A narrative review of the definition of ‘flare’ in hidradenitis suppurativa

Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta-analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta-analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02–3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12–0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment-related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents. Linked Comment:   Doiron. Br J Dermatol 2020; 183 :5–6 .     

Hidradenitis suppurativa: a disease of the absent sebaceous gland? Sebaceous gland number and volume are significantly reduced in uninvolved hair follicles from patients with hidradenitis suppurativa

Background The pathogenesis of hidradenitis suppurativa (HS) is not clearly understood. The nomenclature suggests an important role for the apocrine glands but recent evidence implicates the pilosebaceous unit as a more likely candidate to play a central role in the pathogenesis. Objectives Our aim was to estimate the volume of the follicular epithelium, the follicular lumen and the sebaceous glands of patients with HS and healthy controls by means of stereology. Methods Four‐millimetre punch biopsies were taken from 21 patients with HS and nine healthy controls, fixed in formalin, embedded in paraffin and stained with haematoxylin and eosin prior to volume estimation using the Cavalieri principle. Results Sebaceous gland tissue could be visualized in only 10 of 15 suitable hair follicle biopsies from patients with HS but was present in all biopsies from healthy controls (P = 0·05) and the mean sebaceous gland volume per follicle was one‐seventh of that of healthy controls (P = 0·03). There was no significant difference between patients with HS and healthy controls with regard to follicular epithelium and follicle lumen volume. Conclusions Our results suggest that the absence or reduced volume of the sebaceous gland may play a role in the pathogenesis of HS. The presence of fibrosis suggests that sebaceous glands are obliterated early in the pathogenesis of HS.     

Clinical and histological characteristics,and management of melanoma in French Guiana, 2007–2018

There are few studies available on melanoma in Afro-Caribbean and Amerindian populations of South America. French Guiana deserves a study due to its specific health system and diversity of phototypes. The objectives of this study were to evaluate the incidence, histological and clinical characteristics of melanoma in French Guiana. A retrospective study was conducted from October 2007 to January 2018 on all primary melanomas observed at the Cayenne Hospital Centre. Thirty-nine patients were included. The incidence rate (1.61/10⁶ inhabitants/year) was low compared with mainland France. Median age was 58, and gender ratio 1 : 16. Clear phototype (I/II) patients were the most frequent (38.5%), but a significant amount of melanoma also occurred in darker skin. Median Breslow was higher in dark phototypes than in fair-skinned patients. Superficial spreading melanoma (SSM) was the most common histological type (33.3%), particularly in patients with clear phototype (61.5%). Acral lentiginous melanoma was found only in darker-skinned patients (29.1%). The trunk was involved in 66.6% in the clearest group whereas foot was the most common location in the darkest group (60% in V/VI phototypes). Surgery was the most frequently used treatment (79.5%). At the end of the study period, 53.8% had been lost to follow-up. In conclusion, the incidence of melanoma in French Guiana is lower than in mainland France but remains a public health concern, as dark-skinned populations often present with advanced diseases. Awareness and prevention in these communities must be improved.     

Relationship between bacilloscopy and operational classification of Hansen’s disease in patients with reactions

Leprosy can be classified according to its operational form as paucibacillary or multibacillary. Bacilloscopy integrates its diagnostic armamentarium. Patients with the disease may present leprosy reactions. This study describes the association of bacilloscopy results and the type of operational classification of leprosy in patients with leprosy reactions. Medical records were analyzed at a reference center between 2010 and 2015. Reactions occurred in almost half of the patients, making their identification important. The bacilloscopic and operational characterization indicates a greater occurrence of leprosy reactions in patients with positive bacilloscopy and also in multibacillary.     

Evaluation of leptin level and Ob gene polymorphism in patients with Behcet’s disease

The present study was aimed to evaluate serum leptin level and the frequency of oligopolymorphic codon 25 (CAA/CAG) of Ob gene in Behcet’s disease. Eighty-seven patients with Behcet’s disease and 85 healthy controls with matched age, gender and body mass index were included in the study. Serum leptin level was determined and genotype of codon 25 of Ob gene was performed by using the PCR amplification after DNA extraction. Serum leptin concentration of the patients with Behcet’s disease (23.8 ± 22.8 ng/ml) was higher than that of the control groups (17.1 ± 14.7 ng/ml). The patients with Behcet’s disease and control subjects showed CAA/CAA genotype, indicating the presence of no polymorphism. Neither Behcet’s disease nor serum leptin level was found to be related to codon 25 polymorphism. We concluded that leptin 25CAG polymorphism is not associated with Behcet’s disease and serum leptin level.     

Adalimumab (antitumour necrosis factor-α) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study

Background Hidradenitis suppurativa (HS) is a difficult‐to‐manage disease. Randomized controlled trials with antitumour necrosis factor (TNF)‐α biologics have been conducted and in most studies disease activity was reduced. However, the mechanism of action in HS skin is so far unknown. Objectives To assess whether anti‐TNF‐α treatment affects in situ cytokine production and frequency of inflammatory cell populations in HS lesional skin. Methods Nine patients with HS, participating in a larger placebo‐controlled, double‐blind phase IIb clinical trial on the efficacy and safety of adalimumab in patients with moderate to severe HS (M10‐467), were randomized and treated for 16 weeks. In a mechanism‐of‐action substudy, biopsies were obtained at fixed time points pre‐ and post‐treatment. One part of the biopsy was cultured for 24 h for cytokine release in the culture medium, while another part was used for in situ analysis. Results Secretion of cytokines, including interleukin (IL)‐1β, CXCL9 [monokine induced by interferon‐γ (MIG)], IL‐10, IL‐11, B‐lymphocyte chemoattractant (BLC) and IL‐17A, was significantly elevated in HS. Adalimumab treatment was associated with decreased production of cytokines in HS skin, especially IL‐1β, CXCL9 (MIG) and BLC. Treatment significantly reduced the number of CD11c+, CD14+ and CD68+ cells in HS lesional skin. The numbers of CD3+ and CD4+ T cells, and CD20+ and CD138+ B cells were also reduced by adalimumab treatment. Conclusions Adalimumab treatment inhibits important cytokines and inflammatory cell numbers in lesional HS skin, especially levels of IL‐1β and numbers of inflammatory CD11c+ dendritic cells.     

The demonstration of serum interleukin-8 and superoxide dismutase in Adamantiades-Behçet’s disease

Serum interleukin-8 (IL-8) production was measured in 43 Adamantiades-Behçet’s disease (A-BD) patients and in 46 healthy volunteers using a sandwich enzyme-linked immunosorbent assay (ELISA). The mean serum IL-8 level of the patients (14.6 ± 3 pg/ml) was significantly higher than that of controls (10.8 ± 3 pg/ml, P < 0.05). Since IL-8 is known to have proinflammatory properties, it may play some role in the pathogenesis of A-BD. We also investigated the activity of serum superoxide dismutase (SOD) in the 43 patients with A-BD and in the 46 healthy volunteers. Serum SOD activity was markedly increased in the patients with A-BD (13.1 ± 3%), especially in active A-BD, compared with that in the healthy volunteers (6.7 ± 3%, P < 0.01). Our results suggest the involvement of IL-8 and SOD in the pathogenesis of A-BD as seen in other inflammatory diseases.     

Evaluation of the association between null genotypes of glutathione-S-transferases and Behcet’s disease

Glutathione S-transferases (GST) play an important role in oxidative stress related syndromes. An imbalance of the oxidant and antioxidant systems is important in the pathogenesis of Behcet’s disease (BD). The objective of this study was to evaluate the association of null genotypes of GST-M1 and GST-T1 with BD since some preliminary molecular genetic data were recently published. Ninety-four Turkish BD patients (42 male, 52 female, 37.1±10.4 years) and 140 healthy volunteers (70 male, 70 female, 36.8±11.7 years) matched for age and gender with the patients as the control group were included in the study. Distributions of GST-M1 and GST-T1 genotypes were determined by multiplexed PCR using three sets of primers for GST-M1, GST-T1, and β-globulin genes. There was no association between BD and the frequencies of GST-M1 and GST-T1 null genotypes when compared to controls by separate analysis. However, by cross and pooled combination analysis there was a significant association between the frequencies of pooled GSTs with one or both null genotypes in BD and controls. This is the first evidence that the association between the frequencies of GST-M1 and GST-T1 null genotypes and BD might be dependent on the interaction of multiple null allele polymorphisms rather than a single null allele of GST-M1 and GST-T1.     

High levels of endothelial progenitor cells and circulating endothelial cells in patients with Behcet’s disease and their relationship to disease activity

Background: Behcet’s disease is a multisystemic vasculitis, associated with vascular endothelial dysfunction. Currently, the prognosis is unpredictable, because there is still no valid laboratory marker indicating the disease activity in Behcet’s disease. Endothelial progenitor cells and circulating endothelial cells are newly introduced hematological markers which are presumed to take part in the pathogenesis of vasculitis.Objectives: To evaluate the levels of endothelial progenitor cells and subtypes and circulating endothelial cells in patients with Behcet’s disease and to describe their relationship with the disease activity.Methods: A total of 45 patients with Behcet’s disease and 28 healthy controls were included in the study. Endothelial progenitor cells (CD34+CD133+KDR+ as early endothelial progenitor cells and CD34+KDR+ as late endothelial progenitor cells), and circulating endothelial cells (CD34+CD133+) were measured by flow cytometry.Results: The mean plasma level of endothelial progenitor cells and circulating endothelial cells, vascular endothelial growth factor, matrix metalloproteinase-9, C-reactive protein, and erythrocyte sedimentation rate were significantly higher in patients with Behcet’s disease. All of these parameters except circulating endothelial cells were also found to be higher in patients with active disease than in patients with inactive disease. Early endothelial progenitor cells showed significant correlations with C-reactive protein and circulating endothelial cells.Study limitations: The cross-sectional nature of the study and patient characteristics such as being under treatment, which can affect endothelial progenitor cells numbers.Conclusion: The increase in endothelial progenitor cells may play an essential role in the repair of endothelial injury in Behcet’s disease, especially in the active period of the disease. Thus, endothelial progenitor cells can indicate the disease activity. In addition, endothelial progenitor cells and circulating endothelial cells can be used as endothelial repair and injury markers for Behcet’s disease, respectively.     

Photosensitizers and light sources for photodynamic therapy of the Bowen’s disease

Bowen’s disease is a neoplastic skin disease, known as squamous cell carcinoma in situ. The treatment options for Bowen’s disease are: cryotherapy, curettage, surgery, topical therapy and radiotherapy. In the past recent years, photodynamic therapy was used as a new treatment method. The purpose of this paper is to summarize the results of clinical and research studies with respect to the photodynamic therapy of Bowen’s disease. A search of three databases was conducted using specific keywords and explicit inclusion and exclusion criteria for the study of photosensitizers, light sources and their efficacy in photodynamic therapy of Bowen’s disease. Two photosensitizers have been used mainly for photodynamic therapy of Bowen’s disease therapy: δ-aminolevulinic acid and methyl aminolevulinate. These photosensitizers have been activated with both coherent (lasers) and non-coherent (lamps and LEDs) light sources. Fluence has been set in a large domain (10–240 J/cm²) and irradiance was 0.23–100 mW/cm². All these light sources have the same efficacy. The high response rates were obtained using methyl aminolevulinate and light emitting diode as light source. These results have demonstrated that photodynamic therapy using methyl aminolevulinate as photosensitizer could be considered as one of the first therapeutic options for Bowen’ disease.     

Serum salusin-α and salusin-β levels in patients with Behcet’s disease

Background

Behcet’s disease (BD) is a chronic, relapsing, systemic vasculitis of unknown etiology. There is an increased predisposition to insulin resistance and metabolic syndrome (MetS) in BD patients.

Objective

The aim of this study was to determine serum salusin-α and salusin-β levels in BD patients and healthy controls and to investigate their association with MetS.

Patients and Methods

Twenty-five BD patients and 25 healthy controls were included in the study. Salusin-α and salusin-β levels were measured in blood samples using ELISA. In addition, BD patients and healthy controls were evaluated in terms of MetS.

Results

The mean serum salusin-α level in BD patients was significantly lower compared to healthy controls (p = 0.03), whereas the mean serum salusin-β level in BD patients was significantly higher compared to healthy controls (p = 0.03). The mean serum salusin-α level was significantly lower in BD patients with MetS compared to BD patients without MetS (p = 0.04).

Conclusions

Serum salusin-α level (an anti-atherogenic molecule) was lower, while serum salusin-β level (a pro-atherogenic molecule) was higher in BD patients. We consider that the decrease in salusin-α and the increase in salusin-β levels contribute to the development of MetS.

     

XRCC1 Arg194Trp polymorphism, risk of nonmelanoma skin cancer and extramammary Paget’s disease in a Japanese population

The X-ray repair cross-complementing groups 1 gene plays an important role in base excision repair. At least three common single nucleotide polymorphisms frequently occur in this gene (Arg399Gln, Arg194Trp and Arg280His). Recent studies reported that these polymorphisms were associated with not only risk of visceral malignancy but also that of skin cancer such as basal cell carcinoma and squamous cell carcinoma, whereas the results of previous study vary among races. In this case-control study, we investigated whether these single nucleotide polymorphisms were associated with the risk of skin cancer in a Japanese population. The study population was composed of 197 patients with skin cancer (27 actinic keratoses, 47 basal cell carcinomas, 27 squamous cell carcinomas, 29 Bowen's diseases, 46 malignant melanomas and 21 extramammary Paget's diseases) and 93 control subjects. We genotyped two single nucleotide polymorphisms (Arg194Trp and Arg399Gln) using polymerase chain reaction-restriction fragments length polymorphism analysis. We found a significantly increased risk for basal cell carcinoma, squamous cell carcinoma and extramammary Paget's disease associated with Arg194Trp [adjusted odds ratio (AOR) = 2.347, 3.587, 3.741, 95 % confidence interval (CI) 1.02-5.39, 1.19-10.8, 1.15-12.2, respectively]. We also found a significantly decreased risk for basal cell carcinoma associated with Gln399Gln (AOR = 0.259, 95 % CI 0.07-0.96). Our data suggest that the Arg194Trp polymorphism could be associated with nonmelanoma skin cancer and extramammary Paget's disease risk in a Japanese population.