Dapsone induced cholangitis as a part of dapsone syndrome: a case report

Background

Dapsone can rarely cause a hypersensitivity reaction called dapsone syndrome, consisting of fever, hepatitis, exfoliative dermatitis, lymphadenopathy and hemolytic anemia. Dapsone syndrome is a manifestation of the DRESS (drug rash with eosinophilia and systemic symptoms) syndrome which is a serious condition that has been reported in association with various drugs. Cholangitis in dapsone syndrome has not been reported so far in the world literature.

Case presentation

We report a patient who presented with fever, exfoliative dermatitis, jaundice and anemia within three weeks of starting of dapsone therapy. These features are typical of dapsone syndrome, which is due to dapsone hypersensitivity and is potentially fatal. Unlike previous reports of hepatitic or cholestatic injury in dapsone syndrome we report here a case that had cholangitic liver injury. It responded to corticosteroids.

Conclusion

We conclude that cholangitis, though unusual, can also form a part of dapsone syndrome. Physicians should be aware of this unusual picture of potentially fatal dapsone syndrome.

     

Lupus anticoagulant in a child with celiac disease: a rare association

Celiac disease or gluten-sensitive enteropathy is characterized by malabsorption, chronic inflammation of the small intestine mucosa, villous atrophy and crypt hyperplasia. Association of auto-immunity has been reported to be almost threefold higher in patients with celiac disease. While there are several reports of celiac disease in association with autoimmune diseases, there is paucity of literature on its association with antiphospholipid antibodies. We report here an 8-year-old girl child with celiac disease who was found to have lupus anticoagulant positivity, an extremely uncommon association. This child is perhaps the youngest ever patient of celiac disease in association with lupus anticoagulant.     

Hemoglobin E Syndromes: Emerging Diagnostic Challenge in North India

Hemoglobin E (HbE) is one of the world’s most common and important mutations. HbE disorders may be found in heterozygous (AE), homozygous (EE) and compound heterozygous state. It is important to distinguish HbE disorders diagnostically because of marked differences in clinical course among different genotypes. To find out whether RBC indices as obtained from automated cell counter can provide a clue to the diagnosis of HbE disease. This study was carried out in the Department of Clinical Pathology, PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi. It included antenatal pregnant females brought for routine check-up as well as referred patients suspected of having hemoglobinopathies. High Performance liquid chromatography was used as a confirmatory test for identification of hemoglobinopathy. Total 20 cases of subtype homozygous HbE (3), HbE trait (12) and Eβ-thalassemia (5) were identified. Statistical analysis was done to find out correlation between levels of HBA2, HBF with RBC indices. (a) There was negative correlation between HbA2/E peak values and RBC indices (Mean corpuscular volume (MCV) and Mean corpuscular hemoglobin) among all the three groups taken together. (b) There was positive correlation between HbA2/E and Red cell distribution width (RDW). (c) There was positive correlation between HbF values with MCV. The finding of positive correlation between HbA2/E and RDW may help in differentiating βthal (RDW normal) from HbE/βthal. In a patient with microcytic hypochromic blood picture and increased RDW, diagnosis of HbE/βthal should also be considered along with the more common Iron deficiency anemia. Thus, new insights into the knowledge of these diseases are important because they impart diagnostic challenges to all the experts involved in the treatment of anemic patients.     

Pancreatic ascites and Pleural Effusion in Children: Clinical Profile,Management and Outcomes

BackgroundPancreatic ascites (PA) and pleural effusion (PPE) are rarely encountered in children. They develop due to disruption of the pancreatic duct (PD) or leakage from an associated pancreatic fluid collection (PFC). The literature on childhood PA/PPE and its management is scarce.MethodsA retrospective review of children with PA/PPE diagnosed and managed at our center over the last 4 years was performed. The clinical, biochemical, radiological and management profiles were analyzed. Conservative management included nil per oral, octreotide and drainage using either percutaneous catheter or repeated paracentesis. Endotherapy included endoscopic retrograde cholangiopancreatography (ERCP) and transpapillary stenting.ResultsOf the 214 children with pancreatitis, 15 (7%) had PA/PPE. Median age was 9 years with a third under 2 years. Median ascitic fluid amylase was 8840 U/L and all had elevated protein (>2.5 g/dl) and low serum ascites-albumin gradient ascites (<1.1). While PA/PPE was the first manifestation of underlying chronic pancreatitis (CP) in 10 children (67%), trauma was seen in 4 (26%) and hypertriglyceridemia in 1 (7%). On imaging, PD disruption could be identified in 10 (67%) children. ERCP and stenting was done in 10 children. Conservative management alone (n = 4) and endotherapy (n = 10) was successful in 93% with only one requiring surgery. The younger children (n = 4), were managed conservatively and only 1 of them required surgery. Resolution of PA/PPE was achieved in all with no recurrences.ConclusionsConservative management and ERCP plus transpapillary stenting results in resolution of majority of pediatric PA/PPE. Children presenting with PA/PPE needs to be evaluated for CP.     

Late Life Immigration and Quality of Life among Asian Indian Older Adults

Late-life immigration among seniors for purposes of family reunification is a growing phenomenon in developed countries. Using the World Health Organization’s Quality of Life instrument short form (WHOQOL-BREF) and other psychosocial measures related to the political/legal context of immigration, and personal and environmental autonomy (mastery, immigration status, access to transportation, and language barrier), this study examined quality of life (QoL) in Asian Indian seniors (N = 109), who immigrated to the United States to reunite with their adult children. The sample scores on Overall QoL and QoL domains (physical and psychological health, social relationships, and environment) were similar to established norms. Although all QoL domains correlated significantly with Overall QoL at the bivariate level, multivariate analysis showed that only environmental domain contributed significantly to Overall QoL. Linear regressions indicated: Mastery contributed significantly to Overall QoL and all QoL domains; access to transport contributed to Overall QoL, physical health, and environmental QoL; immigration status (a proxy for political/legal context) contributed to environmental QoL whereas language barrier contributed to none. Implications for improving perceptions of QoL, mastery, access to transport and other services are discussed.     

Orthotopic liver transplantation: reversible Doppler US findings in the immediate postoperative period

Orthotopic liver transplantation (OLT) is the only definitive treatment for irreversible acute liver failure and chronic liver disease. In the immediate postoperative period after OLT, patients are closely monitored with Doppler ultrasonography (US) to detect treatable vascular complications and ensure graft survival. The first postoperative Doppler US examination is performed fairly early on the first postoperative day, before surgical wound closure has been performed. The immediate postoperative images, obtained when the effects of surgery are very recent, often reveal an array of findings that may appear alarming but that tend to normalize within a few days and are compatible with changes related to the surgery itself. These findings include a starry-sky appearance of reperfusion hepatic edema, transient foci of increased echogenicity, pneumobilia, small fluid collections, perihepatic hematomas, pleural effusion, temporary elevation of hepatic arterial velocity, transient elevation of resistive index (RI), decreased RI with tardus parvus waveform, increased portal venous flow and mono- or biphasic waveforms of the hepatic veins. Most of these changes revert to normal in the first postoperative week; deterioration atypical of transient changes requires further evaluation.     

In utero exposure to female hormones and germ cell tumors in children

BACKGROUND: Maternal exposure to exogenous female hormones during pregnancy has been implicated as a risk factor for malignant germ cell tumors (GCTs) in the offspring in some epidemiologic studies of testicular and ovarian carcinoma in adults. METHODS: From 1996 to 2002, 278 children younger than 15 years of age with malignant GCTs and 423 healthy controls, frequency-matched for geographic location, age, and sex were enrolled in a case-control study to investigate whether in utero exposure to female hormones is associated with the risk of malignant GCT in children. Cases were recruited from 84 institutions in the U.S. and controls were enrolled through random digit dialing. Information was obtained through telephone interview with the biological mothers of the subjects and through blinded review of the mothers' medical records. RESULTS: Neither self-reported (odds ratio [OR] = 1.15; 95% confidence interval [CI], 0.63, 2.12) nor medical chart based (OR = 1.14; 95% CI, 0.75, 1.73) maternal exposure to exogenous female hormones was related to malignant GCT risk. Pregnancy-related conditions that may have altered serum levels of circulating female hormones were also unrelated to the risk of GCT in the offspring. CONCLUSION: This study failed to provide strong evidence to support the hypothesis that maternal exposure to exogenous female hormones during pregnancy increases the risk of GCT in the offspring.     

Evaluation of antipyretic activity of Calotropis gigantea (Asclepiadaceae) in experimental animals

The roots of Calotropis gigantea have been used in leprosy, eczema, syphilis, elephantiasis, ulceration and cough in the Indian system of traditional medicine. The present communication evaluated its antipyretic activity by using yeast-induced and TAB (Typhoid) vaccine-induced pyrexia in rats and rabbits. In both yeast-induced and TAB vaccine-induced fever, the fever was significantly reduced and the body temperature was normalized by administration of 200 and 400 mg/kg dose intraperitoneally. Based on the results of the present study it can be concluded that the extract of C. gigantea has potential antipyretic activity against both yeast-induced and TAB vaccine-induced fever, indicating the possibility of developing C. gigantea as a cheaper and potent antipyretic agent.     

A comparative proteomic study of sera in paediatric systemic lupus erythematosus patients and in healthy controls using MALDI-TOF-TOF and LC MS-A pilot study

ABSTRACT: BACKGROUND: Paediatric systemic lupus erythematosus (pSLE) exhibits an aggressive clinical phenotype with severe complications and overall poor prognosis. The aim of this study was to analyse differential expression of low molecular weight (LMW) serum protein molecules of pSLE patients with active disease in comparison to sera of healthy age matched controls. Further, some of the differential expressed spots were characterised and identified by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) and liquid chromatography (LC-MS). METHODS: 2D-PAGE was performed using pooled sera of active pSLE and age matched healthy controls. Gels were silver-stained and differentially expressed protein spots were detected by automated image master platinum 2D software. 79 +/- 17 protein spots were detected for control gels and 78 +/- 17 protein spots for patient gels. Of these eleven protein spots were selected randomly and characterized by MALDI-TOF MS (five protein spots) and LC MS (six protein spots) techniques. RESULTS: Out of the 11 protein spots, 5 protein spots were significantly upregulated viz., leiomodin 2 (LMOD2); epidermal cytokeratin 2; immunoglobulin kappa light chain variable region; keratin 1 and transthyretin (TTR). Three protein spots were significantly down regulated e.g., apolipoprotein A1 (APOA1); chain B human complement component C3c; campath antibody antigen complex. Two protein spots (complement component C3; retinol binding protein (RBP) were found to be expressed only in disease and one protein spot cyclohydrolase 2 was only expressed in controls. CONCLUSIONS: We conclude that 2-D maps of patients with active pSLE and controls differ significantly. In this pilot study, using proteomic approach we have identified differential expressed proteins (of LMW) e.g., RBP, LMOD 2, TTR, Component C3c Chain B and APO A1. However, in future, further studies need to confirm the physiological and pathological role of these proteins in similar cohorts of pSLE.     

Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology

Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry–based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with a 5-y survival rate of 9% for all stages (1). Among patients with resectable tumors, surgical resection with microscopically negative margins is required for prolonged disease-free survival (2). Thus, differentiating normal tissue from tumor is the cornerstone of effective pancreatic oncologic surgery (3, 4). In practice, delineation of pancreatic resection margins is difficult and variable. Tumor margin status is commonly assessed intraoperatively by microscopic histopathological evaluation of frozen sections prepared from excised pancreatic neck and common bile duct margins prior to completion of the operation (5, 6). However, artifacts on tissue histology from frozen section preparation complicates histopathologic evaluation, further accentuated by the complex pathology of PDAC, with high desmoplastic stromal content and chronic pancreatitis (CP) at the pancreatic resection margins as well as inflammation induced by surgical manipulation of bile duct tissue–mimicking tumor (7, 8). Moreover, the reported accuracy of frozen section analysis is variable center-to-center and depends on the methodology, skillset, and subspecialty of the pathologist on call (9–12).Several optical and molecular technologies are being developed with the expectation of improving pancreatic cancer detection during surgery (SI Appendix, Text) (13–15). In particular, mass spectrometry (MS) technologies are powerful for investigating molecular differences between normal and cancerous tissues with high sensitivity, chemical specificity, and speed and have also been explored for surgical use and margin evaluation (16). Desorption electrospray ionization (DESI) MS, for example, has been used to investigate molecular differences between normal and cancerous tissues ex vivo cancerous and normal tissue sections (17–19). In particular, Zare and coworkers applied DESI-MS imaging to analyze the metabolic and lipid profiles of adjacent histologic tissue sections of margin regions collected from pancreatic surgery (20). Other techniques (i.e., rapid evaporative ionization MS and laser-based MS devices) have been developed for in vivo cancer detection (21–24). However, these techniques have not yet been demonstrated for pancreatic cancer tissue detection.We developed the MasSpec Pen system as a biocompatible handheld device coupled to a mass spectrometer for rapid (∼15 s) and nondestructive tissue analysis (25). Upon contact with a tissue and activation by a foot pedal, a discrete water droplet is formed and contained at the MasSpec Pen tip reservoir, allowing metabolites and lipids to be gently extracted into the water droplet, which is then transported to the mass spectrometer for analysis. To date, we have applied the MasSpec Pen in conjunction with least absolute shrinkage and selector operator (Lasso) penalized logistic regression to classify several tumor types ex vivo, achieving 96% overall accuracy in cross-validation (CV) (25–27). More recently, we translated the MasSpec Pen technology to an operating room (OR) to evaluate technical feasibility in open human surgeries and as a laparoscopic device in a robotic surgical procedure (28, 29).Here, we describe the application and first use of the MasSpec Pen for the acquisition and statistical prediction of molecular data acquired from pancreatic and biliary tissues, including in vivo data of surgical margins collected in an OR from patients undergoing pancreatic surgery. Collectively, our results indicate that the MasSpec Pen technology may be useful to enhance surgical margin evaluation in pancreatic cancer procedures by providing near–real-time diagnostic feedback to surgeons and physicians.