Patients who respond to IT report periodic exacerbation of their symptoms as an apparent direct response to Benicar and pulsed antibiotics. This phenomenon is known as the Jarisch-Herxheimer Reaction and is often referred to informally as herx or herxing.
Herxing is believed to occur when injured or dead bacteria release their endotoxins into the blood and tissues faster than the body can comfortably handle it. This provokes a sudden and exaggerated inflammatory response.
History of the Herxheimer reaction
The treatment of many bacterial infections provokes a Herxheimer reaction. Herxing was originally observed in patients with acute infections such as syphilis who received mercury treatment (a weak antibiotic). The immune system response to acute infection is sometimes referred to as the immune cascade. For example, in the infamous anthrax attacks people died because by the time they got to hospital the anthrax organisms had multiplied to the point where killing them also killed the patient.
It has been reported that patients with chronic conditions or infections such as rheumatoid arthritis, Lyme, tuberculosis and louse-borne relapsing fever have also experienced herxing when treated with the appropriate antibiotics.
Jarisch-Herxheimer reaction is seen in many diseases:
Borreliosis - Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever. PMID: 9846580
Tick-borne relapsing fever - Relapsing fever in Gondar, Ethiopia. PMID: 12380884
Multiple sclerosis - Is Multiple sclerosis caused by a silent infection with malarial parasites? A historico-epidemiological approach: part II PMID: 11516219
Whipple disease - [Whipple disease associated with pulmonary arterial hypertension. Jarisch-Herxheimer reaction after antibiotic therapy] PMID: 11721494
Syphilitic slopecia - Syphilitic alopecia and Jarisch-Herxheimer reaction. PMID: 606336
Chronically ill patients are carrying a heavy load of intracellular pathogens by the time they become symptomatic because the Th1/Th17 infection has been growing, unhindered, for most of a patient's life. The immune system response when these intracellular bacteria are recognized and killed causes a similar immune cascade.
Immunopathology is a term, similar to Herxheimer, used by the scientific community. It describes all the collateral pathological effects on the body (e.g., hormonal, endocrine, cell death and blood count changes) caused by the immune system during normal function.
It’s normal for the body to generate an immune response when challenged by foreign matter such as microbes and allergens. Research has led to the hypothesis that this reaction in chronically ill patients is triggered by cell wall deficient, polymorphic L-form microbes. It is believed these intracellular bacteria have learned to live inside the macrophages (phagocytes) of the immune system. Apparently, they fail to be destroyed by the phagocytes which are supposed to kill them because they have adapted mechanisms to prevent being identified by the immune system.
When the intraphagocytic bacteria are killed by the immune system, the cells they lived in also die (apoptosis). As the immune system tries to clear up this cellular debris, it releases a host of inflammatory molecules which, along with the toxins released by the bacteria as they die, cause a rise in symptoms in the area in which the bacteria are being killed.
Identifying the bacteria
It’s difficult (and unnecessary) to determine which of the many species of intracellular mycoplasma might be responsible for individual Th1/Th17 inflammatory diseases. These bacteria are difficult to see even with an electron microscope, very slow growing and tedious to culture. This is only done in a research lab and makes it impractical to cross-match species to find the appropriate antibiotics.
Thus, the elicitation of a Herxheimer reaction is a key component of IT to determine, by therapeutic probe, which antibiotics are effective.
Identifying the Herxheimer reaction
Herxheimer symptoms are varied, may be unexpected, subjective or objective. Patients report that a Herxheimer reaction makes them feel as though their disease symptoms have suddenly gotten worse. They may describe reactivation of previous symptoms, exacerbation of current symptoms, or new symptoms. The onset of herxing is from 1-2 hrs to 10 days after the antibiotic/s are administered. Patients who have received other therapies prior to starting IT may have delayed or reduced Herxheimer reactions.
The intensity of the reaction is thought to be dependent on many factors; location of the inflammation, appropriateness of the antibiotic/s, the antibiotic dosage, the presence of immunosuppressants, the level of 25 hydroxyvitamin-D and the prophylactic dosing schedule of Benicar used to interrupt the inflammatory cascade.
Herxheimer symptoms usually wax and wane with antibiotic administration but dramatic waxing and waning of symptoms doesn’t always happen. An increase in symptoms may be constant for varying intervals. Patients with effective detoxification and elimination systems may not experience significant aggravation of symptoms.
Most, if not all, symptoms experienced while on IT are due to Th1/Th17 inflammation, although patients are still susceptible to acute infections (e.g., bacterial, viral, etc.). Patients may correctly attribute any or all symptoms as being due to immunopathology and not a progression of the disease.
Since chronically ill patients are believed to have acquired many different species of intracellular bacteria over a long period of time, the effectiveness of a different antibiotic combination probe with a positive Herxheimer reaction demonstrates the presence of another species, or of bacteria previously hidden within tissues poorly perfused by the antibiotics.
Patients will continue to experience Herxheimer reactions as long as effective antibiotic therapy continues. Trial and error with carefully selected antibiotic combinations provokes a resumption of herxing when symptoms have subsided.
Symptoms of Herxheimer reactions
IT unavoidably increases disease symptoms; some of them are subclinical.
The most common symptoms reported include increased fatigue, joint or muscle pain, skin rashes, photosensitivity, irritability, paresthesia, dizziness, sleep disturbances, asthenia, muscle cramps, night sweats, hypertension, hypotension, headaches (especially migraines) and swollen glands. 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, flu-like syndrome, conjunctivitis and throat swelling.
Physicians may note objective symptoms of a Herxheimer reaction such as elevated creatinine, blood urea nitrogen, liver enzymes, sedimentation rate, gamma globulin or a decrease in white blood cells, hemoglobin, or platelets.
Any symptom, including abnormal lab results, that correlates with IT may be due to herxing.
Lab tests results may be used to help determine the pace of therapy, especially if the degree of Herxheimer reaction is difficult for the patient to interpret. Chronically ill patients, who have been ‘down so long it begins to look like up’, may disassociate from their feelings and find it difficult to assess the sometimes subtle symptom shifts associated with Herxheimer reactions.
IT doesn’t create new inflammation because it can't make bacteria appear where there weren't any bacteria before. When patients experience new symptoms they haven't had before, it's probably because the therapy is exposing more bacteria.
Without therapy, these hidden bacteria would not remain hidden for ever. Eventually they would multiply to the point where they reveal themselves in new symptoms. If patients stop therapy prematurely, not only will the 'new' symptoms remain and worsen, but also further new symptoms will gradually develop, just as they would have done if the patient had never started IT.
Most symptoms have been reported by other patients on IT. The exact molecular mechanism for them is obscure and a topic best left to the scientists. The simple explanation is that Th1/Th17 inflammation during the disease process and during Herxheimer reactions affects a wide variety of biochemical processes.
The disease process causes symptoms and patients with chronic inflammatory diseases are systemically ill. Likely, no part of the body has escaped some damage even if it isn’t readily apparent.
Wanting to know specifically why certain symptoms occur is micromanaging the process and unnecessary. It’s best not to try to fit every symptom into a category (herx, hormone readjustment, old symptom revisited, etc.). If patients are patient with the therapeutic process and have confidence it will work, they will eventually forget they ever had these symptoms.
Severe Herxheimer reactions
Unexpected serious Herxheimer reactions needing Emergency Room treatment occur rarely. Cardiac involvement may be unsuspected and diagnosed only when herxing elicits chest pain or arrhythmia. If physicians are aware that symptoms are likely due to herxing, they can avoid unnecessary testing or medications. Adjusting the Benicar and/or antibiotics dose/schedule is the most effective treatment for serious herx symptoms.
Herxheimer symptoms versus disease progression
Most disease symptoms progress slowly. Herxheimer symptoms usually flare quickly. If the underlying cause of chronic illness, intracellular bacteria, is being eliminated it is unlikely the disease process is progressing.
Herxheimer symptoms are not a 'side effect' of IT medications. Herxheimer symptoms are caused by the disease process, not directly by Benicar or the antibiotics.
Allergy versus Herxheimer reaction
A Herxheimer reaction is sometimes mistaken for a “hypersensitivity reaction” or even the cause of a related, (probably preexisting) disease such as lupus. Pruritus, hives and rash induced by herxing can be misdiagnosed as an allergic (T-helper2) reaction to the antibiotic. IT patients, however, have reported safely taking antibiotics, although eliciting herxing, despite a history of ‘allergy’.
Herx symptoms might linger for weeks, rather than the hours that would be expected from an allergic reaction. Although rarely necessary, laboratory tests can help differentiate between a Herxheimer reaction to microbial toxins and an allergic reaction to medication. BUN (blood urea nitrogen) and 1,25-D will be elevated in a Herxheimer reaction. A marked increase in eosinophils (about 30%), or the presence of specific antibodies, is an indication of an allergic reaction.
Managing expected Herxheimer reactions
Herxheimer reactions are an unavoidable part of the long journey to recovery. Although herxing is often unpredictable, it can be managed with the correct use of Benicar, the judicious choice of antibiotic combinations, careful antibiotic dosing schedules, adjustment of antibiotic dosing and palliative medications. IT does not require eliciting a more severe herxing than a patient can tolerate in order to eliminate the bacteria.
As the number of dying bacteria is reduced with subsequent antibiotic doses, effective treatment requires increasing doses and changing antibiotic combinations to continue eliciting a Herxheimer response. The occurrence of herxing is seen as evidence of continuing elimination of these very persistent bacteria. Details of Herxheimer symptom management are in our Library of Information.
The goal is tolerable Herxheimer reactions
The goal of IT is to achieve and maintain tolerable Herxheimer reactions (physically, mentally, and emotionally) by adjustment of medications dosing and schedule, combined with the essential aspects of diligently avoiding sun/lights and vitamin D.
Those who have had to bear strong disease symptoms may have more difficulty defining the line between tolerable and intolerable immunopathology symptoms.
Understanding and acceptance is key
IT patients have made a determined choice to recover from, not just manage, their chronic illness. They understand and welcome Herxheimer reactions even when they must endure temporary increased suffering. They accept it as the ‘price’ they must pay in order to get well and even find it gratifying to experience tangible evidence of bacterial elimination. The gradual resolution of inflammatory symptoms as the treatment progresses is ample incentive to persist with this sometimes uncomfortable treatment.
Many IT patients say their doctors were initially unaware of the Herxheimer phenomenon. An increased awareness of the Herxheimer reaction by those who order IT will be of benefit to patients. Benicar and antibiotics then might be seen as the ally they are proving to be in fighting chronic inflammatory diseases.
How to reduce disability caused by Herxheimer reactions
Patients can help lessen the disability experienced during Inflammation Therapy if they:
The patient is expected to experience episodic Herxheimer reactions as long as antibiotic therapy is needed. The gradual resolution of symptoms has been noted to require months or years depending on the extent of Th1/Th17 inflammation. The Herxheimer reaction is a key component in evaluating the efficacy of each IT antibiotic, antibiotic combination or dosing schedule. The lack of a Herxheimer reaction when disease symptoms are still present signals a need for a change in dosing schedule or antibiotic.
Remission is determined by absence of symptoms, both objective and subjective.
Patient comments regarding Herxheimer reactions
”It is my observation and experience that the Herx is one of the most difficult things for people to understand. When symptoms "act up" they get the jitters - understandably, due to the years of disease and being so symptomatic. Many feel they are getting worse... But when the symptoms do occur as they do with Herx - I have witnessed that symptoms begin to fade and then never re-appear.
”Herx is an ongoing process of healing and very much a part of IT. It takes time - patience - and great deal of perseverance - to ride this out. For many who have been on the therapy for a long period of time - the valley and mountain feelings have been plentiful. But the end result is so worth the journey.”
Updated August 7, 2015