Insulin resistance in various grades of acanthosis nigricans.

INTRODUCTION: Insulin resistance (IR) is a metabolism disorder that contributes to the pathophysiology of acanthosis nigricans (AN). In turn, AN is a self-determining risk factor and cutaneous marker of IR. However, conflicting evidence makes the AN-IR relationship debatable and open to exploration. If established, it could provide opportunities for early diagnosis and management of IR before the onset of diabetes mellitus and its complications by screening AN patients. This study investigates the prevalence of IR among AN patients and evaluates the association between IR and AN severity. METHODS: Eighty-seven patients, 18 to 60 years old, with untreated AN and absence of diabetes mellitus, underwent detailed history, systemic, and cutaneous examinations, as well as measurement of their body mass index (BMI), waist and hip circumference and their ratio (WHR), fasting blood glucose (FBG) and lipid profile, fasting serum insulin levels, and quantitative insulin-sensitivity check index (QUICKI). Severity of the neck lesions was graded according to Burke et al.'s grading system. RESULTS: AN was noted most commonly in younger age groups with 93.1% of the cases younger than 45. All patients had lesions on the neck, and 63.3% of the cases had multiple site involvement. Nearly 84% of the cases were overweight or obese. AN grades exhibited a significant positive association with BMI (p = 0.002) and WHR (p = 0.016). High IR (< 0.35 QUICKI) was seen in 55 (63.2%) AN patients. IR, QUICKI, and triglyceride levels showed no significant association with AN severity and the number of AN lesion sites (p > 0.05). LDL levels (p = 0.02) and WHR (p = 0.049) showed a significant positive association with the number of AN lesion sites, but not with AN severity grading (p > 0.05). CONCLUSIONS: IR is present in AN patients, but the association between IR and AN severity is not significant enough to qualify AN as a screening tool for IR.

Efficacy and safety comparison of combination of 0.04% tretinoin microspheres plus 1% clindamycin versus their monotherapy in patients with acne vulgaris: a phase 3, randomized, double-blind study.

BACKGROUND AND OBJECTIVES: There is an unmet need for topical treatments with good tolerability in management of acne vulgaris. The present study aimed to evaluate efficacy and safety of a novel tretinoin (microsphere, 0.04%) formulation in combination with clindamycin (1%) gel for treatment of acne vulgaris. MATERIALS AND METHODS: This phase 3 randomized, double-blind study included patients with moderate-to-severe acne. Patients were treated with tretinoin (microsphere, 0.04%) + clindamycin (1%) or one of the monotherapies (tretinoin, 0.025%; clindamycin, 1%). Key endpoints included percent change in lesion counts, and improvement in Investigator's Static Global Assessment (ISGA) score. RESULTS: 750 patients were randomized (combination, n = 300; tretinoin and clindamycin, each n = 150). At week 12, reductions in inflammatory (77%), non-inflammatory (71%) and total lesions (73%) were significantly greater with combination treatment versus either monotherapy (p < .03). Proportion of patients rated 'clear' or 'almost clear' with ≥2-grade ISGA improvement was higher with combination (46%) versus monotherapies (p < .02). Adverse events occurred in 20 patients, most were mild-moderate; no deaths or serious adverse events were reported. The discontinuation rates due to adverse events with combination therapy were low (≤1%). CONCLUSION: The once-daily, microsphere-based formulation was generally tolerable with a positive impact on therapeutic outcomes and patients' compliance. CLINICALTRIAL REGISTRATION NO.: CTRI/2014/08/004830.

Delving Deeper into Dermal and Transdermal Drug Delivery: Factors and Mechanisms Associated with Nanocarrier-mediated Strategies.

BACKGROUND: Advances in material science and particle engineering have led to the development of a rapidly growing number of nanoparticulate carriers for drug and gene delivery. These carriers are increasingly being investigated in dermal and transdermal routes of drug administration. OBJECTIVE: To critically examine and summarize the primary factors and mechanisms involved in nanocarriermediated dermal and transdermal delivery of drugs. METHOD: Thorough literature search was undertaken, spanning the early development of nanocarrier-mediated dermal and transdermal drug delivery approaches, to the current state of the art, using online search tools. RESULTS: Physicochemical, formulation, experimental and morphological factors, such as, material of construction or type of nanoparticle (NP), surface chemistry, particle size, particle shape, surface charge, dispersion medium, duration of exposure of skin to NPs, combination of NPs with physical agents, and aspects related to skin were identified and discussed. CONCLUSION: The key factors and mechanisms which influence NPs-skin interactions in dermal and transdermal drug delivery are discussed in this article in-line with the current advances in the field.

Role of direct immunofluorescence in dermatological disorders.

BACKGROUND: Direct immunofluorescence (DIF) test for tissue-bound autoantibodies, has been found to be of value in the diagnosis of several dermatological disorders. The location and pattern of deposition of immunoreactants helps in classifying various immune-mediated diseases. AIMS AND OBJECTIVES: The aim of this study was to analyze the concordance between the clinical, histopathological and DIF diagnosis in bullous and nonbullous lesions of the skin, and thus determine the impact of immunofluorescence on diagnosis. MATERIALS AND METHODS: A total of 215 skin biopsies performed in suspected immune-mediated vesiculobullous disease, vasculitis or dermatosis, were studied. Histopathological examination was done along with DIF study for deposits of immunoglobulin G(IgG), IgA, IgM, and C3. RESULTS: Direct immunofluorescence was positive in 103/215 cases. There was very good concordance between the clinical, histological and DIF results (observed agreement = 93.4%, κ =0.90, with 95% confidence interval = 0.86-0.94). The overall sensitivity of DIF in immune-mediated skin disorders was 98.0%. DIF was positive in 52/53 cases (98.1%) in the pemphigus group and 24/25 (96.0%) bullous pemphigoid cases. None of the clinically suspected cases of dermatitis herpetiformis showed DIF positivity. A positive lupus band test was seen in 9/9 (100%) cases of lupus erythematosus. DIF was positive in 10/10 (100%) clinically suspected cases of Henoch-Schönlein purpura. In 110 cases, negative DIF results helped to rule out immune-mediated vesiculobullous disorders, lupus erythematosus and vasculitis, and the final diagnosis was made on the basis of the clinical features and/or histopathology. CONCLUSION: Direct immunofluorescence is a useful supplement for the accurate diagnosis of immune-mediated dermatological disorders, and helps to classify various autoimmune bullous disorders. When the clinical features/histopathology are inconclusive, the diagnosis often can be made on the basis of the DIF findings alone. A combination of the clinical features, histopathology and DIF usually gives the best results.

Efficacy and safety of itolizumab, a novel anti-CD6 monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, phase-III study.

BACKGROUND: Itolizumab, a humanized monoclonal antibody to CD6, is a novel therapeutic agent evaluated in chronic plaque psoriasis. OBJECTIVE: We sought to assess the safety and efficacy of itolizumab in moderate to severe chronic plaque psoriasis. METHODS: A total of 225 patients were randomized (2:2:1) to 2 different itolizumab arms (A or B; A = 4-week loading dose of 0.4 mg/kg/wk followed by 1.6 mg/kg every 2 weeks; B = 1.6/mg every 2 weeks) or placebo. At week 12, the placebo arm was switched to 1.6 mg/kg itolizumab every 2 weeks. The primary end point was the proportion of patients with at least 75% improvement in Psoriasis Area and Severity Index score at week 12. RESULTS: At week 12, 27.0% in arm A (P = .0172 vs placebo), 36.4% in B (P = .0043 vs placebo), and 2.3% in the placebo arm had at least 75% improvement in Psoriasis Area and Severity Index score. At week 28, the proportion with at least 75% improvement in Psoriasis Area and Severity Index score was comparable: 46.1%, 45.5%, and 41.9% for A, B, and placebo, respectively. In weeks 1 to 12, the incidence of all adverse events was comparable across arms (A, 43%; B, 38%; placebo, 47%) and the incidence of infections was not greater than placebo (11.1%, 8.9%, and 18.6% for A, B, and placebo). LIMITATIONS: No active comparator is a limitation. CONCLUSIONS: Itolizumab is an effective and well-tolerated novel biological therapy in moderate to severe psoriasis.

Acute-Onset of Multiple Painful Nodules over Forearms and Back.

Angiolipomas are benign encapsulated, well circumscribed tumours, which show excessive degree of vascular proliferation. Clinically, lesions present as sudden onset of multiple painful nodules. Pain usually does not respond to analgesics. We herein, report a case of a young male, presenting with multiple painful nodules over the forearm and back, which on histopathological examination revealed, encapsulated benign tumour, comprising of proliferated small-caliber vascular channels with microthrombi and variable amounts of mature adipose tissue. Pain subsided on treatment with intralesional steroids and the nodules were excised through a narrow-hole extrusion technique.

Clinico histopathological correlation in leprosy.

INTRODUCTION: Leprosy is a chronic infectious disease caused by M. leprae, which presents in different clinico-pathological forms, depending upon the immune status of the host. Clinical classification gives recognition only to gross appearances of the lesions, whereas the parameters used for the histopathological classification are well defined, precise, and also take into account the immunological features. RESULTS: Of the 182 suspected cases of leprosy which were biopsied, the clinical diagnosis was TT in 32 (17.5%), BT in 70 (38.4%), BB in 5(2.7%), BL in 24 (13.1%), LL in 23 (12.6%), and indeterminate in 28 (15.3%) cases. Of the 182 cases, which were biopsied, only 136 (74.7%) showed histological features consistent with any one type of leprosy. The overall clinicohistological correlation was 74.7 percent. A comparison of the histopathological pattern with that of clinical pattern revealed that the maximum correlation was seen with LL (84.2%), followed by BL (73.3%), BT (64.1%), TT (56%), BB, and IL (50%). CONCLUSION: Because there is some degree of overlap in different types of leprosy, especially the unstable forms, the correlation can be made more accurate by combining clinical and histopathological features.

Efficacy and safety of topical halometasone in eczematous dermatoses in Indian population: an open label, noncomparative study.

BACKGROUND: Topical steroids remain the mainstay of treatment in eczema, an inflammatory skin reaction characterized by pruritus, redness, scaling, and clustered oozing papulovesicles. Halometasone is a new potent corticosteroid approved in the Indian market for topical application in the treatment of dermatitis. AIMS: To evaluate the efficacy and safety of halometasone in the treatment of acute or chronic noninfected eczematous dermatosis in Indian population. MATERIALS AND METHODS: A prospective, open, multicentric, phase 3, noncomparative clinical trial conducted at outpatient departments of seven centres. Two hundred endogenous eczema patients meeting study criteria were enrolled. Halometasone 0.05% cream was applied twice daily for 30 days in chronic and 20 days in acute eczema patients. Calculation of eczema area and severity index, and assessment of investigator's global assessment of severity of eczema and severity of pruritus score were done at each visit and compared with baseline. All adverse events (AE) were captured and documented. Laboratory investigations including haematological tests, urinalysis, renal and liver function tests were performed at baseline and at end of treatment. RESULTS: Of the 200 patients enrolled, 180 were chronic and 20 were acute eczema patients. It was found that there was a significant (P<0.001) improvement in all efficacy parameters compared with baseline. The treatment was shown to be successful in 91% patients. AE were reported in 30 patients and there was no serious AE reported. There was no clinically significant difference in laboratory investigations with treatment. CONCLUSIONS: Halometasone was shown to be safe and very effective in Indian patients with acute and chronic eczema and the drug was well tolerated.

An unusual presentation of primary cutaneous nocardiosis at a rare site: succesful treatment with a modified Welsh regimen.

INTRODUCTION: Primary cutaneous nocardiosis can present in various forms. Clinically, it can present as acute infection (abscess or cellulitis), mycetoma, or sporotrichoid infection. Mycetoma over the back is rare. CASE REPORT: We herein describe a case of primary cutaneous nocardiosis presenting as a mycetoma, caused by Nocardia brasiliensis. The patient had extensive lesions over the back, which can be attributed to the fact that the patient, being an agriculturist, has been exposed to recurrent trauma while carrying firewood and soiled sacks. He responded well to a modified Welsh regimen. Initially, within 2 cycles, the patient showed dramatic improvement clinically, wherein the sinuses, granulation tissue, and induration were no longer apparent. However, the patient showed a small discharging sinus at the end of 3rd pulse, so a total of 6 cycles were given. An additional 2 months of maintenance phase treatment with cotrimoxazole and rifampicin were given. On follow-up, the patient showed no recurrence at 6 months. CONCLUSION: We report a case of primary cutaneous nocardiosis presenting as a mycetoma on the back. Enlisting the help of a microbiologist allowed us to isolate the causative organism. Early recognition and prompt treatment prevents unwarranted surgical debridement and complications.

Gorlin syndrome or basal cell nevus syndrome (BCNS): A case report.

Gorlin syndrome, also known as Basal Cell Nevus Syndrome (BCNS), is a rare autosomal dominant disorder with complete penetrance and variable expressivity. This syndrome is characterized by developmental anomalies, such as odentogenic keratocysts of the mandible and postnatal tumors, especially multiple basal cell carcinomas (BCCs). The prevalence of this syndrome is variously estimated to be 1 in 60,000 to 1 in 120,000 persons. Mutation in a tumor suppressor, the PTCH1 gene residing on long arm of Ch 9, is responsible for the development of many postnatal tumors. Patients with Gorlin syndrome show multiple abnormalities, none of which is unique to this condition. Our case had almost all the features of this rare syndrome.

Kyrle's Disease with Diabetes Meuxfus and Chronic Renal Failure.

A 54 year old male had Kyrle's disease manifestion as multiple, discrete papules with cone-shaped keratotic plugs. The lesions were severly pruritic and located symmetrically on the extensor aspects of the limbs and the trunk. Histopatholggical examination confirmed the diagnosis. The patient was known to be diabetic for 18 years and developed chronic renal failure 4 months prior to the onset of the skin lesions. Treatment with 6% salicylic acid topically did not produce any improvement of the lesions.

Dapsone Induced Methaemoglobinemia.

A 33 old I female developed methaemoglobinemia manifesting as cyanosis fatigue, malaise and headache 3 weeks after being put on l00 mg of dapsone daily for borderline - tuberculoid leprosy. Similar manifestations develope4 in a 15 year old boy 9 days after he, was put on 50 mg of dapsone daily for suspected indeterminate leprosy. withdrawal of dapsone resulted in reversal of methaemoglobinemia.

Xeroderma Pigmentosum with Mailgnant Melanoma and Squamous Cell Carcinoma.

A 25 year old female with xeroderma pigmentosum since 3 ye4ws of age, developed a nodular growth on the left ala of the nose since 4 months. Histopathology revealed m ant melanoma of the nodular variety. A squamous cell carcinoma was also detected at the fimbus in the right eye. There were no metastases.