During the past several years, it has become quite evident that positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) imaging can play a major role in the management of patients with suspected infection. Particularly, several groups have demonstrated that this powerful imaging methodology is very effective in the evaluation of osteomyelitis, infected prostheses, fever of unknown origin, and AIDS. In view of its extraordinary sensitivity in detecting disease activity and the ability to quantitate the degree of FDG uptake, PET might prove to be an appropriate modality for monitoring disease activity and evaluating response to therapy. FDG-PET has many advantages over existing imaging techniques for the diagnosis of infectious diseases. These include feasibility of securing diagnostic results within 1.5 to 2 h, excellent spatial resolution, and accurate anatomical localization of sites of abnormality. The availability of PET/computed tomography as a practical tool has further enhanced the role of metabolic imaging in many settings. In the future, this modality is very likely to be employed on a routine basis for detecting, characterizing, and monitoring patients with suspected and proven infection.

Noninfectious inflammatory diseases (connective tissue diseases, vasculitis syndromes, granulomatous diseases) emerged as the most frequent cause of fever of unknown origin in western countries. Among these diseases, giant cell arteritis and polymyalgia rheumatica are the most frequent specific diagnosis in the elderly and adult-onset Still's disease the most frequent in younger patients. This article focuses on noninfectious inflammatory diseases as a cause of classic fever of unknown origin (mainly rheumatic diseases, such as vasculitis and connective tissue diseases).

Fever of unknown origin (FUO) refers to disorders that present with prolonged and perplexing fevers that are difficult to diagnose. This article presents a clinical overview of classic and current causes of FUOs, which may be due to infectious, rheumatic/inflammatory, neoplastic, or miscellaneous disorders. Comprehensive but nonfocused diagnostic testing is ineffective and should be avoided. The FUO workup should be directed by the key history, physical, and laboratory findings in clinical presentation. The clinical syndromic approach in the differential diagnosis of FUOs is emphasized, and the diagnostic importance and significance of fever patterns are discussed.

Peritonitis is not an infrequent complication of inpatients with chronic ambulatory peritoneal dialysis (CAPD). CAPD peritonitis may be related to the catheter or secondary to perforation of an intra-abdominal viscus. The most common organisms usually associated with CAPD peritonitis are Staphylococcus aureus and Staphylococcus epidermidis (coagulase-negative staphylococci). Rarely, aerobic gram-negative bacilli have been the causative agents of CAPD peritonitis. The treatment of CAPD peritonitis usually requires removal of the peritoneal catheter and treatment with parenteral antibiotics active against the causative pathogen. We report a case of CAPD-associated peritonitis caused by an extended spectrum beta-lactamase-producing strain of Klebsiella pneumoniae. The case presented had this strain of multidrug-resistant K. pneumoniae present in blood cultures and the peritoneal fluid. Extended spectrum beta-lactamase-producing bacteria, for example, K. pneumoniae, are multidrug-resistant and sensitive to few antibiotics. This isolate was intermediately sensitive to amikacin and meropenem, but the patient did not clinically improve on these 2 antibiotics. Polymyxin B therapy was initiated after lack of clinical improvement after dialysis catheter removal and 1 week of meropenem and amikacin therapy. The patient responded rapidly to therapy with polymyxin B. Polymyxin B has a unique mechanism of action on bacterial cells and is highly active against all multidrug-resistant gram-negative organisms except Proteus species and Serratia marcescens. No toxicity was observed during therapy. Polymyxin B is being used increasingly as a therapeutic alternative to multidrug-resistant gram-negative organisms.

Subacute (de Quervain's) thyroiditis is a rare but important cause of fever of unknown origin. Most cases of subacute thyroiditis are caused by a variety of viruses, for example, Coxsackie, cytomegalovirus, Epstein-Barr virus, and adenovirus. Influenza immunization or infection may cause subacute thyroiditis. We present the first reported case of a fever of unknown origin due to seasonal influenza A in a 67-year-old woman.

We describe fever of unknown origin (FUO) in a 57-year-old woman with hepatosplenomegaly. The diagnostic workup was directed at diagnosing a lymphoma. Her history of travel and exposures to food and water did not make typhoid fever a likely diagnostic possibility. Because she presented with prolonged fevers, fatigue, anorexia, weight loss, and night sweats with hepatosplenomegaly, lymphoma was likely. Initially, Epstein-Barr virus (EBV) was not considered because of her age, the absence of pharyngitis and cervical adenopathy, and the higher likelihood of another diagnosis, ie, lymphoma. Eventually, her FUO was diagnosed as EBV presenting as "typhoidal mononucleosis." Typhoidal mononucleosis is an extremely rare presentation of EBV as a cause of FUO in an adult. All of her symptoms as well as her clinical and laboratory findings resolved spontaneously.

Prosthetic valve endocarditis (PVE) may be classified clinically as early (<60 days) or late (>60 days) post-valve replacement PVE. The pathogens of early versus late PVE differ in type and virulence. Early PVE pathogens are virulent, for example, Pseudomonas aeruginosa and Staphylococcus aureus. Late PVE pathogens resemble those of subacute bacterial endocarditis and are due to relatively avirulent and noninvasive organisms, for example, viridans streptococci. Viridans streptococci vary in their invasiveness and abscess potential. Myocardial abscess and complete heart block are rare complications of late PVE due to viridans streptococci. We present an unusual case of Streptococcus mitis late aortic PVE complicated by aortic root abscess, myocardial abscess, and complete heart block.

Often patients with fevers of unknown origin (FUOs) present with loss of appetite, weight loss, and night sweats, without localizing signs. Some are found to have a renal mass during diagnostic evaluation. In patients with FUOs and a renal mass, the differential diagnosis includes renal tuberculosis, renal cell carcinoma (hypernephroma), renal malakoplakia, and xanthogranulomatous pyelonephritis. A 68-year-old woman presented with an FUO during her diagnostic workup. She manifested an irregularly enlarged kidney on abdominal computed tomography (CT) scan, as well as a highly elevated erythrocyte sedimentation rate of more than 100 mm/hour, an elevated serum ferritin level, and chronic thrombocytosis, which favored a diagnosis of renal cell carcinoma. Renal malakoplakia and renal tuberculosis comprised further differential diagnostic considerations. Microscopic hematuria may be present with any of the disorders in the differential diagnosis, but was absent in this case. An abdominal CT scan was suggestive of xanthogranulomatous pyelonephritis. Because of concerns regarding renal cell carcinoma, the patient received a nephrectomy. The pathologic diagnosis was of xanthogranulomatous pyelonephritis, without renal cell carcinoma.

Objective To investigate the clinical characteristics, diagnostic approaches, short-term efficacy of treatment and prognosis of lymphoma patients presenting with a fever of unknown origin (FUO). Methods We reviewed the records of 132 patients finally diagnosed with lymphoma in Huashan Hospital, half of whom initially presented with a FUO. The other 66 lymphoma patients without a history of FUO were diagnosed within a month when several patients in the FUO group were also diagnosed. Results The patients presenting with a FUO were predominantly young men (71.21%, p=0.35) characterized by a temperature ≥39°C (55/66, 83.33%). Compared with the non-FUO group, patients in the FUO group more often had pancytopenia and hypohepatia, 61.54% with hypoalbuminemia (p<0.0001), 15.50% with significantly elevated lactate dehydrogenase (LDH)(p<0.0001), 92.45% with elevated serum β(2) microglobulin (p=0.017), 93.48% with elevated urine β(2) microglobulin (p=0.002) and 30.77% with elevated alkaline phosphatase (p=0.001). Ninety-four percent of the FUO patients had aggressive lymphomas (p=0.012), with a poor performance status (96.97%, p=0.003), stage III/IV disease (96.97%, p<0.0001), night sweats (21.21%, p=0.026), unexplained weight loss (46.97%, p=0.002) and more than one extranodal site involved (65.15%, p=0.002). The patients in the FUO group also showed poor prognoses, and most of them were in the high-intermediate or high risk classification of the disease (96.61%, p<0.0001), with a low complete remission (CR) rate (61.11% vs. 93.75%, p=0.043). Twenty-one (15.91%) of all the patients were diagnosed based on the finding of lesion sites by Positron Emission Tomography/Computed Tomography (PET/CT) scanning, which had not been detected by conventional scans. Conclusion Lymphoma presenting as FUO has a rapid progression and poor prognosis, and is difficult to diagnose. PET/CT scans can provide complementary information for an etiological diagnosis of a FUO and biopsy examinations are significant to establish an early diagnosis for patients presenting with a FUO.

Often patients with fevers of unknown origin (FUOs) present with loss of appetite, weight loss, and night sweats, without localizing signs. Some are found to have a renal mass during diagnostic evaluation. In patients with FUOs and a renal mass, the differential diagnosis includes renal tuberculosis, renal cell carcinoma (hypernephroma), renal malakoplakia, and xanthogranulomatous pyelonephritis. A 68-year-old woman presented with an FUO during her diagnostic workup. She manifested an irregularly enlarged kidney on abdominal computed tomography (CT) scan, as well as a highly elevated erythrocyte sedimentation rate of more than 100 mm/hour, an elevated serum ferritin level, and chronic thrombocytosis, which favored a diagnosis of renal cell carcinoma. Renal malakoplakia and renal tuberculosis comprised further differential diagnostic considerations. Microscopic hematuria may be present with any of the disorders in the differential diagnosis, but was absent in this case. An abdominal CT scan was suggestive of xanthogranulomatous pyelonephritis. Because of concerns regarding renal cell carcinoma, the patient received a nephrectomy. The pathologic diagnosis was of xanthogranulomatous pyelonephritis, without renal cell carcinoma.

BACKGROUND: Fever of unknown origin (FUO) has been defined as a fever of ≥101°F that persists for 3 weeks or more. It is not readily diagnosed after 1 week of intensive in-hospital testing or after intensive outpatient or inpatient testing. Fevers of unknown origin may be caused by infectious diseases, malignancies, collagen vascular diseases, or a variety of miscellaneous disorders. The relative distribution of causes of FUOs is partly age-related. In the elderly, the preponderance of FUOs is attributable to neoplastic and infectious etiologies, whereas in children, collagen vascular diseases, neoplasms, and viral infectious disease predominate. The diagnostic approach to FUOs depends on a careful analysis of the history, physical findings, and laboratory tests. Most patients with FUOs exhibit localizing findings that should direct the diagnostic workup and limit diagnostic possibilities. The most perplexing causes of FUOs involve those without specific diagnostic tests, e.g., juvenile rheumatoid arthritis (JRA) or adult Still's disease. In a young adult with FUO, if all of the cardinal symptoms are present, JRA may present either a straightforward or an elusive diagnosis, if key findings are absent or if the diagnosis goes unsuspected. METHODS: We present a 19-year-old man with a recurrent FUO. His illness began 3 years before admission and has recurred twice since. In the past, he did not manifest arthralgias, arthritis, or a truncal rash. On admission, he presented with an FUO with hepatosplenomegaly, aseptic meningitis, and pericarditis. An extensive diagnostic workup ruled out lymphoma and leukemia. Moreover, a further extensive workup eliminated infectious causes of FUO appropriate to his clinical presentation, ie, tuberculosis, histoplasmosis, brucellosis, Q fever, typhoid fever, Epstein-Barr virus, infectious mononucleosis, cytomegalovirus, human herpes virus (HHV)-6, babesiosis, ehrlichiosis, viral hepatitis, and Whipple's disease. RESULTS: The diagnosis of JRA was based on the exclusion of infectious and neoplastic disorders in a young adult with hepatosplenomegaly, aseptic meningitis, pericarditis, and a double quotidian fever. With JRA, tests for rheumatic diseases are negative, as they were in this case. The only laboratory abnormalities in this patient included elevated serum transaminases, a mildly elevated erythrocyte sedimentation rate, and a moderately elevated level of serum ferritin. CONCLUSION: Diagnostic fever curves are most helpful in cases where the diagnosis is most elusive, as was the case here. Relatively few disorders are associated with a double quotidian fever, ie, visceral leishmaniasis, mixed malarial infections, right-sided gonococcal acute bacterial endocarditis, and JRA. Because the patient received antipyretics during the first week of admission, fever was not present. After infectious disease consultation during week 2 of hospitalization, antipyretics were discontinued, and a double quotidian fever was present, which provided the key diagnostic clue in this case.

Fever of unknown origin (FUO) is the clinical designation for patients who have fevers >101F that have persisted for >3 weeks that remain undiagnosed, after an intensive ambulatory/in-hospital workup. Fevers of unknown origin may be due to wide variety of infectious, neoplastic, or rheumatic/inflammatory disorders. The most common causes of FUOs in elderly patients are infectious and neoplastic diseases. With FUOs, the clinical presentation and routine laboratory tests are usually sufficient to narrow differential diagnostic possibilities. We present a case of an elderly Italian woman who presented with an FUO and a solitary, thick-walled cavitary lesion on chest x-ray (CXR). The infectious disease differential diagnosis of her FUO included lung abscess, M. tuberculosis (TB), systemic mycoses, and echinococcal-cyst (or hydatid-cyst) disease. The malignancy and neoplastic differential diagnosis included bronchogenic carcinoma, lymphoma, and metastatic carcinoma. Her nonspecific laboratory tests indicated a highly elevated erythrocyte sedimentation rate (ESR)>100 mm/hour, chronic thrombocytosis, relative lymphopenia, and highly elevated serum ferritin levels. Excluding highly elevated serum ferritin levels, the differential diagnosis of her FUO with a solitary, thick-walled cavitary lesion was lung abscess vs tuberculosis. However, her highly elevated serum ferritin levels proved to be the critical diagnostic clue in predicting the diagnosis of squamous-cell carcinoma. We conclude that serum ferritin levels are an important part of the laboratory workup. As with other nonspecific laboratory tests, the diagnostic significance of highly elevated ferritin levels depends associated clinical features in the clinical presentation.

Kawasaki's disease is a disease of unknown cause. The characteristic clinical features of Kawasaki's disease are fever> or =102 degrees F for> or =5 days accompanied by a bilateral bulbar conjunctivitis/conjunctival suffusion, erythematous rash, cervical adenopathy, pharyngeal erythema, and swelling of the dorsum of the hands/feet. Kawasaki's disease primarily affects children and is rare in adults. In children, Kawasaki's disease is more likely to be associated with aseptic meningitis, coronary artery aneurysms, and thrombocytosis. In adult Kawasaki's disease, unilateral cervical adenopathy, arthritis, conjunctival suffusion/conjunctivitis, and elevated serum transaminases (serum glutamic oxaloacetic transaminase [SGOT]/serum glutamate pyruvate transaminase [SGPT]) are more likely. Kawasaki's disease in adults may be mimicked by other acute infections with fever and rash, that is, group A streptococcal scarlet fever, toxic shock syndrome (TSS), and Rocky Mountain Spotted Fever (RMSF). Because there are no specific tests for Kawasaki's disease, diagnosis is based on clinical criteria and the syndromic approach. In addition to rash and fever, scarlet fever is characterized by circumoral pallor, oropharyngeal edema, Pastia's lines, and peripheral eosinophilia, but not conjunctival suffusion, splenomegaly, swelling of the dorsum of the hands/feet, thrombocytosis, or an elevated SGOT/SGPT. In TSS, in addition to rash and fever, there is conjunctival suffusion, oropharyngeal erythema, and edema of the dorsum of the hands/feet, an elevated SGOT/SGPT, and thrombocytopenia. Patients with TSS do not have cervical adenopathy or splenomegaly. RMSF presents with fever and a maculopapular rash that becomes petechial, first appearing on the wrists/ankles after 3 to 5 days. RMSF is accompanied by a prominent headache, periorbital edema, conjunctival suffusion, splenomegaly, thrombocytopenia, an elevated SGOT/SGPT, swelling of the dorsum of the hands/feet, but not oropharyngeal erythema. We present a case of adult Kawasaki's disease with myocarditis and splenomegaly. The patient's myocarditis rapidly resolved, and he did not develop coronary artery aneurysms. In addition to splenomegaly, this case of adult Kawasaki's disease is remarkable because the patient had highly elevated serum ferritin levels of 944-1303 ng/mL;(normal<189 ng/mL). To the best of our knowledge, this is the first report of adult Kawasaki's disease with highly elevated serum ferritin levels. This is also the first report of splenomegaly in adult Kawasaki's disease. We conclude that Kawasaki's disease should be considered in the differential diagnosis in adult patients with rash/fever for> or =5 days with conjunctival suffusion, cervical adenopathy, swelling of the dorsum of the hands/feet, thrombocytosis and otherwise unexplained highly elevated ferritin levels.

Fever of unknown origin (FUO) refers to prolonged fevers of > or = 101 degrees F and that persists for > 3 weeks that remain undiagnosed after an intensive in-hospital/outpatient workup. The most common FUO categories of are infectious, neoplastic, rheumatic/inflammatory, and miscellaneous causes. Malignancies have supplanted infectious diseases as the most common cause of FUOs in the adult population. Rheumatic/inflammatory causes of FUO are relatively less common than previously because of the introduction over the years of sophisticated diagnostic tests for most rheumatic diseases. The rheumatic/inflammatory disorders that remain important causes of FUO today are those that cannot be readily diagnosed by readily available/noninvasive tests, for example, adult Still's disease and temporal arteritis (TA). In older patients with FUO, TA can be a difficult diagnosis when the characteristic findings (ie, scalp tenderness, jaw claudication) are not present. Patients with TA presenting as FUO often have only headaches that may be accompanied by bilateral jaw discomfort. Endocrine causes of FUOs are rare. The most common endocrine disorder rarely presenting as an FUO is de Quervain's subacute thyroiditis. As in TA, subacute thyroiditis may present with headache and pain at the angle of the jaw. Both TA and subacute thyroiditis may be accompanied by fatigue, weight loss, and night sweats. We present a case of 55-year-old woman who presented with an FUO with clinical and laboratory findings suggesting TA. However, the absence of thrombocytosis and a normal alkaline phosphatase argued against the diagnosis of TA. Also against the diagnosis of TA was weight loss without loss of appetite and a slightly increased pulse. After nonspecific laboratory test results suggested that TA was not the cause of her FUO, additional tests were ordered. Thyroid function test results suggested the possibility of de Quervain's subacute thyroiditis as the cause of her FUO. To the best of our knowledge, this is the first case of de Quervain's subacute thyroiditis presenting as an FUO with elevated ferritin levels.

BACKGROUND: Fever of unknown origin (FUO) is common among HIV-infected patients with a CD4+ T-lymphocyte cell count below 200 cells/ml. The use of HAART has transformed the evolution of AIDS and related diseases. DESIGN AND METHOD: Case-control study, nested on a historical cohort of 3777 HIV-infected patients who were attended at "12 de Octubre" University Hospital in Madrid, Spain, between 1994 and 2000. RESULTS: 276 FUO episodes were recorded, 58 of which occurred in patients receiving HAART. The significant decrease on the accumulated FUO incidence along the study period of 7.3 episodes per 100 HIV-infected patients after 1997 corresponded with the introduction of HAART. FUO was more frequent in patients who did not receive HAART. The aetiological spectrum of FUO was transformed by the introduction of HAART: the incidence of tuberculosis decreased while that of leishmaniasis increased. The four year survival in the non-FUO group increased when compared to that of patients who had had FUO. Similarly, this four year survival increased in patients who received HAART at the time of FUO versus those not receiving it. CONCLUSIONS: Our results confirm that the incidence of FUO has significantly decreased with the introduction of HAART. HAART has also transformed the aetiological spectrum related to FUO considerably. The most frequent cause of FUO in non-HAART patients on this study was the disseminated infection by Mycobacterium avium intracellulare (MAI), followed by tuberculosis, while leishmaniasis was its most common cause in patients receiving HAART. Survival decreased in patients who developed FUO; however, patients who received HAART at the time of FUO had longer survival than patients who did not.

Fever of unknown origin (FUO) characterizes febrile disorders that are accompanied by prolonged fevers of 101 degrees F or greater for 3 weeks or more that remain undiagnosed after comprehensive inpatient and outpatient diagnostic testing. At the present time, malignancies are the most common cause of FUOs. Among malignant FUOs, lymphomas are the most common. We present the case of a non-Asian young adult man who presented with FUO. He had no peripheral adenopathy or splenomegaly but was found to have anterior/superior mediastinal adenopathy and right paratracheal adenopathy. His diagnostic workup was negative for rheumatic/inflammatory and infectious diseases. Laboratory test results were unremarkable except for a highly elevated erythrocyte sedimentation rate and highly elevated serum ferritin level. Otherwise unexplained highly elevated serum ferritin levels in patients with FUOs suggest rheumatic and inflammatory disorders, for example, systemic lupus erythematosus flare or malignancy. The findings of mediastinal adenopathy combined with a highly elevated ESR and highly elevated serum ferritin levels indicate lymphoma as the most likely diagnosis. He also had polyclonal gammopathy on serum protein electrophoresis (SPEP). In a patient with FUO, negative blood cultures, and a heart murmur, polyclonal gammopathy on SPEP suggests atrial myxoma. Lymphomas are often associated with elevated alpha(1)/alpha(2) globulins on SPEP. Lymph node biopsy of the mediastinal nodes was negative for lymphoma but did not show characteristic emperiopolesis, pathognomonic of Rosai-Dorfman disease, a benign lymphoproliferative disorder. Rosai-Dorfman disease usually presents with massive bilateral cervical adenopathy but may present with lymph node involvement in other sites, as in this case. In patients with lymphadenopathy and a negative FUO workup, clinicians should consider the possibility of Rosai-Dorfman disease, particularly if accompanied by an otherwise unexplained highly elevated serum ferritin levels and polyclonal gammopathy on SPEP.

Polymyalgia rheumatica and giant-cell arteritis are closely related disorders that affect people of middle age and older. They frequently occur together. Both are syndromes of unknown cause, but genetic and environmental factors might have a role in their pathogenesis. The symptoms of polymyalgia rheumatica seem to be related to synovitis of proximal joints and extra-articular synovial structures. Giant-cell arteritis primarily affects the aorta and its extracranial branches. The clinical findings in giant-cell arteritis are broad, but commonly include visual loss, headache, scalp tenderness, jaw claudication, cerebrovascular accidents, aortic arch syndrome, thoracic aorta aneurysm, and dissection. Glucocorticosteroids are the cornerstone of treatment of both polymyalgia rheumatica and giant-cell arteritis. Some patients have a chronic course and might need glucocorticosteroids for several years. Adverse events of glucocorticosteroids affect more than 50% of patients. Trials of steroid-sparing drugs have yielded conflicting results. A greater understanding of the molecular mechanisms involved in the pathogenesis should provide new targets for therapy.

Polymyalgia rheumatica (PMR) is a common disease of the elderly. It is characterized by pain and stiffness in the neck, shoulders and the pelvic girdle. In most cases erythrocyte sedimentation rate and C-reactive protein levels are highly elevated. Polymyalgia rheumatica is frequently associated with giant cell arteritis. Steroids are the standard treatment for PMR but their dosage requires adjustment depending on clinical picture, co-morbid conditions and adverse effects. The most prominent features of the disease as well as the main principles of treatment are presented.