Herxing......interesting

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http://www.arthritistrust.org/topics/herxheim.htm

The Herxheimer Effect

Medical data is for informational purposes only. You should

always

consult your family physician, or one of our referral physicians

prior to

treatment

.

Sources are given in references.

Authors of contributions\quotations are alphabetically

arranged; major

author, if any, is underlined: Henry W. , W. Bradford,

D.Sc., Dr.

A.H. Davies, K. Fleishman, Haraldur Gudjonsson, Adolf Herxheimer, Dr.

Karl

Herxheimer, Dr. A. Heyman, J. Jadassohn, Dr. Jarisch, Kwang Jeon,

Ph.D., P.

Joulia, J.F. Mahoney, Russ McMillan, D.D.S., M.P.H., Dr. P.H., G.

Milian, J.E.

, Gus J. Prosch, Jr., M.D., Dr. K. Pybus, Vice Admiral

Stamm,

Wyburn-Mason, M.D., Ph.D./Responsible editor/writer di Fabio.

Copyright 1991

All rights reserved byThe Wyburn-Mason and Jack M. Blount

Foundation for the Eradication of Rheumatoid Disease; AKA The

Arthritis Society

of America, 5106 Old Harding Road, lin, TN 37064

Permission to publish granted to Townsend Letter for Doctors,

911 Tyler

St., Port Townsend, WA 98368-6541, May 1991, p. 370.

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 desireable

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 pehnomenon 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

administraiton of antiobiotics 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

whatosever.

" The Jarisch Herxheimer reaction occurs in other diseases

treated with

anitbiotics. It has been noted in:

a.. Yaws treated with penicillin.

b.. s Angina treated with metronidazole.

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

tetracycline.

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

penicillin or

tetracycline.

e.. Leprosy where it is known as the Lucia phenomenon treated

with

Dapsone.

f.. Brucellosis treated with chloramphenicol.

g.. Glanders treated with erythromycin.

h.. Anthrax treated with aureomycin.

i.. Rheumatoid Disease treated with metronidazole [and other

drugs:

Ed.]

j.. Psoriasis treated with metronidazole [and other drugs:

Ed.]

k.. [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 analysed 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 contaiminating amterial 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 Rheumatoid

Disease

Foundation, 5106 Old Harding Road, lin, TN 37064.

14.. Prosch, Gus J., Jr.: Personal communcation: 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 Rheumatoid Disease Foundation/The Arthritis Fund, June 13, 1994.

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

Test as an

Indicator of Oxidative Injry & 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).]