Fever of Unknown Origin in Turkey

Abstract. Background: The etiology of fever of unknown origin (FUO) includes primarily infectious, collagen-vascular and neoplastic diseases. The distribution of the disorders causing FUO may differ according to the geographic area and the socioeconomical status of the country. Moreover, the developments in radiographic and microbiologic methods have changed the spectrum of diseases causing FUO. Materials and Methods: We reviewed 117 cases that fulfilled the criteria of FUO followed in our department during the period 1984 to 2001. Results: The etiology of FUO was infectious diseases in 34% of the patients, collagen-vascular diseases in 23%, neoplasms in 19% and miscellaneous diseases in 10%. In 14% of the cases the etiology could not be found. The three leading diseases were tuberculosis (24%), lymphomas (19%) and adult-onset Stills disease (11%). Tuberculosis was found to be a more common cause of FUO than reported in studies in developed countries. Invasive procedures helped to establish the diagnosis in 50 out of 92 patients (43%). As a final diagnostic procedure, laparotomy aided the establishment of a diagnosis in 15 out of 20 patients (75%). Conclusion: Although the relative rate of infectious disease as etiologic category is less commonly encountered, infectious disease, especially tuberculosis, remains a common cause of FUO. Although several diseases may lead to FUO, lymphomas, adult-onset Stills disease and particularly tuberculosis should be considered in the differential diagnosis of a patient admitted with FUO.     

不明原因发热449例临床分析

目的探讨不明原因发热(FUO)的原因。方法回顾性分析2000年1月∽2003年12月间在我院住院诊治的符合不明原因发热诊断标准的患者449例。结果449例患者中经各种检查或诊断性治疗最终明确诊断者387例,确诊率为86．2％。病因包括：感染性疾病220例(56．8％),其中结核病96例,占43．6％(96／220);结缔组织病76例(19．6％),其中Still病占34．2％(26／76),系统性红斑狼疮占18．4％(14／76),血管炎占13．2％(10／76);肿瘤性疾病64例(16．5％),其中淋巴瘤占39．1％(25／64);其他疾病27例(7．0％),其中坏死性淋巴结炎占33．3％(9／27),伪热占22．2％(6／27),药物热占26％(7／27);出院时仍未确诊的62例(13．8％)。结论感染性疾病是本组FUO患者的主要病因,结核病是其中的主要病种,结缔组织病和肿瘤性疾病在本组FUO病因中也占重要地位;大多数FUO经仔细的临床检查和分析是可以得到确诊的。     

长期不明原因发热388例临床分析

目的 探讨不明原因长期发热患者的病因.方法 分析在我院住院诊治且符合不明原因发热诊断标准的388例患者的临床资料.结果 388例患者中经各种检查或诊断性治疗最终明确诊断者253例,确诊率为65.2%.病因：感染性疾病131例,占51.8%,其中结核病55例,占感染性疾病的42.0%（55/131）;结缔组织病69例,占27.3%,成人still病占结缔组织病的30.3%（20/69）;肿瘤37例,占14.6%,其中淋巴瘤占86.4%（32/37）;其他疾病16例,占6.3%;原因未明者135例,占34.8%.结论 感染性疾病仍然是不明原因发热的主要病因,结核病尤其是肺外结核占较大比例.肿瘤性疾病和结缔组织病在发热待查中也占有相当比例,淋巴瘤和成人still疾病是这两类疾病的主要病种.     

Fever of unknown origin in uremic patients: a controlled prospective study.

Twenty-nine uremic patients with fever of unknown origin (FUO) admitted to our clinic between 1994 and 1998 were evaluated prospectively. A group of 50 consecutive non-uremic patients with FUO followed up during the same period was used for comparison. The causes of FUO found in the uremic and non-uremic groups, respectively were as follows: infectious diseases, 69 vs. 44% (p = 0.03); collagen vascular diseases, 6.9 vs. 6%; neoplasms, 3.4 vs. 26%; miscellaneous causes, 3.4 vs. 16%; and undiagnosed, 17.2 vs. 8%. Tuberculosis was the most common cause of FUO in both groups. The spectrum of underlying conditions for FUO in our uremic patients differed from that in the non-uremic patients and the uremic patients had a very high propensity for infectious diseases, especially tuberculosis.     

发热待查75例临床分析

目的探讨不明原因发热(FUO)的病因和临床特征。方法回顾性分析2005年1月～2012年1月在我科住院且符合FUO诊断标准的75例患者的临床资料,总结了病因、诊断方法和临床表现。结果 75例患者中,68例(90.7%)最终确诊,感染性疾病22例(32.4%),其中结核病9例(40.9%)、传染性单核细胞增多症5例(22.7%);结缔组织病29例(42.6%),其中成人Still病17例(58.6%)、系统性红斑狼疮6例(20.7%);恶性肿瘤10例(14.7%),其中淋巴瘤6例(60.0%);其他疾病7例(10.3%),其中组织细胞坏死性淋巴结炎4例(57.1%)。结论 FUO涉及的病因众多,发病机制复杂,感染性疾病、结缔组织病仍是发热待查的主要原因,肿瘤性疾病在发热待查中也占相当的比例,临床工作中要开阔思路,全面搜集资料,以利于明确诊断。     

常规实验室检查对不明原因发热的诊断价值

目的 探讨6项常规实验室检查项目在不明原因发热(fever of unknown origin,FUO)诊断中的价值,为提高发热待查患者的确诊率提供参考.方法 回顾性分析我院2002年1月-2009年12月确诊的132例FUO患者入院时白细胞、中性粒细胞、淋巴细胞、红细胞沉降率、C-反应蛋白及免疫球蛋白(IgG、IgM...     

Fever of Unknown Origin in Taiwan

Abstract Background: Fever of unknown origin (FUO) is a challenging problem worldwide. There was no prospective study of FUO in the past two decades in Taiwan. A prospective study was conducted. Materials and Methods: The prospective study was undertaken from March 2001 to May 2002. All patients fulfilling the modified criteria for FUO, either admitted, referred or consulted in a medical center in southern Taiwan, were enrolled for analysis. Results: A total of 94 cases met the criteria of FUO. The final diagnoses of FUO consisted of 54 infectious diseases (57.4%), 8 hematologic/neoplastic (8.5%), 7 noninfectious inflammatory (7.4%), 8 miscellaneous (8.5%) and 17 undiagnosed (18.1%) cases. The single most common cause of FUO was tuberculosis. Some infectious diseases, such as rickettsiosis and melioidosis, were rarely reported in western countries. Three patients with hemophagocytotic syndrome without ascertainable etiologies were present with FUO in this study. Between the patients with and those without a final diagnosis, the short-term survival (3 months) was compared by the Kaplan–Meier analysis, which revealed no difference. Conclusions: Mycobacteriosis is still the leading cause of FUO in Taiwan and it is important to identify this treatable disease from all causes of FUO. This study has showed geographical variation among the studies of FUO.     

Fever of unknown origin in Turkey: evaluation of 87 cases during a nine-year-period of study

OBJECTIVES: To investigate fever of unknown origin (FUO) in 87 patients. METHODS: We investigated 87 (61 male) patients with FUO using the criteria of Petersdorf and Beeson [Medicine 40 (1961) 1] hospitalized between January 1994 and August 2002 at Cukurova University Hospital. RESULTS: The median age of the patients was 38.5 years (range: 14-80 years). Eleven patients (12.6%) were over 65. The mean duration of hospitalization was 22.5+/-13 days. Infectious diseases were the most common causes of FUO. Tuberculosis (n=15, 17.2%), infective endocarditis (n=6), abdominal abscess (n=6), brucellosis (n=5), urinary tract infection (n=5), visceral leishmaniasis (n=4), salmonellosis (n=3), rhinocerebral mucormycosis (n=4), atypical pneumonia, cerebral toxoplasmosis, Cytomegalovirus infection or encephalitis were diagnosed in 51 (58.6%) patients. The second most common causes of FUO were collagen vascular diseases (n=16, 18.3%) determined as vasculitis syndrome, adult Still's disease (n=4), systemic lupus erythematosus, Beh?et's disease, juvenile ankylosing spondylitis. Neoplasm was found in 12 (13.7%) patients; (non-Hodgkin lymphoma, Hodgkin lymphoma, chronic myeloid leukemia, gastrointestinal tract carcinoma, glioma). Miscellaneous diseases thyroiditis, granulomatous hepatitis were diagnosed in two (2.2%) patients. On admission, six patients (6.8%) were neutropenic. CONCLUSIONS: Infectious diseases, especially tuberculosis, were the leading diagnostic category of FUO in this study. Adult Still's disease was more common than expected. An aetiological diagnosis could not be reached in six (7%) patients who were followed for 1 year. Five of these patients completely recovered, and one patient died.     

Revised definition of 'fever of unknown origin': limitations and opportunities

AIM: The limitations and opportunities of revised definition of fevers of unknown origin (FUO) in comparison to conventional definition were investigated, and prehospital characteristics of the patients were detailed. METHOD: The patients were grouped according to both revised and classic definitions of FUO. RESULTS: Fifty-nine of the 80 patients (74%) met the conventional definition of FUO. Before their admissions, all patients had at least one course of antibiotic therapy. The aetiology was infectious in 52%, autoimmune in 19%, and neoplastic in 17%. In 12% of the cases, the reason for high fever could not be explained. The most common infectious aetiologies were various forms of tuberculosis (12%), brucellosis (12%), salmonella (7%) and malaria (5%). The revised definition inflated the rate of infectious aetiology. CONCLUSION: A standardized set of diagnostic tools used in this study was suggested. The subjects of FUO series have to be screened for endemic infections.     

不明原因长期发热110例临床分析

目的探讨我国不明原因长期发热的病因。方法回顾性地总结分析１９９５年１月至１９９６年１２月间在我科住院且符合不明原因长期发热（ＦＵＯ）诊断标准的患者１１０例。结果１１０例患者经各种检查或特异性治疗最后明确诊断者有１０２例，确诊率为９２７％。病因：感染性疾病５８例，占５２７％，其中结核病２７例，占感染性疾病的４６６％（２７／５８）；自身免疫性疾病２１例，占１９１％，Ｓｔｉｌ病占自身免疫性疾病的４２９％（９／２１）；肿瘤性疾病７例，占６４％；其他疾病１６例，占１４５％；原因仍未明者８例，占７３％。结论感染性疾病仍然是ＦＵＯ的主要病因，结核病尤其是肺外结核的发病率有增高趋势，本组肺外结核占３１０％（１８／５８）；其次自身免疫性疾病和肿瘤性疾病在ＦＵＯ中也占有相当比例，Ｓｔｉｌ病和不典型淋巴瘤诊断比较困难，但大多数ＦＵＯ通过仔细检查和分析最终可明确诊断     

Fever of unknown origin in North Jordan

This is a retrospective study of all patients admitted to Basma Teaching Hospital with a diagnosis of fever of unknown origin (FUO). The study took place from January 1995 to December 2001. Fifty-two patients fulfilled the criteria of FUO. Infections were responsible for 26 cases (50%), malignancy for eight cases (15%), connective tissue disorder for six cases (12%) and others for 12 cases (23%). Infections remain the most common causes of FUO in Jordan, mainly tuberculosis, brucellosis and typhoid fever.     

Fever of undetermined origin in patients with the acquired immunodeficiency syndrome in Brazil: report on 55 cases.

The medical records of patients with AIDS admitted to a general hospital in Brazil from 1989 to 1997 were reviewed retrospectively with the aim at defining the frequency and etiology of fever of undetermined origin (FUO) in HIV-infected patients of a tropical country and to evaluate the usefulness of the main diagnostic procedures. 188 (58.4%) out of 322 patients reported fever at admission to hospital and 55 (17.1%) had FUO. Those with FUO had a mean CD4+ cell count of 98/ml. A cause of fever was identified for 45 patients (81.8%). Tuberculosis (32.7%), Pneumocystis carinii pneumonia (10.9%), and Mycobacterium avium complex (9.1%) were the most frequent diagnoses. Other infectious diseases are also of note, such as cryptococcal meningitis (5.5%), sinusitis (3.6%), Salmonella-S. mansoni association (3.6%), disseminated histoplasmosis (3.6%), neurosyphilis (1.8%), and isosporiasis (1.8%). Four patients had non-Hodgkin's lymphoma (7.3%). We conclude that an initial aggressive diagnostic approach should be always considered because biopsies (lymph node, liver and bone marrow) produced the highest yield in the diagnosis of FUO and the majority of the diagnosed diseases are treatable. The association of diseases is common and have contributed to delay the final diagnosis of FUO in most cases. In our study area the routine request of hemocultures for Salmonella infection and the investigation of cryptococcal antigen in the serum should be considered.     

Fever of unknown origin: analysis of 71 consecutive cases

BACKGROUND: Fever of unknown origin (FUO) is still an important problem in clinical practice. Evaluation of patient characteristics may clarify the utility of diagnostic tests and etiologies of FUO. METHODS: Fever of unknown origin in 71 patients was investigated at Ankara Numune Education and Research Hospital in Turkey between February 2001 and December 2004. RESULTS: Mean hospital stay and fever duration was 20.5 days and 44 days, respectively. Etiologies of FUO were as follows: infections 32 (45.1%), collagen vascular disease 19 (26.8%), neoplasm 10 (14.1%), and miscellaneous diseases 4 (5.6%). Diagnosis remained obscure in 6 patients (8.5 %). Tuberculosis was found to be 40% of the infectious causes of FUO. Mean hospital stay and fever duration were prolonged in infectious cases. Female predominance was observed in collagen vascular diseases (P = 0.047). Splenomegaly and lymphadenopathy were common in the neoplasm group (P = 0.017, P = 0.017, respectively). Erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase and lactate hydrogenase levels were elevated in patients with collagen vascular diseases. Nine (12.7%) patients died during the follow-up period. CONCLUSIONS: Hospital stay and fever duration were prolonged in the infectious group of FUO patients. Infectious diseases, particularly tuberculosis, were the most important cause of FUO in our series. Tuberculosis should be kept in mind as an important etiology of FUO countries where tuberculosis is endemic.     

Fever of unknown origin: review of 86 patients treated in community hospitals.

This study describes the clinical features of fever of unknown origin (FUO) in 86 patients in a community setting from 1984 to 1990. Infectious diseases remain the most common category of illnesses causing FUO; in this study, infectious diseases including recently described diseases--such as AIDS (three cases) and Lyme disease (one case)--caused FUO in 28 patients. Although percutaneous computed tomography-guided procedures were useful for obtaining diagnostic specimens (15 cases), a noninvasive approach established the diagnosis in many instances (37 cases). In all but nine cases, diagnostic testing was guided by abnormalities detected during the physical examination or routine laboratory tests.     

Fever of unknown origin: subacute thyroiditis versus typhoid fever

Fever of unknown origin (FUO) is not infrequently a diagnostic dilemma for clinicians. Common infectious causes include endocarditis and abscesses in adults, and noninfectious causes include neoplasms and certain collagen vascular diseases, for example, polymyalgia rheumatica, various vasculitides, and juvenile rheumatoid arthritis (adult Still's disease). Subacute thyroiditis is a rare cause of FUO. Among the infectious causes of FUO, typhoid fever is relatively uncommon. We present a case of FUO in a traveler returning from India whose initial complaints were that of left-sided neck pain and angle of the jaw pain, which initially suggested the diagnosis of subacute thyroiditis. After an extensive FUO workup, when typhoid fever is a likely diagnostic possibility, an empiric trial of anti- Salmonella therapy has diagnostic and therapeutic significance. The presence of relative bradycardia, and response to quinolone therapy, was the basis of the clinical diagnosis of typhoid fever as the explanation for this patients FUO. This case illustrates the diagnostic difficulties in assessing patients with FUO with few diagnostic findings.     

Utility of polymerase chain reaction in diagnosis of tuberculosis from samples of bone marrow aspirate

Fever of unknown origin (FUO) poses a diagnostic challenge to the clinicians, with a differential diagnosis as varied as neoplastic and infectious diseases. In developing countries, the infectious causes are responsible for more cases of FUO, with tuberculosis as one of the main causes of classic FUO. Disseminated tuberculosis with negative pulmonary findings is a diagnostic problem. This study examines the diagnostic utility of the polymerase chain reaction (PCR) in samples of bone marrow aspirate in 85 patients presenting with diverse clinical symptoms. Using primers specific for Mycobacterium tuberculosis, tubercular etiology was detected in 33% of patients clinically suspected of tuberculosis while culture on Lowenstein-Jensen medium grew M. tuberculosis in only one patient (2.5%). None of these patients had been diagnosed by microscopy. Clinical improvement with ATT was observed in 85% of the patients with positive PCR. PCR demonstrated much higher sensitivity and specificity, thereby facilitating early therapeutic decisions for suspected extrapulmonary tuberculosis.     

A retrospective study of hospitalized patients with fever of unknown origin (FUO) past six years

We analysed retrospectively 48 hospitalized patients with fever of unknown origin (FUO) from 1982 through 1988. The criteria of FUO were (1) temperature of more than 38.3 degrees C documented on several occasions (2) overall duration of illness more than three weeks, (3) uncertain diagnosis till one week after hospitalization. Of this group of FUO, 25 patients (52.1%) were found to have infections, 8 patients (16.7%) had collagen disorders, 7 patients (14.6%) had neoplastic disorders, 3 patients (6.3%) were crohn disease and 5 patients (10.4%) were undiagnosed. Among infectious diseases, chronic tonsillitis was the most frequent (5 patients: 20%) and they were diagnosed by the provocative examination. Non bacterial meningitis and cervical lymphadenitis were diagnosed in all 3 patients (12% in all), Adult Still's disease was found in 3 patients (37.5%) and systemic lupus erythematosus (SLE) in 2 patients (25%) in collagen disease. Immunoblastic lymphadenopathy was diagnosed in 3 patients (42.9%) of malignant diseases. Three cases of Crohn disease were revealed in all the patients of the miscellaneous group. Duration of fever was relatively short in infection diseases compared to malignant and Crohn diseases. The most common laboratory abnormality is an elevated erythrocyte sedimentation rate (89.6%). As the final diagnosis of FUO are changing with the development of diagnostic techniques, a new criteria of FUO is necessary.     

Infektionen als Ursache von Fieber unklarer Genese

Infectious diseases are important causes of fever of unknown origin (FUO). The spectrum of infectious agents is broad and diagnosis depends on careful evaluation of individual risk factors. Infectious diseases presenting as FUO are frequently atypical presentations of well known infections, e.g. tuberculosis or infectious endocarditis. In this review we present an overview of infectious causes of FUO classified into community acquired infections, nosocomial infections, and infections in immunocompromised hosts.     

Fever of unknown origin in older adults

Evaluation of elderly patients who have fever of unknown origin (FUO) requires a different perspective from that needed for young patients. Differential diagnosis often varies with age, and presentation of the disease frequently is nonspecific and symptoms difficult to interpret. Noninfectious diseases are the most frequent cause of FUO in the elderly and temporal arteritis the most frequent specific cause. Tuberculosis is the most common infectious disease associated with FUO in elderly patients. FUO often is associated with treatable conditions in the elderly. Therefore, intensive, accelerated evaluation is necessary, as the lack of physiologic reserve makes this population vulnerable to irreversible changes and functional deterioration.     

The spectrum of diseases causing fever of unknown origin in Turkey: a multicenter study.

OBJECTIVE: The purpose of this trial was to determine the spectrum of diseases with fever of unknown origin (FUO) in Turkey. METHODS: A prospective multicenter study of 154 patients with FUO in twelve Turkish tertiary-care hospitals was conducted. RESULTS: The mean age of the patients was 42+/-17 years (range 17-75). Fifty-three (34.4%) had infectious diseases (ID), 47 (30.5%) had non-infectious inflammatory diseases (NIID), 22 (14.3%) had malignant diseases (MD), and eight (5.2%) had miscellaneous diseases (Mi). In 24 (15.6%) of the cases, the reason for high fever could not be determined despite intensive efforts. The most common ID etiologies were tuberculosis (13.6%) and cytomegalovirus (CMV) infection (3.2%). Adult Still's disease was the most common NIID (13.6%) and hematological malignancy was the most common MD (7.8%). In patients with NIID, the mean duration of reaching a definite diagnosis (37+/-23 days) was significantly longer compared to the patients with ID (25+/-12 days) (p=0.007). In patients with MD, the mean duration of fever (51+/-35 days) was longer compared to patients with ID (37+/-38 days) (p=0.052). CONCLUSIONS: Although infection remains the most common cause of FUO, with the highest percentage for tuberculosis, non-infectious etiologies seem to have increased when compared with previous studies.