Fever, FUO and Febrile Neutropenia Cases Flashcards
what is the key difference between the pathogenesis of fever and hyperthermia?
- Fever
altered hypothalamic temperature set point
thermoregulatory function is maintained - Hyperthermia
disrupted thermoregulation (increased heat production) - Hyperpyrexia
Marked elevation in fever – same physiologic mechanisms as fever
what is the criteria for fever of unknown origin (FUO)?
Temperature >38.3 degrees C
Duration > 3 weeks
No diagnosis despite 1 week of investigations in hospital (original definition)
No diagnosis despite 3 days in hospital or 3 outpatient visits (updated definition)
what is the take home point about FUO?
Patients presenting with complaints of fever often:
Have never actually checked their temperature.
Decide they have fever based on unreliable subjective symptoms.
Don’t actually have fever!
When a patient presents complaining of fever and is not febrile at the time of presentation, ask how they know they had fever.
If their diagnosis of fever is not based on actual temperature assessment, unless they are acutely ill, before embarking on extensive investigations, make sure you prove they have fever!
Monitor, record and report temperatures twice daily plus any time they have subjective fever for 1-2 weeks.
what if you get a confirmed FUO?
Keep going back to history and PE with FUO
Blood cultures
HIV serology
Repeat CBC, CRP, LFTs (CRP is C reactive protein, LFT is liver function test)
Autoantibody screen
(don’t do the more invasive procedures right now)
what are the four main etiologic categories of FUO?
infection, miscellaneous, neoplasm, connective tissue disease.
what are B symptoms?
fever, night sweats, weight loss - associated with malignancy, particularly lymphoma.
Fever
Drenching sweats, typically at night*
Weight loss – unintentional, > 10%
Typical of Hodgkin’s or non Hodgkin’s lymphomas
Not specific or sensitive
In lymphoma, of prognostic value
Strictly speaking should only be used when referring to HD or NHL but often used to describe these symptoms in other conditions.
what is an important cause of FUO?
adult onset still’s disease
fever - high spiking > 39 degrees and greater than one week
rash - evanescent, with fever. Salmon colored, trunk and extremeties
joints - arthalgias sometimes arthritis, greater than 2 weeks
labs - marked elevation of serum ferritin, negative rheumatoid factor and autoantibodies
what are cancers that are most likely to present with fever? remember 4H
Hematologic: HD (hodgkins disease), NHL (non-hodgkin’s lymphoma) and others
Hypernephroma: renal cell carcinoma
Hepatic: hepatocellular carcinoma and hepatic metastases
Head cancers: brain cancers
Histiocytosis: Malignant histiocytosis (rare – you will be forgiven if you forget this one)
And common cancers that quite don’t fit the mnemonic
Breast, colon, pancreatic (often metastatic)
what are infections presenting as FUO?
Tuberculosis Typhoid fever Brucellosis Q fever Infective endocarditis Endemic fungal infections HIV Mononucleosis syndromes EBV, CMV, Toxoplasma Cat scratch disease Trichinellosis Sinusitis - Intra-abdominal or pelvic abscesses Diverticulitis Post intra peritoneal surgery Post gyne procedures PID - Dental infections - Osteomyelitis
what is the approach to investigation of FUO?
Very careful and detailed history and physical exam, repeated by different physicians and on multiple occasions
Tiered investigations rather than a shot gun approach
Basic investigations – Level 1
CBC, Inflammatory markers (ESR, CRP)
Routine chemistry: Liver enzymes, bilirubin, LDH
Blood and urine cultures, urinalysis
Autoantibody panel: RF, ANA
Chest Xray
Second level Investigations – consider risk factors and presentation to decide which ones are needed. Serum protein electrophoresis Fecal Occult blood TB skin test CK HIV test (+/- other serology for mono syndromes: EBV, CMV, Toxoplasma) Other serology: Q fever, endemic fungi CT scan: chest, abdomen
Third level investigations
CT pelvis, head and neck
Nuclear med scans – gallium, WBC
Biopsy
Lymph node – if enlarged, preferred sites are posterior cervical, epitrochlear, supraclavicular. Avoid groin nodes.
Bone marrow biopsy – if suspected hematologic malignancy, granulomatous disease, miliary TB, endemic fungal infections, visceral leishmaniasis.
Liver biopsy – if suspected granulomatous disease, miliary TB
Are there no diagnosis in many cases of FUO?
Accounts for up to 10% of cases of FUO
Prognosis is generally good
50-100% recover spontaneously over time
5 year mortality is 3.2%
what is the diagnostic criteria for febrile neutropenia?
Temperature > 38.3 (x1) - OR- > 38 for > 1 hour
+
Patient has received chemotherapy in the last one month
+
Neutrophils < 0.5 or expected to fall to < 0.5 (shortly)
what are the principles of managment of febrile neutropenia
Immediate assessment for foci of infection
Thorough review of symptoms
Meticulous physical examination
Pay special attention to indwelling oral mucosa, lines, respiratory system, skin, abdomen (RLQ tenderness esp.), signs of sepsis syndrome
ALWAYS assess the perianal area for signs if inflammation / infection but NEVER do a rectal exam in a neutropenic patient.
The absence of neutrophils blunts the clinical presentation of focal infection - less erythema, swelling, pain, etc
perianal sepsis is common in neutropenia
Do NOT do rectal exam because you could introduce bacteria and induce bacteremia
Investigations
Obtain appropriate cultures – blood, sputum, urine, wound
Blood cultures are positive in up to 30% of FN cases
Stool cultures are usually not indicated
CXR is indicated even in the absence of respiratory symptoms
CXR changes may not appear until recovery of neutrophils.
Clinical features of cough, tachypnea, hypoxemia are important indicators of respiratory infection and should be sought carefully.
Treatment
Immediately initiate broad spectrum antibiotics.
Gram positives are the most commonly identified pathogens in febrile neutropenic episodes, especially bloodstream infections.
Gram negative infections are more virulent and more likely to result in sepsis; gram negatives cause the majority of infections outside the bloodstream – respiratory, GI, urinary, skin.
Gram negative coverage should include Pseudomonas.
Anaerobic coverage is not required except in high risk situations: necrotizing mucositis, sinusitis, perianal cellulitis, intra-abdominal infection, pelvic infection.
what are the antibiotic options for febrile neutropenia?
Carbapenem : imipenem or meropenem
Antipseudomonal cephalosporin: cefepime*
Piperacillin / Tazobactam
*Ceftazidime is an antipseudomonal cephalosporin but has limited activity against gram positives therefore is not appropriate as monotherapy
Vancomycin is not recommended as initial therapy unless there are features of line infection, skin and soft tissue infection (where MRSA is of concern), pulmonary infection or sepsis (and has no Gram negative activity).
Persistent fevers in febrile neutropenia…
may persist until neutrophil recovery, may indicate occult fungal infection
Median Time to Defervesence
Hematologic malignancies and hematopoietic stem cell transplants = 5 day
Solid tumors = 2 days
Modification of antibiotic therapy because of ongoing fever alone is NOT indicated
Careful re-examination for evolution of clinical signs is essential
