Skin IL-17A and IFN-γ Production Correlate with Disease Severity in Patients with Psoriasis and Streptococcal Infection.

Psoriasis is a multisystemic inflammatory disorder mainly involving the skin and joints, whose etiopathogenesis is still not completely understood. An association with streptococcal throat infection has been suggested. We aim to investigate a correlation between IL-17A and IFN-γ production by T cells infiltrating skin lesions and PASI in 313 patients with psoriasis, compared with that in 252 healthy controls. The phenotype of ß-hemolytic Streptococci-specific infiltrating T cells in skin lesions was evaluated and characterized for IFN-γ, IL-4, and IL-17A production. In addition, PBMCs were tested by ELISpot for IFN-γ and IL-17A after streptococcal antigen exposure. A total of 64 of 313 (20.4%) patients with psoriasis had throat streptococcal infection. Of the 3,868 skin-derived T-cell clones from psoriasis with streptococcal infection, 66% proliferated in response to ß-hemolytic Streptococci antigens. Most ß-hemolytic Streptococci-specific T cells displayed T helper 17 and T helper 1 phenotypes. The levels of IFN-γ and IL-17A secreted by skin-infiltrating T cells of patients with psoriasis significantly correlated with PASI score. In ß-hemolytic Streptococci-positive patients, IFN-γ and IL-17A production by peripheral blood T cells after stimulation with streptococcal antigens was quantified by ELISpot. The results obtained may suggest ELISpot as a useful diagnostic tool to identify patients with psoriasis that may deserve antibiotic treatment.

Clinical characteristics of itch in cutaneous lupus erythematosus: A prospective, multicenter, multinational, cross-sectional study.

OBJECTIVE: Pruritus is an important symptom frequently accompanying various inflammatory skin conditions and some recent data indicated that it may be associated with autoimmune connective tissue diseases. The aim of this study was to assess the frequency and clinical presentation of itch in CLE. METHODS: A multinational, prospective, cross-sectional study was performed to assess the prevalence, intensity and clinical characteristic of pruritus in various subtypes of CLE. A total of 153 patients with active CLE lesions were included. Their age ranged between 17 and 82 years (mean 49.8 ± 15.4 years), and 115 patients (75.2%) were women. The disease activity and damage were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Pruritus severity was assessed with Numeric Rating Scale (NRS) and the 12-Item Pruritus Severity Scale. Dermatology Life Quality Index and EQ-5D questionnaire were used to measure quality of life. RESULTS: Pruritus was present in 116 (76.8%) of patients of whom half had NRS scoring equal or above 4 points indicating moderate or severe pruritus. Most commonly itch was localized on the scalp, face (excluding ears and nose) and arms (40.5%, 36.2%, 31.9%, respectively). Sensations connected with pruritus were most frequently described as burning, tingling and like ants crawling feeling, but 31.9% patients described it as "pure itch". More than half of patients reported that pruritus was present every day, and it was most frequent during the evenings. The pruritus scoring and the CLASI activity score were significantly correlated (r = 0.42, p = 0.0001), while no correlation was found with the CLASI damage score (p = 0.16). Both the maximum and average itch intensity were correlated with systemic lupus erythematosus (SLE) activity measured with the Systemic Lupus Erythematosus Disease Activity Index. CONCLUSIONS: Pruritus is a common, but frequently overlooked symptom of CLE. Its intensity correlates with the activity of CLE, but not with the skin damage. In more than a half of patients it occurs on a daily basis. The correlation between the intensity of pruritus and the activity of the skin lesions and the systemic involvement indicate that pruritus could be an individual indicator of both SLE and CLE activity.

New Insight in Noninvasive Rejuvenation: The Role of a Rhodamine-Intense Pulsed Light System.

Background: Rhodamine-intense pulsed light (r-IPL) is a noncoherent, noncollimated, polychromatic light energy optimized for a double-peak wavelength emission, ranging between 550-680 and 850-1200 nm. Traditional IPL works within visible and infrared spectra, targeting hemoglobin and melanin, are effective to treat rosacea and pigmentary disorders. r-IPL, a new technology in dermatology, emits high-intensity light with a wavelength peak similar to the one of the pulsed dye lasers, showing a good safety and efficacy profile in nonablative photorejuvenation. Objective: Assess efficacy and safety of r-IPL on photodamaged facial skin showing hyperpigmentation, telangiectasias, fine lines, and textural changes. Methods: Five sessions of r-IPL treatment (fluence ranged between 13.5 and 14 J/cm2) have been performed on one 75-year-old lady affected by facial photodamaged skin. Efficacy of treatment was evaluated using the Fitzpatrick Elastosis and Wrinkles Scale (FEWS) and the Global Aesthetic Improvement (GAI) Scale assessed by an investigator, compared with baseline. Treatment safety and tolerance were also evaluated using the Visual Analog Scale (VAS). Results: Photographic and multispectral evaluation demonstrated relevant improvement (vascular, pigment, and texture) of photodamaged facial skin. One month after the last treatment, significant improvement in facial wrinkle and texture was noted. FEWS scores decreased significantly from 7 to 2. According to the GAI scale, the patient had an improvement in skin texture. Immediate response included mild-to-moderate erythema and only trace-mild edema in the treatment area. Pain during the treatment was minimal with a mean VAS pain score of 3/10. No other adverse events were reported. No post-treatment downtime was recorded. Conclusions: r-IPL may represent a valid therapeutic approach in noninvasive photorejuvenation.

Dermatitis Herpetiformis: Novel Perspectives.

Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.

Fractional CO2 Laser: From Skin Rejuvenation to Vulvo-Vaginal Reshaping.

BACKGROUND: The CO2 laser has become the gold standard treatment in dermatologic surgery for the treatment of a large number of skin and mucosal lesions. The introduction of the fractional micro-ablative technology represented an integration to the ablative resurfacing technique, reducing the healing time and the side effects. OBJECTIVE: Vaginal rejuvenation performed with this technique is a minimally invasive procedure that stimulates internal tissues of the female lower genital tract to regenerate the mucosa, improving tissue trophism and restoring the correct functionality. METHODS: In our experience, 386 menopausal women affected with vulvo-vaginal atrophy (VVA) were treated with three section of fractional micro-ablative CO2 laser. RESULTS: After three treatments, patients reported a complete improvement of the symptoms (59.94% dryness, 56.26% burn, sensation, 48.75% dyspareunia, 56.37% itch, 73.15% soreness, and 48.79% vaginal introitus pain). CONCLUSIONS: Fractional micro-ablative CO2 laser seems to reduce symptoms related to vaginal atrophy. The beneficial effects were reported just after the first session and confirmed 12 months after the last session.

Homocysteine serum levels are increased and correlate with disease severity in patients with lupus erythematosus.

OBJECTIVES: To determine homocysteine (Hcy) serum levels in patients with cutaneous lupus erythematosus (CLE) and a possible correlation with the disease activity. METHODS: Ninety-three patients with LE and 30 healthy controls were included in the study. For each patient, disease activity was calculated and plasma levels of Hcy was measured by enzymatic colorimetric assay. RESULTS: Forty-six patients had chronic cutaneous LE (CCLE), 14 had LE tumidus (LET), 17 had subacute CLE (SCLE) and 16 had SLE. Median values [25°-75° percentile] were 7[4-9] for CCLE, 3.5[2.3-4.8] for LET, and 8[7-10] for SCLE; for SLE the RCLASI score was 7.5[4.8-13] and the SELENA/SLEDAI score was 10.5[9-13.3]. HHcy was present in 73.9% of patients with CCLE, 35.7% with LET, 82.4% with SCLE, 81.2% with SLE, 20% of healthy controls. Overall, patients with LE showed a higher median serum Hcy level than the control group (15[13-18.2] vs. 11[8.8-12.2], p<0.001). There was a significant correlation between Hcy serum levels and disease activity, both in patients with CLE and SLE. CONCLUSIONS: We demonstrated that Hcy levels were higher in patients with different forms of CLE and correlated with disease activity calculated by CLASI. Therefore, HHcy could be related to LE pathogenesis and might be a triggering factor in predisposed individuals.

Ultrasound detects occult entheseal involvement in early psoriatic arthritis independently of clinical features and psoriasis severity.

OBJECTIVES: Entheseal involvement is a frequent and distinctive feature of psoriatic arthritis (PsA), and is often under-diagnosed. The aim of the present study is to investigate using ultrasound (US), lower limb entheseal abnormalities in patients with early psoriatic arthritis (ePsA) and to evaluate their correlation with ePsA clinical characteristics. METHODS: Ninety-two ePsA patients (with duration of symptoms less than 1 year), diagnosed according to CASPAR criteria, were consecutively scored with Glasgow Ultrasound Enthesitis Scoring System (GUESS) and Power Doppler (PD) US (My Lab 70 Esaote) of lower limbs entheses (quadriceps, patellar, achilles tendons and plantar fascia). Patients were clinically examined by palpation of lower limbs entheses, Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) and total Psoriasis Area and Severity Index (PASI). Correlations were investigated between GUESS and PD with other ePsA clinical characteristics (duration of symptoms and morning stiffness, pain and fatigue visual analogue scale [VAS], Health Assessment Questionnaire SpA-modified [S-HAQ]). RESULTS: All patients had GUESS>1 and 40.2% showed positive PD signal on entheses, at a higher percentage than tenderness revealed by clinical examination (29.3%). GUESS and PD did not correlate with MASES, PASI and other clinical characteristics. No significant differences in GUESS and PD were detected between positive or negative findings of MASES and PASI. CONCLUSIONS: US detects subclinical entheseal involvement in ePsA, independently of ePsA clinical examination and symptoms.

Hailey-Hailey disease treated with methotrexate.

BACKGROUND: Hailey-Hailey disease (HHD) is a chronic, recurrent blistering disorder characterized clinically by erosions occurring primarily in intertriginous regions and histologically by suprabasal acantholysis. MAIN OBSERVATIONS: We report a long standing case of HHD initially unresponsive to cyclosporin, multiple topical and systemic steroids. Good response was achieved with methotrexate 7,5 mg weekly for 16 week, intramuscularly, and topical steroids as needed. CONCLUSION: In conclusion, we suggest that methotrexate could be considered a therapeutic option for the treatment of HHD and in particular as a maintaining therapy to control the disease flares.

Dermatitis herpetiformis: from the genetics to the development of skin lesions.

Dermatitis herpetiformis (DH) is a rare autoimmune disease linked to gluten sensitivity with a chronic-relapsing course. It is currently considered to be the specific cutaneous manifestation of celiac disease (CD). Both conditions are mediated by the IgA class of autoantibodies, and the diagnosis of DH is dependent on the detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH, but environmental factors are also important. This paper describes these different factors and discusses the known mechanism that lead to the development of skin lesions.

Newly described clinical and immunopathological feature of dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is an inflammatory cutaneous disease with typical histopathological and immunopathological findings clinically characterized by intensely pruritic polymorphic lesions with a chronic-relapsing course. In addition to classic clinical manifestations of DH, atypical variants are more and more frequently reported and histological and immunological are added to them, whereas the impact on quality of life of patients with DH is increasingly important to a certain diagnosis. The aim of this paper is to describe all the possible clinical, histological, and immunological variants of DH in order to facilitate the diagnosis of a rare disease and, therefore, little known.

Why is Kikuchi-Fujimoto disease misleading?

BACKGROUND: Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis is a rare, benign, autoimmune condition characterized by lymphadenopathy, fever, and neutropenia. KFD has also been frequently reported in association with systemic lupus erythematosus (SLE). REPORT: We report a case of skin manifestations in KFD characterized by malar rash, photosensitivity, panniculitic lesions, positive antinuclear antibodies and nDNA, and negative extractable nuclear antigen. A biopsy performed on deep nodules on the arms revealed an infiltrate of monocytic cells. Electron microscopy showed no lymphocytic infiltrate at or below the basal membrane and no necrotic keratinocytes within the basal cells of the epidermis. CONCLUSION: Histological and ultrastructural data showed that skin manifestations of KFD and SLE share some common features. Electron microscopy analysis can help discriminate between the two diagnoses.

A study of fractional CO2 laser resurfacing: the best fluences through a clinical, histological, and ultrastructural evaluation.

BACKGROUND: Fractional resurfacing is a laser treatment modality to create numerous microscopic thermal injury zones of controlled width, depth, and density that are surrounded by a reservoir of spared epidermal and dermal tissue, allowing rapid repair of laser-induced thermal injury. OBJECTIVE: To evaluate the safety and efficacy of a fractional CO(2) laser system in the treatment of photo-damaged skin with clinical, histological, and ultrastructural evaluation, with special attention to one of the parameters of this laser system: the fluences. MATERIALS AND METHODS: Twelve patients with Fitzpatrick skin types II to III with photo-damage skin underwent fractional laser treatment with one single-pass superficial on the face and forearm. Clinical outcome and histological and ultrastructural changes were assessed. RESULTS: Light microscopy of biopsies gave important information about skin changes at three different times after fractional treatment, especially revealing some differences between the fluences used in the three groups of patients. CONCLUSION: Fractional resurfacing offers significant surgical advantages allowing to achieve excellent esthetic results in balance with the biological structure. Besides, our study shows already that with 2.07 and 2.77 J/cm(2) , instead of 4.15 J/cm(2) , it is possible to reach a biological response without scar formation.