Recurrence Of Fever Research Articles

‘Aortic valve prolapse’ in rheumatic heart disease

A 14-year-old girl was referred for evaluation of aortic regurgitation. She had an episode of acute rheumatic fever at the age of 6 years that was managed elsewhere. Her parents denied any history of blunt trauma to the chest or long-standing fever other than rheumatic fever. There was no clinical or laboratory evidence of recurrence of rheumatic fever at presentation. Echocardiogram revealed thickened mitral valve, restricted mobility of posterior mitral leaflet and low moderate mitral regurgitation. The aortic valve was trileaflet with severe aortic regurgitation. Interestingly, however, the non-coronary cusp of the aortic valve was prolapsing into the left ventricle. The regurgitant jet was eccentric through the non-coapting right coronary cusp and the non-coronary cusp (Fig. 1a, online video 1). The non-coronary cusp was thick and redundant (Fig. 1b). The prolapse of the non-coronary cusp and non-coaptation was better visualised on multi-planar review of the 3D full-volume dataset (Fig. 2, online video 3). Aortic valve prolapse is not an uncommon mechanism of aortic regurgitation, most commonly being in association with bicuspid aortic valve [1]. In addition, association with ventricular septal defect, mitral valve prolapse, infective endocarditis, blunt trauma to the chest and Marfan syndrome is well known. In an elegant study by Vasan et al., only 2.5 % of patients with active carditis had aortic valve prolapse. On the other hand, none of the patients with the absence of active carditis had aortic valve prolapse [2]. It is extremely unusual, however, to have aortic valve prolapse causing aortic regurgitation in a patient with rheumatic heart disease, especially without active carditis [1, 2]. Understandably, the history of acute rheumatic fever alone may not be considered as evidence to support the underlying aetiology as rheumatic. However, in the presence of abnormalities of the mitral valve, trileaflet aortic valve and lack of support to any alternative aetiology, rheumatic heart disease is the most likely cause of aortic valve prolapse in this case. It is important to recognise aortic valve prolapse, as it entails the possibility of valve repair.

Fiebre recurrente transmitida por garrapatas en área rural del sur de España

IntroductionTick-borne relapsing fever (TBRF) is a zoonotic disease caused by spirochetes of the genus Borrelia. This disease is underdiagnosed in our area due to a low index of suspicion among clinicians, as well as its difficult diagnosis.This study aims to present our experience in the diagnosis and therapeutic management of TBRF and a literature review. MethodsA retrospective medical chart review was carried out on children diagnosed of TBRF from 2002 to 2012 in our hospital, and included clinical, epidemiological, microbiological, treatment, and outcome data. ResultsNine children with TBRF were identified. Median age was 11years. All cases occurred during warm months. The most frequent presenting clinical findings were fever, chills, headache, vomiting, myalgia and abdominal pain. Meningeal involvement was identified in 2 cases. In the case of 2 patients, Borrelia infection was identified in several relatives at the time of diagnosis. Mean C-protein reactive was 187mg/L, and low platelet counts were observed in 56% of the cases. Borreliaspp. was visualized in peripheral blood smears in 67% of cases. All of the patients received antibiotic treatment. Doxycycline was used in children older than 8years and erythromycin and penicillin in the younger ones. Jarisch-Herxheiner reaction occurred in one patient. All cases resolved without sequelae. ConclusionsWe emphasize the importance of maintaining a high level of suspicion in endemic regions of TBRF. Early diagnosis and a correct therapy can prevent the appearance of subsequent fever recurrences and potential complications.

English

INTRODUCTION: Acute rheumatic fever is an auto-immune response to bacterial infection with group A streptococcus (GAS). Despite the dramatic nature of the acute episode, acute rheumatic fever leaves no lasting damage to the brain, joints or skin. Recurrences of acute rheumatic fever may cause further valve damage, leading to steady worsening of rheumatic heart disease. AIMS AND OBJECTIVE: To study prevalence of acute rheumatic fever and rheumatic heart disease as detected by 2D ECHOCARDIOGRAPHY in patients 05 years to 40 years of age attending OPD and IPD of medicine and pediatrics department Rama Medical College, Kanpur. MATERIAL AND METHODS: The present study was conducted on patients of 05 to 40 years of age. All patients were examined clinically and relevant investigations including 2D ECHOCARDIOGRAPHY was done in all patients. RESULTS: A total of 734 patients belonging to age group 05 to 40 years & attending the OPD & IPD of Medicine & pediatrics Department of Rama Medical College, Kanpur, were studied, Out of 734 patients, 42 patients (5.72%) had findings of RF & RHD on 2D ECHO. RF were present in 10 patients (1.36%), RHD in 28 patients (3.81%), and 04 patients (0.54%) had evidence of both RF & RHD, 38.09% had findings of RF & RHD, were >25 years of age, Out of 42 patients 61.90% were females & 38.09% were males, RF & RHD occurred more frequently (57.14%) in rural population as compared to urban population (42.86%). Among the Jones Minor Criteria, the most common manifestation (57.14%) was Arthralgia followed by Fever (50%). ESR was raised in 28.57%, CRP was elevated in 28.57% and PR-interval prolongation was seen in 14.28%.Clinically 04 patients had evidence of carditis. All these patients also had ECHO findings suggesting carditis. Other than that ECHO also identified 10 more patients with carditis. Mitral valve was most commonly involved. Isolated mitral stenosis was present in 25% of patients, isolated mitral regurgitation in 18.75% of patients, while combined mitral valve stenosis & regurgitation was present in 37.50% of patients. Multi valvular lesions were present in 18.25% of patients. CONCLUSION: Our study shows prevalence of RF to be 19.07 per 1000 patients and prevalence of RHD to be 43.59 per 1000 patients, there is higher sensitivity and positive predictive value of 2D ECHO in detecting RF and RHD. Maximum number of patients of RF and RHD belong to the >25 years age group, followed by 20-25 years, 15-20 years and 05-10 years with prevalence is higher in females than male, Polyarthritis was the most common manifestation among the Jones major criteria seen in 35.71% patients.2D ECHO had a sensitivity and positive predictive value of 100% in identifying carditis as compared to clinical methods of detecting carditis with sensitivity of 28.57%.

Gammaglobulin Treatment in an Unusual Meningococcal Case

To the Editor: Prolonged fever is a possible complication of meningococcal meningitis, appearing in approximately 10 % of cases. Defined as fever lasting from four to ten days after the symptoms of meningitis begin, it can be classified as persistent, secondary or recurrent [1]. In the persistent type, the fever never disappears, and intracranial causes such as brain abscesses, subdural empyema, and vasculitis must be ruled out [1]. The secondary fever re-appears atleast 24 h after being afebrile. Extracranial causes should be suspected, including viral and bacterial infections [2, 3]. Finally, with the recurrent fever, a parameningeal focus of infection and congenital defects should be investigated [1]. We report an 11-mo-old male infant with meningococcal meningitis septicemia, who remained afebrile between 24 and 72 h after starting the antibiotic therapy. Fever re-appeared on the fourth day of antibiotic treatment, associated with palpable nodules on his left arm. Four days later, despite non-steroidal anti-inflammatory drugs (NSAIDs) being administered, vasculitis by immune complexes was suspected, and oral steroid treatment with prednisolone was initiated with doses of 2 mg/ kg/d. He remained afebrile afterwards and was discharged two days later, receiving antibiotic treatment and oral steroids for a week. Fever re-appeared 24 h after steroid treatment was completed. Palpable nodular elements persisted together with the appearance of new ones, and arthralgia and a systolic murmur were detected. We restarted 2 mg/kg/d prednisolone dose with subsequent tapering to 0.3 mg/kg/d, with new fever recurrence after it was suspended. Laboratory studies showed declining levels of C-reactive protein and the erythrocyte sedimentation rate, rising levels of complement factors, negative antinuclear antibody and rheumatoid factor. An echocardiography and urinalysis were normal. The immune complex vasculitis-arthritis was controlled with steroid treatment but was not resolved yet. Two doses of 2 g/kg/d of intravenous gammaglobulin were needed, after which the fever and arthralgia disappeared. The presence of palpable nodules, arthralgia and increased acute phase reactants lead to the diagnosis of vasculitis-athritis by immune complexes [4, 5]. Although there are no protocols involving immunoglobulins for vasculitis management, it has been an effective and extensive treatment over the years in medical practice. Our patient required two doses of gammaglobulin with subsequent complete remission of symptoms.

Artemisinin therapy and severe delayed haemolysis

In April, 2012, a 32-year-old white man came to our hospital with fever, lethargy, dyspnoea, and bilateral ankle oedema. He had spent the last 4 months in Togo and had not taken malaria prophylaxis. 15 days previously, he had developed fever and lethargy, and had attended a clinic at which Plasmodium falciparum malaria was diagnosed, with an initial parasitaemia of 1650 para sites per μL. His haemoglobin (Hb) was 128 g/L. He was given 160 mg intramuscular artemether daily for 3 days, followed by a 3-day course of oral dihydroartemisinin/piperaquine, with a good symptomatic response. 2 days later, he had a recurrence of fever, in addition to dyspnoea and ankle swelling. A blood fi lm showed no malaria parasites, but his Hb was 108 g/L. During the next 3 days he deteriorated and was transferred to hospital in Lome. A blood fi lm was again negative for malaria parasites, but the Hb had dropped to 70 g/L. He was prescribed intravenous (IV) ofl oxacin with oral doxycycline and was fl own to London. On arrival at this hospital he was febrile at 38·5°C, tachycardic, clinically anaemic, and jaundiced, had hepato splenomegaly, and was passing dark brown urine. Urinalysis confi rmed moderate haemoglobinuria. His Hb was 41 g/L with a mean corpuscular volume of 83 fL, anisocytosis and mild polychromasia, platelets of 112×109/L, and a white cell count of 4·2×109/L. Reticulocyte count was 5%, haptoglobin <100 mg/L, and direct agglutinin test was negative. Bilirubin was 35 μmol/L. Urea, electrolytes, and liver function tests were within normal limits. Lactate dehydrogenase was raised at 28·17 μkat/L, glucose-6-phosphate dehydrogenase activity was normal at 0·14 nkat/g haemoglobin, haemo globinopathy screen was negative, and iron, folate, and vitamin B12 values were normal. A rapid diagnostic test detecting histidine-rich protein 2 from P falciparum was positive. In-house nested PCR detected P falciparum DNA. However, thick and thin blood fi lms were consis tently negative. A comprehensive infection screen was negative. A fl uorodeoxyglucose positron emission tomography scan was unremarkable. Bone marrow biopsy showed pro nounced erythroid hyperplasia that was consistent with rapid red cell turnover. There was no evidence of any infi ltrative process, haemophagocytosis, or macrophage activation, and perforin expression was normal. No cold antibodies or other atypical auto antibodies or alloanti bodies were detected. A diagnosis of artemisinin induced haemolysis was made, on the basis of having excluded other potential causes of haemolysis. The patient received four blood transfusions over the next 6 days, with evidence of continuing severe intra vascular haemolysis (appendix). On the 7th day after admission, his fever stopped and haemolysis spon taneously resolved. He was discharged home and made a full recovery without further transfusion or treatment and remained well when last followed up in December, 2012. Artemisinin combination therapy has recently become the recommended fi rst-line treatment for both complicated and uncomplicated malaria in endemic areas, and is increasingly used in both Europe and the USA. Artemisinin derivatives are especially valuable for severe malaria because of the rapid rates of parasite clearance, and data from large clinical trials have shown the superiority of IV artesunate over IV quinine. Although the safety profi le of oral and parenteral artemisinins seems excellent in reported clinical trials, severe delayed haem olysis is emerging as a problem in European patients treated with parenteral artemisinins. 10% of patients (seven of 68) treated with IV artesunate in a recent Dutch and Belgian series developed severe haemolysis, with a median lowest Hb of 38 g/L occurring 7–31 days after treatment. Haemolysis persisted for up to 7 weeks. A second European series of 25 patients reported a similar syndrome, with 24% (6/25) developing profound haemo lytic anaemia 14–31 days after IV artesunate. Four additional cases have now been reported from other European centres, and despite extensive investigation in most of these cases, alternative explanations for haemolysis have not been identifi ed. As artemisinin-based therapy becomes the standard of care for severe imported malaria, caution must be taken to monitor for the increasingly recognised and serious com pli cation of severe delayed haemolysis.

Should Infliximab be Used as an Adjuvant to IVIG in the Treatment of Children With Kawasaki Disease Who Are at High Risk for Resistance to Conventional Therapy?

The recently published article, entitled “Extensive Coronary Aneurysms with Thrombosis in Resistant Kawasaki Disease” by Sivakumar and Pavithran [5], concisely delineates the limitations in the treatment of Kawasaki disease (KD). There is no one accepted treatment algorithm for treatment-refractory patients, and the efficacy of infliximab as a first-line therapy adjunct has not yet been studied. Although a retrospective study showed improvement in various clinical outcomes, use of infliximab as second-line therapy is not convincingly supported by highly powered studies [1]. As this case illustrates, the treatment of KD is neither universal nor intuitive. The efficacy of infliximab in this population would perhaps be enhanced if administered at an earlier time point, especially in children who are at high risk for resistance to therapy. Children who are resistant to first-line treatment with IVIG carry a higher risk for development of coronary artery aneurysms [4]. Therefore, to avoid such devastating outcomes, should infliximab be used as an adjunct to IVIG in the treatment of children with KD who are at high risk? These high-risk patients (male, young age, recurrence of fever) could possibly be identified with a risk stratification algorithm and may benefit from more aggressive early therapy. It has been shown that tumor-necrosis factor (TNF)-alpha inhibitors decrease inflammation and endoarteritis in murine models, specifically the inhibition of neutrophil adhesion to endothelial cells, which is seen in the early phase of vasculitis [2]. This proof of concept experiment further elucidates the role of TNF-alpha inhibitors in the treatment of panvasculitis. Based on the mechanism of endoarteritis and the success of other patients treated with infliximab, we believe that high-risk KD patients may benefit from early treatment with infliximab in conjunction with conventional IVIG therapy [3,4]. In keeping with this hypothesis, researchers at The University of California at San Diego recently completed a phase III placebo-controlled, multicenter, randomized clinical trial of infliximab plus standard therapy versus placebo plus standard therapy in children with acute KD to determine if the addition of infliximab to primary therapy can decrease the percentage of children who are resistant to therapy. Results of this study will perhaps further guide our primary management of KD.

Cardiovascular complications in newly diagnosed rheumatic heart disease patients at Mulago Hospital, Uganda : cardiovascular topics

Complications of rheumatic heart disease are associated with severe morbidity and mortality in developing countries where the disease prevalence remains high. Due to lack of screening services, many patients present late, with severe valve disease. In Uganda, the disease and its complications are still not well studied. To profile and describe cardiovascular complications in newly diagnosed rheumatic heart disease patients attending the Mulago National Referral Hospital in Uganda. This was a cross-sectional study where consecutive, newly diagnosed rheumatic heart disease patients were assessed and followed up for complications, such as heart failure, pulmonary hypertension, atrial fibrillation, recurrence of acute rheumatic fever, and stroke. A total of 309 (115 males and 196 females) definite rheumatic heart disease patients aged 15-60 years were enrolled in the study and analysed. Complications occurred in 49% (152/309) of the newly diagnosed rheumatic heart disease cases, with heart failure (46.9%) the most common complication, followed by pulmonary arterial hypertension (32.7%), atrial fibrillation (13.9%), recurrence of acute rheumatic fever (11.4%), infective endocarditis (4.5%) and stroke (1.3%). Atrial fibrillation and acute rheumatic fever were the most common complications associated with heart failure. In this study we found that about 50% of newly diagnosed rheumatic heart disease patients in Uganda presented with complications. Heart failure and pulmonary arterial hypertension were the most commonly observed complications.

A Novel Approach for Measuring the Burden of Uncomplicated Plasmodium falciparum Malaria: Application to Data from Zambia

Measurement of malaria burden is fraught with complexity, due to the natural history of the disease, delays in seeking treatment or failure of case management. Attempts to establish an appropriate case definition for a malaria episode has often resulted in ambiguities and challenges because of poor information about treatment seeking, patterns of infection, recurrence of fever and asymptomatic infection. While the primary reason for treating malaria is to reduce disease burden, the effects of treatment are generally ignored in estimates of the burden of malaria morbidity, which are usually presented in terms of numbers of clinical cases or episodes, with the main data sources being reports from health facilities and parasite prevalence surveys. The use of burden estimates that do not consider effects of treatment, leads to under-estimation of the impact of improvements in case management. Official estimates of burden very likely massively underestimate the impact of the roll-out of ACT as first-line therapy across Africa. This paper proposes a novel approach for estimating burden of disease based on the point prevalence of malaria attributable disease, or equivalently, the days with malaria fever in unit time. The technique makes use of data available from standard community surveys, analyses of fever patterns in malaria therapy patients, and data on recall bias. Application of this approach to data from Zambia for 2009–2010 gave an estimate of 2.6 (95% credible interval: 1.5–3.7) malaria attributable fever days per child-year. The estimates of recall bias, and of the numbers of days with illness contributing to single illness recalls, could be applied more generally. To obtain valid estimates of the overall malaria burden using these methods, there remains a need for surveys to include the whole range of ages of hosts in the population and for data on seasonality patterns in confirmed case series.

Determinants of poor adherence to secondary antibiotic prophylaxis for rheumatic fever recurrence on Lifou, New Caledonia: a retrospective cohort study

BackgroundIncidence of acute rheumatic fever (ARF) and prevalence of rheumatic heart disease (RHD) in the Pacific region, including New Caledonia, are amongst the highest in the world. The main priority of long-term management of ARF or RHD is to ensure secondary prophylaxis is adhered to. The objectives of this study were to evaluate rates of adherence in people receiving antibiotic prophylaxis by intramuscular injections of penicillin in Lifou and to determine the factors associated with a poor adherence in this population.MethodsWe conducted a retrospective cohort study and we included 70 patients receiving injections of antibiotic prophylaxis to prevent ARF recurrence on the island of Lifou. Patients were classified as “good-adherent” when the rate of adherence was ≥80% of the expected injections and as “poor-adherent” when it was <80%. Statistical analysis to identify factors associated with adherence was performed using a multivariate logistic regression model.ResultsOur study showed that 46% of patients from Lifou receiving antibiotic prophylaxis for ARF or RHD had a rate of adherence <80% and were therefore at high risk of recurrence of ARF. Three independent factors were protective against poor adherence: a household with more than five people (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.75), a previous medical history of symptomatic ARF (odds ratio, 0.20; 95% CI, 0.04 to 0.98) and an adequate healthcare coverage (odds ratio, 0.21; 95% CI 0.06 to 0.72).ConclusionsTo improve adherence to secondary prophylaxis in Lifou, we therefore propose the following recommendations arising from the results of this study: i) identifying patients receiving antibiotic prophylaxis without medical history of ARF to strengthen their therapeutic education and ii) improving the medical coverage in patients with ARF or RHD. We also recommend that the nurse designated for the ARF prevention program in Lifou coordinate an active recall system based on an updated local register. But the key point to improve adherence among Melanesian patients is probably to give appropriate information regarding the disease and the treatment, taking into account the Melanesian perceptions of the disease.

Breakthrough Treatment of “Dengue Viral Infection” The Report on the Dengue Viral Epidemic of 2011 in Province of Punjab Pakistan.

The present paper aimed to overcome the Viral Pathology in the emerging Dengue Virus Epidemic. Since 2010 it is a second epidemic of dengue Fever (DF) and dengue Hemorrhagic fever (DHF) that has claimed over 300 lives in the Punjab area. There has been no set treatment protocol other than the World Health Organization (WHO) guidelines to treat this viral infection. Many physicians tried to follow the same and achieved some degree of success but unfortunately mismanagement of Dengue inflicted patients led to a high mortality. Malaysian physicians reported to have modified the WHO protocol to fit the needs of the local epidemic in 2009. However; the mainstay of the treatment was the balance of fluid dynamics of the patient's body. Unfortunately, the depleting platelets counts have been a media promoted scare of the dengue fever and dengue hemorrhage fever. The depleting Platelets count is not the only indication of the DF and DHF. However, its drastic reduction below 150,000 is the leading cause of bleeding (Internal & External) and eventual death. To date, the Pathophysiology that causes the symptoms of DF & DHF and the neurological deficits have been very poorly understood. Therefore, the treatment protocol presented by the WHO and the local medical practioners has been deemed partial or insufficient. Great number of patients has been seen with the recurrence of the dengue fever or incomplete treatment or the extensive dengue infection leading to bleeding, neurological deficit or directly comatose and death. Ever changing patient admission guidelines also led to the high risk of patient mortality. Therefore, the treatment protocol designed by us has successfully addressed the DF & DHF challenged patient population most effectively, resulting into no platelets transfusion and zero patient mortality. This unique project entertained 1298 patients from the greater community of city of Lahore. Majority of patients were seen as a direct visit to the UCH Dengue clinic, and many were received as a referral from other hospitals.

The Natural History of Cyclic Neutropenia: Long-Term Prospective Observations and Current Perspectives.

AbstractAbstract 2141Cyclic neutropenia (CyN) is an autosomal dominant and sporadically occurring hematological disease first described in 1910. Cyclic neutropenia is usually diagnosed in children before age 2 years based of regularly occurring fever, mouth ulcers, and recurrent skin or respiratory infections. In affected families, recognition is generally earlier than for the sporadic cases. Serial neutrophil counts usually show periods of very severe neutropenia (ANC< 0.2 × 109/L) at three week intervals and an intervening peak ANC less than 2.0 × 109/L. A reciprocal monocytosis often occurs during the neutropenic period. Mild anemia is common, particularly in patients with recurrent infections. Cycling of blood neutrophils is more apparent in young children than in adults, who often report severe childhood symptoms ameliorating near puberty or soon thereafter.Through the Severe Chronic Neutropenia International Registry and Repository- Seattle (SCNIR-Seattle) we have prospectively studied the natural history of 348 patients with a clinical diagnosis of CyN, 181 sporadic cases and 167 patients from 36 families whose pedigrees illustrate autosomal dominant inheritance. Sequencing results for the gene for neutrophil elastase, ELANE, are available for 119 of these patients including at least one member of 18 families. We have prospectively followed all of these patients for up to 25 years.Patients with typical, 21 day oscillations of blood neutrophils almost always have mutations of ELANE, most frequently mutation in exons 4 or 5. Neutropenic relatives (ANC < 1.5 × 109/L) of an index case of CyN with an ELANE mutation uniformly have the same ELANE mutation, even if they have few symptoms and the neutropenia is not severe. Patients with severe congenital neutropenia and CyN may also have the same or nearly identical mutations; thus the diagnosis of cyclic neutropenia can not be made solely from mutation analysis.Since 1987 we have treated cyclic neutropenic patients with G-CSF; some patients have been on G-CSF on a daily or alternate-day basis for 25 years. For the population of 209 treated patients enrolled in the SCNIR and treated for a median of 14.8 years, the median daily G-CSF dose is 2.1 mcg/kg/day. We have observed that the dose established during the first year of treatment can be adjusted for body weight and usually maintained indefinitely. Adverse effects are infrequent, particularly with daily or alternate-day treatment, although development of osteopenia remains a concern. A few patients who have transiently interrupted G-CSF; almost all have resumed G-CSF because of recurrence of fever, mouth ulcers, infections or fatigue. We are currently aware of only two CyN patients who have discontinued G-CSF treatment for greater than 2 months without recurrence of symptoms or returning to G-CSF therapy.In this population, there has been no hematopoietic stem cell transplantation for treatment of CyN and no G-CSF treatment failures. 15 deaths have occurred: 1 from ovarian cancer, 2 related to discontinuation of G-CSF, 2 from cardiac causes, 3 from homicide or accidents, 5 from complicated illnesses with multi-system problems. One closely followed patient never treated with G-CSF developed CML and one patient treated long term with immunosuppressive drugs and G-CSF developed AML. Other than this case, there have been not CyN patients developing AML in more than 5000 years of patient observation. Clostridial sepsis, the frequent cause of death in CyN patients in the pre-G-CSF era, has not been observed in CyN patients on G-CSF.These long-term observations serve to characterize cyclic neutropenia is a distinctive hematological disorder, very responsive to treatment with G-CSF and without recognized risk of evolution to AML. Disclosures:Dale:AMGEN: Consultancy. Boxer:Amgen: Equity Ownership.

Nontyphoid Salmonella-infected mycotic aneurysm in a patient with rheumatoid arthritis

A 60-year-old male presented, and was admitted, to our hospital with a 1-week history of intermittent chills and high fever. He has rheumatoid arthritis for 2 years with regular medication of hydroxychloroquine, methotrexate, sulfasalazine, and low-dose prednisolone (5 mg daily). The patient had a history of type 2 diabetes for which he was under regular medication. General malaise and dyspnea would occur during the episode of fever. On admission to our hospital, his blood pressure was 129/74 mm Hg, and his body temperature was 39 C. His heart sounds were normal with no murmur; the lungs were clear to auscultation. The abdomen was soft without palpable masses or tenderness; the liver and spleen were not palpable. The patient had mild back pain. A complete blood count revealed 9,000 leukocytes/lL and 221,000 platelets/uL, with mild anemia (hemoglobin: 9.4 g/dL). The C-reactive protein (CRP) level was 24.1 mg/dL (normal\0.5 mg/dL) and the erythrocyte sedimentation rate (ESR), 64 mm/h (normal \15 mm/h). Urine analysis and culture yielded negative results. Two blood cultures obtained before intravenous antibiotic administration tested positive for salmonella group D. No vegetations or signs of infective endocarditis were detected on transthoracic echocardiography. Computed tomography (CT) showed a saccular aneurysm arising from the abdominal aorta, with fatty stranding, free air-bubbles (arrow indicates air-bubbles and asterisk indicates aneurysm; Fig. 1) and periaortic fluid accumulation (Fig. 2). Mycotic aneurysm was confirmed. The patient received surgical management for debridement of abscess and intravenous ceftriaxone 2 gm daily continuously for 8 weeks. The patient had an excellent clinical response and was discharged 2 months later with no recurrence of fever. Mycotic aneurysms are uncommon of all aortic aneurysms, and the overall mortality is about 50 % after treatment. The common initial symptoms include pain over abdomen or back, fever, general discomfort, and hypovolaemic shock [1]. The most frequent site of mycotic aneurysms is abdominal aorta, followed by the thoracic and suprarenal abdominal aorta. High level of ESR and CRP can be found from the laboratory data. Abdominal CT can be used for early detection of mycotic aneurysms. Saccular, multilobulate, periaortic soft tissue stranding, and irregular peripheral enhancement of arterial walls can be found from the image study. The cultures from blood or the aneurismal content include Salmonella species, staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis [1]. Immunocompromised patients including HIV infection, patients with received immunosuppressive agent may develop fulminating bacteremia, which leads to the formation of infected aneurysms [2, 3]. Antimicrobial treatment alone usually results in poor prognosis; therefore, surgery may play a major role in reducing mortality. The combination of antimicrobial treatment and surgical debridement of surrounding necrotic tissue with revascularization is indicated in the patient with mycotic aneurysm. D.-H. Yang (&) Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Taichung Armed Forces General Hospital, No 348, Sec. 2, Chung Shan Road, Taiping 411, Taichung, Taiwan, Republic of China e-mail: deng6263@ms71.hinet.net

Management of Macrolide-resistant Mycoplasma pneumoniae Infection

To the Editors: In April 2012, Yamada et al1 reported an increasing trend of macrolide resistance in Mycoplasma pneumoniae strains in the United States. In Europe, reports of macrolide resistance in M. pneumoniae are still uncommon. This is the first Belgian case report describing the course and management of an infection with a proven macrolide-resistant M. pneumoniae strain. An 8-year-old girl presented with high fever, cough, mild tachypnea and left basal crepitations on lung auscultation. The white blood cell count was 5800/µL with 45% neutrophils and the C-reactive protein was 14.4 mg/L. Chest radiograph showed alveolar consolidation in the lingula and right middle lobe. Oral amoxicillin was started. The following day, she was admitted to hospital with persisting fever (up to 40.1°C) and dehydration. Testing by polymerase chain reaction (PCR) for M. pneumoniae on an upper airway swab specimen was positive, and azithromycin (200 mg daily for 5 days, ie, 10 mg/kg) was prescribed. She was discharged from hospital when she had been afebrile for 48 hours. One week later, she presented because of persistent severe cough and recurrence of high fever. Clinical examination revealed crepitations mainly in the right chest. The white blood cell count was 9600/µL with 59% neutrophils, and the C-reactive protein was 2 mg/L. Erythrocyte sedimentation rate was 40 mm/h. An upper airway swab specimen was negative for influenza virus A and B, parainfluenza virus type 1–4, respiratory syncytial virus, human metapneumovirus and adenovirus. M. pneumoniae PCR was still positive. Chest roentgenogram showed an alveolar consolidation in the right upper and left lower lobes and in the lingula. Azithromycin was restarted but without clinical improvement during the next 3 days. Antibiotic therapy was changed to ciprofloxacin (20 mg/kg/d in 3 doses) because a macrolide-resistant M. pneumoniae strain was suspected. The girl became afebrile after 24 hours. Ciprofloxacin was continued for 14 days. Lung auscultation and chest radiograph slowly normalized. A few days after discontinuation of ciprofloxacin, a new cough developed. A control throat swab still showed M. pneumoniae by PCR testing. The cough cleared spontaneously. Extensive investigations to exclude underlying humoral or cellular immunodeficiency were performed after resolution of the Mycoplasma infection but were all negative. To confirm the macrolide resistance of the M. pneumoniae strain, DNA extracts from the respiratory samples were taken before starting antibiotics, 4 days after the 5-day course of azithromycin, 3 days after changing to ciprofloxacin and 3 weeks after stopping ciprofloxacin therapy. All samples were analyzed for mutations in the 23S ribosomal RNA of M. pneumoniae associated with macrolide resistance.2 Sequencing showed that the strain in the first sample was macrolide-susceptible whereas the sequences obtained from later samples showed a mutation at position 2063 (A–G) of 23S ribosomal RNA representing the most common cause of macrolide resistance in M. pneumoniae. Because the strain initially had the macrolide-susceptible genotype, the mutation could have occurred de novo during therapy.3 Otherwise, the patient might have been infected by different genotypes of M. pneumoniae. However, all strains in the 4 samples belonged to the same genotype: variant 2b (P1-type) and VNTR-type 5/3/6/6/2 indicating the persistence of an identical strain.4 Out of concern for development of fluoroquinolone resistance of the strain obtained after ciprofloxacin therapy, nested PCRs were performed that revealed no differences in the partly sequenced gyrA, gyrB, parB and parC genes. The cause of the cough after ciprofloxacin treatment remains unclear. This case confirms the development of macrolide resistance during adequate therapy for M. pneumoniae pneumonia. We recommend molecular characterization of strains in infections not responding to treatment with macrolides. Veroniek Saegeman, MD, PhD Department of Laboratory Medicine UZ Leuven Marijke Proesmans, MD, PhD Department of Paediatrics UZ Leuven Leuven, Belgium Roger Dumke, PhD Dresden University of Technology Institute of Medical Microbiology and Hygiene Dresden, Germany

882 Hepatosplenic Cat-Scratch Disease in A 12-Years-Old Girl

BackgroundCat-scratch disease (CSD) is an infectious disease typically characterized by a self-limited regional lymphadenopathy. However, CSD can include hepatic and splenic involvement. There are few data in the literature regarding...

Levetiracetam-Induced Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome

To describe a case of levetiracetam-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. A 31-year-old white male with a low-grade astrocytoma presenting with tonic-clonic seizures was treated with levetiracetam 1 g twice daily and dexamethasone (initial dosage 12 mg/day, tapered down to 2 mg/day). On day 45 after levetiracetam initiation, dexamethasone was discontinued and levetiracetam continued. The patient developed fever and dyspnea on day 46 and was admitted to the hospital on day 49. A chest X-ray showed bilateral pulmonary interstitial infiltrates, and laboratory tests showed elevated lactate dehydrogenase (LDH; 288 U/L [reference range <204]), ferritin (223 ng/mL [13-178]), and C-reactive protein (CRP; 3.1 mg/dL [<0.5]). Neurologic fever was suspected and the reinitiation of dexamethasone at 6 mg/day was followed by improvement of all symptoms; the patient was discharged on day 55 with dexamethasone 4 mg/day for 2 more days. On day 59, 2 days after the withdrawal of dexamethasone for the second time, the patient presented with a pruritic erythematous maculopapular rash along with recurrence of fever and dyspnea, and was admitted to the hospital. A chest X-ray showed reappearance of the bilateral pulmonary interstitial infiltrates, and laboratory tests showed impaired liver function (alanine aminotransferase 60 U/L [reference range <56], aspartate aminotransferase 53 U/L [<30], LDH 516 U/L, ferritin 419 ng/mL, and CRP 2.6). A diagnosis of DRESS syndrome was suspected and levetiracetam was discontinued. Upon levetiracetam withdrawal, the patient's symptoms resolved by day 66, and radiological images showed resolution of the interstitial infiltrate by day 68. The patient was discharged on day 68. Low-grade fever persisted until day 71, with no other symptoms. During a 2-month follow-up period, liver function test results returned to normal. DRESS is a hypersensitivity reaction to several drugs, mainly antiepileptic drugs (AEDs), characterized by cutaneous, hematologic, and visceral involvement. Levetiracetam is structurally and pharmacologically unrelated to other AEDs. Previously, only one case of levetiracetam-induced DRESS syndrome had been reported, which required corticosteroids to control symptoms. We describe a case of levetiracetam-induced DRESS syndrome presenting with pneumonitis and hepatitis that resolved with levetiracetam withdrawal. Our patient was classified as a definitive DRESS case according to the RegiSCAR scoring system, which grades DRESS cases. According to the Naranjo probability scale, the adverse drug reaction was considered probable. Although levetiracetam is usually well tolerated, clinicians should be aware of the potential for it to cause DRESS syndrome.

Burkholderia cepacia Septicemia in a Pediatric Oncology Patient: A Pharmacotherapy Challenge

To discuss pharmacotherapy challenges encountered during treatment of a pediatric oncology patient with Burkholderia cepacia septicemia. An 11-year-old male with a history of aplastic anemia presented to the emergency department with a 1-day history of cough and purulent nasal discharge 6 months after undergoing bone marrow transplant. Blood cultures obtained from the patient's Broviac catheter revealed gram-negative rods. Piperacillin/tazobactam and tobramycin were administered, but the patient worsened clinically, with fever and chills. B. cepacia was identified as the offending pathogen, and the therapy was changed to meropenem and ciprofloxacin, as piperacillin/ tazobactam and tobramycin are ineffective against Burkholderia spp. Intravenous trimethoprim/sulfamethoxazole, the drug of choice for Burkholderia spp. infections, was unavailable as it had been placed on national manufacturer backorder. The patient improved initially, but he later experienced recurrence of fever, and blood culture results were positive for Burkholderia spp. Infection was eradicated after removal of the central line and administration of ceftazidime and oral minocycline. Literature reveals few cases of B. cepacia in pediatric oncology patients, and to our knowledge, no cases have been reported in bone marrow transplant patients in the US. Burkholderia spp. is highly resistant to many antibiotics, and commonly used agents for the empiric treatment of febrile neutropenia are not active against this organism. This indicates that most oncology patients who present with this infection would not receive appropriate initial treatment. In addition, antibiotic therapy may need to be modified, based on drug availability. B. cepacia is an emerging multidrug-resistant pathogen that can produce severe infection in immunocompromised patients. It is pertinent to consider this organism in oncology patients who do not improve with standard therapy, as prompt use of correct pharmacotherapy is necessary to avoid serious morbidity as well as mortality in this population.

Variations in the Number of CCL3L1 Gene Copies and Kawasaki Disease in Korean Children

High-dose intravenous immunoglobulin (IVIG) therapy is the highly effective and standard treatment for Kawasaki disease (KD). However, ~20 % of KD patients have persistent fever or recurrence of fever after the initial IVIG treatment, which increases the risk for coronary artery lesions (CALs). Furthermore, the mechanism of IVIG resistance in KD patients still is unknown. The number of CC chemokine ligand 3-like 1 (CCL3L1) gene copies is reported to be associated with KD and IVIG resistance in Japanese patients. In addition, the authors observed significant upregulation of the CCL3L1 gene expression after in vitro immunoglobulin treatment in B cell lines derived from KD patients. Therefore, this study of 459 KD patients and 496 healthy control subjects tested whether the number of CCL3L1 gene copies is associated with a risk of KD, CALs, and/or IVIG resistance in Korean KD patients. However, the number of CCL3L1 gene copies was not associated with KD (P = 0.18), CAL formation (P = 0.062), or the IVIG resistance (P = 0.90). Therefore, the results indicate that the number of CCL3L1 gene copies does not have a role in susceptibility to KD or CALs nor with IVIG resistance in Korean KD patients.

Sulphasalazine-induced aseptic meningitis with facial and nuchal edema in a patient with spondyloarthritis

Sulphasalazine-induced aseptic meningitis with facial and nuchal edema in a patient with spondyloarthritis

Adult-onset Acute Rheumatic Fever

A 62-year-old man was hospitalized for acute rheumatic fever. He had previously suffered from rheumatic fever at 15 years of age. The rheumatic fever was complicated by carditis, which caused valve disease that required surgical treatment. The incidence of rheumatic fever has decreased in most developed countries with improvements in sanitary conditions. The low incidence of this disease makes a timely and accurate diagnosis difficult. Due to the fact that both the first occurrence and recurrence of acute rheumatic fever can occur in the elderly and adults, this potential disease should not be overlooked when making a differential diagnosis.

Once weekly azithromycin in secondary prevention of rheumatic fever

Rheumatic fever and rheumatic heart disease (RHD) are still important problems in developing countries. Secondary prophylaxis which is the most cost-effective method in preventing recurrences of rheumatic fever is fraught with problems of drug compliance. The utility of 500 mg once weekly azithromycin (AZT), an orally effective long-acting antibiotic was evaluated against oral penicillin (phenoxy methyl penicillin 250 mg twice daily) in this study. Forty-eight consecutive patients (44% males, mean age 29.4 years) with established RHD were randomised into two groups-26 patients received AZT and 22 received oral penicillin. Patients were evaluated at randomisation, at 1 month, 3 months, and 6 months, clinically, serologically and by throat swab culture. End points were absence of streptococcal colonisation, infection or fever at the end of 6 months. During the study, 4 patients (15.4%) in the AZT group developed sore throat and fever, had positive throat culture and positive serology indicating streptococcal infection. None satisfied the criteria for rheumatic fever reactivation. None in the oral penicillin group developed streptococcal infection. In conclusion, weekly 500 mg of AZT is not effective in the prevention of streptococcal throat infection compared to oral penicillin therapy in adult patients with established RHD.