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Year : 1995  |  Volume : 61  |  Issue : 3  |  Page : 180-181

Febrile herxheimer reaction

Neena Khanna, RK Pandhi 

Correspondence Address:
Neena Khanna

How to cite this article:
Khanna N, Pandhi R K. Febrile herxheimer reaction.Indian J Dermatol Venereol Leprol 1995;61:180-181

How to cite this URL:
Khanna N, Pandhi R K. Febrile herxheimer reaction. Indian J Dermatol Venereol Leprol [serial online] 1995 [cited 2019 Oct 21 ];61:180-181
Available from: http://www.ijdvl.com/text.asp?1995/61/3/180/4199

Full Text

 To the Editor,

Febrile Herxheimer reaction (FHR) is a transient exacerbation of mucocutaneous lesions along with fever, occurring when patients of early syphilis are treated with treponemicidal drugs. To the best of our knowledge, there are no studies on the incidence and symptomatology of FHR in patients of early syphilis.

Fifty-eight patients of previously untreated syphilis (19 with primary and 39 with secondary) were treated with 2.4 mega units of benzathine penicillin injected intramuscularly after ruling out sensitivity to pencillin. The diagnosis was confirmed in all cases by DGI and/or serology. The axillary temperature was recorded immediately before the injection and thereafter at hourly intervals for 48 hours. A rise in the axillary temperature to at least 37.4C was considered as a positive reaction. The patients were questioned regarding any change in preexisting skin lesions and/or appearance of any new lesions. They were also asked if any constitutional symptoms had developed during this period.

Fifteen (78.9%) patients with primary syphilis developed FHR. Eleven (73.3%) of these patients were seropositive, while 4 (26.7%) were seronegative. All the 4(100%) patients who did not develop FHR were seronegative. The mean of maximum axillary temperature recorded was 37.9C (0.77) and this was recorded on an average 7.5 (4.2) hours after the injection. Though the number of patients was small, there was a suggestion that patients with seronegative primary syphilis are less likely to develop FHR than those with seropositive primary lesions.

Four (26.7%) patients also developed swelling and tenderness of the primary ulcer and 2 patients developed a temporary phimosis. Two (13.4%) patients developed a transient maculopapular rash, and one developed generalised lymphadenopathy.

Thirty-five (89.7%) patients with secondary syphilis developed FHR. Of the 4 (10.3%) patients who did not 3(75%) had nodular syphilis, a manifestation of late secondary syphilis. The mean of maximum axillary temperature recorded was 38.0C(0.6) and this was recorded on an average 6.5(0.28) hours after treatment was initiated. In all but one patient, the febrile reaction subsided within 48 hours.

In 2 of the 5 patients who had evidence of concomitant chancre, there was oedema of the ulcer. Interestingly one patient developed oedema and ulceration at the site of healed primary ulcer. Eight (22.9%) patients developed new mucocutaneous lesions or noticed exacerbation of pre-existing lesions. Symptoms like headache, arthralgia, giddiness and sore throat developed in 18(51.4%) patients.

In an earlier study, Farmer[2] observed that FHR occurred with equal frequency in seronegative and seropositive primary syphilis. However, the present study corroborates the findings of Putkonen et al[3] who found that FHR occurred more frequently in seropositive than seronegative syphilis.

The reported frequency of FHR in secondary syphilis varies from 45% to 76%.[4]In the present study 89.7% of patients of secondary syphilis developed FHR. Of the 4 patients who did not develop the febrile reaction, 75% had nodular syphilis, a manifestation of late secondary syphilis. This suggests that FHR may be less common in late secondary syphilis.


1Morton RS. The Treponematosis. In: Textbook of dermatology (Champion RH, Burton JL, Ebling FJG, eds). 5th edn. Oxford: Blackwell Scientific Publications, 1992:1112-1113.
2Farmer TW. The Herxheimer reaction in early syphilis treated with crystalline penicillin G. JAMA 1948:138:480-5.
3Putkonen T, Salo OP, Mustakallio K. Febrile Herxheimer reaction in different phases of primary and secondary syphilis. Br J Ven Dis 1966;42:181-4.
4Aronson IK, Soltani K. The enigma of pathogenesis of the Jarisch-Herxheimer reaction. Br J Ven Dis 1976;52:313-5.


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