A Novel Topical Formulation of the Leishmaniasis Drug Glucantime as a Nanostructured Lipid Carrier-Based Hydrogel.

Leishmaniasis is a parasitic disease caused by Leishmania parasites. Meglumine antimoniate, or Glucantime, is the primary drug used to treat this disease. Glucantime with a standard painful injection administration route has high aqueous solubility, burst release, a significant tendency to cross into aqueous medium, rapid clearance from the body, and insufficient residence time at the injury site. Topical delivery of Glucantime can be a favorable option in the treatment of localized cutaneous leishmaniasis. In this study, a suitable transdermal formulation in the form of nanostructured lipid carrier (NLC)-based hydrogel containing Glucantime was prepared. In vitro drug release studies confirmed controllable drug release behavior for hydrogel formulation. An in vivo permeation study on healthy BALB/C female mice confirmed appropriate penetration of hydrogel into the skin and sufficient residence time in the skin. In vivo performance of the new topical formulation on the BALB/C female mice showed a significant improvement in reduction of leishmaniasis wound size, lowering parasites number in lesions, liver, and spleen compared with commercial ampule. Hematological analysis showed a significant reduction of the drug's side effects, including variance of enzymes and blood factors. NLC-based hydrogel formulation is proposed as a new topical administration to replace the commercial ampule.

Higher Serum Vitamin D Levels have a Positive Association with the Incidence of Recidivans Form of Cutaneous Leishmaniasis; A Cross-Sectional Study.

Background: Several manifestations of cutaneous leishmaniasis are related to the host's immune system and the species of parasite. Objective: There have been some studies on the relationship between vitamin D statuses in infectious diseases including cutaneous leishmaniasis. However, the results of these studies have been inconsistent. Materials and Methods: In this cross-sectional study, 147 patients with leishmaniasis were recruited and divided into the following categories: acute cutaneous leishmaniasis (<1 year) (n = 51), chronic cutaneous leishmaniasis (more than 1 year) (n = 26), and leishmaniasis recidivans (the appearance of new papular lesions around a previous scar) (n = 20), and a group of participants without leishmaniasis (n = 50), as a control group. Serum 25-hydroxyvitamin D [25(OH) D] level was analyzed. Result: There were significant differences in serum 25(OH) D between the groups with acute or chronic leishmaniasis and those with recidivans leishmaniasis (P = 0.013 and P = 0.022, respectively). The median serum level of vitamin D in the acute group was 13.7 ng/mL, in the chronic group was 16.05 ng/mL, in the recidivans group was 21.75 ng/mL, and in the control group was 17.97 ng/mL. Conclusion: Higher serum concentrations of 25(OH) vitamin D levels being associated with leishmaniasis recidivans.

Treatment of Cutaneous Leishmaniasis with Allopurinol Plus Itraconazole in Iran.

Cutaneous leishmaniasis (CL) is a serious tropical disease and a neglected health challenge in Iran. Although limited data are available regarding anthroponotic CL, cases resistant to meglumine antimoniate (Glucantime) are increasingly being reported. Via an open-label noncontrolled case series, allopurinol (10 mg/kg/day) plus itraconazole (3-4 mg/kg/day) were orally administered for 1 month to 27 patients (56 lesions) with anthroponotic CL, most of whom were resistant to Glucantime. A mean lesion size of 3.5 ± 1.9 cm at baseline was reduced to 0.6 ± 1.0 after 1 month of treatment. Excellent treatment response was observed in 85.7% of lesions after 1 month. Recurrence only occurred in one patient in the 3-month follow-up session. This study presents preliminary evidence that oral allopurinol plus itraconazole could be an effective treatment in patients with anthroponotic CL.

Cognitive behavioral therapy as an adjuvant therapy in acne excoriée: a randomized controlled clinical trial.

BACKGROUND: Acne excoriée (AE) is a difficult challenge in dermatology practice. AE is mostly associated with some psychiatric disorders particularly mood disorders. Thus, patients generally continue to manipulate their lesions. It was aimed to compare the effectiveness of cognitive behavioral therapy (CBT) as an adjuvant treatment for AE in a randomized controlled clinical trial. METHODS: Thirty-two adults with AE were randomly assigned to CBT or control group. Both the groups received similar standard medication. Furthermore, eight sessions of CBT were held during 2 months in CBT group. Self-reported Skin Picking Scale (SPS), clinical severity rating, beck anxiety and depression inventories were determined at the baseline and after 2-month follow-up. RESULTS: Participants in CBT group showed significantly more improvement on clinical severity score (p=.01) as well as SPS score (p=.02) after 2-month follow-up, in comparison to the control group. Depression and anxiety scores were significantly diminished after two months among CBT group in comparison to controls (p value .01 for both anxiety and depression). CONCLUSION: CBT constitutes a utile treatment option for AE and should be considered as an adjuvant therapy in clinical setting.

Immunomodulatory effects of topical diphencyprone for the treatment of acute urban cutaneous leishmaniasis.

BACKGROUND AND OBJECTIVE: Efficacious and safe treatments are lacking for cutaneous leishmaniasis (CL). This study investigates the efficacy of adding diphencyprone immunotherapy to conventional meglumine antimoniate (MA) treatment for acute urban CL. METHODS: This randomized controlled pilot study included 46 patients with acute CL. They were randomly allocated to receive either combination of diphencyprone immunotherapy with intralesional MA (intervention; N = 23) or intralesional MA alone (control; N = 23) weekly. The size and duration of lesions were measured at the baseline and after that at 4th, 8th, 12th, and 24th weeks. Data were analyzed in SPSS and p < .05 was considered significant. RESULTS: The groups showed no significant difference in duration of lesions, but number of injections was significantly higher in the control group compared with the intervention group (p < .001). Size and induration of lesions was significantly reduced in both groups during the course of study (p < .001). The intervention group showed significantly lower induration of lesions in 4th, 8th, and 12th week compared with controls (p < .05). CONCLUSION: Combination of diphencyprone with MA resulted in earlier resolution of acute CL lesions with a relatively acceptable rate of adverse effects, compared with intralesional MA alone.

Evaluating the efficacy and safety of vascular IPL for treatment of acute cutaneous leishmaniasis: a randomized controlled trial.

Treatment of cutaneous leishmaniasis (CL) continues to be a health concern, and alternative therapies with fewer side effects are substantially needed. This study aimed to determine the efficacy of intense pulsed light (IPL) with wavelength spectrum affecting vascular lesions on acute cutaneous leishmaniasis. In this randomized clinical trial study, 30 patients with acute CL were enrolled. Baseline clinical and demographic data were recorded in the checklist after obtaining written informed consent. Patients were randomly allocated to receive either IPL fortnightly (intervention group) or intralesional meglumine antimoniate (MA) weekly (control group) over 10 weeks. Patients were assessed every 2 weeks to determine the size of induration and improvement rate of lesions. Follow-up visits were arranged at 3rd and 6th months. Overall, 15 patients (21 lesions) in the intervention group and 15 patients (22 lesions) in the control group were studied. The size of lesions in the control group was significantly higher at the baseline (P = 0.014) and the second week (P = 0.034), and significantly lower in the eighth week (P = 0.009), compared with the intervention group. The size of lesions in the control group changed during the study (P < 0.001), whereas changes were not significant in the intervention group. The trend of changes in size of lesions was faster in the control group (P < 0.001). More patients in the control group had higher improvement rate at the sixth (P = 0.005) and tenth (P < 0.001) weeks. At the end of study, the cure rate was 35% (7 out of 20 lesions) in intervention group and 81.8% (18 out of 22 lesions) in the control group. Complete response happened earlier in the control group (P < 0.001). None of the lesions that were cured before the tenth week relapsed after 6 months. The frequency of blistering was significantly higher in intervention group (P = 0.001). Our results indicated that IPL with wavelength spectrum affecting vascular lesions was inferior to intralesional MA in treatment of CL. However, it can be considered as a second-line option, especially in patients with limitations for use of MA. Trial registry:  https://www.irct.ir/trial/34246 IRCT20140414017271N5.

Molecular signatures of anthroponotic cutaneous leishmaniasis in the lesions of patients infected with Leishmania tropica.

Anthroponotic cutaneous leishmaniasis (CL) caused by Leishmania tropica (L. tropica) represents a public health challenge in several resource poor settings. We herein employed a systems analysis approach to study molecular signatures of CL caused by L. tropica in the skin lesions of ulcerative CL (UCL) and non-ulcerative CL (NUCL) patients. Results from RNA-seq analysis determined shared and unique functional transcriptional pathways in the lesions of the UCL and NUCL patients. Several transcriptional pathways involved in inflammatory response were positively enriched in the CL lesions. A multiplexed inflammatory protein analysis showed differential profiles of inflammatory cytokines and chemokines in the UCL and NUCL lesions. Transcriptional pathways for Fcγ receptor dependent phagocytosis were among shared enriched pathways. Using L. tropica specific antibody (Ab)-mediated phagocytosis assays, we could substantiate Ab-dependent cellular phagocytosis (ADCP) and Ab-dependent neutrophil phagocytosis (ADNP) activities in the lesions of the UCL and NUCL patients, which correlated with L. tropica specific IgG Abs. Interestingly, a negative correlation was observed between parasite load and L. tropica specific IgG/ADCP/ADNP in the skin lesions of CL patients. These results enhance our understanding of human skin response to CL caused by L. tropica.

Nutritional Intake and Chronicity Associated with the Old World Cutaneous Leishmaniasis: Role of Vitamin A.

BACKGROUND: Old world cutaneous leishmaniasis (CL) is known as a self-healing cutaneous parasitic infection. Host immunity has a fundamental role in the course of this infection. This study was designed to investigate the relationship between nutritional status and vitamin A intake with the clinical course of CL. METHODS: Overall, 250 patients with CL attending a dermatology clinic in Imam Reza Hospital Mashhad, Iran, were enrolled from Apr 2011 to Aug 2012. For data gathering, a semi-quantitative 302-item food frequency questionnaire was utilized. They received routine treatment protocols for leishmaniasis and 1 year of follow-up. RESULTS: As for the 149 patients who completed the study, a deficiency of macro and micronutrients, particularly vitamin A, was significantly related to a chronic clinical disease course. CONCLUSION: Imbalanced or insufficient nutritional intake including vitamin A deficiency, may influence the clinical course of CL.

Non-Ablative Fractional 1,540-nm Er:Glass Laser in the Treatment of Atrophic Cutaneous Leishmaniasis Scars.

OBJECTIVES: To evaluate the efficacy of nonablative fractional 1,540 nm laser to treat the atrophic scars caused by the cutaneous leishmaniasis (CL). METHODS: This clinical trial with a pre- and a posttreatment measurement was conducted on patients with atrophic CL scars. The lesions were treated with nonablative fractional 1,540 nm laser. We evaluated the patients initially and then monthly, before each treatment session. The final follow-up was done 6 months after the end of study for all patients. Patient assessment was performed by two physicians using the modified Manchester Scar Scale (MSS) as well as the interpretation of captured digital photographs. Moreover, the patients performed a self-assessment by filling in a researcher-made questionnaire. The data were statistically analyzed by SPSS software. P < 0.05 was considered statistically significant. RESULTS: Thirty patients with 37 skin lesions participated in the study. The pairwise comparison demonstrated a statistically significant difference between the modified MSS parameters (P < 0.05); however, no significant difference was observed between the modified MSS of the third and fourth (P = 0.82) as well as fourth and fifth (P = 0.636) sessions. The lesions improvement was significant based on the physician's evaluation (P < 0.001). Furthermore, patients' level of satisfaction was significantly increased in all six follow-ups (P < 0.001). No persistent complication was found. CONCLUSIONS: Nonablative fractional 1,540 nm laser is an effective and safe therapeutic choice for atrophic CL, even in darker skins. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Efficacy of erbium glass laser in the treatment of Old World cutaneous leishmaniasis: A case series.

BACKGROUND: Treatment of cutaneous leishmaniasis remains a challenge; new physical treatment modalities including laser systems are of interest in the treatment of localized lesions. METHOD: Fourteen patients (10 females) with 20 lesions of Old World cutaneous leishmaniasis underwent weekly treatments of 1540 nm erbium glass fractional laser (Palomar) using 10 mm spot size hand piece in four passes of 50-70 mJ/cm2 fluence and 10 ms pulse duration. RESULTS: Twelve lesions were available for assessment: six (50%) improved at 6 weeks and eleven lesions (91.7%) at 12 weeks. There were no recurrences at 6- and 12-month follow-ups. CONCLUSION: Erbium glass fractional laser may be an alternative treatment for localized cases of Old World cutaneous leishmaniasis.

Plasma levels of interlukin-4 and Interferon-γ in patients with chronic or healed cutaneous leishmaniasis.

OBJECTIVE(S): In this study, the serum level of interferon-γ (IFN- γ) and interlukin-4 (IL-4) was evaluated as a marker of Th1 and Th2 immune response that influence the clinical course of cutaneous leishmaniasis . MATERIALS AND METHODS: This cross-sectional study was conducted on 44 cases of cutaneous leishmaniasis (21 cases with healed lesions and 23 cases with chronic non-healing lesions. Thirty-two non-infected persons living in the area were considered as controls. Serum levels of IFN- γ and IL-4 were determined using ELISA, and the results along with clinical data were analyzed using SPSS 11.5. RESULTS: Serum IFN-γ level was not significantly different between various patient groups and control (P=0.27), but the serum level of IL-4 in patient groups was higher than in healthy subjects, and it was higher in patients with non-healed chronic cutaneous leishmaniasis than those with healed lesions (P<0.01). CONCLUSION: Serum IL-4 level is a good marker for evaluation of the clinical course of cutaneous leishmaniasis.

Serotonin transporter protein overexpression and association to Th17 and T regulatory cells in lupoid leishmaniasis.

The immunopathogenesis of chronic non-healing Old World cutaneous leishmaniasis is challenging. There is a bidirectional communication between the nervous and immune systems, serotonin being an important mediator in this respect. Our aim was to study the role of the serotonin transporter protein (SERT) and its relation to T cell-related immune responses in lupoid leishmaniasis. Paraffin-embedded skin biopsies of 12 cases of lupoid and 12 cases of usual types of cutaneous leishmaniasis were investigated using immunohistochemistry regarding expression of SERT, Th1, Th2, Th17 and T regulatory cell (Treg) markers. SERT as well as Tregs and interleukin (IL)-17 positive cells were more prevalent while IL-5 (Th2) and interferon (IFN)-γ (Th1) expressing cells were less numerous in the lupoid tissue compared to those from the usual type of leishmaniasis. The majority of the SERT(+) cells were also tryptase(+) (mast cells). There was a positive correlation between a higher number of SERT(+) and IL-17(+) cells in the lupoid type, while lower numbers of SERT(+) cells were significantly related to lower percentages of CD25(+) cells in the usual type of leishmaniasis. These results might indicate a role for SERT, Th17 and Tregs in the pathogenesis of lupoid leishmaniasis.

Interleukin-2 expression in lupoid and usual types of old world cutaneous leishmaniasis.

BACKGROUND: Interleukin (IL)-2 plays a central role in T cell-dependent immune responses. OBJECTIVES: We conducted this study to determine and compare IL-2 expression in lupoid and usual types of Old World Cutaneous Leishmaniasis (OWCL), using immunohistochemistry. PATIENTS AND METHODS: Thirteen paraffin-embedded specimens of lupoid and 12 specimens of usual types of OWCL were used. A mouse monoclonal anti IL-2 antibody was used for staining by the envision technique. RESULTS: There were strongly stained discrete foci of staining through inflammatory infiltrates of dermis and also in basal layers of epidermis and adnexal structures, with a distinctive pattern of hot spot activity foci (mean of 9.31 ± 6.4 versus 8.17 ± 6.9 foci per HPF for lupoid and usual types, respectively). The expression of IL-2 had no correlation with the pattern of granulomatous inflammation (tuberculoid, sarcoidal or mixed suppurative). CONCLUSIONS: Interleukin-2 takes part in the immunological response of the granulomatous reaction of OWCL and is not statistically different between lupoid and usual types (P = 0.674).