Info
🌱 來自: Huppert’s Notes
Primary Fever Syndromes🚧 施工中
Primary Fever Syndromes
Fever
• Definition: A regulated elevation in core body temperature, usually defined as ≥38.3°C, as part of the body’s inflammatory response
• Differential diagnosis: Infectious, autoimmune/inflammatory conditions, malignancy, drug reactions, transfusion reactions, deep venous thrombosis (DVT)
• Workup and management: See Table 8.13
Fever of unknown origin (FUO)
• Definitions:
- Classic FUO: 1) Fever >38.3°C, 2) Continuing 3 weeks in duration, 3) No diagnosis despite a thorough evaluation (3 days inpatient or three outpatient visits)
- Nosocomial FUO: Fever >38.3°C starting after a patient is hospitalized, lasting for 3 or more days, with an unclear source of fever despite a thorough evaluation
- Neutropenic FUO: Fever >38.3ºC on multiple occasions in a patient with an absolute neutrophil count (ANC) >500 cells/µL (or expected to fall to that level in 1–2 days). Also see Hematology/Oncology Chapter 7
- HIV-associated FUO: Fever >38.3ºC (100.9ºF) on multiple occasions over more than 4 weeks (or more than 3 days for hospitalized patients with HIV)
• Differential diagnosis: See Table 8.14
• Workup:
- History: Localizing symptoms, sick contacts, travel history, exposures, systemic symptoms
- Physical exam
- Labs and imaging:
• The initial workup should focus on key features identified in the history and physical
• Focus on organ systems with localizing symptoms (e.g., chest imaging in those with pulmonary symptoms, a transthoracic echocardiogram in those with a new murmur, etc.)
• Consider the following diagnostic tests: CBC with diff, CMP, urinalysis and urine culture, blood cultures (3 sets), HIV Ag/Ab, ESR, CRP, latent TB testing, ANA, RF, SPEP, CXR and/or CT chest, CT of the abdomen and pelvis. Consider testing for viral (e.g., EBV, CMV) and atypical pathogens (e.g., Q fever, Bartonella, Brucella) if the patient has risk factors and a compatible syndrome
- Advanced diagnostics: If the above diagnostic workup is unrevealing, consider FDG-PET (now preferred over indium-111-labeled leukocyte scanning)
TABLE 8.13 • Steps in Evaluation of a Fever
TABLE 8.14 • Common Etiologies of Fever of Unknown Origin (FUO) in Adults
Febrile neutropenia (FN)
• Definition: Fever and neutropenia
- Fever: Defined as a single oral temperature of ≥38.3°C (101.0°F) or a temperature of 38.0°C (100.4°F) for over 1 hour
- Neutropenia: Definition varies, often absolute neutrophil count (ANC) <1000/μL or sometimes defined as ANC <500/μL
• Pathogenesis:
- Cytotoxic chemotherapy nonspecifically targets rapidly proliferating cells, including myelopoietic stem cells, resulting in decreased cell counts, including decreased absolute neutrophil count
- Other conditions that cause bone marrow suppression (infections, medications, autoimmune conditions, fibrotic conditions, etc.) can also result in neutropenia
- Cytotoxic chemotherapy can also destroy rapidly proliferating gastrointestinal mucosal cells, resulting in decreased integrity of the gastrointestinal mucosa. This results in an increased frequency of bacterial translocation across the gut barrier and, as a result, bacteremia, which is the most common cause of infection in patients with FN
• Pathogens**:**
- Bacterial infections: Most common cause of FN
- Fungal infections: Most invasive fungal infections that cause FN are due to Candida spp., which develop after translocation across the gut barrier, and Aspergillus spp., which develop after inhalation of spores
- Viral: Human herpesviruses are the most common viral pathogens to cause FN. These include herpes simplex viruses (HSV) 1 and 2, herpes zoster, Epstein Barr virus (EBV), or cytomegalovirus (CMV)
• Diagnostics: History, physical exam, labs, pan-culture
• Treatment:
- Many institutions have institution-specific guidelines, which should be followed if present
- Various national guidelines help risk stratify patients that can be treated as outpatients vs. those that should be hospitalized (see IDSA, NCCN, and/or MASCC Risk Index)
• For those patients deemed safe for outpatient management: Oral antibiotic regimens should include anti-pseudomonal coverage with a fluoroquinolone. Potential regimens include (adjust for renal dysfunction if needed):
- Levofloxacin 750 mg orally once daily
- Ciprofloxacin 500 mg orally twice daily + amoxicillin-clavulanate (500 mg/125 mg orally three times daily or 1000 mg/250 mg orally twice daily)
• For those patients who warrant inpatient management: IV antibiotics that include anti-pseudomonal coverage should be administered immediately. Potential therapeutic regimens include (adjust for renal/hepatic dysfunction if needed):
- Cefepime 2 g IV q8 hr
- Meropenem 1 g IV q8 hr
- Piperacillin-tazobactam 4.5 g IV q6 hr
- Consider addition of Gram-positive coverage and fungal coverage pending patient risk factors and clinical stability.
• Indications for Gram-positive coverage (e.g., vancomycin) include shock, pulmonary infection, indwelling central venous catheters, skin and soft-tissue infections
• Indications for fungal coverage (e.g., an echinocandin or liposomal amphotericin B) include shock or persistent fevers for 4+ days with no source identified
Fever in a “returning traveler”
• Approach:
- When considering travel-related fevers, consider geography and incubation period to narrow the differential diagnosis
- It is important to note that a patient can have a fever due to their travel OR independent of it
- Thus, alongside travel-dependent fevers, it is important to consider the usual, travel-independent categories of fever, including infectious (e.g., CAP, UTI, etc.) and non-infectious (e.g., malignancy, rheumatologic, medications/toxins, etc.)
• History:
- Travel history (destination, urban/rural, vaccinations and malaria prophylaxis)
- Exposures (animals, bites, water, diet, tattoos, sexual contact)
- Timing (incubation period)
• Pathogens to consider by geography:
- Caribbean, Central America, and South America: Chikungunya, dengue, malaria, zika, typhoid and paratyphoid fever (in South America)
- South-Central Asia and Southeast Asia: Dengue, malaria, and typhoid and paratyphoid fever (in South-Central Asia)
- Sub-Saharan Africa: Dengue, malaria, tickborne rickettsial infections, schistosomiasis
• Infections with an incubation period <21 days:
- Bacterial: Typhoid, non-typhoidal salmonellosis, leptospirosis, meniingococcemia, rickettsial diseases
- Viral: Zika, dengue, chikungunya, EBV (mononucleosis), West Nile virus (WNV), Japanese encephalitis, yellow fever
- Parasitic: Malaria
• Infections with an incubation period >21 days:
- Bacterial: Q-fever
- Mycobacterial: Tuberculosis
- Viral: Viral hepatitis (e.g., hepatitis A, hepatitis E), acute HIV, rabies
- Fungal: Endemic fungi (check prevalence by region)
- Parasitic: Leishmaniasis