Zoon's Balanitis - Update of Clinical Spectrum and Management.

Zoon's balanitis or balanitis plasmacellularis circumscripta is a chronic inflammatory disorder of the genital mucosa that can affect both males and females (Zoon's vulvitis). It is not a sexually transmitted disease but can still cause anxiety to the patients because of its chronic nature. Hence, proper diagnosis and early management are necessary. It is a clinical mimicker of other commoner genital dermatoses and is mostly a diagnosis of exclusion when other diseases have been ruled out. It is characterised by a well-demarcated shiny erythematous patch or plaque over the genital mucosa. Histopathological examination becomes necessary when we are unable to differentiate it from premalignant lesions. It reveals lozenge-shaped keratinocytes with siderophages, haemorrhages and variable plasma cell infiltrate in the dermis. Dermoscopy shows spermatozoa-like, convoluted vessels with structureless red orange areas. Response to topical therapy alone is not always satisfactory. However, lasers and surgical management can provide long-term remission.

A comparative interventional study of narrowband ultraviolet B alone and narrowband ultraviolet B in combination with microneedling in patients with stable vitiligo.

BACKGROUND: Vitiligo is a cosmetically concerning common disorder of depigmentation. Narrowband Ultraviolet B (NB-UVB) phototherapy is a well-established mode of treatment for vitiligo. Microneedling is a simple method that has been used for vitiligo treatment in adjunct with NB-UVB and has been shown to induce repigmentation in a few studies; however, there is limited study in the literature. AIMS: To compare the efficacy of NB-UVB alone versus NB-UVB in conjunction with microneedling in patients of stable vitiligo. METHODS: Thirty patients of non-segmental vitiligo with patches tending toward symmetry, stable for at least 6 months were included. Patches on right side of body (side A) were subjected to both microneedling every 2 weeks and NB-UVB three times a week, while patches on left side of body (side B) were subjected to NB-UVB alone thrice weekly for 4 months or till complete resolution of lesions whichever was earlier. Patients were followed up for another 2 months. Response was assessed by photographic record and Vitiligo Area Severity Index (VASI score) calculated at baseline and every month for 6 months. RESULTS: The mean VASI score improvement in both the groups as compared to baseline was statistically significant (p-value < .01). However, the difference in mean VASI scores between the two groups was not statistically significant (p-value = .17). CONCLUSION: NB-UVB is an effective modality for treatment of vitiligo, but there is no additional benefit of combining microneedling with it.

Safety of immune checkpoint inhibitors in patients with cancer and pre-existing autoimmune disease.

BACKGROUND: Patients with pre-existing autoimmune disease (AD) have been largely excluded from clinical trials of immune checkpoint inhibitors (ICI), so data on safety of ICIs among patients with pre-existing AD are relatively limited. There is a need for deeper understanding of the type and management of complications from ICI in patients with pre-existing AD. We sought to investigate the safety of ICIs in patients with pre-existing ADs as well as factors associated with AD flare. METHODS: Consecutive patients with pre-existing AD who received monotherapy as well as combination of ICI therapies at our institution from September 2015 through September 1st, 2018 were identified. Clinical information was abstracted via manual chart review. Clinical factors associated with AD flare were determined using multivariable logistic regression. RESULTS: A total of 42 patients were identified of whom 12 developed AD flare. All flares were treated with oral or topical corticosteroids, while a patient with flare of rheumatoid arthritis was treated with tofacitinib and another patient with Crohn's flare was treated with infliximab. Female sex, smoking status, higher age at the start of ICI therapy, cancer type, such as melanoma and lung cancer as compared to other cancers, were not significantly associated with AD flare, however, patients with underlying rheumatologic AD were noted to have a five times greater likelihood of flare as compared to other non-rheumatologic AD. Nine patients developed new immune related adverse events (IRAEs) unrelated to underlying AD, such as inflammatory poly-arthropathy, neuropathy, hypothyroidism, diarrhea, lichenoid drug eruptions, which were managed with oral and/or topical corticosteroids. ICI was stopped in six patients due to AD flare, in four patients due to IRAE flare (out of which one resumed ICI after resolution of IRAE). CONCLUSIONS: In patients with pre-existing AD treated with ICI, AD flare occurred in 28% of patients and were managed successfully with corticosteroids alone or with additional disease-modifying therapies. ICI could be considered in patients with AD, but with very close monitoring and preemptive multidisciplinary collaboration.

Atypical Large Vessel Vasculitis Presenting With Cholestatic Liver Abnormalities: Case-Based Review.

ABSTRACT: Clinicians usually easily recognize cranial manifestations of giant cell arteritis (GCA) such as new-onset headache, jaw claudication, scalp tenderness, and abrupt changes in visual acuity or blindness; however, when presented with an aberrant clinical course, the diagnosis becomes more elusive. In addition to temporal arteries and other extracranial branches of the carotid arteries, large vessel vasculitis (LVV) can also affect other blood vessels including coronary arteries, aorta with its major branches, intracranial blood vessels, and hepatic arteries.Over time, the scope of the symptoms typically associated with LVV has broadened and includes cases of fever of unknown origin accompanied with other constitutional symptoms that can mimic a range of neoplastic and infectious diseases. In up to half of patients with atypical LVV, liver enzyme level elevations with a cholestatic pattern have been observed. Alkaline phosphatase level and γ-glutamyl transferase level elevations tend to be more prevalent in those LVV patients with vigorous inflammatory responses, particularly in those with fever and other nonspecific constitutional symptoms. These patients also have more profound anemia and thrombocytosis. With the exception of rare instances of vasculitides and granulomas affecting the liver tissue, liver biopsy is generally of little help and primarily shows nonspecific changes of fatty liver.In this article, we review 3 patients who were eventually diagnosed with atypical LVV. The diagnosis was confirmed with temporal artery biopsy in 2 patients and with positron emission tomography/computed tomography in 1 patient. The common hepatic abnormality observed in all patients was the elevation of alkaline phosphatase level, which tended to respond rapidly to initiation of immunosuppressive treatment.

Immune-related adverse events in cancer patients treated with immune checkpoint inhibitors: A single-center experience.

Immune checkpoint inhibitors (ICIs) like cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and programmed death cell protein 1 (anti-PD1) have revolutionized cancer treatment. As ICI use becomes widespread, more immune-related adverse events (irAE's) are being reported. Our aim was to investigate the frequency and nature of new irAE's as well as report the frequency of flare-ups of pre-existing autoimmune conditions occurring after ICI therapy.We performed a retrospective chart review of all patients treated for cancer with anti-PD1 or anti-CTLA4 or combination therapy at our tertiary care center from January 2014 to April 2016. Demographic data, cancer type and stage, irAE's (new immune disorders and disease flares of pre-existing autoimmune disorders on ICI therapy), and drug treatment information were extracted.We identified 220 patients treated with ICI therapy during the study period out of which 27% (60/220) developed irAE's. 11% in anti-CTLA4 group and 16% among anti-PD1 treated patients developed irAE's. IrAE's resulted in discontinuation of cancer therapy in 28% of those who developed irAE's. 21.4% had a flare of their autoimmune disease but only 1 required discontinuation of immunotherapy.IrAE's are an important emerging clinical disease entity for specialists to be aware of. Our study shows that ICI's can be safely used in patients with pre-existing autoimmune conditions with close monitoring. However, there is still a large unmet need to have a better understanding of how to systematically evaluate and manage patients with irAE's as well as for identifying the predictors of irAE's.

FIBROVASCULAR POLYP: AN UNUSUAL MASS IN THE ESOPHAGUS CAUSING DYSPHAGIA.

We present a case of a 56-year-old Caucasian women with long-standing gastroesophageal reflux disease complicated with non-dysplastic Barrett's esophagus and stricture presented with difficulty in swallowing.

Helicobacter pylori-negative Russell body gastritis: does the diagnosis call for screening for plasmacytic malignancies, especially multiple myeloma?

Russell body gastritis (RBG) is a rare entity with unestablished pathophysiology, endoscopic findings, clinical manifestations and treatments. Literature is scarce on this clinical entity with unclear clinical significance. Of 18 cases reported, 12 tested (+) for Helicobacter pylori and improved with treatment, but it remains unclear whether this link is coincidental or bears some clinical significance. We describe a case of elderly woman who had a follow-up oesophagogastroduodenoscopy for chronic peptic ulcers, and biopsy showed positive immunohistochemical stains for κ and λ, indicating a polytypic population of plasma cells. Immunostaining for H pylori was negative. Biopsies were also (-) for gastric carcinoma, lymphoma and plasmacytoma. Considering her RGB-suggestive histology and her symptoms of bone pains and anaemia, multiple myeloma screening was considered clinically relevant. The purpose of this review was to educate clinicians and gastroenterologists about this unique entity and explore its association with multiple myeloma or other plamacytic malignancies.

Transvaginal ultrasonography in first trimester of pregnancy and its comparison with transabdominal ultrasonography.

OBJECTIVES: Examination of pregnant women in the first trimester with transvaginal ultrasonography with the aim to study various fetal development markers, e.g., gestation sac, yolk sac, fetal heart motion, CRL length, and fetal anatomy in both normal and abnormal pregnancies. Comparative evaluation of transvaginal ultrasonography vis-à-vis transabdominal scanning in the study of first trimester of pregnancy and its complications. To assess the relative merits and demerits of transvaginal ultrasonography in comparison with the transabdominal technique. MATERIALS AND METHODS: The study will be conducted on 50 females patients during the first trimester of pregnancy. The study population will consist of both normal and abnormal pregnancies. These patients will be included on the basis of suspicion of or proven pregnancy of duration up to 12 weeks from LMP. The evaluation of the patients will include the following: Record of patients obstetrical history and clinical examination, record of pregnancy test and relevant investigations, ultrasonic examination of pregnancy. (a) Transabdominal ultrasound scanning will be done with moderately distended bladder by using real time scanners with low frequency probe (3/3.5 MHz); (b) transvaginal sonography will be done with the real-time sector scanner using high-frequency endovaginal probe (5/7.5 MHz), after the patient voids urine. Relevant images will be taken by using the multiformat automatic camera. RESULTS AND CONCLUSIONS: In the study of 46 normal intrauterine pregnancies, TVS showed additional information in 36 patients (78.3%) as compared to TAS, in detection of gestation sac, yolk sac, double bleb sign, or better visualization of embryonic anatomy. In the abnormal pregnancy (n=17), TVS provided more information in 11 cases (64.9%), which included detection of embryonic demise, yolk sac, double bleb sign, or subchorionic hemorrhage. Regarding ectopic gestations (n=7), TVS gave additional information in 5 cases (71.4%) which included detection of ectopic fetal pole, yolk sac, decidual cast, adnexal mass, and fluid in cul de sac. In two cases, both TAS and TVS gave equal information. However, in 2 cases TAS demonstrated the extent of intraabdominal fluid better than TVS. The other advantages of TVS over TAS are that there is no need for the patient to have uncomfortably full bladder and time is saved from having to wait for bladder to fill. Thus, the potential preoperative patient can be kept fasting. TVS is also superior in obese patients, in patients with retroverted uterus and it also bypasses obstacles such as bone, gas filled bowel, and extensive pelvic adhesions. The limitations encountered with TVS were limited manoveuribility of probe and because of the unorthodox position and angle of the transducer, correct orientation was difficult initially.

Molecular characterization and enzymatic hydrolysis of naringin extracted from kinnow peel waste.

Kinnow peel, a waste rich in glycosylated phenolic substances, is the principal by-product of the citrus fruit processing industry and its disposal is becoming a major problem. This peel is rich in naringin and may be used for rhamnose production by utilizing α-L-rhamnosidase (EC 3.2.1.40), an enzyme that catalyzes the cleavage of terminal rhamnosyl groups from naringin to yield prunin and rhamnose. In this work, infrared (IR) spectroscopy confirmed molecular characteristics of naringin extracted from kinnow peel waste. Further, recombinant α-L-rhamnosidase purified from Escherichia coli cells using immobilized metal-chelate affinity chromatography (IMAC) was used for naringin hydrolysis. The purified enzyme was inhibited by Hg2+ (1 mM), 4-hydroxymercuribenzoate (0.1 mM) and cyanamide (0.1 mM). The purified enzyme established hydrolysis of naringin extracted from kinnow peel and thus endorses its industrial applicability for producing rhamnose.

Citrus peel influences the production of an extracellular naringinase by Staphylococcus xylosus MAK2 in a stirred tank reactor.

Staphylococcus xylosus MAK2, Gram-positive coccus, a nonpathogenic member of the coagulase-negative Staphylococcus family was isolated from soil and used to produce naringinase in a stirred tank reactor. An initial medium at pH 5.5 and a cultivation temperature of 30°C was found to be optimal for enzyme production. The addition of Ca(+)² caused stimulation of enzyme activity. The effect of various physico-chemical parameters, such as pH, temperature, agitation, and inducer concentration was studied. The enzyme production was enhanced by the addition of citrus peel powder (CPP) in the optimized medium. A twofold increase in naringinase production was achieved using different technological combinations. The process optimization using technological combinations allowed rapid optimization of large number of variables, which significantly improved enzyme production in a 5-l reactor in 34 h. An increase in sugar concentration (15 g l⁻¹) in the fermentation medium further increased naringinase production (8.9 IU ml⁻¹) in the bioreactor. Thus, availability of naringinase renders it attractive for potential biotechnological applications in citrus processing industry.

Response surface optimization of medium components for naringinase production from Staphylococcus xylosus MAK2.

Response surface methodology was used to optimize the fermentation medium for enhancing naringinase production by Staphylococcus xylosus. The first step of this process involved the individual adjustment and optimization of various medium components at shake flask level. Sources of carbon (sucrose) and nitrogen (sodium nitrate), as well as an inducer (naringin) and pH levels were all found to be the important factors significantly affecting naringinase production. In the second step, a 22 full factorial central composite design was applied to determine the optimal levels of each of the significant variables. A second-order polynomial was derived by multiple regression analysis on the experimental data. Using this methodology, the optimum values for the critical components were obtained as follows: sucrose, 10.0%; sodium nitrate, 10.0%; pH 5.6; biomass concentration, 1.58%; and naringin, 0.50% (w/v), respectively. Under optimal conditions, the experimental naringinase production was 8.45 U/mL. The determination coefficients (R(2)) were 0.9908 and 0.9950 for naringinase activity and biomass production, respectively, indicating an adequate degree of reliability in the model.

Cell disruption optimization and covalent immobilization of beta-D-galactosidase from Kluyveromyces marxianus YW-1 for lactose hydrolysis in milk.

beta-D-galactosidase (EC 3.2.1.23) from Kluyveromyces marxianus YW-1, an isolate from whey, has been studied in terms of cell disruption to liberate the useful enzyme. The enzyme produced in a bioreactor on a wheat bran medium has been successfully immobilized with a view to developing a commercially usable technology for lactose hydrolysis in the food industry. Three chemical and three physical methods of cell disruption were tested and a method of grinding with river sand was found to give highest enzyme activity (720 U). The enzyme was covalently immobilized on gelatin. Immobilized enzyme had optimum pH and temperature of 7.0 and 40 degrees C, respectively and was found to give 49% hydrolysis of lactose in milk after 4 h of incubation. The immobilized enzyme was used for eight hydrolysis batches without appreciable loss in activity. The retention of high catalytic activity compared with the losses experienced with several previously reported immobilized versions of the enzyme is significant. The method of immobilization is simple, effective, and can be used for the immobilization of other enzymes.