The Jarisch–Herxheimer reaction: Revisited

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Summary

The Jarisch–Herxheimer reaction (JHR) is a transient immunological phenomenon seen commonly in patients during treatment for syphilis, and it manifests clinically with short-term constitutional symptoms such as fever, chills, headache and myalgias, besides exacerbation of existing cutaneous lesions. The complex interplay of its underlying patho-physiological mechanisms continues to elude modern medicine, ever since it was described over a century ago. An increase in the incidence of JHR may be expected among patients co-infected with HIV and other infectious diseases including syphilis. Since this subject has not received much attention in recent literature except for brief mentions in standard textbooks, we felt it important to provide an overview of its various attributes including the current concepts in pathophysiology and management.

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Background

The Jarisch–Herxheimer reaction (JHR) is a well-known entity, the knowledge of which dates back to the 15th century, when arsenical ointment was used to treat the “great pox” (syphilis). The initial literary description was given by Adolf Jarisch (Austrian dermatologist) in 1895, when he noted exacerbation of lesions in roseolar syphilis patients after treatment with mercury.1 Subsequently, in 1902, Karl Herxheimer (German dermatologist) independently reported a similar phenomenon.2 The terms

Pathophysiological considerations

Despite advances in medicine, the exact mechanism of JHR remains obscure. Most of our understanding stems from research done in spirochetal infections in general. Over the years, many theories have been previously advanced to describe its pathophysiology.

Herxheimer postulated that the liberation of an endotoxin from degenerating treponemes following treatment of syphilis was the underlying mechanism. These products react with the “sensitized” syphilitic tissues and cause aggravation of lesions.2

Clinical characteristics of JHR

The reaction occurs within a few hours (2–8 h) after the administration of the first dose of an appropriate antibiotic, and usually resolves even without any intervention, in 24 h. The JHR is more severe in situations where the number of organisms is abundant and is characterized by a triad of transient events (fluctuation in body temperature, flare, physiological changes) as detailed below.6, 50

Fluctuation in body temperature is reflected by an elevation (39 °C–42 °C) and accompanied by

Investigations

The JHR is a transient clinical event and as such, no specific tests are available to diagnose the condition. However, a polymorphonuclear leucocytosis, lymphopenia and raised ESR have been reported.61 Histopathology of skin lesions during JHR reveals acute inflammatory changes (dermal edema, dilatation of small blood vessels and capillaries, perivascular and interstitial polymorphonuclear leucocytic and round cell infiltration) besides the existing syphilitic pathology. Subsiding lesions may

Differential diagnosis

The JHR is often mistaken for a drug reaction, especially to penicillin. Absence of features such as generalized urticaria/wheals and eosinophilia or specific antibodies to penicillin in the serum of patients with JHR, permit differentiation from penicillin allergy.50

A pseudo-anaphylactic reaction (Procaine Reaction or Hoigné syndrome) which is associated with inadvertent intracapillary infusion of procaine penicillin during an intramuscular injection, leading to microembolization of crystals

Complications

In early syphilis, the reaction may not be associated with major problems except for constitutional symptoms. However, complications due to JHR are predominantly seen in the late stages of syphilis and are a reflection of local flares in the organs involved. In neurosyphilis, febrile reactions occur more frequently when the CSF contains an increased number of cells and protein. The JHR assumes special importance in GPI where patients may be expected to experience sudden worsening of psychotic

Management

The JHR is a self-resolving condition that can be managed symptomatically. Patients must be forewarned about the possibility of a reaction, and the antibiotic treatment started initially must be fully completed. Complete bed rest, fluids and antipyretics such as aspirin or acetaminophen are adequate for mild cases (early syphilis) associated with constitutional symptoms. It is important to note that the symptoms and duration of JHR can only be minimised; it is not possible to prevent the

Conclusion

The JHR is a self-limiting reaction, the treatment of which is predominantly supportive. Its occurrence cannot be prevented, and therefore, it should be anticipated in all patients receiving antibiotic treatment for syphilis and other infectious diseases (Table 1), and the course of antibiotic treatment started initially must be fully completed. It is important to note that the occurrence of a JHR, at times, may point toward an undiagnosed syphilitic pathology in a patient receiving antibiotic

Source of support

None.

Conflict of interest

None.

Acknowledgments

None.

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    Formerly at Skin & VD Clinic, Hyderabad, AP, India.

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