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13-cis retinoic acid Poison/"Vitamin A" causes autoimmunity, 13-cis retinoic acid is the MAIN Poison/"Vitamin A" retinoic acid in the body from consuming Poison/"Vitamin A" in foods

Before we head into the DEMONSTRATED CASES of Accutane aka isotretinoin aka 13-cis retinoic acid DIRECTLY INDUCING autoimmune disease in multiple documented case studies, in multiple different body systems, you should know something.

You're probably saying, "Well, I may have an autoimmune condition (or three), but I NEVER took Accutane, so you're obviously off track!"

Please read this post first.  What it shows is that any Poison/"Vitamin A" source you eat or put on your skin, food or pill, natural or synthetic, carotenoid or retinoid...it all raises your blood retinoic acid(s) level, and some of it (much of it, really) gets turned directly into the exact same chemical compound as Accutane (some goes to Retin-A too!). The importance of realizing this truth is paramount to understanding the nature of Poison/"Vitamin A".

Next, did you know that Poison/"Vitamin A" retinoic acid(s) have been studied to be used in vaccines as adjuvants? Did you know that adjuvants have been so strongly associated with causing autoimmunity that there is now an Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA) discussed in the scientific literature?

So...all Poison/"Vitamin A" raises retinoic acids, including the EXACT SAME retinoic acids--including ACCUTANE--that are used in pharmaceutical drugs.  Poison/"Vitamin A" has been studied as an adjuvant, and adjuvants are well-observed to be associated with causing autoimmunity.  Now that we have established that foundation, let's go through the case studies in the literature of autoimmunity being directly caused by 13-cis-retinoic acid, aka Accutane!

Let me just review this one quote, in case you didn't read one of the important links I put above:

“The presence of 13-cis-RA as the predominant form of RA in human urine under normal physiological conditions recently has been reported (18).

The main form of retinoic acid in the body, under "normal" conditions--coming from"normal" food--is 13-cis-retinoic acid aka Accutane.

Here we go.

Hashimoto's Disease, aka autoimmune HYPOthyroid, AND autoimmune Ocular Myasthenia Gravis:

Presumed Isotretinoin-Induced, Concomitant Autoimmune Thyroid Disease and Ocular Myasthenia Gravis: A Case Report

Introduction
There are many adverse effects that have been described for isotretinoin. To the best of our knowledge, this is the first report of a possible association of oral isotretinoin intake with autoimmune thyroiditis and ocular myasthenia gravis (OMG).

Case Presentation
A 19-year-old Caucasian male, who had used oral isotretinoin for severe acne disease for the previous six months, was referred to our clinic. He had a three-week history of diplopia and variable bilateral ptosis. Physical examination showed moderate periorbital edema and limitations of up- and down-gaze in the left eye. Laboratory findings and thyroid ultrasound were consistent with autoimmune thyroiditis. Antithyroid therapy did not relieve the clinical symptoms. Concomitant OMG was suspected. Variable ptosis and a positive response to oral prednisolone of 40 mg/day and pyridostigmine of 360 mg/day supported the diagnosis of concomitant autoimmune thyroiditis and OMG.

Conclusion
Autoimmune disorders may be triggered by oral isotretinoin treatment. Clinicians prescribing isotretinoin should be aware of the possible association between isotretinoin intake and concomitant autoimmune thyroiditis and OMG.

Graves' Disease, aka autoimmune HYPERthyroid:

Isotretinoin as a Possible Environmental Trigger to Autoimmunity in Genetically Susceptible Patients

Introduction. Isotretinoin is commonly used to treat cystic acne. Definitive mechanisms of action for isotretinoin are not known though despite many side effects having been documented. Various case reports have noted autoimmune diseases succeeding isotretinoin treatment. Case Report. A 16-year-old female presents with symptoms of tremors, lack of focus, sleeplessness, emotional liability, bulging eyes, loose stools, heat intolerance, and missed menstrual periods. Symptoms manifested shortly after the patient finished a course of oral isotretinoin treatment for acne. Physical exam showed resting tremors, bilateral proptosis, hyperactivity, and rapid speech. A diagnosis of Graves' Disease was made by correlating symptoms, physical exam findings, ultrasound, and positive family history of autoimmune thyroid disease.Conclusion. Emergence of autoimmune thyroid diseases depends upon genetic predisposition and environmental triggers. Mechanism of action for isotretinoin is not known but the drug may play a role in triggering autoimmunity in genetically susceptible individuals.
[...]
Side effects of isotretinoin range from fatigue to depression, muscle aches, constipation, teratogenicity, and, more commonly, mucocutaneous side effects leading to irritable bowel syndrome [23]. Various case reports have also reported emergence of autoimmune disease such as diabetes, autoimmune hepatitis, Guillain-Barre syndrome, and thyroiditis shortly after completing a regime of isotretinoin or during last week of treatment [48]. The case presented below describes a patient with a positive family history of autoimmune thyroid disease who develops Graves' Disease shortly after completing a course of isotretinoin treatment for cystic acne.

Autoimmune (rheumatoid) arthritis:

Rheumatologic complications of vitamin A and retinoids.

Retinoids are synthetic derivatives of vitamin A. They are administered primarily for dermatological conditions, such as psoriasis, acne, and disorders of keratinization. Toxicity has proven a significant problem with long-term administration of the retinoids. Bone abnormalities mimicking seronegative spondyloarthropathy or diffuse idiopathic skeletal hyperostosis have been described in many cases, as well as other rheumatologic manifestations such as arthritis, myopathy, and vasculitis. These retinoid-related adverse effects are reviewed.

Isotretinoin-induced arthritis mimicking both rheumatoid arthritis and axial spondyloarthritis.

Isotretinoin is used for the treatment of various acne lesions that are resistant to other treatments. The most frequent rheumatologic side effect of isotretinoin is transient muscle and/or joint pains. Here, we report a case with bilateral wrist and metacarpophalangeal joint arthritis and unilateral sacroiliitis associated with isotretinoin usage to attract attention, particularly from physiatrists, rheumatologists and dermatologists, to this rare adverse effect of isotretinoin.

Autoimmune Ulcerative Colitis (UC), Crohn's, and Inflammatory Bowel Disease:

Isotretinoin-induced inflammatory bowel disease.

Three case reports on inflammatory bowel disease associated with use of isotretinoin are described. All three patients were male adolescents, in good health when starting isotretinoin (for acne treatment for about six months). Several weeks after discontinuation of isotretinoin the patients developed severe symptoms requiring hospitalisation. The diagnosis of ulcerative colitis was made in two of these patients, while in the third patient Crohn's disease was diagnosed. Although inflammatory bowel disease is described as an adverse drug reaction in the product information of isotretinoin, few cases have been described so far. The link with prior isotretinoin use may not be recognised by the patient or the physician, since the diagnosis of inflammatory bowel disease is often preceded by several years of vague symptoms.

Possible association between isotretinoin and inflammatory bowel disease.

RESULTS:  All of the adverse reports filed with the FDA between 1997 and 2002 were accessed and reviewed. Eighty-five cases of IBD associated with isotretinoin use were reported. According to the Naranjo ADR probability scale, 4 cases (5%) scored in the "highly probable" range for isotretinoin as the cause of IBD, 58 cases (68%) were "probable," 23 cases (27%) were "possible," and no cases were "doubtful."

CONCLUSIONS:  In a subgroup of patients, isotretinoin might serve as a trigger for IBD.

Isotretinoin and intestinal damage.

(1) Isotretinoin, a vitamin A derivative, is marketed as an oral treatment for refractory severe acne. It is known to carry a risk of severe birth defects. The skin tends to become dry and fragile during isotretinoin treatment; (2) Some adverse effects of isotretinoin are caused by damage to the intestinal mucosae. These effects include bloody and mucousy diarrhoea, colitis, ileitis (sometimes severe and necessitating surgery), and aggravation of inflammatory bowel disease such as Crohn's disease; (3) Isotretinoin can affect all mucous membranes, causing multiple disorders of varying severity, affecting: the eyes (conjunctivitis); ear, nose and throat (epistaxis); respiratory tract; gastrointestinal tract (colitis); and urinary tract; (4) Patients must be informed of the risk of mucosal damage and especially of intestinal disorders associated with isotretinoin therapy. Isotretinoin should be borne in mind as a possible cause when a young patient presents with gastrointestinal disorders, and its withdrawal should be envisaged. Isotretinoin is an additional risk factor in patients with a personal or familial history of inflammatory bowel disease.

Isotretinoin Use and the Risk of Inflammatory Bowel Disease: A Case Control Study

Ulcerative colitis but not Crohn’s disease is associated with prior isotretinoin exposure. Higher dose of isotretinoin appears to augment this risk.

Autoimmune diabetes:

Association Between Oral Isotretinoin Therapy and Unmasked Latent Immuno-Mediated Diabetes

Isotretinoin is an effective drug for the treatment of acne, but elevated liver enzymes, dyslipidemia, insulin resistance, and type 2 diabetes during isotretinoin therapy have been reported.
[...]
It is reasonable that latent autoimmune diabetes in adults (LADA) could be clinically revealed by drug-induced insulin resistance. In this case, the only remarkable change of lipid profile consisted in a reduction of HDL cholesterol during isotretinoin treatment; therefore, the previously reported physiopathological hypothesis (14) is not completely supported. However, this is the first report of an association between isotretinoin and an unmasking case of autoimmune diabetes.

Autoimmune hepatitis:

[Autoimmune hepatitis induced by isotretionine].

We describe a case of a teenage patient with the diagnosis of drug induced autoimmune hepatitis. The patient is a 16 years old female, with the past medical history of Hashimoto's hypothyroidism controlled with levothyroxine, who started treatment with Isotretionin (Accutane) 20 mg q/12 hours for a total of 3 months for the treatment of severe acne. The physical examination was within normal limits and the results of the laboratory exams are: Baseline values of ALT 28 U/L, AST 28 U/L. Three months later: AST 756 U/L, ALT 1199U/L, alkaline phosphatase 114 U/L, with normal bilirubin levels throughout the process. The serology studies were negative for all viral hepatitis; ANA titers were positive (1/160) and igG levels were also elevated. A liver biopsy was performed, and was compatible with the diagnosis of autoimmune hepatitis. Corticosteroid therapy was started with Prednisone 40 mg per day one week after stopping the treatment with isotretionin, observing an improvement in the laboratory values. We describe this case and review the world literature since there are no reported cases of Isotretinoin-induced autoimmune hepatitis.

Autoimmune epilepsy (Epilepsy: an autoimmune disease? and Epilepsy Associated with Systemic Autoimmune Disorders):

Neuromuscular adverse effects associated with systemic retinoid dermatotherapy: monitoring and treatment algorithm for clinicians.

Isolated cases of stiff-person-like syndrome, epileptic seizures and generalized muscle stiffness syndrome, possibly or probably related to oral treatment with isotretinoin, have also been reported.

Isotretinoin: possible cause of acute seizure and confusion.

[Isotretinoin, a possible cause of epileptic seizures].

Autoimmune Guillain-Barre:

Guillain-Barré syndrome seen in users of isotretinoin

We report Guillain-Barré syndrome in people taking oral isotretinoin, a retinoid drug used in secondary care for severe acne.1 The Committee on Safety of Medicines has received one other report of Guillain-Barré syndrome after oral isotretinoin (Committee on Safety of Medicines, private communication).

Case 1—A 31 year old man took 80 mg of oral isotretinoin a day for five weeks, during which he had epistaxis, dry lips, cough, and arthralgia before developing paraesthesiae in his feet and influenza-like symptoms. The next day he could not stand due to an areflexic tetraparesis and needed ventilatory support. Within four days he could only blink.

Case 2—A 13 year old boy took 50 mg of oral isotretinoin a day for two months, stopped for one week, and then took 30 mg a day for six weeks but had epistaxis, lethargy, and headaches. After stopping isotretinoin again for 10 days he developed a flaccid areflexic tetraparesis needing ventilatory support.

Both patients displayed cerebrospinal fluid albuminocytological dissociation. Nerve conduction studies in case 1 showed a motor axonal neuropathy with unrecordable sensory potentials and F waves, those in case 2, done after 21 months, showed borderline increased F wave latencies. Both patients received intravenous immunoglobulin IVIg 2 g/kg and left hospital within three months. Neither patient has been rechallenged with oral isotretinoin, although the first continued to use topical isotretinoin gel 0.05% which is not absorbed.

Note how much worse the first case was, and he continued to use topical Accutane!  3 MONTHS in the hospital, he couldn't move, he could only blink!  There are no coincidences.

Autoimmune skin conditions, including vitiligo, eczema, and cheilitis:

Vitiligo Appearing after Oral Isotretinoin Therapy for Acne

In this report, we describe a case of vitiligo appearing for the first time after using oral isotretinoin for scarring acne. The most common side effects with oral isotretinoin therapy are skin dryness and chelitis. In a study of 1743 cases reviewing the side effects of isotretinoin, chelitis was reported to be the most common side effect followed by eczema and tiredness [9]. Of note, vitiligo was not reported in this study. Some rare complications have been reported like acute myocardial infarction linked with the increase in lipids [10], inflammatory bowel disease [11], and severe myopathy [12].

Vitiligo was reported around lips in a patient treated with isotretinoin owing to the chelitis as a Koebner phenomenon. This patient suffered from vitiligo prior to the initiation of isotretinoin [13]. Our case is different as she developed vitiligo lesions for the first time after isotretinoin therapy. One patient out of 50 developed vitiligo while on low-dose (20 mg/day for 3 months) isotretinoin therapy for acne [14], while larger-scale studies did not report vitiligo as a side effect (150 patients) [15].

Autoimmune vasculitis (disorder causing inflammation and bleeding in the small blood vessels):

Henoch-Schönlein Purpura during Isotretinoin Therapy

Henoch-Schönlein purpura (HSP) is a leucocytoclastic vasculitis that typically presents with a palpable purpuric rash. The disease primarily affects children and has rarely been seen in adults (3.4 to 14.3 cases per million)1. Hereby, we present a 20-year-old patient with HSP that developed during isotretinoin treatment for his acne.

A 20-year-old man presented at our outpatient clinic with palpable purpuric lesions developed after the fourth week of isotreinoin (30 mg/day) treatment for severe inflammatory acne. Examination revealed multiple palpable purpura on the legs, 1 mm to 15 mm in diameter (Fig. 1). Furthermore, the patient had arthralgia in both ankles and knees.
[...]
The patient also denied any vaccination or drug use other than isotretinoin over the last 2 months. A skin biopsy of from one of the lower limb lesions showed leukocytoclastic vasculitis with IgA and C3 deposition (Fig. 2). On histopathological examination, in support of the relationship between vasculitis and the drug, quite a few eosinophilic infiltration in addition to perivascular neutrophilic infiltration was observed (Fig. 2B). According to these clinical and histopathological findings, the patient was diagnosed with having HSP. Isotretinoin treatment was discontinued; low-dose steroid therapy (fluocortolon 20 mg/day) was initiated and continued 3 weeks. All lesions disappeared by 2 weeks and the disease did not relapse during the 2 months' follow-up.
[...]
Other well-known triggering factors of the disease are hepatic infections, inflammatory bowel disease, autoimmune rheumatic diseases, hematological and solid organ malignancies, vaccinations and adverse drug reactions to diverse drugs. Use of isotretinoin was the sole suspected cause of HSP in our case. Isotretinoin induced vasculitis is very rare in the literature. Dwyer et al.3 reviewed 11 isolated vasculitis cases, which could have been associated with isotretinoin and were gathered by manufacturer of isotretinoin. In the manufacturer's judgment, 5 of the 11 patients the leucocytoclastic vasculitis was associated with the use of systemic isotretinoin. There were no other factors other than retinoid use that may have caused vasculitis in these patients
except for 1 patient who had streptococcal infection.

Reynolds et al.4 reported a case of disseminated vasculitis, which developed 6 weeks after completion of isotretinoin treatment. However, some authors argued that this cause was controversial considering a serum half-life of isotretinoin5. Epstein et al.6 described 2 patients who developed severe vasculitis in whom one patient with Wegener's granulomatosis and the other patient with small-vessel angiitis, while receiving isotretinoin for severe cystic acne. Chochrad et al.7 reported a case of 'polyarteritis-like vasculitis' associated with isotretinoin.

It is interesting that despite these early reports of vasculitis associated with isotretinoin, in a PubMed search we could not detect any other reports after 1997. The reason may be associated with a rare occurrence of cases, alternatively further cases may have not been reported. In addition, it is not possible to make a definitive diagnosis. Instead, the diagnosis of drug induced vasculitis is based on a temporal relationship between exposure to the agent and the development of vasculitis and the exclusion of other factors.

In our case, we couldn't find any causal factor other than treatment with isotretinoin. Although rare, the clinicians should remember retinoid medications as a possible cause of vasculitis.

This one has so many problems caused by Accutane (isotretinoin) in it, you just need to read it:

Autoimmune thyroiditis and isotretinoin: real association or coincidence?

N.Q and N.T are twins borne from non-consanguineous [not blood-related] parents. Since the age of 1 year, they developed inflammatory acne conglobata initially treated with oral zinc (30 mg/day) and topical benzoyl peroxide without success. Systemic isotretinoin was then started at the age of 2 years at 0.5 mg/kg/day up to a cumulative dose of 140 mg/kg spread over 12 monthsThe treatment was remarkably efficient within the first month. Apart cheilitis, isotretinoin was well tolerated. Eighteen months after stopping treatment, the brothers complained of increased weakness, frequent falls, myalgia, constipation and lower reactivity in school. Clinical examination revealed a failure to thrive, skin pallor and hirsutism. Laboratory tests showed normocytic anaemia, rhabdomyolysis and deep peripheral autoimmune hypothyroidism (Table 1). Cervical ultrasound showed hypotrophy of the thyroid gland that indicated no fixation at the I-123 scintigraphy. No autoimmune disease was associated (Table 1). Hormone replacement with levothyroxine allowed a gradual amendment of the clinicaland biological disorders, notably with a recovery of normal growth and psychomotor development.
[...]
The mechanism by which isotretinoin may induce autoimmune thyroiditis remains uncertain. However, the occurrence of the autoimmune thyroiditis in the two brothers who received the same treatment, and the absence of a clear aetiological factor or autoimmune-associated disorder suggest that isotretinoin may be responsible through its immunomodulatory effect.3 Isotretinoin may have triggered an insidious autoimmune reaction that became symptomatic after treatment discontinuation.

This article demonstrates many important things that are pertinent to what I have observed/learned about Poison/"Vitamin A".

  1. The "Duration Paradox".  This is discussed elsewhere in this blog-forum in more detail.  In short, it is the concept that whatever tissues/issues that Poison/"Vitamin A" may seem to help in the beginning, it will completely destroy those tissues (and the rest of the body if given long enough and in high enough doses) in the long-term.  Note how the isotretinoin was "remarkably efficient within the first month", only to end up completely ruining everything about these poor children's health over the next 18 months.  Note the skin/dermatological-related issues that came up later:  cheilitis (inflammation of the lips), skin pallor (paleness or loss of color, likely related to the deeper anemia), hirsutism (this is excessive body hair growing in areas where grown men typically have hair, such as the face, back and chest...these boys were only around 4 years old!!!).  THAT is the definition of the "Duration Paradox".  The improvements at the beginning will completely fool people into completely disbelieving that their later problems couldn't possibly be from Poison/"Vitamin A".  How wrong they are, sadly.
  2. These kids started out with a rare and severe type of acne.  I'm going to tell you that the very FACT that their acne IMPROVED from the isotretinoin in the beginning means that their acne problem had a FOUNDATION in Poison/"Vitamin A" toxicity.  When higher doses of Poison/"Vitamin A" are given to someone who is already toxic (ie. these boys), it can/will improve things for a while...and then everything turns disastrous later, just as you read.  Severe acne turned into the picture of a poisoning:  cheilitis, increased weakness, frequent falls, myalgia (muscle pain), constipation, lower reactivity in school (I'm translating this to learning disability), failure to thrive, skin pallor, hirsutism, anaemia, rhabdomyolysis (rapid destruction of skeletal muscle resulting in leakage into the urine of the muscle protein myoglobin, can cause kidney damage/failure), and autoimmune hypothyroidism (Hashimoto's is the common term). 
  3. Kids are more susceptible to Poison/"Vitamin A" toxicity.  That said, they also recover much faster from it than adults once the offending sources of Poison/"Vitamin A" are removed completely and the body is allowed time to repair/recover/restore the damage done.  This is evident in the "recovery of normal growth and psychomotor development."  The thyroid hormone helped correct a symptom, but it was stopping the isotretinoin and being off it long enough that was what really fixed most of the problems.

Did you know that once a person is diagnosed with ONE autoimmune disease, the research suggests that more are to come? Did you know that the phenomenon of the same person having multiple autoimmune diseases together (MAS, see below) is increasing?  See below.

Multiple autoimmune syndrome

ABSTRACT
The co-occurrence of autoimmune diseases has been epidemiologically studied and has aided in our understanding of autoimmunity. The combination of at least three autoimmune diseases in the same patient has defined as multiple autoimmune syndrome (MAS). About 25 percent of patients with autoimmune diseases have a tendency to develop additional autoimmune diseases. MAS is recognized with increasing frequency. Several associations have been proposed as a form of MAS. Multiple autoimmune syndrome can be classified into three groups according to the prevalence of their associations with one another: type 1, type 2 and type 3. Genetic, infectious, immunologic and psychological factors have all been implicated in the development of MAS. In MAS, patients often have at least one dermatological condition, usually vitiligo or alopecia areata. The pathogenesis of multiple autoimmune disorders is not known yet, perhaps environmental triggers and genetic susceptibility are involved. Abnormalities of both humoral and cell-mediated immunity have been described. However, as new perspectives develop on the pathogenesis and natural history of autoimmune diseases, a refinement in the methodology for the study of the co-occurrence of disease is warranted in order to maximize the information that one may realize from such studies. This paper presents some recent results of studies in light of current understanding of the natural history of autoimmune diseases.

Note these things:

  • If autoimmunity is a chronic poisoning of a substance that accumulates over time, then if someone was becoming more poisoned over time, it only makes sense that the "same type of problems" (we call it "autoimmune") would spread to other areas.
  • Autoimmune skin issues (don't forget to include psoriasis and eczema!) are commonly present with other autoimmune diseases.
  • They suggest an "environmental trigger" may be involved.  I have two suggestions of what these triggers are that build upon each other that I believe--and will demonstrate through the research that is already present--are causing this Modern Chronic Disease epidemic in combination.  The two main things are glyphosate/Roundup and Poison/"Vitamin A" toxicity.  Everything else--all the relatively "minor" problems that the interwebz loves to obsess about--is at best merely additive to this main problem.

Modern medicine seems to be quite clueless as to what "causes" autoimmunity.  There is really no need to be confused any longer.

We have a starting point.

13-cis-retinoic acid quite obviously can induce autoimmunity in nearly any part of the body. 

13-cis retinoic acid is the MAIN retinoic acid breakdown product of ANY and ALL Poison/"Vitamin A" (including carotenoids!) you consume.

Make the connection...Poison/"Vitamin A" toxicity IS THE FOUNDATION OF ALL AUTOIMMUNE DISEASE.

There's no need to wonder any longer.  We can fix this problem.

Dr. Garrett Smith, the "Nutrition Detective"
Licensed Naturopathic Physician (NMD) in Arizona
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