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Metagenomic Deep Sequencing for Uveitis Enhances Traditional Diagnostic Testing



Type of Spiritual Experience


Thus, the person had rubella.  He developed a cataract [causes unknown and not investigated] and was put on an immunosuppressant.  Needless to say the virus spread and turned into uveitus and skin diseases [the rash].

Uveitis is the inflammation of the uvea, the pigmented layer that lies between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and includes the iris, ciliary body, and choroid. Uveitis is an ophthalmic emergency.

So far we have a sad history of incompetence.

Then he is seen by people who are determined to find the cause of the disease.  They do MDS testing, and find the rubella virus.

The statement "Because of the German vaccination policies at the time, he had not been immunized against rubella virus." is a red herring and somewhat nasty, as it implies it was his fault for not getting vaccinated.  But rubella is a latent virus - vaccinated or not he would have it in his body whether he caught it or was vaccinated with it.

The culprit was the use of immunosuppressants.  To be on immunosuppressants for a year was guaranteed to make him very very ill and he was.

A description of the experience

Metagenomic Deep Sequencing for Uveitis Enhances Traditional Diagnostic Testing

March 20, 2017 • By Thuy Doan, MD, PhD, Michael R. Wilson, MD, MAS, & Joseph L. DeRisi, PhD

......    He eventually developed a white cataract in the right eye and underwent cataract surgery and IOL placement. His immunosuppression was discontinued after one year due to treatment futility [sic]. There was a discussion to transition the patient to another antimetabolite, CellCept, but he never started the medication due to recurrent lower extremity rashes.

The Rheumatologist: Vol 11 – No 3 – March 2017

The patient relocated to San Francisco in 2012 and sought care at the Proctor Foundation at the University of California, San Francisco. His exam was notable for inflammatory cells in the anterior and vitreous cavity bilaterally. Further, he had heterochromia (different iris color between the two eyes) suggestive of chronic viral infection.

An anterior chamber paracentesis was performed, and aqueous fluid was tested for HSV, VZV and CMV by polymerase chain reaction (PCR). Although the results were negative for herpesvirus infection, the patient was maintained on systemic and intravitreal antivirals because of the high degree of clinical suspicion. When he had to undergo a pars plana vitrectomy to remove an epiretinal membrane in the left eye, another diagnostic work-up was initiated, which included cytology, bacterial and fungal cultures, HSV, VZV and CMV PCRs. Again, all tests were nondiagnostic.

The patient’s aqueous fluid was finally evaluated by unbiased MDS. After filtering out host sequencing reads and environmental reads, the most predominant remaining viral reads aligned to rubella virus, a known infectious cause of uveitis. More importantly, a near full-length genome (99.3%) of the rubella virus was obtained. Phylogenetic analysis revealed that the rubella virus detected in the patient’s eye was mostly closely related to a rubella virus isolated in Stuttgart, Germany, in 1992.

Upon further questioning, the patient reported that he had had a three-day fever and whole body rash in 1993 when he was living in Germany. Because of the German vaccination policies at the time, he had not been immunized against rubella virus [see comment above]. Thus, it appears as if his ocular history actually began in 1993, a full six years prior to the onset of his uveitis.

In this case, MDS not only identified a very unusual cause of infectious uveitis, it also highlighted the Achilles heel of pattern recognition as a primary means of diagnosis in patients with inflammatory disease. In the vast majority of cases, a patient’s three-day fever and rash that had occurred six years prior to the onset of their current clinical syndrome would not be considered clinically relevant—or even asked about by most clinicians. Thus, MDS has the ability to not only identify unusual pathogens, but it will also help redefine clinical syndromes by its unbiased and comprehensive approach

The source of the experience


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