User:Taiwo2845/sandbox/Fever of Unknown Origin

Fever of Unknown Origin
Fever of unknown origin (FUO) was first described by Dr. Petersdorf and Dr. Beesom in 1961. FUO was defined as a temperature of 101 degrees Fahrenheit (38.3 degrees Centigrade) or higher with a minimum duration of three weeks without an established diagnosis after an intensive one-week investigation in the hospital. Today, due to technological advances allowing for sophisticated outpatient evaluations, the one-week inpatient investigation is no longer required. This activity reviews the cause and presentation of fever of unknown origin and highlights the role of the interprofessional team in its management.

Objectives:

 * Describe the workup of a patient with a fever of unknown origin.
 * Outline the causes for fever of unknown origin.
 * Summarize the treatment of patients with fever of unknown origin.
 * Review the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by fever of unknown origin.

Introduction
Fever of unknown origin (FUO) was first described by Dr. Petersdorf and Dr. Beesom in 1961. FUO was defined as a temperature of 101 degrees Fahrenheit (38.3 degrees Centigrade) or higher with a minimum duration of three weeks without an established diagnosis despite at least one week's investigation in the hospital. This definition was later changed to accommodate technological advances allowing for sophisticated outpatient evaluations, increasing numbers of immunocompromised individuals including those with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), and more complex treatment options becoming available. The revised definition proposed by Durack and Street in 1991 divided cases into four distinct subclasses: classic FUO, nosocomial FUO, neutropenic FUO, and HIV-related FUO

A comprehensive history and physical examination can aid in diagnosis and direct diagnostic testing. Recommended investigations for work-up include complete blood count (CBC) with differential, three sets of blood cultures (from different sites, several hours apart, and before initiation of antibiotic therapy, if indicated), chest radiograph, complete metabolic panel (including hepatitis serologies if liver function tests are abnormal), urinalysis with microscopy and urine culture, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibodies (ANA), rheumatoid factor (RA), cytomegalovirus IgM antibodies or virus detection in blood, heterophile antibody test, tuberculin skin test, HIV testing and computed tomography (CT) scan of the abdomen

Over 200 malignant/neoplastic, infectious, rheumatic/inflammatory, and miscellaneous disorders can cause FUO. Providers often order non-clue-based imaging and specific testing early in the FUO workup, which may be misleading and is certainly not economical.[4] Despite extensive workup and diagnostic advances, up to 51% of FUO cases remain undiagnosed.[5][6] In modern medicine, FUO remains one of the most challenging diagnoses.

It is important to note that immunocompromised and HIV patients may require an entirely different approach in diagnosing and treatment of recurrent fevers. This article focuses on FUO in immunocompetent adult patients.

Etiology
The causes of fever of unknown origin (FUO) are often common conditions presenting atypically. The list of causes is extensive, and it is broken down into broader categories, such as infection, noninfectious inflammatory conditions, malignancies, and miscellaneous.

Noninfectious Inflammatory Causes of FUO

 * Giant cell (temporal) arteritis
 * Adult Still disease (juvenile rheumatoid arthritis)
 * Systemic lupus erythematosus (SLE)
 * Periarteritis nodosa/microscopic polyangiitis (PAN/MPA)
 * Rheumatoid arthritis (RA)
 * Antiphospholipid syndrome (APS)
 * Gout
 * Pseudogout
 * Behçet disease
 * Sarcoidosis
 * Felty syndrome
 * Takayasu arteritis
 * Kikuchi disease
 * Periodic fever adenitis pharyngitis aphthous ulcer (PFAPA) syndrome

Infectious Causes of FUO
Malignant and Neoplastic Causes of FUO
 * Tuberculosis (TB)
 * Q fever
 * Brucellosis
 * HIV infection
 * Abdominopelvic abscesses
 * Cat scratch disease (CSD)
 * Epstein-Barr virus (EBV) infection
 * Cytomegalovirus (CMV) infection
 * Enteric (typhoid) fever
 * Toxoplasmosis
 * Extrapulmonary TB
 * Organ-based infectious causes of FUO:
 * Subacute bacterial endocarditis (SBE)
 * Chronic sinusitis/mastoiditis
 * Chronic prostatitis
 * Discitis
 * Vascular graft infections
 * Whipple disease
 * Multicentric Castleman disease (MCD)
 * Cholecystitis
 * Lymphogranuloma venereum (LGV)
 * Tickborne infections:
 * Babesiosis, Ehrlichiosis
 * Anaplasmosis
 * Tickborne relapsing fever (rodent-infested cabins)
 * Regional infections:
 * Histoplasmosis
 * Coccidioidomycosis
 * Leptospirosis
 * Visceral leishmaniasis
 * Rat-bite fever
 * Louse-borne relapsing fever


 * Lymphoma
 * Renal cell carcinoma
 * Myeloproliferative disorder
 * Acute myelogenous leukemia
 * Multiple myeloma
 * Breast/liver/pancreatic/colon cancer
 * Atrial myxoma
 * Metastases to brain/liver
 * Malignant histiocytosis

Miscellaneous Causes of FUO

 * Cirrhosis (due to portal endotoxins)
 * Drug fever
 * Thyroiditis
 * Crohn disease
 * Pulmonary emboli
 * Hypothalamic syndrome
 * Familial periodic fever syndromes
 * Cyclic neutropenia
 * Factitious fever

Common Causes of Fever in the Different Subclasses


 * Classic FUO: The frequency of each category varies by both time and location, although, endocarditis, complicated urinary tract infections, abscesses, and tuberculosis (TB) are consistently reported in patients with classic FUO. In patients over the age of 65, connective tissue diseases are determined to be the cause of fever more frequently. Fever in travelers is more likely to be secondary to infections such as malaria, typhoid fever, and acute HIV.
 * Nosocomial FUO: Healthcare-associated fevers can be due to drug fever, complications post-operatively, venous thromboembolic disease, malignancy, transfusion-related reactions, or Clostridium difficile infection. Risk factors such as surgical procedures, instrumentation, intravascular devices, immobilization, and medications can help determine the diagnostic testing necessary to obtain a diagnosis.
 * Neutropenic FUO: Fevers are common in this subclass and are frequently due to infection.
 * HIV-related FUO: Fevers can be present during acute illness, but are also common in the setting of untreated infection signifying additional infection with opportunistic organisms.

Epidemiology
Epidemiology of fever of unknown origin (FUO) varies based on etiology of fever, age group, geography, environmental exposure, and immune/HIV status. In developing countries, an infectious etiology of FUO is most prevalent whereas, in developed countries, FUO is likely due to non-infectious inflammatory disease.

History and Physical
There is no clear-cut diagnostic approach to fever of unknown origin (FUO). Thorough history with a focus on the most probable etiology based on the patient’s symptoms is the key to pinpoint the origin of FUO. Information about previous illnesses, localizing symptoms, alcohol intake, home medications, occupational exposures, pets, travel, and familial disorders should not be overlooked. Constellation of patient-reported symptoms should help providers narrow down the etiology of the etiologic category of fevers as each of these has clinical hallmarks. For example, if a patient presents with B-symptoms, early satiety, and significant weight loss, the provider should pursue a malignancy workup. On the other hand, if a patient presents with rigors, an infectious etiology should be considered, while joint involvement is a hallmark of rheumatologic disorders.