Skin Lesions from Injecting Buprenorphine: The Sign of the Cross

Skin lesions from injecting buprenorphine

Skin lesions from injecting buprenorphine

 

 

Trapped in my house due to nine inches of snow and a slick driveway, last weekend I worked to catch up on my medical journals. An article in the January 2017 issue of The American Journal of Medicine caught my eye.

The article was titled “Curious Crosses: Injection-Induced Lesions” and it described the clinical course of a patient on buprenorphine monoproduct who sought care for recurrent, painful nodules. These nodules would erupt, exuding bloody pus. The article’s author described a fairly extensive work up of these lesions.

This patient was checked for all sorts of exotic diseases which can lead to skin eruptions of this sort, including tuberculosis, sporotrichosis and other fungal diseases, Sweet’s syndrome and Behcet’s disease.

Finally, one of this patient’s blood cultures grew Pantoea species. This was an important clue, because this bacterium is thought to be the cause of “cotton fever,” a syndrome of severe body aches, fever, and intense fatigue.  Cotton fever occurs in some drug users because cotton used to filter injected drugs often harbors Pantoea bacteria. Once the bacteria are injected along with the drug, they release an endotoxin, which produces the symptoms of cotton fever.

With this information, the patient was again questioned about injection drug use. The physicians already knew the patient had a history of intravenous drug use, but this patient told them he was doing well in medication-assisted treatment on buprenorphine.  The patient denied any ongoing injection drug use.

All pills and tablets meant to be taken orally contain fillers. These are usually inert substances that stabilize the active drug, and help the pill or tablet keep its shape. Substances that are formed with the active drug and serve to stabilize it are called “excipients.”

Buprenorphine sublingual tablets contain an excipient called amidon. As near as I can tell by internet search, this is a starch-type substance. This amidon, when injected, causes skin reactions and gives a distinct finding under the microscope.

Under polarized light microscopy, some substances refract light in a distinct manner that can help identify the substance. This property is called birefringence. Amidon is birefringent. Under polarized light microscopy, amidon crystals have the distinct shape of a Maltese cross.

Physicians treating the patient described in the article obtained skin biopsies of some of the patient’s sores. Polarized light microscopy showed the Maltese crosses from the amidon filler in buprenorphine, which more or less confirmed the diagnosis. Other substances can also cause Maltese crosses in skin biopsies, but of course, the most obvious cause in this patient was injection use of the prescribed buprenorphine monoproduct.

I got interested in this finding, and looked online to see if this had been reported before. It has.

In France, where injection use of buprenorphine monoproduct has been problematic, doctors have reported this distinct finding under light microscopy.

In fact, I copied the picture at the beginning of this blog from one of those articles (Schneider et al, “Livedoid and Necrotic Skin Lesions Due to Intra-arterial Buprenorphine Injections Evidenced by Maltese Cross-Shaped Histologic Bodies,” Archives of Dermatology, 2010;145(2):208-209.) In this case report, the patient was injecting into an artery, which is much riskier than into a vein, but the appearance of the Maltese cross in the same.

At the end of the report I found in the American Journal of Medicine, the authors said the patient continued to deny injecting his buprenorphine. All of the lesions he had upon admission were in locations where track marks are usually seen. During his hospitalization, no new lesions appeared on his skin.

The article’s authors state they reported their findings to this patient’s buprenorphine prescriber, who planned to discontinue buprenorphine in favor of other treatment options.

This case was interesting, informative, and reminds me to monitor patients closely when prescribing the buprenorphine monoproduct, often better known under its past brand name, Subutex.

I do prescribe the monoproduct buprenorphine, mostly for patients at the opioid treatment program where I work. In that setting, we do observed daily dosing. After getting their dose, the patients sit and are observed for however long it takes to dissolve the medication, and must show a staff member under their tongue prior to leaving the facility. We do this to help reduce diversion and promote proper use of the medication. We don’t grant take home doses unless and until patients have a degree of stability.

I have also prescribed buprenorphine monoproduct for some of my long-term patients in my office-based practice. If one of these patients, doing well for years, loses their medical insurance, I will switch them to the cheapest form of medication, which is the buprenorphine generic monoproduct. I do this only because I know them so well, and don’t want them to relapse, or have to switch to methadone at an opioid treatment program.

In other words, I have to judge that the benefits far outweigh the risks.

Even with the medical problems illustrated in this interesting article, buprenorphine monoproduct has a place in the treatment of opioid use disorder. And this article reminds physicians we must use the monoproduct medication thoughtfully.

Many of the new patients I see entering treatment at the opioid treatment program have injected buprenorphine pills. I’ve seen some really terrible looking tracks, and now I suspect the scarring and inflammation may be due to these Maltese crosses from amidon crystals.

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10 responses to this post.

  1. Posted by Mikael Langner on January 15, 2017 at 11:10 pm

    Thank you for an informative and interesting blog. It took me a minute to see the Maltese Cross on the histology, but then I saw it. I come to medication-assisted therapy from a general practice setting, but with my research experience in dermatology this blog for the first the first time provides a link for me between MAT and dermatology. Knowing what I do about reimbursement rates, one can imagine that the four or five diagnostic misses, the skin culture, and the hospitalizatin probably ran into the tens of thousands of dollars. I would imagine the patient had some idea of this cost to his insurance company, and one could also surmise that his denial of IV injection until the very end may have had something to do with his concern that maybe he would be stuck with the bill if it was found the lesions were the product of his bad behavior. Maybe not too far afield from those early days when doctors would wonder if the endocarditis patient with the aortic valve replacement could be turned away when they came back with yet further compications. After all, what benefit would it be to the patient to at the end say, “you caught me, I was injecting my buprenorphine?”

    Reply

  2. Posted by mike on January 16, 2017 at 3:27 pm

    Howdy! I just can’t overstate how much I appreciate your blog! I’m a clinical supervisor at an OTP in Baltimore and have been there for almost 20 years. In that time, I have to say that your blog is the best internet resource I’ve found. THANK YOU! I’m actually home from work today because of MLK Day and will be doing a lot of reading through your blog, so I’ll probably be leaving other questions and comments throughout the day. Our program does methadone only, though we have tried bupe a few times without much success and I wasn’t directly involved with that service line, so my knowledge about bupe is a little deficient. Here’s my question: Doesn’t someone who snorts or injects bupe, or at least Suboxone, go into withdrawal? I thought that was why it was being marketed as a wonder drug back when it first came around. I thought if used properly, under the tongue, the Naloxone was not released, but if it was abused, i.e. injected or snorted, it produced a withdrawal response. Thanks in advance for your time!

    Reply

    • since buprenorphine is a partial opioid agonist with a high affinity for opioid receptors, patients accustomed to using full opioids CAN be put into withdrawal by buprenorphine alone, unless they wait until they are already in moderate withdrawal prior to taking the first buprenorphine dose.
      Naloxone isn’t supposed to be absorbed sublingually. However, since doctors have done drug screen that do show naloxone levels, I think some patients still absorb some of the naloxone, even though they are not “supposed” to do so. The combination product of buprenorphine plus naloxone will put most addicts into withdrawal if they inject the combination, since the naloxone would be fully put into the patients’ systems.

      Reply

  3. Posted by mike on January 16, 2017 at 6:09 pm

    Oh, I think I may have figured out the answer to my question. I just noticed your use of the word “monoproduct,” which I imagine means just bupe, as opposed to Suboxone. Then I guess a secondary question would be why use just the monoproduct? I guess part of my knowledge deficit about buprenorphine is that I thought Suboxone was so prevalent that it was almost synonymous with the word buprenorphine. Apparently not…?

    Reply

    • I try to stay away from brand names, since we now have several on the market: Zubsolv, which is a combo product, of course Suboxone, and also Bunavail.
      Why use monoproduct? Some patients DO get ill with the naloxone, even though they aren’t “supposed” to. But it’s a risk, since it’s much more desirable for IV use. Plus, the generic monoproduct is the cheapest form of buprenorphine on the market. In my area, it’s about a quarter of the price of the name brands.

      Reply

  4. Posted by Ron Kaes on January 17, 2017 at 12:41 am

    I don’t think that the combination product (containing naloxone) would have prevented injection in this circumstance, because the binding affinity of bupe is higher than naloxone. I think that the only time that the naloxone has an impact is during the induction phase, while switching from a full to partial agonist.

    After that, if you are dependent on bupe only, I believe that the combination product can be injected without experiencing precipitated withdrawal. With that being the case, the patient in question would probably have injected suboxone just as they were injecting subutex. What do you think?

    Reply

    • I know that the monoproduct commands a higher price on the black market than the combo product. I think that’s because the monoproduct is more desirable for injection.

      Reply

  5. Posted by Dominique on January 22, 2017 at 5:49 pm

    I’m curious if the people injecting Buprenorphen are straining it through cotton like many of them do with heroin. Is this where or a likely source of the bacteria? Are they using cotton to filter?
    Very interesting blog. Thank you as they are always informative.

    Reply

  6. Posted by karen brown on January 30, 2017 at 2:42 am

    will the lesions take longto heal and is it from sittingup under there skin not absorbing b/c of them fillers in their meds? wow horrible how long be no paid. from it

    Reply

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