Vitamin D Receptor Expression in Vitiligo

Background:

Vitiligo is a progressive depigmenting disorder characterized by loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Vitamin D has stimulatory effects on melanocytes and acts through its nuclear Vitamin D receptor (VDR) on target cells.

Aims and Objectives:

The purpose of this study was to declare the role of Vitamin D in the pathogenesis of vitiligo.

Materials and Methods:

This case-control study included 30 vitiligo patients and 30 age, gender-matched healthy controls. Blood samples were withdrawn from the study subjects, and the serum 25(OH) D level was determined by an enzyme-linked immunosorbent assay technique. Serum 25(OH) D levels were divided into: Normal or sufficient (≥30 ng/ml), insufficient (< 30-> 20ng/ml), and deficient (≤20 ng/ml) levels. Skin biopsies were obtained from the depigmented lesions and clinically normal skin of vitiligo patients and from the controls, and VDR gene expression was determined using real-time polymerase chain reaction.

Results:

Only 10 patients with vitiligo (33.3%) had sufficient serum 25(OH) D levels (≥30 ng/ml), 12 patients (40%) had insufficient levels, and 8 patients (26.7%) had deficient levels. On the other hand, most of the controls (96.7%) had sufficient levels. The mean serum 25(OH) D level in patients was significantly decreased compared to controls (P < 0.001). The VDR-mRNA expression was also significantly decreased in lesional and nonlesional skin of patients compared to controls (P < 0.001, P < 0.001, respectively).

Conclusion:

Vitamin D deficiency influences the extent of vitiligo and could contribute to the pathogenesis of vitiligo through its immunomodulatory role and its role in melanogenesis.     

热休克蛋白70在过敏性紫癜中的表达及其临床意义

目的探讨热休克蛋白70表达在过敏性紫癜发病机制中的作用及其与临床的关联。方法采用逆转录聚合酶链反应(RT-PCR)方法检测了66例过敏性紫癜患者和30例正常对照组外周血单一核细胞中热休克蛋白70表达,采用免疫速率散射比浊法检测患者血沉、C反应蛋白和血清IgA。结果过敏性紫癜患者治疗前热休克蛋白70的表达明显高于治疗后和对照组,其在肾型表达明显高于其他类型,治疗后其表达与对照组无明显差异,治疗前热休克蛋白70表达与血沉、C反应蛋白、血清IgA明显正相关,其表达和上呼吸道感染、腹痛、关节痛、蛋白尿、血尿明显相关。结论热休克蛋白70表达在过敏性紫癜活动期明显升高,恢复期则明显下降,且与临床表现密切相关,提示其在该病发生发展中具有一定的作用,可作为疾病活动的指标之一。     

Role of Histamine as a Toxic Mediator in the Pathogenesis of Vitiligo

Background:

The precise cause of vitiligo is still unclear. Multiple theories have been proposed, including genetic, autoimmune, neural, and biochemical mechanisms. An immune mediated pathogenesis is indeed the most popular theory. The autoimmune hypothesis considers the role of toxic mediator that might cause an injury to the melanocytes with the release of an antigenic substance and subsequent autoimmunization.

Aims:

This study performed over a period of 10 years (February 1975 to June 1985) aims at exploring the role that histamine might play in the pathogenesis of vitiligo.

Materials and Methods:

Fifty patients with a particular type of vitiligo characterized by faint white patches occurring with significant pruritus and a history of atopy were selected and blood histamine levels were determined by Bio-Assay method.

Results:

Blood histamine values of patients with vitiligo of short duration and with pruritus were significantly increased in comparison with values of matched controls.

Conclusion:

Histamine appears to play a significant role in the pathogenesis of a particular type of vitiligo characterized by faint hypopigmented patches with significant itching.     

Serum Homocysteine and Total Antioxidant Status in Vitiligo: A Case Control Study in Indian Population

Background:Oxidative stress is considered as an initial pathogenic event in melanocyte destruction. These free radicals are scavenged by antioxidants, whose sum of activity in serum is measured by total antioxidant status (TAS). In addition, homocysteine (Hcy) may mediate melanocyte destruction via increased oxidative damage. However, previous studies investigating these parameters in vitiligo provide equivocal results.Aims:To study and compare serum Hcy and TAS levels in vitiligo patients with controls and also to correlate these parameters with the various disease characteristics. The present study further looked into any correlation between serum Hcy and TAS in vitiligo.Results:TAS levels were lower in vitiligo patients than controls (1.79 ± 0.51 vs. 2.16 ± 0.63 mmol/L; P < 0.001) and had a negative correlation with disease activity (r = −0.410, P < 0.001). However, serum Hcy levels were comparable between vitiligo patients (18.68 ± 9.90 μmol/L) and controls (20.21 ± 13.39 μmol/L) (P = 0.406). No significant correlation was found between serum Hcy and serum TAS levels.Conclusions:Serum TAS may be further investigated to establish its role as biomarker for vitiligo since its levels also correlate with disease activity. However, serum Hcy may not be a reliable marker in Indian population probably because of differences in dietary habits.     

Quality of Life and Psychological Morbidity in Vitiligo Patients: A Study in a Teaching Hospital from North-East India

Background:

Vitiligo is an acquired discoloration of skin and mucous membrane of great cosmetic importance affecting 1-4% of the world''s population. It causes disfiguration in all races, more so in dark-skinned people because of strong contrast. Men, women, and children with vitiligo face severe psychological and social disadvantage.

Aim:

To assess the impact of the disease on the quality of life of patients suffering from vitiligo, also to ascertain any psychological morbidity like depression associated with the disease and to compare the results with that of healthy control group.

Materials and Methods:

Dermatology Life Quality Index (DLQI) and Hamilton Depression Rating Scale (HAMD) are administered to 100 vitiligo patients presenting to the Dermatology OPD and 50 age- and sex-matched healthy controls. Results were analyzed and compared with that of control group. Findings are also correlated in relation to demographic and clinical profile of the disease. Statistical analysis is made to see the significance.

Results:

Vitiligo-affected patients had significantly elevated total DLQI scores (P < 0.001) compared to healthy controls. There is increase in parameters like itch, embarrassment, social and leisure activities in the patient cohort than the control group. Patients of vitiligo are also found to be more depressed (P < 0.001) than the controls.

Conclusion:

Quality of life (QOL) in patients affected with vitiligo declined more severely, and also there is increase in incidence of depression than in the control group. These changes are critical for the psychosocial life of the affected people.     

Serum Prolactin Levels in Psoriasis and its Association with Disease Activity: A Case-Control Study

Background:Psoriasis is a T-cell-mediated autoimmune chronic skin disorder in which an environmental factor, perhaps a viral antigen, induces T cells to produce cytokines. These cytokines stimulate keratinocyte proliferation and production of antigenic adhesion molecules in the dermal blood vessels. Several mediators and hormones have been implicated in keratinocyte hyperproliferation and among these hormones, prolactin (PRL) has been found to have an effect on epithelial cells, lymphocytes and keratinocytes, thus an effect on the etiopathogenesis of psoriasis.Aim:The present study was designed to compare serum PRL levels in psoriatic patients with a control group.Results:Serum PRL levels were significantly increased in patients as compared to the control group (P value: 0.002). There was a positive correlation between pretreatment serum PRL levels and PASI score (r value: 0.379; P value: 0.003). An insignificant association was found between the pretreatment PRL level and serum PRL level after treatment (P value: 0.22). Also, a negative correlation between the duration of psoriasis and serum PRL was seen (r value: -0.008; P value: 0.954).Conclusion:PRL may have a role to play in the etiopathogenesis of psoriasis. However, further studies with large sample size should be carried out so as to validate this hypothesis.     

A Comprehensive Study of Tumor Necrosis Factor-Alpha Genetic Polymorphisms,its Expression in Skin and Relation to Histopathological Features in Psoriasis

Background:

Tumor necrosis factor-alpha (TNFα) is an important inflammatory mediator in psoriasis and several genetic polymorphisms of this cytokine have been reported. Majority of studies have focused on the increased G– A polymorphism at the –308 position in psoriasis. There has been no comprehensive study evaluating the genetic polymorphisms, TNFα expression in the skin and histopathology. We are undertaking this study to outline TNFα genetic polymorphisms, its skin expression and histopathological correlation to help determine its role at the genetic and protein level.

Materials and Methods

112 patients of psoriasis and 243 healthy controls were included in this prospective study. 5 ml of peripheral blood was collected to study the TNFα genetic polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. Histopathological analysis of biopsies from the 112 patients were done using visual analogue scale and correlated with the findings. 61 of these cases were analyzed for TNFα expression by immunohistochemistry. The results of study were statistically analyzed using SPSS 13.0 statistical package program.

Results:

A strong association of TNFα –308 G/A polymorphism in psoriasis cases was detected. The A allele of the TNFα –308 G/A polymorphism occurs rarely in the Indian population, however there is an over representation of this allele in psoriatic patients. There was no association seen between TNFα genotype and histopathological severity of psoriasis.

Conclusion:

The study emphasized the central role of TNFα in the pathogenesis of psoriasis. TNFα genotyping may be helpful in identifying subjects in whom anti-TNFα therapeutic strategies may be tried.     

No Evidence of Human Papilloma Virus Infection in Basal Cell Carcinoma

Background:

Basal cell carcinoma (BCC) is the most common skin cancer among whites, and several risk factors have been discussed in itsdevelopment and progress. Detection of human papilloma virus (HPV) deoxyribonucleic acid (DNA) BCCs in some studies suggests that the virus may play a role in the pathogenesis of this disease. Several molecular studies showed conflicting reports.

Aims:

The purpose of this study was to investigate the association between HPV and BCC using polymerase chain reaction (PCR).

Materials and Methods:

HPV DNA detection was done for 42 paraffin-embedded tissue specimens of BCC and 42 normal skin samples around the lesions by PCR using GP5+/GP6+ primers.

Results:

HPV DNA was not found in any of the 42 samples of BCC, and only one normal skin sample around the lesions was positive for HPV DNA by PCR.

Conclusion:

In this study, no statistically significant difference was seen between the presence of HPV DNA in BCC and normal skin around the lesion, and HPV is not likely to have an important role in pathogenesis of BCC.     

Long-Term Follow-up and Donor Site Changes Evaluation in Suction Blister Epidermal Grafting Done for Stable Vitiligo: A Retrospective Study

Background:

Suction blister epidermal grafting (SBEG) is one of the most commonly performed types of vitiligo surgery for stable vitiligo. The advantages of SBEG include cost-effectiveness and a relatively easier learning curve for the surgeon.

Aims:

To evaluate the outcome in terms of both recipient and donor site changes, on long-term follow-up of the patients who underwent SBEG in our center.

Methods:

Thirty patients, 21 females and 9 males ages ranging from 9 to 55 years, all having either stable vitiligo not responding to medical line of treatment, were included in the study done which involved a variable follow-up period ranging from 2 to 62 months (mean 23.6, standard deviation 17.79). SBEG was done as day care procedure. The patients were reviewed after 1-week and thereafter followed-up in the subsequent months and years. The results of the procedures were graded as poor (0–24%), fair (24–64%), good (64–94) and excellent (95–100%) depending on the patient satisfaction. Donor site changes were also analyzed.

Results:

The face and lips showed an excellent result and color match and persistent pigment retention. The larger areas, especially the lesions on the limbs showed comparatively less response. Of the total, 6.7% showed poor, 13.3% fair, 30% good and 50% excellent response to treatment. Patient satisfaction wise, 53.3% of the patients were very happy, 26.7% were happy, 10% satisfied and 10% unhappy. Significant positive correlation between patient satisfaction and physician observation was seen (Spearman''s rho 0.866).

Conclusions:

In spite of recent advances in surgical modalities like cellular grafting, SBEG continues to be a good, cost-effective, surgical method of treating vitiligo especially on the face and lip. The donor site also tends to show good healing tendency with minimal scarring and postinflammatory pigmentation.     

Finger Nail Pitting in Psoriasis and its Relation with Different Variables

Incidence of pitting, vary considerably in different types of psoriasis. In clinical practice, toe nail examination is inconvenient. There are inadequate studies which show relation of nail pitting with duration and severity of the disease. The objective was to examine the incidence of finger nail pitting in all types of cutaneous psoriasis and its relation with different variables. This is a clinico-epidemiological study. A careful clinical examination of finger nails was done in day time. Severity of disease was calculated by psoriasis area severity index (PASI). Statistical analysis was done using Microcomputer statistics software (MSTAT). In study group, 621 patients and in control group 350 people were taken. Finger nail pitting was present in 37% (total number was < 20 in 17%; 20-60 in 8% and > 60 in 12%) in study group. In control group, it was present in 10% (in all cases total number was < 20). In < 1 year duration group, pitting was present in 32% of cases, while in > 1 year duration group it was 40.5%. In mild psoriasis, pitting was present in 34.2%, while in severe cases it was 47.6%. Finger nail pitting is an important nail finding in psoriasis and its incidence increases with duration and severity of disease.     

Human Papillomavirus Deoxyribonucleic Acid may not be Detected in Non-genital Benign Papillomatous Skin Lesions by Polymerase Chain Reaction

Background:

Papillomatosis is a known histopathologic pattern usually seen in human papillomavirus (HPV) infection and verruca vulgaris is the typical example. This pattern is also detected in some other benign cutaneous lesions such as nevus sebaceous (NS), seborrheic keratosis (SK), trichilemmoma (TL) and inverted follicular keratosis (IFK). The association between papillomatous lesions and HPV infection is questionable.

Objective:

The objective of this study was to investigate the presence of HPV deoxyribonucleic acid (DNA) in non-genital benign papillomatous skin lesions (NS, SK, TL and IFK) by polymerase chain reaction (PCR).

Materials and Methods:

A total of 100 specimens of non-genital NS, SK, TL and IFK were retrieved from archives of Dermatopathology Department of Razi Hospital, between 2003 and 2010. The conventional PCR using consensus GP5+/GP6+ primer and hydroxymethylbilane synthase gene as inner control was performed.

Results:

PCR for HPV DNA revealed no positive results in any of 28 seborrheic keratosis (SK), 28 nevus sebaceous (NS), 28 inverted follicular keratosis (IFK) and 13 trichilemmoma (TL) studied specimens.

Conclusion:

Papillomatosis is usually a characteristic pattern of HPV infection. However, we found no association between HPV infection and non-genital benign papillomatous lesions.     

Poor neurological sequelae of herpes simplex virus encephalitis in an infant despite adequate antiviral and adjunct corticosteroid therapy

A 2-month-old infant presented to our emergency department with fever, altered consciousness, and focal seizures of acute onset. He had vesicular skin lesions over the right preauricular region. CT brain showed a large hypodense lesion involving the left temporo-parietal region, left basal ganglia and left thalamus. MRI brain revealed bilateral multifocal corticomedullary lesions suggestive of encephalitis. CSF-PCR was positive for herpes simplex virus (HSV) type I. He was treated with standard dose intravenous acyclovir for 15 days along with a trial of pulse methylprednisolone, but was readmitted within a week with features of an early relapse. The infant survived but developed significant neurological sequelae. Although treatment of HSV is available, the neurological outcome is guarded even with adequate antiviral therapy. Adjunct corticosteroid therapy did not appear to attenuate the neurological sequelae.     

Prevalence of Metabolic Syndrome In South Indian Patients with Psoriasis Vulgaris and the Relation Between Disease Severity and Metabolic Syndrome: A Hospital-Based Case-Control Study

Background:

Psoriasis is a chronic inflammatory disease of the skin and joints with an increased cardiovascular risk. Previous studies have shown a higher prevalence of metabolic syndrome (MS) in psoriatic patients.

Objective:

To investigate the prevalence of MS in patients with psoriasis and healthy controls, and to determine the relation between disease severity and the presence of MS.

Materials and Methods:

We performed a hospital-based case-control study on 118 adult patients with psoriasis vulgaris and 120 controls matched for age, sex and body mass index. MS was diagnosed by the presence of three or more of the South Asian Modified National Cholesterol Education Program''s Adult Panel III criteria.

Results:

MS was significantly more common in psoriatic patients than in controls (44.1% vs. 30%, P value = 0.025). Psoriatic patients also had a higher prevalence of triglyceridemia (33.9% vs. 20.8%, P value = 0.011), abdominal obesity (34.7% vs. 32.5%, P value = 0.035) and elevated blood sugar. There was no difference in the high density lipoprotein (HDL) levels and presence of hypertension among patients with psoriasis and normal controls. There was no correlation between the severity and duration of psoriasis with MS.

Conclusion:

MS is frequent in patients with psoriasis. We have found no relationship between disease severity and presence of MS. Hence, we suggest that all patients must be evaluated for the MS, irrespective of the disease severity.     

Assessing the autoantibody levels in relation to disease severity and therapy response in pemphigus patients

Background:

In pemphigus, autoantibodies are directed against adhesion molecules, which make the junctions between keratinocytes, and thus determining their level can reflect the disease activity.

Aim:

The purpose of this study is to determine the clinical significance of the autoantibody levels in pemphigus management.

Materials and Methods:

The clinical features of 47 pemphigus vulgaris patients were assessed and patients′ sera were investigated by indirect immunofluorescence using monkey esophagus as a substrate for autoantibody levels.

Results:

We found a significant correlation between antibody titers and mucosal severity scores. Initial antibody titers of the patients with at least one mucosal lesion at the end of the first month of the therapy were found significantly higher than the patients who had no mucosal lesion. With the therapy, lesions resolved earlier than the antibody titers.

Conclusion:

In patients with pemphigus, especially in cases who were not treated before, sera antibody levels are a valuable tool in evaluating disease severity and choosing initial treatment. In patients who had been taking any systemic treatment, it is difficult to make a relationship between antibody levels and disease severity, because therapy improves disease earlier than the antibody titers. However, estimating antibody levels can be helpful for clinicians in disease management, in reducing or ceasing treatment dosage and anticipating recurrence.     

Comparison of Bacillary Index on Slit Skin Smear with Bacillary Index of Granuloma in Leprosy and its Relevance to Present Therapeutic Regimens

Background:

As the world moves toward elimination of leprosy, persistence of infective cases in endemic pockets remains a significant problem. The use of clinical criteria to decide the paucibacillary (PB) versus multibacillary (MB) regimens has greatly simplified therapy at the field setting. However, a small but significant risk of under-treatment of so-called “PB” cases which actually have significant bacillary load exists. This study was undertaken to assess this risk and compare two methods of assessment of bacillary load, namely bacillary index on slit skin smear (BIS) versus bacillary index of granuloma (BIG).

Aims:

To compare BIS with BIG on skin biopsy in consecutive untreated cases of leprosy.

Materials and Methods:

This prospective study was conducted over a period of 12 months, wherein new untreated patients with leprosy were consecutively recruited. After a thorough clinical examination, each patient underwent slit skin smear (SSS) where the BIS was calculated. The same patient also underwent a skin biopsy from a clinical lesion where, the BIG was calculated. SSS and skin biopsy for BIS and BIG respectively were repeated for all patients at the end of therapy for comparison. All patients received therapy according to World Health Organization-Multidrug Therapy Guidelines.

Results:

The BIG was positive in all cases where the BIS was positive. Significantly, BIG was positive in three cases of borderline tuberculoid leprosy with <5 lesions who received PB regimen, whereas the BIS was negative in all three cases.

Conclusion:

This study suggests that BIG may be a better indicator of the true bacillary load in leprosy as compared to BIS. Its role in management is significant, at least in tertiary care centers to prevent “under-treatment” of so called PB cases, which may actually warrant MB regimens.     

Efficacy and Tolerability of Topical Fixed Combination of Nadifloxacin 1% and Adapalene 0.1% in the Treatment of Mild to Moderate Acne Vulgaris in Indian Patients: A Multicenter,Open-Labelled,Prospective Study

Background:

A combination of topical retinoid and antibacterial therapy is often advocated for acne to enhance therapeutic efficacy.

Aims:

A preliminary study to evaluate the efficacy and tolerability of a topical fixed combination of nadifloxacin (1%) and adapalene (0.1%) in the treatment of mild to moderate acne in Indian patients.

Materials and Methods:

This was an open-labeled, phase 3 non-randomized, non-comparative study conducted at five centers (Ahmedabad, Nagpur, Thane, Bangalore, and Mumbai) across India. Of 119 enrolled patients with mild to moderate acne, 117 patients were evaluated at the end of the study for efficacy parameters. A fixed combination of nadifloxacin (1%) and adapalene (0.1%) topical gel was applied at the affected area once at night for a period of 8 weeks. Reduction in the total, inflammatory and non-inflammatory lesion counts from the baseline, investigator global assessment (IGA) and reduction in the severity of acne as per combined acne severity classification were the primary efficacy variables measured at 2 weeks, 4 weeks, and 8 weeks.

Results:

Overall, 98.3% patients showed a statistically significant progressive reduction in non-inflammatory lesion counts, inflammatory lesion counts, and total lesion counts over the study duration. By the end of 8 weeks, 75% of the patients had their global assessment scores approaching to normal healthy skin score. The adverse events were mild to moderate in severity.

Conclusion:

This preliminary study shows that a fixed combination of 1% nadifloxacin and 0.1% adapalene topical gel could be an effective and well-tolerated option for the treatment of mild to moderate acne vulgaris. However, further well-controlled, randomized and comparative evaluation of this combination is necessary.     

Papular Acantholytic Dyskeratosis Localized to the Perineal and Perianal Area in a Young Male

A case of Papular acantholytic dermatosis restricted to the perianal area is being reported in a 26 year old male without involvement of the genitalia, groin and upper thighs for the first time in English literature. The patient presented with long standing grayish white confluent papules with eroded areas in the perianal region which were asymptomatic for a long time before the area got macerated. He did not respond to many weeks of topical steroids but is now showing improvement with topical tacrolimus ointment 0.1% applied twice daily. This entity appears to be very uncommon and also underreported. It is also suggested that this entity be included in the long list of non venereal anogenital lesions as it may mimic perianal warts or molluscum contagiosum.     

A Six-Month Prospective Study to Find Out the Treatment Outcome,Prognosis and Offending Drugs in Toxic Epidermal Necrolysis from an Urban Institution in Kolkata

Toxic epidermal necrolysis is the life-threatening dermatological emergency, most often an adverse cutaneous drug reaction with high mortality. A 6-month prospective study was conducted in our institution to find out the offending drugs, to assess the prognosis on admission using SCORTEN: Severity of illness score and to find out the treatment outcome. Anticonvulsants, NSAIDs and sulphonamides are the common offending agents; but in our study, 2 were due to homeopathic medicines. Out of 20 patients, on the date of admission SCORTEN prognostic score was 2 in 11 patients, 3 in 8 patients and 4 in 1 patient. Eighteen patients were treated with dexamethasone intramuscular injection and 2 patients got intravenous immunoglobulin (IVIG). All patients survived without any mortality. Though improvement was slightly faster with IVIG, early administration of corticosteroids was also of encouraging efficacy and should be considered in developing countries due to low cost. No mortality in our study suggests need to validate the SCORTEN index in our country in a large number of patients.     

Analysis of 70 KD Heat Shock Protein (HSP70) Expression in the Lesional Skin of Lupus Erythematosus (LE) and LE Related Diseases

Biopsied specimens from skin lesions of SLE were studied for expression of 70 KD heat shock protein (HSP70). The pattern of HSP70 expression in SLE was diffuse in whole epidermis, hair follicles, and sweat gland cells and rather more intense than that in other control groups or normal skin. No significant differences in HSP70 expression were observed between sun-exposed and protected areas of SLE skin lesions. Unlike SLE, reduced or no expression of HSP70 was observed in skin lesions of DLE. In tissue culture, UVB radiation in vitro induced relatively intense expression of HSP70 in the nuclear area of keratinocytes. A few γδT cell receptor positive cells which might respond to HSP70 expressing cells were detected in the basal layer of skin lesions of diseases. These studies suggest that abberant expression of HSP70 in skin lesions of SLE might contribute to both skin lesions and antibody formation in SLE.