Histopathologic and direct immunofluorescence findings of the papulopustular lesions in Behçet's disease

Although papulopustular lesions are common in patients with Beh?et's disease (BD), clinically they may not be differentiated from other diseases with papulopustular presentation such as acne vulgaris or folliculitis. Therefore, there is disagreement as to whether they should be used as a diagnostic criterion in BD. The aim of this study was to determine whether the histopathologic evaluation of the papulopustular lesions may assist in the diagnosis of BD. Eighteen patients with BD and 16 control patients consisting of eleven patients with bacterial folliculitis and five patients with acne vulgaris were included in the study. After the detailed histopathologic evaluation by two pathologists who were blinded to the clinical diagnoses, the histopathologic findings were classified into three patterns as follows; pattern I: vasculitis (lymphocytic or leucocytoclastic); pattern II: folliculitis and/or perifolliculitis; pattern III: superficial and/or deep perivascular, and/or interstitial dermatitis. In addition, direct immunofluorescence studies were performed in order to evaluate the deposition of IgM, IgG, IgA, C3, or fibrinogen in dermal blood vessels. 27.8% of the patients with BD (5 patients) revealed lymphocytic vasculitis, while none of the control group did; and the difference was found statistically significant (P=0.046). The rate of pattern II which included folliculitis and/or perifolliculitis was 50.0% in control patients and 16.7% in the patients with BD; and the difference was found statistically significant (P=0.038). No difference was found between the two groups with regard to pattern III or direct immunofluorescence findings (P>0.05). Our results indicate that only vasculitic changes can be useful when histopathological features of papulopustular lesions are to be employed as a diagnostic criterion in patients with suspected BD.     

Increased advanced oxidation protein products in Behçet's disease: a new activity marker?

Background Behçet's disease (BD) is a chronic inflammatory disease with unknown pathogenesis. As various functions of neutrophils in peripheral blood, such as chemotaxis, phagocytosis and generation of reactive oxygen species (ROS) increase in BD, ROS‐mediated oxidative stress related to neutrophil activation may have an important role in the pathogenesis of BD. Objectives To investigate the importance of neutrophil activation as the main source of oxidative stress through protein oxidation in the pathogenesis of BD, and also to investigate whether one of the products of protein oxidation, advanced oxidation protein products (AOPP), may be used as an activity marker for BD. Methods Patients with BD (n = 49), at active and inactive stages, with or without evidence of uveitis, and healthy volunteers (n = 40) were entered into the study. A full blood count, peripheral blood smears, routine biochemical analyses, C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) measurements were performed in all patients preceding the study. Plasma myeloperoxidase (MPO) activity, representing neutrophil activation, and biomarkers of oxidative stress reflecting protein oxidation, such as levels of AOPP and thiol, were measured spectrophotometrically. Statistical comparisons were made using Mann–Whitney U‐tests, Student's t‐tests, anova /post‐anova tests and correlation analyses. Results In all patients, the results of full blood count, peripheral blood smears and routine biochemical analyses were in the normal range, but mean values of CRP and ESR were higher than laboratory reference values. Plasma MPO activity and AOPP levels were found to be higher and thiol values lower in the total patient group and individual subgroups than in controls. Patients with active BD had significantly higher MPO and AOPP levels and lower thiol levels than patients with inactive BD. There was no difference between uveitis‐positive and uveitis‐negative subgroups in MPO and thiol levels, but AOPP levels were lower in the latter group. Patients with active BD ± uveitis were shown to have increased MPO and AOPP but decreased thiol levels in comparison with the inactive BD, uveitis‐negative subgroup. There were strong positive correlations between ESR and CRP, ESR and MPO, ESR and thiol, ESR and AOPP, CRP and MPO, CRP and AOPP, MPO and AOPP, and thiol and AOPP levels in patients with BD. Conclusions Based on this first study, in which MPO‐mediated AOPP formation has been demonstrated, it may be suggested that activated neutrophils may play an important role in the pathogenesis of BD and that chlorinated oxidants of neutrophil origin may lead to oxidative stress, notably protein oxidation. Therefore, AOPP may be a useful marker for monitoring the progress and the severity of the disease activity.     

Can serum level of N‐terminal pro B‐type natriuretic peptide be used in patients with psoriasis as a predictor of cardiovascular disease?

Past studies have reported associations between psoriasis, metabolic syndrome, and atherosclerotic cardiovascular disease. According to studies, N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) is a useful screening test for cardiac disease. We examined the serum NT‐proBNP level in patients with psoriasis and compared them with nonpsoriatic healthy control subjects. Sixty‐one patients with psoriasis were enrolled, along with 61 age, sex, and body mass index (BMI) matched control subjects. In both groups, NT‐proBNP serum levels and lipid profile parameters were investigated. Means and 95% confidence intervals (CIs) were reported. The median serum concentration of NT‐proBNP was higher in psoriatic patients than the control group (26.67 [interquartile range (IQR): 15.15–43.03 and range: 5–250] vs. 17.45 [IQR: 12.35–20.80 and range: 5–45.09, p < 0.0001). NT‐proBNP serum level in psoriatic arthritis patients (11%; 55.6 ± 25.7 pg/mL, 95% CI: 31.9–79.4 pg/mL) was higher than psoriasis patients without arthritis (35.8 ± 40.6 pg/mL, CI: 24.7–46.9, p < 0.001). NT‐proBNP levels were also positively correlated with BMI, lipid profile, and disease duration. NT‐proBNP is elevated in patients with psoriasis, consistent with the high risk of cardiovascular disease associated with psoriasis.     

Detection of herpes virus genomes in skin lesions from patients with Behçet's disease and other related inflammatory diseases

Although the aetiology of Beh?et's disease is still poorly understood, viral infection has long been postulated as one of the factors. To investigate the relationship between herpes viruses and Beh?et's disease, we used polymerase chain reaction to detect herpes simplex virus 1 (HSV-1) and 2 (HSV-2), and human herpes virus 6 (HHV-6) and 7 (HHV-7) DNA in samples of lesional tissues from patients with Beh?et's disease and other related inflammatory disorders. Four cases were positive for HSV-1; 1 of 11 Beh?et's disease cases, 2 of 3 Sweet's disease cases and 1 of 3 erythema nodosum cases. Two cases were positive for both HSV-1 and HSV-2; one Beh?et's disease and one erythema nodosum. All cases were negative for HHV-6 and HHV-7. These findings indicate that there might be some relationship between Beh?et's disease and the presence of HSV-1 and/or HSV-2 DNA and that HHV-6 and HHV-7 do not seem to be involved in the pathogenesis of Beh?et's disease. However, HSV-1 and HSV-2 DNAs were also detected in non-Beh?et's disease lesions, suggesting that HSV-1/2 is not correlated to the direct pathogenesis of Beh?et's disease.     

Variants of the melanocortin‐1 receptor: do they matter clinically?

The melanocortin 1 receptor (MC1R) gene encodes for a seven‐pass transmembrane receptor primarily expressed on melanocytes and melanoma cells. Single nucleotide polymorphisms (SNPs, also termed variants) in MC1R frequently cause red hair, fair skin and are associated with melanoma and keratinocyte‐derived skin cancer development. Activation of wild‐type (WT) MC1R in skin assists cutaneous photoprotection whereas reduced MC1R signalling, seen with MC1R variants, impairs ultraviolet radiation (UVR)‐protective responses. As ancestral humans migrated out of Africa, the evolutionary advantage of MC1R variants may have related to improved cutaneous vitamin D synthesis and higher birthweight reported with certain MC1R variants. Reduced photoprotection secondary to MC1R dysfunction involves pigmentary and non‐pigmentary mechanisms (reduced DNA repair, effects on cell proliferation and possibly immunological parameters), leading to clonal expansion of mutated cells within skin and subsequent carcinogenesis. Recent investigations suggest an association between MC1R genotype and vitiligo, with preliminary evidence that a MC1R agonist, [Nle4‐D‐Phe7]‐alpha‐MSH, in combination with UVB, assists repigmentation. Future development of compounds to correct defective MC1R responses secondary to MC1R variants could result in photoprotective benefits for fair‐skinned individuals and reduce their skin cancer risk.     

Can rituximab be used in the treatment of pemphigus vulgaris during the COVID‐19 pandemic?

Rituximab is a monoclonal antibody that targets CD20, a B‐lymphocyte antigen; that leads to a decline in the B‐cell counts for at least a year. The patients who have received rituximab treatment in the previous 5 years with the diagnosis of pemphigus group of diseases at Cerrahpa?a Medical Faculty were questioned for COVID‐19 infection. A total of 48 patients were included in this study; only one male patient had COVID‐19 infection which had a mild course. There is no significant difference in the total number of lymphocytes between patients who have received rituximab within the previous 5 years or last year. The number of lymphocytes is independent of the number of courses of rituximab treatment received. Therefore, we suggest that all pemphigus patients who have received rituximab treatment within the previous 5 years should be careful of the preventive measures against the COVID‐19 infection irrespective of the number of treatment courses or the number of years which has passed since the treatment. The disease course was mild in the only infected patient. Thus, rituximab may be used in the treatment of pemphigus vulgaris during the COVID‐19 pandemic if its use is necessary.     

Can a simple outpatient‐based treatment be used to treat cutaneous leishmaniasis in young children? A Critically Appraised Topic

A 5‐year‐old boy from rural Afghanistan presented with a 1‐year history of a skin lesion on his left knee, confirmed by polymerase chain reaction to be cutaneous leishmaniasis (Leishmania tropica). Conventional treatment of cutaneous leishmaniasis involves intravenous or intralesional pentavalent antimonials. The aim of this Critically Appraised Topic (CAT) is therefore to determine what alternative effective but less painful treatments (such as oral or topical therapies) can be used to treat cutaneous leishmaniasis in children. Embase and PubMed were searched for ‘cutaneous leishmania*’ AND ‘treatment’ AND ‘children’ in August 2014. All abstracts from April 2008 to August 2014 were reviewed. This search period was chosen to follow on from the Cochrane reviews on Old World and American leishmaniasis. Five randomized controlled trials met our inclusion criteria and have been included in this CAT. The study design and reporting quality in most of the trials included in both Cochrane reviews was found to be poor, and neither Cochrane review investigated the effect of patient age on response to treatment. This CAT identified two nonpainful treatments, topical paromomycin and oral miltefosine, whose effective use in children is supported in the literature. However, both of these treatments are currently unlicensed in the U.K. Our patient was successfully treated with miltefosine 20 mg twice daily for 4 weeks, leading to good resolution of the leishmaniasis plaque but with residual scarring.     

A study of the cutaneous manifestations of Beh?et's disease in patients from the United States.

BACKGROUND: The type and frequency of different manifestations of Beh?et's disease (BD) vary in different geographic areas. This variability could affect the ability to diagnose the disease in certain areas by using standardized criteria. The frequency of cutaneous lesions in patients from the United States, where the disease is less prevalent, is not known. OBJECTIVE: We sought to determine the frequency and type of skin lesions in a series of patients with BD from the United States and to identify methods of confirmation of these lesions as part of the disease process. RESULTS: Cutaneous manifestations were present in 64% of patients with BD. Clinicians most often relied on their clinical diagnosis to identify lesions as part of the spectrum of BD. Skin biopsy specimens were generally nonspecific. CONCLUSION: Cutaneous manifestations were common in patients with BD from the United States and usually were necessary to fulfill the diagnostic criteria of the disease in most cases.     

Is the prevalence of psoriasis increasing? A 30‐year follow‐up of a population‐based cohort

Background  There is indication of an increasing prevalence of psoriasis in some western populations. However, the results are not conclusive. Objectives  To analyse trends in the prevalence of psoriasis over the past 30 years, separating age, birth cohort and time period effects. Methods  Five population‐based surveys in North Norway, the Tromsø Studies 2–6, collected between 1979 and 2008, were studied. Participants aged 20–79 years with self‐reported psoriasis data in at least one of the surveys were included, yielding a total of 69 539 observations from 33 387 unique individuals born between 1915 and 1977. Trends in psoriasis prevalence were examined using cross‐sectional, time lag and longitudinal designs of graphical plots. Observed trends were further evaluated in generalized linear‐regression models. Results  The self‐reported lifetime prevalence of psoriasis increased from 4·8% in 1979–1980 to 11·4% in 2007–2008. Graphical plots showed an increasing prevalence of psoriasis with each consecutive survey in all examined age groups and birth cohorts, leaving time period effects as the explanation for the increase. The odds for psoriasis in the cohort were 2·5 times higher in 2007–2008 than in 1979–1980 (adjusted odds ratio 2·49, 95% confidence interval 2·08–2·99). The prevalence of persons reporting a doctor’s diagnosis of psoriasis was 9·9% in the last survey. In subgroups of the study population, psoriasis was associated with higher body mass index, lower physical activity during work and leisure time, lower educational level and smoking. Conclusions  Our findings indicate an increasing prevalence of self‐reported psoriasis. This could represent a true increase in prevalence, possibly due to changes in lifestyle and environmental factors, or an increased awareness of the disease.     

Can the response of port‐wine stains to laser treatment be reliably assessed using subjective methods?

Assessing the results of laser treatment of port-wine stains (PWS) is very subjective. Most publications use scoring systems that physically describe the change in PWS after treatment. For results derived from such an analysis to be meaningful, the observers must be able to produce results that not only have a small interobserver variability but are also reproducible. Previous studies have addressed the former but not the latter. The present study was undertaken to investigate this area of concern. Six professionals, experienced in laser work, blindly assessed the response to laser treatment of 20 PWS, on two occasions, 1 month apart. Twenty pairs of comparable clinical photographs (one pretreatment and one post-treatment) were assessed using three different scoring systems commonly used in previous publications. Intrarater concordance between the two sessions was then assessed. Our results demonstrated that the judges could only consistently score results at the extremes of outcome. There was little agreement in the assessment of results lying between these. The judges were, however, consistently able to place a similar proportion of patients in each outcome category. We conclude that, as yet, there is no satisfactory method of monitoring the progress of an individual's PWS following laser treatment. However, the scoring systems examined would seem to be reasonable for presenting the data from patient series.     

Can we safely diagnose pigmented lesions from stored video images? A diagnostic comparison between clinical examination and stored video images of pigmented lesions removed for histology

Rapid expansion of communication technology has permitted the clinician to perform a consultation with a patient located at a different site. Assuming adequate diagnostic accuracy, it could theoretically be possible to use telemedical techniques as a triage tool. Images of pigmented lesions sent by the primary care physician could be viewed by the consultant dermatologist, and those with banal lesions spared from attending clinic. Previous studies assessing diagnostic accuracy of images of lesions have used 'face-to-face' diagnoses as the 'gold standard'. We set out to compare diagnostic accuracy of image examination compared with that of clinical examination, using histological examination as the diagnostic benchmark. We found that pigmented lesions may be diagnosed as accurately by stored video image evaluation as by conventional clinical examination. None of the malignant skin tumours was misdiagnosed as benign in either group. Whilst these results are encouraging in terms of the clinical safety of store-and-forward imaging, the inability to examine the whole patient or to palpate the lesions may limit the acceptability of the technique severely. Further evaluation of the cost : benefit ratio of such a system to the health care provider must be undertaken before considering this technique as a potential adjunct to managing outpatient referrals.     

Can exposure limitations for well‐known contact allergens be simplified? An analysis of dose–response patch test data

Background. Allergic contact dermatitis is triggered by chemicals in the environment. Primary prevention is aimed at minimizing the risk of induction, whereas secondary and tertiary prevention are aimed at reducing elicitation. Objectives. To identify the elicitation doses that will elicit an allergic reaction in 10% of allergic individuals under patch test conditions (ED₁₀ patch test) for different allergens, and to compare the results with those for different allergens and with animal data indicating sensitizing potency from the literature. Materials and methods. The literature was searched for patch test elicitation studies that fulfilled six selected criteria. The elicitation doses were calculated, and fitted dose–response curves were drawn. Results. Sixteen studies with eight different allergens–methylchloroisothiazolinone/ methylisothiazolinone, formaldehyde, nickel, cobalt, chromium, isoeugenol, hydroxyiso hexyl 3‐cyclohexene carboxaldehyde, and methyldibromo glutaronitrile–were selected. The median ED₁₀ value was 0.835 µg/cm². The ED₁₀ patch test values were all within a factor of 7 from the lowest to the highest value, leaving out three outliers. No obvious patterns between the sensitization and elicitation doses for the allergens were found. Conclusions. We found a rather small variation in the ED₁₀ patch test between the allergens, and no clear relationship between induction potency and elicitation threshold of a range of allergens. This knowledge may stimulate thoughts on introducing a generic approach for limitations in exposure to well‐known allergens.     

Is There Any Association between Hepatitis G Virus (HGV), Other Hepatitis Viruses (HBV,HCV) and Behçet's Disease?

Infectious agents, especially viruses, have been implicated in the pathogenesis of Behçet's disease (BD). The aim of this study was to determine whether BD is associated with hepatitis viruses. In this study, the serological markers of hepatitis (HBsAg, anti‐HBs, anti‐HBc and anti‐HCV) and viral nucleic acid (HGV‐RNA) were studied in the sera of 35 patients, all of whom fulfilled the diagnostic criteria of the International Study Group for BD, and the results were compared with those of 36 healthy controls. The prevalences of HBsAg, anti‐HBs, anti‐HBc in BD patients were 2.9%, 45.7%, and 31.4%, respectively, which were not significantly different from those in healthy controls. None of the subjects in either group were found to be positive for anti‐HCV. HGV‐RNA was detected in two patients with BD and in none of the healthy controls. In conclusion, BD does not seem to be associated with hepatitis viral infections including hepatitis B, C, or G.