Crohn's and itraconazole

In 2010, Samuel and colleagues published a small retrospective study describing five Crohn’s patients who had contracted the soil fungus Histoplasma capsulatum, and how they responded to treatment. This fungus is endemic in the Ohio and Mississippi river valleys, and causes histoplasmosis, a possibly life-threatening fungal infection of the lungs.

These patients were told to cease taking immunosuppressants, which they had been using to reduce their Crohn’s symptoms. This would help their immune systems fight-off Histoplasma capsulatum in their lungs. In addition, they were given a very long course of the antifungal drug itraconazole.

This is weird… These researchers were surprised that four out of five patients did not suffer severe Crohn’s symptoms during treatment for histoplasmosis, as they expected would occur following discontinuation of immunosuppressants. Instead, these patients seemed to be getting better! It wasn’t immediately obvious how itraconazole was improving Crohn’s symptoms:

1. Is itraconazole killing a fungus in the gut which causes Crohn’s?

2. Is itraconazole an immunosuppressant too?

3. Maybe itraconazole isn’t doing anything at all to Crohn’s symptoms (they can wax and wane naturally), and these results are a fluke.

Back in 2010, it is was not yet known that the fungus Malassezia colonized our internal organs, including our guts. However, it had been widely known for two decades that the immunological hallmark of Crohn’s disease was an immune response against fungi (Main et al 1988; Dotan et al 2006). By principle of parsimony, this means that Crohn’s patients’ immune systems are likely fighting a fungus which is the root cause of Crohn’s disease. There are a number of other possible explanations for the above observations, but these are much more complex and difficult to prove.

Given that (a) an immune response against fungi is the immunological hallmark of Crohn’s disease, and (b) a small study showed that a broad-spectrum antifungal drug seemed to cause remission, it follows that this small study needs to replicated with proper controls. This is one of the lowest hanging fruits in medical research.

If it is in fact itraconazole’s fungicidal properties which are causing remission, then other antifungal regimens or drugs might be more effective than itraconazole alone. For the sake of those suffering from Crohn's, it is imperative to sort this out as soon as possible.

Short video explaining this: https://youtu.be/6B6-bPlX7VQ

Full video explaining this: https://youtu.be/TYInWH4fzA0