Ashim Das

Fungal Rhinosinusitis: A Categorization and Definitional Schema Addressing Current Controversies

Fungal (rhino‐) sinusitis encompasses a wide spectrum of immune and pathological responses, including invasive, chronic, granulomatous, and allergic disease. However, consensus on terminology, pathogenesis, and optimal management is lacking. The International Society for Human and Animal Mycology convened a working group to attempt consensus on terminology and disease classification.

The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus

Zygomycosis is an emerging infection worldwide. A study was conducted to understand its spectrum in the Indian scenario. All patients diagnosed for invasive zygomycosis at a tertiary care center in north India from 2000-2004, were retrospectively analyzed. A total of 178 cases (mean average of 35.6 cases/year) of zygomycosis were diagnosed. Rhino-orbito-cerebral type (54.5%) was the commonest presentation followed by cutaneous (14.6%), disseminated (9.0%), and gastrointestinal (8.4%) zygomycosis. Renal and pulmonary zygomycosis were seen in 6.7% patients each. Uncontrolled diabetes mellitus (in 73.6% of cases) was the significant risk factor in all types (Odds Ratio 1.5-8.0) except renal zygomycosis. Breach of skin was the risk factor in 46.2% patients with cutaneous zygomycosis. However, no risk factor could be detected in 11.8% patients. Antemortem diagnosis was possible in 83.7% cases. The commonest (61.5%) isolate was Rhizopus oryzae followed by Apophysomyces elegans in 27% patients. Combination of debridement surgery and amphotericin B therapy was significantly better in survival of the patients (P<0.005) than amphotericin B alone (79.6% vs. 51.7% survival). Thus, a rising trend of invasive zygomycosis was observed in patients with uncontrolled diabetes mellitus in India. Consistent diagnosis of renal zygomycosis in apparently healthy hosts and the emergence of A. elegans in India demand further study.

The Clinicopathological Profile of Indian Patients with Nonalcoholic Fatty Liver Disease (NAFLD) is Different from That in the West

There are limited data on nonalcoholic fatty liver disease (NAFLD) from India. The clinicopathological profile of Indian patients with NAFLD may be different from that of Western patients. One hundred NAFLD patients with increased liver enzymes were prospectively evaluated for clinical presentation, associated diseases, overweight/obesity, central obesity (n=54), presence of diabetes mellitus, lipid abnormalities, insulin resistance (n=39), metabolic syndrome (n=54), serum iron, serum ferritin, and transferrin saturation (n=60), and HFE gene mutations (n=30). Risk factors for the grade and stage of the disease on histology were studied in 38 biopsy-proven patients. Patients were treated with lifestyle modifications and ursodeoxycholic acid (UDCA). Seventeen nonresponder patients were treated with metformin. The majority of patients were males (n=70). Twenty percent of patients were overweight, 68% had obesity, and 78% had central obesity. Abnormal cholesterol, HDL, and triglycerides were present in 36%, 66%, and 53% of patients, respectively. Twelve percent of patients had diabetes mellitus and 16% patients had various associated diseases. All 22 (100%) patients studied by ITT and all but 1 (98%) studied by HOMA-IR were found to have reduced insulin sensitivity and 50% were found to have metabolic syndrome by the modified ATP III criteria. Two (3%) patients were found to have high serum iron, 4 (7%) patients had high ferritin, 5 (8%) patients had increased transferrin saturation, and 4 (13%) patients were found to be heterozygotes for H63D HFE gene mutation. Twenty patients of 38 (53%) had histological evidence of NASH (class 3=6, class 4=14). The other 18 (47%) qualified for class I (n=1) or class II (n=17) NAFLD. Four (10.5%) patients had bridging fibrosis and none had evidence of cirrhosis liver. Seventy-four (74%) patients achieved a biochemical response to lifestyle modification and UDCA. All 17 patients treated with metformin had a reduction in ALT level and 10 (59%) of them had normalization of their enzymes. We conclude that the clinicopathological profile of NAFLD in Indian patients is different from that in the West.

Apophysomyces elegans: an Emerging Zygomycete in India

ABSTRACT Apophysomyces elegans was considered a rare but medically important zygomycete. We analyzed the clinical records of eight patients from a single center in whom zygomycosis due to A. elegans was diagnosed over a span of 25 months. We also attempted a DNA-based method for rapid identification of the fungi and looked for interstrain polymorphism using microsattelite primers. Three patients had cutaneous and subcutaneous infections, three had isolated renal involvement, one had rhino-orbital tissue infection, and the final patient had a disseminated infection involving the spleen and kidney. Underlying illnesses were found in two patients, one with diabetes mellitus and the other with chronic alcoholism. A history of traumatic implantation was available for three patients. All except two of the patients responded to surgical and/or medical therapy; the diagnosis for the two exceptions was made at the terminal stage of infection. Restriction enzyme (MboI, MspI, HinfI) digestion of the PCR-amplified internal transcribed spacer region helped with the rapid and specific identification of A. elegans. The strains could be divided into two groups according to their patterns, with clustering into one pattern obtained by using microsatellite [(GTG)5 and (GAC)5] PCR fingerprinting. The study highlights the epidemiology, clinical spectrum, and diagnosis of emerging A. elegans infections.

Spectrum of fungal rhinosinusitis; histopathologist's perspective

Aims: Clinical presentation can provide a clue to the subcategories of fungal rhinosinusitis (FRS); however, tissue examination provides accurate classification. The aim was to analyse the incidence and histopathological spectrum of FRS.

Invasive aspergillosis in developing countries

To review invasive aspergillosis (IA) in developing countries, we included those countries, which are mentioned in the document of the International Monetary Fund (IMF), called the Emerging and Developing Economies List, 2009. A PubMed/Medline literature search was performed for studies concerning IA reported during 1970 through March 2010 from these countries. IA is an important cause of morbidity and mortality of hospitalized patients of developing countries, though the exact frequency of the disease is not known due to inadequate reporting and facilities to diagnose. Only a handful of centers from India, China, Thailand, Pakistan, Bangladesh, Sri Lanka, Malaysia, Iran, Iraq, Saudi Arabia, Egypt, Sudan, South Africa, Turkey, Hungary, Brazil, Chile, Colombia, and Argentina had reported case series of IA. As sub-optimum hospital care practice, hospital renovation work in the vicinity of immunocompromised patients, overuse or misuse of steroids and broad-spectrum antibiotics, use of contaminated infusion sets/fluid, and increase in intravenous drug abusers have been reported from those countries, it is expected to find a high rate of IA among patients with high risk, though hard data is missing in most situations. Besides classical risk factors for IA, liver failure, chronic obstructive pulmonary disease, diabetes, and tuberculosis are the newly recognized underlying diseases associated with IA. In Asia, Africa and Middle East sino-orbital or cerebral aspergillosis, and Aspergillus endophthalmitis are emerging diseases and Aspergillus flavus is the predominant species isolated from these infections. The high frequency of A. flavus isolation from these patients may be due to higher prevalence of the fungus in the environment. Cerebral aspergillosis cases are largely due to an extension of the lesion from invasive Aspergillus sinusitis. The majority of the centers rely on conventional techniques including direct microscopy, histopathology, and culture to diagnose IA. Galactomannan, β-D glucan test, and DNA detection in IA are available only in a few centers. Mortality of the patients with IA is very high due to delays in diagnosis and therapy. Antifungal use is largely restricted to amphotericin B deoxycholate and itraconazole, though other anti-Aspergillus antifungal agents are available in those countries. Clinicians are aware of good outcome after use of voriconazole/liposomal amphotericin B/caspofungin, but they are forced to use amphotericin B deoxycholate or itraconazole in public-sector hospitals due to economic reasons.

Morphological and immunohistochemical analysis of ductal plate malformation: correlation with fetal liver.

Aims : Ductal plate malformation (DPM) is the persistence of excess of embryonic bile duct structures in the portal tracts. Most of the congenital diseases of intrahepatic bile ducts represent examples of DPM at different levels of the biliary tree. The aim of the present study was to evaluate the histopathological spectrum and immunohistochemical properties of DPM in various paediatric liver diseases and compare them with those of the normal embryonic ductal plates of human fetuses.

CONTROVERSIES SURROUNDING THE CATEGORIZATION OF FUNGAL SINUSITIS

Though rhinosinusitis is a common disorder, controversies surround the categorization of chronic rhinosinusitis (CRS) and the role of fungus in CRS. The diagnosis of each category is important for optimum therapy and predicting the course. Based on histopathological findings, fungal rhinosinusitis (FRS) can be broadly divided into two categories: the invasive and non-invasive depending on invasion of the mucosal layer. Three types of FRS are tissue-invasive: acute invasive, chronic invasive, & granulomatous. The two non-invasive FRS disorders are fungal ball, and fungus related eosinophilic rhinosinusitis including allergic fungal rhinosinusitis (AFRS). The distinction of granulomatous from chronic invasive type is not beyond controversy as both types have a chronic course and predominant orbital involvement. Maximum confusion surrounds the entity of fungus-related eosinophilic rhinosinusitis, and the definition of AFRS. In the diagnosis of AFRS, the detection of fungi in allergic mucin is considered important, although hyphae are sparse in sinus content. This leads to confusion in definition of this entity, especially with the description of two more closely related entities--eosinophilic fungal rhinosinusitis (EFRS) and eosinophilic mucin rhinosinusitis (EMRS). Recently reports of histologic invasion in possible cases of AFRS were also documented. Currently, there are more questions than answers concerning the categorization of FRS.

Elevation of interleukin‐18 in chronic hepatitis C: implications for hepatitis C virus pathogenesis

The outcome of hepatitis C virus (HCV) infection is determined by the interplay between the virus and the host immune response. Interleukin (IL)‐18, an interferon‐γ‐inducing factor, plays a critical role in the T helper type 1 (Th1) response required for host defence against viruses, and antibodies to IL‐18 have been found to prevent liver damage in a murine model. The present study was conducted to investigate the possible role of IL‐18 in the pathogenesis and persistence of HCV. IL‐18 levels were measured in sera of 50 patients at various stages of HCV infection (resolved, chronic and cirrhosis) and compared with those of normal controls. IL‐18 gene expression was studied in peripheral blood mononuclear cells (PBMC) from each group, and in liver biopsy tissue from patients with chronic hepatitis C. The mean levels of IL‐18 in sera were markedly elevated in patients with chronic hepatitis and cirrhosis, and were reduced in patients with resolved HCV infection. The serum IL‐18 concentrations were related to the Child–Pugh severity of liver disease in cirrhotic patients. There also existed a strong positive correlation of IL‐18 levels with histological activity score and necrosis. IL‐18 mRNA expression was significantly up‐regulated in the PBMC of cirrhotic patients when compared with other groups, while in the liver, higher levels of IL‐18 transcripts were expressed in patients with chronic hepatitis C. The results of our study indicate that IL‐18 levels reflect the severity and activity of HCV infection, and may contribute to the pathogenesis and progression of liver disease associated with HCV.

Cytology of Primary Skin Tumors

OBJECTIVE To evaluate the role of fine needle aspiration biopsy (FNAB) in the diagnosis of primary skin and adnexal tumors and to study the cytomorphology of various primary skin and adnexal tumors. STUDY DESIGN FNAB was routinely done in 18 cases of skin and adnexal tumors, and the cytologic diagnosis, along with detailed cytomorphology, was correlated with subsequent histology. RESULTS FNAB was done on 15 cases of primary skin tumors and 3 cases of recurrent lesions. FNAB successfully established the benign or malignant nature of skin tumors in 16 of 18 cases (88.9%). However, subtyping was possible in only 12 of 18 cases (66.7%). CONCLUSION Clinical history and physical findings are essential to the proper diagnosis of adnexal tumors. Knowing the cytologic features of primary skin neoplasms helps distinguish them from tumors metastatic to the skin and more commonly referred for FNAB.