A comparative study of modulatory interaction between cytokines and apoptotic proteins among Scleroderma patients with and without pulmonary involvement.

BACKGROUND: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the most eminent forms of pulmonary involvement in Scleroderma. In this study we investigate the interaction between cytokines and apoptotic proteins in treatment naive Scleroderma (SSc) patients with and without pulmonary involvement. METHODS: Newly diagnosed treatment naïve Scleroderma (SSc) patients (n = 100) and healthy controls (n = 100) were enrolled. Patients were classified as ILD-SSc, PAH-SSc and non-pulmonary SSc (np-SSc). Study variables like mRSS score, autoantibody profile, serum cytokines, serum TGF-ß (1,2,3) and apoptotic proteins were assessed for these patients. RESULTS: Scleroderma patients showed elevated levels of serum cytokines, but significantly lower IL-22 and TGF- ß1 when compared to healthy controls (p < 0.05). Apoptotic proteins were significantly elevated among Scleroderma patients, but the patient groups also showed significant lower caspase 1/3/9 levels when compared to healthy controls (p < 0.05). ILD-SSc patients reported higher mRSS score (p = 0.0436) when compared with PAH-SSc and np-SSc. In ILD-SSc patients, finger tightening (p = 0.0481) and calcinosis/lesions (p = 0.0481) were significant clinical presentations whereas, digital ulcers were significantly prominent in np-SSc patients (p = 0.0132). Elevated TGF-ß3 levels (p = 0.02) in SSC-ILD and reduced IL-4 levels (p = 0.02) in SSC-PAH were significant cytokines as compared to np-SSc. Significant correlations were obtained among serum cytokines and apoptotic proteins in Scleroderma patients with and without pulmonary involvement. (p < 0.05) CONCLUSION: Our study highlights the correlation between mRSS score, cytokines and apoptotic proteins in SSc patients with pulmonary involvement. A longitudinal follow up in these patients with assessment of these immunological parameters may be helpful in monitoring the disease.

Fibrotic Cytokine Interplay in Evaluation of Disease Activity in Treatment Naïve Systemic Sclerosis Patients from Western India.

BACKGROUND: : Systemic sclerosis (SSc) is a demyelinating disease of skin, subcutaneous tissue, muscles and internal organs, with fibrosis as an important pathological event. AIM: : To understand cytokine interplay of IL-1ß, IL-4 and IL-6 and their association with disease activity in treatment naïve active cases of systemic sclerosis from Western India. METHODS: Twenty-five SSc patients as per ACR-EULAR 2013 criteria (classified based on pulmonary fibrosis and generalized fibrosis) and 25 age-sex matched controls were enrolled. Serum cytokine levels of IL-1ß, IL-4 and IL-6 were assessed by multiplex bead based immunoassay. RESULTS: Ten patients had Interstitial lung disease (ILD), whereas, 16 patients had generalized fibrosis. Anti-nuclear antibodies were seen in 22 patients (88%); antiScl70 in 15 patients (60%) and anti-Centromere antibodies in 5 patients (20%). Serum levels of IL-1ß in patients were significantly higher than healthy controls (p=0.0006). IL-4 levels in all SSc patients were marginally raised (p=0.0102), while IL-6 levels were significantly raised (p<0.0001). IL-4 was found to be significantly raised in SSc patients with ILD (p=0.021) as compared to patients without ILD. IL-1ß (p=0.0293) and IL-4 (p<0.0001) were significantly higher in SSc patients with fibrosis. On the contrary, IL-6 levels in patients with fibrosis were found to be lower than in patients without fibrosis. CONCLUSION: Significantly raised cytokine levels among treatment naïve systemic sclerosis patients were found to be associated with higher disease severity in our study. Higher levels of IL-1ß and IL-6 indicated an active inflammatory status, whereas significantly raised IL-4 levels indicated at higher fibrotic activity.

Multiple acquired smooth muscle hamartomas with thick-walled blood vessels on scalp.

Smooth muscle hamartoma (SMH) is a benign hamartomatous condition that consists of a dermal proliferation of smooth muscle cells. We hereby report a case of multiple, acquired SMHs on scalp. A 25-year-old male had a 6-year history of multiple, asymptomatic, hyperpigmented plaques on the scalp which were progressively increasing in number and size. Histopathological examination revealed large thick-walled blood vessels, in addition to the haphazardly arranged discrete smooth muscle bundles in the reticular dermis. This case of SMH is unusual in being acquired, having multiple lesions, involving scalp, and having thick-walled blood vessels apart from arrector pili muscle bundles. It emphasizes the wide spectrum of clinical and histopathological variations that may be associated with acquired SMH.

Antibodies to group A streptococcal virulence factors, SIC and DRS, increase predilection to GAS pyoderma.

BACKGROUND: Streptococcus pyogenes (group A streptococcus; GAS) is an etiological agent for pharyngitis, pyoderma, and invasive infections in humans. Pharyngitis and pyoderma may lead to serious immune sequelae such as rheumatic heart disease and post-streptococcal glomerulonephritis (PSGN). Streptococcal Inhibitor of Complement (SIC) and its orthologue, distantly related to SIC (DRS), are virulence factors expressed by only four of more than 100 M types of GAS. These four types (M1, M57, M12 and M55) are among the M types, which are associated with PSGN. In several populations PSGN has been shown to be a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). Previous studies showed SIC or DRS antibody-prevalence was associated with PSGN, and seroprevalence of SIC antibodies is significantly high among CKD and ESRD patients in Mumbai. METHODS: Streptococcal isolates recovered from GAS pyoderma cases were typed. Seropositivity for SIC and DRS antibodies in subjects with pyoderma, PSGN pediatric cases, age matched healthy controls and non-GAS pyoderma cases were determined. RESULTS: We confirm in this study an association between seroprevalence to SIC and DRS antibodies, and PSGN in Mumbai population despite low point prevalence of M1, M12, M55 and M57. In addition we extended the study to GAS-pyoderma and non-GAS pyoderma cases. To our surprise, we found a positive association between the seroprevalence to SIC and DRS antibodies, and GAS-pyoderma owing to infection with diverse M types. The mechanism of increased predisposition to pyoderma owing to infection by diverse GAS among SIC or DRS antibody-positive population is not clear. Nonetheless, our findings could be explained by a phenomenon akin to antibody-dependent enhancement (ADE). CONCLUSIONS: This is the first report showing a small number of GAS M types conferring predisposition to pyoderma by diverse types. Implications of this ADE-like phenomenon are discussed in the light of evolutionary advantage to GAS, vaccine design and control of renal diseases.

A study of depression and quality of life in patients of lichen planus.

The precise cause of lichen planus is unknown, but the disease seems to be immunologically mediated. It is a psychocutaneous disorder. Due to scarcity of Indian studies in this field, we decided to study in patients of lichen planus the prevalence of depression and quality of life with comparison of the same in both the genders. Patients diagnosed as having lichen planus by consultant dermatologist were enrolled after informed consent and ethics approval. 45 patients were screened, of which 35 who satisfied the criteria were taken up for the study. A semistructured proforma was designed to collect the necessary information with administration of dermatology life quality index and Beck's depression inventory. While 25% were depressed with females being more affected than males, quality of life was impaired in more than 90% patients. Impairment was maximum due to symptoms and illness feelings, disturbed daily activities, or work and time consumption in treatment. There was a strong association between depression and impairment in quality of life in both the genders. This study helps in early identification of psychological problems in lichen planus patients and in planning their future course of management, hence reducing the lack of productivity and improving the prognosis and quality of life.

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.

Allopurinol Induced DRESS Syndrome.

A 45 years old female on allopurinol for 3 months presented with itching, rash, facial oedema and eosinophilia with hepatic and renal dysfunction. Skin biopsy revealed interface dermatitis, suggesting the diagnosis of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome.

Granulomatous variant of giant centrifugal miliaria profunda.

Two infants presented with multiple asymptomatic papules and geographic and annular plaques over the extensor aspect of the upper and lower extremities and trunk. Skin biopsy of both lesions showed plugged and hyperplastic dilated acrosryingia and deep dermal ducts, along with granulomatous inflammatory reaction. These lesions showed self-healing with complete resolution. A previous report described similar clinical and histopathologic features and labeled it giant centrifugal miliaria profunda. Because of the large granulomatous plaques and deep infiltrate, we propose that it was a granulomatous variant of giant centrifugal miliaria profunda. We report these cases for their rarity and self-healing nature.

Unusual cutaneous manifestations of dracunculiasis: Two rare case reports.

A nematode parasite, Dracunculus medinensis, causes dracunculiasis. Despite being non-fatal, this condition causes significant morbidity. Dracunculiasis is considered an eradicated disease in India since 1999. We report two cases that document the unusual linear morphea-like morphology of the calcified D. medinensis and the rare periorbital location of the worm. The cases presented here are rare and a diagnostic challenge, considering the eradicated status of dracunculiasis.

Disseminated cutaneous with nasopharyngeal rhinosporidiosis: Light microscopy changes following dapsone therapy.

We report a case of disseminated cutaneous and nasopharyngeal rhinosporidiosis in a 48-year-old man. The patient complained of a 6-month history of six subcutaneous skin-coloured swellings on the body and a 5-year history of a pea-sized swelling on the inner aspect of the left lower eyelid. Histopathological examination from one of these lesions showed multiple globular cysts packed with endospores that were typical of rhinosporidiosis. We report this case because of its rarity and to describe the morphological effects of dapsone in promotion of a host inflammatory response to the organism.

Unknown: Multiple asymptomatic skin colored to yellowish papules over vulva.

Multiple syringomas of the vulva are an unusal finding. We report a 42-year-old woman with a 2 year history of asymptomatic yellow papules on the vulva that were proven to be syringomas by histopathologic examination.

A Cross-Sectional Study to Correlate Disease Severity in Bullous Pemphigoid Patients with Serum Levels of Autoantibodies Against BP180 and BP230.

CONTEXT: Enzyme-linked immunosorbent assay (ELISA) for BP 180 and 230 antibodies is commonly done in patients with bullous pemphigoid. We could not find much data regarding the usefulness of this test to predict the disease severity in Indian population. AIMS: We studied the correlation of IgG anti BP180 and anti BP230 antibody titer with disease severity and clinical features in bullous pemphigoid. SETTINGS AND DESIGN: This cross-sectional study was conducted at a tertiary care center in western India. MATERIALS AND METHODS: Forty-two clinically diagnosed treatment-naive cases of bullous pemphigoid were enrolled and investigated with skin punch biopsy, IgG anti BP180, and anti BP230 ELISA, direct immunofluorescence, and indirect immunofluorescence tests. Disease severity was assessed by calculating modified Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) score. Thirty patients with a final diagnosis of bullous pemphigoid were included in the statistical analysis. Pearson's correlation coefficient (r) was used to study correlation. RESULTS: The mean ABSIS skin score was 32.81 when both tests were negative, 42.13 when only BP230 was positive, 76.28 when only BP180 was positive, and 78.16 when both were positive. Pearson's correlation coefficient (r) for BP180 and ABSIS skin score was 0.6 (P value: 0.0005), and for BP230 was -0.055 (P value: 0.600). CONCLUSIONS: BP antibody titers correlate partially with disease severity. Anti-BP180 antibody is associated with more severe disease. Anti-BP230 antibody titer does not correlate with disease severity.

A case of disseminated subcutaneous phaeohyphomycosis caused by Exserohilum rostratum with CARD9 mutation.

Phaeohypomycosis is a rare cutaneous and subcutaneous fungal infection caused by dematiaceous fungi. They have a widespread global distribution occasionally affecting humans. A 26-year-old woman presented with multiple skin lesions over her face and extremities for last 7 years, unresponsive to systemic amphotericin B and itraconazole. Further investigations revealed CARD9 mutation and phaeohyphomycosis caused by the pigmented fungus Exserohilum rosatratum. Lesions subsequently improved with oral flucytosine and itraconazole.

Cutaneous plasmacytosis with mast cell infiltration.

Cutaneous plasmacytosis is a rare disorder of uncertain etiology, described mainly in patients of Japanese descent. Clinically, it is characterized by multiple pigmented papules and plaques distributed primarily on the trunk. Histopathologically, it is marked by a dense dermal plasma cell infiltrate. Here, we describe a case of cutaneous plasmacytosis in a 55-year-old Indian male who presented with hyperpigmented plaques on the body. Histopathological examination revealed dense superficial and deep perivascular and periappendageal infiltrate composed mainly of plasma cells, lymphoid follicles with reactive germinal centres, perineural distribution of plasma cells, mast cell infiltration and increased dermal small blood vessels. Immunohistochemical analysis confirmed the polyclonal nature of the plasma cells. Laboratory investigations were within normal limits, except for the presence of polyclonal hypergammaglobulinemia without any M band. There was no evidence of autoimmune disease or any infection. There was no systemic involvement in this patient. The patient was diagnosed as cutaneous plasmacytosis and advised long-term follow-up. Peculiar histopathological finding in this case of cutaneous plasmacytosis was the presence of abundant mast cells in the dermis.

Comparison of Dermoscopic Patterns at the Center and Periphery of Alopecia Areata Patch - A Cross-sectional Study in 100 Patients.

BACKGROUND: Dermoscopy is a noninvasive tool for the diagnosis of various dermatological disorders. Dermoscopy of alopecia areata (AA) aids in confirming the diagnosis and severity of the disease. MATERIALS AND METHODS: A total of 100 patients of AA were evaluated with a dermoscope (×20 and × 200) to determine the dermoscopic features at the center and periphery of patches of AA. RESULTS: Black dots were the most common dermoscopic finding at the periphery of AA patch among the study population, followed by yellow dots, vellus hair, broken hair, tapering/exclamation mark hair, kinking at the point of emergence of a hair shaft, piggy tail hair, and depressed follicular opening. At the center of the patch, yellow dots were the most common dermoscopic findings among the study population, followed by black dots, vellus hair, broken hair, and piggy tail hair. CONCLUSION: Black dots were the most common dermoscopic findings at the periphery of the patch. Yellow dots were the most common dermoscopic findings at the center of patch among the study population. Kinking at the point of emergence of the hair shaft was a new sign in this study seen at the periphery of the patches in 19 patients. It is the latest finding which requires further elaboration with larger sample size studies.

A descriptive observational study on clinical and dermoscopic features of benign melanocytic neoplasms.

BACKGROUND: Benign melanocytic neoplasms have nests of melanocytic cells and show characteristic dermoscopic features. Clinical and dermoscopic features have not been studied previously in the Indian population. AIMS: To study the clinical, epidemiological and dermoscopic patterns of benign melanocytic neoplasms. METHODS: This was a descriptive, observational, single centre study. In 107 patients with melanocytic neoplasms, 167 lesions were clinically examined and studied under the dermoscope and histopathological examination was done when indicated. The lesions were broadly divided as acquired and congenital. Five main dermoscopic patterns were seen-globular, homogenous, reticular, parallel and streaks. If there were two of these patterns in a particular lesion, it was termed 'mixed pattern'. The presence of three or more patterns was called 'multicomponent pattern'. Various other features were also observed. RESULTS: The majority of patients belonged to the third decade with a female preponderance. History of increased UV exposure and family history was significant in acquired nevi. The dermoscopic pattern progressed from predominantly reticular in junctional nevi to predominantly globular in compound nevi and lesser pigment in intradermal nevi, with more vascular structures. The congenital melanocytic nevi showed additional features of comedo- like lesions, milia- like cysts, perifollicular pigmentary changes and increased colour variation. Even though colour variation was observed in both acquired and congenital lesions, no signs of dysplasia were seen on histopathology. LIMITATIONS: A larger sample size is required, with follow up of lesions. No parallel studies in brown skinned population were found for exact comparison. CONCLUSION: Benign melanocytic proliferations are often neglected in our country. This study will help in understanding the course, clinical features and dermoscopic patterns of various benign melanocytic neoplasms, and will be a step forward towards research in our population. To the best of our knowledge, this is the first study of its kind in India.