Herxheim

Medical data is for informational purposes only. You should always consult your family physician, or one of our referral physicians prior to treatment.
It is a phenomena that results when there is an intensification of the disease symptoms and often an expansionof similar symptoms to other places all of a temporary nature,after which the patient is improved or well. Often it appears to someas if they have the flu, and so is described as "the patient having flu-like symptoms." "Flu-like symptoms" is an over-simplification ofwhat happens in varying cases and with varying patients.
When treating Leishmaniasis, Syphilis or Tuberculosis, the phenomena is called Herxheimer, when treating Leprosy it's called The Art of Getting Well
Lucio's Phenomena. Other rare tropical diseases also call it theHerxheimer. When treating Candidiasis, patient's and doctors call The Herxheimer Effect
it the "die-off effect." Sources are given in references.
In all cases of the Herxheimer, there is the appearance of a war or tussle going on inside the body akin to the antigen/antibody Authors of contributions quotations are alphabetically arranged; warfare, where the body produces fever, sweat, aching and major author, if any, is underlined.
swollen joints, diarrhea, nausea, and so on, in varying proportions Henry W. Allen, Robert W. Bradford, D.Sc., Dr. A.H. Davies, with varying degrees depending upon state of metabolism, genet- K. Fleishman, Haraldur Gudjonsson, Adolf Herxheimer, Dr. Karl ics, source of disturbance and so on.
Herxheimer, Dr. A. Heyman, J. Jadassohn, Dr. Jarisch, Kwang It is my belief that some prescription drugs wrongly are Jeon, Ph.D., P. Joulia, J.F. Mahoney, Russ McMillan, D.D.S., described to be toxic in a certain way because, on observing an M.P.H., Dr. P.H., G. Milian, J.E. Moore, Gus J. Prosch, Jr., M.D., Herxheimer reaction in the patient trying the new drug, the drug Dr. Paul K. Pybus, Vice Admiral Stamm, Roger Wyburn-Mason, researchers (and others' observations during subsequent follow- M.D., Ph.D./Responsible editor/writer Anthony di Fabio. on research and use of the drug) do not fully understand the Herxheimer and believe the cause is the drug's "toxicity." Even All rights reserved byThe Roger Wyburn-Mason and Jack M. Blount with a full understanding of the Herxheimer effect, a pharmaceu- the Eradication of Rheumatoid Disease tical company must follow the "rule of over-caution," to satisfy AKA The Arthritis Trust of America®, FDA requirements for the "health and safety" of us more ignorant 7376 Walker Road, Fairview, Tn 37062 citizens. Thus, even with knowledge of the Herxheimer effect, Permission to publish granted to Townsend Letter for Doctors, 911 Tyler St., Port a physician researcher is not necessarily in a position whereby hecan, or wants to, discriminate between drug toxicity and the Townsend, WA 98368-6541, May 1991, p. 370.
Herxheimer effect.
It is necessary for the successful treatment of Rheumatoid Diseases, therefore, that a physician attend the patient who usesour treatment protocol, and that the physician fully comprehendthe distinctions between specific drug toxicities and the Herxheimereffect. This distinction probably can come only through theexperiences of applied clinical practices.
Drugs do have toxicities of their own, but the essential importance for Rheumatoid Arthritics is to be able todiscriminate between the two: Herxheimer effect and toxicity.
This is unfortunate, as it clouds otherwise desireable Dr. Paul K. Pybus treatment modes, not just those recommended in our treatmentprotocols for arthritics. From another viewpoint, those who fully Dr. Paul Pybus, a surgeon and Englishman who resided in understand the distinction between the Herxheimer effect and South Africa, was my friend and former Chief Medical Advisor for drug toxicities find themselves with a guiding clinical tool that The Rheumatoid Disease Foundation.
permits the physician early in the treatment regime to determine In the 1960s he worked with Roger Wyburn-Mason, M.D. the the probability of success for a given patient.
man who brought us our first consistently successful treatment for Through our Physicians, we have learned that, generally otherwise crippling arthritis.
speaking, the more severe the induced Herxheimer, the more From early teachings by his mentor, Wyburn-Mason, Paul probability of wellness — which is not to say that one who has a Pybus developed our technique of intraneural injections that is so very light Herxheimer may not also get well.
successful for the pain of both Osteoarthritis and Rheumatoid Prior to Dr. Paul Pybus' work developing intraneural Arthritis, and which may be the foundation for explaining one of injections, it was felt that Osteoarthritis and Rheumatoid Arthritis the causative factors of Osteoarthritis. That story is elsewhere13.
had little in common, except that here and there folks with An article prepared by Dr. Paul Pybus at the same time as the Rheumatoid Arthritis might also have some Osteoarthritis.
above mentioned Intraneural Injections. . booklet was titled "The Perhaps it is still true, that the causes are indeed distinguish- Herxheimer Reaction History." Paul prepared this material because of the extreme importance of noting and accounting for the But one very interesting set of experiences has come forth Herxheimer effect when treating arthritics. It is a pity that many from the application of the Wyburn-Mason/Pybus/Prosch modern-day physicians have not been taught the Herxheimer, or, Intraneural Treatment on both Rheumatoid and Osteo victims: joint if they have, do not understand its importance when treating a pain and joint damage in both diseases seem to stem from the same number of diseases. [Also see http://www.arthritistrust.org.] source, namely a disturbance in certain key trigger points alongthe peripheral nervous system. The peripheral nerves are usually Medical data is for informational purposes only. You should always consult your family physician, or one of our referral physicians prior to treatment.
those nerves close to the surface of the body, and have no insulative
for what has become known as the Herxheimer reaction in which a layers — similar to an electric wire passing current without patient becomes worse following the administraiton of anti-biotics insulation — called the C fibers, or "unmyelinated" fibers.
or other form of treatment that kills the causative organism20.] It might very well be that Osteoarthritis can be halted with 3. Jadassohn.9 Suggested that the direct effect of the anti- Pybus' intraneurals, along with good diet, including proper syphilitic drug on the tissue was an entirely toxic reaction.
supplements, hormones and changes in life style.
4. Fleishman.4 Suggested this reaction was of a vascular reflex Those possibilities, along with Pybus' Intraneural injections mediated by the autonomic nervous system.
are told elsewhere in our literature. [Also see http:// "In 1943 Mahoney et al5 first described Jarisch Herxheimer Reaction in syphilitic patients treated with penicillin and since The Herxheimer Reaction History
then it has been observed that other chemotherapeutic agents that by Dr. Paul K. Pybus, are effective with syphilis also produce a Herxheimer reaction.
M.A., M.B., B. Chir (Cambridge), M.R.C.S., "Moore et al6 regard the reaction as all or none phenomenon M.R.C.P. (London), D.R.C.G. (London) but it was found that if the dose was less than 10 international units F.R.C.S. (England) per kilogram bodyweight the reaction did not occur. The increase "This reaction was first described by an Austrian of the dose, however, did not increase the degree of the reaction.
dermatologist Jarisch Adolf Herxheimer10 working in Vienna and It also occurred equally in the seropositive and seronegative patient.
Innsbruck in 1895 and shortly after this, confirmed by his brother "Joulia et al7 reported that during the Jarisch Herxheimer Karl Herxheimer1,2 also a dermatologist working in Frankfort.
reaction the eosinophils decreased showing it to be an antigen "They were both mainly called upon to treat syphilitic lesions antibody reaction. However, Heyman found that using antihista- of skin by means of mercury and later arsenical and bismuth mines had no effect on the reaction whatosever.
preparations. They both noticed that when treating these patients "The Jarisch Herxheimer reaction occurs in other diseases many of them developed signs of high fever, profuse perspiration, treated with anitbiotics. It has been noted in: night sweats, nausea and vomiting. What was more they also 1. Yaws treated with penicillin.
observed that the skin lesions became larger and inflamed before 2. Vincents Angina treated with metronidazole.
settling down and healing. In addition they found that those cases 3. Relapsing fever (also a spirochaetal disease) treated with that responded in this most violent manner healed the best and fastest. The patient was quite ill for 2-3 days after which the 4. Rat bite fever (also due to a spirillum) treated with penicillin syphilitic lesions resolved.
or tetracycline.
"Jarisch Herxheimer accounted for this reaction as a toxic 5. Leprosy where it is known as the Lucia phenomenon manifestation caused by the foreign proteins released from the treated with Dapsone.
dying spirocheates. Meanwhile his brother Karl1,2 described in 6. Brucellosis treated with chloramphenicol.
detail the Herxheimer fever. There is first a febrile phase with 7. Glanders treated with erythromycin.
pyrexia, malaise and often a sore throat. The lesions are then 8. Anthrax treated with aureomycin.
aggravated and the ash if present becomes more marked with 9. Rheumatoid Disease treated with metronidazole [and other tension in the regional lymph nodes being more pronounced. In addition the primary ulcer would become oedematous and painful 10. Psoriasis treated with metronidazole [and other drugs: (the primary chancre is characterized by its painlessness). [In a letter to The Lancet, p. 340, Feb. 12, 1977, it is suggested that two 11. [Systemic Lupus Erythematosus and Scleroderma treated of the three identifying features of a Herxheimer were known since with metronidazole and other drugs: Ed.] the end of the 15th century when arsenical ointment was first used "In 1972 Gudjonsson11 investigated the Herxheimer to treat the great pox which had just arrived in Europe from the New reaction in adult seropositive and negative syphilitics and found a febrile reaction in 60%. It could be produced with doses above 10 "During this reaction many other signs appeared such as International units per kilogram. However, in 30% of cases no histologic changes such as transient acute inflammation in the reaction occurred until as much as 600,000 I.U. per kg, were given lesion, a leucocytosis and lymphopaenia which was greatest as and so it would appear that the higher doses produced a stronger the pyrexia was at its zenith.
reaction than the lower ones and this was at variance with the "It was suggested by another surgeon Heyman8 that these observations of Moore.
histologic changes indicate that the reaction was "He also noted an increase in the neutrophils and a decrease hypersensitivity pehnomenon of the delayed type similar to the in the lymphocyte count which occurs when the temperature is tuberculin hypersensitivity type of reaction.
greatest. The Eosinophil decreased and may be due to the de- "Theories as to Cause
granulation of their cells as they phagacytose the breakdown 1. Herxheimer et al.1,2,10 The phenomenon is caused by the products of the treponemes. This is also an observation in my own release of endotoxin of spirochaetal breakdown products following series of treated rheumatoid arthritic cases with metronidazole as treatment. These products are reacting with sensitized syphilitic the eosinophils are completely removed from the blood in most tissue to produce exacerbation of the lesion.
cases with a positive Herxheimer reaction.
2. Milian.3 Suggested it was due to stimulation of the "Effect of Prednisone on Herxheimer reaction. Here the spirochaetes and inadequate medication. [Bradford and Allen state Prednisone clearly influences the febrile response at a daily dose of that "The purpose of endotoxin to the bacterium that produces it is 40 mg. The leucocyte changes are not effected and so the Pred- to act as a semipermeable membrane, limiting and regulating the nisone influences only the febrile component and not the other nature of substances that may enter and provide nutrient for that manifestations of the reaction. Gudjonsson concludes that the organism. for this reason endotoxins reside solely on or near the reaction is not of an allergic nature, but is caused by some leucocyte surface (cell wall) and are shed into the surrounding medium only pyrogen released by phagocytosis of the treponemes.
upon the death of the organism. This fact may well be an explanation Medical data is for informational purposes only. You should always consult your family physician, or one of our referral physicians prior to treatment.
"If we say that Gudjonsson is correct and that the reaction is due to the release by the leucocytes of a pyrogen when something is phagocytosed, then this further suggests that the Herxheimer reaction seen when treating rheumatoid arthritis with certain drugs, is due to the phagocytosis of an infective agent. Thus, although no Pain in other joints one apart from Stamm and Wyburn-Mason12 have found amoebae previously unaffected . 79 for certain, this is strong evidence for an infective cause of the Burning micturition . 21 disease. [See "Free Living Amoeba & The Effects of Anti-amoebic Drugs on Rheumatoid Disease," "The Free-living Amoebic Causa- tion and Cure of Activity in Rheumatoid and Auto-Immune Dis- Flushing of skin and red patches . 39 eases," http://www.arthritistrust.org.] An Herxheimer reac- "These figures are all the more remarkable when one tion is the one constant finding in all our search and the considers that in the normal person without rheumatoid disease, strength of the reaction correlates very closely to clinical this dose of metronidazole produces no symptoms whatsoever.
improvement as shown separately by Prosch, Bingham and "Thus, in our campaign in the treatment of rheumatoid disease, two points stand out markedly: 13 [and now others: Ed.].
1. Metronidazole and our other recommended medicines "Furthermore in my own recent series the correlation is shown to be 100% correct.
2. That a Herxheimer reaction occurs in at least 83% of "I have also shown what would occur should these cases that I have done be analysed on a double-blind study by someone who "These two points seem to prove that an infection must be at was not acquainted with the Herxheimer reaction.
least at the root of the rheumatoid disease problem." "Herxheimer reaction is becoming the cornerstone of our [I find it most interesting — and consistent — that Dr. Pybus present research and unless full account is taken of its occurrence found 83% suffer a Herxheimer reaction, and subsequently show any double-blind trial performed will tend to be misleading. The improvement or alleviation of this disease, and that Gus Prosch, mere fact that it occurs will influence any such trial and would Jr.14, M.D. has shown a cure/remission rate of about 80% since probably be more advantageous if the final assessor could be 1982, using these oral medications combined with intraneurals and suitably blinded as to the previous occurrences of the Herxheimer proper diet: Ed.] [It is stated and referenced in Roger Wyburn-Mason's12 "I had sincerely hoped that this was being done at our double- various works that The Herxheimer response only occurs when an blind studies. I have strongly advocated that it be done." [The organism more complex than a bacillus is being killed by an Herxheimer reaction was not taken into account at our double-blind antibiotic and due to the Herxheimer, this fact "proves" that the studies at Bowman Gray School of Medicine. This study was infective agent must be of a complicated structure. Ed.] reported separately: Ed.] "In South Africa, our research has been based on the effect "The symptoms of the Herxheimer can be most severe. They of metronidazole on moving cells found in joint fluid. It has been can discourage not only the patient, but also the doctor and anyone shown that the macrophage-like cells found in the rheumatoid fluid, running a trial not knowing of these, will assume they are toxic when challenged with metronidazole, first respond with an symptoms and remove the patient from the trial [as occurred at our increased movement of a writhing character. These movements Bowman Gray School of Medicine study on use of Clotrimazole: after 15 minutes largely subside to be replaced by the slower movement and eventually after 309 minutes they are mostly "This also occurred in the original Guy's18 trial when they crenated and absorbed. Thus, the metronidazole would appear to came to the conclusion that metronidazole had no effect on kill the macrophage [in vitro: Ed.].
rheumatoid arthritis and this lack of recognition of the Herxheimer "Wyburn-Mason stressed that the Amoeba chromatosa was reaction did untold damage to our cause. Not only were the often confused with macrophages, and that they had the power of numbers in the trial inadequate, only 20, but other medications independent existence for a long time, which fact some of us have were not stopped [Nonsteroidal anti-inflammatories: Ed.] Follow corroborated." [He may have viewed clusters of cell-wall deficient up was only for 6 weeks (they should have waited at least two months), strike dosage was usually inadequate either to produce "Kwang Jeon15 [University of Tennessee, U.S.A.] cultured an Herxheimer or clinical improvement (400 mg b.d.) and the one these cells in joint fluid that were up to one week old and showed case that did produce a reaction was withdrawn because of these that they would develop into fibroblasts. However, the fluid that had ‘side effects.'" [The Herxheimer effect: Ed.] been treated with metronidazole grew nothing.
"Davies16 has noted these macrophages in penassy fluid left "This year I have made an analysis of 24 cases of at room temperature were still fresh (active) for as long as 24 days.
Rheumatoid Arthritis (RA) and this revealed many interesting [See last page of this article for photos of Pybus/Davies observa- "In a total of 288 metronidazole nights there were only 47 "Wyburn-Mason17 described the macrophage in great detail nights or 16.32% when nothing happened at all. All the rest (241 and gave it great prominence in his book on the reticulo- or 83.68%) showed some reaction and were divided up according to endothelial system. He concluded it was not mesodermal in origin as is so often claimed and said, but not proved, to develop from the Heavy perspiration and night sweats . 54 monocyte, but rather was it neuroectodermal in origin and was Flu-like symptoms . 47 developed from the trophic nerve ending.
"Later, when working with Stamm12, he was convinced that these were in all probability amoebae. Furthermore, they both claimed that they had cultured them, but attempts by all of us have Medical data is for informational purposes only. You should always consult your family physician, or one of our referral physicians prior to treatment.
failed to repeat this.
inoculation of rabbits with Treponema pallidum. Jarisch- "However, these macrophages have been grown at the Herxheimer reaction? Proc. 18. Meeting Scand. Dermatol. University of Tennessee by Kwang Jeon and this, I feel, is a great Ass., Turku 1968.
d. Gudjonsson, H. and Skog, E.: Fever after For those who are interested in pursing the easing of the inoculation of rabbits with Treponema pallidum. Brit. J. Herxheimer, the following suggestions have made made, in addi- vener. Dis. 46:318, 1970.
tion to various traditional allopathic remedies. e. Gudjonsson, H., Newman, B. and Turner, T.B.: As the "die-off effect" is the same as the well-known Herxheimer Demonstration of a virus-like agent contaiminating amterial effect, one might also ease the pain of temporarily increasing toxins containing the Stockholm substrain of the Nichols pathogenic by use of a steam (dry or hot) sauna or sign-up for a complete Treponema pallidum. Brit. J. vener. Dis. 46:435, 1970.
detoxification as practiced by members of the Church of Scientology.
f. Gudjonsson, H. Newman, B. and Turner, T.B.: Any Church outlet can steer you to the closest detox center. This Screening out a virus-like agent from the testicular detoxification is rather severe, requiring a physician's approval, and suspension of the Nichols pathogenic Treponema pallidum.
also the daily replacement of specific vitamins, minerals and fatty Brit. J. vener. Dis. In press at time summary was written.
acids, as it is the lipids (fats) in the cells that hold toxins and g. Gudjonsson, H.: Experiments to induce febrile therefore must release them. [See "Allergies and Biodetoxification Jarisch-Herxheimer reaction on syphilitic rabbits with for the Arthritic," http://www.arthritistrust.org.] penicillin and erythromycin. Acta Dermatovener. (Stock- Russ McMillan, D.D.S., D.P.H., Dr. P.H. suggests "something holm). In press at time summary was written.
that helps with the rather debilitating symptoms that accompany the 12. Wyburn-Mason, Roger: The Causation of Rheumatoid Herxheimer effect after medication. I take a saltz bath which consists Disease and Many Human Cancers, IJI Publishing Co., Ltd., of adding 1 cup salt, 1 cup soda, 1 cup epsom salts, 1 cup aloe vera, Tokyo, Japan, 1978. [Summary available through The Rheumatoid to a hot bath which I remain in and keep hot for about 1-1/2 hours Disease Foundation, Rt. 4, Box 137, Franklin, TN 37064, same all the while consuming about 2 quarts of warm water. Evidently the perspiration and osmotic pressure removes the causative toxins. I 13. Arthritis: Osteoarthritis and Rheumatoid Disease Includ- find it quite helpful19." ing Rheumatoid Arthritis, Anthony di Fabio, & Gus J. Prosch, Jr., Also see "Universal Oral Vaccine -- With Patents," http:// M.D., Rheumatoid Diseases Cured at Last (1985); Anthony di Fabio, The Art of Getting Well, Anthony di Fabio (1988); Intraneural Injections for Rheumatoid Arthritis and Osteoarthritis 1. Herxheimer, K. Krause: "Uber eine bei Syphilitische & The Control of Pain in Arthritis of the Knee, Dr. Paul K. Pybus, vorkommende Quecksilerberreaktion. Deutsch. Med. Wschr. (1989), The Arthritis Trust of America/The Rheumatoid Disease 28:50, 1902.
Foundation, 7376 Walker Road, Fairview, TN 37062-8141 2. Herxheimer, K. and Martin, H.: So-called Herxheimer 14. Prosch, Gus J., Jr.: Personal communcation: Ed.
reactions. Arch. Derm. Syph. 13:115, 1926.
15. Jeon, Kwang: Research proposal and paper (based on 3. Millian, G.: Syphilis: Reaction d' Herxheimer.
arthritic knee effusion samples submitted by our referral Biotropisme. Paris nd.: 37:91, 1920.
physicians from their patients) submitted to The Rheumatoid 4. Fleishman, K. and Kreibich, C.: Zum Wesen der Reaktion Disease Foundation.
nach Jarish-Herxheimer. Me. Klin. 21:1157, 1925.
16. Pybus, Paul K. P, Davies, A.H.: Paper submitted to The 5. Mahoney, J.F., Arnold, R.C., and Harris, A.: Penicillin Rheumatoid Disease Foundation (based on knee effusions treatment of early syphilis. Amer. J. Public Health 33:1387, 1943.
submitted by our referral physicians.) 6. Moore, J.E., Farmer, T.W. and Hoekenga, M.T.: 17. Wyburn-Mason, Roger: The Reticulo-Endothellial System Penicillin and the Jarisch-Herxheimer reaction in early, in Growth and Tumour Formation, Henry Kimpton, London, cardiovasculaar and nuerosyphilis. rans. Ass. Amer. Phycns. England, 1958.
61:176, 1948.
18. Guy [study performed in South Africa by a Rheumatolo- 7. Joulia, P., Pautrizell, R., Texier, L. and Sebra, De.: La chute gist], reference source lost.
des eosinophiles sanguines apre une premiere injeciton de 19. Personal letter from Russ McMillan, D.D.S., M.P.H., Dr.
penicilline au cours de la syphilis primo-secondaire: temoin du P.H. to The Arthritis Trust of America/The Rheumatoid Disease conflit antigene-anticorps. ull. Soc. Franc. Derm. Syph. 58:399, Foundation, June 13, 1994.
20. Robert W. Bradford, D.Sc., Henry Allen, "The HLB Blood 8. Heyman, A., Sheldon, W.H. and Evans, L.D.: Pathogenesis Test as an Indicator of Oxidative Injry & Disseminated Intravascu- of the Jarisch-Herxheimer reaction. rit. J. vener. Dis. 28:50, 1952.
lar Coagulation," Townsend Letter for Doctors, 911 Tyler Street, 9. Jadassohn, J.: Beitrag zur Jarisch-Herxheimer Reaktion. Z. Port Townsend, WA 98368-6541, April 1995, p. 30. [From Morrison, Haut Geschlechtskr 19:158, 1965.
D.C., et. al., The effects of bacterial endotoxins on host mediation 10. Jarisch, A. Wien. med Wschr. 45:721, 1895.
systems, American Journal of Pathology 93 526 (1978).] 11. Gudjonsson, Haraldur: The Jarisch-Herxheimer Reaction, Stockholm 1972 (A summary based on the following sevenpublications: a. Skok, E. and Gudjonsson, H.: On the allergic origin of the jarisch-Herxheimer reaction. Acta Dermatovfener(Stockholm) 46:136, 1966.
b. Gudjonsson, H. and Skog, E.: The effect of prednisolone on the Jarisch-Herxheimer reaction. ActaDermatovener (Stockholm) 48:15, 1968.
c. Gudjonsson, H. and Skog, E.: Fever after

Medical data is for informational purposes only. You should always consult your family physician, or one of our referral physicians prior to treatment.

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