Rapid recovery in a child with febrile ulceronecrotic Mucha-Habermann disease following intravenous immunoglobulin administration.

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD), a lymphocyte-mediated inflammatory skin disorder, is considered a severe variant of pityriasis lichenoides et varioliformis acuta that can lead to a fatal outcome if not managed in a timely fashion. Children with FUMHD can have systemic complications involving various organs. The scarcity of reported cases and the absence of well-designed studies or randomized clinical trials to evaluate different therapeutic modalities pose a major challenge in treating this potentially life-threatening disorder. We report a five-year-old child with FUMHD and seizures treated unsuccessfully with a combination of systemic steroids, methotrexate, dapsone, and oral erythromycin, who improved rapidly and achieved disease control with just a single infusion of low-dose intravenous immunoglobulin.

Hepatitis C virus NS5A binds to the mRNA cap-binding eukaryotic translation initiation 4F (eIF4F) complex and up-regulates host translation initiation machinery through eIF4E-binding protein 1 inactivation.

Initiation, a major rate-limiting step of host protein translation, is a critical target in many viral infections. Chronic hepatitis C virus (HCV) infection results in hepatocellular carcinoma. Translation initiation, up-regulated in many cancers, plays a critical role in tumorigenesis. mTOR is a major regulator of host protein translation. Even though activation of PI3K-AKT-mTOR by HCV non-structural protein 5A (NS5A) is known, not much is understood about the regulation of host translation initiation by this virus. Here for the first time we show that HCV up-regulates host cap-dependent translation machinery in Huh7.5 cells through simultaneous activation of mTORC1 and eukaryotic translation initiation factor 4E (eIF4E) by NS5A. NS5A, interestingly, overexpressed and subsequently hyperphosphorylated 4EBP1. NS5A phosphorylated eIF4E through the p38 MAPK-MNK pathway. Both HCV infection and NS5A expression augmented eIF4F complex assembly, an indicator of cap-dependent translation efficiency. Global translation, however, was not altered by HCV NS5A. 4EBP1 phosphorylation, but not that of S6K1, was uniquely resistant to rapamycin in NS5A-Huh7.5 cells, indicative of an alternate phosphorylation mechanism of 4EBP1. Resistance of Ser-473, but not Thr-308, phosphorylation of AKT to PI3K inhibitors suggested an activation of mTORC2 by NS5A. NS5A associated with eIF4F complex and polysomes, suggesting its active involvement in host translation. This is the first report that implicates an HCV protein in the up-regulation of host translation initiation apparatus through concomitant regulation of multiple pathways. Because both mTORC1 activation and eIF4E phosphorylation are involved in tumorigenesis, we propose that their simultaneous activation by NS5A might contribute significantly to the development of hepatocellular carcinoma.

A Case of de novo Annular-plaque Type Psoriasis Following Oxford- AstraZeneca COVID-19 Vaccination.

BACKGROUND: There have been increasing reported cases of new-onset or aggravation of pre-existing dermatoses after the implementation of COVID-19 vaccination. CASE PRESENTATION: An elderly male was presented with multiple annular scaly plaques all over the body two weeks following administration of the first dose of Oxford-AstraZeneca COVID-19 vaccine. The lesions further aggravated after taking the second dose of the vaccine. The clinical and histopathology features were suggestive of annular plaque psoriasis. CONCLUSION: We report this first case of de novo plaque psoriasis following the Oxford- AstraZeneca COVID-19 vaccine, and it signifies a potential side effect of autoimmune reactivation after COVID vaccination.

A Rare Occurrence of Claw Hand and Wrist Drop Deformity in Herpes Zoster.

Our patient, a 37-year-old nondiabetic woman, presented with severe pain, blistering eruptions, and weakness in the right arm. About a month prior to reporting, had felt mild pain over the length of the arm followed by erythematous after 4-5 days in the same distribution. The dermatitis increased over next 10-15 days along with the onset of weakness. In anamnesis, she recalled that she also had intraoral lesions.

VirhostlncR: A comprehensive database to explore lncRNAs and their targets in viral infections.

Long non-coding-RNAs (lncRNAs) are an expanding set of cis-/trans-regulatory RNA genes that outnumber the protein-coding genes. Although being increasingly discovered, the functional role of the majority of lncRNAs in diverse biological conditions is undefined. Increasing evidence supports the critical role of lncRNAs in the emergence, regulation, and progression of various viral infections including influenza, hepatitis, coronavirus, and human immunodeficiency virus. Hence, the identification of signature lncRNAs would facilitate focused analysis of their functional roles accounting for their targets and regulatory mechanisms associated with infections. Towards this, we compiled 2803 lncRNAs identified to be modulated by 33 viral strains in various mammalian cell types and are provided through the resource named VirhostlncR (http://ciods.in/VirhostlncR/). The information on each of the viral strains, their multiplicity of infection, duration of infection, host cell name and cell types, fold change of lncRNA expression, and their specific identification methods are integrated into VirhostlncR. Based on the current datasets, we report 150 lncRNAs including differentiation antagonizing non-protein coding RNA (DANCR), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), maternally expressed gene 3 (MEG3), nuclear paraspeckle assembly transcript 1 (NEAT1), and plasmacytoma variant translocation 1 (PVT1) to be perturbed by two or more viruses. Analysis of viral protein interactions with human transcription factors (TFs) or TF-containing protein complexes identified that distinct viruses can transcriptionally regulate many of these lncRNAs through multiple protein complexes. Together, we believe that the current dataset will enable priority selection of lncRNAs for identification of their targets and serve as an effective platform for the analysis of noncoding RNA-mediated regulations in viral infections.

Update on Management of Morphea (Localized Scleroderma) in Children.

Juvenile localized scleroderma (morphea) is the predominant scleroderma in childhood which affects the skin and may extend to the underlying fascia, muscle, joints and bone. The assessment of activity and damage can be done with a validated instrument like LoSCAT. Disease classified as "low severity" which includes superficial plaque morphea can be treated with topical mid potent- potent steroids, tacrolimus, calcipotriol or imiquimod in combination with phototherapy. Methotrexate is recommended for linear, deep and generalized morphea. Steroids are effective in the early inflammatory stage and used in combination with methotrexate. Methotrexate is continued for at least 12 months after adequate response is achieved. Mycophenolate mofetil is given in cases where methotrexate is contraindicated or for those who do not respond to methotrexate. There are also reports of improvement of disease with ciclosporine and hydroxychloroquine. In severe cases, recalcitrant to standard therapy there may be a role for biologics, JAK inhibitors, and IVIG. Supportive measures like physiotherapy and psychiatric counseling are also important in the management of morphea. Orthopedic surgery and other measures like autologous fat transfer may be advocated once the disease is inactive.

Dowling-Degos Disease with Hidradenitis Suppurativa and Inflammatory Arthritis in Two Generations.

Dowling-Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by reticulate brown-to-black pigmentation of the flexures, pitted perioral acneiform scars, and comedo-like follicular papules on the flexures. The diagnosis is based on characteristic clinical and histopathological features. DDD has been found to occur in association with hidradenitis suppurativa (HS), arthritis, epidermoid cysts, keratoacanthomas, and squamous cell carcinoma. To date, there is only one report of DDD associated with HS and polyarticular arthritis.

Squamous Cell Carcinoma and Lymph Node Metastasis with Hypertrophic Lichen Planus in a 12 Year Old Boy.

Hypertrophic lichen planus (HLP) is a chronic variant of lichen planus with an estimated risk of 0.4% developing squamous cell carcinoma (SCC) in later years. We report the case of a 12-year- old boy with history of hypertrophic lichen planus since 4 years of age, with malignant transformation into squamous cell carcinoma along with lymph node metastasis.

Vegetating Plaques in the Groin: A Manifestation of Metastatic Crohn's Disease.

Crohn's disease (CD) is a type of inflammatory bowel disease that can affect any part of the gut from mouth to anus. It also may occur at contiguous sites, like, lip, perineal or peristomal regions or may occur at sites separated from the bowel by normal tissue referred to as metastatic CD. The condition is relatively rare and may mimic or coexist with other dermatoses. The presence of noncaseating granuloma on histopathological examination confirms the diagnosis. Here, we report a case of metastatic CD with cutaneous symptoms of long duration and presenting with vegetating plaques in the lower abdomen, groins, and vulva. The gastrointestinal disease was under remission. The diagnosis was confirmed by histopathological examination and patient responded well to topical as well as systemic steroids.

Medication Adherence Apps: Review and Content Analysis.

BACKGROUND: Medication adherence is an expensive and damaging problem for patients and health care providers. Patients adhere to only 50% of drugs prescribed for chronic diseases in developed nations. Digital health has paved the way for innovative smartphone solutions to tackle this challenge. However, despite numerous apps available claiming to improve adherence, a thorough review of adherence apps has not been carried out to date. OBJECTIVE: The aims of this study were to (1) review medication adherence apps available in app repositories in terms of their evidence base, medical professional involvement in development, and strategies used to facilitate behavior change and improve adherence and (2) provide a system of classification for these apps. METHODS: In April 2015, relevant medication adherence apps were identified by searching the Apple App Store and the Google Play Store using a combination of relevant search terms. Data extracted included app store source, app price, documentation of health care professional (HCP) involvement during app development, and evidence base for each respective app. Free apps were downloaded to explore the strategies used to promote medication adherence. Testing involved a standardized medication regimen of three reminders over a 4-hour period. Nonadherence features designed to enhance user experience were also documented. RESULTS: The app repository search identified a total of 5881 apps. Of these, 805 fulfilled the inclusion criteria initially and were tested. Furthermore, 681 apps were further analyzed for data extraction. Of these, 420 apps were free for testing, 58 were inaccessible and 203 required payment. Of the 420 free apps, 57 apps were developed with HCP involvement and an evidence base was identified in only 4 apps. Of the paid apps, 9 apps had HCP involvement, 1 app had a documented evidence base, and 1 app had both. In addition, 18 inaccessible apps were produced with HCP involvement, whereas 2 apps had a documented evidence base. The 420 free apps were further analyzed to identify strategies used to improve medication adherence. This identified three broad categories of adherence strategies, reminder, behavioral, and educational. A total of 250 apps utilized a single method, 149 apps used two methods, and only 22 apps utilized all three methods. CONCLUSIONS: To our knowledge, this is the first study to systematically review all available medication adherence apps on the two largest app repositories. The results demonstrate a concerning lack of HCP involvement in app development and evidence base of effectiveness. More collaboration is required between relevant stakeholders to ensure development of high quality and relevant adherence apps with well-powered and robust clinical trials investigating the effectiveness of these interventions. A sound evidence base will encourage the adoption of effective adherence apps, and thus improve patient welfare in the process.

Comparative Study of Efficacy and Safety of Botulinum Toxin a Injections and Subcutaneous Curettage in the Treatment of Axillary Hyperhidrosis.

BACKGROUND: Primary focal axillary hyperhidrosis is a chronic distressing disorder affecting both the sexes. When the condition is refractory to conservative management, we should go for more promising therapies like intradermal botulinum toxin A (BtxA) injections in the axilla, and surgical therapies like subcutaneous curettage of sweat glands. AIMS AND OBJECTIVES: The aim of this study is to compare the efficacy, safety and duration of action of intradermal BtxA injections in one axilla and subcutaneous curettage of sweat glands in the other axilla of the same patient with axillary hyperhidrosis. MATERIALS AND METHODS: Twenty patients (40 axillae) received intradermal BtxA injections on the right side (20 axillae) and underwent tumescent subcutaneous curettage of sweat glands on the left side (20 axillae). Sweat production rate was measured using gravimetry analyses at baseline and at 3 months after the procedure. Subjective analyses were done using hyperhidrosis disease severity scale (HDSS) score at baseline, at 3rd and 6th month after the procedure. RESULTS: At 3 months post-treatment, the resting sweat rate in the toxin group improved by 80.32% versus 79.79% in the subcutaneous curettage method (P = 0.21). Exercise-induced sweat rate in the toxin group improved by 88.76% versus 88.8% in the subcutaneous curettage group (P = 0.9). There was a significant difference in the HDSS score after treatment with both the modalities. There were no adverse events with BtxA treatment compared to very minor adverse events with the surgical method. CONCLUSION: Both intradermal BtxA injections and tumescent subcutaneous curettage of sweat glands had a significant decrease in the sweat rates with no significant difference between the two modalities. Hence, in resource poor settings where affordability of BtxA injection is a constraint, subcutaneous curettage of sweat glands can be preferred which has been found equally effective with no or minimal adverse events.

Hansen's disease in association with immune reconstitution inflammatory syndrome.

Immune reconstitution inflammatory syndrome is characterized by a paradoxical worsening of an existing infection or disease process, soon after initiation of highly active antiretroviral therapy. The first case of leprosy presenting as immune reconstitution inflammatory syndrome was published in 2003. Here we report a case of Hansen's disease borderline tuberculoid presenting with type 1 lepra reaction 5 months after initiation of highly active antiretroviral therapy.