AUTOIMMUNE DISEASES CAUSED BY AN INFECTION?

[Laura]

Something interesting that might be related to the infectious causes of autoimmune diseases:

- Blood biomarker predicts death from serious infection
Anna Salleh
ABC Science, Australia
Fri, 23 Oct 2015 02:15 UTC

Scientists have found a biomarker in the blood that can tell if a person is more likely than others to die early from pneumonia or sepsis.

The biomarker is associated with chronic inflammation, perhaps due to microbial infection, and predicts death from infection up to 14 years in the future, said researchers today in the journal Cell Systems.

But, the researchers warned further research was needed before a test for the biomarker would be warranted.

In the past year, scientists have found that when a collection of common proteins called GlycA is elevated in the blood, a person is more likely to die prematurely.

"Per unit increase of GlycA, you get an increased risk of death, from any cause, of between 40 and 50 per cent," said Dr Michael Inouye from the University of Melbourne's Centre for System Genomics. But little was known about the biology of the GlycA biomarker, and how it could lead to early death.

"We wanted to understand why, because without that you can't remove the risk," said Dr Inouye.

He and colleagues analysed data, much of it electronic records, on over 10,000 adults from Finland and found that those who had elevated GlycA tended to be more likely to die from sepsis and pneumonia.

"As GlycA increases, your risk of disease increase," Dr Inouye said.

"There were some strong associations. People who had one unit increase in GlycA levels were at 2.2 fold increased risk from sepsis, which makes up the majority of systemic infections."

Importantly, the study showed that when GlycA levels became elevated they tended to remain so for up to a decade, and GlycA predicted death from infection up to 14 years in the future.

GlycA linked to elevated inflammatory markers

Given that GlycA is involved in the initiation of the body's inflammatory response, Dr Inouye and colleagues decided to use a computer model to look at the relationship between these elevated levels and other parts of the immune system.

The model showed that when GlycA blood levels were high, so were the levels of 30 different immune-signalling molecules, called cytokines.

High levels of cytokines are a sign of an overactive immune system and have been linked to disease, said Dr Inouye.

The study also showed that people who recently had an acute infection had both elevated GlycA and elevated neutrophils, which are cells that are also involved the inflammatory response, particularly to microbial infection.

This suggests that GlycA is linked to premature death because it is a marker of chronic inflammation, which may be triggered by microbial infection, said the researchers.

"Chronic inflammation is a low-level risk factor for all sorts of things," said Dr Inouye.

The link between GlycA and increased risk of death from sepsis seen in the study could be as a result of chronic inflammation making it more difficult for the body to cope with acute infection, he said.

Dr Inouye said further research was needed to confirm the predictive power of GlycA and to understand how it might be possible to intervene to lower the risk it posed.

"It's not a particularly useful biomarker unless you can do something about it," he said.

"In a clinical setting you wouldn't want to be offering a test for GlycA to your patient unless you can do something about it."

 

[Gaby]

A heads up on metronidazole benzoate Vs metronidazol USP.

It seems that metro benzoate is used for oral suspensions and topical versions. The dose needs to be adjusted though. From _http://www.pharmacytimes.com/publications/issue/2004/2004-07/2004-07-8039:

Another suggestion is the use of metronidazole benzoate, a salt of metronidazole with virtually no associated taste issues. A weight conversion to obtain the correct dose is necessary, because the benzoate moiety contributes a large percentage of the molecular weight [...]

Metronidazole benzoate 400 mg = metronidazole 250 mg

Metronidazole benzoate 200 mg = metronidazole 125 mg

More basic info on metro benzoate:

_https://www.ebi.ac.uk/chebi/chebiOntology.do?chebiId=CHEBI:50688

FWIW.

 

[Str!ke]

Now, here’s some information about the works done at Hansa Centre on Lyme disease and other ailments:

Sounds more like a promo job. I'd like to hear from REAL patients. Is there a discussion forum somewhere online talking about treatments?

I believe you already know this forum (_http://forums.phoenixrising.me/), right?

It may be worth another look. Searching for authors/doctors results in some useful posts IMO, mainly experiences with various treatments (although still not conclusive). For instance, there’s a Horowitz patient who didn’t recover for some reason. Other posts also mention Buhner and Cowen’s herbs/protocols with mixed results. Apparently they seem to discuss a lot about a doctor named KDM (Kenny de Meirleir), who according to a user, he “follows and uses Horowtiz's idea of MSIDS” whose some patients improved.

Personally, I’m very interested in this, as I’ve had, for the past 8 years, several pains that keep intensifying… and low energy. I also got 70 on the questionnaire… So I feel the need to move quickly and carefully. Maybe it will help me a lot. Thank you all for bringing this up.

 

[Altair]

I have a short question (sorry if it's offtopic). I had root end surgery today and the doctor prescribed me Clindamycin 600 mg for 2 weeks. I don't have any autoimmune disorders and currently don't plan to go on the protocol. Does it make sense to take this antibiotic or colloidal silver and oregano oil will be enough to prevent possible infection?

The later ones could well be enough. Some vitamin C will be helpful too. I think it is a little bit over the top to prevent an infection with clindamycin. I would file the antibiotic though, keep it in stock and/or take it at the first sign of infection.

My 2 cents.

Thank you, Gaby! And yes, I bought the antibiotic. Just in case.

I started taking this antibiotic since my nasal cavity got infected (either before the surgery due to deep root canal inflammation or during the surgery). I used to have chronic sinusitis as I was a child (due to deformed nasal septum). After a correction surgery many years ago all the symptoms of sinusitis gone. Also I had a peptic ulcer for many years which ended in severe internal bleeding, surgery and consequent antiobiotics treatment 12 years ago. Since then I don't have any symptoms. Apart from that I currently have only wasp allergy and no autoimmune disorders. So I dunno, does it make sense to try antibiotics challenge directly after Clindamycin treatment? Currently I don't have any reaction to Clindamycin and feel much better after taking it. I take it with NAC, nattokinase and serrapeptase to break possible biofilms.

 

[Gaby]

So I dunno, does it make sense to try antibiotics challenge directly after Clindamycin treatment? Currently I don't have any reaction to Clindamycin and feel much better after taking it. I take it with NAC, nattokinase and serrapeptase to break possible biofilms.

I'm not sure if that is an enough good reason, so I would take it step by step. First finish your current prescription, repopulate gut flora with good probiotics and see if you feel better. Later on, you could do a doxy challenge test to see if there are Herx reactions or if it makes you feel better. But it can be done later, if it comes to it.

Speedy recovery!

 

[Altair]

So I dunno, does it make sense to try antibiotics challenge directly after Clindamycin treatment? Currently I don't have any reaction to Clindamycin and feel much better after taking it. I take it with NAC, nattokinase and serrapeptase to break possible biofilms.

I'm not sure if that is an enough good reason, so I would take it step by step. First finish your current prescription, repopulate gut flora with good probiotics and see if you feel better. Later on, you could do a doxy challenge test to see if there are Herx reactions or if it makes you feel better. But it can be done later, if it comes to it.

Speedy recovery!

Thank you, Gaby! :)

 

[Gaby]

Attached as a .doc, a simplified version of the protocol with updates.

In "Combatting Biofilms" by James Schaller and Kimberly Mountjoy, it says that one concern in complex biofilms is that infections caught in the biofilms can be released by biofilm killers, making the cure actually a mechanism to spread the infection. They suggest using as many infection killing options as possible, since more is better to prevent "seeding" of a dispersed infection. Second, they suggest several biofilm killing options to destroy biofilms by different mechanisms. This makes the dispersed seeded infections naked to the immune system. Third, biofilm tools can be given initially at low doses and then increased to large doses since often at the beginning people have massive inflammation which make people miserable (i.e. Herx reaction, "cytokine storm").

They say that you may need to pulse (use every other day) or fully stop this treatment (biofilm destroyers) because once a wave of biofilm eroding agents strips off or severely damages a biofilm of an infection, the same antibiotics that were useless in the past can become very effective.

Attacking biofilms through means like apple cider vinegar, xylitol or erythritol, oil pulling with coconut oil, enzymes such as serrapeptase, etc... are some of the options. The .doc has already good enough biofilm destroyers which also have other functions such as supporting detox pathways. Doxy and azithromycin are also good biofilm destroyers, other than being good anti-microbials. But some people might want to keep in mind other biofilm destroying options just in case, specially if they feel they're not going anywhere with the protocol.

 

[Mr.Cyan]

Thanks Gaby for the updated protocol, much appreciated as always :)

 

[riclapaz]

Thanks Gaby for the updated protocol, much appreciated as always :)

Ditto!, Thanks Gaby

 

[Skyalmian]

Attached as a .doc, a simplified version of the protocol with updates.

Can it be in PDF form as well? (For Android/iPhones etc. non-PC.)

 

[griffin]

Attached as a .doc, a simplified version of the protocol with updates.

Can it be in PDF form as well? (For Android/iPhones etc. non-PC.)

Here you go.

 

[Laura]

An interesting side effect of the protocol showed up with one of our house peeps. Since Metro wasn't producing any reaction, cipro was tried. But this immediately led to the manifestation of erythema nodosum.
https://en.wikipedia.org/wiki/Erythema_nodosum

Nothing seemed to be working on clearing this up so I did what I normally do: research. I noted in the wikipedia article the following: "Potassium iodide can be used for persistent lesions whose cause remains unknown."

Having those keywords: erythema nodosum and potassium iodide, enabled me to find the things that I posted on the potassium iodide thread here: https://cassiopaea.org/forum/index.php/topic,13371.0.html

Having read a number of papers about it, I think that what happened/happens is that an antibiotic kills off the bacterial elements and then a fungal type microbe takes over and goes nuts the same way antibiotics allows the emergence of yeast in the gut.

In the above mentioned case, a sample was taken from the suppurating wound and "nothing pathologically interesting" was found. That is, despite the fact that the dr. thought it might be staph in the skin, it wasn't.

Anyway, the potassium iodide cure route proves to be VERY interesting and also application of potassium permanganate to the wound itself which made a dramatic difference in 24 hours.

Reading about the potassium iodide has given me the idea that it should be included in the protocol in addition to nystatin, as a means of killing opportunistic fungal infections during the course of the protocol. I even wonder if the potassium iodide itself, perhaps along with biofilm busters and some herbal antimicrobials might be a less brutal means of solving the problems altogether? One of the papers I read noted outright that research into the benefits of potassium iodide was not a priority because it can't be patented. It reminds me of the benefits of turpentine that are also not studied because it can't be patented either.

Then, of course, there is boron which apparently works well too.

One thing that I found was one paper that specifically mentioned lung problems that could be caused by fungi and was cured by potassium iodide. How many people have COPD and could benefit from this simple remedy? It is noted on the PI thread that selenium is a co-factor, so that would need to be added as well.

See this post:
https://cassiopaea.org/forum/index.php/topic,13371.msg98521.html#msg98521
...which includes:

Iodine is by far the best antibiotic,
antiviral and antiseptic of all time.
Dr. David Derry

The antiseptic properties of iodine are used to sterilize every surface and material in hospitals. Iodine is an excellent microbicide with a broad range of action that includes almost all of the important health-related microorganisms, such as enteric bacteria, enteric viruses, bacterial viruses, fungi and protozoan cysts.[v] The minimum number of iodine molecules required to destroy one bacterium varies with the species. For H. influenzae it was calculated to be 15000 molecules of iodine per cell. When bacteria are treated with iodine, the inorganic phosphate up-take and oxygen consumption by the cells immediately ceases. [vi]

Though iodine kills all single celled organisms such as these it is not exploited for internal use by modern day physicians to combat internal infections, which of course is a great mistake. Dr. Derry says iodine is effective "for standard pathogens such as Staphylococcus, but also iodine has the broadest range of action, fewest side effects and no development of bacterial resistance." Some doctors have reported that it is excellent for the treatment of mononucleosis.

Iodine is able to penetrate quickly
through the cell walls of microorganisms.

Iodine is a deadly enemy of single cell microorganisms thus it can be our best friend. Iodine was not available to these life forms at the beginning of evolution and it was not until seaweed concentrated it did it become involved in higher life forms. It is for this reason that the simplest level of life cannot tolerate iodine. Iodine kills single celled organisms by combining with the amino acids tyrosine or histidine when they are exposed to the extra-cellular environment. All single cells showing tyrosine on their outer cell membranes are killed instantly by a simple chemical reaction with iodine that denatures proteins. Nature and evolution have given us an important mechanism to control pathogenic life forms and we should use it and trust it to protect us in ways that antibiotics can't. As we shall see directly below, so powerful is iodine in a protective sense that it also helps us rid the body, not only of harmful chemicals and heavy metals, but also rids the body of abnormal cells meaning it qualifies as an anticancer agent.

Can we dig into this a bit more?

 

[ka]

Hi, Laura and all:

I have also experienced real benefit from supplementing with potassium iodide.

About 4 years ago I a friend suggested it might help me, and it is one of the few things that made an unmistakable improvement: better energy levels, and raised body temperature (better metabolism).

My complaints are much the same list that Laura and other people have mentioned on this forum. I had modified my diet to discourage candida, taken nystatin, tried a whole list of supplements—but things just got worse.

Boswellia and glucosamine chondroitin are the other supplements that clearly did me good, and I’m still taking them to reduce joint pain.

Exactly 2 years ago I began the keto diet, and that helped immensely. But this year, all my complaints began to flare up again. So I was eager audience for all the information on this thread about combatting microbial infection.

Since late May of this year I have been taking boron, neem, enzymes, artemisa, chaga and other mushrooms, and most of the non-pharmaceutical remedies recommended on this thread—and I’m feeling better again.

Many thanks to Laura and all contributors here!

 

[Gaby]

Can we dig into this a bit more?

I'll quote some of the same papers already posted on the Iodine and Potassium Iodide thread. Maybe will notice a pattern of what could be the ideal experimental dose as well as potential contraindications.

I remember that Richard Horowitz used 1 drop of lugol solution when there was iodine deficiency linked with breast and ovarian issues.

First paper is a review:

Use of potassium iodide in Dermatology: updates on an old drug

_http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754371/

An Bras Dermatol. 2013 May-Jun; 88(3): 396–402.

Abstract

Potassium iodide, as a saturated solution, is a valuable drug in the dermatologist's therapeutic arsenal and is useful for the treatment of different diseases due to its immunomodulatory features. However, its prescription has become increasingly less frequent in dermatology practice. Little knowledge about its exact mechanism of action, lack of interest from the pharmaceutical industry, the advent of new drugs, and the toxicity caused by the use of high doses of the drug are some possible explanations for that. Consequently, there are few scientific studies on the pharmacological aspects, dosage and efficacy of this drug. Also, there is no conventional standard on how to manipulate and prescribe the saturated solution of potassium iodide, which leads to unawareness of the exact amount of the salt being delivered in grams to patients. Considering that dosage is directly related to toxicity and the immunomodulatory features of this drug, it is essential to define the amount to be prescribed and to reduce it to a minimum effective dose in order to minimize the risks of intolerance and thus improve treatment adherence. This review is relevant due to the fact that the saturated solution of potassium iodide is often the only therapeutic choice available for the treatment of some infectious, inflammatory and immune-mediated dermatoses, no matter whether the reason is specific indication, failure of a previous therapy or cost-effectiveness.

INTRODUCTION

Iodine, which was originally obtained from seaweed early in the 19th century, was initially used in the treatment of thyroid disorders only. Over time, new applications made the drug useful and versatile, especially when treatment of inflammatory, immunemediated or infectious diseases fails. Psoriasis, eczema, lupus vulgaris and syphilis are examples of old targets of iodine.1 {Interesting, considering that there are a lot of similarities between Lymes disease and syphilis} It was later used in the treatment of inflammatory dermatoses such as erythema nodosum, erythema multiforme and granuloma annulare; neutrophilic dermatoses such as Sweet's syndrome and pyoderma gangrenosum; and infectious dermatoses such as sporotrichosis and zygomycosis.1,2

Powerful new drugs replaced potassium iodide in dermatology practice, under the pretext that its therapeutic dose was too close to being toxic. On the other hand, better understanding of its mechanism of action resulted in new questions regarding its optimal dose and proper use, generating optimistic future perspectives for a known, safe, inexpensive and effective drug.

The aim of this paper is to show the versatility of an old drug that continues to be a safe and effective therapeutic option for the treatment of skin diseases, as long as it is properly prescribed and administered. We will discuss topics such as pharmacology, mechanism of action, indications and contraindications, and appropriate manipulation of the drug.[...]

PHARMACOLOGICAL ASPECTS AND MECHANISM OF ACTION

Potassium iodide (KI) is a salt composed of 76% of iodine and 23% of potassium which presents itself as transparent or white hexahedral crystals.1,4 "It is photosensitive and has slightly hygroscopic properties, being highly soluble in water."4 Its solubility limit varies depending on the solvent used. One gram (1 g) of the solute is soluble in 0.7 mL of water, 0.5 mL of boiling water, 22 mL of alcohol and 2 mL of glycerol. The solution has neutral to alkaline properties.4,5

"Iodine is poorly absorbed when applied to the skin. By the oral route, solutions of iodide salts are converted into iodine, which is transported and concentrated in the thyroid gland. The remainder is eliminated in the urine, and a small amount appears in the feces, saliva and sweat. It is excreted in breast milk and goes through the placenta."4

The various hypotheses regarding its mechanism of action justify the therapeutic versatility of iodide, which helps to protect the thyroid gland in nuclear accidents or gland disorders, in interactions with cells of the immune system and in direct action against infectious agents. Some of them are exemplified below.

Diseases whose pathogenesis involves the action of neutrophils respond well to iodide. It has been demonstrated that iodine, as well as dapsone, has the ability to suppress the production of toxic oxygen intermediates by polymorphonuclear cells and thus exert its anti-inflammatory effect.6 It also inhibits neutrophil chemotaxis, which is observed in vivo in peripheral blood when KI is taken by the oral route at a dose of 15 mg/kg/day for three days.7 It is speculated that iodine participates in halogenation reactions by myeloperoxidases, which are fundamental for the action of phagocytes.8 This mechanism also helps to understand, in part, the usefulness of this medicine against infectious diseases.

When topical, iodide acts as a disinfectant and an antiseptic.4 The ability of potassium iodide to directly destroy microorganisms continues to be speculated. Although the pharmacological literature states that potassium iodide has no antifungal activity in vitro, a study shows that cell lysis occurs when Sporothrix schenckii yeast is exposed to increasing concentrations of the drug through the release of lysosomal enzymes.4,9 Also, considering the immunological action of iodide in vivo, it is possible that it has some direct effect on the infectious agent. However, more studies are needed to confirm these mechanisms of action.

The immunomodulatory characteristic of the drug justifies its mechanism of action in relation to other inflammatory and immune-mediated disorders. However, the exact target of the complex immunological pathway on which iodide acts in each of these diseases is unknown. The lack of scientific investigations in this area could be justified by the lack of interest from the pharmaceutical industry in this old and unprofitable drug.

NON-DERMATOLOGICAL INDICATIONS

Thyroid diseases

It is the most classic and pioneer indication regarding therapeutic experiences. Iodine is essential for the metabolism of the thyroid gland in order for it to maintain homeostasis resulting from the action of hormones. In cases of deficiencies that cause hypothyroidism and goiter, iodine supplementation is important. Hyperthyroidism can also be treated with radioiodine ablation when there are hormone-secreting solitary hot nodules. Radioiodine ablation can also be used to treat toxic multinodular goiter. Some cases of Graves' disease can also be treated this way, especially in cases that are refractory to antithyroid agents.10,11 Iodine is also used as a radioactive tracer in thyroid scintigraphy.

Respiratory tract diseases

Potassium iodide can be used as expectorant syrup at a concentration of 2% (20mg/mL) in cases of infectious diseases of the respiratory tract or in cases of pulmonary diseases in which anatomical changes impair expectoration, such as emphysema and cystic fibrosis. It acts as an "irritating" expectorant whose mechanism of action will occur by direct irritation of the glands of the respiratory mucosa.4,12

Nuclear accidents

Potassium iodide has been used to block the absorption of radioactive iodine (131) by the thyroid gland through saturation of the receptors in case of nuclear accidents, such as the one that occurred at the Chernobyl Nuclear Power Plant. It reduces the risk of thyroid cancer and hypothyroidism induced by radioactive iodine. It is administered in tablets, generally in a single dose a few hours after exposure to radiation, and its dosage varies according to age.13

Colposcopy

Iodine is also used in diagnostic tests such as colposcopy. The iodine solution, or Lugol's solution, used in Schiller's test stains glycogen-rich areas. In neoplastic cells, the cytoplasm is smaller because the size of the nucleus increases due to greater DNA replication. Thus, iodine-negative areas will reveal the site to be biopsied.14


DERMATOSES

Infectious dermatoses

Topical iodine has bactericidal, antiseptic and disinfectant effects.4 In the past, it was used to treat syphilis and lupus vulgaris.1 Currently, it is used to treat some diseases of infectious etiology.

Sporotrichosis

The saturated solution of potassium iodide (SSKI) has been the first choice for the treatment of lymphocutaneous and fixed cutaneous forms of sporotrichosis since 1900.1,15,16,17 Its efficacy and low cost allowed this drug to be safely used for a long period of time. However, the ease of dosage of itraconazole, which was introduced in the 1990s, caused it to be considered the first-line drug in some centers, although it is more expensive and not different from SSKI in terms of efficacy. In the main international guidelines on the treatment of this disease, the authors classify the different therapeutic options according to levels of evidence and scientific quality. SSKI and itraconazole are at the same level, that is, IIA. Therefore, they are equally effective and indicated as a therapeutic option for the treatment of lymphocutaneous and fixed cutaneous forms of sporotrichosis

Entomophthoromycoses

Entomophthoromycoses are subcutaneous mycoses caused by zygomycetes of the genus Basiodiobolus and Conidiobolus. They can be treated with SSKI, which is considered the gold standard treatment even when compared to the most recent antifungal drugs. Case reports show satisfactory results even in exuberant cases, with good cure rates.

Other

The use of SSKI has been described in the literature as a therapeutic alternative for the treatment of some infections, especially when it is impossible to use other medications. Surgical procedures such as electrocoagulation, exeresis, surgical drainage, thermotherapy or cryotherapy may often be associated. Here are some indications: chromomycosis, mycetoma, cutaneous nocardiosis, cutaneous cryptococcosis and human pythiosis. Therapeutic success is directly linked to the size and duration of the lesion and to the immunological status of the host.1,20,21,22

Inflammatory and immune-mediated dermatoses

The two best indications in this group are neutrophilic dermatoses and panniculitis.1,2 The pathophysiology of pyoderma gangrenosum, Sweet's syndrome and Behçet's disease involves the action of neutrophils. 1 These cells are especially present in early stages, when the intense attraction and toxicity of polymorphonuclear cells produce an exuberant inflammatory response and sterile purulent discharge. Behçet's disease exhibits clear manifestations of this mechanism, such as acne, hypopyon and aseptic meningitis. Potassium iodide has an inhibitory effect on the chemotaxis of neutrophils and on the production of toxic radicals by these cells, which justifies its use in this group of disorders.6,7,23,24

It is possible to assume that potassium iodide has an important anti-inflammatory role in panniculitis, since the patients that show better response also present systemic symptoms and increased C-reactive protein. It usually improves fast, with fever, pain and erythema reduction in two days and complete remission in up to two weeks. The main indications are the following: erythema nodosum, nodular vasculitis and subacute nodular migratory panniculitis.1,2

Miscellaneous

Potassium iodide has been successfully used for the treatment of erythema multiforme, even when associated with infection with herpes simplex; granuloma annulare, including reports of good response to widespread cases of the disease; Erythema annulare centrifugum; and Wegener's granulomatosis.1,2,25


PRESENTATION AND DOSAGE

The recommended dose of potassium iodide to treat infectious diseases varies from 4 to 6g/day or 6 to 7.5 g/day for adults, depending on the scientific reference. The pediatric dose is about half or a third of the adult dose.1,17,26,27,28

However, the recommended dose for inflammatory dermatoses is lower. It is approximately 1g/day for adults, taken in three doses.1,27,28

As an expectorant, the syrup is formulated at 2% (20mg/mL) and administered at a dose of 5 mL, 3-4x /day. 4

To make its use more convenient, potassium iodide is administered in the form of a saturated solution (SSKI).1 A saturated solution should be understood as one in which the addition of any solute will result in its precipitation. Considering the solubility limit for distilled water, which is the vehicle usually used, we found that 1g of the salt to a volume of 0.7 mL of this solvent results in a solution of approximately 1.42 g/mL.4

A discrepancy regarding the dosage of SSKI to be administered is observed in the scientific literature. This can be evidenced in the formulations recommended by WHO or even by some reference books and scientific articles on pharmacology, which define the concentration of the saturated solution of potassium iodide as 1g/mL.4,17,26-31 They probably use already prepared saturated solutions and dilute them to obtain a concentrated solution (not saturated) of 1g/mL. In Brazil, we typically use the pure potassium iodide salt (PA) in the therapeutic formulations.

It is important to have all these considerations in mind before administering the drug to a patient so that the actual dose can be known. Toxicity or absence of therapeutic response is often due to inadequate dosage. Most studies address the number of drops to be administered in the treatment, without even mentioning the characteristics of the solution and the volume of drops used, that is, the amount in grams that is being administered to the patient.

For these reasons, it can be inferred that the knowledge and standardization of the proper use of SSKI are important so that treatment can be tolerable, safe and correct.

When using pure potassium iodide crystals (PA), the correct formula for a final volume of 100 mL is 100 g of salt to 70 mL of distilled water or 50 g of salt to 35 mL of water if the desired final volume is 50 mL.

Considering a standard dropper in which each drop has a volume of 0.05 mL, there will be 0.07 g of KI per drop (1.42 g/mL) in the solution. Thus, by administering 20 drops of the solution 3x/day, the daily intake of potassium iodide is approximately 4g. It is also possible to use the concentrated solution, in which there is 1g of potassium iodide in each mL of water. However, if we consider the same drop volume of 0.05 mL, the daily dose taken by administering 20 drops 3x/day will be 3g.

The studies on dosage recommendation are based on the most classic indication, that is, on the treatment of sporotrichosis. According to the official publication of IDSA (Infectious Diseases Society of America), the recommendation for the treatment of lymphocutaneous or fixed cutaneous sporotrichosis is 40-50 drops 3x/day of a saturated solution, but they do not say how the solution is prepared.18 If it were saturated, the daily total dose would be unbearable, between 8.4 and 10.5 g/day. It is possible that they have considered the concentrated solution, even though the daily dose of 6-7.5g is not always well tolerated.

Another standardization to be reviewed is related to drop volume. A standard dropper usually has 0.05 mL/drop, but there are variations.32 In Brazil, we usually administer 4-6g/day in the treatment of sporotrichosis, which is taken in three doses (Table 2).1,17,26-28 In summary, no matter whether the solution is concentrated or saturated, it is important to know the formulation being used so that the daily dose for inflammatory, infectious or immune-mediated diseases can be adjusted.

CONTRAINDICATIONS AND ADVERSE EFFECTS

The use of KI is contraindicated in cases of previous thyroid diseases such as hypo or hyperthyroidism, presence of nodules and thyroid cancer. Family history of thyroid disease is a relative contraindication. However, positivity for autoantibodies such as anti-TPO antibodies (anti-thyroid peroxidase) and TRAb (TSH receptor antibodies) show a predisposition to autoimmune thyroid diseases that can be triggered by exposure to iodine.1,33

KI is also contraindicated in patients with any type of allergy to iodine.4,28,29,30 Its use should be avoided in patients with chronic renal failure because of the presence of potassium in its formulation and is proscribed in those whose renal function is greatly impaired. Similarly, those using potassium-sparing diuretics or angiotensin-converting-enzyme inhibitors should be closely monitored.1,4,28

It is prudent to avoid the concomitant use of other medications such as lithium, because of its drug interaction, and of medications containing iodine in its formulation such as amiodarone.4,28

Transplant patients and patients with cancer, a history of alcoholic disease, poorly controlled diabetes mellitus and insulin-dependency, autoimmune diseases and immunosuppressive characteristics such as AIDS, and patients who use corticosteroids and immunosuppressive medications should not use this medicine, for its mechanism of action affects the immune system. Active tuberculosis is also included in this group.30

It should not be used by pregnant and lactating women, for it causes neonatal hypothyroidism, thyromegaly, fetal airway obstruction and prolonged labor, being among the category D drugs.1,4,28,30

It should also not be administered to patients with Addison's disease, since they do not only present an autoimmune condition but also changes similar to those that occur with the use of angiotensin-converting-enzyme inhibitors.28

Regarding infectious diseases, KI is not recommended in cases of extensive disease or in cases of involvement of internal organs such as systemic or disseminated cutaneous forms of sporotrichosis, because it is believed that these patients' immune system is impaired.18

Adverse effects, usually mild to moderate, may occur due to the high doses administered, especially for the treatment of infectious skin disorders. They are often related to the digestive system, with a predominance of gastrointestinal intolerance and a metallic or bitter taste in the mouth.1,30

To relieve these symptoms, it is recommended to start the treatment with low doses of the drug, usually five drops of 1.42 mg/mL (0.35 g) three times a day, with daily increases of a drop every time the medicine is taken until the target dosage is reached, for both adults and children.1,4,17,18,29,30 Another recommendation is to take the medicine after meals, with the intake of juice or milk soon afterwards.29 Some pharmacological references recommend mixing the medicine with these drinks.1,17,30 Reducing the dose every time the medicine is taken often eliminates the gastrointestinal complaint without reducing its efficacy.

Due to the presence of large amounts of iodine in the drug, it is possible that it has some effects on the metabolism of the thyroid. There is a physiological mechanism of autoregulation in the human body that aims to keep the pool of stored iodine balanced. Thus, an excess of iodine causes an acute inhibitory effect with a temporary increase in TSH called adaptive block. However, there are escape mechanisms that help maintain the normal function of the gland.1,10

The Wolff-Chaikoff phenomenon is described as an interruption in the thyroid hormone synthesis due to the inability of the thyroid to overcome the acute inhibitory effect resulting from inefficient escape mechanisms in individuals with underlying thyroid disorders, especially Hashimoto's thyroiditis. In these cases, there is axis suppression and increased TSH levels, with consequent hypothyroidism (decreased free T4).1,33

On the other hand, if the patient presents autonomous hormone production in toxic multinodular goiter or in Graves' disease, there may be hyperthyroidism or thyrotoxicosis, which is called Jod-Basedow.1,33

Other adverse effects are occasionally found in the scientific literature, such as acneiform eruption, dermatitis herpetiformis, pustular psoriasis, bullous pemphigoid and iododerma, possibly related to the action on the chemotaxis of polymorphonuclear cells, with iododerma being the most frequent condition in patients with underlying systemic diseases. The syndrome caused by iodine poisoning is called iodism. It is characterized by conjunctival hyperemia, lacrimation, blurred vision, rhinorrhea and sialorrhea.1,28,30

As with any drug, allergic reactions such as urticaria and angioedema should be considered.1,29 Cases of congestive heart failure with pulmonary edema and cases of toxicity related to potassium iodine, such as renal dysfunction, cardiac arrhythmia and metabolic acidosis, have been described.30,34,35 Headaches, arthralgia and prolonged fever have also been reported.1,30

CONCLUSION

Despite being used in Medicine for over a century, potassium iodine remains a good therapeutic option for the treatment of several dermatoses as a drug of first or second choice and may be part of the dermatologist's therapeutic arsenal. When treatment with potassium iodide is considered, it is important to know the exact dose being administered, since the toxicity is directly related to dosage and not to the drug. This involves knowing the formulation being used and the effective dose per drop (in grams) for each individual and therapeutic indication. The toxicity of a drug alone does not constitute a reason to abandon its use, since deeper knowledge of the drug may generate benefits to the patient who does not have access or cannot use other medications due to high cost, adverse effects, drug interactions or even therapeutic failure, in case adverse effects can be controlled, of course. Simply recommending the number of drops may lead to misuse and undue dose administration with risks for the patient.

 

[Gaby]

Sporotrichosis: An Overview and Therapeutic Options

Dermatol Res Pract. 2014; 2014: 272376.

_http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295339/

5.1. Saturated Solution of Potassium Iodide

Saturated solution of potassium iodide (SSKI) administered orally remains the low cost, first choice of the treatment for uncomplicated cutaneous sporotrichosis especially when high cost of itraconazole is precluding. However, it is not effective in extracutaneous form of sporotrichosis. The exact mechanism of its action against S. Schenckii remains poorly elucidated. Possibly, it inhibits granuloma formation through some immunologic and nonimmunologic mechanisms thereby exposing the fungus to the host defenses or other antifungal agents used concurrently [67]. However, it does not appear to increase monocyte or neutrophil killing of S. Schenckii. Interestingly, S. Schenckii can grow when plated with 10% SSKI suggesting that it has no fungistatic or fungicidal activity. It has been suggested that it gets converted to iodine in-vivo by myeloperoxidase, a hydrogen peroxide system of polymorphonuclear cells, and exerts its cidal effect as has been demonstrated from its inhibitory effect on germination of cells and their direct destruction on ultrastructure examination of S. Schenckii exposed to iodine-potassium-iodine solution [68].

SSKI is the most extensively used mode of treatment in both fixed cutaneous and lymphocutaneous sporotrichosis across countries especially from developing world where most cases occur and that too is without specific treatment trials. Failure of therapy unrelated to compliance is reported exceptionally [69, 70] and most reports delineate its efficacy to an extent that a favorable therapeutic response is considered nearly diagnostic in the absence of mycologic support [1, 13, 14, 17, 18, 39, 58, 71, 72]. It has been found effective even in cases not responding to itraconazole [73, 74]. However, no specific recommendations/guidelines or treatment schedules are available. SSKI, containing 1 g/mL of potassium iodide, is usually prescribed in a starting dose of 5 drops (using a standard eye dropper) three times a day (t.i.d.), taken orally mixed with fruit juice or milk to mask its unpalatable taste. The dose is increased daily by 5 drops t.i.d. up to a maximum dose of 30 to 40 drops t.i.d. until complete healing. The response becomes evident within 2 weeks and healing occurs in 4–32 weeks [14, 72]. However, this schedule remains incomprehensive particularly for patients working outdoors for long hours resulting in poor compliance. Cabezas et al. [75] compared the safety and efficacy of once-daily versus 3-times daily dosing in a randomized nonblinded clinical trial on 57 pediatric patients with culture confirmed fixed cutaneous or lymphocutaneous sporotrichosis. The starting dose of SSKI 150 mg/day was increased to maximum of 160 mg/day in both groups. Although, adverse events were higher (61% versus 42%) with once-daily dose, the cure rates were comparable in both groups.

Adverse effects such as metallic taste, flu-like syndrome, excessive lacrimation, gastrointestinal upsets, parotid swelling, acneiform or papulopustular eruptions, exacerbation of dermatitis herpetiformis, and lesional pain and inflammation in rare instances may lead to noncompliance in as high as 60% cases but rarely need discontinuation of treatment [13, 15, 17, 39]. Metallic taste signifies threshold of maximum tolerable dose and the dosage is adjusted at a lower level. Hypothyroidism or hyperthyroidism, iododerma, cardiac irritability, vasculitis, pustular psoriasis, pulmonary edema, urticaria and angioedema, myalgia, lymphadenopathy, and eosinophilia are some potential adverse reactions [14, 76]. Hypothyroidism associated with SSKI therapy is usually precipitated in patients already having defective (partial) autoregulation mechanism (as from Hashimoto's thyroiditis, surgery, or radioactive iodide therapy for Graves' disease) that maintains thyroid hormone synthesis. Thyroid gland stops producing thyroid hormone by negative feedback mechanism when excess quantities of iodine exist (Wolff-Chaikoff effect). Inbuilt autoregulation mechanism maintains a storage pool of organic iodine in the thyroid gland and ensures that it produces enough thyroid hormone for the patient to remain euthyroid (escape phenomenon) [76]. In the complete absence of autoregulation mechanism (as in patients from areas of iodine deficiency having long-standing goiter) due to presence of autonomous thyroid foci the thyroid synthesizes excess thyroid hormone leading to thyrotoxicosis (Jod-Basedow disease). However, unless preexisting thyroid disease is suspected baseline thyroid function studies are not required as the therapeutic effect usually occurs in few weeks and within the period of “escape phenomenon.” Discontinuation of SSKI will usually restore normal thyroid functioning within a month in case of iatrogenic hypothyroidism. Patients taking angiotensin-converting enzyme inhibitors, potassium-sparing diuretics, or with renal impairment may develop potassium toxicity and need careful monitoring during SSKI therapy. SSKI is currently pregnancy category D drug. Therapy with SSKI should not be reinstituted in patients developing “flu-like syndrome”/hypersensitivity to SSKI as they will suffer adverse reactions even at low doses.