General theory of inflammation: patient self-administration of hydrocortisone safely achieves superior control of hydrocortisone-responding disorders by matching dosage with symptom intensity – free full-text /PMC6581742/ – J Inflamm Res. 2019;
Objective: To determine if patient self-administration of hydrocortisone will safely achieve superior symptom control for all hydrocortisone-responding disorders as it does for Addison’s disease and rheumatoid arthritis.
Methods: 2,480 participants with hydrocortisone-responding disorders were brought to a minimum symptom state using daily administered hydrocortisone tablets in a 24-week, open study.
Thereafter, participants used 5-day, low-dose hydrocortisone regimens to quench subsequent disorder exacerbations (flares) to maintain the minimum symptom state. Stressors such as emotional traumas, infections, allergies, and injuries were minimized to reduce disorder intensity, hydrocortisone consumption, and participant discomfort.
Results:
2,015 participants… completed the 24-week study [~6 months] to achieve a composite average symptom improvement of 76% with equal response rates. The participants averaged ingesting 12 mg of hydrocortisone per day.
No significant adverse reactions were observed.
Conclusions:
Patient self-administration of hydrocortisone safely achieves superior symptom control for 38 hydrocortisone-responding disorders at equal rates and symptom improvements to confirm and amplify an earlier double-blind study finding on rheumatoid arthritis.
These results are consistent with the body having an inflammation control system and chronic inflammation being a disorder unto itself with differing symptoms sets dependent on its location.
Clinical Trials Government Identifier: NCT03558971
– – – – abstract above – full study excerpts beow – – – –
Introduction
patient self-administration of prednisone was proven effective to control the symptom variability of rheumatoid arthritis safely. In a double-blind trial, superior to standard-of-care treatment effectiveness was achieved with no significant adverse reactions.
A hypothesis has been proposed that hydrocortisone-responding disorders arise from a defect in an inflammation control system.
When the defect occurs, short-term, beneficial inflammation evolves unhindered into long-term, destructive inflammation.
The hypothesis assumes the common denominator of hydrocortisone-responding disorders is chronic inflammation and the differing symptom sets observed are consequences of chronic inflammation existing in various locations.
If this hypothesis were true, all hydrocortisone-responding disorders should respond with equal rates and efficacies to one effective chronic inflammation treatment.
Methods
The method of this study is that of the preceding double-blind study on rheumatoid arthritis modified by
- adding stress management,
- increasing the induction period length and
- relating hydrocortisone dosages to body mass.
I’ve gotten so used to physical patient characteristics, like weight or age (or pain levels), being ignored that I was surprised to see it mentioned here. I suspect this unusual protocol may have been a critical factor in the study’s success.
The study protocol was:
- week 1) qualifying medical examination, food sensitivity laboratory test, daily monitoring of symptom intensities for establishing baseline;
- weeks 2-4) daily ingesting hydrocortisone tablets to achieve a minimum symptom state, monitoring symptom intensities for daily change from baseline and hydrocortisone response to dosage, laboratory-determined sensitive foods eliminated from diets, medical examination 2 at the end of week 4;
- weeks 5-24) patient education, participant self-administration of hydrocortisone, monitoring of symptom intensities for daily change from baseline, laboratory-determined sensitive foods eliminated from diets, medical examination 3 at the end of week 24.
Hydrocortisone was administered daily for 3 weeks to achieve a minimum symptom state.
Table 1
Hydrocortisone dosages of the induction period
Body mass Week 1 Week 2 Week 3 >68 kg 60 mg/day 40 mg/day 20 mg/day 68 to 114 kg 80 60 40 >114 kg 100 80 60 Those who failed to attain significant symptom improvement during the induction period were disqualified from the study.
This would be troubling if they weren’t limiting the study to hydrocortisone-responding disorders.
For those who responded to hydrocortisone administration but failed to achieve the objective 75% symptom improvement, the induction period was repeated with the daily addition of adult dosage doxycycline to optimize symptom control.
To maintain the minimum symptom state after the induction period, participants were taught for what reasons and when to ingest 5-day hydrocortisone regimens (boosters) for quenching disorder flares.
I think this is a brilliant innovation: educating patients on how to manage their pain according to how severe they perceive it to be instead of just writing the same “standardized” prescription all pain patients
After all, doctors cannot measure our pain and we are the only ones who truly know how bad it is. Prescribing for us to act according to our needs and accepting how we assess our own pain would be a tremendous advance in medical care.
The 5-day flare-quenching regimen consisted of ingesting hydrocortisone tablets during day 1 immediately upon flare recognition and during days 2–5 at 7–9 am.
The booster hydrocortisone dosages are given in Table 2.
Table 2
Hydrocortisone of the 5-day flare-quenching booster
Body mass Day 1 Day 2 Day 3 Day 4 Day 5 <68 kg 30 mg 20 mg 20 mg 20 mg 10 mg 150 to 250 kg 40 30 20 20 10 >114 kg 50 40 30 20 10 Education principles were:
- restrict total hydrocortisone available to within its safe use limit per month;
- limit booster use to four times a month;
- implement boosters at the early onset of a flare; ingest hydrocortisone between 7 and 9 am except for the first day dose of the booster that is to be taken immediately upon flare recognition;
- take the daily hydrocortisone dosage at one time and do not spread it out throughout the day;
- minimize emotional traumas; restrict each participant’s diet to exclude participant-specific, laboratory-determined sensitive foods; and
- minimize strenuous work and exercise of inflamed areas.
Table 3
The average symptom improvement (efficacy) of participants arranged by decreasing number of participants (n)
Disorder n Efficacy, % Fibromyalgia 601 77 Osteoarthritis 579 77 Rheumatoid arthritis 246 78 Arthritis, undifferentiated 226 76 Back pain 75 70 Parkinson’s disease 51 62 Polymyalgia rheumatica 44 80 Chronic fatigue syndrome 25 78 Neuropathy 25 74 Dementia, Parkinson’s disease 22 67 Headache, migraine 21 86 Multiple sclerosis 19 67 Asthma 11 68 Systemic lupus erythematosis 9 60 Bursitis 6 79 Irritable bowel syndrome 6 71 Psoriatic arthritis 6 63 Crohn’s disease 5 92 Carpal tunnel syndrome 5 86 Spinal stenosis 4 78 Headache 3 84 Nervous system symptoms 3 63 Ankylosing spondylitis 3 60 Urinary tract inflammation 3 58 Post traumatic stress disorder 2 71 Acid reflux 1 100 Bowel inflammation 1 100 Scoliosis 1 100 Dementia, rheumatoid arthritis 1 92 Dementia 1 86 Eye inflammation 1 85 Eczema 1 77 Myofacial syndrome 1 73 Meniere’s disease 1 69 Sjogren’s syndrome 1 69 Dementia, multiple sclerosis 1 67 Restless leg syndrome 1 47
Discussion
General theory of inflammation
The inflammation control system of the body terminates acute inflammation at its due time. In normal operation, an inflammation-initiating event causes acute inflammation to occur which in turn activates the HPA axis to make an approximate 12-fold, 4 hrs, hydrocortisone surge concentration in the blood (surge). This surge then terminates the very inflammation that activated the HPA axis in the first place much as an electrical switch turns off a light.
As the surge weakens with age, injury, and heredity, acute inflammation evolves into chronic inflammation proportionately while being manifested as bad days (flares) for patients.
Resolution of chronic inflammation
The solution is teaching patients to ingest hydrocortisone tablets on the bad days and not on the good ones to manually restore the pulse to its effective concentration in the blood. In this way, only the missing hydrocortisone is replaced thereby avoiding overdosing adverse effects.
Patient self-administration is mandated since only patients experience the bad days.
How true this is!
I’d love to see more such personalized studies because, to me, they are the only ones that are appropriate to inform clinical practice. Using standards can prove a theory or show trends, but medicine is practiced on individuals who are often far from “standard”.
Flares should be terminated during their earliest stages to minimize hydrocortisone consumption and patient discomfort since the amount of hydrocortisone required to terminate inflammation is related to inflammation intensity.
This is what they used to tell us about opioids too, at least after surgery. I was told to take one as soon as I felt any pain to catch the pain early before it got bad and became more resistant to medication.
Patients must be brought to a minimum symptom state before employing patient self-administration. If they were not to do this, they would be unable to judge flare occurrences from background symptom intensities satisfactorily.
- Patients are expected to experience 3.3 flares each month.
- The hydrocortisone amount in each booster is 25% of the monthly safe use limit.
- With the restriction of using a maximum of 4 boosters per month, this limits hydrocortisone use to its safe use limit.
Adrenal suppression is avoided by incorporating hydrocortisone holidays.
Participants using the maximum 4 boosters per month would have 8–11 hydrocortisone holidays irregularly interspersed throughout a month during which natural production of hydrocortisone by the adrenal glands is exercised.
In implementation,
- participants excluded laboratory-determined allergenic foods from their diets,
- took a broad-spectrum antibiotic, and
- avoided strenuous exercise of inflamed tissues.
This seems to be the catch: because you’re expressing your immune system, you become more vulnerable to infectious diseases and the antibiotic is supposed to compensate for that.
I believe taking an antibiotic consistently could have horrible health consequences over time as it disrupts our gut biome (which is proving to be more important all the time).
The 3-week induction period left 21 weeks of this 24-week study to learn if patients were capable of maintaining the minimum symptom state using patient self-administration of hydrocortisone.
Patients were expected to average 17.3 flares during the 21 weeks at the rate of 3.3 flares per month. This number of flares was judged adequate for judging patient capability.
Outcome measurement
The monitoring process was designed to encourage patient compliance, allow computer-assisted data analyses, and facilitate communication among participants, physicians, and educators. An average of sequential day measurements avoided 1-day measurement risk error.
This digital monitoring system gave participants a numerical value as to when to treat a flare. It removed much of the guesswork out of the patient self-administration of hydrocortisone and gave participants confidence to initiate treatment quickly with less hydrocortisone.
The ultimate test
Self-administration if hydrocortisone symptom improvements observed during this study approximately doubled that of standard treatments.
How about self-administration of opioids? If they didn’t give some people euphoria we wouldn’t be having this problem.
I’m lucky to have a doctor that understands the varied nature of my pain and allows me discretion in my doses (within the bounds of my monthly prescriptions, of course).
The pain patients I know would also do very well on such a self-service plan. They could be prescribed a long-acting opioid (for almost daily use), several daily breakthrough pain killers, maybe a low dose steroid, and some non-opioid pain relievers like acetaminophen or gabapentin or Lyrica.
Then pain patients could take doses as needed, when needed, and how needed. Different pains respond to different pain relievers and differing levels of pain require different doses.
During each day, I evaluate my pain in light of what functionality I need at that time and adjust my doses and their timing accordingly.
If I plan to exercise, I’ll need breakthrough medication before I even start. Without opioids to control the pain provoked by activity, I could not exercise or even be functional in daily living.
If I have a day free of obligations and not much activity, I need far lower doses and can get away with close to half of what I need on busier days.
No significant hydrocortisone adverse effects were observed. Participants averaged ingesting 12 mg hydrocortisone per day during self-administration.
This consumption rate is less than the 15 mg hydrocortisone per day that gives rise to hydrocortisone adverse effects in the most sensitive adults
Salient features
Compatibility of the protocol of this study with other medicines is inherent. All medicines are designed to be compatible with hydrocortisone that is ever present in the blood.
The increased vasopermeability of inflammation allows extra plasma and immune cells to enter inflaming tissues from the pressurized blood system to cause swelling and the immune response. The HPA axis hydrocortisone surge re-establishes normal vasopermeability to terminate inflammation.
Once the surge is weakened, the patients become overly sensitive to all inflammation-initiating and exacerbating events.
Patient self-administration of hydrocortisone features dosage flexibility.
Pharmacological and physiological doses of hydrocortisone are mingled with hydrocortisone holidays to provide the needed flexibility to counteract the dynamic exacerbation and remission character of chronic inflammation.
responses to hormone hydrocortisone treatment can be attributed to the responsible chronic inflammation being located within the brain protected by the blood-brain barrier.
Patient self-administration of hydrocortisone eliminates most chronic pain by extinguishing chronic inflammation.
Patient self-administration of hydrocortisone is FDA-compliant for hydrocortisone use applied to corticosteroid-responding disorders.
Conclusions
Patient self-administration of hydrocortisone safely achieves superior symptom control for 38 hydrocortisone-responding disorders at equal rates and efficacies.
These results are consistent with the body having an inflammation control system and chronic inflammation being a disorder unto itself with differing symptoms sets dependent on its location.
You can read the full article at General theory of inflammation: patient self-administration of hydrocortisone
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