Unveiling the TGF- ß1 paradox: Significant implication of TGF- ß1 promoter variants and its mRNA and protein expression in atopic dermatitis.

BACKGROUND: Atopic Dermatitis (AD) is a chronic inflammatory skin disorder with evidence of lichenification in later stages. There is mounting evidence supporting the role of TGF- ß1 in mediating inflammation as well as subsequent tissue remodeling, often resulting in fibrosis. Given the role of genetic variants in the differential expression of TGF-ß1 in various diseases, this study seeks to ascertain the role of TGF-ß1 promoter variants (rs1800469 and rs1800468) in AD susceptibility, as well as their association with TGF- ß1 mRNA expression, TGF- ß1 serum levels and skin prick test positivity in Atopic Dermatitis patients. METHODS: An aggregate of 246 subjects including 134 AD cases and 112 matched healthy controls were genotyped for TGF-ß1 promoter polymorphisms by PCR-RFLP. TGF- ß1 mRNA was quantified by quantitative Real-Time PCR (qRT-PCR), Vitamin-D levels by chemiluminescence, and serum TGF- ß1, and total IgE levels were determined by ELISA. In-vivo allergy testing was performed for the evaluation of allergic reactions to house dust mites and food allergens. RESULTS: A higher frequency of TT genotypes of rs1800469 (OR = 7.7, p = 0.0001) and GA+AA genotypes of rs1800468 (OR-4.4, p < 0.0001) were observed in AD cases than those in controls. Haplotype analysis demonstrated that TG haplotype carriers had an increased risk of AD (p = 0.013). Quantitative analysis revealed a significant upregulation of both mRNA (p = 0.0002) and serum levels (p < 0.0001) of TGF- ß1 with a substantial positive correlation between them (Correlation coefficient=0.504; p = 0.01). Moreover, serum TGF-ß1 levels were associated with quality of life (p = 0.03), the severity of the disease (p = 0.03), and House dust mite allergy (p = 0.01) whereas TGF-ß1 mRNA levels positively correlated with disease severity(p = 0.02). Stratification analysis revealed that the TT genotype of rs1800469 was associated with higher IgE levels (p = 0.01) and eosinophil percentage(p = 0.007) whereas the AA genotype of rs1800468 correlated with elevated serum IgE levels (p = 0.01). Besides, no significant association of genotypes with mRNA and serum expression of TGF-ß1 was observed. CONCLUSION: Our study indicates that TGF-ß1 promoter SNPs bear a significant risk of AD development. Moreover, upregulation of TGF-ß1 mRNA and serum levels and their association with disease severity, quality of life, and HDM allergy suggests its role as a diagnostic/prognostic biomarker that could help in the development of new therapeutic and prevention strategies.

Management of Pre-malignant and Malignant Non-melanoma Skin Cancers: A Study from a Tertiary Care Hospital of North India.

Introduction: The incidence of non-melanoma skin cancers (NMSCs) is increasing over the last few decades. This necessitates an early diagnosis which is nowadays aided by dermoscopy. Once diagnosed early, the treatment armamentarium is diverse and includes both topical and surgical modalities. Objective: Our aim was to diagnose pre-malignant and malignant NMSCs at an early stage and treat them as per the standard protocol. Materials and Materials: Out of 136 patients of pre-malignant and malignant tumors enrolled, 100 were taken up for treatment. These were then classified into various subtypes on the basis of clinical examination and dermoscopy. The selected patients were subjected to topical treatment or surgical modalities, wide local excision or flap excision, based on the type of tumor and its size. Results: The pre-malignant group included actinic keratoses, Bowen's disease, and keratoacanthoma, whereas the malignant group included undifferentiated squamous cell carcinoma (SCC), differentiated SCC, pigmented basal cell carcinoma (BCC), nodulo-ulcerative BCC, and superficial BCC. Actinic keratoses, superficial BCCs, and five cases of keratoacanthoma were treated with topical therapies with a resolution of 90% in 86.8% cases. All the remaining cases (62 in number) were treated with conventional and flap surgery with 88% and 89.1% clearance rates, respectively, with complications in only 7 patients. Conclusion: A prompt identification of NMSCs can enable selection of the appropriate treatment modality for a specific lesion and thus reduce their associated morbidity and mortality.

Efficacy of Fractional CO2 Laser for Improvement of Limited Mouth Opening in Systemic Sclerosis.

Background: Systemic sclerosis is a multisystem auto-inflammatory disease-causing fibrosis in the skin and internal organs. A frequent complication of systemic sclerosis is the limited mouth opening (LMO), a difficult-to-treat condition with only a few treatment options available. Aims and Objectives: The aim of this study was to evaluate the response of fractional carbon dioxide (CO2) laser resurfacing in LMO associated with systemic sclerosis. Materials and Methods: This was a hospital-based prospective study in which diagnosed cases of systemic sclerosis were taken. Patients who had significant LMO and who gave informed consent were included in the study. Fractional CO2 laser treatment was performed in the perioral area. Patients were assessed at baseline, after three and six sessions, and 3 months after the last session. Assessment was done by measurement of the interincisor distance (IID) using a ruler and calculation of the mouth handicap in systemic sclerosis (MHISS) scale. Results: Improvement in IID occurred 3 months after the first session with a mean gain of +5 mm (range 2-7). At 6 months, a mean gain of +8.5 mm (range 7-10) in IID was observed (P < 0.001). The MHISS score decreased by a mean of 14 (range 11-17) (P < 0.001). All patients showed improvement of mouth opening, which allowed the patients to have better phonation and the patients were able to have proper dental care posttreatment in the form of brushing of teeth and other dental procedures. The adverse effects noted in these patients included erythema that resolved spontaneously or after icing posttreatment. Other adverse effects noted were stinging and burning sensations that were mild and transient. Conclusion: Fractional CO2 laser forms a safe, effective, and well-tolerated treatment modality for improvement of LMO in systemic sclerosis. Limitations: The limitations of this study were less number of patients and no long-term follow-up.

Comparative study of the clinico-trichoscopic response to treatment of hirsutism with long pulsed (1064 nm) Nd:YAG laser in idiopathic hirsutism and polycystic ovarian syndrome patients.

Treatment of hirsutism is usually resistant, and from medical management to laser hair reduction, the treatment of hirsutism and its assessment are the most challenging. The aim of the study was to compare the response to treatment by laser hair reduction with long pulsed (1064 nm) Nd:YAG laser in patients of idiopathic hirsutism and polycystic ovarian syndrome (PCOS) by clinical and trichoscopic assessment. A hospital-based comparative, observational prospective study was carried out on female patients with hirsutism over a period of 18 months with two groups of participants: fifty women with idiopathic hirsutism (group A) and fifty with PCOS (group B). Laser hair reduction was done with long pulsed (1064 nm) Nd:YAG laser in both groups up to six sessions, 4 weeks apart and followed for 3 months post last laser session. After the sixth session of laser hair reduction, excellent response (> 75% reduction) from baseline was seen in 70% of patients in group A and in 54% of patients in group B. After 3 months of follow-up of the last laser session, it was found that the results persisted in patients with idiopathic cause than in those due to PCOS, seen both clinically and trichoscopically with decrease in hair shaft thickness, hair shaft colour, terminal vs. vellus hair ratio and hair density per cm2. Hirsutism due to idiopathic cause responds better to laser hair reduction with long pulsed (1064 nm) Nd:YAG laser than that due to PCOS, due to underlying hormonal imbalance in the latter group. Follow-up of only up to 3 months after last laser session was done and tricoscan was not done.

Assessment, reliability, and validity of trichoscopy in the evaluation of alopecia in women.

BACKGROUND: Alopecia in women is generally difficult to diagnose clinically. Trichoscopy may help make the correct diagnosis in doubtful cases. OBJECTIVE: The aims of the study were to assess the trichoscopic features of different types of alopecia in women, the reliability of trichoscopy vis-à-vis clinical findings, and the validity of trichoscopy in cases with a doubtful clinical diagnosis. METHODS: A hospital-based observational, cross-sectional study was carried out on female patients with alopecia. A trichoscopic diagnosis was made and correlated with a clinical diagnosis. The validity of trichoscopy in doubtful cases was evaluated by reporting the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic value. RESULTS: On trichoscopy, increased hair diameter diversity > 20%, single-hair follicular unit, vellus hair, peripilar sign, and focal atrichia were commonly seen in female pattern hair loss. In telogen effluvium, there was a scarceness of specific findings. In cicatricial alopecias, loss of follicular ostia, erythema, white macules, blue-gray dots, white dots, tufted hair, and keratotic follicular plugging were observed. A good agreement between trichoscopy and clinical diagnosis was found (Cohen's Kappa = 0.824; 95% confidence interval, 0.756-0.892). The validity of trichoscopy in doubtful cases was evaluated using the validity parameters, which were high in all alopecias. LIMITATIONS: Histopathology testing was not done in all patients. CONCLUSION: Trichoscopy helped reach a definitive diagnosis in patients in whom the clinical diagnosis was doubtful. Thus, trichoscopy is a sensitive and specific investigation that can be valuable in women with alopecia.

Clinical Pattern and Patch Test Profile of Hand Eczema in Hospital Employees in a Tertiary Care Hospital of North India.

INTRODUCTION: Health care workers form an important occupational group with a high risk of hand eczema. All health care professionals are exposed to a variety of allergens and irritants which can cause hand dermatitis, resulting in significant morbidity. AIMS AND OBJECTIVES: To assess the clinical profile of hand eczema in hospital employees, to perform patch test in relevant cases and to find out the most common sensitizers in them. MATERIALS AND METHODS: This was a cross-sectional, hospital-based study in which the staff was screened for features of hand eczema and patch testing was done in the suspected cases of allergic contact dermatitis. RESULTS: Out of 340 employees screened, 46 employees (13.5%) suffered from hand eczema. The most common type was wear and tear dermatitis accounting for 17 (36.9%) cases, followed by discoid eczema, pompholyx, focal palmar peeling, finger-tip eczema, hyperkeratotic eczema, ring eczema, and unspecified types. Patch testing was positive in 15 (32.6%) cases. The most common allergen was paraphenylene diamine, followed by fragrance mix, nitrofurazone, mercaptobenzothiazole, potassium bichromate, black rubber mix, and thiuram mix. A statistically significant association (0.001) was found with an underlying history of atopy. CONCLUSION: Hand eczema is a commonly encountered dermatological complaint in many hospital employees. Proper counseling, work, up, patch testing, and treatment can mitigate the symptoms in such employees.

Cutaneous Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Clinical Study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, affecting 5-10% of reproductive-aged women. The dermatologic manifestations of hyperandrogenism, chiefly hirsutism, acne vulgaris, androgenic alopecia, and acanthosis nigricans, are among the cardinal manifestations of PCOS. AIM: To study the incidence and prevalence of various cutaneous manifestations in patients with PCOS and to correlate these skin manifestations with hormonal changes. SETTINGS AND DESIGN: This study was conducted at a dermatology centre over a period of 1 year from November 2012 to 2013. MATERIALS AND METHODS: The present study included 100 women diagnosed to have PCOS. Hormonal analysis as well as radiological assessment was done in all the cases. Cutaneous manifestations were ascertained and inferences were drawn. STATISTICAL ANALYSIS: Statistical analysis was carried out by the Chi-square test and independent samples t-test. Statistical significance was determined at a level of P < 0.05. RESULTS: In our study, the prevalence of hirsutism, acne, female pattern hair loss, acanthosis nigricans, seborrhea, striae and acrochordons was 78%, 48%, 31%, 30%, 29%, 13%, and 9%, respectively. CONCLUSION: Dermatologic manifestations of PCOS play a significant role in making the diagnosis and constitute a substantial portion of the symptoms experienced by women with this syndrome.

Hirsutism in Kashmir: an etiological study.

BACKGROUND: Hirsutism refers to the presence of terminal hairs at the body sites under androgenic control. Various factors, including genetic makeup and hormonal status, influence the rate and pattern of hair growth at these sites. PURPOSE: To study the pattern of hirsutism in Kashmir. MATERIALS AND METHODS: Thirty five consecutive patients of hirsutism were included in the study. After detailed history taking, physical examination and relevant investigations, scoring of hirsutism was done using the Ferriman Gallwey (FG) scoring system. FINDINGS: The FG score ranged from 10-34. Twenty patients had associated menstrual abnormalities. Polycystic ovarian syndrome (PCOS) was diagnosed in four patients, hypothyroidism in two and congenital adrenal hyperplasia (CAH) in one. The rest of the patients had idiopathic hirsutism. CONCLUSION: Idiopathic hirsutism was the most common category, whilst PCOS, hypothyroidism and CAH were also seen.

Cardiac involvement in patients of systemic sclerosis.

BACKGROUND: Systemic sclerosis is a multi-systemic autoimmune disorder. Cardiac involvement by the disease, although not included in the diagnostic criteria, may be seen either clinically, histologically or may be revealed by various investigative modalities. PURPOSE: To see the profile of cardiac involvement in patients of systemic sclerosis. MATERIALS AND METHODS: Forty-seven patients of systemic sclerosis were included in the study. After taking a complete history and doing a detailed physical examination, the patients were submitted to electrocardiogram ECG (all leads), echocardiography and x-ray chest. Furst's organ indices scoring system for cardiac involvement was followed. FINDINGS: Forty-seven patients of systemic sclerosis were included in the study. Five females gave a history of palpitations. A loud pulmonic heart sound was heard in 1. Arrhythmias were observed in 5 patients. Significantly, echocardiography revealed valvular involvement in 5 patients. Left ventricular hypertrophy was seen in 2 patients. CONCLUSIONS: In our patients, cardiac involvement was rare. In contrast to other studies, valvular involvement was a prominent feature. LIMITATIONS: Complete evaluation for arrhythmias with 24-h Holter monitor was not used.

Increased incidence of tuberculosis in patients of systemic sclerosis on dexamethasone pulse therapy: a short communication from Kashmir.

BACKGROUND: Systemic sclerosis is a multi-systemic autoimmune disorder affecting predominantly the skin, lungs, gut and kidneys. PURPOSE: To report the increased incidence of tuberculosis in patients of systemic sclerosis on dexamethasone pulse (DP) therapy. METHODS: Forty-seven patients of systemic sclerosis were included in the study. After taking a complete history and doing a detailed physical examination, the patients were submitted to a battery of investigations including complete hemogram (CBC) with erythrocyte sedimentation rate (ESR(F)), Chest X-ray CXR (PA view) Mantoux test and urine analysis. CBC, ESR and urine examination was done monthly and CXR were repeated six-monthly. FINDINGS: Seven patients on DP therapy developed genitourinary tuberculosis. Four had pulmonary tuberculosis. One patient developed tubercular lymphadenitis, one patient succumbed to miliary tuberculosis. CONCLUSION: There is an increased incidence of tuberculosis amongst patients of systemic sclerosis on DP therapy. LIMITATION OF THE STUDY: There was no control group of systemic sclerosis patients not on DP therapy to rule out the confounding effect of the disease per se predisposing to tuberculosis as all our patients as a matter of routine were put on steroid pulse. Also, the increased incidence of tuberculosis was detected incidentally while on monthly follow-up.