Jarisch–Herxheimer Reaction
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A Jarisch–Herxheimer reaction is a sudden and typically transient reaction that may occur within 24 hours of being administered
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
for an infection by a
spirochete A spirochaete () or spirochete is a member of the phylum Spirochaetota (also called Spirochaetes ), which contains distinctive diderm (double-membrane) Gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or ...
, including
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...
,
leptospirosis Leptospirosis is a blood infection caused by the bacterium ''Leptospira'' that can infect humans, dogs, rodents and many other wild and domesticated animals. Signs and symptoms can range from none to mild (headaches, Myalgia, muscle pains, a ...
,
Lyme disease Lyme disease, also known as Lyme borreliosis, is a tick-borne disease caused by species of ''Borrelia'' bacteria, Disease vector, transmitted by blood-feeding ticks in the genus ''Ixodes''. It is the most common disease spread by ticks in th ...
, and
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, soft-bodied ticks (genus '' Ornithodoros''), or hard-bodied ticks (Genus Ixodes). ...
. Signs and symptoms include
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
,
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 ...
, shivers, feeling sick, headache, fast heart beat, low blood pressure, breathing fast, flushing of skin, muscle aches, and worsening of skin lesions. It may sometimes be mistaken as an allergy to the antibiotic. Jarisch–Herxheimer reactions can be life-threatening because 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 is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
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. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'' and louse- and tick-borne infections. It usually manifests in 1–3 hours after the first dose of antibiotics as
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
,
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, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...
,
headache A headache, also known as cephalalgia, 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 (mood), depression in those with severe ...
,
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 blo ...
,
vasodilation Vasodilation, also known as vasorelaxation, 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. Blood vessel wa ...
with flushing,
myalgia Myalgia or muscle pain is a painful sensation evolving from muscle tissue. It is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likely cause is viral infection, espec ...
(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 this ...
s and anxiety. The intensity of the reaction indicates the severity of
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
. 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: the process of dealing with or controlling things or people. ** Administrative assistant, traditionally known as a se ...
, 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 depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...
. The reaction is also seen in the other diseases caused by
spirochete A spirochaete () or spirochete is a member of the phylum Spirochaetota (also called 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 tick-borne disease caused by species of ''Borrelia'' bacteria, Disease vector, transmitted by blood-feeding ticks in the genus ''Ixodes''. It is the most common disease spread by ticks in th ...
,
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, soft-bodied ticks (genus '' Ornithodoros''), or hard-bodied ticks (Genus Ixodes). ...
, and
leptospirosis Leptospirosis is a blood infection caused by the bacterium ''Leptospira'' that can infect humans, dogs, rodents and many other wild and domesticated animals. Signs and symptoms can range from none to mild (headaches, Myalgia, muscle pains, a ...
. 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,
brucellosis Brucellosis is a zoonosis spread primarily via ingestion of raw milk, unpasteurized milk from infected animals. It is also known as undulant fever, Malta fever, and Mediterranean fever. The bacteria causing this disease, ''Brucella'', are small ...
, trichinellosis, and
African trypanosomiasis African trypanosomiasis is an insect-borne parasitic infection of humans and other animals. Human African trypanosomiasis (HAT), also known as African sleeping sickness or simply sleeping sickness, is caused by the species ''Trypanosoma bru ...
.


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, sur ...
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 produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s during the period of exacerbation, including
tumor necrosis factor alpha Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...
,
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, is the application of healthcare measures to prevent diseases.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental health a ...
and treatment with an
anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...
agent may stop progression of the reaction. Oral
aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...
or
ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...
every four hours for a day or 60 mg of
prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, 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 ...
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 nutr ...
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, 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 medi ...
, 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
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...
treated with mercury. The reaction was first seen following treatment in early and later stages of syphilis treated with
Salvarsan Arsphenamine, also known as Salvarsan or compound 606, is an antibiotic drug that was introduced at the beginning of the 1910s as the first effective treatment for the deadly infectious diseases syphilis, relapsing fever, and African trypanosomias ...
, 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 pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
. Jarisch thought that the reaction was caused by a toxin released from the dying spirochetes.


See also

* Jarisch-Bezold reflex * Immune reconstitution inflammatory syndrome, another systemic inflammatory syndrome that arises after antimicrobial treatment


References


External links

{{DEFAULTSORT:Jarisch-Herxheimer reaction Spirochaetes Symptoms Complications of surgical and medical care Diseases named after discoverers