Oxidative Stress in Patients With Melasma: An Evaluation of the Correlation of the Thiol/Disulfide Homeostasis Parameters and Modified MASI Score.

Melasma is a common acquired hyperpigmentation disorder that affects mostly women and individuals with darker skin types. Oxidative stress may play a role in the pathogenesis of melasma. Dynamic thiol/disulfide homeostasis is one of the most important indicators of oxidative stress. This study aimed to investigate the presence of oxidative stress in patients with melasma by evaluating thiol/disulfide homeostasis. Sixty-seven patients with melasma and 41 healthy age- and sex-matched controls were included in the study. Disease severity was evaluated using the modified melasma area and severity index (mMASI). Thiol/disulfide homeostasis parameters of the melasma and control groups were measured using a novel, fully automated spectrophotometric method. Our data indicated the presence of oxidative stress in melasma, which may be correlated with disease severity. Because research on the presence of oxidative stress in melasma is limited, further studies are needed to support these conclusions.

Analysis of factors influencing target PASI responses and side effects of methotrexate monotherapy in plaque psoriasis: a multicenter study of 1521 patients.

Methotrexate (MTX) is commonly used as first-line systemic treatment agent in psoriasis. We aimed to evaluate the clinical characteristics and treatment responses of patients with psoriasis undergoing MTX monotherapy. Data from adult patients with plaque psoriasis who received MTX monotherapy for at least 3 months between April 2012 and April 2022 were retrospectively evaluated in 19 tertiary care centers. Our study included 722 female and 799 male patients, a total of 1521 participants. The average age of the patients was 44.3 ± 15.5 years. Mode of treatment was oral in 20.4% of patients while in 79.4% it was subcutaneous. The median treatment duration was 8 months (IQR = 5-15). The median weekly dose was 15 mg (IQR = 11-15). 1448 (95.2%) patients were taking folic acid supplementation. At week 12, 16.3% of the patients achieved PASI (Psoriasis Area and Severity Index) 90 response while at week 24, 37.3% achieved it. Logistic regression analysis for week 12 identified the following independent factors affecting PASI 90 achievement positively: median weekly MTX dose ≤ 15 mg (P = 0.011), subcutaneous administration (P = 0.005), no prior systemic treatment (< 0.001) and folic acid use (0.021). In logistic regression analysis for week 24; median weekly MTX dose ≤ 15 mg (P = 0.001), baseline PASI ≥ 10 (P < 0.001), no prior systemic treatment (P < 0.004), folic acid use (P = 0.001) and absence of comorbidities (P = 0.009) were determined as independent factors affecting the achievement of PASI 90. Adverse effects were observed in 38.8% of the patients, with nausea/vomiting (23.9%) and transaminase elevation (13%) being the most common. The most common reasons for interruptions (15.3%) and discontinuations (27.1%) of the treatment were patient related individual factors. The use of MTX as the first systemic treatment agent, at doses ≤ 15 mg/week and concurrent folic acid application are positive predictive factors for achieving the target PASI response both at weeks 12 and 24. In our study, which is one of the most comprehensive studies on MTX treatment in psoriasis, we observed that MTX is an effective and safe treatment option.

Evaluation of the Factors Influencing Mortality in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Multicenter Study of 166 Patients.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening acute mucocutaneous disorders usually triggered by drugs. In this study, we aimed to evaluate the factors affecting mortality in patients with SJS-TEN. METHODS: Our study is a retrospective cohort study, analyzing data collected from a total of 12 tertiary care centers between April 2012 and April 2022. RESULTS: The study included 59 males and 107 females, a total of 166 patients, with an average age of 50.91 ± 21.25 years. Disease classification was TEN in 50% of cases, SJS in 33.1%, and SJS-TEN overlap in 16.9%. The average SCORTEN within the first 24 h was 2.44 ± 1.42. Supportive care was provided to 99.4% of patients. The most commonly used systemic immunomodulatory treatments were systemic steroids (84.3%), IVIG (intravenous immunoglobulin) (49.3%), and cyclosporine (38.6%). Plasmapheresis was administered to five patients. While 66.3% of patients were discharged, 24.1% resulted in exitus. Our comparative analysis of survivors and deceased patients found no effect of systemic steroids, IVIG, and cyclosporine treatments on mortality. Univariate analysis revealed that the SCORTEN scores on days 1 and 3 as well as the rates of detachment at the onset and during follow-up were significantly higher in deceased patients compared to survivors. The rates of fever, positive blood cultures, and systemic antibiotic use were higher in deceased patients compared to survivors. The presence of comorbidities, diabetes, and malignancy were significantly more common in deceased patients. Multivariate regression analysis indicated that over SCORTEN 2, the mortality risk exponentially rose with each SCORTEN increment, culminating in an 84-fold increase in mortality at SCORTEN 5-6 (odds ratio [95% confidence interval]: 13.902-507.537, p < 0.001) compared to SCORTEN 0-1. Additionally, the utilization of plasmapheresis was associated with a 22-fold increase in mortality (odds ratio [95% confidence interval]: 1.96-247.2, p = 0.012). CONCLUSION: Our study found that a high SCORTEN score within the first 24 h and the use of plasmapheresis were related to increased mortality, while systemic steroids, IVIG, and cyclosporine treatments had no impact on mortality. We believe that data gathered from one of the most comprehensive studies which we conducted on SJS-TEN will enrich the literature, although additional research is warranted.

The reliability and quality of YouTube videos about isotretinoin treatment and suicide.

BACKGROUND: Seeking health information online has drastically increased. Isotretinoin is one of the agents used to treat acne. OBJECTIVES: In this study, we aimed to investigate the reliability and quality of YouTube videos related to acne treatment. There is a misconception that use of isotretinoin increases risk of suicide. METHODS: We used the terms 'isotretinoin suicide' and 'acne treatment suicide' to search YouTube videos. Videos that were not in English, were irrelevant, or were devoid of audio were not included. The information in the videos was primarily categorized as 'reliable' or 'unreliable' based on its scientific validation. DISCERN and the Global Quality Score were used to evaluate the videos' overall quality. RESULTS: In total, 200 videos were examined and 112 videos were included in the study. Of these, 39 videos (34.8%) were found to be reliable, and 73 videos (65.2%) were found to be unreliable. The DISCERN values of videos uploaded by physicians or professional organizations, and health information websites were found to be significantly higher. There were statistically significant negative correlations between DISCERN score and both video length and the length of time the video was on YouTube, while a positive correlation was observed between DISCERN score and the number of subscribers. CONCLUSIONS: Although videos created by dermatologists have become widespread in recent years, they are still insufficient. Patient experience videos mostly contain information that does not reflect reality, and they emphasize that isotretinoin increases the risk of suicide without evidence. As the number of dermatologists posting videos on YouTube increases, the chances of people accessing correct information will increase.

Investigation of the PD-1/PD-L1 Expression in the Lesional Skins of Patients With Psoriasis.

INTRODUCTION: Psoriasis is an immune-mediated, chronic and inflammatory disease whose pathogenesis is affected by the interactions of several immune cells and cytokines. PD-1 is an inhibitor receptor that is expressed to a large extent in T lymphocytes and responsible for regulating autoimmunity and self-tolerance. OBJECTIVES: In this study, we aimed to investigate the expression of PD-1/PD-L molecules in the lesioned skins of psoriasis patients. METHODS: The study included 30 psoriasis patients, and 15 healthy volunteers as the control group. Anti PD-1 and PD-L1 antibodies were applied to the skin biopsy samples that were collected from the patient and control groups. Cytoplasmic and membranous staining of PD-1 and PD-L1 were considered positive. The number of stained immune cells that was examined for each case. RESULTS: The percentage of the tissues with high PD-1 (+) and PDL-1 (+) immune cell counts were significantly higher in the psoriasis patients compared to healthy controls (P values = 0.004 and 0.002, respectively). A negative and statistically significant correlation was detected between PDL-1(+) immune cell numbers and PASI scores (P = 0.033, r=-0.57). CONCLUSIONS: In the lesioned skin samples of psoriasis patients, the PD-1 and PD-L1 expressions were significantly higher in immune cells than that in the skin samples of the healthy controls. This study was the first investigation of the expression of PD-1/PD-L molecules in the immune cells in found the lesioned skins of psoriasis patients.

Skin manifestations following anti-COVID-19 vaccination: A multicentricstudy from Turkey.

PURPOSE: After the emergence of the pandemic caused by the COVID-19 virus, vaccination with various vaccines has started to be implemented across the world. To identify dermatological reactions developing after the COVID-19 vaccines administered in Turkey and determine their clinical features and risk factors that may play a role in their development. MATERIALS AND METHODS: The study included patients aged ≥18 years, who presented to 13 different dermatology clinics in Turkey between July 2021 and September 2021 after developing dermatological reactions following the administration of the COVID-19 vaccine. After providing written consent, the patients were asked to complete a standard survey including questions related to age, gender, occupation, comorbidities, the regular medication used, the onset of cutaneous reactions after vaccination, and localization of reactions. Dermatological reactions were categorized according to whether they developed after the first or second dose of the vaccine or whether they occurred after the inactivated or messenger RNA (mRNA) vaccine. The relationship between dermatological reactions and some variables such as gender and comorbidities was also evaluated. RESULTS: A total of 269 patients [116 women (43.1%), 153 men (56.9%)] were included in the study. It was observed that the dermatological diseases and reactions that most frequently developed after vaccination were urticaria (25.7%), herpes zoster (24.9%), maculopapular eruption (12.3%), and pityriasis rosea (4.5%). The rate of dermatological reactions was 60.6% after the administration of the mRNA vaccine and 39.4% after that of the inactivated vaccine. There was a statistically significantly higher number of reactions among the patients that received the mRNA vaccine (p = 0.001). CONCLUSION: The most common reactions in our sample were urticaria, herpes zoster, and maculopapular eruption. Physicians should know the dermatological side effects of COVID-19 vaccines and their clinical features.

The effect of COVID-19 on development of hair and nail disorders: a Turkish multicenter, controlled study.

BACKGROUND: A broad spectrum of skin diseases, including hair and nails, can be directly or indirectly triggered by COVID-19. It is aimed to examine the type and frequency of hair and nail disorders after COVID-19 infection. METHODS: This is a multicenter study conducted on consecutive 2171 post-COVID-19 patients. Patients who developed hair and nail disorders and did not develop hair and nail disorders were recruited as subject and control groups. The type and frequency of hair and nail disorders were examined. RESULTS: The rate of the previous admission in hospital due to COVID-19 was statistically significantly more common in patients who developed hair loss after getting infected with COVID-19 (P < 0.001). Telogen effluvium (85%) was the most common hair loss type followed by worsening of androgenetic alopecia (7%) after COVID-19 infection. The mean stress scores during and after getting infected with COVID-19 were 6.88 ± 2.77 and 3.64 ± 3.04, respectively, in the hair loss group and were 5.77 ± 3.18 and 2.81 ± 2.84, respectively, in the control group (P < 0.001, P < 0.001). The frequency of recurrent COVID-19 was statistically significantly higher in men with severe androgenetic alopecia (Grades 4-7 HNS) (P = 0.012; Odds ratio: 2.931 [1.222-7.027]). The most common nail disorders were leukonychia, onycholysis, Beau's lines, onychomadesis, and onychoschisis, respectively. The symptoms of COVID-19 were statistically significantly more common in patients having nail disorders after getting infected with COVID-19 when compared to the control group (P < 0.05). CONCLUSION: The development of both nail and hair disorders after COVID-19 seems to be related to a history of severe COVID-19.

Patient Use of Complementary and Alternative Medicine for Psoriasis Vulgaris and Factors Believed to Trigger the Disease: a Multicenter Cross-Sectional Study With 1621 Patients.

Introduction: Due to the chronic recurrent nature of psoriasis vulgaris (PV) and lack of definitive treatment for the disease, patients often resort to alternative treatments. Physicians seem to have low awareness of this issue. Objectives: To elicit the perceptions of 1,621 PV patients on complementary and alternative medicine (CAM) and examine factors reported to worsen PV. Methods: The patients sociodemographic characteristics, Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), disease duration, and severity were recorded, and the patients CAM use was questioned in detail. The patients were also asked about factors that worsened PV and their experiences with a gluten-free diet. Results: Of the patients, 56.51% had used CAM. The mean age, illness duration, PASI scores and DLQI of those using CAM were significantly higher. CAM use was significantly higher in those with facial, genital involvement, and arthralgia/arthritis. The patients mostly referred to CAM when PV became severe (46.4%). Of the CAM users, 45.52% used herbal topicals. The physicians of 67.03% did not inquire whether they used CAM. Of the participants, 37.73% considered that stress worsened their disease. Gluten-free diet did not affect PV symptoms in 52.22%. Conclusions: Patients CAM use is often overlooked by dermatologists. Our results showed that more than half the patients used CAM and did not share this information with their physicians. Therefore, the awareness of physicians should be increased and patients should be asked about the use of CAM and directed to the appropriate medical treatment options by physicians.

Has the COVID-19 pandemic changed attitudes and behaviors concerning cosmetic care and procedures among patients presenting to the dermatology outpatient clinic? A multicenter study with 1437 participants.

BACKGROUND: The rate of cosmetic procedures and use of skincare products is considered to be affected during the pandemic period; however, this has not been investigated yet. OBJECTIVE: To determine whether the ongoing pandemic has changed people's habits related to skincare products and cosmetic procedures. METHODS: We conducted a multicenter survey study covering both private and public hospitals. Sociodemographic characteristics and clinical diagnoses of the patients were noted by dermatologists. A survey was used to determine the type and application areas of skincare products and cosmetic procedures before and during the pandemic, whether the patients were concerned about being infected, and any change in the make-up habits of female patients. RESULTS: Of the 1437 patients, 86.7% presented to the hospital due to dermatological complaints and 13.3% for cosmetic procedures. The rate of those that did not use skincare products was 0.05% before and 0.06% during the pandemic. Of the participants, 43.2% had undergone cosmetic procedures before and 38.1% during the pandemic. For both periods, the most frequent cosmetic procedure applied was laser epilation, followed by skincare treatment and chemical peeling. While undergoing these procedures, 34.9% of the patients were concerned about contracting coronavirus. CONCLUSION: There was no significant difference in the use of skincare products and cosmetic procedures before and during the pandemic. The majority of the patients continued to undergo these procedures despite their fear of being infected. This shows that during the pandemic period, patients are concerned with their appearance and continue to undergo cosmetic procedures and pay attention to their skincare.

Acne in pregnancy: A prospective multicenter, cross-sectional study of 295 patients in Turkey.

BACKGROUND: There are only a few studies on acne in pregnancy. This study was aimed to investigate the demographic, clinical, and familial characteristics of acne in pregnancy, triggering factors including endocrine diseases, and association of these findings with acne in different trimesters of pregnancy. METHODS: Pregnant women aged 18 years and older with acne at any stage of pregnancy were consecutively interviewed at the participating centers during the study period from 2016 to 2019. Acne severity was evaluated using the Comprehensive Acne Severity Scale. RESULTS: A total of 295 pregnant women with acne were included, with 167 (56.6%) patients showing mild, 87 (29.5%) moderate, six (12.2%) severe, and five (1.7%) very severe acne. Truncal acne was significantly higher in the third trimester than in the other stages (P < 0.001). Onset of acne before pregnancy, prepubertal, pubertal or adult onset, or acne history in previous pregnancies did not influence acne severity in pregnancy. Women with irregular menstruation before pregnancy, polycystic ovary syndrome, hirsutism, and higher body weight index tended to show severe acne in pregnancy. CONCLUSIONS: Severe acne during pregnancy is generally uncommon, while severity of facial acne, truncal acne, and hirsutism is higher in the third trimester than in other trimesters. Acne in pregnancy shares many characteristics with female adult acne. Substantial changes in different kinds of hormones play a more complex role in acne during pregnancy, but the pathogenesis remains to be determined.

Dynamic Thiol/Disulfide Balance in Patients with Seborrheic Dermatitis: A Case-Control Study.

BACKGROUND: Seborrheic dermatitis is a chronic, inflammatory skin disease, in which many endogenous and exogenous factors play a role. Recent studies have shown that oxidative stress increases in these patients. The role of the dynamic thiol/disulfide homeostasis, an important component of the oxidative stress, in the pathogenesis of seborrheic dermatitis has not yet been investigated. OBJECTIVES: The objective was to investigate the relationship between the dynamic thiol/disulfide balance in the plasma of seborrheic dermatitis patients and disease severity. METHODS: In this case-control study, 70 seborrheic dermatitis patients and 61 age- and sex-matched healthy controls were included. Thiol/disulfide homeostasis was calculated from venous blood samples, and tests were performed by automated spectrophotometric method. The thiol/disulfide balance between the patient and control groups was compared. In addition, disease severity and other demographic characteristics and thiol/disulfide balance parameters were compared. RESULTS: Native and total thiols were significantly higher in the patient group than that in the control group (P < 0.001). Disulfide levels were nonsignificantly lower in the patient group than controls (P = 0.821). Patients' age and age at the onset of disease were found to have a negative correlation with native and total thiol levels. CONCLUSION: Higher levels of thiols in the serum may be responsible for the increased proliferation of seborrheic dermatitis lesions. To the best of the authors' knowledge, this is the first report on the correlation between thiol/disulfide homeostasis in patients with seborrheic dermatitis.

Internalized Stigma in Pediatric Psoriasis: A Comparative Multicenter Study.

BACKGROUND: Internalized stigma, adoption of negative attitudes and stereotypes of the society regarding persons' illness, has not been studied previously in pediatric psoriasis patients. OBJECTIVE: We aimed to investigate the internalized stigma in pediatric psoriasis patients and to determine differences according to factors affecting internalized stigma compared to adult psoriasis patients. METHODS: This multicenter, cross-sectional, comparative study included 125 pediatric (55 female, 70 male; mean age±standard deviation [SD], 14.59±2.87 years) and 1,235 adult psoriasis patients (577 female, 658 male; mean age±SD, 43.3±13.7 years). Psoriasis Internalized Stigma Scale (PISS), Dermatology Life Quality Index (DLQI), Perceived Health Status (PHS), and the General Health Questionnaire (GHQ)-12 were the scales used in the study. RESULTS: The mean PISS was 58.48±14.9 in pediatric group. When PISS subscales of groups were compared, the pediatric group had significantly higher stigma resistance (p=0.01) whereas adult group had higher scores of alienation (p=0.01) and stereotype endorsement (p=0.04). There was a strong correlation between mean values of PISS and DLQI (r=0.423, p=0.001). High internalized stigma scores had no relation to either the severity or localization of disease in pediatric group. However, poor PHS (p=0.007) and low-income levels (p=0.03) in both groups, and body mass index (r=0.181, p=0.04) in the pediatric group were related to high PISS scores. CONCLUSION: Internalized stigma in pediatric patients is as high as adults and is related to poor quality of life, general health, and psychological illnesses. Unlike adults, internalized stigma was mainly determined by psoriasis per se, rather than disease severity or involvement of visible body parts, genitalia or folds.

Recurrent radiation recall dermatitis triggered by radiological procedures in a patient with breast cancer.

Radiation recall dermatitis is an acute inflammatory reaction that occurs on previously irradiated skin by usage of chemotherapeutic agents and other triggering drugs. The recall reaction is usually associated with drugs but may also occur following ultraviolet radiation. We report a patient with radiation recall dermatitis, triggered after imaging procedures that involved radiation.

Intravenous immunoglobulin treatment: Where do dermatologists stand?

Intravenous immunoglobulins (IVIG) are therapeutic products, comprising polyclonal IgGs, which are obtained from human plasma pool of healthy blood donors. Despite the lack of Food and Drug Administration (FDA) approval, the experience of using IVIG in various dermatological diseases increases day by day and exciting results are reported. However, experience with the use of IVIG in dermatological indications are mostly case reports whereas randomized, controlled, double-blind, multicentric studies have not been performed. Dermatological diseases treated with IVIG are autoimmune bullous skin diseases, Stevens-Johnson syndrome and toxic epidermal necrolysis, connective tissue diseases, pyoderma gangrenosum, severe atopic dermatitis, chronic urticaria, Kawasaki disease, pretibial myxoedema, scleredema, and graft-versus-host disease.

Dynamic thiol/disulfide homeostasis in patients with lichen planus.

OBJECTIVE: Lichen planus (LP) is an autoimmune inflammatory disease of the mucocutaneous tissue, whose exact pathological course remains unclear. Abnormal thiol/disulfide homeostasis has been postulated to be responsible for a number of diseases predominated by chronic inflammation. To be able to contribute complicated and unclear pathogenesis of LP, we aimed to investigate dynamic thiol/disulfide homeostasis in patients with LP, using an original automated method developed by Erel and Neselioglu in this study. METHODS: The study group consisted of 81 unrelated patients with LP and 80 unrelated healthy controls with no LP lesions in their personal history or on clinical examination. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. RESULTS: Native thiol and total thiol levels were found as significantly higher in patients with LP than the control group (P = 0.026 and 0.035, respectively). There was no significant difference between the disulfide levels of the patients with LP and the control group. CONCLUSIONS: We provide evidence that that thiol/disulphide homeostasis impaired in favor of thiol levels in LP patients compared to the control group based on the data of our study. To the best of our knowledge, the present study is the first examination on the correlation between thiol and disulfide homeostasis in patients with LP.

A case of severe erythema nodosum induced by methimazole.

Erythema nodosum (EN), is the most common variant of septal panniculitis and is possibly a delayed hypersensitivity reaction triggered by a wide range of antigenic stimuli. Hypersensitivity reactions due to medications have been recognized as a cause of 3-10% of EN cases. Case reports of EN associated with the anti-thyroid drugs are quite rarely reported in the literature even if there is a common use of anti-thyroid drugs. We report an EN case due to methimazole. The complaints of patients arose immediately fifteen days after the beginning of methimazole treatment. To the best of our knowledge, this case report is the first of an erythema nodosum induced by methimazole.

Dynamic thiol/disulfide homeostasis and effects of smoking on homeostasis parameters in patients with psoriasis.

PURPOSE: Recently, increased reactive oxygen species (ROS), reduced antioxidant capacity, and oxidative stress have been suggested in the pathogenesis of psoriasis. The aim of this study to evaluate the thiol/disulfide homeostasis in patients with psoriasis. MATERIALS AND METHODS: Ninety patients with psoriasis who did not receive any systemic treatment in the last six months were included in the study. Seventy-six age and gender-matched healthy volunteers served as control group. Thiol/disulfide homeostasis was measured in venous blood samples obtained from patient and control groups. RESULTS: Native thiol and total thiol levels were significantly higher in patients than in control group. When thiol/disulfide hemostasis parameters and clinical and demographic characteristics were compared, a negative correlation was detected between native thiol and total thiol with age. The levels of total thiols had also negative correlation with PASI and duration of the disease. When we divided the patients into smokers and non-smokers, native thiol and total thiol levels were significantly higher in smokers than in controls, whereas native thiol and total thiol levels were comparable in non-smoker patients and controls. CONCLUSIONS: Thiol/disulfide balance shifted towards thiol in psoriasis patients and this may be responsible for increased keratinocyte proliferation in the pathogenesis of psoriasis.

Internalized stigma in psoriasis: A multicenter study.

Internalized stigma is the adoption of negative attitudes and stereotypes of the society regarding a person's illness. It causes decreased self-esteem and life-satisfaction, increased depression and suicidality, and difficulty in coping with the illness. The primary aim of this study was to investigate the internalized stigma state of psoriatic patients and to identify the factors influencing internalized stigma. The secondary aim was to identify the correlation of internalized stigma with quality of life and perceived health status. This multicentre, cross-sectional study comprised 1485 patients. There was a significant positive correlation between mean values of Psoriasis Internalized Stigma Scale (PISS) and Psoriasis Area and Severity Index, Body Surface Area, Dermatological Life Quality Index and General Health Questionnaire-12 (P < 0.001 in all). Lower percieved health score (P = 0.001), early onset psoriasis (P = 0.016), family history of psoriasis (P = 0.0034), being illiterate (P < 0.001) and lower income level (P < 0.001) were determinants of high PISS scores. Mean PISS values were higher in erythrodermic and generalized pustular psoriasis. Involvement of scalp, face, hand, genitalia and finger nails as well as arthropathic and inverse psoriasis were also related to significantly higher PISS scores (P = 0.001). Our findings imply that psoriatic patients experience high levels of internalized stigma which are associated with psoriasis severity, involvement of visible body parts, genital area, folds or joints, poorer quality of life, negative perceptions of general health and psychological illnesses. Therefore, internalized stigma may be one of the major factors responsible from psychosocial burden of the disease.