Tag: #prednisone

The latest on my uveitis

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I’ve spent this year going to the University of Washington Medical’s Karalis Johnson Retina Center on a monthly basis in an attempt to get my uveitis under control. Last winter, in addition to prednisone, I started taking Cellcept, first 1000mg twice a day, then 1500mg twice a day.  

Cellcept (mycophenolate) is an anti metabolite, which slows down the immune system, and is most often used as an anti-rejection medication after organ transplants. (Read about uveitis treatments here). It gave me an upset stomach at first, but a month in, I no longer experienced that side effect. The worst part about Cellcept for me is just the timing of taking it. You can’t eat an hour before or two hours after taking it, which means I have to get up and take it awhile before breakfast and I have to schedule my Saturday night snacking around it. This I can handle.

Yet Cellcept, in addition to 20 mg of prednisone was still not controlling my inflammation. So, we introduced Humira, which is a self-administered injection to the thigh or stomach every other week. Humira is a “biologic” that blocks a protein called TNF-alpha, which is believed to be produced in excess in those with non-infectious uveitis.

I can’t say I’ve noticed any side effects specifically from the Humira. In my experience, the company goes almost overboard with assistance. The only thing I don’t like is that it is mailed in a large styrofoam box every month (with ice packs to keep it cold), which I feel guilty about throwing away. I even tried to give the boxes away online… Surprisingly no one wants medication boxes during a pandemic… go figure.

Cellcept and Humira are both known to take a few months to reach full efficacy, so I received two Ozurdex injections in the spring. 

In terms of overall side effects, I have noticed I am bruising super easily, am more dried out than before and my hair is thinning a bit. These are potential side effects of pretty much all immunosuppressants so it’s hard to isolate what’s causing what, or if it’s just the fact that I’m on three different medications. I’m down to 7.5 mg of prednisone at this point, so I’m sleeping much better. 

Thus, the good news is, my inflammation seems to be under control. However, in July my optical coherence topography (OCT; see Tools, Tests, and Terminology) showed a bit of fluid in the retina, and there was a new hemorrhage that showed up on my fundus photos. So, I received an Avastin injection. 

In August, my doctor had a few diagnostics run. A Fluorescein Angiogram (FA) and Indocyanine Green Angiogram (ICGA), along with another OCT, pointed to choroidal neovascularization membrane (CNVM) or choroidal neovascularization (CNV). This is another side effect of uveitis; it’s listed in the “Terminology” section of my website. [Side note: this experience is making me think that maybe I need to take the “terms” on that page which are actually complications of uveitis and make a separate page that goes further into detail about each. So, stay tuned for that if you’re interested.]

For now, neovascularization means ‘new blood vessels’. When damaged by disease, the retina may produce too much vascular endothelial growth factor (VEGF) which leads to the production of new blood vessels. The blood vessels grow from the choroid into the retina. However, unlike normal vessels, these vessels are leaky and allow fluid from blood or blood cells to enter the retina because the tissue is damaged. (Choroidal neovascular membrane, 2017)

“This fluid can immediately distort the vision because it forms a blister in the retina, which is normally flat. Over the course of days to months, this fluid can damage the retina, killing the light-sensing cells, called photoreceptors” (What is Choroidal Neovascularization?, 2020). 

According to one article, CNV is commonly associated with Multifocal Choroiditis, which is what I have, and is found in 32-46% of patients (Neri, Piergiorgi, et al., 2009). Just when I feel like I’ve about filled up my punch card of uveitis complications, I discover I have another! 

As with many other complications and side effects of uveitis, and uveitis itself, CNV is treated with medication to tell the body to chill out. In this case, Avastin works because it blocks VEGF. It’s an intravitreal injection that is typically done in conjunction with systemic immunosuppressants. (Read: Is Avastin beneficial for choroidal neovascularization?, 2008; and Inflammatory Choroidal Neovascular Membranes in Patients With Noninfectious Uveitis: The Place of Intravitreal Anti-VEGF Therapy, 2020)

In September, the swelling looked like it was dying down after the first Avastin injection, so I made the choice not to receive another injection. At my October appointment, however, the fluid and hemorrhage were not gone, so I received the first of my series of three, to be done 4-6 weeks apart.

Speaking of injections, a common side effect of injections or surgical procedures involving the eye is Ptosis, or drooping of the upper eyelid. I had this pretty noticeably after my Retisert implant surgery, so much so that I considered surgery to fix it! Luckily my lid “bounced back.” Lately, since I’ve been seeing myself on all these Zoom and Teams virtual meetings, I feel that my right eyelid is getting there again (my husband says I notice it more than others… which may be the case, but it still bugs me!). I recently read that there is a new drop out to fix this issue. Upneeq was approved by the FDA this year to treat acquired Ptosis (First Prescription Fix for Droopy Eyelid, 2020). I am anxious to try these drops but am choosing to wait until my CNV is resolved before adding in another variable. In the meantime, I’ll continue to just use my eyelash curler in an attempt to keep my right eye looking peppy…

Lastly, because I’ve been on varying dosages of prednisone for quite a while, I had a Dual-energy X-ray Absorptiometry (DEXA) Scan done in 2018. A DEXA scan measures bone mineral density and bone loss, which is a side effect of long term systemic cortical steroid use. At that time, my results showed minor osteopenia in my lumbar spine and left hip. (Read Prednisone: The Good, the Bad & the Ugly Part I and Part II.)

Osteopenia is the precursor to osteoporosis, which is when bones are weak and brittle due to too much bone loss. Since that time, although I have continued to be on steroids, more so this last year than the previous, I have increased my weight-bearing exercise and been very diligent about taking calcium supplements daily. 

I had a follow-up DEXA Scan in October and both areas of osteopenia are now in the “normal/ expected range for age.” My bone mineral density increased 3% in the lumbar spine and 1.5% in the left hip. Diet and exercise do work!

So, that’s what’s been going on with my uveitis as of late. Here’s to hoping the new year will bring fewer visits to the Retina Center!

Prednisone: The Good, The Bad, & the Ugly (Part II)

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It’s a new season in this crazy pandemic year. With fires blazing, school in session, and elections and holidays on the horizon, life is not easy right now, and on medication, it can be even more challenging to navigate. With that said, the following is Part II of information on Prednisone that I think is useful. Drop me a line if you think I missed something important! 

Interactions

In Part I,  I discussed interactions with prednisone by way of calcium and potassium absorption (i.e. it inhibits absorption, so supplements are recommended), and also the interactions between insulin and sugar (i.e. limit sugar on prednisone, this includes alcohol). Other interactions include some anti-infectives, anti-diabetic agents, and non-steroid anti-inflammatory drugs (NSAIDs). If you are taking other medications along with prednisone, talk to your doctor, and check interactions on drugs.com or another trusted website (https://www.drugs.com/tips/prednisone-patient-tips).

Tapering and Withdrawal

I’ve tapered down in dosage many times and gone completely off of prednisone a couple of times. The importance of tapering cannot be overstated. In Part I, I talked about Adrenocortical Insufficiency. When on prednisone for more than three weeks, the body becomes reliant on it for cortisol and stops making its own (How do you to taper off prednisone?). So, it’s important to wean your body off the supplemented steroid so it does not crash and leave you with a whole host of painful (and potentially dangerous) withdrawal symptoms. Even with tapering, you may have withdrawal symptoms; the longer you’ve been on prednisone, the more likely it is that you will have them.

Withdrawal Symptoms may include: 

  • Severe fatigue
  • Joint pain
  • Fever
  • Stiff or tender muscles
  • Body aches
  • Lightheaded feeling
  • No appetite
  • Labored breathing
  • Vomiting
  • Weight loss
  • Headaches
  • Adrenal crisis, a rare, possibly fatal reaction to a lack of steroid hormone in your body
  • Depression
  • Anxiety

For me, fatigue, or just being able to sleep better, is always the first and most common symptom of tapering off of higher doses, All of the bad side effects slowly start to fade away. However, when I have gone to taper off of prednisone, from only 10 mg, even when I thought I was tapering slowly, I have had excruciating joint pain. I was convinced that I had arthritis or another autoimmune condition had been revealed last time I tapered. I would wake up and barely be able to move my fingers! My knees and back just ached. I felt like I was 80 years old! I thought I was insane; I was only coming off of 10 mg! Then I read the following statement, from Adrenal Insufficiency United’s “Glucocorticoid tapering and adrenal suppression testing guide,” which was such a relief to me: 

“[Withdrawl] Symptoms are milder at high cortisol amounts and intensify when milligrams are reduced below a certain point. A longer adjustment period is recommended at lower doses.” 

The guide linked above includes tapering recommendations. There are others available online, such as these on RheumInfo.com. I recommend reviewing some and thinking about what might work for you; different methodologies exist (stair steps, alternating dosage days, etc) and it might take trial and error to discover to which your body responds best. Take examples to your doctor before you start your taper or if you are experiencing painful withdrawal symptoms. Tapering can take weeks or months, depending on your dosage and the duration of treatment. 

Pregnancy and Breastfeeding

I’ve made it no secret that I took a low dosage (~10 mg if I recall correctly) during my two pregnancies and while breastfeeding, and my sons incurred no known side effects. I’m not advocating one way or another, this is just my experience and it coincides with the latest information out there, which is that taking prednisone during pregnancy does not significantly increase the background chance of having a baby born with a birth defect (Mother To Baby, 2018, linked below).  I did make the choice to not donate breast milk to anyone because of my medication. I discuss my pregnancy experience in my blog post: Women and Uveitis: my pregnancy journey and I’ll link the articles I cite in the post regarding prednisone here:

Mother to Baby: Medications and More During Pregnancy – Prednisone / Prednisolone Fact Sheet. References for the Fact Sheet can be found at the link at the bottom of the article: https://mothertobaby.org/fact-sheet-reference/prednisone-prednisolone-ref/

Bandoli, G., Palmsten, K., Forbess Smith, C. J., & Chambers, C. D. (2017). A Review of Systemic Corticosteroid Use in Pregnancy and the Risk of Select Pregnancy and Birth Outcomes. Rheumatic diseases clinics of North America, 43(3), 489–502. https://doi.org/10.1016/j.rdc.2017.04.013

I also recommend reviewing Prednisone on “LACTMED” the Drugs and Lactation Database. This page includes information like drug levels detected after certain amounts of time which can be useful in trying to time feedings or pumpings to have the least amount of drug present possible.

COVID-19

Although COVID-19 is a new pandemic, there has already been work done compiling information regarding the impacts for patients on corticosteroid treatment, as well as recommendations for further treatment. I have a handful of links and papers on the home page of this website. Taking immunosuppressants during a pandemic is something to consider carefully. 

A collection of COVID-19 cases among 600 patients with rheumatic diseases found that “glucocorticoid use at a prednisone-equivalent dose ≥10mg/day was associated with an increased odds of hospitalisation, which is in agreement with prior studies showing an increased risk of infection with higher dose of glucocorticoids. The study also demonstrated “that most individuals with rheumatological diseases or on immunosuppressive therapies recover from COVID-19, which should provide some reassurance to patients” (Gianfrancesco M, Hyrich KL, Al-Adely S, 2020).

In another paper, 139 uveitis experts from around the globe were given statements and answered questions about treatment options for Non-Infectious Uveitis (NIU) patients and Immunomodulatory Treatment (IMT). [IMT is the treatment of disease by activating or suppressing the immune system. In the case of treating uveitis, the medications are reducing or suppressing the immune system.] Statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents, and biologics in patients with NIU in increased risk, high risk, and very high-risk categories. 

This paper contains helpful tables and flow charts on recommendations based on your risk category and specific treatment types.

Summarized results related to corticosteroids:

  • Surveyed uveitis experts recommended to not begin systemic corticosteroid or immunosuppression for NIU treatment in sick patients with suspected or confirmed COVID-19, irrespective of risk group. 
  • Among sick patients receiving high-dose corticosteroid, consensus was to taper the dose in all risk groups and to taper even low-dose corticosteroid in high-risk patients or very high-risk patients. Tapering instead of abrupt cessation of the oral corticosteroids was recommended in view of the risk of adrenal insufficiency. This paper is full of useful tables and flow charts to follow based on which risk level you’re at.
  • In healthy patients, experts agreed to start oral corticosteroids only in increased risk patients and not in high-risk or very high-risk patients. 
  • Low-dose oral corticosteroids and conventional IMT should be maintained, while only in increased risk or high-risk patients, higher-dose corticosteroids should not be tapered and stopped.
  • In healthy patients with a contact history, the overall agreement is lower. Low oral dose corticosteroids and conventional IMT should be maintained in increased risk patients.
  • Although first-line treatment for NIU consists of local or systemic corticosteroids, overall consensus emerged that in the setting of the COVID-19 pandemic, the use of systemic corticosteroids should be avoided in sick patients and local therapy (regional corticosteroid injections) should be preferred to systemic treatment in all patients, irrespective of their risk and health, except in healthy patients not already on corticosteroids. Systemic corticosteroids might be harmful, given their mechanism of action that inhibits the immune responses and affects the pathogen clearance. 

COVID-19 Related Works Cited

Agrawal R, Testi I, Lee CS, et al. Evolving consensus for immunomodulatory therapy in non-infectious uveitis during the COVID-19 pandemic. British Journal of Ophthalmology Published Online First: 25 June 2020. doi: 10.1136/bjophthalmol-2020-316776

Gianfrancesco M, Hyrich KL, Al-Adely S On behalf of the COVID-19 Global Rheumatology Alliance, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Annals of the Rheumatic Diseases 2020;79:859-866.

Further Reading: There are more links related to prednisone on the Corticosteroids section of my Treatments page.

Prednisone: The Good, the Bad, & the Ugly (Part I)

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Prednisone was synthesized in the mid-1950s by Arthur Nobile and has since been a miracle and a misery for people with autoimmune and inflammatory disease.

When I first started taking prednisone in 2011, I had no idea what I was in for and it showed. I gained about 10 pounds pretty quickly, “moon face” and all. When my brother came to visit he told me he barely recognized me. I had terrible acne that covered my chest and neck. My knees ached so badly I couldn’t stay in bed, and since I couldn’t sleep anyway, I was up early and late. I was completely miserable.

I was on 40-60 milligrams (mg) at the time, which is a lot.  A dose above 40 mg is considered a “high dose,” while anything below 7.5 mg is considered a “low dose” and to be “steroid sparing” (most patients don’t experience the side effects known to be associated with prednisone at this level) (https://www.aocd.org/page/SteroidsOral).

The prednisone did its job; my uveitis was brought to a screeching halt. But I couldn’t stay on the high dosage forever (thankfully) due to all of the side effects. I transitioned to combinations of prednisone and methotrexate and cyclosporine, eventually turning to RETISERT (see Treatments page).

I’ve been on and off prednisone since then, more time on than off, but at a much lower dosage. Typically I’ve been on 5-10 mg with pulses when I have a flare. And, I can honestly say, it’s often the only thing that keeps my uveitis at bay. That’s why prednisone is prescribed so regularly for a myriad of different conditions; it works and it works fast. Although the side effects of prednisone at high doses are likely unavoidable, I now am aware of them, long and short term, and what I can do to lessen them.

Let’s start at the beginning. 

What is prednisone and what does it do?

Prednisone is a synthetic glucosteroid. It is a type of corticosteroid that is closely related to and mimics cortisol, which is a hormone naturally produced by the adrenal gland in the body. 

When the body becomes stressed, the pituitary gland at the base of the brain releases ACTH (adrenocorticotropic hormone), which stimulates the adrenal glands to produce cortisol.

The extra cortisol allows the body to cope with stressful situations, such as infection, trauma, surgery, or emotional problems. When the stressful situation ends, adrenal hormone production returns to normal. 

The adrenal glands usually produce about 20 mg of cortisol per day, mostly in the morning, but they can produce five times that much when needed in a stressful (or perceived to be stressful) situation. Prednisone, the most commonly prescribed synthetic corticosteroid, is four to five times as potent as cortisol. Therefore, roughly 5 mg of prednisone is equivalent to the body’s daily output of cortisol. There are other synthetic corticosteroids available which differ in potency and half-life (Eustice, 2020).

During a stressful scenario your body is in “fight or flight” mode and thinks of little other than dealing with the stressor. Therefore, when you have increased corticosteroids in the body, your body blocks substances that create inflammatory actions called prostaglandins (which initiate healing and deal with allergic reactions) and white blood cells (which destroy foreign cells and allow the immune system to function properly). In this way, corticosteroids suppress the immune system.

Cortisol also helps to control the salt and water balance in the body as well as regulates carbohydrate, fat, and protein metabolism. When you have a heightened amount of corticosteroid in your body, this system too is thrown out of whack. And thus, we have side effects. 

Side Effects of prednisone

There are known side effects of prednisone, particularly with prolonged use, for virtually every system in the body. I’ve summarized some of the more common side effects below. Check out Drugs.com for a more complete list and more details.

When reading through some of these, it’s clear that many are connected and all are impacted by daily actions such as diet, exercise, stress response and sleep.

Adrenocortical Insufficiency

When given in a stronger dose than the amount the body can produce on its own, for prolonged periods, glucocorticoids may cause decreased secretion of endogenous (self-made) corticosteroids by suppressing pituitary release of corticotropin (secondary adrenocortical insufficiency). Basically, since you’re taking prednisone, the body senses the level of steroid is “high enough” and stops making as much. This is why it is dangerous to stop taking prednisone cold turkey (I’ll post about tapering off prednisone next month). The degree and duration of adrenocortical insufficiency is highly variable among patients and depends on the dose, frequency and time of administration, and duration of therapy. Talk to your doctor about adrenal supplements and lifestyle changes if you are feeling sluggish and tired all of the time (especially on high doses of prednisone). 

Immunosuppression and Increased Susceptibility to Infection

Increased susceptibility to infections is common on prednisone. It’s easier to get sick when the immune system is suppressed. This can mean anything from serious and potentially fatal infections like chicken pox and measles to persistent athlete’s foot and candida. Read Study Warns about higher infection Risk.

Remember that administration of live virus vaccines, including smallpox, is contraindicated (advised against) in patients receiving an immunosuppressive dosage of glucocorticoids. Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection.

Infections with any pathogen, including viral, bacterial,or fungal infections in any organ system, may be associated with glucocorticoids. There are a variety of ways to get rid of or lessen the severity of infections such as fungal infections, both with and without medication. In my experience, diligence is paramount if you are going to be on prednisone for a while. 

Musculoskeletal Effects

Muscle wasting, muscle pain or weakness, and atrophy of the protein matrix of the bone resulting in osteoporosis or osteopenia can all be side effects of prednisone. Osteoporosis and related fractures are one of the most serious adverse effects of long-term glucocorticoid therapy. The American College of Rheumatology (ACR) currently considers patients receiving or planning to receive greater than 2.5 mg of prednisone daily for three months or longer to be at risk for bone loss (Glucocorticoid-Induced Osteoporosis).

A high protein diet may help to prevent adverse effects associated with protein catabolism. Calcium and vitamin D supplementation and weight-bearing exercise that maintains muscle mass are suitable first-line therapies aimed at reducing the risk of adverse bone effects.

I had a Dexascan in 2018 which showed slight osteopenia in my hips. It surprised me because I’ve always been pretty active and wasn’t on a high dose of prednisone at the time (I was nursing my second son at the time which may have contributed). I’ve since increased my calcium and vitamin D and my weight lifting. My insurance covers another scan this December, so we will see if it worked!

I also remember when I was on 60 mg, the pain in my lower back and knees was so bad I would wake up at night and not be able to sleep. 

Ocular Effects

As many of us with uveitis know, the treatments often involve the side effect of cataracts and increased intraocular pressure. Prolonged use of prednisone may result in posterior subcapsular and nuclear cataracts  and/or increased intraocular pressure (IOP) which may result in glaucoma or may damage the optic nerve if left unchecked. 

Nervous System Effects

Side effects of prednisone include insomnia, mood swings, and depression. I tend more toward the “intense” side of personalities at times (hey, I’m a Scoprio.. what can I say?!) and when I’m on higher doses of prednisone I have to consciously remind myself to tone it down a little. Especially when I haven’t slept much due to high doses; I usually notice trouble sleeping when I’m on 20 mg or more. Another side effect I’ve noticed, but don’t generally read in the literature is feeling warm all of the time, which can also impact mood and sleeping. Altering your sleep schedule (can you fit in a nap?) based on when you sleep best can help as well as just giving yourself down time and plenty of grace… and space.. from other people (sort of kidding). 

Endocrine and Metabolic Effects 

Prednisone may decrease glucose tolerance, produce hyperglycemia (high levels of sugar in the blood), and aggravate or precipitate diabetes mellitus, especially in predisposed patients. If glucocorticoid therapy is required in patients with diabetes mellitus, it may be necessary to change insulin or oral antidiabetic agent dosage or diet. Read What is the link between prednisone and diabetes?

The increased requirement for insulin, accompanied by potassium loss, sodium (and fluid) retention and increased appetite often lead to weight gain when uncontrolled. Monitoring carbohydrate and refined sugar, and sodium intake can help with these side effects. See the Prednisone Friendly Diet from Stop Sarcoidosis and Prednisone Weight Gain by Dr. Megan, Prednisone Pharmacist, who has really great info on her site.

Patients with hypothyroidism may have an exaggerated response to glucocorticoids. Glucocorticoids can lower serum TSH levels and decrease TSH secretion through direct effects on TRH in the hypothalamus. Chronic use of high dose glucocorticoids do not appear to cause clinically significant central hypothyroidism (Haugen, 2009).

Sodium retention with resultant swelling, potassium loss, and elevation of blood pressure may occur, but is less common with prednisone. Along with swelling is the less-than-fun phenomenon known as “moon face.” Read Embrace Moon Face and supplement potassium.

Dermatologic Effects

I’ve always struggled with acne, but let me tell you that prednisone acne is real. When I was on 60 mg, I literally bought turtle necks and wore them all the time because my neck and chest were so broken out (luckily it was winter). Prednisone impairs wound healing (remember, it’s telling your immune system to chill out) which can make acne last longer. 

Prednisone also thins out the skin which can cause you to bruise more easily (Bruising for No Reason? It Could Be Due to These Medications). 

So there you have the (abbreviated) long list of side effects of the miracle drug that is prednisone.

Next month I’ll talk about interactions, tapering and withdrawal, touch on pregnancy on prednisone, and COVID-19 risks on prednisone.