FEVER OF UNKNOWN ORIGIN (ADULT) Clinical Impression SLE with persistent typhoid fever Differentials Persistent typhoid Rule

e In - fever - tachypnea - headache (an atypical manifestation of typhoid fever) - epigastric (abdominal) pain - hematuria (rare 5-35% cases; reports of renal insufficiency and acute renal failure in typhoid fever) - hyperpigmented patches on skin: could be rose spots (Rose spots develop on the back, arms, and legs in up to 25% of cases late in the first week of fever) - Typhidot positive for IgG and IgM

Rule Out - cannot rule out (Typhoid Fever has protean and atypical manifestations)

SLE Rule Out - cannot rule out (SLE's presentation and course are highly variable ranging from indolent to fulminant)

Rule In - 23 yo Female - woman of childbearing age - fever - hyperpigmented patches on both legs (could be photosensitive discoid lesions that do not itch or hurt-more common in face and scalp, could be cutaneous vasculitis lesions-small, red-purple spots and bumps on the lower legs) - edema (due to renal problems) - anemia - proteinuria, hematuria (lupus nephritis) Chikungunya Fever Rule In - Travel to Batangas (where there was a recent outbreak of Chikungunya Fever) - Fever - Headache - Abdominal Pain - hyperpigmentation in legs (Maculopapular rash in trunk and limbs) Genitourinary TB Rule In - malaise, general symptoms of TB - fever - pus cells and red cells in urine, but no bacterial growth on routine bacterial culture - painless intermittent microscopic hematuria - endemicity Leptospirosis

Rule Out - Acute febrile myalgia and polyarthritis - Patient has no joint pain/arthritis - Fever usually resolves in 3-4 days

Rule Out - persistent cystitis (unresponsive to antibiotics) - urination - burning sensation - frequency - groin pain - perianal sinus, genital ulcer

Rule In - fever - high temperature 38-40*C (but typically should subside within 7 days) - tachycardia - headache

Rule Out - history of possible exposure (like flood wading) - rigors - nausea and vomiting - anorexia

- non pruritic skin rash (hyperpigmentation?)

- diarrhea - cough - pharyngitis - hypotension, oliguria - early in disease: skin is warm and flushed - conjunctival suffusion - muscle tenderness - meningitis

UTI Rule In Rule Out - no growth in urine cutlure - (-) dysuria

- fever - urinalysis results: WBC: 3-5/hpf RBC: 10-15/hpf Albumin - +1 Other History Questions Where did patient eat? (Streetfood?) Patient's source of water? Did patient wade in floodwater? Exposure to TB? Drug intake prior to fever? Immunizations? Animal contact? History of surgery, trauma, blood transfusion?

Other Physical Signs chills? decreased appetite? weight loss? altered behavior? muscle pain? neurologic deficits?

Diagnostic Tests CBC, Urinalysis, Cultures, Chest Xray Serologic Tests - rule out other infectious agents both bacteria and viruses Other Imaging - CT/MRI Endoscopic exam - gastrointestinal? Other Tests to Request For Bone marrow aspiration - for typhoid fever KUB radiograph - for genitourinary TB Tuberculin skin test ANA and Anti-dsDNA - for SLE Fever of Unknown Origin Temp of >38.3 C (>101 F) on several occasions A duration of fever >3 weeks 3 outpatient visits or 3 days in the hospital w/o elucidation of cause or 1 week of intelligent and invasive ambulatory investigation Therapy Since Typhoid testing yielded a positive result, one should consider to treat for typhoid. o Options include: Chloramphenicol, Amoxicillin, Ciprofloxacin o Antimicrobial sensitivity pattern should be established. Since blood and urine cultures are negative, bone marrow culture may be considered for 80 to 90% chance of obtaining more accurate findings. Empiric Therapy Continued observation and examination In the presence of vital sign instability or neutropenia, give fluoroquinolones plus piperacillin If TST is +, therapeutic trial for TB up to 6 weeks If still no cause identified after prolonged observation (> 6 months) and there are debilitating symptoms, these are treated with NSAIDS and glucocorticoids

FEVER OF UNKNOWN ORIGIN (PEDIA) Clinical Impression Differentials Acute Lymphoblastic Leukemia (ALL) Rule In young down syndrome (+) family hx of leukemia weight loss fever pallor (nailbeds, conjunctivae) anemia Acute Myeloid Leukemia (AML) Rule In down syndrome (+) family hx of leukemia weight loss fever anemia pallor (nailbeds, palpebral conjunctivae) cardiac flow murmur Tuberculosis Rule Out

Rule Out (-) petecchiae (-) thrombocytopenia (-) lymphadenopathy (-) hepatosplenomegaly (-) neutropenia (-) fatigue

Rule Out (-) petecchiae (-) thrombocytopenia (-) lymphadenopathy (-) hepatosplenomegaly (-) neutropenia (-) fatigue

Rule In anti-TB meds given for 1 month with resolution of fever (+) fever (+) weight loss (+) family hx of TB (grandfather) Infective Endocarditis Rule In (+) fever of 38 degrees or higher (+) Hx of neonatal sepsis (+) VSD (+) pallor (+) weight loss Other History Questions What is the characteristic of the fever? Is it intermittent? What are the drugs being taken? Travel history? Are there any recurrent infections? Is there any encounter with a person who has TB? Exposure to animals? Is nutrition adequate? Diagnostic Tests CBC PBS PT/PTT determination; Chemistry profile CXR

Rule Out

Other Physical Signs head circumference? edema? Bruising? gum problems? visual problems? Enlarged tongue?

Other Tests to Request For Blood culture PPD or AFB smear or sputum culture ~ CT - degree of lymphadenopathy ECG - therapy may be cardiotoxic Bone Marrow Aspiration and Biopsy - definitive diagnosis Histology - classification Immunohistochemistry - diagnosis flow cytometry and cytogenetics; PCR or cytogenics; Gene expression profiling Lumbar puncture (spinal tap) to check for leukemia cells in the spinal fluid and to check for infection Diagnostic Options CBC with differential blood count and urinalysis (always part of initial laboratory evaluation) ESR or CRP (ESR > 100mm/hr suggests TB, Kawasaki, malignancy or autoimmune disease) Blood cultures (to detect bacteremia eg. infective endocarditis or deep seated abscesses) Tuberculin Skin Test with PPD (Purified Protein Derivative) Examination of Bone Marrow Aspirate (Leukemia, also culture bacteria and fungi) Echocardiogram (may demonstrate presence of vegetation on leaflets of heart valves - IE) Ultrasonography (intra-abdominal abscesses) Fever of Unknown Origin Children w/ fever documented by a health care provider The cause of the fever could not be identified after 3 weeks of evaluation as an outpatient or after 1 week evaluation in the hospital Patients with fever not meeting these criteria, and specifically those admitted to the hospital o No apparent site of infection nor a noninfectious diagnosis o Considered to have fever without localizing signs Charaterized by non-specific and atypical presentation of common disease entities Pediatric ALL Treatment consists of a remission-induction phase, intensification (consolidation) phase, and continuation therapy targeted at eliminating residual disease Induction Phase: goal to achieve remission (<5% blasts in the bone marrow); consists of 3 or 4 drugs, which includes a glucocorticoid, vincristine, asparaginase, and possibly an anthracycline. Consolidation Phase: after remission is achieved to further reduce leukemic cell burden; given different drugs eg cyclophosphamide, cytarabine and/or 6-mercaptopurine [6-MP] Maintenance Phase: (longest); consists of intrathecal MTX every 3 months, monthly vincristine and steroid pulses, daily 6MP, and weekly MTX. * Immediately admit any patient who is neutropenic and who develops chills or fever to administer intravenous (IV) broad-spectrum antibiotics. Pediatric AML Treatment Unlike most children with AML who should receive intense therapy, young children (< 4 y) with Down syndrome fare best with reduced-intensity therapy, which results in an improved likelihood of long-term, disease-free remission supportive care until their bone marrow achieves hematologic remission chemotherapeutic drug regimens include some combination of an anthracycline (most often daunorubicin [daunomycin]) with cytosine arabinoside (cytarabine). Other drugs: fludarabine, etoposide, amsacrine, dexamethasone, 6-thioguanine, cyclophosphamide, and mitoxantrone. Tuberculosis 2HRZ/4HR Infective Endocarditis Gram-positive: Vancomycin Gram-negative: Ceftriaxone