A Jarisch–Herxheimer reaction is a reaction to

endotoxin Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

-like products released by the death of harmful

microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in old ...

s within the body during antibiotic treatment.

Efficacious Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made between ...

antimicrobial therapy results in lysis (destruction) of bacterial cell membranes, and in the consequent release into the bloodstream of bacterial toxins, resulting in a systemic inflammatory response. Jarisch–Herxheimer reactions can be life-threatening as they can cause a significant drop in blood pressure and cause acute end-organ injury, eventually leading to multi-organ failure.

Signs and symptoms

It comprises part of what is known as

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

and occurs after initiation of

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

s when treating Gram-negative infections such as ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'' and louse- and tick-borne infections. It usually manifests in 1–3 hours after the first dose of antibiotics as

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

chills Chills is a feeling of coldness occurring during a high fever, but sometimes is also a common symptom which occurs alone in specific people. It occurs during fever due to the release of cytokines and prostaglandins as part of the inflammatory ...

rigor Rigour (British English) or rigor (American English; see spelling differences) describes a condition of stiffness or strictness. These constraints may be environmentally imposed, such as "the rigours of famine"; logically imposed, such as ma ...

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

hyperventilation Hyperventilation is irregular breathing that occurs when the rate or tidal volume of breathing eliminates more carbon dioxide than the body can produce. This leads to hypocapnia, a reduced concentration of carbon dioxide dissolved in the bloo ...

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...

with

flushing Flushing may refer to: Places * Flushing, Cornwall, a village in the United Kingdom * Flushing, Queens, New York City ** Flushing Bay, a bay off the north shore of Queens ** Flushing Chinatown (法拉盛華埠), a community in Queens ** Flushin ...

myalgia Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another li ...

(muscle pain), exacerbation of

skin lesion A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of th ...

s and anxiety. The intensity of the reaction indicates the severity of

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

. Reaction commonly occurs within two hours of drug

administration Administration may refer to: Management of organizations * Management, the act of directing people towards accomplishing a goal ** Administrative Assistant, traditionally known as a Secretary, or also known as an administrative officer, admini ...

, but is usually self-limiting.

Causes

The Jarisch–Herxheimer reaction is traditionally associated with antimicrobial treatment of

syphilis Syphilis () is a sexually transmitted infection caused by the bacterium '' Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, a ...

. The reaction is also seen in the other diseases caused by

spirochete A spirochaete () or spirochete is a member of the phylum Spirochaetota (), (synonym Spirochaetes) which contains distinctive diderm (double-membrane) gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or s ...

Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the '' Borrelia'' bacterium, which is spread by ticks in the genus '' Ixodes''. The most common sign of infection is an expanding red rash, known as erythema ...

relapsing fever Relapsing fever is a vector-borne disease caused by infection with certain bacteria in the genus '' Borrelia'', which is transmitted through the bites of lice or soft-bodied ticks (genus ''Ornithodoros''). Signs and symptoms Most people who ar ...

, and

leptospirosis Leptospirosis is a blood infection caused by the bacteria '' Leptospira''. Signs and symptoms can range from none to mild (headaches, muscle pains, and fevers) to severe ( bleeding in the lungs or meningitis). Weil's disease, the acute, sever ...

. There have been case reports of the Jarisch–Herxheimer reaction accompanying treatment of other infections, including

Q fever Q fever or query fever is a disease caused by infection with ''Coxiella burnetii'', a bacterium that affects humans and other animals. This organism is uncommon, but may be found in cattle, sheep, goats, and other domestic mammals, including ...

bartonellosis Bartonellosis is an infectious disease produced by bacteria of the genus ''Bartonella''. ''Bartonella'' species cause diseases such as Carrión's disease, trench fever, cat-scratch disease, bacillary angiomatosis, peliosis hepatis, chronic bac ...

brucellosis Brucellosis is a highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions. It is also known as undulant fever, Malta fever, and Mediterranean fever. The ...

trichinellosis Trichinosis, also known as trichinellosis, is a parasitic disease caused by roundworms of the ''Trichinella'' type. During the initial infection, invasion of the intestines can result in diarrhea, abdominal pain, and vomiting. Migration of l ...

, and

African trypanosomiasis African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species '' Trypanosoma brucei''. Humans are infected by two t ...

Pathophysiology

Lipoproteins A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, su ...

released from treatment of ''Treponema pallidum'' infections are believed to induce the Jarisch–Herxheimer reaction. The Herxheimer reaction has shown an increase in inflammatory

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...

s during the period of exacerbation, including

tumor necrosis factor alpha Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolo ...

interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...

and

interleukin-8 Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage ...

Treatments

Prophylaxis Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

and treatment with an

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...

agent may stop progression of the reaction. Oral

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus ar ...

every four hours for a day or 60 mg of

prednisone Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and ad ...

orally or

intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

has been used as an adjunctive treatment . However, steroids are generally of no benefit. Patients must be closely monitored for the potential complications (collapse and shock) and may require IV fluids to maintain adequate blood pressure. If available,

meptazinol Meptazinol (trade name Meptid) is an opioid analgesic developed by Wyeth in the 1970s. Indications for use in moderate to severe pain, most commonly used to treat pain in obstetrics (childbirth). Meptazinol is a 3-phenylazepane derivative, wher ...

, an opioid analgesic of the mixed agonist/antagonist type, should be administered to reduce the severity of the reaction. Anti TNF-α may also be effective.

History

Both Adolf Jarisch, an Austrian

dermatologist Dermatology is the branch of medicine dealing with the skin.''Random House Webster's Unabridged Dictionary.'' Random House, Inc. 2001. Page 537. . It is a speciality with both medical and surgical aspects. A dermatologist is a specialist medica ...

, and Karl Herxheimer, a German dermatologist, are credited with the discovery of the Jarisch–Herxheimer reaction. Both Jarisch and Herxheimer observed reactions in patients with

treated with mercury. The reaction was first seen following treatment in early and later stages of syphilis treated with Salvarsan, mercury, or

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and preventio ...

. Jarisch thought that the reaction was caused by a toxin released from the dying spirochetes.

References

External links

{{DEFAULTSORT:Jarisch-Herxheimer reaction Spirochaetes Symptoms Complications of surgical and medical care