Defining a disease: how often are atypical presentations due to multiple agents?

It's been a long time since I was a real doctor, but occasionally I play one when the kids are sick (my wife is still a real doctor). In the latest episode our six year old had a week of vomiting, persistent fevers, hand and foot complaints and rashes that, to tired and worried parents, looked a bit like Kawaski's Disease. Happily a set of bloodlettings cured him and he never made the diagnostic criteria.

So what did he "really" have? "Bad adenovirus" is the story our most excellent pediatrican gave, though he admits he really doesn't know. In reality, of course, there's no reason why he had to have just one virus. There's nothing about being infected with, say, an enterovirus, that makes one immune to infection with an adenovirus. Likewise a strep infection, for example, does not prevent coronavirus infection. They're all around us in Minnesota at this time of year.

We're used to thinking about multi-organism infections in the context of HIV and ICUs, but they must happen reasonably often in the ambulatory setting. How many unusual presentations, including some with persistent injury or even death, are really the result of coincidental simultaneous viral (or bacterial) infections that together produce far more disease than each would alone? How often does a pathogen cause a commensal to become pathogenic? Our models of disease are, like all models in science, only approximations. We haven't had the instruments to further refine these models, and thus to reconsider the nature and definition of infectious diseases. It will be interesting to see how these things change as we get cheaper and better rapid tests for viral and bacterial infections.

Of course I'm sure all of these speculations are old hat in the infectious disease and microbiology communities, but my background is in primary care. I think changing from a simplified model of disease to a multifactorial and 'emergent' model, will have some interesting consequences in many domains. (I've omitted mention of additional genetic and environmental interactions because that's kind of obvious ...)

PS. Incidentally, when reading about KD both my wife and I were struck yet again about how feeble the descriptions of disease are in the biomedical literature. Most of the descriptions are a list of uncorrelated and unsequenced complaints and findings, as though combinations and temporal evolution were irrelevant -- when in fact those are often the key 'signatures' of a disease. If I didn't know better I'd say our medical writers are encrypting their knowledge, but in fact this I know there's no conspiracy here. It's simply that the audience doesn't demand better.

By comparison layperson stories are often much richer; one parent's website featured a terrific slideshow and description of the evolution of their daughter's successful treatment that shamed every medical text we reviewed. Osler's descriptions of disease in the early 20th century are far better than what we read nowadays.

Some curmudgeon needs to write a paper about this!

PPS. And then there's the remarkable paucity of data in most reviews and articles on the prevalence of cardiac aneurysms in treated Kawasaki's Disease. Come on gang! Applied biomedicine could use a kick in the old pants ...