Polly Wants a Steroid: a small clinical observation

If you develop polymyalgia rheumatica (PMR), you will be as sick as a parrot. It is no fun at all.

Textbooks describe it is a common autoimmune inflammatory disease affecting older adults. Typical symptoms include bilateral shoulder and hip pain, with an aching neck and prolonged morning joint stiffness. Patients tell you it hurts to move, it hurts to be still, joints are stiff and painful (although not swollen), sleep fleeting, the aching and fatigue ever-present, life barely worth living.

Until the condition is diagnosed, and the doctor prescribes (typically) prednisolone, or prednisone. Within a day or two the pain fades and is gone. The rapid rate of recovery may be enough to confirm the original diagnosis.

And then the trouble starts …

Niccolo Macchiavelli famously said “Wars begin when you will, but they do not end when you please”.

Using steroids in the war against inflamed joints is a Macchiavellian move. You can start them when you (and your physician) want, but weaning yourself off them is more problematic. You have to taper. This is not as easy as it sounds.

Online PMR patient groups are full of sad stories about the difficulties of coming off steroids. Sufferers bemoan the recurrence of breakthrough symptoms and the emotional toll of going back to an earlier, higher dose (or even back to the start), and they worry about the long-term adverse effects of these drugs.

What I find particularly striking, however, is the range of steroid dependency. Some patients are able to quit their medications within a year or so, and may not ever need them again. A second group drops off the radar by year 5, a select few become lifers. Half experience one drug relapse, up to a fifth have multiple relapses. What is it that differentiates these groups?

My guess, which is informed by a mere half handful of personal experiences, is that the ease of becoming steroid-independent is closely related to the patient’s metabolism; and more specifically, whether this is configured in a pro- or anti-inflammatory mode.

Before we get there, a little epidemiology.

In common with other autoimmune diseases, PMR trends are increasing and affect primarily women (ie 1). Incidence rates varying significantly by region, and follow a North / South gradient; Scandinavians are worst affected, Mediterranean folk less so and non-white populations less again. This pattern is similar to Giant Cell Arteritis, an autoimmune condition often associated with PMR. The above, plus a frequent seasonal component and a possible link to diet (2-5) and diverticular disease (6), suggests complex gene / environment interactions. Might a higher fiber diet be protective (7)?

Back to the steroids.

Weaning patients off these drugs is always done very gradually. A typical tapering protocol:
Initial Dose: 12.5 to 15mg daily for 3-4 weeks.
Reduction Phase: Reduce by 1 mg every 4-8 weeks to 10 mg/day, then continue reducing by 1 mg monthly if symptoms allow.
Unfortunately, in about a half of patients, symptoms do not allow. They relapse, go back to the previously effective dose or if necessary, further back. Then after a while, they start to taper off again, but this time more slowly. And this is where it can become problematic.

Long-term steroids increase the risk of damage to almost every system in the body.

They raise the risk of hypertension via multiple mechanisms (8). They raise the risk of connective tissue disorders such as osteoporosis, arthritis, spinal disc deterioration, and dermatoporosis, via their adverse effects on ECM modeling; they alter fibroblast activity, collagen synthesis, and matrix metalloproteinases (MMPs) regulation (9, 10), leading to an overall degradation of ECM in multiple tissues. Then there is immuno-suppression, adrenal insufficiency, neurotoxicity, loss of glycemic control, depression, anxiety– the list is a long one.

The patient is left in a cleft stick, as is the physician. Come off steroids too fast and risk a relapse, which means starting again, and an increased risk of adverse long-term effects. Taper too slowly, and run the risk of longer-term problems anyway. Over half of PMR patients on prednisolone will experience at least one adverse event within the first year of treatment (11).

Enabling more PMR patients to withdraw from steroids more rapidly would be a boon for patients and physicians alike. Might there may be a way to achieve this?

I have recently seen two PMR patients taper rapidly and successfully off their initial 15mg dose of prednisolone, becoming drug- and symptom-free within 6 months. The one thing they had in common was the health protocol. One had already started the protocol, the other began taking it a week after the initial diagnosis.

Both had originally been consuming the Standard American (SAD) Diet and were therefore metabolically mal-configured (12), with a pro-inflammatory bias (ie 13). After using the protocol their internal environment shifted towards neutral or anti-inflammatory, as evidenced by significantly reduced inflammatory symptoms (14). Against this backdrop, steroid withdrawal appeared to become significantly easier.

Two swallows (or parrots) may not make a summer but they do make, when sufficiently stretched, a testable hypothesis. Clinicians dealing with PMR patients might find it useful to co-prescribe prednisolone and the health protocol to their next case or two, and monitor them during the taper.

This strategy may also be helpful in managing cases of SLE, COPD, sarcoidosis, Crohn’s etc resistant to other treatments, where tapering off after long-term steroids is likely to pose similar problems.

To sum up, the ‘wonder drugs’ of the 1950’s are still among the most widely prescribed medication classes because they are such effective anti-inflammatory agents. Their negative effects can be reduced by co-prescribing other drugs such as antihypertensives, anti-glycemics, bone protective agents, and selective estrogen receptor modulators – which come, of course, with their own adverse effects (15).

Or they could be co-prescribed with the appropriate pharmaco-nutritional tools. I believe this approach will make glucocorticoids safer by enabling lower doses, and simultaneously protect the multiple physiological systems that would otherwise be exposed.

References:

1. Raheel S, Shbeeb I, Crowson CS, Matteson EL. Epidemiology of Polymyalgia Rheumatica 2000-2014 and Examination of Incidence and Survival Trends Over 45 Years: A Population-Based Study. Arthritis Care Res (Hoboken). 2017 Aug;69(8):1282-1285.
2. Dellaripa P.F., Howard D. Nutritional Issues in Vasculitis. In: Coleman L.A., editor. Nutrition and Rheumatic Disease. Nutrition and Health. Humana Press; Totowa, NJ, USA: 2008.
3. Zhao Y., Lv L., Cui L., Yao Q., Zhang H., Yu X. Dietary patterns and polymyalgia rheumatica: A case-control study. Clin. Rheumatol. 2019;38:197–205.
4. Sato W., Ishibashi K.I., Yamanaka D., Adachi Y., Ohno N. Effects of Natural and Chemically Defined Nutrients on Candida albicans Water-soluble Fraction (CAWS) Vasculitis in Mice. Med. Mycol. J. 2017;58:E47–E62. doi: 10.3314/mmj.16-00014.
5. https://www.healthcentral.com/condition/polymyalgia-rheumatica/diet-for-polymyalgia-rheumatica
6. Scrivo R, Gerardi MC, Rutigliano I, Sessa P, Mipatrini D, Stricchiola GMG, Pacella E, Altobelli A, Castellani C, Alessandri C, Ceccarelli F, Di Franco M, Priori R, Riccieri V, Sili Scavalli A, Spinelli FR, La Torre G, Conti F, Valesini G. Polymyalgia rheumatica and diverticular disease: just two distinct age-related disorders or more? Results from a case-control study. Clin Rheumatol. 2018 Sep;37(9):2573-2577.
7. Wegermann K, Roper J. An Insoluble Mystery: Fiber and Diverticulitis. Gastroenterology. 2020 Mar;158(4):1167-1168.
8. Saruta T. Mechanism of glucocorticoid-induced hypertension. Hypertens Res. 1996 Mar;19(1):1-8.
9. Clutterbuck AL, Asplin KE, Harris P, Allaway D, Mobasheri A. Targeting matrix metalloproteinases in inflammatory conditions. Curr Drug Targets. 2009 Dec;10(12):1245-54.
10. Nakamura T, Liu M, Mourgeon E, Slutsky A, Post M. Mechanical strain and dexamethasone selectively increase surfactant protein C and tropoelastin gene expression. Am J Physiol Lung Cell Mol Physiol. 2000 May;278(5):L974-80.
11. Tanaka Y, Tanaka S, Fukasawa T, Inokuchi S, Uenaka H, Kimura T, Takahashi T, Kato N. Glucocorticoid treatment and clinical outcomes in patients with polymyalgia rheumatica: A cohort study using routinely collected health data. Joint Bone Spine. 2024 May;91(3):105680. 
12. O’Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D. Trends and Disparities in Cardiometabolic Health Among U.S. Adults, 1999-2018. J Am Coll Cardiol. 2022 Jul 12;80(2):138-151.
13. Sawalha K, Tripathi V, Alkhatib D, Alalawi L, Mahmood A, Alexander T. Our Hidden Enemy: Ultra-Processed Foods, Inflammation, and the Battle for Heart Health. Cureus. 2023 Oct 22;15(10):e47484.
14. Personal experience and in-house data (Zinzino AG).
15. Pofi R, Caratti G, Ray DW, Tomlinson JW. Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad? Endocr Rev. 2023 Nov 9;44(6):975-1011.