Laxmisha Chandrashekar

Effect of treatment with methotrexate and coal tar on adipokine levels and indices of insulin resistance and sensitivity in patients with psoriasis vulgaris.

Recent studies have implicated adipokines in the pathogenesis of the immune‐mediated inflammatory disease, psoriasis and its associated comorbidities. Hence, we undertook to study adipokine levels and indices of insulin resistance and sensitivity in patients with psoriasis vulgaris, in comparison with controls and their association with disease severity and response to therapy.

Platelet activation in chronic urticaria and its correlation with disease severity

Abstract Chronic urticaria (CU) is characterized by the occurrence of wheals lasting for more than 6 weeks. The role of platelet activation in the pathophysiology of this condition has not been clearly studied. We undertook a cross-sectional study among 45 patients with CU and 45 age- and gender-matched healthy controls. The severity of the disease was assessed using the urticaria severity score. The autologous plasma skin test (APST) was done in all cases of CU. The platelet count and indices were estimated by an automated haematological laser optical analyzer. Platelet aggregation and soluble P-selectin levels were estimated in all study participants. It was observed that there was a significantly higher mean platelet volume (MPV) and platelet distribution width (PDW) in patients with CU when compared to controls. Platelet aggregation and soluble P-selectin levels were significantly higher in patients with CU, as compared to controls. Urticaria severity score correlated positively with platelet aggregability and soluble P-selectin levels. APST-positive patients had significantly higher platelet aggregation and higher soluble P-selectin levels, when compared to the APST-negative patients, indicating more platelet activation in the autoimmune group. There is significant platelet activation in patients with CU, especially in those with autoreactivity.

Platelet oxidative stress and systemic inflammation in chronic spontaneous urticaria.

Abstract Background: Recent studies implicate the role of immune-inflammatory responses in chronic spontaneous urticaria (CSU). Although it is well known that platelets release inflammatory mediators and reactive oxygen species upon activation, their role in CSU is poorly characterized. The present study was designed to evaluate platelet oxidative stress [platelet malondialdehyde (MDA), platelet superoxide dismutase (SOD), platelet glutathione peroxidase (GPx)] and systemic inflammatory markers [plasma Interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP)] in patients with CSU and their association with disease severity. Methods: Forty-five patients with CSU and 45 age- and gender-matched healthy controls were included in the study. Severity grading was completed according to the urticaria severity score (USS). Autologous plasma skin test (APST) was done in all patients with CSU. Platelet MDA, SOD and GPx and inflammatory markers plasma IL-6 and hs-CRP were assayed in all study participants. Results: In patients with CSU, platelet SOD and GPx were significantly lowered, while platelet MDA levels were significantly elevated in comparison to healthy controls. Both IL-6 and hs-CRP were significantly elevated in patients with CSU and correlated with platelet oxidative stress parameters (p<0.05). Platelet MDA, SOD and GPx and inflammatory markers (plasma IL-6 and hs-CRP) showed a significant correlation with USS in patients with CSU. Conclusions: Our results indicate significant systemic inflammation and platelet oxidative stress in patients with CSU.

Is enhanced platelet activation the missing link leading to increased cardiovascular risk in psoriasis

BACKGROUND Psoriasis is an immune mediated inflammatory skin disease associated with systemic inflammation resulting in increased risk for associated cardiovascular co-morbidities. The role of platelet activation in the pathophysiology of this condition has not been clearly studied. We undertook to study the platelet activation markers in psoriasis, as compared to controls and to identify its association with disease severity in psoriasis. METHODS Sixty-two patients with psoriasis and 62 age and gender matched healthy controls were enrolled in this cross-sectional study. The severity of the disease was assessed using the psoriasis area severity index (PASI) scoring. The platelet indices [mean platelet volume (MPV) and platelet distribution width (PDW)] were estimated by an automated haematological laser optical analyzer. Plasma soluble P-selectin and platelet derived microparticle (PDMP) concentrations, serum high sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 concentrations were estimated in all study participants. Platelet aggregation was assessed using adenosine diphosphate (ADP) as aggregating agent. RESULTS We observed that there was significantly higher platelet indices (MPV and PDW) in patients with psoriasis, when compared to controls. Plasma soluble P-selectin concentrations, PDMP and platelet aggregation were significantly elevated in patients with psoriasis, as compared to controls. We also found significantly higher concentrations of hs-CRP and IL-6 in patients with psoriasis, as compared to controls. Platelet activation and systemic inflammation markers correlated positively with PASI, except PDW. We also observed significant positive correlation between platelet activation and systemic inflammation in psoriasis. CONCLUSION Significant platelet activation and systemic inflammation were observed in patients with psoriasis, especially when associated with severe disease. The increased platelet activation might be the missing link between the persistent inflammation and the development of atherosclerotic plaque leading onto cardiovascular co-morbidities seen associated with psoriasis.

25-hydroxy vitamin D and ischaemia-modified albumin levels in psoriasis and their association with disease severity

ABSTRACT Psoriasis is a T-helper-1 (TM)/TM7-mediated chronic inflammatory skin disease, characterised by hyperproliferation of keratinocytes. Psoriasis and cardiovascular disease share similar pathogenic mechanisms such as vascular endothelial cell dysfunction, oxidative stress and metabolic syndrome. 25-hydroxy vitamin D is an immune-regulatory hormone, with the ability to reduce cellular proliferation in psoriasis. Ischaemia-modified albumin (IMA) is a marker of oxidative stress. This study examined 25-hydroxy vitamin D, IMA and high-sensitivity C-reactive protein (hs-CRP) levels in patients with psoriasis, in comparison with healthy controls and their possible association with disease severity. A total of 43 cases of psoriasis and 43 controls were included in this cross-sectional study, and severity grading was performed according to psoriasis area severity index (PASI) scoring. Serum 25-hydroxy vitamin D, IMA and hs-CRP were evaluated in all study subjects. In psoriasis, 25-hydroxy vitamin D showed a significant decline, while hs-CRP and IMA levels were significantly elevated, as compared with controls. Serum 25-hydroxy vitamin D showed a significant negative correlation with PASI score. hs-CRP and IMA showed a significant positive correlation with PASI score. Significant negative correlation was observed between 25-hydroxy vitamin D and hs-CRP; 25-hydroxy vitamin D and IMA levels in psoriasis. The results indicate that psoriasis is associated with significantly lowered 25-hydroxy vitamin D levels, along with increased systemic inflammation and oxidative stress, especially in severe disease. Thus, vitamin D supplementation might reduce systemic inflammation and oxidative stress and help in delaying the pathogenesis of co-morbidities associated with psoriasis.

Psychosocial impact of cicatricial alopecias

Background: Cicatricial alopecias have a significant impact on the psychological status, quality of life, and social interaction of those suffering from it. Till date, limited or no data have been available regarding the psychosocial and quality of life aspects of cicatricial alopecias. Aims: To assess the psychosocial impact of cicatricial alopecias. Materials and Methods: Thirty patients fulfilling the criteria for cicatricial alopecia irrespective of their age and sex were included in the study. Psychosocial assessment was carried out in 23 patients who were capable of responding to the questionnaire, using an adopted and suitably modified version of Womens Androgenetic Alopecia Quality of Life Questionnaire. Results: We observed that 73.9% of our patients with cicatricial alopecias had moderate to severe psychosocial impact due to their hair loss. Patients of younger age group and with inactive disease, suffered from greater psychosocial impact of the disease. Patients with slight hair loss also had considerable psychological distress. The chronicity of disease duration did not seem to reduce the psychosocial impact of the disease. Both married and unmarried patients suffered equally from the psychosocial impact of the disease. Conclusion: The management of cicatricial alopecias needs a holistic approach. In addition to laying an emphasis on early diagnosis aided by clinco-pathological correlation, to prevent irreversible hair loss, the psychosocial impact of the disease should also be taken into consideration and addressed by the treating dermatologist.

Is it lucio phenomenon or necrotic erythema nodosum leprosum

Lucio phenomenon (LP) or erythema necroticans is a relatively rare, peculiar reaction pattern occurring in untreated lepromatous (LL) or borderline lepromatous (BL) leprosy cases. A 38-year-old male, a cook by occupation, was referred to the dermatology clinic from otolaryngology department with blistering over both the hands and feet of 2 days duration. He had been admitted 1 week back with epistaxis and nasopharyngeal myiasis in otolaryngology department. He was started on systemic antibiotics gentamycin, crystalline penicillin, and metronidazole with nasal instillation of turpentine oil 2 drops 6 times a day. Two days later, he had developed edema with painless hemorrhagic blistering over the dorsum of left hand followed by involvement of the right hand, dorsa of both feet, and both the earlobes within a day. Histopathology of the blister showed sub-epidermal blister, with necrotizing leukocytoclastic vasculitis of papillary dermal vessels with thrombosis, numerous acid-fast bacilli in macrophages, and macrophage granulomas extending up to subcutis. In view of the absent fever or constitutional symptoms, and the classical angular infarcts and hemorrhagic blisters evolving into ulcers with angulated margins, we considered LP as the most likely diagnosis. The patient was started on a combination of WHO recommended multibacillary anti-leprosy therapy and prednisolone (40 mg/day).

Correlation of antimuscarinic acetylcholine receptor antibody titers and antidesmoglein antibody titers with the severity of disease in patients with pemphigus

Background: Acetylcholine receptor (AchR) antibody levels significantly correlate with disease severity at initial pemphigus diagnosis and during follow‐up. However, it is not clear if they are just an epiphenomenon or a potential trigger of the known pathogenic process in pemphigus vulgaris. Objective: We sought to assess the changes in anti‐muscarinic (M3) AchR and anti‐desmoglein (Dsg) antibody titers with therapy. Methods: This was a hospital‐based cohort study involving 45 patients with active pemphigus. Disease was graded clinically using Pemphigus Disease Area Index. Antibody titers were estimated using enzyme‐linked immunosorbent assay at baseline, 3 months, and 15 months. Results: All patients with pemphigus had significantly higher anti‐M3 AchR titers when compared with a control group. Only 95.5% of patients had anti‐Dsg1 antibodies and 84.4% of patients had anti‐Dsg3 antibodies. A statistically significant reduction in all 3 antibody titers from baseline to follow‐up with treatment was observed. There was a good correlation between all 3 antibody titer and Pemphigus Disease Area Index score at baseline and after therapy and between anti‐M3 AchR and anti‐Dsg1 antibody titers. Limitations: Sample size was small and follow‐up period was short. Conclusions: Anti‐M3 AchR antibodies are strongly associated with pemphigus. They significantly correlate with disease activity and their titers decline with therapy along with anti‐Dsg antibodies.

Familial gastrointestinal stromal tumors, lentigines, and café-au-lait macules associated with germline c-kit mutation treated with imatinib.

Familial lentiginosis syndromes are characterized by a wide array of manifestations resulting from activation of molecular pathways which control growth, proliferation, and differentiation of a broad range of tissues. Familial gastrointestinal stromal tumors (GISTs) are often accompanied by additional features like hyperpigmentation, mastocytosis, and dysphagia. They have been described with mutations in c‐kit (most commonly), platelet‐derived growth factor receptor A, neurofibromatosis‐1, and succinate dehydrogenase genes.

Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis

IntroductionDespite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date.ObjectivesWe aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis.MethodsOf the 360 patients recruited, 189 patients with moderate to severe psoriasis were treated with methotrexate. Of the 189 patients, 132 patients responded to methotrexate and the remaining 57 patients were non-responders. We analyzed the association of aforesaid polymorphisms with the methotrexate treatment outcome using binary logistic regression.ResultsWe observed that there were significant differences between genotype frequencies of HLA-Cw6 and FOXP3 (rs3761548) among the responders compared to non-responders, with conservative estimation. We observed that pro-inflammatory cytokines such as IFN-γ, IL-2, IL-12, and IL-23 were markedly reduced with the use of methotrexate, in comparison to the baseline levels, while the plasma IL-4 levels were increased posttreatment.ConclusionOur results serve as preliminary evidence for the clinical use of genetic markers as predictors of response to methotrexate in psoriasis. This might aid in the future in the development of a point-of-care testing (POCT) gene chip, to predict optimal treatment response in patients with psoriasis, based on their individual genotypic profile.