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Sethuraman G.,All India Institute of Medical Sciences | Ramesh V.,Safdarjung Hospital
Pediatric Dermatology

Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis that accounts for 1% to 2% of cases. Childhood skin tuberculosis represents 18% to 82% of all cutaneous tuberculosis cases. Scrofuloderma and lupus vulgaris are the two most common clinical forms in children. An increase in the number of tuberculids, especially lichen scrofulosorum, has been observed in the last several years. Cutaneous tuberculosis in children can be severe and have a protracted course. Multiplicity of lesions and multifocal disseminated involvement in scrofuloderma and lupus vulgaris is common. Scrofuloderma progressing to gummatous lesions (scrofulous gumma) is mostly described in children. Morbidities and deformities are more severe in children. © 2012 Wiley Periodicals, Inc. Source

Singh A.,Institute of Pathology ICMR | Ramesh V.,Safdarjung Hospital
Indian Journal of Dermatology, Venereology and Leprology

Primary adenoid cystic carcinoma (PCACC) of skin is a rare tumor, and those who show distant metastasis are even rarer. We report a case of PCACC on the face of a 55-year-old man who showed bilateral lung metastasis and on palliative chemotherapy showed significant regression of the primary tumor. The patient was alive at a 15-month follow-up. A brief literature review of the eight cases including ours is described. Source

Katara G.K.,Institute of Pathology ICMR | Ansari N.A.,Institute of Pathology ICMR | Ansari N.A.,U.S. National Institutes of Health | Verma S.,Institute of Pathology ICMR | And 2 more authors.
PLoS Neglected Tropical Diseases

Background: Post kala-azar dermal leishmaniasis (PKDL), a sequel to visceral leishamaniasis (VL) in 5-15% cases, constitutes a parasite reservoir important in disease transmission. The precise immunological cause of PKDL outcome remains obscure. However, overlapping counter regulatory responses with elevated IFN-γ and IL-10 are reported. Methodology/Principal Findings: Present study deals with ex-vivo mRNA and protein analysis of natural regulatory T cells (nTreg) markers (Foxp3, CD25 and CTLA-4) and IL-10 levels in lesion tissues of PKDL patients at pre and post treatment stages. In addition, correlation of nTreg markers and IL-10 with parasite load in tissue lesions was investigated. mRNA levels of nTreg markers and IL-10 were found significantly elevated in pre-treatment PKDL cases compared to controls (Foxp3, P = 0.0009; CD25 & CTLA-4, P<0.0001; IL-10, P<0.0001), and were restored after treatment. Analysis of nTreg cell markers and IL-10 in different clinical manifestations of disease revealed elevated levels in nodular lesions compared to macules/papules. Further, Foxp3, CD25 and IL-10 mRNA levels directly correlated with parasite load in lesions tissues. Conclusion/Significance: Data demonstrated accumulation of nTreg cells in infected tissue and a correlation of both IL-10 and nTreg levels with parasite burden suggesting their role in disease severity in PKDL. © 2011 Katara et al. Source

Ramesh V.,Safdarjung Hospital | Katara G.K.,Institute of Pathology ICMR | Verma S.,Institute of Pathology ICMR | Salotra P.,Institute of Pathology ICMR
British Journal of Dermatology

Background Post-kala-azar dermal leishmaniasis (PKDL) constitutes a parasite reservoir important in the transmission of visceral leishmaniasis (VL). Unacceptable treatment regimens and increasing drug resistance blight control programmes. The success of oral miltefosine in VL prompted a clinical, histopathological and parasitological study of this drug in PKDL. Objectives To define the dose and duration of miltefosine for treatment of PKDL. Methods Twenty-six patients confirmed by slit-skin smear, histopathology and molecular tests were enrolled in the study. They received miltefosine capsules 50 mg thrice daily after food. Treatment was for 60 days with a provision to increase by 30 days if a responder had not attained a cure. Cure was ascertained by clinical and histopathological examination, and measuring parasite burden using real-time polymerase chain reaction. Results Twenty-four patients with a wide range of parasite burden completed the study. Twenty-three achieved a cure giving an initial cure rate of 96% (95% confidence interval 79-99%). Sixteen patients were cured with 50 mg thrice daily, 13 in 60 days and three within 90 days. In seven cases, miltefosine had to be reduced, because of gastrointestinal intolerance, to 50 mg twice daily to a total of 180 capsules. Lesional parasites were undetectable at 1 month post-treatment. Treatment was safe with no relapses at 1-year follow-up. Conclusion Oral miltefosine, 50 mg thrice daily for 60 days or twice daily for 90 days, could be an effective treatment for PKDL. © 2011 British Association of Dermatologists. Source

Katara G.K.,National Institute of Pathology ICMR | Ansari N.A.,National Institute of Pathology ICMR | Singh A.,National Institute of Pathology ICMR | Ramesh V.,Safdarjung Hospital | Salotra P.,National Institute of Pathology ICMR
PLoS Neglected Tropical Diseases

Background: Post kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis, caused by Leishmania donovani, constitutes an important reservoir for the parasite. Parallel functioning of counter acting immune responses (Th1/Th2) reflects a complex immunological scenario, suggesting the involvement of additional regulatory molecules in the disease pathogenesis. Methodology/Principal Findings: In the present study, human cytokine/chemokine/receptor specific cDNA array technique was employed to identify modulations in gene expression of host immuno-determinants during PKDL, followed by evaluation of Th17 type responses by analyzing mRNA and protein expression of Th17 markers (IL-23, IL-17, RORγt) and performing functional assays using Leishmania antigen (TSLA) or recombinant (rec)IL-17. Array analysis identified key immuno-regulatory molecules including cytokines (TNF-α, IFN-γ, IL-10, IL-17), chemokines (MCP-1, MIP-1α), apoptotic molecules (FasL, TRAIL, IRF-1) and receptors (CD40, Fas). Up regulation in lesional expression of Th17 markers was observed during PKDL compared to control (IL-17 and IL-23, P = 0.0008; RORγt, P = 0.02). In follow-up samples, chemotherapy significantly down regulated expression of all markers. In addition, lesional expression of IL-17 was confirmed at protein level by Immuno-histochemistry. Further, systemic presence of Th17 responses (IL-17 and IL-23) was observed in plasma samples from PKDL patients. In functional assays, TSLA stimulated the secretion of IL-17 and IL-23 from PBMCs of PKDL patients, while recIL-17 enhanced the production of TNF-α as well as nitric oxide (NO) in PKDL compared to control (TNF-α, P = 0.0002; NO, P = 0.0013). Further, a positive correlation was evident between lesional mRNA expression of IL-17 and TNF-α during PKDL. Conclusion/Significance: The results highlight key immune modulators in PKDL and provide evidence for the involvement of Th17 type responses in the disease pathogenesis. © 2012 Katara et al. Source

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