Patients present with symptoms 1 to 12 hours after antibiotic administration and the reaction lasts for a few hours and a day and is not seen on follow-up treatment. Prominent symptoms include fatigue, mild to moderate temperature elevation, flushing caused by vasodilation and an increased heart rate. Laboratory tests may show elevated white blood cell count. New skin lesions may appear in patients and existing lesions can worsen. There is an initial elevation of blood pressure in conjunction with tachycardia and hyperventilation but is usually followed by a drop in blood pressure due to decreased peripheral resistance and vasodilation.

• Fever

  All samples taken while the patients had fever were pyrogenic. After incubation with normal rabbit plasma these samples failed to produce fever in endotoxin-refractory rabbits. 4. [clinsci.org]

  ", abstract = "Relapsing fever is a disease caused by one of the species of Borrelia. [research.vu.nl]

  In patients with louse-borne relapsing fever (Borrelia recurrentis infection), antimicrobial treatment is often followed by sudden fever, rigors, and persistent hypotension (Jarisch-Herxheimer reactions) that are associated with increases in plasma concentrations [ncbi.nlm.nih.gov]

  Jarisch-Herxheimer reaction associated with ciprofloxacin administration for tick-borne relapsing fever. [scholars.northwestern.edu]

  At first there are rigors, fever, tachycardia, tachypnea and hypertension. [journals.lww.com]

• Chills

  Peripheral vasoconstriction immediately preceded the chill phase and profound vasodilation accompanied the flush phase. 2. [clinsci.org]

  The patient described feeling cold with worsening headache and chills approximately one hour after infusion of the first dose of penicillin. On examination, rigors, shallow inspirations, and chills were noted. [ncbi.nlm.nih.gov]

  Manifestations include fever, chills, headache, myalgias, and exacerbation of cutaneous lesions. [medical-dictionary.thefreedictionary.com]

  Two hours after the first dose of gentamicin, he developed high fever (40.5°C axillary), chills and prostration. The temporal relationship between beginning of the antibiotic treatment and high fever with chills suggested the diagnosis of JHR. [journals.lww.com]

• Fatigue

  Patients usually complain of fever, palpitations, flushing and fatigue. In some cases, skin lesions may worsen or new lesions may appear. [symptoma.com]

  Too strong a reaction may also presuppose fatality through physical and/or emotional fatigue and depression. [mdjunction.com]

  A primary care doctor had prescribed a couple of weeks of antibiotics for possible Lyme following a tick bite, bull’s-eye rash, pain and fatigue. [lifelovelyme.com]

  The toxins remain in circulation and can effect the brain stem region leading to nausea, poor coordination, headaches, fatigue, malaise, fever, etc ( 1, 2 ). [drjockers.com]

  Due to the poor cerebral blood flow, fatigue, dizziness, poor concentration problems and nearly or actually passing out are common symptoms. [Dr. Horowitz] Adjusting Doses - Can adjust dose to patient tolerance to minimize Herx responses. [Dr. [sites.google.com]

• Rigor

  Ten of the 20 patients given anti-TNF-alpha Fab had Jarisch-Herxheimer reactions with rigors, as compared with 26 of the 29 control patients (P = 0.006). [ncbi.nlm.nih.gov]

  It usually manifests as fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, myalgia, and exacerbation of skin lesions. [pubmed.ncbi.nlm.nih.gov]

  Symptoms can include fever (generally low grade), chills, headache, myalgias, rigors, hyperventilation, tachycardia, hypertension followed by hypotension (due to vasodilation and declining peripheral resistance), and an exacerbation of cutaneous lesions [ticktwister.co.uk]

• Malaise

  She presented with a 2 day history of fever, headache, general body malaise and vomiting. She was misdiagnosed as having severe malaria and was treated with quinine. The blood slide showed Borrelia duttoni. [research.vu.nl]

  The reaction consists of shaking chills, fever, malaise, sore throat, myalgia, headache, tachycardia and exacerbation of the inflammatory reaction at sites of localized spirochetal infection.1 Severe complications, including an exacerbation of neurologic [nejm.org]

• Diarrhea

  You may find you have flatulence, bloating or diarrhea. Some people develop flu-like symptoms such as fever, chills, muscle pain and headaches, or a worsening of allergies. The herx reaction normally last for only a few days. [probiotics-lovethatbug.com]

  Here’s a list of the general symptoms of poisoning: nausea vomiting diarrhoea (diarrhea) stomach pain drowsiness, dizziness or weakness fever and chills (shivering) loss of appetite headache or irritability difficulty swallowing producing more saliva [healingnaturallybybee.com]

  Typical herxheimer reaction symptoms from probiotics usually include flu-like symptoms, joint pain, headache and digestive issues such as bloating, gas, constipation, diarrhea, abdominal pain, skin rash, acne and itching. [candidaspecialists.com]

  Symptoms Of Yeast Die Off nausea headache swollen glands bloating constipation or diarrhea increased joint or muscle pain elevated heart rate chills, cold extremeties itching scratching nail biting unusual perspiration fever (usually low grade) hypotension [homeopathyforwomen.org]

• Abdominal Pain

  A 14-year-old girl was seen at a community clinic with a chief complaint of abdominal pain and fevers and was treated with oral ciprofloxacin for presumed pyelonephritis. [scholars.northwestern.edu]

  Headache, myalgias and abdominal pain accompanied our patient’s presentation. Arthralgias, photophobia and cough are common symptoms as well. [journals.lww.com]

  Elevated or racing heartbeat, chest pain. Joint and muscle pain, body aches. Brain fog. Headache. Constipation or diarrhea. Digestive issues and intestinal discomfort such as bloating, gas, abdominal pain. [candidaspecialists.com]

  pain 1.37 0.73 19 Diarrhoea 1.29 0.77 20 Angioedema 1.02 0.98 21 Paraesthesia 0.97 1.03 22 Dyspnoea 0.80 1.25 23 Arthralgia 0.79 1.26 24 Pain 0.76 1.32 25 Abdominal pain upper 0.72 1.38 26 Pain in extremity 0.62 1.62 27 Dizziness 0.59 1.69 28 Hyperhidrosis [earthmedresearch.org]

• Hypotension

  She became tachycardic and hypotensive after her first dose of antibiotic, and she developed disseminated intravascular coagulation. She was admitted to our hospital for presumed sepsis. [scholars.northwestern.edu]

  Penicillin given on the first day and tetracycline on subsequent days to avoid severe Jarisch-Herxheimer reactions, has the disadvantage of a longer period of spirochetemia and hypotension as compared with tetracycline on the first day. [ncbi.nlm.nih.gov]

  Later, there is often vasodilation and decreased peripheral resistance, leading to hypotension. There have been few reports of severe reactions requiring vasopressors for hypotension in patients with JHR after treatment of leptospirosis [6,7]. [cureus.com]

• Tachycardia

  During pregnancy, it can cause signs and symptoms in both the mother and fetus, including fever, tachycardia, uterine contractions, and fetal heart rate pattern changes. [ncbi.nlm.nih.gov]

  Occurs 2 to 6 hours after treatment started; symptoms can last for 24 hours Malaise Fever Rigors Flushing (due to vasodilation) Hypotension Tachycardia Tachycardia and hyperventilation are accompanied by hypertension, and then by a drop in blood pressure [wikem.org]

  It usually manifests as fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, myalgia, and exacerbation of skin lesions. [pubmed.ncbi.nlm.nih.gov]

• Hypertension

  She developed hypertension, fever, and rigors. Shortly afterward, she became hypotensive and required fluid resuscitation. [ncbi.nlm.nih.gov]

  Symptoms can include fever (generally low grade), chills, headache, myalgias, rigors, hyperventilation, tachycardia, hypertension followed by hypotension (due to vasodilation and declining peripheral resistance), and an exacerbation of cutaneous lesions [ticktwister.co.uk]

  Occurs 2 to 6 hours after treatment started; symptoms can last for 24 hours Malaise Fever Rigors Flushing (due to vasodilation) Hypotension Tachycardia Tachycardia and hyperventilation are accompanied by hypertension, and then by a drop in blood pressure [wikem.org]

• Palpitations

  Patients usually complain of fever, palpitations, flushing and fatigue. In some cases, skin lesions may worsen or new lesions may appear. [symptoma.com]

  Any neurological symptoms, severe gastrointestinal upset, palpitations, vomiting, or blurred vision need to be investigated by a qualified medical doctor and should not be presumed to be ‘herxing’. [lymediseaseguide.net]

  Also reported are heavy perspiration, metallic taste in mouth, chills, nausea, bloating, constipation or diarrhea, low grade fever, heart palpitations, tachycardia, facial palsy, tinnitus, mental confusion, uncoordinated movement, pruritus, bone pain, [lemonandlyme.com]

• Sweating

  Its clinical manifestations include fever, sweating, headache, hypotension, and worsening of cutaneous lesions. Many aspects of its etiology are still unknown. [scielo.br]

  A 36 year old white man was diagnosed as having Whipple's disease after a prolonged illness of lethargy, night sweats, and weight loss associated with lymphadenopathy and splenomegaly. [ncbi.nlm.nih.gov]

  Some of it, especially the toxins from the parasitic tick-borne co-infection babesia, is sweated out. I’d wake two or three times a night completely soaked from head to toe, as if I’d just showered. [globallymealliance.org]

  S kin and dermal: Expel neurotoxins through sweat, sebaceous glands and tears. [lyme-symptoms.com]

• Angioedema

  *of course don't brush off your patient's symptoms if they include: diffuse rash, wheals, angioedema, wheezing, because don't forget: penicillin can cause allergies in individuals sensitive to it!! [rememberx2.blogspot.com]

  […] includes the following: “1. systemic or generalized anaphylaxis; a type I hypersensitivity reaction (see under hypersensitivity reaction ) in which exposure of a sensitized individual to a specific antigen or hapten results in urticaria, pruritis, and angioedema [lymeandals.wordpress.com]

  […] oedema 2.32 0.43 11 Vomiting 2.09 0.48 12 Dysgeusia 2.07 0.48 13 Chills 2.03 0.49 14 Hypersensitivity 1.80 0.56 15 Drug hypersensitivity 1.78 0.56 16 Chest discomfort 1.51 0.66 17 Nausea 1.44 0.69 18 Abdominal pain 1.37 0.73 19 Diarrhoea 1.29 0.77 20 Angioedema [earthmedresearch.org]

• Withdrawn

  Blood was withdrawn for spirochete and white-cell counts and cytokine assays 30 minutes before penicillin treatment and 1, 1.5, 2, 4, 8, and 24 hours afterward. [doi.org]

• Headache

  She presented with a 2 day history of fever, headache, general body malaise and vomiting. She was misdiagnosed as having severe malaria and was treated with quinine. The blood slide showed Borrelia duttoni. [research.vu.nl]

  Manifestations include fever, chills, headache, myalgias, and exacerbation of cutaneous lesions. [medical-dictionary.thefreedictionary.com]

  Its clinical manifestations include fever, sweating, headache, hypotension, and worsening of cutaneous lesions. Many aspects of its etiology are still unknown. [scielo.br]

  The patient described feeling cold with worsening headache and chills approximately one hour after infusion of the first dose of penicillin. On examination, rigors, shallow inspirations, and chills were noted. [ncbi.nlm.nih.gov]

No specific diagnostic testing is necessary after the development of the reaction. It is critical, however, to properly identify what is happening and not ascribe the symptoms to antibiotic treatment, so as not to stop the dosage course. In some cases, patients may be diagnosed with another infection than syphilis, and the development of the reaction may prompt physicians to change their working diagnosis. This most commonly occurs when a treatment for gonorrhea is started. In this case, serological testing for syphilis is required with a subsequent adjustment in medication dosage. The development of JHR can also indicate that the treatment is properly working. The Jarisch Herxheimer reaction is not exclusive to syphilis and can occur with various infections including Lyme disease and relapsing fever.

• Neisseria Gonorrhoeae

  Day 3: Neisseria gonorrhoeae was isolated from the rectal culture. The serological tests for syphilis showed a rapid plasma reagin titre of 1:8 and a reactive Treponema pallidum haemagglutination assay. [mja.com.au]

The Jarisch Herxheimer reaction does not require any treatment as it is usually self-limiting and resolves on its own within a day. A severe reaction associated with leptospirosis may sometimes require intensive treatment in the form of corticosteroids, fluid injections, vasopressors and transient dialysis [13].

Prognosis is excellent and patients recover quickly without alteration of the treatment course.

The disorder is caused by an excessive inflammatory reaction of the human body in response to the release of endotoxins by dead or injured bacteria. JHR occurs after the administration of antibiotics in the presence of various infections including syphilis, Q fever, leptospirosis, Lyme disease, tick-borne relapsing fever. Similar forms of the reaction have been reported in cat-scratch disease, trichinosis, cerebral trypanosomiasis and typhoid fever.

The Jarisch Herxheimer reaction occurs as frequently in primary syphilis as it does in early secondary syphilis. Nonetheless, the incidence is reported to decrease with the duration of the illness and seronegativity. Studies indicate that 95% of seropositive patients develop an elevation of axillary fever up to 37.6-degree celsius but only 55% of seronegative patients do [4]. Additionally, fever occurs in only 32% of patients with late secondary syphilis and condylomata lata. The incidence of JHR in tertiary syphilis are imprecise, given the scarcity of the condition. However, it is almost certain that it occurs less frequently and less severely than in infectious primary syphilis. Some reports indicate that the reaction can occur in up to 34% of patients with neurosyphilis, including 74% in patients with general paralysis and 23% with tabes dorsalis. Incidence was also closely correlated with elevated cell count and protein concentration in the cerebral spinal fluid [5] [6]. JHR is very rare in the antibiotic treatment of other bacterial infections.

There have been many proposed explanations for the JHR. Herxheimer initially postulated the treponemal products released after the administration of the drug directly target syphilitic tissue, leading to an exacerbation of the lesions. This theory, however, has been abandoned because it has been observed that the reaction is independent of the number of microorganisms at the time of the treatment [7]. Furthermore, the reaction can occur in late syphilis, a stage characterized by a low number of organisms [8]. Other scientists stated that bacterial endotoxins ultimately result in the release of inflammatory molecules and pyrogens [9].

When metal therapy was the treatment of choice, it was thought that JHR is caused by a direct toxic effect of the drug on blood vessels. This theory was later disproved when it was shown that the reaction also occurs with penicillin treatment but not for all diseases [7].

Histamine signaling has been also ruled out as a major cause because the reaction does not respond to antihistamine treatment. Furthermore, there is no concomitant release of kinins with the presence of large quantities of bacterial substances [10].

On the other hand, scientists have observed strong similarities between cell-mediated immune responses and the pathophysiological mechanisms involved in the JHR despite the divergent time courses [7]. It is also established that the cellular immune response plays an important role in the body's response to syphilis, although it is dependent on the stage of the disease. Production of macrophage inhibition factor (MIF) by lymphocytes results in inhibition of migration in the late active syphilis but not in primary syphilis. In contrast, a positive lymphocytic response to Reiter antigen is associated with an absence of MIF production in secondary syphilis [11] [12].

The response of JHR to corticosteroids administration may provide a useful opportunity to investigate the underlying pathophysiological mechanisms. Corticosteroids lead to a significant reduction in febrile reactions but they do not affect other forms of JHR in primary syphilis. In fact, there is evidence that the macular rash observed in JHR can worsen with steroid administration. Furthermore, steroids have no tangible effects on leukocyte patterns. This indicates that their effects in early syphilis are limited to fever reduction. Other evidence nonetheless suggests that steroids have much broader effects on the inflammatory response in late syphilis.

The Jarisch Herxheimer reaction can be prevented or contained by following specific measures. An alternative selection of antibodies is recommended in clinical situations, for example, treatment of HIV-positive patients suffering from early syphilis with azithromycin.

The administration of corticosteroids has been also shown to decrease the severity and frequency of the reaction in late symptomatic syphilis. It is advisable to give 30 mg prednisone on the day of antibiotic administration, followed by tapering of the dose in the following day. Administration of TNF-alpha antibody after penicillin treatment can also reduce the incidence of the reaction from 90% to 50%, and result in decreased temperature elevation, cardiac rate, blood pressure and serum levels of interleukin 6 and 8.

Incidence in pregnancy amounts to 40% and fetal monitoring is important because of a risk of regular uterine contractions.

The Jarisch Herxheimer reaction (JHR) occurs after administration of antibiotics, frequently penicillin in the presence of a syphilis infection. It might also occur in the context of other diseases that are mostly caused by spirochetes such as Lyme disease, leptospirosis, and Q fever [1]. The underlying pathophysiological mechanisms have not been fully understood, but it is thought that injured or dead bacteria release substances that trigger an inflammatory reaction in the human body. It was hypothesized previously that it occurs due to an interaction between bacterial pathogens and syphilitic tissue but this theory has been disproved, as the reaction is independent of the number of organisms and can occur when the number of microorganisms is minimal. The cell-mediated immune response is considered now critical in the pathogenesis, despite the fact that JHR develops very rapidly. The Jarisch Herxheimer reaction is usually more severe in HIV patients and occurs in about 75% of cases of primary and secondary syphilis and is extremely rare in late syphilis [2] [3].

Patients usually present with fever, fatigue, tachycardia and flushing 1 to 12 hours after initiation of antibiotic treatment. An initial rise in blood pressure is followed by hypotension due to vasodilation. In some cases, there is a worsening of already present cutaneous lesions or the appearance of new ones. The reaction is self-limited, resolves in 24 hours and usually requires no intervention. It is not recommended to stop antibiotic treatment in case it occurs. No diagnostic laboratory tests are needed either and the diagnosis can be made clinically. It is important however not to ascribe the symptoms to an allergic reaction to medications so as not to stop the treatment. In selective cases, the development of the reaction to penicillin administration can be a clue to the diagnosis of syphilis and may prompt additional serological testing. Preventive measures that may ameliorate the reaction include corticosteroid treatment on the day of antibiotic administration followed by subsequent tapering. Administration of TNF-alpha antibodies has been also shown to significantly reduce incidence.

The Jarisch Herxheimer reaction describes a reaction of the human body to antibiotic treatment of certain bacterial infections, frequently penicillin treatment in the presence of a syphilis infection. This is a normal reaction and can indicate that the body is responding well to the treatment. JHR can be known by several names, including Herx reaction, Herxheimer effect, Herx or Herks. It is thought to be caused by the release of substances from dead and injured bacteria that subsequently trigger inflammatory reactions in the human body. The major issue associated with JHR is not the reaction itself but the fact that many patients stop taking the medication after they develop symptoms. This can lead to a worsening of the infection and a deterioration in their condition.

JHR usually develops very rapidly after intake of antibiotics, in around 1 to 12 hours. It is self-limiting and resolves by itself in less than a day. Patients usually complain of fever, palpitations, flushing and fatigue. In some cases, skin lesions may worsen or new lesions may appear. JHR requires no treatment and diagnosis is established by the physician clinically, with no need for any laboratory tests. Sometimes the presence of the reaction can tell the physician what the likely infection is and may prompt him or her to test for syphilis. However, it is very important not to confuse JHR with an allergic reaction to the medication. Otherwise, the treatment course may be stopped or dosage reduced, leading to an exacerbation of the infection.

JHR does not occur with the same frequency in all disease stages of syphilis. It is usually more common in the early phases and becomes very rare in the more developed stages. It can also be associated with diseases other than syphilis. These are usually caused by similar but not identical bacteria and include Q fever, leptospirosis, and Lyme disease.

Some medications can be useful to lessen the symptoms or reduce the incidence. For example, a course of prednisone at the day of antibiotic treatment can ameliorate many of the bothering symptoms. Novel medications such as antibodies to an inflammatory mediator called TNF-alpha can also reduce incidence.

Mild reaction with no significant discomfort may require only limited action described below and the treatment should be continued. If the reaction is very severe, reducing the dosage or stopping treatment for a day or two may be appropriate, but with the condition of later continuing the recommended dosage. Other steps that can help in the prevention or amelioration of the symptoms include a decrease in exercise level, drinking a lot of water, following a light diet that does not load the body with toxins and foreign chemicals and making sure to get adequate sunlight.

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