Evaluation of tolerability and efficacy of a topical emulgel containing nanoliposomal ruxolitinib phosphate in the treatment of mild atopic dermatitis: a before-after single group pilot study.

BACKGROUND: Ruxolitinib is a JAK1/2 inhibitor, which inhibits the signal transduction of interferon-gamma, a cytokine implicated in the pathogenesis of atopic dermatitis (AD). In this before-after single group phase IIA pilot study, we investigated the efficacy of topical nanoliposomal ruxolitinib phosphate (RuxoLip) emulgel in mild AD. METHODS: Clinical evaluation was conducted on 10 patients with mild AD. The efficacy of the product as well as patient satisfaction was evaluated by local scoring atopic dermatitis (SCORAD) of AD. In addition, trans-epidermal water loss (TEWL), stratum corneum (SC) hydration, sebum, erythema, melanin content, and ultrasonographic parameters were measured before, and two and four weeks after treatment. RESULTS: Four weeks of treatment reduced SCORAD, itching, and burning (p = .001, .001, and .001, respectively) and increased hydration, sebum, and epidermal density (p = .001, .018, and .037, respectively). SCORAD and other skin biophysical parameters improved within two weeks of treatment and then were in plateau for up to four weeks. CONCLUSIONS: The topical ruxolitinib emulgel has good short-term efficacy and tolerability.

The Immunogenetics of Alopecia areata.

Alopecia areata (AA) is an autoimmune disease that targets the hair follicles (HF) and results in non-scarring hair loss. AA results from the collapse of the HF's immune privilege due to a combination of environmental and genetic factors that either change the local HF dynamics or dysregulate the central immune tolerance. Multiple genetic studies have attempted to identify AA susceptibility genes through candidate gene approaches and genome-wide analysis. These studies were able to show an association between AA and multiple immune-related genes such as those encoding cytokines, chemokines, molecules involved in regulatory T-cell functions, and adaptor molecules along with genes involved in autophagy, melanogenesis, and hair cycling pathways. This chapter aims to explore these genes and their contribution to the pathogenesis of the AA.

Efficacy assessments of tretinoin-loaded nano lipid carriers in acne vulgaris: a double blind, split-face randomized clinical study.

Here, we assessed the efficacy and safety of Nano lipid carrier (NLC) drug delivery system containing tretinoin (NLC-TRE) in comparison with the conventional 0.05% tretinoin cream (TRE cream) in mild to moderate acne vulgaris. A stable and appropriate NLC-TRE formulation was prepared using a high-pressure homogenizer and particle characterization and physicochemical properties were evaluated under accelerated conditions. Efficacy assessment was performed via a split-face clinical study, by comparing the number of acne lesions, porphyrin production and skin biophysical parameters in both sides of the face randomly treated with NLC-TRE and TRE cream. Plasma concentration of tretinoin after topical application of NLC-TRE was measured for primary safety evaluation. We acquired a stable, spherical nanoparticles with particle size of 118.5 nm, PI equal to 0.485 and ZP of - 44.7 mV. The rate of decrease of acne lesions was significantly higher in NLC- TRE side (p value < 0.001). The size and intensity of porphyrin production in pilosebaceous follicles were significantly reduced only on NLC-TRE side (p value < 0.01). The plasma concentration of the tretinoin, after 8 weeks' application remained lower than the toxic levels. The NLC-TRE formula provides better efficiency and good loading capacity of TRE in the drug delivery system.

Combination of topical liposomal amphotericin B and Glucantime in comparison with glucantime alone for the treatment of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica: study protocol for a randomized, controlled trial.

BACKGROUND AND OBJECTIVES: Cutaneous leishmaniasis (CL) treatment is a challenging issue, although numerous modalities have been introduced as candidate treatment for CL yet only antimonial agents are commonly used to treat CL, a different form of amphotericin B is used to treat visceral form of leishmaniasis but the efficacy against CL is not high. There are a few reliable clinical trials on CL, the main reason is the nature of the disease which required a well design protocol to evaluate the efficacy of any candidate treatment against CL. In this study, a protocol was developed and used to evaluate a topical formulation of a nano-liposomal form of amphotericin B in addition to glucantime to treat CL caused by L. tropica. MATERIALS AND METHODS: This study is a phase 3, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topical nano-liposomal amphotericin B (SinaAmpholeish 0.4%) in combination with intralesional injections of meglumine antimoniate in the treatment of ACL caused by L. tropica. Overall, 130 patients, aged 12-60 years, with a diagnosis of ACL caused by L. tropica are recruited and treated according to the protocol. RESULTS: A total of 130 patients with CL lesion will be recruited and doubleblind randomly treated with received intralesional injections of Glucantime weekly or Glucantime plus SinaAmpholeish for 4 weeks. CONCLUSION: The results of this study showed that the protocol works well and the treatment was tolerated by both groups of patients.

Drug Sensitivity Profile of Fungi Isolated from Onychomycosis Patients and Evaluation of Squalene Epoxidase Mutation in One Terbinafine-Resistant Trichophyton mentagrophytes Species.

Background: The resistance to treatment of onychomycosis is increasingly reported. The present study aimed to assess the antifungal activity of itraconazole, terbinafine, luliconazole, and efinaconazole against dermatophytes, molds, and also yeast isolated from patients with onychomycosis. Furthermore, the mechanism of resistance to terbinafine in resistant Trichophyton mentagrophytes species was evaluated using the squalene epoxidase (SQLE) gene sequence. Methods: A total of 71 fungal isolates were collected from 97 patients with suspected onychomycosis. The identification of fungal species was performed using conventional and molecular approaches. In vitro drug susceptibility for itraconazole, terbinafine, luliconazole, and efinaconazole was carried out using the broth microdilution method according to the CLSI-M60 and CLSI-M38 3rd ed., respectively. The SQLE gene of one terbinafine-resistant T. mentagrophytes was amplified using the specific primers. Results: Efinaconazole and luliconazole demonstrated higher effectiveness against all isolates in the study. One mismatch was detected at position 1177, which showed A → C change associated with Phe397Leu amino acid substitution of the SQLE protein in terbinafine-resistant T. mentagrophytes. Conclusion: The occurrence of resistant strains of organisms causing onychomycosis should be considered and evaluated. Furthermore, the identification of amino acid changes responsible for resistance to antifungals is a useful consideration in drug-target interaction.

Old world cutaneous leishmaniasis in Iran: clinical variants and treatments.

BACKGROUND: Old World cutaneous leishmaniasis (OWCL) is endemic in Iran and most cases of cutaneous leishmaniasis (CL) are caused by Leishmania major, and then Leishmania tropica, and rarely by Leishmania infantum. OBJECTIVE: We aimed to describe clinical variants of OWCL and their treatments. METHOD: Through literature search in PubMed, Scopus and Embase and google scholar, we have found articles about variant clinical pictures of OWCL and their treatments. RESULTS: The following clinical variants of OWCL namely; localized forms, zosteriform, erysipeloid, eczematoid, warty, localized Leishmania lymphadenitis, sporotrichoid, hyperkeratotic, impetiginized, mucosal involvement in CL, lupoid leishmaniasis, chronic lesions due to leishmanization, disseminated cutaneous leishmaniasis, reactivation of CL after transplantation and coexistence of CL with other diseases, are reported from Iran. The mainstay of therapy remains pentavalent antimonial compounds and cryotherapy is an adjuvant to therapy. Treatment with antifungal agents, miltefosine, amphotericin B and herbal extract such as ZH-E have also been used. Treatment of CL in chronic cases and in immunosuppressed patients is difficult and relapse may occur. CONCLUSION: In clinical variants of CL with long duration and multiple lesions, systemic pentavalent antimonial compounds are first step of therapy. In case of incomplete response or resistant to classic treatment, combination therapy is indicated.

Safety Evaluation of Topical Application of Nano-Liposomal Form of Amphotericin B (SinaAmpholeish) on Healthy Volunteers: Phase I Clinical Trial.

BACKGROUND: We aimed to evaluate the safety of SinaAmpholeish in a double-blind, randomized, phase 1 clinical trial in healthy human volunteers. METHODS: The study was carried out in DermaLab of Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran in 2012. A topical Nano-liposomal formulation of 0.4% Amphotericin B was developed against Leishmania under trade name of SinaAmpholeish. In this randomized, double-blind, right-left, comparative, phase I clinical trial, in 2 steps; 7 and 20 healthy volunteers were recruited and applied SinaAmpholeish on the right and its vehicle on the left volar side of forearm, twice a day for one week or 3 times a day for two weeks. Seven biophysical skin parameters were measured in standard conditions before and 2 wk after application. RESULTS: There was no adverse effect when SinaAmpholeish and its vehicle were used twice a day for seven days. However, when were used 3 times a day for two weeks, both SinaAmpholeish and its vehicle induced severe local skin reactions in 2 volunteers leading to discontinuation of application. Mild and temporary local reactions were observed in about half of the application sides and there was no significant difference between SinaAmpholeish and its vehicle. CONCLUSION: The new formulation is safe and worth to be tested in further phase 2 clinical trial and since there was no adverse effect with twice a day application it was decided to use SinaAmpholeish twice a day in phase 2 clinical trial.

Safety Evaluation of Nano-Liposomal Formulation of Amphotericin B (Sina Ampholeish) in Animal Model as a Candidate for Treatment of Cutaneous Leishmaniasis.

BACKGROUND: Development of a topical treatment for cutaneous leishmaniasis (CL) is an important step in the improvement of lesion management. Amphotericin B (AmB) is effective against Leishmania species but it is toxic, a Nano-liposomal form of AmB with a size of about 100nm (Lip-AmB) was developed and showed to be effective against Leishmania major, and Leishmania tropica in vitro and against L. major in vivo in animal model. This study was designed to check the irritancy Draize test in rabbits and was completed in the Center for Research and Training in Skin Diseases and Leprosy, TUMS, in 2012. METHODS: Twenty rabbits in 3 steps were housed individually with artificial lighting (12/12h light/dark). SinaAmpholeish cream or empty liposomes (prepared under GMP condition at Minoo Company, Tehran, Iran), was applied on a gauze patch and the patches were placed on the designated sites of the skin in the back of the rabbits. At 48 and 72h later, the erythema and oedema were checked, scored and recorded. RESULTS: The erythema score in rabbits was 0.83+0.41 for the SinaAmpholeish and 0.5+0.55 for empty liposomes (P= 0.16). The average score for oedema was 0.67+0.52 for SinaAmpholeish and 0.33+0.52 for empty liposomes (P= 0.16). CONCLUSION: Based on skin irritancy reactions the topical formulation of SinaAmpholeish is safe and could be further checked in human trials.

Tretinoin Loaded Nanoemulsion for Acne Vulgaris: Fabrication, Physicochemical and Clinical Efficacy Assessments.

BACKGROUND AND AIM: Acne vulgaris is a common inflammatory skin condition which is treated using Tretinoin (TRE), a widely used retinoid. Nano emulations (NEs) are colloidal nano-sized particles that enhance the therapeutic efficacy of TRE and minimize adverse effects. This study is aimed at developing a TRE-loaded NE (NE-TRE) and at assessing the therapeutic effects of the formulation in acne vulgaris lesions, compared to conventional 0.05% TRE emulsion. METHOD: The high energy emulsification method was used to make NE-TRE. After obtaining stable NE, particle characterization and physicochemical properties were evaluated under accelerated conditions. Conducting a clinical study, we compared the therapeutic effects of NE-TRE and 0.05% TRE emulsion by comparing the number of acne lesions and porphyrin production in both sides of the face. RESULTS AND CONCLUSION: We successfully developed stable nanoparticles. It was a stable oil-in-water emulsion with particle size of about 150 nm, and containing circular and separated particles. In a pilot clinical study, the number of acne lesions as well as the size and intensity of porphyrin production significantly reduced after topical application of NE-TRE. This formula shows proper efficiency and good loading capacity of TRE in the drug delivery system.

Janus kinase (JAK) inhibitors for the treatment of skin and hair disorders: a review of literature.

Janus kinase family (JAKs) has recently attracted the attention of many researchers, and several JAK inhibitor drugs have been developed targeting different members of the JAK family. Tofacitinib and ruxolitinib are US FDA approved drugs in this family for rheumatoid arthritis and myeloproliferative diseases, respectively. Dysregulation of JAK/STAT pathway is also involved in many skin diseases, specifically inflammatory disorders. The JAK/STAT signaling pathway and its involvement in skin diseases are overviewed in this study. We also review clinical studies of JAK inhibitors in field of dermatology, including psoriasis, atopic dermatitis, alopecia areata and vitiligo. Although the available evidence shows promising results, it is still too early to draw a firm conclusion about the place of these drugs in dermatological treatment.

Evaluation of occupational allergic contact dermatitis and its related factors in Iran.

Background: Occupational contact dermatitis, especially in hand, is one of the most common occupational disorders. The present study aimed at evaluating patients with occupational allergic contact dermatitis (ACD) caused by common allergens based on occupation type and disease history. Methods: This cross-sectional study aimed at evaluating the data of the patients with probable diagnosis of ACD in Center for Research and Training in Skin Diseases and Leprosy (CRTSDL) in Iran. In the present study, 946 patients were assessed from different regions of Iran. One hundred fifty-one cases with positive patch test and relevant exposure were entered into the study; data related to their occupation and disease activity history were evaluated and recorded. Then, factors related to disease activity history were assessed considering the occupational groups and common exposures. Results: Nickel sulphate was the most common allergen in the 151 patients. Disease activity was constant in 29.8% of the patients; it increased in 27.8%, and decreased just before doing the patch test in 42.4%. Of the patients, 52.3% were getting worse during the working days. Occupational groups were significantly different in age and gender. Disease duration was also different in the occupational groups (p=0.001). The least disease duration was observed in healthcare workers, and the most in service workers. Lesions in the foot were related to period of employment. In administrative work group, (teachers, technicians and housewives) disease activity was decreased in the most cases, while it was increased in most patients of service workers (p=0.086). Conclusion: The present study, similar to previous reports, revealed that nickel sulphate is the most common allergen in ACD cases. Moreover, it was found that the symptoms of disease activity remained constant or increased in a significant proportion of the cases during the working days. Therefore, these workers should seriously follow up on this matter and change their occupation, or limit the exposure to allergens.

Comparison of intradermal injection with iontophoresis of abobotulinum toxin A for the treatment of primary axillary hyperhidrosis: a randomized, controlled trial.

BACKGROUND: Botulinum neurotoxin type A (BTX-A) injection is the treatment of choice for idiopathic axillary hyperhidrosis (IAH) refractory to conventional treatments. OBJECTIVE: This study compared the efficacy of BTX-A injection and iontophoresis for treatment of IAH in a randomized controlled trial. METHODS: In eleven patients with the diagnosis of IAH, one axilla was randomly treated with injections of 1.5 mL (250 MU) of BTX-A, and the other side was treated with BTX-A administered by iontophoresis. The amount of sweating, skin hydration, transepidermal water loss, pain, and patient satisfaction on both axilla were compared with baseline levels, and also between both sides 1 week, 1 month, and 6 months after treatment. RESULTS: The injection side had significantly less sweat production than the iontophoresis side 1 week, 1 month, and 6 months after treatment (84%, 76%, and 50% vs. 73%, 22%, and 32%, respectively). The response to iontophoresis was more stable than that to injection. Participants' pain perception during the procedure score was significantly less on the iontophoresis side compared with the injection side (15.0 vs. 20.0, p < 0.05). CONCLUSION: This study has shown that injection is a more effective method for the administration of BTX-A, though iontophoresis can also be considered a non-invasive and painless method in some patients.

Allergic contact dermatitis to metal allergens in Iran.

BACKGROUND: Metallic allergens such as nickel are among the most common causes of allergic contact dermatitis (ACD), but frequencies of contact dermatitis to these allergens may vary in different areas. OBJECTIVES: This study aimed to determine the frequencies of ACD caused by three common metallic allergens: nickel sulfate; potassium dichromate; and cobalt chloride. METHODS: Data for 1137 patients with clinical diagnoses of contact dermatitis and/or atopic dermatitis evaluated by patch testing in Iran during a 5-year period were retrospectively studied to establish the frequencies of hypersensitivity to these metallic allergens. RESULTS: A total of 313 patients (27.5%) gave positive patch test results for at least one metallic allergen. Allergy to nickel (229 cases, 20.0%) was the most commonly observed, followed by allergy to cobalt (90 cases, 8.0%) and allergy to chromium (70 cases, 6.2%). Nickel allergy was significantly more frequent in females and in subjects aged <40 years, whereas chromium hypersensitivity was more common in males and in subjects aged >40 years. Sensitivity to nickel or chromium was a risk factor for cobalt allergy. CONCLUSIONS: Nickel was most commonly identified as a metallic allergen in Iran and tended to affect women aged <40 years. Regulations pertaining to nickel release may decrease the frequency of nickel hypersensitivity in Iran.

Pre-operative assessment of basal cell carcinoma dimensions using high frequency ultrasonography and its correlation with histopathology.

INTRODUCTION: High frequency ultrasonography (HFUS) is a non-invasive, low risk method which can provide real-time visual information regarding different processes in cutaneous tissue. The goal of this study is to compare the accuracy of HFUS in determining depth and width of basal cell carcinoma (BCC) lesions compared with histopathology as a reference standard. METHODS: The depth and width of 56 primary BCCs in various locations were measured in vivo using the ultrasound system device Digital Taberna Promedica (Luneburg, FRG DUB 20 Ultrasound Scanner), with a 50-MHz hand-held transducer and compared with the depth and width reported in histopathologic examination of these lesions after complete excision. The intraclass correlation coefficient (ICC) was calculated using a one-way ANOVA table to compare measured dimensions for the same tumors with the two diagnostic methods. RESULTS: The mean depth of tumor in HFUS (1353.68 ± 656.456 microns) was lower than the amount measured by the dermatopathologist (1560.71 ± 1044.323 microns). However, the difference was not statistically significant (P > 0.05). The means of largest diameter of tumors in HFUS and pathology were 5996.77 ± 2271.783 and 3891.07 ± 1995.452 microns, respectively (P < 0.001). There was a low correlation in diameter (r = 0.27, P < 0.05) and a moderate correlation in depth (r = 0.45, P < 0.001) of BCCs between these two methods. CONCLUSION: HFUS may be a useful method to assess the dimensions of BCC prior to surgery.

Cutaneous leishmaniasis in suspected patients referred to the center for research and training in skin diseases and leprosy, tehran, iran from 2008 to 2011.

BACKGROUND: Cutaneous leishmaniasis (CL) is a major health problem in many parts of Iran, although diagnosis of CL especially in the endemic area is easy, but treatment and management of the disease is a global dilemma. Diagnosis of CL in non-endemic area is not as simple as in endemic foci. In this study, the status and the proportions of CL induced by Leishmania major and L. tropica among CL suspected patients referred to the Center for Research and Training in Skin Diseases and Leprosy, (CRTSDL) during 2008 to 2011 are described. METHODS: CL patients with suspected lesions were clinically examined. History of trip to zoonotic CL and/or anthroponotic CL endemic areas and the characteristics of their lesion(s) were recorded. Diagnosis of the lesion was done using direct smear microscopy, culture and conventional polymerase chain reaction (PCR). RESULTS: A total of 404 (M = 256, F = 148) patients with 776 lesions were recruited and parasitologically examined. The results showed that 255 of the patients with 613 lesions; patients with lesion(s) induced by L. major=147 (M = 63, 43%, F = 84, 57%) and lesion(s) induced by L. tropica=108 (M = 35, 32%, F = 73, 68%). History of travel to endemic area was not always correlated with isolated Leishmania species. CONCLUSION: Although travel history to endemic area is an important factor to be considered for diagnosis, but parasitological confirmation is necessary initiation of treatment.

Variation of biophysical parameters of the skin with age, gender, and body region.

BACKGROUND: Understanding the physiological, chemical, and biophysical characteristics of the skin helps us to arrange a proper approach to the management of skin diseases. OBJECTIVE: The aim of this study was to measure 6 biophysical characteristics of normal skin (sebum content, hydration, transepidermal water loss (TEWL), erythema index, melanin index, and elasticity) in a normal population and assess the effect of sex, age, and body location on them. METHODS: Fifty healthy volunteers in 5 age groups (5 males and females in each) were enrolled in this study. A multifunctional skin physiology monitor (Courage & Khazaka electronic GmbH, Germany) was used to measure skin sebum content, hydration, TEWL, erythema index, melanin index, and elasticity in 8 different locations of the body. RESULTS: There were significant differences between the hydration, melanin index, and elasticity of different age groups. Regarding the locations, forehead had the highest melanin index, where as palm had the lowest value. The mean values of erythema index and melanin index and TEWL were significantly higher in males and anatomic location was a significant independent factor for all of 6 measured parameters. CONCLUSION: Several biophysical properties of the skin vary among different gender, age groups, and body locations.

BCL-2 and Bax Expression in Skin Flaps Treated with Finasteride or Azelaic Acid.

Despite all modern surgical techniques, skin flap that is considered as the main method in most reconstructive surgeries puts the skin tissue at danger of necrosis and apoptosis derived from ischemia. Therefore, finding a treatment for decreasing the apoptosis derived from flap ischemia will be useful in clinic. In present study, we evaluated the effect of azelaic acid 20% and finasteride on expression of BCL-2 and bax proteins after the skin flap surgery. For this purpose, 21 rats were entered in three groups including control, azelaic acid 20% and finasteride, all experienced skin flap surgery and then flap tissue was assessed for determining the expression of proteins in 5 slices prepared from each rat that were graded between - to +++ scales. Both azelaic acid and finasteride increased the expression of BCL-2 protein (p < 0.05) and decrease the expression of bax protein (p < 0.05). These results suggested an antiapoptotic role for finasteride and azelaic acid in preserving the flap after the ischemia reperfusion insult.

Combination of azelaic acid 5% and clindamycin 2% for the treatment of acne vulgaris.

CONTEXT AND OBJECTIVE: Acne vulgaris, an inflammatory skin disease with different clinical appearances, is a common problem in most adolescents. It seems that using combinations of topical agents can decrease resistance to the treatment and improve the efficacy. Therefore, we evaluated the effects of azelaic acid (AA) 5% and clindamycin (Clin) 2% combination (AA-Clin) on mild-to-moderate acne vulgaris. MATERIALS AND METHODS: The efficacy and safety of 12-week treatment with AA-Clin in patients with mild-to-moderate facial acne vulgaris were evaluated by a multicenter, randomized, and double-blind study. A total of 88 male and 62 female patients were randomly assigned to one of these treatments: AA 5%, Clin 2%, and combination of them. Every 4 weeks, total inflammatory and noninflammatory lesions were counted, acne severity index (ASI) was calculated, and patient satisfaction was recorded. RESULTS: Treatment for 12 weeks with combination gel significantly reduced the total lesion number compared with baseline (p < 0.01), as well as Clin 2% or AA 5% treatment groups (p < 0.05 or p < 0.01). The percentage of reduction in ASI in combination treated group (64.16 ± 6.01) was significantly more than those in the Clin 2% (47.73 ± 6.62, p < 0.05) and 5% AA (32.46 ± 5.27, p < 0.01) groups after 12 weeks. Among the patients in the AA-Clin group, 75.86% of males were satisfied or very satisfied and 85.71% of females were satisfied or very satisfied. This trend was significant in comparison to the number of patients who were satisfied with AA 5% or Clin 2% treatment (p < 0.01). Seven patients in AA-Clin group (incidence = 22%) showed adverse effects that were not statistically significant compared to treatment with individual active ingredients. DISCUSSION AND CONCLUSION: The profound reduction in lesion count and ASI by combination therapy with AA-Clin gel in comparison to individual treatment with 5% AA or Clin 2% suggested the combination formula as an effective alternative in treatment of acne vulgaris.