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We present a case of middle-aged woman whose health problems began 3 months after a registered tick bite in endemic area of Lyme borreliosis. First symptoms included fatigue, chills, cervical lymphadenopathy, neck pain and stiffness. Patient was afebrile. Lyme disease was excluded due to lack of erythema migrans and negative enzyme immunoassay test results for anti-Borrelia antibodies. During the next few months, her condition was getting worse and symptoms were accompanied with brain fog, dizziness, palpitations, irregular menstrual cycles, insomnia, panic attacks, headaches, and muscle aches. This led to multiple medical tests and examinations, but the diagnosis failed to be established. Finally, after occurrence of paresthesia and weakness of leg muscles, clinical diagnosis of disseminated Lyme borreliosis with nervous system involvement was suspected and antibiotic therapy was initiated. After the second dose of ceftriaxone, patient got fever and her condition worsened. However, ceftriaxone therapy was continued for a total of 5 days and was followed by 4 weeks of doxycycline therapy. Upon completion of antibiotic therapy, high specific anti-Borrelia antibodies were detected by Western blot and SeraSpot. Appearance of anti-Borrelia antibodies, in contrast to negative test results performed immediately before the therapy started, indicated seroconversion. 18 months after the therapy, patient was completely without the symptoms. This paper emphasizes importance of clinical evaluation of Lyme disease and shows a unique case of seroconversion in patient with symptoms of disseminated Lyme disease. Seroconversion was likely triggered by release of lipoproteins and other immunogenic molecules from Borrelia once the bacterial die-off began due to antibiotic therapy.

Tick-borne relapsing fever (TBRF) is an infection caused by Borrelia spirochetes. In North America, Borrelia hermsii is the most common cause for TBRF. This vector-borne disease is transmitted by Ornithodoros hermsi, a soft-bodied tick found in high altitudes in northwestern United States and southwestern Canada. Once bitten by the tick and infected by B. hermsii, episodes of fever alternating with afebrile periods can occur. A case of TBRF in a pregnant host was complicated by Jarisch-Herxheimer reaction requiring critical care. This case emphasizes the importance of maintaining a high index of suspicion in TBRF. Clinician recognition, diagnosis and treatment of TBRF as well as public awareness of strategies to prevent tick bites should be strengthened.

ObjectivesThe objective of this article was to present the clinical peculiarity of the Jarisch-Herxheimer reaction (JHR) during antibiotic treatment of Lyme arthritis.Material and methodsCase study presentation as a basis for discussion, literature search of PubMed database particularly in the subject of combination of the JHR and Lyme borreliosis using the combination of words “Jarisch-Herxheimer reaction” and “Lyme borreliosis”, “Lyme arthritis”, “antibiotic treatment”, “generalized inflammation”, “cytokine production”, “children”, “increasing awareness”; discussion of the problem based on a clinical case and cited articles.ResultsThe authors present a case of Lyme arthritis in a 13-year-old boy, as well as a discussion of clinical features of this complication of Lyme disease treatment as the Jarisch-Herxheimer reaction. On the 7th day of doxycycline treatment the patient’s condition deteriorated: a low-grade fever occurred, and severe arthralgias with intense hip, ankle and cervical spine pain and myalgias developed. Erythrocyte sedimentation rate and C-reactive protein were elevated. The Jarisch-Herxheimer reaction was diagnosed. This complication was characterized by severity, long duration and marked signs of inflammation.ConclusionsIn the reviewed literature the Jarisch-Herxheimer reaction in patients with Lyme borreliosis is described more often in adults, with mild course and short duration of the disease. Based on the presented clinical picture this severe complication may also be associated with long duration and marked signs of inflammation. The authors suggest that informing health professionals about occurrence of the Jarisch-Herxheimer reaction should help physicians to distinguish it from allergic reactions or other conditions and improve treatment outcomes.

Objectives The Jarisch-Herxheimer reaction (JHR) is a febrile inflammatory reaction that may occur in patients after treatment of syphilis. The overall rate is estimated to be 10-25% with broad variations over time. It appears to be related to factors like stage of the disease or reagin titres. In this study, we aimed to describe the incidence of and risk factors including strain typing for JHR among patients with syphilis. Methods From January through October 2015, 224 consecutive patients (82 of them with HIV) who were diagnosed with early syphilis were enrolled in this prospective observational study in a referral STI clinic in Barcelona. An appointment was offered to them after 10-14 days of treatment to inquire about the reaction with the use of a standardized form. Treponema pallidum molecular typing was made to detect a possible strain related to reaction. Results Overall, 28% of patients developed JHR. This varied from 56% in secondary, 37% in primary to 7% in early latent syphilis. The most frequent types of reaction were fever (57.5%) and worsening of the lesions (31%). The median time to development of JHR was 6 h [IQR 4-10 h] and lasted a median of 9 h [IQR 4-24 h]. The JHR was less probable in early latent compared to primary/secondary syphilis (P = 0.04) and in patients treated with doxycycline compared to those treated with penicillin (P = 0.01). No differences were seen regarding reagin titres or HIV status, and no association with a specific strain was found. Conclusions In this study, JHR occurred in a similar frequency as in other contemporary studies. Symptomatic syphilis and treatment with penicillin were associated with an increased risk of JHR, whereas the previous episode of syphilis was associated with a low risk of it. We could not find associations with specific strains of T. pallidum.

The Jarisch-Herxheimer reaction (JHR) typically occurs after the initiation of antibiotic treatment in syphilis. Although JHR was identified and looked at over many years, the prevention and management of JHR remain unclear. Previous reports have described the occurrence of JHR due to antibiotic treatment in syphilis, we presented a case of a young man with recurrence of JHR in syphilis, first due to penicillin which later was worsened due to co-trimoxazole.

Jarisch-Herxheimer reaction (JHR) is an acute and self-limited condition, which commonly occurs after treatment for spirochetal infections. Probably, it corresponds to a transient immunological reaction to endotoxin-like products released from the microorganism during the therapy. For this reason, JHR may be associated with many other infectious diseases besides syphilis. Here, we report a case of a patient affected by extended cutaneous candidiasis diagnosed by culture examination; a JHR occurred after an accidental overdose of oral fluconazole.

It has long been acknowledged that syphilis is a disease with a diverse range of presentations. We herein describe a case of a young man who presented with fever, rash, and eosinophilia following the commencement of allopurinol, only to be diagnosed with secondary syphilis on histopathology. His treatment was complicated by a severe exacerbation of his cutaneous eruption following the commencement of penicillin, likely secondary to a Jarisch–Herxheimer reaction, an entity often overlooked by clinicians managing syphilis.

Background Syphilis has returned to china with a vengeance since the 21st century, and the epidemiology of neurosyphilis has largely paralleled that of active syphilis. Prompt therapy with high-dose intravenous benzylpenicillin is critical to alleviate clinical symptoms of neurosyphilis patients. However, patients may experience an exacerbation of mental and/or neurological symptoms following the initiation of treatment due to a severe Jarisch-Herxheimer reaction (JHR) in central nervous system (CNS). We retrospectively analyzed the incidence, risk factors and prognosis for JHR in CNS in Shanghai Skin Disease Hospital, China. Methods From July 1, 2017 to December 31, 2018 at our sexually transmitted disease ward, 574 neurosyphilis patients received the high-dose intravenous benzylpenicillin. Patient factors were recorded, including age, gender, neurosyphilis type, serum and cerebrospinal fluid-venereal disease research laboratory test (CSF-VDRL) titer, white blood cell count and protein level of CSF, accompanying symptoms, clinical management and prognosis. Results All patients were HIV negative. The total incidence of JHR in CNS was 7.14% (41/574, 95% CI: 5.23–9.65%), being the most frequent among patients with general paresis. The mean timing of JHR after the initial dose of benzylpenicillin was to start at 6 hours (range: 0.5–13), peak at 8 hours (range: 0.5–20), and subside by 17 hours (range: 10–30). Besides fever and chills, the main symptoms were hallucination, paranoia, aggressive behavior, mental depression, cognitive impairment, confusion, urinary incontinence, stupor, convulsion and seizures in descending order. The JHR was significantly related to higher CSF-VDRL titer, pleocytosis, no usage of antibiotics in the last 6 months (p Conclusion Higher CSF-VDRL titer, pleocytosis and no recent usage of antibiotics were associated with an increased risk for JHR in CNS. Therapy of neurosyphilis can be continued with intensive surveillance. Disclosure No significant relationships.

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease’s causative pathogen, the spirochete bacteriumBorrelia recurrentis, is confined to humans and transmitted by a single vector, the human body lousePediculus humanus corporis. Since the disease was at its peak before the days of modern medicine, many of its aspects have never been formally studied and to date remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF since the recognition of its mode of transmission in 1907, and summarized the existing data on mortality, Jarisch–Herxheimer reaction (JHR), and impact on pregnancy.Publications were identified by using a predefined search strategy of electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases.The high mortality rates often found in literature are confined to extreme scenarios. The case fatality rate (CFR) of untreated cases is on average significantly lower than frequently assumed. In recent years, a rise in the overall CFRs is documented, for which reasons remain unknown.Lacking standardized criteria, a clear diagnostic threshold defining antibiotic treatment-induced JHR does not exist. This explains the wide range of occurrence rates found in literature. Pre-antibiotic era data suggest the existence of a JHR-like reaction also in cases treated with arsenicals and even in untreated cases.LBRF-related adverse outcomes are observed in 3 out of 4 pregnancies.

Background Leptospirosis is a zoonotic disease known to have wide-ranging clinical manifestations. Despite a number of published case series, culture-confirmed series are few and there is a paucity of data on Jarisch-Herxheimer reaction (JHR) associated with treatment of leptospirosis. Our objective was to describe the clinical and epidemiological factors associated with leptospirosis in an endemic area of Japan, with a focus on the occurrence of JHR, an often unrecognized and likely underestimated phenomenon. Methods We performed a retrospective observational study of laboratory-confirmed leptospirosis at a single center over a 40-year period. Results We report 100 leptospirosis cases in 99 patients during the period 1974-2015. Seventy-four cases were diagnosed by culture, representing eight different serovars. JHR was seen in 23 (82%) of 28 cases, including 19 (90%) of 21 cases treated with bactericidal antibiotics compared to 4 (57%) of seven cases with bacteriostatic antibiotics (p=0.08). Conclusions We found a wide variety of clinical manifestations, epidemiological exposures, and causative serovars of disease in an endemic region of Japan. We also found that JHR occurs frequently, and its recognition may be important for the diagnosis and management of leptospirosis in the early stage when laboratory confirmation is pending.

Background | Relapsing fever is divided into tick borne relapsing fever (TBRF) and louse borne relapsing fever (LBRF). This report describes 25 refugees from East Africa who were diagnosed to suffer from LBRF within a period of 6 month only at a single hospital in Munich / Germany. Material & Methods | The aim was to point out common clinical features as well as laboratory findings and clinical symptoms before and after initiation of treatment in 25 patients with louse borne relapsing fever (LBRF) who were diagnosed and treated at Klinikum Munchen Schwabing from August 2015 to January 2016. To the best of our knowledge this is the largest case series of LBRF in the western world for decades. Main focus of the investigation was put on clinical aspects. Results | All 25 patients suffered from acute onset of high fever with chills, headache and severe prostration. Laboratory analysis showed high CRP and a marked thrombocytopenia. A Giemsa blood stain was procured immediately in order to look for malaria. In the blood smear spirochetes with typical shape and aspect of borrelia species could be detected.The further PCR analysis confirmed infection with Borrelia recurrentis. Treatment with Doxycycline was started forthwith. The condition improved already on the second day after treatment was started and all were restored to health in less than a week. Apart from a mild to moderate Jarisch-Herxheimer-reaction we didn`t see any side effects of the therapy. Conclusion | LBRF has to be taken into account in feverish patients who come as refugees from East-Africa. It seems that our patients belong to a cluster which probably has its origin in Libya and more patients are to be expected in the near future. As LBRF might cause outbreaks in refugee camps it is pivotal to be aware of this emerging infectious disease in refugees from East-Africa.

Objectives The literature suggests that the Jarisch-Herxheimer (J-H) reaction following antimicrobial treatment of syphilis is common and may precipitate uterine activity. Local practice is to treat syphilitic parturients beyond gestational age of viability at a tertiary care centre. The objective of this project was to delineate the local incidence of and risk factors for the J-H reaction among pregnant women receiving treatment for syphilis. Methods A retrospective chart review was conducted including pregnant women diagnosed with syphilis and treated during pregnancy at our centre between 2012–2018. J-H reaction was defined as having one or more of the following within 48 h of antibiotic treatment: fever (temperature >38C), rash, uterine contractions or documented decelerations in FHR. Descriptive statistical analysis was performed using SAS (v9.4) with mean and median used as measures of central tendency for continuous and categorical data, respectively. Results Sixty-six charts were eligible for inclusion. The mean maternal age was 24.8 ± 5.10 years and mean gestational age was 20.4 ± 9.46 weeks when syphilis was diagnosed. The proportion of patients in late latent, early latent, secondary and primary syphilis were 5.26%, 38.5%, 10.5% and 26.3%, respectively. Two patients (2/66, 3%) met criteria for J-H reaction. The mean gestational age of delivery was 37.1 ± 3.46 and one stillbirth (1.5%) was identified. Conclusions The J-H reaction is less common at our center than the literature would suggest. We should re-evaluate the necessity of having syphilitic parturients beyond gestational age of viability travel to tertiary care centres for treatment.

Objective: The worldwide increase in the incidence of syphilis necessitates alertness to the occurrence of neurosyphilis. Early recognition of neurosyphilis allows for timely treatment, leading to a better treatment outcome. This retrospective study aims to describe the clinical presentation of neurosyphilis in a recent series of neurosyphilis patients. Method: All patients were included with a new, laboratory confirmed, diagnosis of neurosyphilis in the period 2004-2018. The clinical data were analysed. Results: 34 neurosyphilis patients (1 woman and 33 men) were identified. Age varied from 31-84 years (median age: 44 years). A history of syphilis infection was known for 11 (32%) patients; 12 (35%) patients were HIV seropositive. The distribution of the clinical syndromes was as follows: 16 patients with early neurosyphilis (acute meningitis, meningovasculitis and/or uveitis), 9 patients with late neurosyphilis (General Paralysis of the Insane and/or Tabes Dorsalis), 2 patients with symptoms of both early and late neurosyphilis, 6 patients with asymptomatic neurosyphilis and in 1 patient insufficient data were available to determine a clinical syndrome. Early neurosyphilis was seen in all age categories, late neurosyphilis only occurred in patients > 40 years. Conclusions: Neurosyphilis occurs in adults in all age groups, in men more frequent than in women, often in HIV-infected patients, and can present with a wide range of clinical syndromes. Usually no previous infection with syphilis is known.

Jarisch-Herxheimer reaction (JHR) is defined as a transient immunologic reaction, classically seen in patients during syphilis treatment. JHR is a rare cause of status epilepticus (SE) in neurosyphilis. We describe a case of generalized convulsive SE (GCSE) probably secondary to JHR in a patient with neurosyphilis.A 23-year-old man presented with progressive behavioral changes with 4 months of onset and pupillary alteration with 9 months of onset. He had experienced blurred vision and had noticed mydriasis in the left eye. Brain magnetic resonance imaging was normal; however, sexually transmitted infections were not investigated. After 1 month, the blurred vision disappeared, but mydriasis remained. Three months passed, and he reported progressive behavioral changes. Laboratory tests were within the normal limits, except by positive blood venereal disease research laboratory. Later, the cerebrospinal fluid analysis was requested, which revealed a positive venereal disease research laboratory. Electroencephalogram and brain magnetic resonance imaging were normal. Treatment was started with crystalline penicillin G. A GCSE began 12 hours after the first dose of penicillin. He did not develop classic signs and symptoms of the JHR. An EEG showed periodic lateralized epileptiform discharges.To the author's knowledge, there are 3 cases in the literature of nonconvulsive SE with JHR in neurosyphilis, and the present report was the first to describe the occurrence of GCSE secondary to JHR in neurosyphilis. Another important finding, in this case, was the isolated unilateral mydriatic tonic pupil, rarely reported as an early isolated symptom of neurosyphilis. In this way, it is essential that patients presenting with isolated unilateral tonic pupil receive an adequate investigation for syphilis.

The Jarisch-Herxheimer reaction (JHR) is a transient inflammatory syndrome triggered hours after the start of antibiotic treatment of spirochete infections, namely syphilis. Clinically, JHR manifests as an abrupt onset of constitutional symptoms and exacerbation of cutaneous lesions that resolve without intervention. JHR's pathogenesis is unclear and it is histopathologically rarely reported. Herein, the authors report a 47-year-old woman, with solitary erythema migrans and positive Lyme disease serology, who presented for medical care 14 days after commencement of doxycycline therapy. She complained of malaise, facial flushing, gingival erythema, and acquisition of additional plaques characterized by swelling, increased erythema, pruritus, and exfoliative scale. Punch biopsies demonstrated subacute to chronic spongiotic psoriasiform reaction patterns with a superficial lymphocytic infiltrate. By Borrelia-specific immunohistochemistry, spirochetes were found in the deep dermis, unassociated with inflammation, and focally in the upper spinous layer, associated with spongiosis. Borrelia burgdorferi DNA was detected by nested polymerase chain reaction. Doxycycline was discontinued, and symptoms and signs resolved within a few days. Liberation of endotoxin-like materials (eg, lipoproteins) from degenerating spirochetes and concomitant cytokine production is the suspected cause of JHR and supported by the finding of lesional spirochetes. Alternatively, a reversal reaction with a delayed-type hypersensitivity reaction is also a plausible cause based on spirochetes found in the lymphocytic spongiotic dermatitis.

Introduction Tuberculosis-associated uveitis remains a diagnostic and therapeutic challenge. After diagnosis of tuberculosis and initiation of anti-tuberculosis therapy for tuberculosis uveitis, the clinical responses are favorable. However, at 4-6 weeks of the therapy, there commonly occurs paradoxical deterioration due to an increase in inflammation which is often accompanied by cystoid macular edema. Thus, adjuvant administration of anti-inflammatory regimen should be considered. For this purpose, systemic and periocular steroids, systemic and intravitreal immunosuppressive agents have been tested. Nevertheless, there is no report in the literature about intravitreal dexamethasone slow-release implants for the treatment of this inflammatory condition.Methods Case presentation.ResultsWe presented a tuberculosis uveitis case whose ocular inflammation is partially modified by systemic and periocular steroid injections and then well controlled by the intravitreal dexamethasone implant.ConclusionIntravitreal dexamethasone implant injection seems to be a safe and potent option for the treatment of macular edema secondary to tuberculosis uveitis.

Background HIV positive patients can suffer many complications due to infectious diseases. A sever drug reaction to some of the drugs involved in the treatment can overlap the symptoms of the infections, making the diagnosis very difficult. We present the case of a 28-year-old-man, HIV positive, with secondary syphilis, who developed a Stevens Johnson Syndrome (SJS) caused by one of the many drugs he received. The SJS was overlapped with a possible Jarisch Herxheimer Reaction, which complicated the diagnosis of the skin reaction. Objective In HIV+ patients, the overlapping of severe drug reactions and infectious diseases could be fatal, thus an accurate diagnosis is mandatory. Material and methods A Rapid Plasma Reagin Test (RPR), an ELISA test, a blood laboratory test, chest radiography and a skin biopsy were realized in order to diagnose the infectious disease and the cause of skin lesions. Intradermal tests and double blind challenge tests were realized in the allergy study. Results The laboratory tests confirmed the diagnosis of syphilis; the skin biopsy confirmed the cause of lesions, a severe allergic reaction as a SJS. The allergy study discharged all the drugs involved, except dypirone which wasn't proved in the study because of the severity of reaction, the high possibility to be the causative drug and the alternative of other similar drugs available. For the inflammatory response, HIV+ patients are especially susceptible to severe reaction, both infectious and allergic, as in this case. Thus, recent patents emphasize the interest in inflammatory molecules that cause inflammatory symptoms. Conclusions Although the diagnose of SJS has established criteria, the possibility of overlapping with infectious illness and/or with its treatment, may complicate the diagnosis.

Clinical case We present the case of a 32 year-old man, HIV positive in treatment, that presented to our hospital. He had erythematous papules scattered through his trunk, limbs (including palms and soles) and genitalia. He denied previous genital, oral or anal ulcer. His previous serological tests for syphilis were negative. We suspected a secondary syphilis and prescribed Benzatin G Penicillin 2.4 M IU. The patient referred to the emergency room for a flu-like reaction and worsening of the skin lesions after the injection. We performed a biopsy that confirmed the clinical diagnosis of syphilis, and the serological test came out positive (RPR 64). After the second injection of penicillin, the patient experienced a second reaction, with fever and malaise. Before the third treatment we administered prednisone for three days, and he had no reaction. The Jarisch-Herxheimer Reaction (JHR) is well known since the Middle Ages, when it was associated with mercury ointments used for the treatment of syphilis. The first literary descriptions came from Jarisch in 1895 and Herxheimer seven years later. Since then it has been described during the antibiotic treatment of various spirochete infections. It begins 2 to 8 hours after the treatment, as a flu like reaction with high fever and is sometimes associated to an aggravation of the syphilis symptoms. It usually resolves in 24 hours without treatment, but the patients usually receive antipyretic treatment. This reaction appears in 50% of primary syphilis, and up to 75% of secondary syphilis. It’s very rare in latent syphilis, but can appear in 30% of neuro-syphilis. There has been only one description of a recurrent JHR, in a patient with a late latent syphilis that had 2 JHR after 2 consecutive penicillin injections. To our knowledge it has not been described in any other syphilis patient.

Bacillary angiomatosis (BA) is a rare complication of human immune deficiency virus (HIV) infection in the post-antiretroviral therapy (ART) era, and few cases of BA-associated immune reconstitution inflammatory syndrome (IRIS) have been described. We report the case of a 50-year-old man who presented with mass lesions involving the skin, subcutaneous tissues, muscle, and bone. The diagnosis of Bartonella quintana BA was confirmed by serum polymerase chain reaction. The patient’s treatment course was complicated by both IRIS and Jarisch-Herxheimer reaction. The case had a favorable outcome with supportive care and continuation of ART and doxycycline.

A Jarisch-Herxheimer reaction (JHR) may be precipitated after initiation of chemotherapy in spirochetal diseases, including leptospirosis. However, a clear idea of the importance of JHR in this disease is lacking. The incidence of and risk factors for JHR were investigated retrospectively among 262 patients with confirmed leptospirosis who received amoxicillin treatment in New Caledonia and Futuna. The overall rate of JHR was 21% (12% in New Caledonia and 44% in Futuna). Two risk factors were independently associated with JHR occurrence: Leptospira interrogans serogroup Australis as the infecting strain (odds ratio [OR] = 2.60, confidence interval [CI] = 1.40-5.62) and delays < 3 days between the onset of symptoms and the initiation of antibiotherapy (OR = 2.14, CI = 1.11-4.38). Clinicians should be aware of JHR as a potential complication of leptospirosis. Strain-related factors associated with JHR occurrence and its impact on outcome remains to be explored.

We present a case of Weil's disease complicated by a Jarisch-Herxheimer reaction (JHR) after initiation of antibiotics while in the emergency department requiring invasive monitoring and vasopressor support. The case is followed by a brief review of the JHR which is rarely observed with treatment of leptospirosis. A healthy 28-year-old female who recently returned from the Caribbean presented to the emergency department with flu-like symptoms. The patient appeared jaundiced with conjunctival suffusion and was ultimately treated with the appropriate antibiotics for leptospirosis in the ED. She decompensated subsequently, requiring supplemental oxygen, central and arterial line placement, and vasopressor support with norepinephrine. Although rarely encountered and not well reported throughout the literature, initiation of antibiotics can cause a JHR reaction given that Leptospira interrogans is a spirochete. This JHR may be self-limited and of short duration, or it can be prolonged and severe, requiring invasive therapies such as central line placement for vasopressor support and intubation. It is suggested that patients started on antibiotics for leptospirosis/Weil's disease should be monitored in the emergency department for a short duration prior to discharge or transfer to a regular medical floor for observation given the possibility for decompensation.

A 61-year-old man presented with a 2 week history of intermittent fever, recurrent headaches, arthralgia’s and a non-pruritic erythematous macular rash on his right lower abdomen. The patient underwent an uncomplicated lumbar puncture and was commenced on antibiotics for suspected early disseminated Lyme disease. Few hours after the first antibiotic dose he had abrupt onset of high fevers, chills, hypotension and tachycardia requiring fluid resuscitation and antipyretics. Jarisch-Herxheimer reaction (JHR) is a transient shock-like syndrome that typically follows initiation of antibiotics and is classically associated with penicillin treatment of syphilis. We discuss a patient of disseminated Lyme disease who developed JHR after commencing antibiotic therapy.

ObjectivesThe objective of this retrospective study was to summarise the clinical manifestations of, and to analyse the incidence and risk factors of, Jarisch–Herxheimer reaction (JHR) during the treatment of children with symptomatic congenital syphilis.MethodsClinical data of 60 children with clinically and laboratory diagnosed congenital syphilis, hospitalised in Beijing Ditan Hospital between January 2010 and November 2015, were collected and analysed.ResultsA total of 11 patients with congenital syphilis (11/60, 18.3%) developed JHR. JHR occurred in 1–6 hour after the first dose of penicillin. Common clinical manifestations included fever (11/11, 100%), irritability (11/11, 100%), rapid pulse and breathing (11/11, 100%), exacerbation of existing rash (5/11, 45.6%) and chills (3/11, 27.3%). Of the 11 patients who developed JHR, 9 patients (9/11, 81.8%) had bone syphilis, 10 (10/11, 90.9%) had more than three organs affected by syphilis and 10 (10/11, 90.9%) had a high plasma concentration of rapid plasma reagin (RPR) (≥1:256); these percentages were significantly higher than in patients who had not developed JHR (pConclusionsClinicians should be familiar with the risk factors for this reaction and its common clinical manifestations.

Relapsing fever is a disease caused by one of the species of Borrelia. It is often misdiagnosed as malaria and can have fatal complications such as the Jarisch-Herxheimer reaction (JHR) after the commencement of treatment with antibiotics. A 19-year-old Tanzanian woman was admitted after a term home delivery that day. She presented with a 2 day history of fever, headache, general body malaise and vomiting. She was misdiagnosed as having severe malaria and was treated with quinine. The blood slide showed Borrelia duttoni. The patient continued treatment with procaine penicillin fortified for relapsing fever. Several hours later the woman died, probably due to JHR. This case of a patient with relapsing fever who died from a JHR stresses the importance of adequate diagnosis and treatment which should include careful monitoring, especially for the first hours after starting antibiotics. © 2013, SAGE Publications. All rights reserved.

1. Certain aspects of the Jarisch—Herxheimer reaction (JHR) after treatment of louse-borne relapsing fever have been studied in nine patients. Peripheral vasoconstriction immediately preceded the chill phase and profound vasodilation accompanied the flush phase. 2. From four patients 50–150 ml of blood was taken at the onset of the chill and reinjected intravenously into the same patient the next day. One patient experienced a reaction identical with JHR 40–60 min after reinjection, suggesting that the mediator of JHR was present in that blood. 3. From five patients 40 ml of blood were taken serially throughout JHR and 2-ml samples of plasma, free of cells and spirochaetes, were injected into pairs of normal rabbits. All samples taken while the patients had fever were pyrogenic. After incubation with normal rabbit plasma these samples failed to produce fever in endotoxin-refractory rabbits. 4. These results suggest that in the plasma of patients with relapsing fever there is a powerful endotoxin. We were unable to show that the concentration of endotoxin increased during JHR, nor could we demonstrate the presence of leucocyte pyrogen. This failure could be a problem of quantity of plasma used or of an endotoxin-refractory state. 5. The bearing of these observations on the mechanism of JHR and the uselessness of cortisol in modifying the reaction are discussed.

Eine 36-jährige Patientin, wurde aufgrund einer einseitigen Visusminderung vorstellig. Die ophthalmologische Untersuchung, im Kontext einer hochreaktiven Syphilis-Serologie, zeigte eine akute syphilitische plakoide Chorioretinitis. Mit einer Plaque opaline der Mundschleimhaut und mottenfrassähnlicher Alopezie lag klinisch eine sekundäre Syphilis mit Augenbeteiligung vor. Die Behandlung wurde mit 6x 4 Mio. IE Penicillin G während 14 Tagen und Prednison 50 mg während fünf Tagen durchgeführt. Anhand dieses Falles gehen wir auf die Diagnostik, Therapie und Nachkontrolle der Syphilis mit okulärer Beteiligung ein., We report a case of a 36-year old patient who suffered from a unilateral painless loss of vision. Ophthalmological examination in the context of a highly reactive syphilis serology revealed an acute syphilitic posterior placoide chorioretinitis (ASPPC). Additional clinical findings were a mucosal lesion on the upper lip, consistent with a plaque opaline and an alopecia specifica as manifestation of secondary syphilis. Treatment consisted in 6x 4 Mio. IE Penicillin G for 14 days and 50 mg Prednison for five days to prevent a Jarisch Herxheimer reaction. The diagnostic measures, therapy and follow up of syphilis, focusing on ocular involvement, are described.

The optimum treatment for louse-borne relapsing fever (LBRF) has not been fully established. Eliminating spirochetes is often associated with the potentially lethal Jarisch-Herxheimer reaction (JHR). The objective of this meta-analysis was to review the evidence supporting the use of antibiotics usually employed for treating LBRF. A systematic review of the literature was performed to identify randomised controlled trials (RCT) comparing antibiotics in LBRF. The primary outcome was mortality, whilst JHR rates, relapse rates, time to fever clearance and time to spirochete disappearance were secondary outcomes. Six RCTs performed in Ethiopia were included. Trials were small and often of limited quality, using single-dose therapy with either penicillin or tetracycline. There was no significant difference between tetracycline and penicillin with regard to mortality rate. Although there was significant heterogeneity between the five trials comparing the rate of JHRs, three of them showed a significant benefit in favour of penicillin. The risk of relapse was reduced with tetracycline. Tetracycline use was associated with a lower mean fever clearance time. Tetracycline appears to be the most efficient drug but also appears to be associated with a higher rate of JHRs. Alternative regimens to treat LBRF should be investigated.

The incidence of and risk factors for Jarisch-Herxheimer (JH) reaction were investigated prospectively among 240 human immunodeficiency virus (HIV)-infected and 115 HIV-uninfected patients with syphilis who received penicillin treatment. The overall rate of JH reaction was 31.5% (34.6% in HIV-infected patients and 25.2% in HIV-uninfected patients). In multivariate analysis, risk factors for JH reaction included high rapid plasma reagin (RPR) titers (per log(2) RPR increase, risk ratio [RR], 1.19; 95% confidence interval [CI], 1.04-1.37), early syphilis (RR, 8.59; 95% CI, 4.75-15.56), and prior penicillin treatment (RR, 0.39; 95% CI, 0.20-0.78).

The Occurrence of plasma CRP during the febrile response after the first injection of penicillin was followed in 10 patients with early syphilis. An increase in CRP was noted after 12 hours, with a maximum after 24 hours. The appearance of this acute phase protein could not be correlated to cutaneous reaction, increased body temperature or leukocytosis, nor were baseline values of CRP correlated to clinical or serological activity of the infection. Patients with high levels of CRP prior to treatment suffered the most intense systemic reactions. No activation of the complement system during the Jarisch-Herxheimer reaction was detected from sequential determinations of C3, C4 and properdin.

Borrelia burgdorferi is highly susceptible to antibiotic treatment and the majority of patients profit from this treatment. Antibiotic selection, dose and route of administration, and duration of therapy for Lyme disease depend on the patient’s clinical manifestations and stage of disease, age, pregnancy status, as well as the presence of other concomitant diseases and/or allergies. Despite an appropriate antibiotic therapy, about 10-20% of patients may show persistent or recurrent symptoms ("post-treatment Lyme disease syndrome").In the present paper we will briefly discuss the post-exposure prophylaxis, before going on to talk over the current therapeutic approach regarding the management of Lyme disease according to the stage of disease/clinical manifestations. Finally, we will discuss the main treatment-related phenomenon, the Jarisch-Herxheimer reaction, and the treatment modalities for special categories of patients, namely pregnant women, subjects suffering from post-treatment Lyme disease syndrome, possible Borrelia-associated skin manifestations, coinfections and Baggio-Yoshinary syndrome.

Summary Objective: To review the aetiologies and preventative methods associated with Jarisch–Herxheimer reactions (JHR). Data sources: Ovid Medline® (1966–June Week 1 2004) was utilized to assess biomedical literature; a review of the bibliographies of articles was also performed. Data synthesis: JHR often occurs with the treatment of spirochete infections. However, the mechanism by which the reaction takes place is not clearly defined. Conclusion: Studies suggest with conflicting evidence that the JHR is caused by release of endotoxin-like material from the spirochete as well as cytokine elevation in the body. It appears the type of drug and the rate of spirochete clearance from the body have little effect on the incidence of the reaction. Many pretreatment options have been explored with limited efficacy with the exception of anti-tumour necrosis factor antibodies.

Apart from its devastating impact on individuals and their families, multiple sclerosis (MS) creates a huge economic burden for society by mainly afflicting young adults in their most productive years. Although effective strategies for symptom management and disease modifying therapies have evolved, there exists no curative treatment yet. Worldwide, MS prevalence parallels the distribution of the Lyme disease pathogen Borrelia (B.) burgdorferi, and in America and Europe, the birth excesses of those individuals who later in life develop MS exactly mirror the seasonal distributions of Borrelia transmitting Ixodes ticks. In addition to known acute infections, no other disease exhibits equally marked epidemiological clusters by season and locality, nurturing the hope that prevention might ultimately be attainable. As minocycline, tinidazole and hydroxychloroquine are reportedly capable of destroying both the spirochaetal and cystic L-form of B. burgdorferi found in MS brains, there emerges also new hope for those already afflicted. The immunomodulating anti-inflammatory potential of minocycline and hydroxychloroquine may furthermore reduce the Jarisch Herxheimer reaction triggered by decaying Borrelia at treatment initiation. Even in those cases unrelated to B. burgdorferi, minocycline is known for its beneficial effect on several factors considered to be detrimental in MS. Patients receiving a combination of these pharmaceuticals are thus expected to be cured or to have a longer period of remission compared to untreated controls. Although the goal of this rational, cost-effective and potentially curative treatment seems simple enough, the importance of a scientifically sound approach cannot be overemphasised. A randomised, prospective, double blinded trial is necessary in patients from B. burgdorferi endemic areas with established MS and/or Borrelia L-forms in their cerebrospinal fluid, and to yield reasonable significance within due time, the groups must be large enough and preferably taken together in a multi-centre study.

In this report, we describe a case of Weil disease. Chest x-ray and computed tomography (CT) findings showed temporary deterioration 1 day after the initiation of antibiotic treatment, and high-resolution CT findings with the patient's physical findings made us suspect pulmonary alveolar hemorrhage (PAH). We believed that the PAH had been induced by Weil disease and subsequently caused Jarisch-Herxheimer reaction. We confirmed the patient's contact history with mice, and symptoms improved immediately after starting appropriate treatments. Leptospirosis is a relatively rare cause of PAH. Therefore, the possibility of this disease should be included in the differential diagnosis, especially when high-resolution CT findings indicate PAH, and the imaging findings deteriorate rapidly after antibiotic therapy.

Copyright 2014 American Medical Association. All rights reserved. IMPORTANCE: The incidence of syphilis in the United States is increasing; it is estimated that more than 55 000 new infections will occur in 2014. Treatment regimens are controversial, especially in specific populations, and assessing treatment response based on serology remains a challenge. OBJECTIVE: To review evidence regarding penicillin and nonpenicillin regimens, implications of the "serofast state," and treatment of specific populations including those with neurosyphilis or human immunodeficiency virus (HIV) infection and pregnant women. EVIDENCE REVIEW: We searched MEDLINE for English-language human treatment studies dating from January 1965 until July 2014. The American Heart Association classification system was used to rate quality of evidence. FINDINGS: We included 102 articles in our review, consisting of randomized trials, meta-analyses, and cohort studies. Case reports and small series were excluded unless they were the only studies providing evidence for a specific treatment strategy. We included 11 randomized trials. Evidence regarding penicillin and nonpenicillin regimens was reviewed from studies involving 11 102 patients. Data on the treatment of early syphilis support the use of a single intramuscular injection of 2.4 million U of benzathine penicillin G, with studies reporting 90% to 100% treatment success rates. The value of multiple-dose treatment of early syphilis is uncertain, especially in HIV-infected individuals. Less evidence is available regarding therapy for late and late latent syphilis. Following treatment, nontreponemal serologic titers should decline in a stable pattern, but a significant proportion of patients may remain seropositive (the "serofast state"). Serologic response to treatment should be evident by 6 months in early syphilis but is generally slower (12-24 months) for latent syphilis. Evidence defining treatment for HIV-infected persons and for pregnant women is limited, but available data support penicillin as first-line therapy. CONCLUSIONS AND RELEVANCE: The mainstay of syphilis treatment is parenteral penicillin G despite the relatively modest clinical trial data that support its use.

Although not commonly seen in Japan, the incidence of leptospirosis reported in 2014 was the highest in the past 6 years. It is important to consider leptospirosis among patients who traveled to Okinawa, Japan, and to keep in mind Jarisch–Herxheimer reaction when administering antimicrobial agents to patients with leptospirosis. A 59-year-old Japanese man with a history of hypertension presented with a complaint of fever and watery diarrhea. He climbed mountains, got lost accidentally and drunk 2 l of fresh water in the swamp in Okinawa, Japan 2 weeks prior to admission. Physical examinations showed blood pressure 129/89 mmHg, heart rate 112/min, respiratory rate 30/min, temperature of 38.5°C and oxygen saturation of 97% on room air. His bilateral palpebral conjunctivas were significantly injected with jaundice. The patient had tenderness to bilateral thighs …