Factors associated with onychomycosis in nail psoriasis: a multicenter study in Pakistan.

BACKGROUND: Treatment of psoriatic nail disease is challenging, and dystrophic psoriatic nails can get secondarily infected with fungi. METHODS: This 2-year, matched case-control study was conducted at three tertiary care centers of Karachi, Pakistan. Data were collected from patients with nail psoriasis as cases with age- and gender-matched controls. A detailed questionnaire was filled for all study participants. Nail Psoriasis Severity Index (NAPSI) scoring tool was used to assess dystrophy. Fungal infection was inferred by nail clippings for fungal hyphae and culture. RESULTS: Among 477 participants, 159 cases and 318 controls completed the study. Their mean age was 44 years, and one-third were female. Fungal culture positivity was statistically significant in cases as compared to the control group (P < 0.001). The most frequent species identified was Candida parapsilosis in both cases and controls. Body mass index, NAPSI scoring, socioeconomic status, elevated diastolic blood pressure, smoking status psoriasis among first-degree relatives, and longstanding disease of more than 10 years were significant factors in univariable analysis. Multivariable logistic regression identified independent factors like low to middle socioeconomic status, history of psoriasis in first-degree relative, current smoker, and obesity. CONCLUSION: We found nearly one-third of the psoriatic patients with nail involvement having concomitant fungal infection. We emphasize that nail clipping for fungal smear and culture should be advised to those patients with coexisting factors found significant in our study results. This opinion can be incorporated in psoriasis management guidelines for improving treatment of psoriatic nails.

SLC11A1 polymorphisms and host susceptibility to cutaneous leishmaniasis in Pakistan.

BACKGROUND: The vector-borne cutaneous leishmaniasis (CL) is endemic in several regions of Pakistan mainly affecting poor populations. Host genetic factors, particularly SLC11A1 (solute carrier transmembrane protein) within macrophages, play a crucial role in disease pathology and susceptibility. Association of SLC11A1 with cutaneous leishmaniasis, a neglected tropical disease, is not well established. Inconsistencies have been observed within different populations worldwide with respect to genetic susceptibility. This study was designed to investigate genetic variation(s) in SLC11A1 and to assess possible association with cutaneous leishmaniasis in Pakistan. RESULTS: Eight polymorphisms (rs2276631, rs3731864, rs2290708, rs2695342, rs201565523, rs17215556, rs17235409, rs17235416) were genotyped across SLC11A1 in 274 patients and 119 healthy controls. Six polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Two single nucleotide polymorphisms were analyzed with newly designed semi-nested PCR assays. Case-control analysis showed no association between selected polymorphisms in SLC11A1 and cutaneous leishmaniasis. No significant difference was observed in the distribution of alleles between leishmaniasis patients and healthy individuals. Strong pairwise linkage disequilibrium was observed between rs2276631 and rs2290708 (r 2 = 64); and rs17235409 and rs17235416 (r 2 = 78). CONCLUSIONS: This study shows that genetic variations in the candidate gene SLC11A1 do not affect susceptibility to cutaneous leishmaniasis in the sample population from Pakistan.

CC chemokine receptor 5 Δ32 polymorphism: association analysis and allele distribution among cutaneous leishmaniasis patients from Pakistan.

BACKGROUND: Human immunodeficiency virus (HIV)/leishmaniasis coinfection is a matter of deep concern worldwide. CC chemokine receptor 5 (CCR5) functions as a co-receptor for HIV entry into host immune cells with an elevated expression observed during leishmaniasis, promoting parasite persistence. A 32 bp deletion (Δ32) in the CCR5 gene provides protection against HIV infection and increased resistance to Leishmania infection. METHODS: In this study, CCR5-Δ32 distribution within Pakistani population with cutaneous leishmaniasis was investigated to evaluate genetic susceptibility to HIV infection. CCR5-Δ32 polymorphism was analyzed in 276 leishmaniasis patients and 119 uninfected healthy controls. Genotypic and allelic frequencies were evaluated and tested for Hardy-Weinberg equilibrium (HWE). RESULTS: The overall Δ32 allele frequency was 6.58% of the population (n = 395). There was a significant difference (p < 0.05) in the geographical distribution of Δ32 allele which was higher in the northern region of the country when compared with the south. Five individuals were identified to be homozygous for the Δ32 allele which has not been reported before from Pakistan. However, no significant association was observed between CCR5-Δ32 and cutaneous leishmaniasis. CONCLUSION: The higher frequency of CCR5 wild-type allele among leishmaniasis patients may suggest an increased risk of HIV infection and also support its facilitative role in Leishmania infection.

Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid proteinosis.

BACKGROUND: The extracellular matrix protein 1 (ECM1) is a glycoprotein, expressed in skin and other tissues. Loss-of-function mutation in ECM1 causes a rare autosomal recessive disorder called lipoid proteinosis. Lipoid proteinosis is presented by varying degrees of skin scars, beaded papules along the eyelid margins, variable signs of hoarseness of voice and respiratory disorders. More than 250 cases of this disorder have been described in the literature, but occurrence of lipoid proteinosis in siblings is very rare. This study was designed to investigate the possible mutation causing lipoid proteinosis in a Pakistani family and to elaborate the scope of possible genetic changes, causing the genodermatosis in Pakistan. MAIN OBSERVATIONS: In this study, two siblings (12 and 9-years sisters) were presented with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother and younger brother were unaffected. Blood samples from clinically affected and unaffected family members were collected with informed consent. The coding region of ECM1 gene containing 10 exons were amplified and sequenced. Both the affected siblings were shown to have homozygous frame shift mutation by deletion of the nucleotide T at 507, codon 169, exon 6. This resulted in a frame shift from codon 169 and appearance of a premature stop codon at 177, causing formation of a mutated protein (176 amino acids) instead of normal ECM1 protein (540 amino acids). CONCLUSION: A case of homozygous 62-bp insertion in ECM1 gene causing lipoid proteinosis has been reported in another Pakistani family. The current study presents a homozygous frame shift mutation supporting an unusual function of ECM1 protein and broadens the spectrum of disease-linked mutations in this rare case of genodermatosis in this region.