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Tacrolimus and Lupus Gene

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Tacrolimus for the Skin?
By A. G. Moore 2/14/2014

Immunofluorescent image of pemphigus
By Emmanuelm
From Wikimedia Commons on share alike license

The first and only time I was prescribed tacrilomus I used it in ointment form. The dermatologist prescribed the medicine as an alternative to a topical steroid.

“This may not work,” she said, as she tore off a sheet from her prescription pad. “But you can try it.”

The ointment proved to be very effective–topical tacrolimus cleared up what had been a minor but persistent issue. The problem not only went away; it never came back.

Since my experience with tacrolimus I’ve learned that this drug is used for many other conditions. According to DermNetNZ, topical, oral and IV tacrolimus have been shown to be effective at curbing the symptoms of some serious dermatologic disorders. These include, among others, discoid lupus, psoriasis, atopic dermatitis and pemphigus.

The oral and IV forms of tacrolimus are also sometimes used to suppress tissue rejection after organ transplant surgery. There is some suggestion that this drug may be helpful in controlling symptoms of ulcerative colitis. While its effectiveness in treating UC has only been demonstrated in clinical trials, these trials indicate that tacrolimus may eventually become a valuable treatment option for people who are challenged by this inflammatory bowel disease.

The topical formulation of the drug may be an alternative to steroids for treating dermatologic conditions on the face–especially around the eyes. That’s because these areas have thinner skin than is found elsewhere on the body and steroids have a tendency to thin the skin. Topical tacrolimus is less inclined to do this.

The use of this drug in the treatment of vitiligo appears promising. The Journal of Dermatology reports a study out of Taiwan that indicates topical tacrolimus was effective in reducing symptoms of vitiligo on the face and neck. The Journal of Dermatology
article states that about 1/4 of participants in the Taiwan study reported “mild” side effects and all patients “showed repigmentation”.

As for safety during pregnancy, an article posted on MedicineNet suggests caution is advisable. This article also indicates that there may be a relationship between long-term use of tacrolimus ointment and skin cancer. While the MedicineNet article explains that absorption of topical tacrolimus is likely minimal, there are exceptions to this. Among children, to whom a reduced dose is administered (.03%), there is a subgroup that experiences significant systemic absorption of the drug. Children with Netherton Syndrome, an inherited skin disorder, have been shown to have high levels of tacrolimus in their blood streams because of transdermal absorption.

Physicians and parents should take care that Netherton Syndrome not be misdiagnosed as atopic dermatitis. The two disorders may be very similar in appearance. Any drug that is powerful enough to suppress the immune system after organ transplant is likely to have serious side effects; this is the case with tacrolimus. In looking at side effects from oral and IV administration, the Mayo Clinic provides a rather daunting list of possible adverse events. Another sobering list can be found on WebMD.

Often, if a patient is dealing with an inflammatory dermatologic condition, options can seem limited. Steroids are the go-to remedy, but they have their drawbacks, especially if treatment of the face or neck is necessary. While tacrolimus may offer an alternative treatment, all benefits and side effects (only a few of them mentioned in this piece) must be considered.

The following websites offer additional information about tacrolimus; a qualified medical professional would be able to guide in any decision about whether use of this medicine is appropriate.

http://www.uofmhealth.org/health-library/d04740a1

http://www.patient.co.uk/medicine/Tacrolimus.htm

The Lupus Gene
By A. G. Moore 2/1/2014

Image by BruceBlause
Wikimedia Commons, share alike, attribution license

Headlines about the discovery of a “lupus gene” created a bit of optimism in the lupus community recently. However, as is usually the case, the reality of the breakthrough is more nuanced than the headlines suggest.

Increasingly, research about lupus has focused on the role of B cells in disease activation; for example, the newest lupus drug approved by the US FDA, Benlysta, targets B cells. Although use of Benlysta has proved to be modestly effective, doctors still look to B cells as an area where lupus therapies may be developed. The new “lupus gene”, not coincidentally, is associated with B cell activity.

So what exactly is it that was discovered and why such optimism? It seems that, for years, researchers have recognized the presence of a B cell “receptor”  called Fc. Fc plays a role in antibody suppression. When an infection is detected by the immune system and antibodies are produced, Fc receptors recognize the presence of these antibodies. As the number of antibodies grows and they are no longer needed to fight infection, Fc shuts down production. That’s a good thing. Too many antibodies floating around can end up attacking healthy tissue rather than foreign bodies. So Fc is an ally in the immune response.

However, what scientists at the University of Alabama claim to have discovered is a variant of Fc, a variant that doesn’t stop antibody production, but stimulates it, leading to over stimulation. Over stimulation is not a good thing. Excess production of antibodies is at the heart of lupus and other autoimmune diseases.

Identifying Fc as a culprit in the chain of events that causes overproduction can be very helpful in understanding and treating autoimmune disease.

Right now, most lupus drugs act by tamping down the immune response; this may curb symptoms but it also generally wreaks havoc on the body. If the variant Fc turns out to be a lupus culprit, as University of Alabama researchers believe, then therapies might be developed that target just this small part of the immune system. To understand the significance of this, think of the fight against lupus as a war. Using Fc-targeted therapies would be like using a sniper to get the enemy rather than using a cluster bomb. It’s obvious that a sniper would cause a lot less collateral damage than a bomb would.

Although headlines may have announced a breakthrough in lupus research, not everyone is in agreement that the “discovery” is indeed valid. Dr. Jeffrey Ravetch of Rockefeller University is a key researcher working with Fc receptors. Dr Ravetch has declared that the University of Alabama’s Fc research is “technically flawed” and doesn’t prove anything. Dr. Ravetch is not likely to be a lone skeptical voice.

Despite the lack of consensus on the variant Fc receptor, it’s important for people who have lupus to understand the ongoing discussion among researchers, no matter how it plays out. Very powerful drugs are prescribed to control lupus–or not, depending on severity of disease. Because lupus drugs are so powerful and taking or not taking them can have profound consequences, patients should understand why the drugs are used and what their use is supposed to achieve. Having at least an idea of what B cells are, what antibody production entails and how this production affects us is part of a discussion we want to be in on. If we’re not in on it, someone else will decide what’s important to us. Whether long-term costs may be exacted for short-term gains, whether the risk of one side effect is more compelling than the risk of another, that’s something we should decide.

An example from my own history illustrates this point: azathioprine was once suggested as a possible therapy to control my lupus symptoms. Azathioprine is a drug that often has good results and may bring about a remission. However, use of this drug also carries a small risk of inducing pancreatitis. This slight risk increases in patients with certain GI conditions. I’ve had pancreatitis and I’ve had serious, recurrent gut issues. My decision, based on my own priorities, was to decline Azathioprine as a treatment option. My doctor had no problem with my decision because it was clear to him that I understood the consequences of my choices.

When it comes to the newly discovered variant of Fc, many more studies need to be conducted before this information can be clinically useful. But a step forward is a step forward. Fc research may be a starting point for more advances.

We can only hope.

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