Expression of IFNγ, coexpression of TNFα and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare

Abstract Granuloma annulare, a prototype noninfectious granulomatous dermatitis, is morphologically characterized by a necrobiotic core surrounded by a cellular infiltrate. Because of many morphological similarities to tuberculosis, granuloma annulare has been suggested to represent a delayed-type hypersensitivity (Th1) reaction in the course of which inflammatory cells elicit matrix degradation. In the present study we (1) investigated the expression of interferon-á as the most important Th1-associated cytokine, (2) sought in situ evidence for the coexpression of the proinflammatory cytokine tumor necrosis factor-· and cytokine-regulated matrix metalloproteinases 2 (gelatinase A) and 9 (gelatinase B), and (3) sought to determine whether shrunken cells seen within necrobiotic areas of granuloma annulare are apoptotic cells. In situ hybridization combined with immunofluorescence showed that large numbers of infiltrating CD3⁺ lymphocytes express interferon-á. Application of catalyzed signal amplification in immunodetection revealed that the vast majority of CD3⁺ lymphocytes and CD68⁺ macrophages contained tumor necrosis factor-·. Immunohistochemistry demonstrated that macrophages producing tumor necrosis factor-· coexpress matrix metalloproteinases 2 and 9. In situ end-labeling combined with immunofluorescence detected few apoptotic T cells in perivascular regions and numerous apoptotic macrophages within necrobiotic areas. These results suggest that in granuloma annulare interferon-á⁺ Th-1 lymphocytes may cause a delayed-type hypersensitivity reaction whereby macrophages are differentiated to aggressive effector cells expressing tumor necrosis factor-α and matrix metalloproteinases. In parallel, activation-induced apoptosis in lymphocytes and macrophages may serve to restrict the destructive potential of the inflammatory cells. Received: 23 November 1999 / Received after revision: 28 March 2000 / Accepted: 14 April 2000     

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.     

Clinical,microbiological, immunological and imaging characteristics of tunnels and fistulas in hidradenitis suppurativa and Crohn’s disease

Hidradenitis suppurativa (HS) tunnels and Crohn's disease (CD) fistulas are a challenge to treat. Although pathogenic similarities have been described between HS and CD, recent studies indicate that clinical, microbiological, immunological and imaging characteristics differ between these diseases. This review highlights the differences between HS tunnels and CD fistulas. Next-generation sequencing studies demonstrate a microbiome in HS tunnels dominated by Porphyromonas spp., Prevotella spp. whereas no specific bacteria have been associated with cutaneous CD. Immunologically, TNF has been found upregulated in HS tunnels along with various interleukins (IL-8, IL-16, IL-1α and IL-1β). In CD fistulas, Th1, Th17, IL-17, IFN-ɤ, TNF and IL-23 are increased. US imaging is an important tool in HS. US of HS tunnels depict hypoechoic band-like structure across skin layers in the dermis and/or hypodermis connected to the base of a widened hair follicle. In CD, MR imaging of simple perianal fistulas illustrates a linear, non-branching inflammatory tract relating to an internal opening in the anus or low rectum and an external opening to the skin surface. An increased awareness of the immediate potential differences between HS tunnels and CD fistulas may optimize treatment regimens of these intractable skin manifestations.     

Sunscreen applied at ≥ 2 mg cm−2 during a sunny holiday prevents erythema,a biomarker of ultraviolet radiation-induced DNA damage and suppression of acquired immunity

Rates of skin cancer are increasing more rapidly in the UK than any other form of cancer. The deadliest form of the disease is melanoma skin cancer, which affects 128% more people now than it did 28 years ago. Sun protection factors (SPFs) are known to protect the skin from sunburn when sunscreen is applied at 2 mg per cm^-2. However, whilst on holiday, people typically apply just 0.8 mg cm^-2 of sunscreen. This study aimed to identify if typical sunscreen application during a holiday with daily sun exposure results in skin cancer risk factors such as sunburn. Participants spent one week in Tenerife, a country with a very high ultraviolet index. 22 participants applied their own sunscreen without instruction and 40 participants were given SPF 15 sunscreen and guidance on effective application (three times daily at 2 mg cm^-2). It was found that participants who followed typical sunscreen application displayed significantly greater levels of sunburn and other risk factors associated with skin cancer compared to those who followed optimal application guidelines to achieve SPF 15. Individuals who followed the effective application guidelines with SPF 15 sunscreen had no sunburn on five exposed body sites. The results of this study highlight how typical sunscreen use is not providing sufficient protection from the sun in the majority of people. As well as this, it is demonstrated that sunburn is associated with an increased risk of developing skin cancer. Therefore, achieving an adequate SPF by teaching the general public how to properly apply sunscreen may be an important step in preventing skin cancer.     

Perception,understanding, and association between psychological stress and skin aging: Quantitative surveys of Asian women aged 18–34 years,dermatologists, and psychologists in China and Japan

Background

Skin aging involves a variety of structural and functional changes, under the influence of various factors. Preaging skin is a relatively new concept describing self-perceived signs of skin aging that appear in the early 20s–30s and may be triggered by psychological stress. However, it is unclear how young women and healthcare professionals (HCP) understand the association between stress and skin aging.

Aims

We sought to explore the perceptions of stress-related skin aging among young women and HCPs.

Methods

We performed online surveys of 403 young women (18–34 years), 60 dermatologists, and 60 psychologists residing in major cities in China and Japan. Questions covered skin signs, understanding/perceptions of stress–aging connection, and demographics. Young women also completed DASS-21 to assess their stress level, which was dichotomized as normal or mild–extremely severe.

Results

The stress level was normal in 52.6% or mild–extremely severe in 47.4% of young women. Greater proportions of women in the mild–extremely severe stress group reported skin manifestations associated with preaging, the top three being “rough skin” (39.3% vs. 24.1%), “slow metabolic rate” (28.8% vs. 14.2%), and “dull skin” (43.5% vs. 29.2%). The top three skin manifestations showing the strongest perceived associations with stress were: “dark eye circles,” “slow metabolic rate,” and “dull skin” (among young women); “acne,” “dry skin,” and “skin rash” (among HCPs).

Conclusions

Young women frequently report high levels of psychological stress and signs of skin aging. Perceptions of stress–skin aging association differ between young women and HCPs.     

Proceedings of the Facial Aesthetics Conference and Exhibition,Royal College of Physicians,London, 24–25 June 2006

BACKGROUND: Treatment of acne scarring is a challenging problem for dermatologists and cosmetic surgeons. Combining skin resurfacing with other procedures, especially the use of filling agents, has proven to be superior to the use of a single modality. Carbon dioxide laser resurfacing has been popularized for the treatment of acne scarring, but post operative morbidity with stimulation of active acne has been problematic. Conventional erbium resurfacing is effective when sufficient fluences are used, particularly when treating relatively superficial acne scars. Deeper resurfacing for acne scars is difficult with erbium lasers, owing to bleeding and heavy exudation, which decreases ablation efficiency and makes 'end points' difficult to visualize. The newer modulated hybrid erbium/CO 2 lasers (Derma K, ESC Sharplan, Yokneam, Israel) produce efficient ablation by the reduction of bleeding, yet at the same time incur little post operative morbidity. This is suitable for treating deeper acne scars, and may be combined with other procedures, e.g. fat grafting. Of particular importance is the lack of acne stimulation associated with the use of the erbium/CO 2 hybrid lasers. RESULTS: In my series of 78 patients, improvement in acne scarring was >70% in the majority of patients. Post operative morbidity and complications were minor compared to conventional CO 2 laser resurfacing.     

RXRα ablation in epidermal keratinocytes enhances UVR-induced DNA damage, apoptosis, and proliferation of keratinocytes and melanocytes

We show here that keratinocytic nuclear receptor retinoid X receptor-α (RXRα) regulates mouse keratinocyte and melanocyte homeostasis following acute UVR. Keratinocytic RXRα has a protective role in UVR-induced keratinocyte and melanocyte proliferation/differentiation, oxidative stress-mediated DNA damage, and cellular apoptosis. We discovered that keratinocytic RXRα, in a cell-autonomous manner, regulates mitogenic growth responses in skin epidermis through secretion of heparin-binding EGF-like growth factor, GM-CSF, IL-1α, and cyclooxygenase-2 and activation of mitogen-activated protein kinase pathways. We identified altered expression of several keratinocyte-derived mitogenic paracrine growth factors such as endothelin 1, hepatocyte growth factor, α-melanocyte stimulating hormone, stem cell factor, and fibroblast growth factor-2 in skin of mice lacking RXRα in epidermal keratinocytes (RXRα(ep-/-) mice), which in a non-cell-autonomous manner modulated melanocyte proliferation and activation after UVR. RXRα(ep-/-) mice represent a unique animal model in which UVR induces melanocyte proliferation/activation in both epidermis and dermis. Considered together, the results of our study suggest that RXR antagonists, together with inhibitors of cell proliferation, can be effective in preventing solar UVR-induced photocarcinogenesis.     

Acne in Lomé, Togo: clinical aspects and quality of life of patients

Background

Acne is a chronic inflammatory condition affecting the pilosebaceous follicle that mainly affects adolescents and young adults. The aim of this study was to assess the quality of life (QOL) of patients with acne, and to determine the correlation between the QOL and the severity of acne, in Lomé (Togo).

Method

From July 2017 to February 2018, we conducted a study in three dermatology departments of Lomé. The clinical evaluation of acne and assessment of the QOL were done using the ECLA (Echelle de Cotation des Lésions d’acné) and CADI (Cardiff Acne Disability Index) scores respectively.

Results

We enrolled 300 patients aged 12 to 52 years; 71.3% of whom were female. The face was affected by acne in 100% of cases and papulopustular acne was the most common clinical form (66.7%). Acne was mild to moderate in 162 patients (54%) and severe in 138 (46%). Impairment was observed in all patients’ QOL (scores ranged from 1 to 14 points). There was a positive correlation between severity of acne and QOL impairment in the patients (r?=?0.21; p?=?0.0002). We also found a positive correlation between overall CADI score and factors F1 and F3 of the ECLA scale: the severity of facial acne (r?=?0.15; p?=?0.0073) and the presence of scars (r?=?0.21; p?=?0.0002). In contrast, the global ECLA score was significantly correlated with items 2, 3, and 5 of the CADI questionnaire: the patient’s relationship (r?=?0.13; p?=?0.0241), avoidance behaviors (r?=?0.21; p?=?0.0002) and perception of acne (r?=?0.16; p?=?0.0067).

Conclusion

Acne negatively impacts the QOL of patients. The severity of acne has an impact on the patient’s relationships, avoidance behaviors and perception of the acne.

     

Daylight photodynamic therapy versus cryosurgery for the treatment and prophylaxis of actinic keratoses of the face − protocol of a multicenter,prospective, randomized,controlled, two-armed study

Background

Photodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated.

Methods/design

In this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire face are conducted over the course of 18 months. After preparation of the lesion and within 30 min after MAL application, patients expose themselves to daylight for 2 h. In the control group, lesion-directed cryosurgery is conducted at the first visit and, in the case of uncleared or new AK lesions, also at visits 2 to 5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all existing and new AK lesions in the face. Cosmetic results and improvement of photoaging parameters are evaluated by means of a modified Dover scale.Primary outcome parameter is the cumulative number of AK lesions observed between visits 2 and 6.Secondary outcome parameters are complete clearance of AK, new AK lesions since the previous visit, cosmetic results independently evaluated by both patient and physician, patient-reported pain (visual analogue scale), patient and physician satisfaction scores with cosmetic results, and patient-reported quality of life (Dermatology Life Quality Index). Safety parameters are also documented (adverse events and serious adverse events).

Discussion

This clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and investigate possible rejuvenating effects of this treatment. (Trial registration: ClinicalTrials.gov Identifier: NCT02736760).

Trial registration

ClinicalTrials.gov Identifier: NCT02736760. Study Code Daylight_01. EudraCT 2014–005121-13.

     

Fiberglass dermatitis: clinical presentations,prevention, and treatment – a review of literatures

Fiberglass dermatitis is a common form of occupational irritant contact dermatitis. Individuals experience a negative reaction to fiberglass fragments because of mechanical irritation. This review comprehensively analyzes the information in the existing literature on fiberglass dermatitis. Recognizing the different environmental risks factors for acquiring fiberglass dermatitis is necessary for better diagnosis and prevention. In addition to the identification of high-risk populations exposed to fiberglass particles, the common clinical presentation and preventive measures that can reduce the risk of acquiring fiberglass dermatitis are thoroughly discussed.     

Serum concentration of IL-6, IL-2, TNF-α, and IFNγ in Vitiligo patients

Background:

Vitiligo is an acquired depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. Although the etiology of vitiligo is unknown, over the last few years, substantial data from clinical research has greatly supported the ‘Autoimmune theory’ and this is supported by the frequent association of vitiligo with disorders that have an autoimmune origin, including Hashimoto''s thyroiditis, Graves disease, type 1 insulin-dependent diabetes mellitus, and Addison''s disease. As cytokines are important mediators of immunity, there is evidence to suggest that they play a major role in the pathogenesis of autoimmune diseases.

Aim:

Keeping this in view we have assayed sera for cytokine IL-6, IL-2, Tumor necrosis factor (TNF)-α, and IFNγ in 80 cases of vitiligo and compared it with healthy subjects, in order to find out whether they play a role in the pathogenesis of vitiligo or not.

Materials and Methods:

Serum IL-6, IL-2, TNF-α, and IFNγ were done by the indirect enzyme linked immunosorbent assay (ELISA).

Results:

The mean serum IL-6 and IL-2 levels in the patient group were significantly higher when compared with those of the normal controls. The mean serum IFNγ level in patients with vitiligo was significantly lower than that in the control group. There was no significant difference in the serum level of TNF-α between vitiligo and healthy controls.

Conclusion:

An increase in the production of proinflammatory cytokines such as IL-6 and IL-2 in vitiligo patients may play an important role in melanocytic cytotoxicity. Thus, we speculate that the cytokine production of epidermal microenvironment may be involved in vitiligo.     

A prospective, rater-blind, randomized comparison of the effectiveness and tolerability of Belotero ® Basic versus Restylane ® for correction of nasolabial folds

The aim of this prospective, rater-blind, randomized, intra-individual, 4-week study was to compare the effectiveness and safety of two hyaluronic acid dermal fillers, Belotero? Basic (monophasic) and Restylane? (biphasic), for correction of nasolabial folds (NLF). Twenty subjects with bilateral, symmetrical NLF were randomized to receive a single injection of Belotero? Basic and Restylane? in a split-face design. The primary endpoint measured intra-individual differences of treatment effects in mean depth and evenness of the NLF target area relative to its edges, from baseline to Week 4, as evaluated by the Phase-shift Rapid In-vivo Measurement of Skin (PRIMOS) system. Assessments were undertaken at Visit 2 (baseline) and Visit 3 (study endpoint). Treatment with Belotero? Basic resulted in a significantly greater improvement in evenness compared with Restylane? at Week 4 (mean intra-individual difference between treatments in PRIMOS measurement: -37.6 μm; 95% CI: -65.4; -9.9). Subject-rated secondary endpoints demonstrated numerical differences in favour of Belotero? Basic when compared with Restylane?. Both dermal fillers were equally well tolerated, as 85% (Belotero? Basic group) and 80% (Restylane? group) rated the tolerability of both treatments as "good" to "very good".