Feline Eosinophilic Keratoconjunctivitis: Nonsteroidal vs Corticosteroid Topical Treatment

Background: Feline eosinophilic keratoconjunctivitis is a proliferative eye lesion of chronic aspect with usually unilateral presentation that may initiate as a superficial vascularization that evolves to a proliferative, granular, irregular lesion of whitish-pink aspect. With its association with an immune-mediated response, nonsteroidal anti-inflammatories do not appear to be efficient, although few studies describe its use. This case report describes a case of a feline eosinophilic keratoconjunctivitis with its clinical evolution since the use of nonsteroidal topical anti-inflammatory drug in an undiagnosed patient and the transition to a topical corticosteroid and cure after 14 days since diagnosis.Case: An 8-year-old female cat was attended at the Veterinary Hospital of the Dom Bosco Catholic University (UCDB), with main complaint being an eye injury with at least 36 days of evolution andunresponsive to treatment (topical tobramycin 0.3% every 12 h / ketorolac trometamol 0.5%/ every 12 h and ophthalmic lubricant/every 4 h). Since the patient had free access to the street, the owners suspected of trauma-induced lesion. At physical examination, it was observed a proliferative lesion at the peri-limbal superotemporal quadrant of the right cornea with approximately 0.4 cm diameter, with color varying of pale to pink, with irregular surface and low vascularity, the adjacent conjunctiva was also affected with similar multiple nodular lesions (0.1 cm). Fluorescein test was negative as well as FIV/FeLV immunochromatography testing. Feline herpesvirus investigation was not possible. The patient was anesthetized and a lesion specimen was acquired with a cotton swab scraping and a fine needle aspiration. Cytology showed predominance of eosinophils and mast cells, with rare corneal epithelial cells, with smear background containing mast cell granules and free eosinophils. Presumptive diagnosis was eosinophilic keratoconjunctivits. After 14 days of topical corticosteroid (prednisolone acetate 1% every 8 h) the patient showed complete remission of the lesions with no relapse in 48 days.Discussion: Misdiagnosis and consequently mistreatment seems a greater prejudice than the risks associated with sample collection of keratoconjunctival proliferative lesions. Due to the lack of cytobrush or cotton swab, apparently, the reported patient was not submitted to ophthalmic cytology due to reluctance of the staff regarding fine needle aspiration of the cornea lesion. Despite a greater risk of iatrogenic trauma with needle aspiration, with eye anatomy well defined, level size and movement amplitude respected, it is unlikely that severe complications could occur. In this case, the undiagnosed patient was submitted to unnecessary 15 days of topical antibiotic and nonsteroidal anti-inflammatory, and no improvement of the clinical signs was observed. Despite non-recommended, few clinical trials as well as case descriptions are available comparing nonsteroidal and corticosteroid treatment of the disease. Once with diagnosis and beginning of topical prednisolone acetate 1% exclusively, the patient showed continuous improvement until complete remission of clinical signs after 14 days. This report reinforces the recommendation of corticosteroid therapy for feline eosinophilic keratoconjunctivitis and the absence of efficacy of nonsteroidal drugs. It also highlights the importance of diagnosis before any medical treatment is considered.

AMELIE 3: Fully Automated Mendelian Patient Reanalysis at Under 1 Alert per Patient per Year

BackgroundMany thousands of patients with a suspected Mendelian disease have their exomes/genomes sequenced every year, but only about 30% receive a definitive diagnosis. Since a novel Mendelian gene-disease association is published on average every business day, thousands of undiagnosed patient cases could receive a diagnosis each year if their genomes were regularly compared to the latest literature. With millions of genomes expected to be sequenced for rare disease analysis by 2025, and considering the current publication rate of 1.1 million new articles per annum in PubMed, manually reanalyzing the growing cases of undiagnosed patients is not sustainable.MethodsWe describe a fully automated reanalysis framework for patients with suspected, but undiagnosed, Mendelian disorders. The presented framework was tested by automatically parsing all ∼100,000 newly published peer reviewed papers every month and matching them on genotype and phenotype with all stored undiagnosed patients. If a new article contains a possible diagnosis for an undiagnosed patient, the system provides notification. We test the accuracy of the automatic reanalysis system on 110 patients, including 61 with available trio data.ResultsEven when trained only on older data, our system identifies 80% of reanalysis diagnoses, while sending only 0.5-1 alerts per patient per year, a 100-1,000-fold efficiency gain over manual literature surveillance of equivalent yield.ConclusionWe show that automatic reanalysis of patients with suspected Mendelian disease is feasible and has the potential to greatly streamline diagnosis. Our system is not intended to replace clinical judgment. Rather, clinical diagnostic services could greatly benefit from a modest re-allocation of time from manual literature exploration to review of automated reanalysis alerts. Our system additionally supports a new paradigm for medical IT systems: proactive, continuously learning and consequently able to autonomously identify valuable insights as they emerge in digital health records. We have launched automated patient reanalysis, trained on the latest data, with user accounts and daily literature updates at https://AMELIE.stanford.edu.

An undiagnosed patient with skin rash, polyarthritis, and edema responding to low-dose colchicine: A case report

A 54-year-old man was referred to our hospital with painful rashes on the extremities. He also developed polyarthritis and pitting pedal edema. Blood tests showed no specific autoantibodies and were negative for human leukocyte antigens B51, B15, and B27. Lower extremity venous ultrasonography and computed tomography angiography showed no vascular disorders. Skin biopsy showed no evidence of thrombosis or vasculitis. Direct fluorescence antibody analysis showed no antibody or complement deposition. Joint ultrasonography showed mild synovial thickening and/or synovial effusion in the extremities. Non-steroidal anti-inflammatory drugs and topical steroids were administered, followed by oral steroids. However, the signs and symptoms did not improve. Oral steroids were discontinued, and colchicine (0.5 mg/day) was administered. Thereafter, the symptoms of arthritis improved, and no skin rash developed. In potentially inflammatory conditions with skin rash, edema, and polyarthritis that are difficult to diagnose, low-dose colchicine administration may be considered for prompt relief of symptoms.

Simultaneously Monitoring Immune Response and Microbial Infections during Pregnancy through Plasma cfRNA Sequencing

BACKGROUND Plasma cell-free RNA (cfRNA) encompasses a broad spectrum of RNA species that can be derived from both human cells and microbes. Because cfRNA is fragmented and of low concentration, it has been challenging to profile its transcriptome using standard RNA-seq methods. METHODS We assessed several recently developed RNA-seq methods on cfRNA samples. We then analyzed the dynamic changes of both the human transcriptome and the microbiome of plasma during pregnancy from 60 women. RESULTS cfRNA reflects a well-orchestrated immune modulation during pregnancy: an up-regulation of antiinflammatory genes and an increased abundance of antimicrobial genes. We observed that the plasma microbiome remained relatively stable during pregnancy. The bacteria Ureaplasma shows an increased prevalence and increased abundance at postpartum, which is likely to be associated with postpartum infection. We demonstrated that cfRNA-seq can be used to monitor viral infections. We detected a number of human pathogens in our patients, including an undiagnosed patient with a high load of human parvovirus B19 virus (B19V), which is known to be a potential cause of complications in pregnancy. CONCLUSIONS Plasma cfRNA-seq demonstrates the potential to simultaneously monitor immune response and microbial infections during pregnancy.