The Herxheimer reaction resembles bacterial sepsis and can occur after initiation of antibiotic therapy (such as penicillin or tetracycline) or treatment of tick-borne relapsing fever. An association has been found between the release of heat-stable proteins from spirochetes and the reaction. The same can be true for candida die-off when toxins from the dying candida leak into the body. Typically the death of these bacteria and the associated release of endotoxin

Endotoxin

Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:...

s occurs faster than the body can remove the toxins. It is manifested by fever, chills, rigor, hypotension, headache, tachycardia, hyperventilation, vasodilation with flushing, myalgia

Myalgia

Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...

 (muscle pain), and exacerbation of skin lesions. The intensity of the reaction reflects the intensity of inflammation present. Reaction commonly occurs within 2 hours of drug administration, but is usually self-limiting. Prophylaxis and treatment with an anti-inflammatory agent may stop progression of the reaction. Oral aspirin every 4 hours for 1-2 days or 60 mg of prednisone by mouth or intravenously has been used as an adjunctive treatment.

It is classically associated with penicillin treatment of syphilis

Syphilis

Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

. Duration in syphilis is normally only a few hours. The reaction is also seen in other diseases caused by spirochetes, such as borreliosis

Borrelia

Borrelia is a genus of bacteria of the spirochete phylum. It causes borreliosis, a zoonotic, vector-borne disease transmitted primarily by ticks and some by lice, depending on the species...

 (Lyme disease

Lyme disease

Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...

 and tick-borne relapsing fever

Relapsing fever

Relapsing fever is an infection caused by certain bacteria in the genus Borrelia. It is a vector-borne disease that is transmitted through the bites of lice or soft-bodied ticks.-Louse-borne relapsing fever:...

) and leptospirosis

Leptospirosis

Leptospirosis is caused by infection with bacteria of the genus Leptospira, and affects humans as well as other mammals, birds, amphibians, and reptiles.The...

, and in Q fever

Q fever

Q 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 cats and dogs...

. Similar reactions have also been reported to occur in bartonellosis

Bartonellosis

Bartonellosis is an infectious disease produced by bacteria of the genus Bartonella. Bartonella species cause diseases such as Carrión´s disease, trench fever, and cat scratch disease, and other recognized diseases, such as bacillary angiomatosis, peliosis hepatis, chronic bacteremia, endocarditis,...

 (including cat scratch disease

Cat scratch disease

Cat scratch disease is a usually benign infectious disease caused by the intracellular bacterium Bartonella. It is most commonly found in children following a scratch or bite from a cat by about one to two weeks...

), brucellosis

Brucellosis

Brucellosis, also called Bang's disease, Crimean fever, Gibraltar fever, Malta fever, Maltese fever, Mediterranean fever, rock fever, or undulant fever, is a highly contagious zoonosis caused by ingestion of unsterilized milk or meat from infected animals or close contact with their secretions...

, typhoid fever

Typhoid fever

Typhoid fever, also known as Typhoid, is a common worldwide bacterial disease, transmitted by the ingestion of food or water contaminated with the feces of an infected person, which contain the bacterium Salmonella enterica, serovar Typhi...

, and trichinosis

Trichinosis

Trichinosis, also called trichinellosis, or trichiniasis, is a parasitic disease caused by eating raw or undercooked pork or wild game infected with the larvae of a species of roundworm Trichinella spiralis, commonly called the trichina worm. There are eight Trichinella species; five are...

.

Pathophysiology

The Herxheimer reaction has shown an increase in inflammatory cytokines during the period of exacerbation, including tumor necrosis factor alpha, interleukin-6 and interleukin-8.

History

Both Adolf Jarisch

Adolf Jarisch

Adolf Jarisch was an Austrian dermatologist born in Vienna. He studied medicine in Vienna, and afterwards worked in the dermatology clinic of Ferdinand von Hebra . Later he became head of the dermatology clinic at the Universities of Innsbruck and Graz...

, an Austrian dermatologist

Dermatology

Dermatology is the branch of medicine dealing with the skin and its diseases, a unique specialty with both medical and surgical aspects. A dermatologist takes care of diseases, in the widest sense, and some cosmetic problems of the skin, scalp, hair, and nails....

, and Karl Herxheimer

Karl Herxheimer

Karl Herxheimer was a German-Jewish dermatologist who was a native of Wiesbaden.In 1885 he received his doctorate at Würzburg, and later worked with his brother, Salomon Herxheimer in Frankfurt-am-Main...

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

Syphilis

Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

 treated with mercury

Mercury (element)

Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...

. The reaction was first seen following treatment in early and later stages of syphilis treated with Salvarsan, mercury, or antibiotics. It is seen in 50% of patients with primary syphilis and about 90% of patients with secondary syphilis.