Basan syndrome in family from South-India: A novel SMARCAD1 variant.

Basan syndrome is a rare ectodermal dysplasia, characterised by adermatoglyphia, mottled acral pigmentation and various nail abnormalities; in addition to transient neonatal findings of acral blistering and facial milia. The genetic basis was established recently as heterozygous mutations affecting the skin specific isoform of the SMARCAD1 gene. It is now considered to be part of the spectrum of disorders resulting from haploinsufficiency of this isoform, which also includes Huriez syndrome and autosomal dominant adermatoglyphia. Here, we describe a family with Basan syndrome from South-India with a novel SMARCAD1 variant [SMARCAD1: c.-10 + 4_-10 + 7del] affecting the known mutational hotspot in non-coding exon 1.

In vitro detection of suspected drug in maculopapular drug reaction to antibiotics using secreted cytokines from drug-specific activated T cells.

BACKGROUND: Maculopapular drug eruption (MPE) in reaction to antibiotics is associated with enhanced expression of T-helper (Th)1 cytokines such as interferon gamma (IFN-gamma) or Th2 cytokines such as interleukin (IL)-5. Identifying the culprit drug usually involves rechallenge, which may not be forthcoming. Memory lymphocytes remain responsive to the culprit drug long after the reaction has resolved. On reactivation in vitro, there is increased proliferation and expression of certain markers, which provides us with an opportunity to predict the causal drug. OBJECTIVES: The study aimed to assess drug-specific cytokine production (IL-5 and IFN-gamma) in peripheral blood mononuclear cell (PBMC) culture supernatants to predict the causal antibiotic in cases of MPE. METHODS: PBMCs of 18 patients who developed MPE to 20 suspected antibiotics (2 patients had 2 suspected antibiotic allergies each), along with 11 drug-matched healthy controls, were incubated for 5 days with the respective drugs at 2 different concentrations. Secreted cytokines were measured in the supernatants, using enzyme-linked immunosorbent assay (ELISA) for IL-5 and IFN-gamma, at 6 h of incubation, then on day 2 and day 5. RESULTS: Drug-specific IL-5 and IFN-gamma production could be demonstrated in 65% and 74% of the cases, respectively. Maximal secretion of IL-5 and IFN-gamma was observed on day 5 and day 2 of incubation, respectively. The cut-off delta values, defined as the difference in cytokine concentration between drug-stimulated and unstimulated samples, were 4 pg mL-1 for IL-5 and 6 pg mL-1 for IFN-gamma. CONCLUSIONS: The measurement of drug-specific secretion of IL-5 and IFN-gamma using ELISA is a valuable method for detecting antibiotic-induced MPE.

Clinical markers of herpes simplex virus infection in patients with pemphigus vulgaris.

BACKGROUND: Herpes simplex virus (HSV) is known to influence the course of pemphigus vulgaris. Relapse, exacerbation, and treatment resistance in patients with pemphigus vulgaris can be due to HSV infection. OBJECTIVES: To characterize the clinical markers of HSV infection among patients with pemphigus. METHODS: This was a hospital-based, descriptive study performed with 60 consecutive patients with pemphigus vulgaris. The clinical and laboratory features of patients with documented HSV infection were then compared with those of patients without infection. RESULTS: HSV infection was confirmed in 23 (38.33%) patients. On univariate analysis, it was noted that male sex (P = .03); presence of fissures (P = .001), hemorrhagic crusts (P = .003), erosions with angulated margins (P = .024), and linear erosions (P = .001); and raised erythrocyte sedimentation rate (P = .015) were found to be significantly associated with HSV infection. In a multivariate analysis, hemorrhagic crusts (P = .015) and linear erosions (P = .008) were found to be independent predictors of HSV infection. LIMITATIONS: We did not use polymerase chain reaction to detect HSV infection, which could have yielded more cases of HSV infection. CONCLUSION: In the clinical setting of pemphigus vulgaris, the presence of fissures, hemorrhagic crusts, linear erosions, erosions with angulated margins and raised erythrocyte sedimentation rate must alert the clinician to the possibility of HSV superinfection.

Clinicopathological Spectrum of Cutaneous Lymphomas and Distinction of Early Mycosis Fungoides from its Mimics-A Retro-Prospective Descriptive Study from Southern India.

Background: Cutaneous lymphomas (CLs) could be either primary (PCL) or secondary; the former comprises cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas (CBCLs). Mycosis fungoides (MF) is the most common PCL. Diagnosis of early MF and distinguishing it from benign inflammatory mimics is challenging. This study aims to assess the clinicopathological spectrum of CL and to characterize early MF from its mimics using clinical characteristics, histopathological features, and ancillary techniques. Materials and Methods: This retro-prospective descriptive study was conducted in a tertiary-care institute, for over 5 years. Clinically as well as histopathologically suspected and biopsy-proven CL and their mimics were included. Cases were reviewed and subgrouped based on clinical and histopathological parameters and immunohistochemistry (IHC). Data were analyzed using descriptive statistics and a Chi-square test at a 5% level of significance. Results: Among PCL, CTCL comprised 84% (21/25) and CBCL was 16% (4/25); the most common CTCL was MF at 81% (17/21). Histologically, atypia of dermal infiltrate (100%), epidermotropism (91.7%), basal alignment of lymphocytes (91.7%), clear haloed cells (91.7%), wiry collagen (66.7%), grandiosity sign (50%), eccrine infiltration (66.7%), and follicular infiltration (50%) were significantly associated with early MF. Spongiosis (84.6%), pigment incontinence (84.6%), exocytosis (76.9%), and parakeratosis (76.9%) were significantly associated with inflammatory mimics. There was no significant difference in the downregulation pattern of CD7 (P = 0.206) between early MF and its mimics. The four cases of CBCL in our study were plasmablastic lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and lymphoblastic lymphoma. Conclusion: MF was the most common PCL. Histological parameters showed a significant difference, whereas IHC did not show any significant difference between early MF and its mimics.

Prevalence and Patterns of Latex Glove Allergy among Healthcare Workers in a Tertiary Care Center In South India - A Cross-Sectional Study.

Background: Latex glove allergy and its impact on healthcare workers (HCWs) have been studied in many countries, but the data is scarce from developing countries. Objectives: We wanted to estimate the prevalence and patterns of latex glove allergy among HCWs and to study the factors associated with it. Materials and Methods: We conducted a cross-sectional study among 1088 HCWs of a tertiary care center in South India with the screening questionnaire adopted from "Allergy and Asthma network." Skin prick test, patch test, and serum total immunoglobulin E (IgE) were performed only in consenting symptomatic HCWs. Results: The prevalence of latex glove allergy in our study subjects was 9.1% (99/1088). This includes latex protein allergy and contact dermatitis to rubber glove allergens. The most common manifestation of latex glove allergy was irritant contact dermatitis observed in 68 HCWs (68.6%). Other presentations were allergic rhinitis (40.4%), allergic contact dermatitis (17.1%), contact urticaria (11.1%), allergic conjunctivitis (6.06%), and asthma (3.03%). The risk factors associated with latex glove allergy in our study were atopy (OR = 20.51), working in both ward and operation theater (OR = 26.6), auxiliary staff (OR = 4.75), and more than ten years of hospital work experience (OR = 3.85). Conclusion: Our study reported a high prevalence of latex glove allergy. With irritant contact dermatitis being the most common manifestation in our study, HCWs at risk shall be educated on the appropriate use of gloves and hand moisturizer to prevent occupational irritant contact dermatitis (ICD). We recommend further research to address the gaps in our knowledge around latex allergy in a healthcare setting.

Is Patch Test Necessary in Children to Solve the Clinical Conundrum of Foot Eczema.

BACKGROUND: Foot eczema in children is a commonly encountered condition but is associated with diverse etiology, thereby posing a diagnostic challenge. These include atopic eczema, juvenile plantar dermatoses, irritant contact dermatitis, and allergic contact dermatitis. Because of the diverse etiology, it is often difficult to distinguish between the conditions clinically, thereby warranting patch testing for the correct diagnosis. OBJECTIVES: The study was conducted to determine the frequency of positive patch tests among children with foot eczema and to compare them with children with and without atopy. METHODS: This was a prospective observational study done on 86 children aged 4 to 17 years presenting with foot eczema in whom patch testing was done using Indian standard series and footwear series and patients' own footwear. RESULTS: The clinical diagnosis of foot eczema in our study was allergic contact dermatitis (37%), followed by atopic eczema (30%), juvenile plantar dermatoses (17%), and lichen simplex chronicus (15%). Patch test positivity was present in 36% of the cases with clinical relevance in 65% of the cases. The common allergens were rubber allergens and disperse dyes. Of the children who were patch tested, highest patch test positivity rates were seen in allergic contact dermatitis (50%) and juvenile plantar dermatoses (53%). No significant differences were observed with regard to patch test positivity or relevance between children with and without atopy. CONCLUSIONS: The diagnosis of foot eczema in children cannot be made on clinical grounds alone, and patch testing should be recommended in children with any morphological pattern of foot eczema irrespective of presence or absence of atopy, especially in those with long-standing and recalcitrant disease with frequent exacerbations.

Therapeutic outcome of diphencyprone and its correlation with serum cytokine profile in alopecia areata.

INTRODUCTION: Diphencyprone (DPCP) is considered as the first line of management in severe and extensive alopecia areata. The present study aims to evaluate the effectiveness of DPCP in alopecia areata and identify various prognostic factors and biomarkers associated with clinical response. MATERIALS AND METHODS: The study included participants with patchy and extensive alopecia areata (>30% scalp hair loss) treated with DPCP. Participants with Macdonald Hull and Norris grade 3 and 4 at the end of 6 months were considered as responders. We performed cytokine analysis prior and post-therapy. The protocol was registered with CTRI (REF/2017/09/015424). RESULTS: The response rate was 54.5%. Longer disease duration, nail involvement, and high severity of alopecia tool (SALT) scores were associated with non-response. There was no significant difference in the cytokine levels among responders and non-responders before therapy. Among the responders, we found a significant decrease in IFN-γ, IL-17A, IL-9, TGF-ß, and IL-13 except for IL-4, which significantly increased whereas, among the non-responders, only IL-17A and IL-13 levels have reduced considerably. DISCUSSION: Diphencyprone reduced the level of Th1, Th17, and Th9 cytokines and increased the level of Th2 cytokines (IL-4) in the present study, which induced remission and promoted hair regrowth.

Evaluation of cytokine gene expression in psoriasis.

INTRODUCTION: Psoriasis is a chronic inflammatory disease affecting the skin with an unclear etiological significance. AIM: In this study, we determined the mRNA expression and circulating levels of T helper (Th)/T regulatory (Treg) cytokines in psoriasis and analyzed their association with disease severity and treatment response. MATERIAL AND METHODS: 189 psoriasis patients and 189 controls were recruited. Circulating Th/Treg cytokines (IL-12, IFN-γ, IL-17, IL-23, TGF-ß and IL-4) were measured at baseline and at follow-up after 12 weeks of methotrexate treatment by ELISA and their relative mRNA expression at baseline was estimated by quantitative PCR. RESULTS: We observed increased levels of Th1/Th17 cytokines (IFN-γ, IL-17, IL-12 and IL-23) and a decrease in levels of Th2/Treg cytokines (IL-4 and TGF-ß) in psoriasis patients at baseline, as compared to controls. Further, we observed that there was a significant decrease in Th1/Th17 cytokines, whilst Th2/Treg cytokine levels were significantly increased on follow-up after treatment with systemic metho trexate, as compared to pre-treatment levels. Our results were further confirmed by the significantly higher mRNA expression of Th1/Th17 cytokine genes and significantly lower mRNA expression of Th2/Treg cytokine genes in patients with psoriasis, as compared to controls. A significant positive correlation of Th1/Th17 cytokines was observed with disease severity in cases, whilst Th2/Treg cytokines correlated negatively with disease severity. CONCLUSIONS: Our results show that increased Th1/Th17 cytokines and decreased Th2/Treg cytokines, both at the circulatory and gene expression level, play an important role in the immunopathogenesis and severity of psoriasis.

Is vitiligo associated with systemic aquaporin-3 deficiency?

INTRODUCTION: Recent studies on pathomechanisms of vitiligo have focused on the abnormality of keratinocytes that affect the melanocytes. Aquaporin-3 (AQP3) was implicated as a mechanism for keratinocyte apoptosis owing to the relationship between the PI3K/AKT pathway and the E-cadherin-catenin complex. AIM: Based on this evidence, we undertook a cross-sectional study to assess the skin and blood AQP-3 levels in patients with non-segmental vitiligo in comparison to controls and to correlate these levels with malondialdehyde (MDA) levels and total antioxidant status (TAS) in the skin and blood of patients with non-segmental vitiligo and also with their disease activity. MATERIAL AND METHODS: Thirty-six patients with non-segmental vitiligo and 36 controls were included in this study. AQP3, TAS and MDA levels were assayed both in skin as well as in circulation. RESULTS: We observed that skin and plasma aquaporin and TAS were lowered and MDA levels were increased in patients with non-segmental vitiligo as compared to controls. There was a significant negative correlation of skin and plasma aquaporin levels with disease activity. We also observed the local and systemic AQP3 deficiency to correlate with the local and systemic oxidative stress in vitiligo. CONCLUSIONS: Our results demonstrate a systemic and local AQP3 deficiency in vitiligo correlating with the disease severity and oxidative stress which might have therapeutic implications.

A Hospital Based Cross Sectional Study of Midline Cutaneous Lesions in Neonates and its Association with Spinal Dysraphism Detected Using Ultrasound.

BACKGROUND: Spinal dysraphism occurs due to incomplete fusion of the midline mesenchymal, bony, or neural elements of the spine. The defects in the spinal cord can be associated with skin lesion since both have same embryonic origin. AIMS AND OBJECTIVES: This study was conducted to determine the association of midline and paramedian cutaneous lesions with spinal dysraphism by using spinal ultrasonography. MATERIALS AND METHODS: Two thousand apparently healthy neonates were screened in the postnatal ward of a tertiary care center in South India. Those neonates with cutaneous lesions in the midline and paramedian region were screened for evidence of spinal dysraphism by using spinal ultrasonography. RESULTS: Among 2000 neonates, 120 (6%) had at least one cutaneous lesion, of which 114 (5.7%) were in the midline and 6 (0.3%) were on the paramedian region of dorsal and ventral aspect of the body. Among these neonates, two cases had more than one skin lesions. The most common cutaneous lesion observed was typical dimple (82, 68%) followed by hypertrichosis (12, 10%). Ultrasonography revealed spinal anomaly in six (5%) of them. The cutaneous lesions associated with spinal dysraphism were obvious midline swelling, dermal sinus, and multiple skin lesions. CONCLUSION: Congenital midline and paramedian skin lesions may be the marker of spinal dysraphism. In the presence of such cutaneous lesions, only 5% of them had associated spinal anomaly in our study.

Assessment of Patients with Periorbital Melanosis for Hyperinsulinemia and Insulin Resistance.

BACKGROUND: Periorbital melanosis (PM) is one of the most common dermatological condition seen in routine practice. Several cutaneous markers such as acanthosis nigricans have been associated with insulin resistance (IR). However, the association of PM with IR needs to be substantiated. OBJECTIVE: The objective of the study is to evaluate the association of circulating adipokines and IR with PM. MATERIALS AND METHODS: In this cross-sectional study, we recruited 100 patients with PM and 100 age- and gender-matched healthy controls. The serum levels of leptin, adiponectin, fasting glucose, fasting insulin, insulin-like growth factor-1 (IGF-1), homeostatic model assessment of insulin resistance (HOMA-IR), and leptin: adiponectin ratio (L/A ratio) were assayed. RESULTS: The serum levels of leptin, fasting glucose, fasting insulin, HOMA-IR, L/A ratio were significantly higher in patients with PM as compared to controls. The serum levels of adiponectin were significantly lower in cases as compared to controls. On multivariate regression analysis, leptin, adiponectin, and HOMA-IR were found to be significant, even after adjusting for BMI, blood pressure and LDL and HDL cholesterol. CONCLUSION: Our findings suggest that patients with PM have hyperinsulinemia, IR, and elevated L/A ratio. PM as a marker of IR in adults may help in identifying patients early and thus aid in the early prevention and management of the disease.

Research Funding-Why, When, and How?

Research funding is defined as a grant obtained for conducting scientific research generally through a competitive process. To apply for grants and securing research funding is an essential part of conducting research. In this article, we will discuss why should one apply for research grants, what are the avenues for getting research grants, and how to go about it in a step-wise manner. We will also discuss how to write research grants and what to be done after funding is received.

Prevalence and speciation of non-tuberculous mycobacteria among pulmonary and extrapulmonary tuberculosis suspects in South India.

BACKGROUND AND OBJECTIVES: Non tuberculous mycobacteria (NTM) is an emerging opportunistic pathogen increasing globally and indistinguishable from tuberculosis (TB), which remains a challenge particularly in developing countries. This study aimed to identify the prevalence and diversity of NTM among both pulmonary TB (PTB) and extrpulmonary TB (EPTB) clinical isolates from south India. METHODOLOGY: A total of 7633 specimens from TB suspects (PTB, n = 4327 and EPTB, n = 3306) were collected during the study period (July 2018-March 2020) in a tertiary care hospital. The study specimens were subjected to Ziehl Neelsen (ZN) staining and Auramine phenol (AP) staining followed by Lowenstein-Jensen (LJ) and mycobacteria growth indicator tube (MGIT) culture. The MPT64 immunochromatographic test (ICT) was performed among mycobacterial cultures and ICT negative isolates were subjected to Line Probe Assay (LPA). In addition, 53 (PTB, 48 and EPTB, 5) NTM MGIT positive cultures were collected from Intermediate Reference Laboratory (IRL), Puducherry and subjected to LPA for speciation. RESULTS: Of the 7633 TB suspects, 0.6% were diagnosed as NTM diseases and 5.5% with Mycobacterium tuberculosis (MTBC). NTM infection was observed among 0.7% (31/4327) of PTB and 0.4% (14/3306) of EPTB. MTBC was detected among 6.1% (264/4327) of PTB and 4.6% (153/3306) of EPTB. Among 98 NTM cultures, 80.6% of isolates were recovered from PTB and 19.4% from EPTB specimens. Among pulmonary specimens, Mycobacterium intracellulare (26.6%), Mycobacterium abscessus (17.7%) and Mycobacterium kansasii (12.7%) were the most frequently detected species, while Mycobacterium intracellulare (21.1%), Mycobacterium scrofulaceum (15.8%) and Mycobacterium fortuitum (10.5%) were common in extrapulmonary specimens. CONCLUSION: The frequency of NTM infection among TB suspects was low at a South Indian tertiary care hospital. The most predominant NTM species isolated from both pulmonary and extrapulmonary specimens was M. intracellulare.