Jarisch-Herxheimer reaction

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
Cobwebby
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Re: Jarisch-Herxheimer reaction

Post by Cobwebby » Wed 11 Aug 2010 18:27

Reading the roadback link led me to investigate the benefits of epsom salts.

So I posted a bunch of articles about those benefits. Makes me wonder why my Orthopedic Doc has not mentioned the epsom salt baths to me and my aching knee. :?:
The greater part of our happiness or misery
depends on our dispositions,
and not on our circumstances.
Martha Washington

RitaA
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Re: Jarisch-Herxheimer reaction

Post by RitaA » Fri 9 Jan 2015 8:10

The following description and explanation of Jarisch-Herxheimer Reaction (abbreviation JHR) is one that most mainstream medical professionals are probably somewhat familiar with:

http://www.patient.co.uk/doctor/jarisch ... r-reaction
Jarisch-Herxheimer Reaction

Description

This systemic reaction, also known as the Herxheimer's reaction, was classically described in the treatment of syphilis. It is believed to be caused by the release of endotoxin-like substances when large numbers of Treponema pallidum are killed by antibiotics. It has been documented in tick-borne diseases like Lyme disease and relapsing fever where the infecting organism is also a spirochete. One study suggested that it was more common in Lyme disease patients treated with cefuroxime.[1] The mechanism may not be straightforward as it is not a feature of neonatal syphilis or non-venereal syphilis in childhood. The reaction can be expected in 50% of primary syphilis, 90% of secondary syphilis, and in 25% of early latent infection, but is very rare in late syphilis. It has been suggested that it is more severe in patients with HIV.[2]

Presentation

The reaction starts between 1 and 12 hours after the first injection of antibiotics and lasts for a few hours or up to a day.

It is not seen with subsequent treatment
.


There is malaise, slight-to-moderate pyrexia, a flush due to vasodilation, tachycardia, and leukocytosis.
Any existing skin lesions become more prominent.
Hyperventilation and tachycardia are accompanied by hypertension, and then by a drop in blood pressure due to vasodilation and declining peripheral resistance.
In some patients with early syphilis, a secondary rash may become visible which was absent before treatment.
Usually, the reaction resolves over a period of 6 to 12 hours.

Differential diagnosis

It is important to recognise the reaction for what it is and not to ascribe it to a sensitivity to the antibiotic. Rarely, syphilis may be suspected by the appearance of the febrile reaction of the Jarisch-Herxheimer, perhaps with a fleeting rash, when treating another infection such as gonorrhoea. It is important to recognise this and to make the diagnosis and give an adequate course for syphilis.

Investigations

Usually no investigation is required but if an unexpected reaction to antibiotic treatment occurs, then serological tests for syphilis are required.

Associated diseases

Although traditionally associated with syphilis, the reaction is well documented with Lyme Disease and relapsing fever.

For many years there has been a suggestion that mycoplasma may be involved in the aetiology of rheumatoid arthritis and other autoimmune diseases including sarcoidosis. Hence, it may be possible to treat the infection to treat the disease. Minocycline would seem to be the drug of choice and there are reports of it producing improvement but only after a Jarisch-Herxheimer reaction.[3] If this is shown to be the case, it could have massive implications for the management of such diseases.[4]

Management

It is customary to give corticosteroids in late symptomatic syphilis, starting a day before the first penicillin injection and tailing it off the day after the first injection. A dose of around 30 mg prednisolone is typical. This does not prevent the Jarisch-Herxheimer reaction but is said to ameliorate it. The analogous reactions in relapsing fever have been modified by meptazinol or pretreatment with infusions of polyclonal anti-TNF alpha Fab with concomitant reduction in the plasma concentration of interleukin 6 and 8.[5]

In pregnancy, the incidence of the reaction when treating syphilis, is about 40%.[6] Fetal monitoring should be performed as similar proportions of patients develop regular uterine contractions and recurrent variable decelerations.

A review of the literature[7] found conflicting evidence that the reaction is caused by release of endotoxin-like material from the spirochete as well as cytokine elevation in the body. The type of drug and the rate of clearance of the spirochetes have little effect on the incidence of the reaction. Many pretreatment options have been explored with limited efficacy with the exception of anti-tumour necrosis factor antibodies.

Complications

In early syphilis the reaction is only a minor nuisance. In late syphilis it can on very rare occasions be more serious. Thus, in neurosyphilis it may lead to epilepsy or a rapid, irreversible progression, and in general paresis it can cause exacerbation amounting to temporary psychosis. Sudden death has been reported in cardiovascular syphilis. In laryngeal gumma, local oedema may necessitate tracheotomy. In the later stages of pregnancy fetal monitoring is advised.

Prognosis

Recovery is usually swift and the course of treatment is completed.

Historical aspects

Adolf Jarisch was an Austrian dermatologist who was born in 1850 and died in 1902. Jarisch published his description of the Jarisch-Herxheimer reaction in 1895, seven years before Herxheimer published his own description. As this was many years before the discovery of penicillin, the original description related to the treatment with mercury.

Karl Herxheimer was a German dermatologist who was born in 1861 and died in 1944. Herxheimer published his description of the Jarisch-Herxheimer reaction in 1902. He had already resigned his positions because of his age when the Nazis took power in 1933 but, despite being Jewish, he stubbornly refused to leave his native country. He was imprisoned in the autumn of 1941 and on August 27 1942, aged 81, he died in a concentration camp.

Further reading & references

Loewen PS, Marra CA, Marra F; Systematic review of the treatment of early Lyme disease.; Drugs. 1999 Feb;57(2):157-73.
van Voorst Vader PC; Syphilis management and treatment. Dermatol Clin. 1998 Oct;16(4):699-711, xi.
Marshall TG, Marshall FE; Sarcoidosis succumbs to antibiotics--implications for autoimmune disease.; Autoimmun Rev. 2004 Jun;3(4):295-300.
Marshall TG, Marshall FE; Antibiotics in Sarcoidosis - Reflections on the First Year; Journal of Independent Medical Research 2003;1(3):2
Fekade D, Knox K, Hussein K, et al; Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha.; N Engl J Med. 1996 Aug 1;335(5):311-5.
Myles TD, Elam G, Park-Hwang E, et al; The Jarisch-Herxheimer reaction and fetal monitoring changes in pregnant women treated for syphilis. Obstet Gynecol. 1998 Nov;92(5):859-64.
Pound MW, May DB; Proposed mechanisms and preventative options of Jarisch-Herxheimer reactions.; J Clin Pharm Ther. 2005 Jun;30(3):291-5.
Unfortunately, the following definition may actually do more harm than good by leaving out the fact that new or worsening symptoms may also be caused by an adverse reaction to one or more medications:

http://www.columbia-lyme.org/patients/key_terms.html
Herxheimer Reaction: This typically refers to an exacerbation of symptoms or new onset of symptoms shortly after starting antibiotic therapy. This is thought to be due to a flare of the immune system in response to the killing of the spirochetes. Because of this reaction, it is often the case that a physician will tell the patient: "You feel worse? Terrific! That's a sign you're getting better."

The onset and duration of JHR (or a similar process) seems to differ for Lyme disease patients -- at least according to this source:

http://www.jemsekspecialty.com/lyme_detail.php?sid=10
The Herxheimer response typically occurs within 3 to 5 days, but may take up to 2 weeks to appear. These symptoms may persist for days or weeks ...
I wonder if this phenomenon has been described in published case reports.

RitaA
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Re: Jarisch-Herxheimer reaction

Post by RitaA » Fri 9 Jan 2015 9:05

http://www.ncbi.nlm.nih.gov/pubmed/25033009
Am J Dermatopathol. 2014 Jul 15. [Epub ahead of print]

Delayed Onset of the Jarisch-Herxheimer Reaction in Doxycycline-Treated Disease: A Case Report and Review of its Histopathology and Implications for Pathogenesis.

Kadam P1, Gregory NA, Zelger B, Carlson JA.

Author information

1*Department of Pathology, Divisions of Dermatology and Dermatopathology, Albany Medical College, Albany, NY; †Upper Hudson Valley Dermatology, Castleton, NY; and ‡Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.

Abstract

The Jarisch-Herxheimer reaction (JHR) is a transient inflammatory syndrome triggered hours after the start of antibiotic treatment of spirochete infections, namely syphilis. Clinically, JHR manifests as an abrupt onset of constitutional symptoms and exacerbation of cutaneous lesions that resolve without intervention. JHR's pathogenesis is unclear and it is histopathologically rarely reported. Herein, the authors report a 47-year-old woman, with solitary erythema migrans and positive Lyme disease serology, who presented for medical care 14 days after commencement of doxycycline therapy. She complained of malaise, facial flushing, gingival erythema, and acquisition of additional plaques characterized by swelling, increased erythema, pruritus, and exfoliative scale. Punch biopsies demonstrated subacute to chronic spongiotic psoriasiform reaction patterns with a superficial lymphocytic infiltrate. By Borrelia-specific immunohistochemistry, spirochetes were found in the deep dermis, unassociated with inflammation, and focally in the upper spinous layer, associated with spongiosis. Borrelia burgdorferi DNA was detected by nested polymerase chain reaction. Doxycycline was discontinued, and symptoms and signs resolved within a few days. Liberation of endotoxin-like materials (eg, lipoproteins) from degenerating spirochetes and concomitant cytokine production is the suspected cause of JHR and supported by the finding of lesional spirochetes. Alternatively, a reversal reaction with a delayed-type hypersensitivity reaction is also a plausible cause based on spirochetes found in the lymphocytic spongiotic dermatitis.

PMID: 25033009 [PubMed - as supplied by publisher]

RitaA
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Re: Jarisch-Herxheimer reaction

Post by RitaA » Fri 9 Jan 2015 9:57

An even older, but related, thread:

What is true about the Jarisch-Herxheimer reaction?

http://www.lymeneteurope.org/forum/view ... p?f=6&t=45

X-member
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Re: Jarisch-Herxheimer reaction

Post by X-member » Fri 6 May 2016 16:12

Bump!

lou
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Re: Jarisch-Herxheimer reaction

Post by lou » Fri 6 May 2016 16:49

That roadback page link does not work. And I was wondering what the date was on the first one? We really need something that works on the herx, because for some people this is a serious concern and affects ability to treat.

RitaA
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Joined: Thu 1 Jul 2010 8:33

Re: Jarisch-Herxheimer reaction

Post by RitaA » Fri 6 May 2016 19:43

Unfortunately, over time, some links no longer work. That's why I often cut-and-paste shorter articles in their entirety or big chunks of really long articles.

It looks like the first article in this thread was published in 1992:

http://www.ncbi.nlm.nih.gov/pubmed/1506345
J Antimicrob Chemother. 1992 Jun;29(6):613-6.

New insights into the pathophysiology of the Jarisch-Herxheimer Reaction.

Griffin GE1.
Author information
1Division of Communicable Diseases, St George's Hospital Medical School, Tooting, London, UK.

PMID: 1506345 [PubMed - indexed for MEDLINE]
There is ongoing research into the Jarisch-Herxheimer reaction, and especially as it pertains to neurosyphilis and leptospirosis. I wasn't able to find any recent published articles that mention both Jarisch-Herxheimer reaction and Lyme disease during a quick internet search.

http://www.ncbi.nlm.nih.gov/pubmed/23732875
JAMA Neurol. 2013 Aug;70(8):1060-4. doi: 10.1001/jamaneurol.2013.2120.

Elevated CSF cytokines in the Jarisch-Herxheimer reaction of general paresis.

Davis LE1, Oyer R, Beckham JD, Tyler KL.

Author information

1 Department of Neurology Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA.

Abstract

IMPORTANCE:

The Jarisch-Herxheimer reaction (JHR) is a well-recognized transient worsening of signs and symptoms occurring soon after the first dose of an appropriate antibiotic for several spirochetal infections. The pathogenesis of this reaction is poorly understood. In this case study of cerebrospinal fluid (CSF) cytokines, we aimed to improve understanding of the pathogenesis of JHR in patients with neurosyphilis who develop transient neurologic signs.

OBSERVATIONS:

Four hours after receiving penicillin for general paresis, a 55-year-old man developed a severe JHR characterized by fever, tachycardia, hypertension, obtundation, seizures, and a neutrophilia lasting 18 hours. Cerebrospinal fluid obtained at the peak of the JHR demonstrated a switch from a mild lymphophilia to a moderate neutrophilia. He had markedly elevated CSF interleukin (IL) 8 and likely elevated IL-1β, IL-10, and IL-15 levels, which returned to normal in follow-up CSF examination results.

CONCLUSIONS AND RELEVANCE:

To our knowledge, this is the first report of elevated CSF cytokines in a patient with a JHR, which possibly contributed to the neurologic signs of JHR. Further studies on the innate inflammatory response during episodes of acute infection and inflammation are needed to develop targeted therapies to modulate this system, which could, in turn, improve future outcomes and modify the JHR.

PMID: 23732875 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/23555644
PLoS One. 2013;8(3):e59266. doi: 10.1371/journal.pone.0059266. Epub 2013 Mar 26.

The Jarisch-Herxheimer reaction in leptospirosis: a systematic review.

Guerrier G1, D'Ortenzio E.

Author information

1 Département d'Anesthésie-Réanimation, Centre Hospitalier Territorial, Noumea, Nouvelle Calédonie.

Abstract

BACKGROUND:

Leptospirosis is an endemo-epidemic zoonotic disease associated with potentially fatal renal, cardiovascular or pulmonary failure. Recommended treatment includes antibiotics, which may induce a Jarisch-Herxheimer reaction (JHR). Since little information on the importance of this adverse event is available, we performed this review to quantify frequency and impact of JHR in leptospirosis management.

METHODOLOGY/PRINCIPAL FINDINGS:

This review systematically summarizes the literature on the JHR in leptospirosis. To approach the broader aspects of the subject, articles considering the treatment of leptospirosis, national leptospirosis guidelines and textbook and technical reports of the World Health Organisation were reviewed. Publications describing JHR in leptospirosis are very limited and consist mainly of single case reports and small case series. A single randomized control trial specifically assessed the JHR occurrence, but it has never been systematically investigated in large trials. Not all guidelines and not all literature on leptospirosis mention this reaction which can be fatal.

CONCLUSIONS/SIGNIFICANCE:

Although generally assumed to be a rare event, the true prevalence of JHR in leptospirosis is unknown and the awareness of this event is insufficient. All leptospirosis guidelines and local leptospirosis protocols should stress on systematic monitoring for clinical status early after antibiotic administration. Large well designed studies are required to precise the incidence and the impact of JHR as well as the severity and rates between various antibiotics.

PMID: 23555644 [PubMed - indexed for MEDLINE] PMCID: PMC3608636 Free PMC Article
Edited to add the following link for an article that is behind a paywall:

http://www.sciencedirect.com/science/ar ... 3913000513
Travel Medicine and Infectious Disease
Volume 11, Issue 4, July–August 2013, Pages 231–237

The Jarisch–Herxheimer reaction: Revisited

Geetanjali Reddy Beluma, , , Viswanath Reddy Beluma, b, e, , Sri Krishna Chaitanya Arudrac, , B.S.N. Reddya, d,

a Skin & VD Clinic, Hyderabad, AP, India
b Memorial Sloan-Kettering Cancer Center, USA
c Department of Pathology, University of Toledo, Toledo, OH, USA
d Department of Dermatology, Mamata Medical College, Khammam, AP, India

Received 4 January 2013, Revised 31 March 2013, Accepted 3 April 2013, Available online 28 April 2013

Summary

The Jarisch–Herxheimer reaction (JHR) is a transient immunological phenomenon seen commonly in patients during treatment for syphilis, and it manifests clinically with short-term constitutional symptoms such as fever, chills, headache and myalgias, besides exacerbation of existing cutaneous lesions. The complex interplay of its underlying patho-physiological mechanisms continues to elude modern medicine, ever since it was described over a century ago. An increase in the incidence of JHR may be expected among patients co-infected with HIV and other infectious diseases including syphilis. Since this subject has not received much attention in recent literature except for brief mentions in standard textbooks, we felt it important to provide an overview of its various attributes including the current concepts in pathophysiology and management.

Keywords: Jarisch–Herxheimer; Syphilis; Herxheimer; Paradoxical reactions; IRIS

RitaA
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Re: Jarisch-Herxheimer reaction

Post by RitaA » Fri 6 May 2016 21:20

Thanks to Virginia Lyme, here's the undated article from the Roadback link that no longer works:

https://sites.google.com/site/virginial ... eimer-herx
Herx or Herxing
aka
Jarisch-Herxheimer Reaction


Always ensure your health by regularly visiting your doctor. Never assume that if you have any of the symptoms below that you are in a healing crisis (herx). You may not be experiencing a herx, you may have an unrelated medical health problem.

[snip]

Treating the Jarisch-Herxheimer(JH) Flare Reaction

Stuart L. Weg, M.D. is certified by the American Board of Anesthesiology with added qualifications in pain management.


The observed temporary worsening of clinical status in patients undergoing anti-infective treatment is called the Jarisch-Herxheimer (JH) reaction. It may be referred to by some of the terms listed below. This phenomenon, described in the cover article, is not just present in rheumatologic disease but is common to all forms of anti-infective therapies that I have used for most chronic painful states. This apparent common etiology of all chronic pain and arthritis is not within the scope of this discussion but will be covered in the future.

The JH reaction can take the mild form of sleepiness and fatigue to full blown anaphylactic shock. The timing varies from almost immediately, as is the case of IV antibiotics, to up to a week or two later. This depends on the rate that toxins are produced and how fast they can be metabolized or eliminated. Drug levels are important, but often cannot explain the timing of a reaction. In some cases an overwhelming, waterfall effect is present, while in other patients there is a slow, gradual building of symptoms. I have seen cases where adding another unrelated medication caused the antibiotic to become more bioavailable and that precipitated a JH. There are cases where simply changing a single 100 mg daily dose of minocycline to two 50 mg split doses has provoked a JH due to an absorption increase. Reducing, suspending or changing the offending medication is the most obvious treatment. Patients must understand that early signs of the JH reaction may not be present; even the most conscientious and observant physicians may not stop or lower the medication in time to avoid patient discomfort.

The classical discussions of a JH describe the presence of bacterial debris or toxins from anti-infective therapies that cause this reaction. This is certainly true, but another byproduct is also formed when cell wall deficient bacteria or L forms are attacked. I have noticed that some JH present as a flu syndrome. Other patients develop purulent drainage from the head and neck, urine and other areas. When I have cultured these patients, I have been able to isolate adult (non L-form) bacteria. Treatment with medications that favor the destruction of L-forms who are unwalled forms will also favor or select for the survival of adult or walled forms of bacteria.1 Microbiologists call this change of the form of bacteria pleomorphism. The induction of walled forms of bacteria has been studied and should be kept in mind when considering treating a JH reaction.

Treatment of a JH should be aimed at eliminating toxins from the killed bacteria and destruction of newly induced adult b acteria. Consideration should also be given to the possibility of overgrowth of endemic yeast infections. Often there are symptoms that clinically indicate the presence of histamine. The physician's diagnostic skills and clinical judgment must be called into place to differentiate between a direct toxic reaction versus the appearance of an adult form organism or the more insidious development of yeast overgrowth.

For the ease of the reader, I am classifying the JH reaction into two categories:

1) Acute - life-threatening. These may also be called anaphilactoid.

2) Non-acute or non-life-threatening- not anaphilactoid.

Acute - Life Threatening

The severe acute reactions are probably related to a massive response of the immune system to toxins. There may be a large release of histamine as well. Such anaphilactoid reactions need immediate attention and should be considered life-threatening. The most severe problems involve swelling of the neck areas and closure of the airway. This must be treated at once with epinephrine followed by transportation to a hospital. The management of severe anaphilactoid emergencies is well known by healthcare personnel and beyond the ability of the patients to handle at home. A drop in blood pressure is also common along with skin changes due to dilation of the blood vessels. This can lead to cardiovascular collapse unless aggressively treated and also needs hospital management. Milder cases featuring asthma may respond to inhaled broncodialator medications, but this can sometimes delay the patient from seeking early medical attention and avoiding catastrophe. Skin rashes are not life threatening but often are quite distressing. A more detailed [snipping lots of text that doesn't seem to belong here] discussion of these kinds of problems is presented in most textbooks of medicine and all manuals for emergency care.

Management of Non-life Threatening JH Reactions or Clinical Flares

The more typical JH reactions to anti-infective therapies are: worsening of symptoms, febrile states such as night sweats, flu-like picture, hot swollen joints, mental depression and fatigue. I recommend home therapies designed to clear the blood and make the patient more comfortable. My routine calls for baths in hydrogen peroxide and Epsom salts. These baths are very effective and have tremendous anti-infective effects. They may work for only a short time at first and may need to be repeated. The peroxide easily enters the body through the skin and rapidly detoxifies and sterilizes the blood. There will be a marked reduction in tight muscles that can be a part of a JH reaction. Unfortunately peroxide can have a JH reaction of its own, but this is more pronounced when it is used IV rather than in a bath. Magnesium in the Epsom salts also passes easily systematically; it has a local anesthetic, antispasmodic effect and an overall improvement in the performance of most systems. Oral peroxide is available but not discussed here. The IV route for both peroxide and magnesium is used to stop the JH reaction in office management. The same benefit of blood detoxification and general enhanced clearing of tissue toxins and bacteria can be claimed for high dose ascorbic acid (20-50 GMs IV). Vitamin C can be given in oral form too. Ascorbic acid powder equals about 5 grams per level teaspoon. This dose can be taken with water or juice as often as needed or until there is GI intolerance such as diarrhea. The clinical effects are similar to peroxide. In fact, the two can be given to a patient on the same day with excellent results. It must be remembered however; the vitamin C will also neutralize peroxide and thus should always be given after the bath. Mild JH reactions are also seen with vitamin C therapy again mainly when given IV. Such therapies as peroxide baths and vitamin C are easy to do at home and extremely effective at helping patients make a quick, safe recovery from a JH reaction.

Other oxidative office therapies can be alternated with these modalities or with antibiotics to hasten detoxification of bacterial toxins. Ultraviolet blood irradiation (UBI) involves removing a small portion of the circulating blood and cleaning it under UV light before returning it to the patient. The mechanism of action is not well known, but such treatment has been used for over fifty years mostly outside the United States for improvement in immunologic function. This treatment also ameliorates the JH phase of anti infective therapy. It is further noticed that direct exposure to sunlight has a similar effect to UBI in many patients. Therefore my patients are asked to get sun exposure if the climate allow s not using sunscreen up to the point of mild burning. I caution them that minocycline will cause them to be sensitive, but that they can go out with care and receive great benefit. And as I had expected, I do see stable patients develop mild JH re actions after such activities as fishing trips which cause a huge UV sun dose and large destruction of circulating bacteria.

Another approach to treating worsening of symptoms after oral antibiotic or other anti-infective therapy is the use of IV antibiotics. I have used IV doxycycline for quelling such problems. Other physicians have used IV minocycline, IV clindamycin and others for this purpose. In my practice the antibiotics are the drugs of last resort. The most preferred treatments involve the home remedies with peroxide and vitamin C.

I have tried to avoid the use of anti-inflammatory remedies for the JH reaction. The corticosteroids will control a rash, but I have noted a general deterioration of the patient's condition weeks later. Such topical steroids as are given in inhaled or skin medications are certainly absorbed. Their use will be a quick fix at a high cost due to the setback they cause. The nonsteroidal anti-inflammatories that are used orally have the effect of irritating the GI system and are implicated as one of the causes of the leaky gut syndrome also linked to many of the chronic pain states. Again they are drugs of a last resort. Topical soothing lotions such as aloe vera can do no harm and may make a rash feel better.

Yeast overgrowth must be considered when new symptoms develop after antibiotics are started. I put all chronic pain patients on continuous oral acidophilus supplements before starting any anti-infective therapy. We were noticing yeast emergence in nearly 100% of the patients. With the addition of acidophilus, this problem is becoming a lot less common.

Summary

Worsening or flaring of symptoms after the commencement of anti-infective therapy should be expected and considered a JH reaction. The patient should be cautioned about the signs of a potentially life threatening anaphilactoid reaction and urged to seek medical attention at once. The more common clinical non-life threatening flares should not cause undo concern to the patient and may be treated by altering the medication dosage and with some of the suggested therapies above. Abandoning of the anti-infective approach to chronic pain and arthritic disease would be unfortunate simply because of these expected temporary setbacks.

For educational purposes only. Consult your physician before you make any changes in your treatment.

[snip]

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