Association and expression of the antigen-processing gene PSMB8, coding for low-molecular-mass protease 7, with vitiligo in North India: case-control study.

BACKGROUND: Vitiligo is a multifactorial, autoimmune, depigmenting disorder of the skin where aberrant presentation of autoantigens may have a role. OBJECTIVES: To study the association of two antigen-processing genes, PSMB8 and PSMB9, with vitiligo. METHODS: In total 1320 cases of vitiligo (1050 generalized and 270 localized) and 752 healthy controls were studied for the PSMB9 exon 3 G/A single-nucleotide polymorphism (SNP), PSMB8 exon 2 C/A SNP and PSMB8 intron 6 G/T SNP at site 37 360 using polymerase chain reaction (PCR)-restriction fragment length polymorphism. Real-time PCR was used for transcriptional expression of PSMB8 and cytokines. Expression of ubiquitinated proteins and phosphorylated-p38 (P-p38) was studied by Western blotting. RESULTS: Significant increases in PSMB8 exon 2 allele A (P < 2.07 × 10-6 , odds ratio 1·93) and genotypes AA (P < 1.03 × 10-6 , odds ratio 2·51) and AC (P < 1.29 × 10-6 , odds ratio 1·63) were observed in patients with vitiligo. Interferon-γ stimulation induced lower expression of PSMB8 in peripheral blood mononuclear cells of cases compared with controls, suggesting impaired antigen processing, which was confirmed by accumulation of ubiquitinated proteins in both lesional and nonlesional skin of patients with vitiligo. Expression of proinflammatory cytokines - interleukin (IL)-6, IL-1ß and IL-8 - was higher in the lesional skin. P-p38 expression was variable but correlated with the amount of ubiquitinated proteins in the lesional and nonlesional skin, suggesting that the inflammatory cytokine responses in lesional skin could be a result of both P-p38-dependent and -independent pathways. CONCLUSIONS: The PSMB8 exon 2 SNP is significantly associated with vitiligo. Accumulation of ubiquitinated proteins in skin of cases of vitiligo suggests their aberrant processing, which may promote the development of the disease.

Comparative efficacy of four treatment regimens in Type 2 Leprosy Reactions (Prednisolone alone, Thalidomide alone, Prednisolone plus Thalidomide and Prednisolone plus Clofazimine).

This study has been carried out to assess the comparative efficacy of Prednisolone alone or thalidomide alone for the first attack of T2R, and combination of prednisolone plus thalidomide or prednisolone plus clofazimine for chronic and recurrent T2R. Efficacy of all four regimens was assessed on the basis of clinical recovery of T2R measured by reaction severity scores (RSS) ,visual analogue scale (VAS) and other relevant parameters, requirement of extra dose of steroid for clinical recovery, recurrence of T2R and side effects observed in each regimen. The designof study was an open prospective longitudinal single centre investigation. In the first episode T2R group I (prednisolone alone) the efficacy was 58.8% (10/17) compared to 93.75% (15/16) in Group 2 treated with thalidomide alone. This difference was statistically significant p <0.05 when compared using unpaired ttest. When clinical outcome was compared in recurrent/relapse of T2R Groups 3 and 4, it was observed to be statistically significant p<0.05 when compared using unpaired t test. It was 82.35% (14/17) in Group 3 (prednisolone plus clofazimine) and 10/16 (62.5%) in Group 4 (prednislone plus clofazimine). To conclude, for the management of recurrent/chronic ENL, both the combinations-prednisolone with thalidomide or clofazimine appear to be efficacious. While prednisolone with thalidomide appears to be better than prednisolone and clofazimine, however, by 20 weeks difference narrows down. As of now these findings may be considered indicative and larger experience on more number of cases using robust statistical design is required for marchingtowards making recommendations for clinical application.

Effect of Steroid Prophylaxis on Nerve Function Impairment in Multi-bacillary Leprosy Patients on MDT-MB.

The effects of corticosteroids in varying doses and duration for the treatment of reaction and nerve function impairment (NFI) in leprosy have been studied extensively. However, an optimal dose and duration of steroid when used as a prophylactic agent for NFI is yet to be established. This study was aimed to determine whether addition of low dose steroid for the initial 8 months of multi drug therapy (MDT) can prevent further deterioration of nerve function (DON) in multibacillary leprosy patients. Sixty multibacillary leprosy patients were randomized into two groups and B consisting of 30 patients each. Group A received MDT-MB for 12 months with prednisolone 20 mg/day from the beginning of treatment for 6 months followed by tapering by 5 mg/2 weeks in 7th and 8th month. Group B received MDT-MB alone for 12 months. Nerve function assessment (NFA) using various modalities was done at the beginning (0 month), at the end of 8 months and at the completion of MDT (12 months). The proportion of patients showing DON was significantly higher in group B, while proportion of patients showing improvement was more in group A. This study thus shows all MB cases with or without NFI at registration should receive prophylactic steroid at least for 8 months. Since preventing deformities using; prophylactic steroids in leprosy is an important issue larger randomized control trials using longer duration of low dose steroid witha longer follow up period should be conducted.

Emergence of decreased susceptibility to extended-spectrum cephalosporins in Neisseria gonorrhoeae in India.

BACKGROUND: In the past, Neisseria gonorrhoeae has developed resistance to antimicrobial agents used for its treatment. Consequently, extended-spectrum cephalosporins form the mainstay of treatment for gonorrhoea. METHODS: Samples from 88 patients attending the sexually transmitted diseases clinics from December 2009 to January 2011 in two referral hospitals in New Delhi were studied. Antimicrobial susceptibility testing was done using the disc diffusion method as per the calibrated dichotomous sensitivity technique against the following antibiotics: penicillin (0.5 i.u.), tetracycline (10 µg), nalidixic acid (30 µg), ciprofloxacin (1 µg), spectinomycin (100 µg), ceftriaxone (0.5 µg) and cefpodoxime (10 µg) (Oxoid UK). Azithromycin (15 µg) (Oxoid, UK) was tested as per the guidelines of the Clinical and Laboratory Standards Institute. Minimum inhibitory concentrations were determined using the Etest for penicillin, tetracycline, ciprofloxacin, ceftriaxone, spectinomycin and azithromycin as per the manufacturer's instruction (Biomerieux, France). RESULTS: Eighteen isolates of Neisseria gonorrhoeae were obtained. Three of these had decreased susceptibility to ceftriaxone and cefpodoxime by the disc diffusion method. The minimum inhibitory concentrations of ceftriaxone for two isolates were 0.064 µg/ml and for one isolate it was 0.125 µg/ml. CONCLUSION: Higher minimum inhibitory concentrations to extended-spectrum cephalosporins is of concern as it has been shown to precede treatment failure. This may warrant its use in increased/multiple dosages alone or possibly in combination (dual therapy), thereby complicating effective disease control. Our report is in accordance with earlier reports from different parts of the world. Therefore, a continuous surveillance of antimicrobial resistance is crucial to tailor treatment schedules for Neisseria gonorrhoeae in a particular geographical region.

Epidemiological trends of leprosy in an urban leprosy centre of Delhi: a retrospective study of 16 years.

This study was done by collecting the retrospective data from 1994 to 2009 of patients attending the urban leprosy centre attached to the department of dermatology, STD & leprosy of PGIMER & Dr. R M L Hospital, New Delhi. The data was analysed according to age, sex, type of leprosy, leprosy reactions, deformities and relapse and compared with the national figures by comparison of proportions after taking the national data per 10,000 population. A total of 3659 patients attended our ULC (Urban Leprosy Centre) among which 2741 were male and 945 females (M:F-3:1). 669 patients (18.2%) were children. The data analysed show a gradual decline in new case detection rate with a marginal rise in 2005 and 2008. Percentage of MB cases was falling consistently till 2005 after which it showed an abrupt rise. The incidence of type 1 reaction varied from 21% in 1994 to 10% in 2009 in PB patients and from 6% in 1994 to 8% in 2009 in MB patients. The trend of type 2 reactions in MB patients showed a slow declining trend. MDT completion rate showed an impressive improvement from 56% in 1994 to 90% in 2009. The number of patients revisiting the ULC with features of relapse also showed a decrease in number. The pattern of visible deformities showed an almost constant trend similar to national figures. Improved MDT completion rate helps in reducing the disease transmission, severity, reactions and disabilities.

Inoculation leprosy and HIV co-infection: a rare case with nerve involvement preceding development of skin patch and type 1 reaction as immune reconstitution syndrome following antiretroviral therapy.

The transmission of leprosy has been universally accepted to be primarily, through nasal dissemination from multibacillary patients to the susceptible persons. However, the possibility of leprosy transmission through prolonged skin contact with abraded leprous skin or through skin inoculation can not be ruled out. We report a case of development of a paucibacillary leprosy patch close to the site of a local trauma, after an interval of about 13-14 years, in a HIV positive subject. Also discussed are the various hypotheses in the aetiopathogenesis of leprosy like entry route of lepra bacilli into the body, viability of lepra bacilli in the environment and evolution of skin and nerve lesions of leprosy.

Annular vesiculobullous eruptions in type 2 reaction in borderline lepromatous leprosy: a case report.

An untreated case of BL presented with clinical features of type 2 reaction (T2R) confirmed by histopathology. The case was a 18-year-old female with borderline lepromatous leprosy who developed annular vesiculobullous eruptions oversome of the pre-existing plaques on arms and upper back along with fever and severe neuritis after a short course of ofloxacin intake prescribed for urinary tract infection. In addition to the above lesions, some of the existing lesions showed acute exacerbation characterized by erythema, oedema, tenderness and vesiculobullous eruption. This can be considered as an example of leprous exacerbation as described in older literature. T2Rs are common in lepromatous leprosy and not so uncommonly are observed in borderline lepromatous leprosy. The vesiculobullous and crusted lesions developing over the existing borderline plaques, some of them presenting in an annular pattern in T2R in the form of leprous exacerbation, have been reported rarely in the literature.

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.

Systemic sarcoidosis in a case of lepromatous leprosy: a case report.

The clinical features of cutaneous sarcoidosis and leprosy are some times difficult to differentiate and there have been many reports where pulmonary sarcoidosis was treated as pulmonary tuberculosis or a case of sarcoidosis was treated with anti-leprosy multidrug therapy, before a correct diagnosis was made. So far there has been only one published case report of leprosy and sarcoidosis co-infection, where tuberculoid leprosy developed in a case of sarcoidosis, known for over a decade. We are reporting a case of dual affliction, where sarcoidosis was discovered (on routine screening) in a case of lepromatous leprosy, after administration of 2 years of multidrug therapy. The role of mycobacterial antigens (among a vast array of different animate or inanimate particles) in causation of sarcoidosis, is still speculative, as reviewed from literature.

New lesions after MDT in PB and MB leprosy: a report of 28 cases.

Appearance of new skin and/or nerve lesions during or after fixed duration of multi drug therapy (MDT), both in multibacillary (MB) and paucibacillary (PB) leprosy, is not uncommon. It could be a lesion due to reaction (type 1 or type 2), relapse due to multiplication of persisting or drug resistant bacilli or reinfection due to re-entry of lepra bacilli from outside. It is relatively easier to recognize the lesions due to classical reaction, both clinically and histopathologically. However, the differentiation could be difficult in other situations, especially when many of the relapse cases may present with features of reaction at the onset. Similarly, sometimes in late reversal reaction in addition to development of classical acute inflammation of old lesions, many of the patients developed multiple fresh new lesions without any sign of inflammation. We report a study of group of 28 relapsed leprosy cases, who developed new skin and/or nerve lesions at greatly varying time intervals (3 months to 22 years) after stopping MDT. Of these 28 patients, 11 were MB (1 LL,6 BL and 4 BB) and 17 were PB (12 BT, 4 TT and 1 Neuritic) at their first treatment. They reported to the Urban Leprosy Center (ULC) of Dr R M L Hospital during the period of 5 years (2002-2007). All patients came through self referral, 13 of them (46.4%) had received MDT outside our hospital (regular in 11 cases and irregular in 2 cases, as per the patient's statement), while the rest 15 had received full MDT regularly from our center (irregular in 1 case). All previously 11 MB cases developed new skin lesions of MB type (1 LL to LL, 3 BL to LL, 3 BL to BL, 1 BB to BL and 3 BB to BB). Of the 17 cases PB at their first treatment, 16 developed new lesions of PB type. Out of 4 TT cases, 1 had new lesions of TT, 1 BT and 2 LRR type lesions. Of the 12 BT cases at first presentation, 9 had BT, 1 secondary neuritic and 1 presented as LRR, while 1 BT case had new lesions of BL type. The one pure neuritic leprosy case presented as neuritic case only, after an interval of over 20 years. The post-MDT intervals of appearance of new lesions were 3-6 months in 5 cases (Group A), 8-30 months in 13 cases (Group B), from 3-10 years in 4 cases (Group C) and 15-22 years in 6 cases (Group D). All patients were successfully treated with a second course of MDT, as per the spectrum of the disease according to the number of fresh lesions. The likely cause of new lesions in group A (<6 months interval) could be either (1) mild type 1 reaction or (2) early relapse due to inadequate MDT. Similarly, the new lesions appearing in group B (0.5-3 years) could also represent mild type 1 reaction following improvement of CMI or a true early relapse. The possible causes of early relapse may be because of original misclassification or inadequate chemotherapy/irregular treatment or insufficient duration of therapy. In group C (3-10 years), the cause would most probably be late relapse, the possible causes of late relapse is either due to drug resistance and M. leprae persisters. When the time interval goes beyond 10 years (Group D), as in 6 of our cases, the possibility of reinfection can not be excluded besides causes of late relapse, since this period is usually considered equivalent to the maximum incubation period of lepra bacilli. In lepromatous leprosy, where the specific CMI against M. leprae is highly compromised, there is always a possibility of reinfection as long as the source of infection persists in the community and in such cases immunotherapy would be highly beneficial for prevention of reinfection. The post MDT time interval, lepromin test or drug resistance study both in vitro and in vivo may provide some clue to the mechanism responsible. All doubtful cases of new lesions with clinical presentation of type 1 reaction were diagnosed as relapse, through the therapeutic trial with oral prednisolone for 4-6 weeks and other cases. All cases with new lesions were treated with a second course of MDT (MB or PB) as per classification of new lesions.

Olmsted syndrome.

Olmsted syndrome is a rare disorder characterized by the combination of periorificial, keratotic plaques and bilateral palmoplantar keratoderma. New associated features are being reported. Olmsted syndrome is particularly rare in a female patient, and we report such a case in a six year-old Indian girl, who presented with keratoderma of her soles since birth and on her palms since the age of two years along with perioral and perinasal hyperkeratosis. She had sparse, light brown, thin hair. Although the psychomotor development of the child was normal until 18 months of age, the keratoderma plaques had restricted the child's mobility after that stage.

New lesions after MDT in PB and MB leprosy: a report of 28 cases

Appearance of new skin and/or nerve lesions during or after fixed duration of multi drug therapy (MDT), both in multibacillary (MB) and paucibacillary (PB) leprosy, is not uncommon. It could be a lesion due to reaction (type 1 or type 2), relapse due to multiplication of persisting or drug resistant bacilli or reinfection due to re-entry of lepra bacilli from outside. It is relatively easier to recognize the lesions due to classical reaction, both clinically and histopathologically. However, the differentiation could be difficult in other situations, especially when many of the relapse cases may present with features of reaction at the onset. Similarly, sometimes in late reversal reaction in addition to development of classical acute inflammation of old lesions, many of the patients developed multiple fresh new lesions without any sign of inflammation. We report a study of group of 28 relapsed leprosy cases, who developed new skin and/or nerve lesions at greatly varying time intervals (3 months to 22 years) after stopping MDT. Of these 28 patients, 11 were MB (1 LL,6 BL and 4 BB) and 17 were PB (12 BT, 4 TT and 1 Neuritic) at their first treatment. They reported to the Urban Leprosy Center (ULC) of Dr R M L Hospital during the period of 5 years (2002-2007). All patients came through self referral, 13 of them (46.4%) had received MDT outside our hospital (regular in 11 cases and irregular in 2 cases, as per the patient's statement), while the rest 15 had received full MDT regularly from our center (irregular in 1 case). All previously 11 MB cases developed new skin lesions of MB type (1 LL to LL, 3 BL to LL, 3 BL to BL, 1 BB to BL and 3 BB to BB). Of the 17 cases PB at their first treatment, 16 developed new lesions of PB type. Out of 4 TT cases, 1 had new lesions of TT, 1 BT and 2 LRR type lesions. Of the 12 BT cases at first presentation, 9 had BT, 1 secondary neuritic and 1 presented as LRR, while 1 BT case had new lesions of BL type. The one pure neuritic leprosy case presented as neuritic case only, after an interval of over 20 years. The post-MDT intervals of appearance of new lesions were 3-6 months in 5 cases (Group A), 8-30 months in 13 cases (Group B), from 3-10 years in 4 cases (Group C) and 15-22 years in 6 cases (Group D). All patients were successfully treated with a second course of MDT, as per the spectrum of the disease according to the number of fresh lesions. The likely cause of new lesions in group A (<6 months interval) could be either (1) mild type 1 reaction or (2) early relapse due to inadequate MDT. Similarly, the new lesions appearing in group B (0.5-3 years) could also represent mild type 1 reaction following improvement of CMI or a true early relapse. The possible causes of early relapse may be because of original misclassification or inadequate chemotherapy/irregular treatment or insufficient duration of therapy. In group C (3-10 years), the cause would most probably be late relapse, the possible causes of late relapse is either due to drug resistance and M. leprae persisters. When the time interval goes beyond 10 years (Group D), as in 6 of our cases, the possibility of reinfection can not be excluded besides causes of late relapse, since this period is usually considered equivalent to the maximum incubation period of lepra bacilli. In lepromatous leprosy, where the specific CMI against M. leprae is highly compromised, there is always a possibility of reinfection as long as the source of infection persists in the community and in such cases immunotherapy would be highly beneficial for prevention of reinfection. The post MDT time interval, lepromin test or drug resistance study both in vitro and in vivo may provide some clue to the mechanism responsible. All doubtful cases of new lesions with clinical presentation of type 1 reaction were diagnosed as relapse, through the therapeutic trial with oral prednisolone for 4-6 weeks and other cases. All cases with new lesions were treated with a second course of MDT (MB or PB) as per classification of new lesions.

Does concomitant hiv infection has any epidemiological, clinical, immunopathological and therapeutic relevance in leprosy?

Co-infection with HIV-1 and M. Leprae is a rare event in endemic areas for leprosy and HIV, such as India. Neither an increased HIV prevalence among leprosy cases, nor any rapid progression to AIDS was observed among dual HIV-leprosy infections. The current situation concerning continued new leprosy case-detection and gradual increase in HIV infection in India and a few other developing countries, such as Brazil, emphasizes the importance of monitoring the occurrence of co-infections. There is so far no change in the clinical spectrum of leprosy, PB/MB ratio, leprosy reactions and neuritis among co-infected patients. All types of leprosy occur in HIV patients [except in one study (Borgdorff et al, 1993) where more MB leprosy cases with HIV infection were seen]. Histopathological observations reveal a normal spectrum of appearance in biopsies of leprosy lesions from co-infected patients suggesting that cell-mediated immune response to M leprae is preserved at the site of the disease, despite evidence that these responses are abrogated systemically. All dual infection cases respond to regular treatment, except in three studies which noted more relapses. Therefore, a longer duration of surveillance is advisable after fixed duration therapy, for the detection of early relapse. Type 2 reaction can be managed with a higher dose of clofazimine. Type 1 reaction when developed as such, or as IRIS, needs oral steroids in adequate doses, particularly when associated with neuritis and motor loss, since lower doses may not be able to reverse the motor loss even of early onset. However, higher doses of corticosteroid when given need to be monitored closely. The impact of immune restoration in co-infected patients receiving ART is commonly observed in cases with borderline leprosy.

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.

Angiosarcoma of scalp: a case report.

Cutaneous angiosarcomas are rare and constitute less than 1% of all malignant mesenchymal tumours. Most angiosarcomas of skin arise in the following clinical settings: 1. face and scalp of elderly 2. following lymphoedema and 3. post radiation. We present a case of an elderly man presenting with scalp lesion of 18 months duration. Histological examination of the biopsy revealed features of an angiosarcoma, which showed imunohistochemical positivity for factor VIII related antigen.

Efficacy of beta-carotene topical application in melasma--an open clinical trial.

Beta-carotene, a structural analogue of vitamin A, works as an agonist of this vitamin, by reversibly sticking the chemical mechanism of melanogenesis by saturating the nuclear receptors of melanocytes and/or binding protein. To study the safety and efficacy of Beta-carotene lotion on topical application in melasma, clinically diagnosed 31 adults (26F and 5M) with melasma were included in this trial. All of them applied Beta-carotene lotion daily, morning and evening to the affected areas. Twenty six of them, completed regular 8 weeks treatment. Nine of them continued same treatment for 16 more weeks. All cases were evaluated clinically using melasma intensity (MPI) index (Grade I, II, III) and size of the lesion. Clinical photograph was taken for each case at 0 week, 8th week and 24th week. Initial 8 weeks treatment revealed that the single case with grade-I pigmentation included in this study recovered completely. Two out of 13 cases with grade-II pigmentation, showed no change, in 10 cases, pigmentation became lighter to grade-I (76.9%) and one case recovered completely. Out of 12 grade-III cases, one did not show any change, 10 (83.3%) converted to grade-II and one to grade-I. At the end of 24 weeks, all the nine cases (2 grade-II and 7 grade-III) showed further clearing of the pigmentation to the next lower grade. Side effects like mild erythemo and local irritation were observed in two cases each, who were advised to discontinue treatment as per the protocol. In control group, out of 12 (two with grade-II, six in grade-II, and four in grade-III) cases 11 showed no improvement, only one case with grade-II melasma revealed reduction of pigmentation to grade-I. One case developed local irritation. In conclusion, topical application of Beta-carotene lotion appears to be an effective and safe for melasma. Longer duration of application is associated with better result.