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.

A large spectrum of clinical patterns and histological characteristics of cutaneous TB exists in children. Lichen scrofulosorum is more commonly seen in comparison to adults. Systemic involvement was a feature in a major proportion of our patients.

Cutaneous tuberculosis in children continues to be an important cause of morbidity, there is a high likelihood of internal involvement, especially in patients with scrofuloderma. A search is required for more sensitive, economic diagnostic tools. Response to treatment at 4 weeks often helps in substantiating the diagnosis of tuberculosis in doubtful cases.

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Histopathological examination of nails is a valuable diagnostic aid, especially in the absence of skin lesions. Examination of the PAS-stained sections is necessary before making a histological diagnosis of nail psoriasis because onychomycosis and psoriasis may show similar histology.

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.

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.

We investigated the Toll-like receptor 2 (TLR2) Arg677Trp polymorphism, associated with lepromatous leprosy in the Korean population and shown to abrogate TLR2-mediated signalling in response to mycobacterial ligands, in 286 Indian leprosy patients and 183 ethnically matched controls. The case-control comparison also involved investigation of possible variation(s) in the promoter region of the TLR2 gene. Genotyping results after direct PCR sequencing showed that the TLR2 Arg677Trp polymorphism associated with lepromatous leprosy in the Korean population is not a true polymorphism of the TLR2 gene and has resulted from the variation present in the 93% homologous duplicated region of TLR2 exon 3 present approximately 23 kb upstream.