Hidradenitis Suppurativa Support Group
Hidradenitis suppurativa (hi-drad-uh-NIE-tis sup-yoo-ruh-TIE-vuh) is rare, long-term skin condition that features small, painful lumps under the skin. The disease manifests as clusters of chronic abscesses or boils, sometimes as large as baseballs, that are extremely painful to the touch and may persist for years with occasional to frequent periods of inflammation,...
Many apologies, I may be misadvising people on the subject of SCV (small colony variant) microbes as the likeliest cause of recurrence of HS following improvements caused by antibiotics. I'm still not entirely sure, it's a pretty complicated subject, but I thought I might owe people a warning.
One place where I may have gone wrong is that I've seen SCVs associated with long courses of antibiotics (without further clarification how long "long" actually is) so that in that sense they try to sound plausible as one of the things that might go wrong in the Pasteur Institute studies (which might have otherwise cured even some of the worst HS patients had the HS not come right back when the antibiotics stopped), because their initial studies involved relatively long courses of antibiotics which sometimes ran as long as six months.
Another reason this may have tried to sound (mistakenly?) attractive as a reason for HS recurrence is that if one goes to wonder how in the very first stages of recurrence, when there is presumably a minimum number of surviving bacteria, how a sprinkling of troublemakers left behind after successful antibiotic treatment are getting the better of the immune system, so microbes that persist as small colonies (small colony variants) might sound somewhat plausible, since these colonies may be more fit to fight off immune cells by sticking together. SCVs also try to sound plausible because they can be created by antibiotic use.
The past week, I've tried to sort out the difference between SCVs and similar bacterial phenomena more carefully than ever, and ended up less sure than ever that SCVs deserve the top nomination. (It's a little hard for me to do the subject much justice, mainly in earlier or simpler cases of HS we'd probably be talking about Staphylococcus, whereas in the last year or so I've been called up on to study other microbes in HS, other pathologies, and now I seem to be having to even study antibiotics themselves in trying to understand why they've failed).
However, if something like this is to blame for HS so famously staging a comeback when antibiotics stop, maybe the L-form phenomena makes a better suspect than SCVs?
It's not even my idea, I'm sure I have at least one research paper on HS specifically where L-forms are is proposed as a reason for HS being difficult to successfully treat (which for some reason isn't coming out of Google today when I look for "L-form" and "HS". I though that at least one of these research papers also mentions biofilms (which may have more to do with some cases that may not be so easy to put into remission with antibiotics in the first place?) but adding "biofilm" for a keyword didn't help either today, I'll try to find it in my notes later. There are plenty of papers that have been written on L-form Staphylococcus aureus, although I'm not sure yet exactly how much of it applies to other common Staphylococcus species in HS.
I haven't taken biofilm as a possible part of HS very seriously yet because even if it were part of my HS, it doesn't seem to have stopped them from saving my life with antibiotics on more than one occasion, and it doesn't seem to have stopped antibiotics from putting HS into remission in numerous cases.
This author seems to be willing to haul off and nearly give biofilms credit for a great deal http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278191
"Because the skin lesions in HS are chronic and recurring and require long courses of antibiotics for treatment, it seems likely that HS is a biofilm disease."
Although I'm not as sure myself that sometimes long course of antibiotics aren't "required" because the doctors don't know quite know when to quit, and that may even include the outstanding studies by the Pasteur Institute workers, just as they still may not be hunting Staphylococcus with the best antibiotics yet even though Staphylococcus dominated their Stage 1 HS cultures. The first thing likely to jump out at someone about L-forms is how they are created in laboratories by feeding them antibiotics that target the cell wall of microbes.
"L-forms can be generated in the laboratory from many bacterial species that usually have cell walls... This is done by inhibiting peptidoglycan synthesis with antibiotics or treating the cells with lysozyme, an enzyme that digests cell walls."
https://en.wikipedia.org/wiki/L-form_bacteria
The Pasteur Institute has done great things with ertapenem for HS, probably because ertapenem kills enough different troublemaking microbes to clean up most of what could be the problem and most bugs haven't shown resistance to it yet, but carbapenems such as ertapenem target the microbial cell wall.
That isn't to say that SCVs don't appear in HS, or play some kind of role - there may be a role for a type of organism that doesn't make a rapid comeback, but might reappear futher down the line, or might remain unnoticed by anyone indefinitely, and one or more of those might be where they fit into the picture. There's a report of several cases of HS that were apparently successfully treated (cured?) where careful inspection years later still revealed some immune system abnormalities that might owe to a persistent infection. I still haven't gotten the literature to be perfectly clear on this, but L-forms and SCVs might also be able to appear simultaneously, since antibiotics can be involved in their creation or selection.
Anyway, I'm sure HS is confusing enough without me misleading anyone, so I truly hope that isn't what I've been doing, and I do apologize. A person probably can't help going out on a limb with this stuff since much of it can be obscure or poorly understood, but I continue in my faith that maybe even the data we've already been given on HS by the Pasteur Institute and others, may be enough to understand HS if we can find the opportunity to think it over carefully enough.
Mainly I'm looking at antibiotics because that is something we can expect most doctors to be at least somewhat familiar with, and may of us may still be able to benefit as long as our doctors don't make too many mistakes.
I've been mulling over this stuff again lately and I'm more suspicious than ever than we may still have a lot of antibiotic failures for explainable reasons, usually involving human error of one kind or another on the doctor's part. Somehow or other molehills may get made into mountains, giving HS a reputation for being much more difficult to treat and much more mysterious than it actually is.
I especially wonder if the biggest setback to progress in treating HS the last 30 years might be that perhaps it's very hard for anyone in the medical community to accept that we've all been outsmarted all these years by something as simple as the combination of Staph and a gut bug (Prevotella and/or Bacteroides).
This might be taking place even at the Pasteur Institute, where it sounds a bit like even they have trouble to accept what their own data seems to be showing (that Staph + gut bug may be the only thing all of at Stage 2 or higher
can be expected to have in common, so maybe they're tempted into a "kill 'em all and let God sort 'em out" approach, with multiple board spectrum antibiotics and trying to target everything on the patient at once instead of targeting the Staph and any more aggressive (but less resistant) gut bugs first.
I wish I had any metabolite studies handy to help clarify this, but the insistence on adding metronidazole to all these experimental antibiotic regimens might be undermining some of the other antibiotics being given with it.
If metronidazole is able to do to other antibiotics inside a microbe what it does to microbe DNA (cause damage), it might explain why they're not getting success from what otherwise sound like some ideal combinations (I cannot quite figure out otherwise how they're failing to kill our Staph with rifampicin or rifampicin + clindamycin). Again, the Pasteur Institute researchers themselves wrote a paper on how rifampicin might undermine the effectiveness of clindamycin if they are given together, but maybe they don't quite yet realize all of the things that might go wrong in this area?
It might also be that a lot of doctors still don't really have guidelines that help them to understand what they're dealing with with biofilm infections. I definitely got this impression from both my personal physician and the infectious disease specialist they sent me to, believe it or not. They may be confusing biofilm bacterial behavior with ordinary bacterial behavior or trying to force-fit diagnostic criteria made for ordinary bacteria onto biofilms.
They may sometimes be confused by finding both biofilm and ordinary virulence, and assume they are seeing one or the other when they're actually seeing the same microbe appear as both forms at the same time.
The best recommendations I've seen for if/when in doubt when dealing with biofilms is to try to hang onto the cultures for longer than is usually necessary, to give the biofilms time to appear because they are often slow-growing, lacking the rapid exponential growth rate associated with ordinary bacterial behavior.
What I've seen so far also suggests that many biofilms may decrease the production of tissue-destructive toxins like proteases or hemolysins, and increase their production of immunosuppressive toxins, which may make it harder for our immune systems to clear these infections, or some of the secondary infections they may invite with their immunosuppressive activities.
They may be a case that requires a slightly different approach than just slowing down bacterial growth as some antibiotics do to allow the immune system to catch up. With what seems to be our signature Staph (Staphylococcus lugdunensis), we do have a great study to rely on that may help immensely (I think the link is earlier in this thread) to know what may kill this Staph in both its ordinary and its biofilm forms even if microbiological tests aren't available.
Just being aware that S. lugdunensis even exists can be a big help, though - I think being misdiagnosed with MRSA may happen to HS patients a lot, and that mistake may lead to the wrong choice of antibiotics, or the doctors jumping to the conclusion that "nothing works on it" when we still have a number of antibiotics that should do the job.
Currently I'm trying to figure out if there's the possibility of some biofilm bacteria getting off the radar because of culture methods themselves, in that I've seen a wealth of material that points out 3 main classes of SCV/biofilms that are all mutants, each lacking the ability to synthesize a particular nutrient that they need to assume the more virulent normal form. One of three nutrients I've most often seen missing in them in hemin, so I really have to wonder if they try to culture these on hemin, if they can force them out of the biofilm state so that they fail to culture a biofilm?
Again, though, I think HS has managed to take on a reputation that may be far beyond what it deserves, and a lot of mystery may have crept in just because some of the best sources (HS textbooks, Mayo Clinic websites) are still dragging along the baggage of what appears to be a mash-up of two studies (Lapins et al + Jemec et al) where during the collision some of the numbers look like they got turned on their heads so that what SHOULD have come out
"HS might be caused by infection because infection is found at least 85% of the time"
Got turned into
"HS probably has nothing to do with infection because infection is not usually found in HS cases"
The best microbiological study ever done is most likely still the work by the Pasteur Institute, which certainly does seem to find infection in HS with remarkable frequency.
Thankfully, I've seen pages that suggest that trusted sources like the Mayo Clinic are starting to become more aware of biofilms and of Staph. lugdunensis both.
https://www.youtube.com/watch?v=aXFl_GGW7x8
Just for the record, I am not necessarily in agreement that large short doses of antibiotics are the most appropriate way to treat biofilm infections (I am probably more of the opinion that antibiotics need to be selected as carefully as possible for this even if requires susceptibility testing) but as the gentleman in the video (Dr. Bill Costerton) points out, we are all still learning about these things and how to best deal with them.