Belum Siva Nagi Reddy

Leprosy and the adaptation of human toll-like receptor 1.

Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7×10−8, OR = 0.31, 95% CI = 0.20–0.48, and HLA-DQA1 rs1071630, case-control P = 4.9×10−14, OR = 0.43, 95% CI = 0.35–0.54). The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases.

IL-10 promoter single nucleotide polymorphisms are significantly associated with resistance to leprosy

The minor haplotype −3575A/-2849G/-2763C in IL-10 promoter has been defined as a marker of disease resistance to leprosy and its severity in Brazilian population. Our investigation of six single-nucleotide polymorphisms (SNPs) in IL-10 promoter in 282 Indian leprosy patients and 266 healthy controls by direct PCR sequencing, however, showed that the extended haplotype: −3575T/-2849G/-2763C/-1082A/-819C/-592C was associated with resistance to leprosy per se and to the development of severe form of leprosy, using either a binomial (controls vs cases, P=0.01, OR=0.58, CI=0.37–0.89) or ordinal (controls vs paucibacillary vs multibacillary, P=0.004) model. Whereas, IL-10 haplotype −3575T/-2849G/-2763C/-1082A/-819T/-592A was associated with the risk of development of severe form of leprosy (P=0.0002) in contrast to the minor risk haplotype −3575T/-2849A/-2763C in the Brazilian population. The role of IL-10 promoter SNPs in Brazilian and Indian population strongly suggests the involvement of IL-10 locus in the outcome of leprosy.

Comparative efficacy of various treatment regimens for androgenetic alopecia in men.

Our understanding of the aetiology of androgenetic alopecia (AGA) has substantially increased in recent years. As a result, several treatment modalities have been tried with promising results especially in early stages of AGA. However, as far as has been ascertained, there is no comprehensive study comparing the efficacy of these agents alone and in combination with each other. One hundered male patients with AGA of Hamilton grades II to IV were enrolled in an open, randomized, parallel‐group study, designed to evaluate and compare the efficacy of oral finasteride (1 mg per day), topical 2% minoxidil solution and topical 2% ketoconazole shampoo alone and in combination. They were randomized into four groups. Group I (30 patients) was administered oral finasteride, Group II (36 patients) was given a combination of finasteride and topical minoxidil, Group III (24 patients) applied minoxidil alone and Group IV (10 patients) was administered finasteride with topical ketoconazole. Treatment efficacy was assessed on the basis of patient and physician assessment scores and global photographic review during the study period of one year. At the end of one year, hair growth was observed in all the groups with best results recorded with a combination of finasteride and minoxidil (Group II) followed by groups IV, I and III. Subjects receiving finasteride alone or in combination with minoxidil or ketoconazole showed statistically significant improvement (p<0.05) over minoxidil only recipients. No signifcant side‐effects related to the drugs were observed. In conclusion, it is inferred that the therapeutic efficacy is enhanced by combining the two drugs acting on different aetiological aspects of AGA.

Diagnosis of nail psoriasis: importance of biopsy and histopathology

Background  Involvement of the nail is quite common in psoriasis and at times may be the sole diagnostic clue. However, the histopathology of nail psoriasis has not been adequately evaluated. A confirmation of the diagnosis is required in cases suspected to have nail psoriasis in order to plan long‐term therapy.

Combination of surgical avulsion and topical therapy for single nail onychomycosis: a randomized controlled trial

Summary Background Conventional therapy of onychomycosis is prolonged and often frustrating, which is why combination therapy involving topical, oral and surgical measures has been advocated as the treatment of choice. There are no controlled studies evaluating the efficacy of nail avulsion followed by topical antifungal therapy.

Association study of major risk single nucleotide polymorphisms in the common regulatory region of PARK2 and PACRG genes with leprosy in an Indian population

Single nucleotide polymorphisms (SNPs) in the regulatory region shared by PARK2 and PACRG have been identified as major risk factors for leprosy susceptibility in two ethnically distinct populations. We investigated the association of six SNPs present in this regulatory region with leprosy susceptibility in an Indian population. Genotyping was performed by direct PCR sequencing in 286 leprosy patients and 350 healthy controls. Our results showed that T allele of SNPs PARK2_e01 (−2599) and 28 kb target_2_1 was significantly associated with susceptibility to leprosy per se (P=0.03 and 0.03, respectively). The T allele of SNPs PARK2_e01 (−2599) showed a significant recessive effect (P=0.04) in susceptibility to leprosy in Indian population as against the dominant effect of haplotype T-C of the major risk SNPs PARK2_e01 (−2599) and rs1040079 in Brazilian and Vietnamese population. However, after bonferroni corrections, these significant differences disappeared. Haplotype analysis also showed a lack of significant association of any haplotype with cases or controls. The noninvolvement of major risk SNPs in the regulatory region of PARK2 and PACRG locus with leprosy susceptibility in Indian population highlights the differential effect of these SNPs in regulating genetic susceptibility to leprosy in different populations.

Cosmetic dermatitis – current perspectives

Background Increasing use of cosmetics by modern society has contributed alarming to an rise in the incidence of cosmetic dermatitis (CD). The causative agents are skin, hair, nail and eye cosmetics. Reported cases of cosmetic dermatitis represent only the tip of the iceberg, as most patients who experience an adverse reaction to cosmetics do not consult a physician but discontinue using the suspected items.

Pyoderma Gangrenosum in Two Siblings: A Familial Predisposition

We report pyoderma gangrenosum in two siblings with onset during childhood and no associated systemic abnormalities. The patients were born of nonconsanguineous, healthy parents. Treatment with oral corticosteroids produced an excellent clinical response, followed by recurrence after cessation of therapy. Steroids were restarted in combination with dapsone to prevent further recurrence.

An Association of Twenty‐Nail Dystrophy with Vitiligo

A rare association of twenty‐nail dystrophy with segmental vitiligo is described in two patients. Vitiligo preceded the nail dystrophy. In both cases, all twenty nails were uniformly affected with the nail plates showing longitudinal striations and loss of luster. Longitudinal nail biopsy revealed a histological picture suggestive of eczematous changes and lichen planus respectively. Intramatrix injections of triamcinolone acetonide into the proximal and lateral nail folds were administered with considerable improvement.

Efficacy of Triamcinolone Acetonide in Various Acquired Nail Dystrophies

The treatment of nail disorders is currently an unsatisfying exercise. Isolated nail involvement generally does not warrant any systemic therapy. At the same time, treatment is requested because of significant cosmetic and functional handicap. Intralesional triamcinolone acetonide (TA) in the proximal nail fold was evaluated as a treatment modality in 30 patients with twenty‐nail dystrophy, 14 with nail lichen planus, and 6 with nail psoriasis. The number of involved nails varied from 1–20, and 1–10 nails were treated with TA. Fourteen patients discontinued treatment after 1–2 sittings. Out of the 28 patients completing the treatment protocol, 16 showed 75–100% improvement. Predominant side effects included pain, subungual hematoma formation, proximal nail fold hypopigmentation, and atrophy. TA given as a single injection in the proximal nail fold produced good improvement in a significant number of patients completing the treatment protocol. Lower concentrations of TA (5 mg/ml) were quite effective in treating various dermatoses affecting the nail unit. Our technique had fewer side effects than needle‐less injection or multiple injection techniques. Careful attention to injection technique further minimized the side effects associated with the procedure. Sixteen patients completed the six‐month follow‐up and a relapse of nail changes was seen in 10. The relapses were equally responsive to retreatment. TA injected into the proximal nail fold area is a useful, cheap and efficacious treatment for dermatoses affecting the nail unit.