Tackling fever and inflammation of unknown origin: the do's and don'ts.

Fever and inflammation of unknown origin continue to challenge the clinician. The differential diagnosis is broad and potential diagnostic pitfalls abound. To guide the approach, the authors discuss the do's and don'ts.

Mortality in patients presenting with fever of unknown origin.

BACKGROUND: Few data exist on the contemporary prognosis of patients presenting with fever of unknown origin (FUO). METHODS: The data of 436 adult immunocompetent patients presenting with FUO between 2000 and 2010 and followed for at least 6 months were analyzed, with a focus on FUO-related deaths. The following variables were assessed in survivors and non-survivors: age, underlying diagnosis, and, in a nested case-control design, fever periodicity, selected laboratory parameters (including peripheral blood counts, enzymes, and inflammatory markers) and organomegaly. RESULTS: Thirty FUO-related deaths occurred (6·9%). Malignancy accounted for 11% of fevers but for 60% of deaths. Especially non-Hodgkin lymphoma carried a disproportionally high death toll. In the non-malignant categories, fatality rates were below 6%. All patients discharged without diagnosis in spite of ample investigations (n = 164) survived. Besides malignancy, age, continuous (as opposed to episodic) fever, anaemia, leucopenia, LDH levels, and hepatomegaly were associated with mortality. CONCLUSIONS: Fatality rates of FUO have continuously declined over the past decades. Malignancy, including lymphoma, remains a cardinal cause of death. Patients with FUO discharged without diagnosis survive.

Lymph node biopsies in a general internal medicine department: algorithm or individualized decision-making?

BACKGROUND: Lymphadenopathy (LA) imposes a diagnostic challenge in internal medicine. Exclusion of malignancy is the primary concern. METHODS: A retrospective case series, including 40 adult patients from the general internal medicine department who underwent lymph node biopsy (LNB) at a single university hospital. Demographics, clinical data and histopathological diagnoses were registered. By means of the latest medical record, we obtained a final diagnosis for each patient and subsequently searched for variables correlated with malignancy. Follow-up was at least one year in 95% of cases. RESULTS: The prevalence of malignancy was 58%. Older age (p = 0.02) was significantly correlated with malignancy. The presence of painful lymphadenopathy at clinical examination (p = 0.02) was significantly associated with a benign outcome. No single or combination of baseline variables satisfactorily excluded malignancy. Histopathological analysis correctly predicted malignancy in 93% of cases. In two cases, an initial diagnosis of benign non-specific lymphadenopathy was reversed to non-Hodgkin lymphoma. In one case the pathological diagnosis was inconclusive. CONCLUSION: Rather than following a universal algorithm to determine the need for LNB in patients with LA, we call for individualized decision-making in each case, carefully appreciating all available information. Additionally, one should keep in mind that false-negative results occur due to sampling errors. Therefore, a minimal number of cases should end with a final diagnosis of benign non-specific lymphadenopathy. Intensive, multidisciplinary cooperation with surgeon and pathologist is needed. Moreover, clinical follow-up should be at least one year.

Diagnostic yield of syncope investigation (initiated) in the emergency department: a pilot study.

OBJECTIVE: To determine the diagnostic yield of investigations in patients presenting to the emergency department (ED) with syncope. To determine the cause of the syncope. PATIENTS AND METHODS: We retrospectively identified consecutive patients presenting to the ED who underwent investigations for syncope at a 1900 bed university teaching hospital during 4 months. From the medical records we abstracted clinical information, results of testing and the cause of syncope. RESULTS: A total of 117 patients participated in the study. The mean age was 57 year (range 6-93 year), and 45% were male. Diagnostic procedures most often performed were blood analysis, ECG, chest X-ray and Holter monitoring (respectively in 94.1%, 88.8%, 74.4% and 36,8% of the patients). The corresponding diagnostic yield for these test was 4.5%, 6.7%, 0% and 16.3%. Other procedures were (% of patients; diagnostic yield): Ct scan of the head (35.1%; 0%), transthoracic echocardiogram (24.8%; 6.9%), ECG monitoring (24.8%; 27.6%), EEG (19.7%; 0%), neurovascular imaging (19.7%; 0%), abdominal ultrasound (11.1%; 0%), Ct scan of the chest (11.1%; 23.1%), head up tilt test (7.7%; 11.1%), carotid sinus massage (3.4%; 0%), pulmonary ventilation perfusion scintigraphy (2.6%; 33%) and exercise test (1.7%; 0%). The most common cause of syncope was neurocardiogenic (58,5% of patients), followed by orthostatic (11.1%), cardiac (11.1%), unknown (9.3%), hyperventilation (3.4%), pulmonary embolism (2.5%), drug related (2.5%) and others (1.7%). CONCLUSION: Patients admitted in the ED for syncope undergo various investigations. However, the diagnostic yield is poor.The most common cause of syncope is neurocardiogenic, followed by orthostatic and cardiac.

Short-term return visits of 'general internal medicine' patients to the emergency department: extent and risk factors.

OBJECTIVES: Although emergency department (ED) return visits are a significant problem universally, it has not been previously studied in our ED. The aim of this study was to determine the extent of the problem in our ED, to identify the relevant clinical predictor variables and to detect diagnostic errors. METHODS: A retrospective observational study of ED return visits by patients managed by the General Internal Medicine (GIM) service was performed. The study was performed over a one year period at a tertiary hospital ED. Data are reported as relative risk (RR) and 95% confidence interval (CI). RESULTS: There were a total of 51.210 ED visits during the study period. The total number of ED return visits within 72 hours was 1.124 (2,19%; 95% CI 2,07 to 2,32). The total number of ED patients managed by the GIM service was 9.511. The percentage of patients treated by the GIM service who returned to the ED within 72 hours was 1,48% (95% CI 1,25 to 1,74) when calculated for the whole group and 2,9 % (95% CI 2,46-3,41) for those discharged home from the ED (n = 4.860). The majority (82,98%) of ED return visits by patients discharged from the GIM service were unscheduled and related to their index presenting complaint. Abdominal pain was the commonest initial presenting symptom in the patients who returned to the ED after discharge. Patients with diarrhoea as the initial initial presenting symptom had the highest relative risk of an ED return visit (RR = 4.07). CONCLUSION: The percentage ED return visits by patients discharged from the ED by the GIM service is 1,48%. Patients presenting with diarrhoea as the initial presenting symptom have the highest relative risk of an early ED return visit. Our main practical conclusion is that patients with abdominal pain need to be re-examined carefully and instructed about potential evolution before discharge.

Intravascular large B-cell lymphoma of the uterus presenting as fever of unknown origin (FUO) and revealed by FDG-PET.

Non-Hodgkin's lymphoma (NHL) is a common cause of Fever of Unknown Origin (FUO) but the presentation as a gynaecologic malignancy is exceedingly rare. To our knowledge, this represents the first report of an intravascular large B-cell lymphoma of the uterus presenting with fever of unknown origin. After a standard clinical work-up for FUO, the endometrial curettage directed by the finding of a localized fluoro-deoxyglucose Positron Emission Tomography (FDG-PET) hot spot in the pelvic area, yielded material revealing an intr avascular B-cell lymphoma. A total abdominal hysterectomy confirmed the presence of an intravascular large B-cell lymphoma in the lumina of small blood vessels of the uterus.

Repetitive 18-fluorodeoxyglucose positron emission tomography in isolated polymyalgia rheumatica: a prospective study in 35 patients.

OBJECTIVE: To study fluorodeoxyglucose (FDG) deposition in different vascular beds and in the large joints of patients with isolated polymyalgia rheumatica (PMR), and to investigate whether there is a relation between FDG-positron emission tomography (PET) results and risk of relapse. METHODS: All consecutive patients with isolated PMR underwent a FDG-PET scan before treatment with steroids was started and--if logistics allowed--at 3 and 6 months. PET scans were scored at seven different vascular areas and a total vascular score (TVS) was calculated, ranging from 0 to 21. FDG uptake in the shoulders, the hips and the processi spinosi of the vertebrae was scored as 0 (no uptake), 1 (moderate uptake) or 2 (intense uptake). RESULTS: Thirty-five patients entered the study. At diagnosis, vascular FDG uptake was noted in 11 patients (31%), predominantly at the subclavian arteries. Mean TVS was low. FDG uptake in the shoulders was noted in 94% of patients, in the hips in 89% and in the processi spinosi of the vertebrae in 51%. The intensity of FDG uptake in the large vessels or in the shoulders, hips or processi spinosi did not correlate with the risk of relapse. CONCLUSIONS: Only one in three patients has an (moderately) increased vascular FDG uptake, especially in the subclavian arteries. The vast majority has inflammation of shoulders and hips, and half of them have increased FDG-uptake at the processi spinosi. Results of FDG-PET scans in patients with PMR did not correlate with their risk of relapse.

Localised plasma-cell type Castleman's disease and AA-amyloidosis cured by resection. A case report and review of the literature.

Castleman's disease (CD) is a rare atypical lymphoproliferative disorder with frequent, yet less well known renal involvement. We describe the case of a 58-year-old woman with localised abdominal plasma-cell type CD complicated by nephrotic syndrome due to renal amyloidosis. 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) confirmed the unicentric nature. Resection of the mass resulted in regression of the signs of inflammation, a negative FDG-PET and complete remission of the nephrotic syndrome. A review of the literature of renal involvement (incidence, clinical and pathological manifestations, treatment and prognosis) in CD is provided.

Fever of unknown origin in adults: 40 years on.

A revision of the criteria of fever of unknown origin (FUO), established in 1961, is desirable because of important evolutions in medical practice and the emergence of new patient populations. The development of rapid laboratory tests and powerful diagnostic tools, such as ultrasonography, computed tomography and magnetic resonance imaging often makes hospitalization unnecessary and new categories of patients such as those with HIV infection, neutropenia, immunosuppression and nosocomial illness require an approach different from classical FUO. The more then 200 reported causes of FUO can be classified into four diagnostic categories; infections, tumours, noninfectious inflammatory diseases (NIID) and miscellaneous. A uniform classification system is highly wanted to allow comparison between different series. The reports of the 1990s show slight changes in the distribution of causes, namely less infections, less tumours, more NIID and more undiagnosed cases. A uniform diagnostic strategy cannot be determined. The initial investigation should be directed by potentially diagnostic clues revealed by extensive history, meticulous physical examination and a standard set of laboratory tests. 18Fluoro-deoxy-glucose-positron-emitted-tomography is a new valuable total body scintigraphy in the search for the site of origin of the fever. In view of the rather good long-term prognosis, a wait-and-see strategy may be more appropriate than a systematic staged approach. Elderly patients and patients with episodic fever represent two specific groups of classical FUO that require a distinct approach. HIV-associated, nosocomial and neutropenic FUO should be considered as separate clinical entities.

Emphysematous pyelonephritis: no longer a surgical disease?

Emphysematous pyelonephritis is a rare, life-threatening infection of the kidney characterized by the presence of gas within the renal parenchyma, the renal collecting system and the perinephric tissue. It usually develops in diabetic patients and often presents abruptly with bacteraemia, septic shock and acute renal failure. Diagnosis can be delayed because the symptoms mimic a classical upper urinary tract infection. Aggressive management, including parenteral antibiotic therapy, treatment of septic shock and control of the glycaemia, is mandatory. Immediate nephrectomy has been considered to be essential to increase the chance of survival. Recently, percutaneous drainage has been reported as a kidney-saving and life-saving alternative to surgery. We present a case of severe emphysematous pyelonephritis in which there was full recovery after antibiotic treatment combined with temporary percutaneous drainage. The therapeutic options in this rare, life-threatening condition are discussed.

Microscopic haematuria in giant cell arteritis.

Giant cell arteritis (GCA) is traditionally considered to spare the kidney, although an uncontrolled study reported microscopic haematuria in 10 out of 30 patients with GCA. To study the frequency and the characteristics of microscopic haematuria in GCA, we retrospectively studied 42 patients with biopsy-proven GCA, 39 patients with polymyalgia rheumatica (PMR) and 62 control patients >or=60 years of age, admitted to the general internal medicine unit. Patients with pyuria, significant bacteriuria or a known haematuric disorder were excluded. Microscopic haematuria was defined as the presence of >5 red blood cells (RBC) per high-power field (sediment counts) or of >8 RBC/microl (direct counting). Microscopic haematuria was present at presentation in 47.6% of the GCA patients, versus 17.9% of the PMR patients (P = 0.005) and 21.0% of the control patients (P = 0.008). Urinary RBC were predominantly dysmorphic in all GCA patients in whom RBC morphology was assessed (n = 7). Presenting symptoms, renal function, arterial blood pressure and degree of leukocyturia did not differ significantly between GCA patients with or without haematuria. After the initiation of corticosteroid therapy, microscopic haematuria was no longer detectable in 25 of 35 GCA patients (71.4%). Microscopic haematuria of renal origin is frequent but generally benign in patients with GCA. Its presence, if unassociated with blood pressure elevation or renal function deterioration, helps to rule in rather than to rule out the diagnosis of GCA. In the typical setting invasive urologic and nephrologic work-up may not be warranted.

Chest pain in the emergency department: the broad spectrum of causes.

We performed a prospective study to describe the broad spectrum of causes of chest pain in patients presenting to the emergency department and to compare the diagnoses in referred patients, self-referred patients and patients rushed in by ambulance. The final diagnosis in a consecutive case series of 578 chest pain patients was established after discharge from the hospital. The underlying disorders were grouped into cardiac, respiratory, gastro-oesophageal disorders, musculoskeletal pathology, somatization disorders, other diseases and unknown. For comparison of the frequencies of the disease categories the Chi-squared test was used. Out of 578 patients, 161 (27.9%) were self-referred, 369 (63.8%) were referred by the general practitioner and 48 (8.3%) were rushed in by ambulance. Cardiac diseases represented 51.7% of the cases, myocardial infarction and unstable angina 19% and 12.8% respectively Cardiac diseases were statistically significantly less common in self-referred patients (p<0.0005). Pulmonary diseases encompassed 14.2% of the population, followed by somatization disorders (9.2%), musculoskeletal pathology (7.1%) and other causes (4.3%). In 11.1% of the cases no definite final diagnosis could be established. Somatization disorders were significantly more frequent in self-referred and ambulance patients. Cardiac and pulmonary problems are the most frequent underlying disorders in acute chest pain patients in the emergency department. Somatization disorders and musculoskeletal pathology represented respectively 19.1% and 14.8% of the non-cardiac causes. The referral pattern influenced significantly the distribution of the disease categories with more cardiac and less psychiatric disorders in referred patients.

Chest pain in general practice or in the hospital emergency department: is it the same?

OBJECTIVE: The aim of the present study was to provide a description of the impact of setting on the diagnostic case mix that is identified in consecutive patients presenting with chest pain. METHODS: A cross-sectional study was carried out of patients presenting with chest pain according to setting: general practice, self-referred, referred or arriving by ambulance at the hospital emergency department (ED). GPs from 25 general practices situated in the Flemish part of Belgium were recruited, and the hospital involved was a major teaching hospital in the same area. A total of 320 patients in general practice and 580 patients in the hospital ED were studied. The difference in prevalence rates for the major diagnostic categories was the main outcome measure. RESULTS: Gastrointestinal disorders, musculoskeletal problems and psychopathology are identified more frequently in general practice; and serious lung diseases and cardiovascular diseases in the hospital ED. Within the hospital, there is a strong trend towards increasing frequency of serious cardiovascular diseases including unstable angina (P = 0.01) from self-referred to referred patients and those rushed in by ambulance. The opposite trend was identified for respiratory (P = 0.02) and musculoskeletal (P = 0.07) diseases. The diagnostic case mix in self-referred patients tends to be more similar to the other groups of hospital patients than to patients in general practice. CONCLUSIONS: There is a large difference between the diagnostic case mix presented in general practice compared with the ED and among referral-related subgroups within the hospital emergency department.

The antibiotic and anti-inflammatory treatment of bacterial meningitis in adults: do we have to change our strategies in an era of increasing antibiotic resistance?

Community acquired bacterial meningitis remains a feared infection because of its high morbidity and mortality. During the last decade, the incidence and the microbial resistance patterns of pathogens causing bacterial meningitis have changed considerably. A sharp increase in meningococcal disease has been observed and meningitis caused by penicillin resistant Streptococcus pneumoniae emerged as a matter of major concern. Since pneumococcal resistance in Belgium to third generation cephalosporins remains rare and low level, addition of vancomycin to the initial empirical therapy including third generation cephalosporins is not yet necessary. However, the evolution of the resistance patterns of invasive S. pneumoniae should be followed very carefully. The emergence of penicillin resistant pneumococci also raises concern about the safety of adjuvant anti-inflammatory therapy with dexamethasone. Although there is a growing evidence suggesting a decrease of neurological complications after administration of adjuvant dexamethasone, this therapy may lower the already borderline penetration through the blood-brain barrier of the currently used antibiotics. This may result in therapeutic failure. We therefore presently do not advocate the routine use of dexamethasone in the therapy of adult bacterial meningitis.