Kar Hk

An open labeled, comparative clinical study on efficacy and tolerability of oral minipulse of steroid (OMP) alone, OMP with PUVA and broad / narrow band UVB phototherapy in progressive vitiligo.

BACKGROUND Several modalities of treatment have been tried in vitiligo with varied results; however, Indian data on comparative studies of two or more therapies are limited. AIMS We compared different phototherapy methods with an oral steroid as an adjunct to determine the method with the best tolerability and efficacy. METHODS Eighty-six patients with progressive vitiligo were randomly assigned to different study groups according to a continuous selection method over a period of one year. Group 1 was given OMP + PUVA, group 2 OMP + UVB (NB), group 3 OMP + UVB (BB) and group 4 was given OMP alone. Each patient was followed up for six months and then released from treatment. Clinical evaluation was made at the end of three and six months. RESULTS In group 1 (OMP + PUVA), marked improvement was seen in 18.51% while moderate improvement was seen in 66.66% of the patients. Marked improvement was seen in 37.03% in group 2 (OMP + NB-UVB) while 44.44% had moderate improvement. In group 3 (OMP + BB UVB), 8.33% showed marked improvement while moderate improvement was seen in 25% of the patients. Marked and moderate improvement was seen in 5 and 10% of group 4 (OMP) patients, respectively. CONCLUSIONS Our study compared four treatment modalities in vitiligo patients, out of which oral minipulse of steroids (OMP) only had an adjunct value and was not very effective by itself. Narrow band UVB has a definite edge over broad band UVB and should be preferred when both options are available. NB-UVB and PUVA showed comparable efficacy.

HLA Alleles and Amino-Acid Signatures of the Peptide-Binding Pockets of HLA Molecules in Vitiligo

Vitiligo is a depigmenting disorder of the skin that is characterized by the loss of functional melanocytes from the lesional sites. Although the exact etiology is not understood, autoimmunity is thought to be a crucial deterministic factor. A recurring theme of several autoimmune disorders is the aberrant presentation of self-antigens to the immune system, which triggers downstream perturbations. Here we examine the role of alleles of HLA class I and class II loci to delineate vitiligo manifestation in two distinct populations. Our studies have identified three specific alleles, HLA-A*33:01, HLA-B*44:03, and HLA-DRB1*07:01, to be significantly increased in vitiligo patients as compared with controls in both the initial study on North Indians (N=1,404) and the replication study in Gujarat (N=355) cases, establishing their positive association with vitiligo. Both generalized and localized vitiligo have the same predisposing major histocompatibility complex alleles, i.e., B*44:03 and DRB1*07:01, in both the populations studied, beside the differences in the frequencies of other alleles, suggesting that localized vitiligo too may be an autoimmune disorder. Significant differences in the amino-acid signatures of the peptide-binding pockets of HLA-A and HLA-B α-chain and HLA-DR β-chain were observed between vitiligo patients and unaffected controls.

Transcriptional Upregulation of Nrf2-Dependent Phase II Detoxification Genes in the Involved Epidermis of Vitiligo Vulgaris

Oxidative stress is widely believed to be a contributing factor in vitiligo pathogenesis. To explore mechanisms by which epidermis responds to mounting oxidative stress, we investigated the involvement of phase II detoxification genes in vitiligo. Phase II detoxification pathways have recently been identified as being important in the regulation of epidermal skin homeostasis. In this study we show that the key transcription factor nuclear factor E2-related factor 2 (Nrf2) and the downstream genes NAD(P)H:quinone oxidase-1 (NQO-1), γ-glutamyl cystine ligase catalytic subunit (GCLC), and γ-glutamyl cystine ligase modifying subunit (GCLM) are upregulated in the lesional epidermal skin of subjects with vitiligo vulgaris. The differences between lesional and nonlesional skin were further investigated by studying the induced expression of Nrf2-dependent transcripts in skin punch biopsies using curcumin and santalol. Surprisingly, nonlesional skin showed induction of all transcripts while a similar effect was not observed for the skin punches from the lesional skin. The use of curcumin and santalol on epidermal cells showed that keratinocytes were more susceptible to apoptosis, whereas melanocytes induced phase II genes under the same concentrations with negligible apoptosis. Our studies provide new insights into the role of phase II detoxification pathway in maintaining skin homeostasis and sustaining redox balance in vitiligo patients.

Correlation of Vitamin D Levels with Pigmentation in Vitiligo Patients Treated with NBUVB Therapy

Cholecalciferol (vitamin D) might play a physiological role in photo-induced melanogenesis in human skin. We estimated the levels of 25-hydroxy vitamin D [25(OH)D] before, during, and after Narrow Band Ultraviolet B (NBUVB) radiation in patients of vitiligo and their correlation with NBUVB induced pigmentation. Thirty patients of vitiligo and equal number of age and sex matched controls were recruited for the study. Vitiligo patients were treated with NBUVB thrice weekly for 12 weeks. [25(OH)D] levels and Vitiligo Area and Severity Index (VASI) were calculated at 0 (baseline), 6, and 12 weeks. Baseline [25(OH)D] levels were measured in controls. Significant reduction in VASI score was observed after 12 weeks of therapy. Comparison and correlation between mean improvement in VASI and [25(OH)D] levels at 12 weeks showed moderate correlation, and the results were statistically insignificant. Mean reduction in VASI and increase in [25(OH)D] levels after 12 weeks of NBUVB showed moderate correlation. Thus, vitamin D might play a significant role in photo-induced melanogenesis. However, there might be additional effects of the phototherapy on melanogenesis. The complete mechanism of NBUVB induced pigmentation in vitiligo needs to be elucidated.

A Comparison of Low-Fluence 1064-nm Q-Switched Nd: YAG Laser with Topical 20% Azelaic Acid Cream and their Combination in Melasma in Indian Patients.

Background: Melasma is an acquired symmetric hypermelanosis characterised by irregular light to gray-brown macules on sun-exposed skin with a predilection for the cheeks, forehead, upper lip, nose and chin. The management of melasma is challenging and requires meticulous use of available therapeutic options. Aims: To compare the therapeutic efficacy of low-fluence Q-switched Nd: YAG laser (QSNYL) with topical 20% azelaic acid cream and their combination in melasma in three study groups of 20 patients each. Materials and Methods: Sixty Indian patients diagnosed as melasma were included. These patients were randomly divided in three groups (group A = 20 patients of melasma treated with low-fluence QSNYL at weekly intervals, group B = 20 patients of melasma treated with twice daily application of 20% azelaic acid cream and group C = 20 patients of melasma treated with combination of both). Study period was of 12 weeks each. Response to treatment was assessed using melasma area and severity index score. Statistical Analysis: The statistical analysis was done using Chi-square test, paired and unpaired student t-test. Results: Significant improvement was recorded in all the three groups. The improvement was statistically highly significant in Group C as compared to group A (P < 0.001) and group B (P < 0.001). Conclusions: This study shows the efficacy of low-fluence QSNYL, topical 20% azelaic acid cream and their combination in melasma. The combination of low-fluence QSNYL and topical 20% azelaic acid cream yields better results as compared to low-fluence QSNYL and azelaic acid alone.

Oral ulcer as an unusual feature of visceral leishmaniasis in an AIDS patient.

Leishmaniasis, a globally prevalent parasitic disease, occurs in three forms, viz, visceral, cutaneous and mucocutaneous. It is transmitted by female Phlebotomus sandflies. Human immunodeficiency virus (HIV) infection is increasing worldwide and several reports indicate a rising trend of VL / HIV co-infection, modifying the traditional anthroponotic pattern of VL transmission. India is one of the countries having the largest burden of leishmaniasis; nevertheless, there are very few HIV / leishmania co-infection cases reported so far. We report a 35-year-old homemaker infected with the human immunodeficiency virus; she presented with an oral ulcer. The investigations carried out on her revealed that she was afflicted by visceral leishmaniasis and the oral ulceration was a part of the same. This is only the second such case from the Indian subcontinent and more significantly from a non-endemic area.

Occurrence of plant sensitivity among patients of photodermatoses: a control-matched study of 156 cases from New Delhi.

BACKGROUND Photodermatitis is an abnormal response to ultraviolet radiation (UVR). The photoallergic contact dermatitis caused by plant allergens is a serious cause of morbidity in India. Airborne contact dermatitis is the classical presentation of plant-induced dermatosis, which may become difficult to differentiate from chronic actinic dermatitis in chronic cases. The rapid growth of parthenium weed in India and its ill effects on the population make it important to detect all cases of parthenium sensitivity, which in some cases might simulate photodermatitis. AIMS This study aims to detect the occurrence of plant sensitivity and photosensitivity in idiopathic-acquired photodermatoses, airborne contact dermatitis and general population taken as controls. METHODS One hundred and fifty six consecutive patients suffering from polymorphic light eruption (PMLE), chronic actinic dermatitis (CAD) and airborne contact dermatitis (ABCD) were enrolled in the study over a period of three years (June 2004 to May 2007). An equal number of age and sex matched healthy subjects were enrolled in the study as controls. All the patients were subjected to detailed history taking, clinical examination and histopathological examination for diagnosis. Patch and photopatch testing were perfomed in all the patients and healthy controls for detection of allergic and photoallergic reactions to parthenium, xanthium and chrysanthemum plant antigens and control antigens. RESULTS Out of 156 patients enrolled in the study, 78 (50%) had CAD, 67 (42.9%) had PMLE and 11 (7.05%) had ABCD. The occurrence of parthenium/xanthium allergy and photoallergy, either to parthenium or both was most commonly found in ABCD (72.7%), followed by CAD (32%). In PMLE 4.5% cases showed photoallergy. Only 1.9% in the control group showed sensitivity to parthenium and xanthium. CONCLUSION This study indicates that parthenium (and possibly xanthium) may act as important environmental factors in the initiation and perpetuation of not only ABCD but of CAD as well. Photoexacerbation to UVA at positive parthenium/xanthium sensitivity sites in ABCD and CAD indicates that ABCD with photosensitivity to compositae can lead to CAD.

Field trials on the use of Mycobacterium w vaccine in conjunction with multidrug therapy in leprosy patients for immunotherapeutic and immunoprophylactic purposes.

A double blind field trial was started with a candidate anti-leprosy vaccine, Mycobacterium w as an immunotherapeutic and immunoprophylactic agent against leprosy in a highly endemic region with a prevalence rate of over 18 per 1000 population. By 31 August 1992, 224 villages have been surveyed, covering a population of 307,981 (1981 census). A total of 979 MB patients and 2801 PB patients have been registered. A total of 19,453 household contacts of leprosy patients have been examined for clinical signs of disease, of which 16,519 have received the initial dose while 10,434 have also received the booster dose of vaccine/placebo. The aims and objectives, study design of the trial, present status as well as the socio-cultural aspect involved are highlighted in this paper.

Immunotherapy with Mycobacterium w vaccine decreases the incidence and severity of type 2 (ENL) reactions.

Immunotherapy with Mycobacterium w (M.w) vaccine was given to 45 patients with multibacillary (MB) leprosy; 41 similarly classified patients served as controls. All patients received standard multidrug therapy (MDT). Incidence, severity and frequency of type 2 (ENL) reactional episodes were monitored in both groups in a follow-up extending up to 4 years. Reactions were seen in fewer vaccinated (10/37) BL and LL patients than in the control group (12/34). A total of 20 episodes were recorded in the vaccine group as against 29 in the controls, 75% of reactions were mild in vaccinated and 51.72% were mild in the control group patients, and 3 patients in the control group had more than 3 reactional episodes. None of the vaccinated patients showed this. No additional incidence of neuritis were seen among vaccinated individuals during reactional episodes.

Reversal reaction in multibacillary leprosy patients following MDT with and without immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium w.

Immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium w, was given in addition to standard multidrug therapy (MDT) to 53 multibacillary lepromin negative patients belonging to BB, BL and LL types of leprosy (vaccine group). An equal control group received MDT and injections of micronized starch as placebo. Both the vaccine and placebo were administered intradermally every 3 months. The patients were evaluated at determined intervals by clinical, bacteriological and histopathological parameters and lepromin testing. Reactional episodes were analysed with reference to incidence, onset, frequency and severity during and after release from treatment (RFT). Incidence of reversal reaction (RR) was marginally higher in the vaccine group (22.6% vaccine group vs 15% control group). All cases with a history of downgrading type 1 reaction developed RR during therapy. Most episodes occurred within the 1st year of the commencement of therapy--50% developing within 3 months. Late reversal reaction (after RFT) were observed in 3.8% of cases in both groups, and 50% of the reactors in the control group and 33% in the vaccine group had repeated reactional episodes. Incidence of neuritis associated with RR as well as isolated neuritis was similar in both groups.