The use of prednisone to treat rheumatoid arthritis and other autoimmune diseases and the link between aging and mitochondrial function are our publisher’s topics in this issue.

Jonathan Collin, MD

Medicine’s Love/Hate Relationship with Prednisone

I was originally going to title this “In Praise of Prednisone,” but I thought I would upset the readership who focus on natural approaches to care.  Prednisone, a synthetic derivative of cortisone, was invented in the 1950s and marketed as a drug in 1955.  When arthritis patients used it during the first year it was released, their joint pains magically disappeared.  It truly was a wonder drug, helpful not just in rheumatoid arthritis but in nearly all inflammatory and auto-immune diseases.

Of course, there were side effects, some mild, some harsh, and some devastating.  For too many patients this was a cruel punishment for using a medical treatment that had so much promise.  People needed to reduce their prednisone dosing or stop it altogether.  One thing was for sure after those first few years of prednisone prescribing—a prescription for prednisone needed to be used judiciously, using a high dose only for a brief period of time and then decreasing the dose as quickly as feasible.

Certainly, the potential for adverse effects with prednisone were lengthy; agitation, anxiety, insomnia, blood sugar dysregulation, emotional lability, abdominal pain, and weight gain were “minor” symptoms.  Major problems with long-term use of prednisone included immune suppression, bone loss, major weight gain with Moon face and central obesity, Cushing’s disease symptomatology, cataracts, muscle atrophy, myopathy, avascular necrosis, and more.

The decision to prescribe prednisone by the physician and to take it by the patient was not made lightly.  Still there was great therapeutic value in its use especially when alternatives were lacking and patient symptoms were anguishing and horrific.

A case reported not in a medical journal but the January 30, 2023, New Yorker illustrated the power, value, effectiveness, and necessity of prednisone.1 A middle-aged woman who was a history professor at Yale, took a swim in the Long Island Sound in September of 2019.  In the course of swimming, she brushed against an aquatic plant, scratching her forearm and immediately developed a skin eruption which initially abated.  Hours later she experienced severe itching in her ankles.  By the next day the dermatitis began to spread up both legs and her neck became stiff.

Over the course of the next week the rash had progressed up her trunk, back, and upper extremities.  She consulted with a dermatologist who prescribed a steroid cream.  Her rash improved, but then she started to experience joint pains.  Unlike the skin rash, the joint pains intensified and persisted affecting her knees, hands, and ankles.  Eventually her shoulders were so incapacitated she was not able to lift them, her knee pain prevented her from climbing the stairs.  She sought specialist care at Yale.

Consulting with a rheumatologist, she was diagnosed with seronegative rheumatoid arthritis.  But the usual markers for inflammatory autoimmune disease were not abnormal.  After being prescribed over months various biologic modifiers for rheumatoid arthritis and not improving with any of these medications, she was prescribed prednisone in high doses, which did provide relief.  Of course, her rheumatologist and she were aware of the consequences of continuing high-dose prednisone.  The dose was lowered, which reduced prednisone’s untoward effects but also brought on breakthrough arthritis pain.

After consulting with a new rheumatologist while her condition was flaring up, she was informed that she had angioedema, but a rare variant.  She was referred to an immunologist who discovered that her immunoglobulins were “wildly out of whack.”  The IgG antibodies were lower than normal while the IgM antibodies were three times normal.  After being administered the pneumococcal vaccine, she had no antibody response to the injection.

Now her diagnosis was common variable immune deficiency, a strangely named disorder given that only 1 person in 25,000 suffers from it.  With the very low IgG levels she began to receive infusions of immunoglobulin. These made laboratory determinations of her antibody levels somewhat muddled to sort out her innate production from the infusions.  Her immunologist ordered genetic testing to be done.  Not only was an abnormality found, she had a “one-of-a-kind” genetic mutation.

Very rare genetic mutations are for medical scientists exciting discoveries.  Not only were the specialists at Yale focusing on understanding her genetic rarity, but geneticists at other academic institutions and the NIH were to share in studying it.  She was referred to the clinical center at the NIH, a super-specialized hospital established to investigate and diagnose patients with very rare disorders.  While the level of specialty care here is exceptional, it is a lonely place for the patient who is often isolated from family for lengthy periods.

Her genetic abnormality is known as a PLCG2 mutation, which has been determined to impair the immune system especially at low temperatures.  The specialist at the NIH has named the medical condition associated with this genetic mutation, PLAID, which stands for PLCG2-associated antibody deficiency and immune dysregulation.  As you might imagine there are very few referrals for this condition but there have been some.

Following her first appointment at the NIH where she had been diagnosed with atypical mycobacteria in her lungs, she was placed on antibiotic therapy for one year.  On her second NIH appointment she was diagnosed with Lyme disease and was treated for two months with oral and intravenous antibiotics.  Other than becoming nauseated, her symptomatic status did not improve.  Most recently she was given an immunosuppressant medication, rapamycin, usually prescribed for patients undergoing kidney transplant surgery.  It should be noted that we have written about the anti-aging effects of rapamycin in the Townsend Letter.

She is now treated only with low-dose prednisone.  No other treatment has benefitted her.  The low-dose prednisone has calmed the arthritis pain. She is functioning adequately, even well, from a symptomatic viewpoint.  Her activity level is essentially normal. The prednisone causes some weight gain and occasionally alters her blood glucose.  She worries that years from now she will suffer from cataracts and osteoporosis.  For all the resources both at Yale and at the NIH, she has not had any definitive diagnosis other than the described mutation.  None of the medications developed since prednisone was invented in the 1950s have made any difference in her condition.

The patient worries about the uncertainty of how her condition will progress in the years ahead.  Perhaps research on other patients at the NIH may yield answers. In the interim prednisone is her best medicine, the only treatment providing her relief.  Undoubtedly if she were open to naturopathic and integrative medicine, she would probably experience further improvement.  For now, prednisone is the answer.

  1. Gage, B. One of a Kind.  The New Yorker.  Jan. 30, 2023.


Anti-Aging Perspective by Prof. Serge Jurasunas

Serge Jurasunas has dedicated much of his career to cancer care and treatment.  He has introduced our readers to theoretical and practical therapeutic concepts in numerous articles available at the Townsend Letter website. As most of his cancer patients are elderly, Jurasunas has observed that many are biologically older than their chronologic age while others are younger.  From Jurasunas’ perspective that difference in aging is not only genetic but reflects the health and integrity of the cell particularly its mitochondria.

When the mitochondria are impaired there always is a poorer cancer prognosis.  The question of what causes mitochondrial functioning to improve not only determines cancer survival, it also establishes overall vitality and longevity.

Jurasunas observes that part of the mitochondrial DNA, mtDNA, is inherited from the mother; thus, the aging process begins in-utero.  If the mother’s mitochondrial DNA is impaired, the fetus will begin to experience aging changes even before birth.  Jurasunas wonders whether Alzheimer’s disease might begin in utero?

Part 1 of Jurasunas’s paper examines the impairment of mitochondria in the aging process.  Part 2 in our next e-Letter discusses interventions in diet, lifestyle, and supplement use facilitating restoration of mitochondrial functioning and slowing the aging process.

 Jonathan Collin, MD

Jonathan Collin, MD practices integrative and conventional medicine in Kirkland, Washington, and Port Townsend, WA. He is the publisher and editor-in-chief of the Townsend e-Letter, the online version of the Townsend Letter, a print magazine which he published from 1983-2023. Dr. Collin has been in medical practice since 1977. He is married to Deborah, has two adult children, and enjoys playing with his grandchildren.