The Herxheimer Effect

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The Herxheimer Effect

Supplement to The Art of Getting Well

Dr. Pybus, a surgeon and Englishman who resided in South Africa,

was my friend and former Chief Medical Advisor for The Rheumatoid

Disease Foundation. Over thirty years ago he worked with

Wyburn-Mason, M.D. the man who brought us our first consistently

successful treatment for otherwise crippling arthritis.

From early teachings by his mentor, Wyburn-Mason, Pybus

developed our technique of intraneural injections that is so

successful for the pain of both Osteoarthritis and Rheumatoid

Arthritis, and which may be the foundation for explaining one of the

causative factors of Osteoarthritis. That story is elsewhere13.

An article prepared by Dr. Pybus at the same time as the above

mentioned Intraneural Injections. . . booklet was titled " The

Herxheimer Reaction History. " prepared this material because of

the extreme importance of noting and accounting for the Herxheimer

effect when treating arthritics. It is a pity that many modern-day

physicians have not been taught the Herxheimer, or, if they have, do

not understand its importance when treating a number of diseases.

It is a phenomena that results when there is an intensification of

the disease symptoms and often an expansion of similar symptoms to

other places all of a temporary nature, after which the patient is

improved or well. Often it appears to some as if they have the flu,

and so is described as " the patient having flu-like symptoms. " " Flu-

like symptoms " is an over-simplification of what 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 Lucio's

Phenomena. Other rare tropical diseases also call it the Herxheimer.

When treating Candidiasis, patient's and doctors call it the " die-off

effect. "

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 warfare,

where the body produces fever, sweat, aching and swollen joints,

diarrhea, nausea, and so on, in varying proportions with varying

degrees depending upon state of metabolism, genetics, source of

disturbance and so on.

It is my belief that some prescription drugs wrongly are described to

be toxic in a certain way because, on observing an Herxheimer

reaction in the patient trying the new drug, the drug researchers

(and others' observations during subsequent follow-on research and

use of the drug) do not fully understand the Herxheimer and believe

the cause is the drug's " toxicity. " Even with a full understanding of

the Herxheimer effect, a pharmaceutical company must follow the " rule

of over-caution, " to satisfy FDA requirements for the " health and

safety " of us more ignorant citizens. Thus, even with knowledge of

the Herxheimer effect, a physician researcher is not necessarily in a

position whereby he can, or wants to, discriminate between drug

toxicity and the Herxheimer effect.

It is necessary for the successful treatment of Rheumatoid Diseases,

therefore, that a physician attend the patient who uses our treatment

protocol, and that the physician fully comprehend the distinctions

between specific drug toxicities and the Herxheimer effect. This

distinction probably can come only through the experiences of applied

clinical practices.

Drugs do have toxicities of their own, but the essential importance

for Rheumatoid Arthritics is to be able to discriminate between the

two: Herxheimer effect and toxicity.

This is unfortunate, as it clouds otherwise desirable treatment

modes, not just those recommended in our treatment protocols for

arthritics. From another viewpoint, those who fully understand the

distinction between the Herxheimer effect and drug toxicities find

themselves with a guiding clinical tool that permits the physician

early in the treatment regime to determine the probability of success

for a given patient.

Through our Physicians, we have learned that, generally speaking, the

more severe the induced Herxheimer, the more probability of wellness -

which is not to say that one who has a very light Herxheimer may not

also get well.

Prior to Dr. Pybus' work developing intraneural injections, it

was felt that Osteoarthritis and Rheumatoid Arthritis had little in

common, except that here and there folks with Rheumatoid Arthritis

might also have some Osteoarthritis.

Perhaps it is still true, that the causes are indeed distinguishable.

But one very interesting set of experiences has come forth from the

application of the Wyburn-Mason/Pybus Intraneural Treatment on both

Rheumatoid and Osteo victims: joint pain and joint damage in both

diseases seem to stem from the same source, namely a disturbance in

certain key trigger points along the peripheral nervous system. The

peripheral nerves are usually those nerves close to the surface of

the body, and have no insulative layers - similar to an electric wire

passing current without insulation - called the C fibers,

or " unmyelinated " fibers.

It might very well be that Osteoarthritis can be halted with Pybus'

intraneurals, along with good diet, including proper supplements,

hormones and changes in life style.

Those possibilities, along with Pybus' Intraneural injections are

told elsewhere in our literature.

The Herxheimer Reaction History

by Dr. K. Pybus,

M.A., M.B., B. Chir (Cambridge), M.R.C.S., M.R.C.P. (London),

D.R.C.G. (London) F.R.C.S. (England)

" This reaction was first described by an Austrian dermatologist

Jarisch Adolf Herxheimer10 working in Vienna and Innsbruck in 1895

and shortly after this, confirmed by his brother Karl Herxheimer1,2

also a dermatologist working in fort.

" They were both mainly called upon to treat syphilitic lesions of

skin by means of mercury and later arsenical and bismuth

preparations. They both noticed that when treating these patients

many of them developed signs of high fever, profuse perspiration,

night sweats, nausea and vomiting. What was more they also observed

that the skin lesions became larger and inflamed before settling down

and healing. In addition they found that those cases that responded

in this most violent manner healed the best and fastest. The patient

was quite ill for 2-3 days after which the syphilitic lesions

resolved.

Jarisch Herxheimer accounted for this reaction as a toxic

manifestation caused by the foreign proteins released from the dying

spirocheates. Meanwhile his brother Karl1,2 described in detail the

Herxheimer fever. There is first a febrile phase with pyrexia,

malaise and often a sore throat. The lesions are then aggravated and

the ash if present becomes more marked with tension in the regional

lymph nodes being more pronounced. In addition the primary ulcer

would become oedematous and painful (the primary chancre is

characterized by its painlessness). [in a letter to The Lancet, p.

340, Feb. 12, 1977, it is suggested that two of the three identifying

features of a Herxheimer were known since the end of the 15th century

when arsenical ointment was first used to treat the great pox which

had just arrived in Europe from the New World: Ed.]

During this reaction many other signs appeared such as histologic

changes such as transient acute inflammation in the lesion, a

leucocytosis and lymphopaenia which was greatest as the pyrexia was

at its zenith.

It was suggested by another surgeon Heyman8 that these histologic

changes indicate that the reaction was hypersensitivity phenomenon of

the delayed type similar to the tuberculin hypersensitivity type of

reaction.

Theories as to Cause

1. Herxheimer et al.1,2,10 The phenomenon is caused by the release of

endotoxin of spirochaetal breakdown products following treatment.

These products are reacting with sensitized syphilitic tissue to

produce exacerbation of the lesion.

2. Milian.3 Suggested it was due to stimulation of the spirochaetes

and inadequate medication. [bradford and state that " The

purpose of endotoxin to the bacterium that produces it is to act as a

semipermeable membrane, limiting and regulating the nature of

substances that may enter and provide nutrient for that organism. for

this reason endotxoins reside solely on or near the surface (cell

wall) and are shed into the surrounding medium only upon the death of

the organism. This fact may well be an explanation for what has

become known as the Herxheimer reaction in which a patient becomes

worse following the administration of antibiotics or other form of

treatment that kills the causative organism20.]

3. Jadassohn.9 Suggested that the direct effect of the anti-

syphilitic drug on the tissue was an entirely toxic reaction.

4. Fleishman.4 Suggested this reaction was of a vascular reflex

mediated by the autonomic nervous system.

In 1943 Mahoney et al5 first described Jarisch Herxheimer Reaction in

syphilitic patients treated with penicillin and since then it has

been observed that other chemotherapeutic agents that are effective

with syphilis also produce a Herxheimer reaction.

et al6 regard the reaction as all or none phenomenon but it was

found that if the dose was less than 10 international units per

kilogram bodyweight the reaction did not occur. The increase of the

dose, however, did not increase the degree of the reaction. It also

occurred equally in the seropositive and seronegative patient.

Joulia et al7 reported that during the Jarisch Herxheimer reaction

the eosinophils decreased showing it to be an antigen antibody

reaction. However, Heyman found that using antihistamines had no

effect on the reaction whatsoever.

The Jarisch Herxheimer reaction occurs in other diseases treated with

antibiotics. It has been noted in:

1. Yaws treated with penicillin.

2. s Angina treated with metronidazole.

3. Relapsing fever (also a spirochaetal disease) treated with

tetracycline.

4. Rat bite fever (also due to a spirillum) treated with penicillin

or tetracycline.

5. Leprosy where it is known as the Lucia phenomenon treated with

Dapsone.

6. Brucellosis treated with chloramphenicol.

7. Glanders treated with erythromycin.

8. Anthrax treated with aureomycin.

9. Rheumatoid Disease treated with metronidazole [and other drugs:

Ed.]

10. Psoriasis treated with metronidazole [and other drugs: Ed.]

11. [systemic Lupus Erythematosus and Scleroderma treated with

metronidazole and other drugs: Ed.]

In 1972 Gudjonsson11 investigated the Herxheimer reaction in adult

seropositive and negative syphilitics and found a febrile reaction in

60%. It could be produced with doses above 10 International units per

kilogram. However, in 30% of cases no reaction occurred until as much

as 600,000 I.U. per kg, were given and so it would appear that the

higher doses produced a stronger reaction than the lower ones and

this was at variance with the observations of .

He also noted an increase in the neutrophils and a decrease in the

lymphocyte count which occurs when the temperature is greatest. The

Eosinophil decreased and may be due to the de-granulation of their

cells as they phagacytose the breakdown products of the treponemes.

This is also an observation in my own series of treated rheumatoid

arthritic cases with metronidazole as the eosinophils are completely

removed from the blood in most cases with a positive Herxheimer

reaction.

Effect of Prednisone on Herxheimer reaction. Here the Prednisone

clearly influences the febrile response at a daily dose of 40 mg. The

leucocyte changes are not effected and so the Prednisone influences

only the febrile component and not the other manifestations of the

reaction. Gudjonsson concludes that the reaction is not of an

allergic nature, but is caused by some leucocyte pyrogen released by

phagocytosis of the treponemes.

Discussion

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 one apart

from Stamm and Wyburn-Mason12 have found amoebae for certain, this is

strong evidence for an infective cause of the disease. An Herxheimer

reaction is the one constant finding in all our search and the

strength of the reaction correlates very closely to clinical

improvement as shown separately by Prosch, Bingham and Pybus13 [and

now others: Ed.].

Furthermore in my own recent series the correlation is shown to be

100% correct.

I have also shown what would occur should these cases that I have

done be analyzed on a double-blind study by someone who was not

acquainted with the Herxheimer reaction.

Herxheimer reaction is becoming the cornerstone of our present

research and unless full account is taken of its occurrence any

double-blind trial performed will tend to be misleading. The mere

fact that it occurs will influence any such trial and would probably

be more advantageous if the final assessor could be suitably blinded

as to the previous occurrences of the Herxheimer reaction.

" I had sincerely hoped that this was being done at our double-blind

studies. I have strongly advocated that it be done. " [The Herxheimer

reaction was not taken into account at our double-blind studies at

Bowman Gray School of Medicine. This study will be reported

separately: Ed.]

The symptoms of the Herxheimer can be most severe. They can

discourage not only the patient, but also the doctor and anyone

running a trial not knowing of these, will assume they are toxic

symptoms and remove the patient from the trial [as occurred at our

Bowman Gray School of Medicine study on use of Clotrimazole: Ed.]

" This also occurred in the original Guy's18 trial when they came to

the conclusion that metronidazole had no effect on rheumatoid

arthritis and this lack of recognition of the Herxheimer reaction did

untold damage to our cause. Not only were the numbers in the trial

inadequate, only 20, but other medications were not stopped

[Nonsteroidal anti-inflammatories: Ed.] Follow up was only for 6

weeks (they should have waited at least two months), strike dosage

was usually inadequate either to produce an Herxheimer or clinical

improvement (400 mg b.d. and the one case that did produce a

reaction was withdrawn because of these 'side effects.' " [The

Herxheimer effect: Ed.]

Recent Progress

This year I have made an analysis of 24 cases of Rheumatoid Arthritis

(RA) and this revealed many interesting facts.

In a total of 288 metronidazole nights there were only 47 nights or

16.32% when nothing happened at all. All the rest (241 or 83.68%)

showed some reaction and were divided up according to the following:

Heavy perspiration and night sweats 54

Flu-like symptoms 47

Rigors 32

Fever 2

Headaches 85

Malaise 43

Diarrhea 19

Nausea 49

Vomiting 8

Pain in other joints previously unaffected 79

Burning micturition 21

Bone pain 39

Itching 33

Flushing of skin and red patches 39

These figures are all the more remarkable when one considers that in

the normal person without rheumatoid disease, this dose of

metronidazole produces no symptoms whatsoever.

Thus, in our campaign in the treatment of rheumatoid disease, two

points stand out markedly:

1. Metronidazole and our other recommended medicines work;

2. That a Herxheimer reaction occurs in at least 83% of metronidazole

nights.

" These two points seem to prove that an infection must be at least at

the root of the rheumatoid disease problem. "

[i find it most interesting - and consistent - that Dr. Pybus found

83% suffer a Herxheimer reaction, and subsequently show improvement

or alleviation of this disease, and that Gus Prosch, Jr.14, M.D. has

shown a cure/remission rate of about 80% since 1982, using these oral

medications combined with intraneurals and proper diet: Ed.]

[it is stated and referenced in Wyburn-Mason's12 various works

that The Herxheimer response only occurs when an organism more

complex than a bacillus is being killed by an antibiotic and due to

the Herxheimer, this fact " proves " that the infective agent must be

of a complicated structure. Ed.]

" In South Africa, our research has been based on the effect of

metronidazole on moving cells found in joint fluid. It has been shown

that the macrophage-like cells found in the rheumatoid fluid, when

challenged with metronidazole, first respond with an increased

movement of a writhing character. These movements after 15 minutes

largely subside to be replaced by the slower movement and eventually

after 309 minutes they are mostly crenated and absorbed. Thus, the

metronidazole would appear to kill the macrophage [in vitro: Ed.].

" Wyburn-Mason stressed that the Amoeba chromatosa was often confused

with macrophages, and that they had the power of independent

existence for a long time, which fact some of us have corroborated. "

[He probably viewed clusters of cell-wall deficient bacteria: Ed.]

Kwang Jeon15 [university of Tennessee, U.S.A.] cultured these cells

in joint fluid that were up to one week old and showed that they

would develop into fibroblasts. However, the fluid that had been

treated with metronidazole grew nothing.

Davies16 has noted these macrophages in penassy fluid left at room

temperature were still fresh (active) for as long as 24 days.

Wyburn-Mason17 described the macrophage in great detail and gave it

great prominence in his book on the reticulo-endothelial system. He

concluded it was not mesodermal in origin as is so often claimed and

said, but not proved, to develop from the monocyte, but rather was it

neuroectodermal in origin and was 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 failed to repeat this.

" However, these macrophages have been grown at the University of

Tennessee by Kwang Jeon and this, I feel, is a great step forward. "

For those who are interested in pursing the easing of the Herxheimer,

the following suggestions have made made, in addition to various

traditional allopathic remedies.

As the " die-off effect " is the same as the well-known Herxheimer

effect, one might also ease the pain of temporarily increasing toxins

by use of a steam (dry or hot) sauna or sign-up for a complete

detoxification as practiced by members of the Church of Scientology.

Any Church outlet can steer you to the closest detox center. This

detoxification is rather severe, requiring a physician's approval,

and also the daily replacement of specific vitamins, minerals and

fatty acids, as it is the lipids (fats) in the cells that hold toxins

and therefore must release them.

Russ McMillan, D.D.S., D.P.H., Dr. P.H. suggests " something that

helps with the rather debilitating symptoms that accompany the

Herxheimer effect after medication. I take a saltz bath which

consists of adding 1 cup salt, 1 cup soda, 1 cup epsom salts, 1 cup

aloe vera, to a hot bath which I remain in and keep hot for about 1-

1/2 hours all the while consuming about 2 quarts of warm water.

Evidently the perspiration and osmotic pressure removes the causative

toxins. I find it quite helpful19. "

" References

1. Herxheimer, K. Krause: " Uber eine bei Syphilitische vorkommende

Quecksilerberreaktion. Deutsch. Med. Wschr. 28:50, 1902.

2. Herxheimer, K. and , H.: So-called Herxheimer reactions.

Arch. Derm. Syph. 13:115, 1926.

3. Millian, G.: Syphilis: Reaction d' Herxheimer. Biotropisme. Paris

nd.: 37:91, 1920.

4. Fleishman, K. and Kreibich, C.: Zum Wesen der Reaktion nach Jarish-

Herxheimer. Me. Klin. 21:1157, 1925.

5. Mahoney, J.F., Arnold, R.C., and , A.: Penicillin treatment

of early syphilis. Amer. J. Public Health 33:1387, 1943.

6. , J.E., Farmer, T.W. and Hoekenga, M.T.: Penicillin and the

Jarisch-Herxheimer reaction in early, cardiovasculaar and

nuerosyphilis. rans. Ass. Amer. Phycns. 61:176, 1948.

7. Joulia, P., Pautrizell, R., Texier, L. and Sebra, De.: La chute

des eosinophiles sanguines apre une premiere injeciton de penicilline

au cours de la syphilis primo-secondaire: temoin du conflit antigene-

anticorps. ull. Soc. Franc. Derm. Syph. 58:399, 1951.

8. Heyman, A., Sheldon, W.H. and , L.D.: Pathogenesis of the

Jarisch-Herxheimer reaction. rit. J. vener. Dis. 28:50, 1952.

9. Jadassohn, J.: Beitrag zur Jarisch-Herxheimer Reaktion. Z. Haut

Geschlechtskr 19:158, 1965.

10. Jarisch, A. Wien. med Wschr. 45:721, 1895.

11. Gudjonsson, Haraldur: The Jarisch-Herxheimer Reaction, Stockholm

1972 (A summary based on the following seven publications:

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. Acta Dermatovener (Stockholm) 48:15,

1968.

c. Gudjonsson, H. and Skog, E.: Fever after inoculation of rabbits

with Treponema pallidum. Jarisch-Herxheimer reaction? Proc. 18.

Meeting Scand. Dermatol. Ass., Turku 1968.

d. Gudjonsson, H. and Skog, E.: Fever after inoculation of rabbits

with Treponema pallidum. Brit. J. vener. Dis. 46:318, 1970.

e. Gudjonsson, H., Newman, B. and , T.B.: Demonstration of a

virus-like agent contaminating material containing the Stockholm

substrain of the Nichols pathogenic Treponema pallidum. Brit. J.

vener. Dis. 46:435, 1970.

f. Gudjonsson, H. Newman, B. and , T.B.: Screening out a virus-

like agent from the testicular suspension of the Nichols pathogenic

Treponema pallidum. Brit. J. vener. Dis. In press at time summary was

written.

g. Gudjonsson, H.: Experiments to induce febrile Jarisch-Herxheimer

reaction on syphilitic rabbits with penicillin and erythromycin. Acta

Dermatovener. (Stockholm). In press at time summary was written.

12. Wyburn-Mason, : The Causation of Rheumatoid Disease and Many

Human Cancers, IJI Publishing Co., Ltd., Tokyo, Japan, 1978. [summary

available through The Rheumatoid Disease Foundation, Rt. 4, Box 137,

lin, TN 37064, same title.]

13. di Fabio, Rheumatoid Diseases Cured at Last (1985);

di Fabio, The Art of Getting Well or (1988); Dr. K.

Pybus, Intraneural Injections for Rheumatoid Arthritis and

Osteoarthritis & The Control of Pain in Arthritis of the Knee,

(1989), The Arthritis Trust of America/The Rheumatoid Disease

Foundation, 7111 Sweetgum Road, Suite A, Fairview, TN 37062-9384.

14. Prosch, Gus J., Jr.: Personal communication: Ed.

15. Jeon, Kwang: Research proposal and paper (based on arthritic knee

effusion samples submitted by our referral physicians from their

patients) submitted to The Rheumatoid Disease Foundation.

16. Pybus, K. P, Davies, A.H.: Paper submitted to The Rheumatoid

Disease Foundation (based on knee effusions submitted by our referral

physicians.)

17. Wyburn-Mason, : The Reticulo-Endothellial System in Growth

and Tumour Formation, Henry Kimpton, London, England, 1958.

18. Guy [study performed in South Africa by a Rheumatologist],

reference source lost.

19. Personal letter from Russ McMillan, D.D.S., M.P.H., Dr. P.H. to

The Arthritis Trust of America/The Rheumatoid Disease Foundation,

June 13, 1994.

20. W. Bradford, D.Sc., Henry , " The HLB Blood Test as an

Indicator of Oxidative Injury & Disseminated Intravascular

Coagulation, " Townsend Letter for Doctors, 911 Tyler Street, Port

Townsend, WA 98368-6541, April 1995, p. 30. [From on, D.C., et.

al., The effects of bacterial endotoxins on host mediation systems,

American Journal of Pathology 93 526 (1978).]

[Guest guest]

Thanks !

Appreciate all this info!

Ruth

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[Guest guest]

Thanks !

Appreciate all this info!

Ruth

________________________________________________________________

The best thing to hit the Internet in years - Juno SpeedBand!

Surf the Web up to FIVE TIMES FASTER!

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