalizations and more ED visits during follow-up. Between-center heterogeneity was high for intestinal resection in Crohn's disease but not colectomy in ulcerative colitis. Conclusion: There is variation in health services utilization among children with IBD and risk of undergoing intestinal resection in those with Crohn's disease, but not colectomy among children with ulcerative colitis, across Canadian pediatric tertiary-care centers. Improvements in clinical care pathways are needed to ensure all children have equitable and timely access to high quality care.

Oncolytic effect of SARS-CoV-2 in a patient with mycosis fungoides: A case report.

The most common variant of cutaneous T-cell lymphomas (CTCL) is mycosis fungoides (MF). Patients with MF often experience a chronic course of disease. The spontaneous regression (SR) of MF is rare, and the factors that predict SR have not been recognized yet. Here, we are reporting a case of persistent MF who had prominent remission after COVID-19. This case report supports the possible antineoplastic effect of SARS-CoV-2. Understanding the underlying etiology of such effect can result in development of new target therapies for MF.

Childhood-onset keratosis lichenoides chronica: A case report.

Keratosis lichenoides chronica (KLC) is a rare dermatosis which represents different clinical characteristics between adult- and pediatric-onset cases. We described a childhood case of KLC with features typical for adult-onset disease. Acitretin led to partial improvement of her skin, but not mucosal, lesions.

Granuloma faciale with disseminated extra facial lesions.

Granuloma faciale (GF) is a rare cutaneous disorder categorized as a localized form of small vessel vasculitis. Clinically, it manifests as single or multiple, well-demarcated, red-brown plaques, papules and nodules, nearly always confined to the face. Herein, we report a 39-year-old man with multiple red-brown, infiltrated plaques on his face and extrafacial lesions on the back, shoulders, and both arms. Skin biopsy revealed typical histopathological findings of GF. The patient failed to respond to pulsed dye laser, but intralesional triamcinolone combined with cryotherapy led to an acceptable response.