Jarisch-Herxheimer Reaction in a Patient with Neurosyphilis

J7ournal ofNeurology, Neurosurgery, and Psychiatry 1994;57:865-867 865

LESSON OF THE MONTH J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.7.865 on 1 July 1994. Downloaded from

Jarisch-Herxheimer reaction in a patient with neurosyphilis

U Zifko, K Lindner, D Wimberger, B Volc, W Grisold

Abstract Case history A 40 year old man. presented with pro- A 40 year old white man, an unskilled gressive personality changes in the pre- worker, was admitted with progressive per- vious six months. Specific serological sonality changes. There was a history of pri- tests for syphilis in blood and CSF were mary syphilitic infection 17 years previously. highly positive and CSF sedimentation Specific serological tests for syphilis in blood showed signs of an inflammatory and CSF were highly positive (table). process. Ten hours after the start of Cytology of CSF showed 24/mm2 cells and penicillin treatment a severe sympto- sedimentation showed signs of an inflamma- matic Jarisch-Herxheimer reaction with tory process with activated lymphocytes, alteration of level of consciousness, granulocytes, and phagocytes. Protein con- pupillary changes, and focal neurological centration in CSF was 1 56 g/l (normal range signs developed. 0-15-0-45 g/1). Jarisch-Herxheimer reaction may The patient was orientated with reduced occur in various settings, particularly in concentration, memory loss, tendency to per- the treatment of syphilis. Investigation of severation, and impairment of reasoning and CSF before the treatment may predict a critical faculties. Productive psychosis did not potential risk. Corticosteroid treatment occur. Physical examination, routine serum has been suggested for prevention. chemistry, EEG, and CT (with and without contrast enhancement) were normal. Cranial (7 Neurol Neurosurg Psychiatry 1994;57:865-867) MRI showed Ti weighted hypointense and Department of T2 weighted hyperintense (not sharply deli- Neurology, Kaiser nated) lesions towards the underlying white Franz Josef Spital, An increase in Jarisch-Herxheimer reaction matter in both frontal lobes. The adjacent 1100 Vienna, Austria U Zifko may be expected, related to an increase in the cortex was thinned, and CSF spaces over K Lindner incidence of neurosyphilis due to a rise in pri- both frontal lobes were slightly enlarged. W Grisold mary and secondary syphilis in connection After starting intravenous treatment with 5 Department of with HIV infections.' 2 In late syphilis treated million units of sodium penicillin G every

Radiology, University with penicillin, neurosyphilis constitutes the four hours, a symptomatic Jarisch- http://jnnp.bmj.com/ ofViennal Neuroradiology, 1090 chief hazard. Jarisch-Herxheimer reaction has Herxheimer reaction developed. Ten hours Vienna, Austria been reported to occur in up to 75% of after the first dose of penicillin the patient D Wimberger patients with dementia paralytica (general was febrile (38 8°C), sweating, and had a Department of paralysis of the insane).3 The clinical spec- heart rate of 120-140 beats/min. The level of Dermatology, trum of Jarisch-Herxheimer reaction varies. consciousness was University ofVienna, fluctuating. He developed 1090 Vienna, Austria Minor reaction includes febrile temperatures, anisocoria with sluggish pupillary light reac- B Volc headache, myalgia, and malaise. Some tion, but unimpaired pupillary near reaction. on October 1, 2021 by guest. Protected copyright. Correspondence to: patients with Jarisch-Herxheimer reaction The next day his temperature returned to Dr Udo Zifko, Neurologische Abteilung, have convulsions, an altered state of con- normal, but he remained disorientated with Kaiser Franz Josef Spital, sciousness, focal neurological signs, and psychomotor restlessness. In the subsequent KundratstraI3e 3, A- 1100 Vienna, Austria. psychiatric manifestations. Fatalities due to days, as well as impaired consciousness, later- Received 24 June 1993 Jarisch-Herxheimer reaction in patients with alisation of tendon reflex accentuation Accepted 14 November 1993 late syphilis have also been described.34 changed several times. Although he could understand plain commands, he was only able to utter simple words. The focal neurological signs disappeared within one week. An atonic bladder with urinary retention and Serological results overflow developed and persisted for several months. March 1991 September 1991 March 1992 An EEG on the first day of Jarisch- Blood CSF Blood CSF Blood CSF Herxheimer reaction showed generalised VDRL 1:1 1:1 - - - - abnormality with 3/s rhythmic activity (peri- TPHA 1:40960 1:20840 1:10240 1:5120 1:10240 1:1280 odic lateralised epileptiform discharges), FTA-ABS + + + + + + IgM-SPHA 1:8 1:4 1:8 1:4 1:8 1:2 which has been described in patients with neurosyphilis.5-7 The rhythmic activity disap- + = Reactive; - = non-reactive; VDRL = venereal disease research laboratory slide test; TPHA = Treponema pallidum haemagglutination assay; FTA-ABS = fluorescent treponemal peared within a week, but generalised antibody-absorption; IgM-SPHA = IgM-Solid-phase haemabsorption. changes persisted; EEG returned to normal 866 Zifko, Lindner, Wimberger, Volc, Grisold

after two weeks. Repeated CT was normal. A migrate through the vessel wall into the sur- meningovascular syphilis therefore seemed rounding oedematous connective tissue.22 A unlikely. peripheral leucocytosis and lymphopenia J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.7.865 on 1 July 1994. Downloaded from The response to treatment was confirmed usually accompanies these histological alter- by specific tests for syphilis six months and ations.4 one year later (table). Jarisch-Herxheimer reaction cannot be pre- dicted on reliable indices. The frequency of reactions increases proportionally with white Discussion cell count and total protein in CSF. Historically the discovery of syphilis was Hoekenga et al 17 found the highest incidence quickly followed by the recognition of an of Jarisch-Herxheimer reaction in patients acute reaction precipitated by specific treat- with dementia paralytica and in whom both ment.8 The overt clinical features of the reac- cell count and protein content in CSF were tion were described in 1895 by Jarisch9 and in raised. Incidence is not related to race or sex, 1902 by Herxheimer and Krause.'0 duration of infection with syphilis, serological Similar reactions have been reported after titre, or dose of penicillin. Luetic manifes- treatment of other spirochetal infections tations such as gummas of the brain and of (louse-borne relapsing fever, Vincent's the larynx,3 aortic aneurysm due to syphilitic angina, rat bite fever, leptospirosis, yaws)," aortitis,3 luetic optic neuritis,23 and involve- other bacterial infections (brucellosis, ment of the auditory nerve24 have been tularaemia, glanders, and anthrax)," and of described as having a potential risk for a dra- African trypanosomiasis. 12 Singular reports matic course ofJarisch-Herxheimer reaction. describe Jarisch-Herxheimer reaction in treat- The value of steroids in prevention of ment of Pneumocystis carinii pneumonia,'3 Jarisch-Herxheimer reaction remains un- meningococcal meningitis,'4 and falciparium proved. Corticosteroids have been reported to malaria. 'I exert some positive effect,2526 and the use of In neurosyphilis Jarisch-Herxheimer reac- corticosteroids (30-50 mg prednisone) before tion may take one or both of two forms: antibiotic treatment is recommended.27 28 either a transient rise in temperature, chill, Although corticosteroids are able to reduce headache, malaise, myalgia during the first 24 fever, they are not thought to prevent symp- hours after treatment with the drug (asympto- tomatic Jarisch-Herxheimer reaction.29 It has matic type) or an exacerbation of mental been argued that the benefits they provide symptoms or other neurological signs during may be outweighed by the risks involved.26 In the first days (symptomatic type). luetic organ manifestations like gumma and In the symptomatic type the variety of mesaortitis luetica, the use of corticosteroids manifestations is related to the type of neu- seems justified. rosyphilis. Patients with asymptomatic neu- Other attempts to prevent Jarisch- rosyphilis rarely have Jarisch-Herxheimer Herxheimer reaction by treatment with reaction. Patients with dementia paralytica antihistamines, bismuth, and initial use of may react with convulsions, exacerbations of low doses of penicillin have been unsuc- the existing psychoses, or focal neurological cessful.430 3' Meptazinol has been shown to signs. The symptoms of patients with tabes diminish the Jarisch-Herxheimer reaction of dorsalis (locomotor ataxia) consisting of louse-born fever,2'32 but its use with treat- lightning pains, urinary retention, and ment of syphilis has not been reported. http://jnnp.bmj.com/ constipation may be temporarily intensified Treatment of Jarisch-Herxheimer reaction during treatment or may appear for the first depends on symptoms. The occurrence of time. Jarisch-Herxheimer reaction may also Jarisch-Herxheimer reaction is not an indica- be lethal, particularly in patients with gum- tion for discontinuing treatment. It is useful mas of the brain or coexisting mesaortitic to monitor cardiovascular function and con- aneurysm.3 trol temperature every two hours during the

No recent data are available concerning the first 48 hours from the start of any treatment on October 1, 2021 by guest. Protected copyright. incidence of Jarisch-Herxheimer reaction in for neurosyphilis. neurosyphilis. In older reports'6 17 asympto- Although Jarisch-Herxheimer reaction in matic reactions occur in 13% to 54%, neurosyphilis is rare and usually the asympto- symptomatic reactions in 1 7% to 1 % of matic type occurs, a symptomatic form may patients. take a dramatic course, as in our patient, with Pathogenesis of Jarisch-Herxheimer reac- deterioration of existing symptoms and the tion remains poorly understood. Numerous occurrence of additional neurological symp- mechanisms, such as release of treponemal toms. breakdown products,9 hypersensitisation phe- nomena,'8 allergic origin,'9 endotoxaemia,2' 1 Berger JR. Neurosyphilis in human immunodeficiency and opioid withdrawal reaction2' have been virus type 1-seropositive individuals. Arch Neurol 1991;48:700-2. proposed, but the exact cause remains 2 Savall R, Cabre M, Grifol M. Neurosyphilis and human obscure. mmunodeficiency virus type 2 infection. Arch Neurol 1992;49:440. Histologically, Jarisch-Herxheimer reaction 3 Scott V, Maxwell RW, Skinner JS. The Jarisch- is manifest by acute inflammatory changes Herxheimer phenomen in late syphilis. JAMA 1949; 139:217-20. within syphilitic lesions. Capillaries and veins 4 Aronson IK, Soltani K. The enigma of the pathogenesis of become congested, followed by swelling of the Jarisch-Herxheimer reaction. Br J Vener Dis 1976; 52:313-5. the endothelial cells. Polymorphonuclear 5 Hooshmand H. Seizure disorders associated with neuro- neutrophils and mononuclear leucocytes syphilis. Dis Nerv Syst 1976;37:133-6. J7arisch-Herxheimer reaction in a patient with neurosyphilis 867

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