m ortality & m orbidity conference c ase s eries - fuo nerissa ang sorrah fiel briones erick...
TRANSCRIPT
MORTALITY & MORBIDITY CONFERENCE CASE SERIES - FUO
NERISSA ANGSORRAH FIEL BRIONES
ERICK VERANO
February 15, 2007Ledesma Hall
Objectives
To present two distinct cases of patients presenting with prolonged fever
To be able to discuss the step by step approach in the management of patients’ with fever of unknown origin
FEVER OF UNKNOWN ORIGIN
Case Presentation
General Data
I.S. 29 year old male single
Chief Complaint
Work up for on and off Fever 1 month duration
History of Present Illness
6 weeks PTA (+) intermittent fever
Tmax: 39.5ºC(-) associated signs and symptoms Temporary relief by paracetamol 500 mg PO
History of Present Illness
5 weeks PTA (+) intermittent fever
Tmax 39ºC(+) 3 episodes LBMAdmitted at a local hospitalDx Typhoid fever(+) Typhidot IgG + IgMRx Chloramphenicol x 7 days(+) fever episodesDischarged for holiday season
History of Present Illness
3 weeks PTA (+) intermittent fever
Tmax 39ºCSelf medicate
Paracetamol Cotrimoxazole Amoxicillin
No reliefReadmitted again
Diagnostics
A. Malarial Smear – NEGATIVE
B. Peripheral Smear – NORMAL
C. Blood GS – NO GROWTH
D. HIV ELISA – NON REACTIVE
E. ANA – 1.054 – WEARLY POSITIVE
F. Thyroid Fxm Test – NORMAL
G. UTZ of the abdomen – NORMAL SONOGRAPHICS
Diagnostics
H. Fecalysis – NO OVA / PARASITE SEEN
I. Urinalysis – NORMAL
J. CT of the Abdomen – RENAL CORTICAL CYST (R)
History of Present Illness
He was given ceftriaxone 3G IV OD x 3 days but developed HPS rxn
Shifted to cefixime 200 mg BID x 7 days Patient remained to have intermittent fever
Tmax 38.5º despite of antibiotic coverage Opted to be discharged Consult Admission
Past Medical History
(-) HPN (-) diabetes mellitus (-) asthma (-) Hs of other hospitalization in the past
Family History
(+) HPN mother (-) heredofamilial diseases
e.g. CA, mumps, leukemia
Personal and Social History
Non smoker Non alcoholic beverage drinker (-) history of travel
Review of System
(-) anorexia (-) weight loss (-) cough and colds (-) rashes (-) photophobia (-) alopecia (-) oral ulcers (-) bleeding tendencus
Physical Examination Conscious, coherent not in cardiorespiratory
distress BP: 120/80 mmHg, CR: 82, RR: 19, Tº: 38.9ºC Pink palpebral conjunctive, anicteric sclerae
(-) TPC, (-) CLAD ECE, (-) Retraction, Clear breath sounds (-)
crackles Adynamic precordium, normal rate regular
rhythm, (-) murmur
Physical Examination
Flat, soft abdomen, NABS, (-) masses, (-) tenderness
(-) gross deformities, full equal pulses, (-) cyanosis (-)edema
Salient Features
29 y/o male 1 month history of intermittent fever Normal physical examination Came in for work-up
Admitting Impression
Fever of unknown origin
Course in the Ward Upon admission
CBC, ESR, CRP Blood CS x 2 sites Monospot test Spec 16 Urinalysis ANA, LE panel CT of the Chest Transesophageal echocardiography Hematology referral for BMA
Laboratory ResultsCBC
Hgb – 12.5 WBC – 4690 Lymphos – 23
HCT – 39.6 Seg – 60 Platelet – 223, 000
ESR – 77 (N- 0.15) CRP – Positive up to 1.0 serum dilution
Spec 15
Na – 139 Bun – 5.0 Alb – 3.0
K – 4.5 Crea – 0.9
Monospot test – Normal
LE Panel
ANA – weakly positive Anti DNA (-) Anti SM (-) Anti RNP (-) Anti SSA (-) Anti SSB (-) Anti JO-1 (-)
Transesophageal Echocardiography
There is no echocardiography evidence of endocardial vegetation on all four cardiac valves
Thickened anterior mitral valve with mild systolic proplase
Mild posterolaterally-directed mitral regurgitation Mild tricuspid regurgitation Normal ventricular size and systolic function Ejection fraction 64%
1st Hospital Day
Patient was scheduled for BMA CT Scan of the chest
Result: INH 300 mg 1 tab OD Rif – 400 mg 1 tab OD PZA – 500 mg 3 tabs OD Ethambutol – 400 mg 3 tabs OD
2nd Hospital Day
CXR PA Lateral view Result
CD4 CD8 Post Bone marrow aspiration biopsy
3rd Hospital Day
Vit A 2500 ml 2 tabs 4 x a day x 8 doses
4th Hospital Day
Bone marrow aspiration GS – No growth Bone marrow aspiration biopsy – normal
Normal cellular component Normal megakaryocytes, erythroid and myeloid
cells No abnormal tumor cells
5th – 7th Hospital Day
Afebrile
8th Hospital Day
Discharged Take home medications c/o DOTS
FINAL DIAGNOSIS
Miliary Tuberculosis
Temperature Pattern
35
36
37
38
39
40
41
42
43
CASE NO. 2
G. F.,a 64 year-old female
Chief complaint: fever
HISTORY OF PRESENT ILLNESS
3 weeks PTA intermittent fever (Tmax 38.8 0C)
(+) loose watery stools x 5 days after taking
Dulcolax
generalized crampy abdominal pain
HISTORY OF PRESENT ILLNESS
admitted at Asian Hospital Dx: Diverticulitis, sigmoid,(confirmed by CT- scan), Infectious diarrhea and UTIgiven Metronidazole and
Ciprofloxacin x 10 dayspending urine C/S
HISTORY OF PRESENT ILLNESS
1 week PTA recurrence of fever(Tmax 39 0C), chills
(+) hypogastric pain, dysuria
CBC: Hgb 11.8 Hct 0.35wbc 9.3 seg 80 lym 11mon 8 plt 533,000
HISTORY OF PRESENT ILLNESS
Urinalysis: rbc: 3-5 wbc: >150bacteria: +1
fecalysis: color: greenish brown
consistency: semi-formed
rbc: 1-2/hpf wbc: 2-4/hpf
ova/parasites: none
HISTORY OF PRESENT ILLNESS3 days PTA persistence of symptoms
ID consult Dx: Diverticulitis vs UTI
given Cotrimoxazole
2 days PTA urine C/S: 1.E.coli 25,000 cfu/mL resistant to Ciprofloxacin2. Klebsiella pneumonia 15,000 sensitive to Ciprofloxacin
ADMISSION
REVIEW OF SYSTEMS
No headache
No alopecia, rash, photophobia
No night sweats
No oral ulcers
No cough, colds, dyspnea
No chest pain, palpitations
(+) weight loss of 10 lbs
No bleeding tendencies
PAST MEDICAL ILLNESS
(+) HPN – 5 months, on Losartan 50mg OD
UBP 120-130/80 HBP 150/80
(-) DM, BA, PTB
Post colonoscopy , November 2006 - normal
Post appendectomy – 15 years old
FAMILY HISTORY
(+) HPN, CVA, CA (breast) – mother
(+) DM – paternal side
PERSONAL & SOCIAL HISTORY
Non smoker
Non alcoholic beverage drinker
No history of travel
PHYSICAL EXAMINATION
Conscious, coherent, not in cardio-respiratory distress
BP 120/70 CR 89bpm RR 18 T 37.7 0C
Wt: 57kg Ht: 156cm BMI 23.4kg/m2
Pink palpebral conjunctivae, anicteric sclerae
Moist buccal mucosae, non- hyperemic posterior pharyngeal walls, tonsils not enlarged
Supple neck, no palpable cervical lymphadenopathies
PHYSICAL EXAMINATION
Symmetrical chest expansion, no retractions, clear lungs
Adynamic precordium, AB 5th LICS MCL, no murmurs
Flabby abdomen, normoactive bowel sounds, soft, non-tender, no hepatosplenomegaly, no CVA tenderness
No edema, no cyanosis, pulses full and equal
IMPRESSION
Fever of Unknown Origin
LABORATORY
Hgb 11.2
Hct 35
WBC 9750
Segmenters 70
Lymphocytes 20
Monocytes 10
Platelets 464,000
CRP Positive up to 1:16 dilution
ESR 125
LABORATORY
Urinalysis: rbc 3.4 WBC 6.3 epi cells 0.7
bacteria: 323.9
Urine C/S: no growth
Fecalysis: color: brown consistency: soft
Pus cells: 8-10/hpf mucus: moderate
Ova/parasite: none
Stool C/S: normal flora
Blood C/S: no growth
LABORATORY
ANA Negative
LE panel Negative
VDRL Negative
CA 125 20.447
CA 19-9 0
2-D ECHO
Normal left ventricular dimension with normal wall thickness, wall motion and contractility. Normal EF 65%. No preicardial effusion nor evidence of vegetation.
CT SCAN OF THE CHEST
Minimal fibrosis, both apices otherwise normal CT of the chest
MRI OF THE WHOLE ABDOMEN
Diverticulitis, ascending and recto-sigmoid colon.
Complex pelvic fluid collections as described. Consider pelvic abscess probably secondary to ruptured diverticulitis.
CT SCAN OF THE WHOLE ABDOMEN
Primary consideration is sigmoid diverticulitis with fistula formation. No discrete abscess formation but no intravenous contrast given.
FEVER PATTERN
35
36
37
38
39
40
41
Co- amoxiclav
Cefuroxime Cefuroxime
Pip- Tazo
FEVER OF UNKNOWN ORIGIN
DISCUSSION
FEVER OF UNKNOWN ORIGIN
Definition: Fever higher than 38.3ºC (100.9°F) on several occasions Duration of fever for > 3 weeks Failure to reach a diagnosis despite 1 week of inpatient
investigation
…by Petersdorf and Beeson from a prospective analysis of 100 cases, which has become the clinical standard
• Petersdorf, RG, Beeson, PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore) 1961; 40:1.
Classification of Fever of Unknown Origin
Minimal diagnostic work ups to qualify as FUO: History Physical examination Complete blood count, including differential and
platelet count Routine blood chemistries, including liver enzymes
and bilirubin Hepatitis serology (if liver tests abnormal) Urinalysis, including microscopic examination, and
urine culture Chest radiograph
FEVER OF UNKNOWN ORIGIN
Risk Factors
History of travel Current medications (including antimicrobials) Immunocompromised state
(Collagen vascular disease /Cancer/ HIV/AIDS) Current or recent hospitalization
FEVER OF UNKNOWN ORIGIN
The percentage of patients with fever of unknown origin by cause during four decades Adapted from Mourad, O, Palda, V, Detsky, AS. Arch Intern Med 2003; 163:545. Adapted from Mourad, O, Palda, V, Detsky, AS. Arch Intern Med 2003; 163:545.
Common Etiologies of Fever of Unknown Origin
Infections Tuberculosis (especially
extrapulmonary) Abdominal Abscesses Pelvic Abscesses Dental Abscesses Endocarditis Osteomyelitis Sinusitis
Cytomegalovirus Epstein Barr Virus Human immunodeficiency
virus Lyme disease Prostatitis Sinusitis Fungal disease
Malignancies Chronic Leukemia Lymphoma Metastatic cancers Renal cell carcinoma Colon carcinoma Hepatoma Myelodysplastic
syndromes Pancreatic carcinoma Sarcomas
Collagen-Vascular Dse Adult Still’s disease Polymyalgia rheumatica Temporal arteritis Rheumatoid arthritis Rheumatoid fever Inflammatory bowel dse Reiter’s syndrome SLE Vasculitides
Common Etiologies of Fever of Unknown Origin
Miscellaneous
Drug-induced fever Complications from cirrhosis Factitious fever Hepatitis
(alcoholic, granulomatous or lupoid) Deep venous thrombosis Sarcoidosis
Common Etiologies of Fever of Unknown Origin
DRUG FEVER
DIAGNOSTIC APPROACH
FEVER OF UNKNOWN ORIGIN
DIAGNOSIS OF FEVER OF UNKNOWN ORIGIN
Fever > 38.30C x 3 weeks;
1 week of “intelligence and invasive investigation”
Physical Exam
CBC, ESR, CRP, urinalysis, liver function tests, electrolytes, blood culture, urine culture, PPD skin test, chest radiograph
Order appropriate follow up and diagnostic testing Positive
NO
CT scan of the chest/ abdomen/pelvisWith contrast
DIAGNOSTIC APPROACH
Erythrocyte sedimentation rate — One study reviewed elevations above 100 mm/h
among 263 patients with FUO: 58 percent had malignancy, most commonly
lymphoma, myeloma or metastatic colon or breast cancer
25 percent had infections such as endocarditis, or inflammatory diseases like rheumatoid arthritis or giant cell arteritis
Zacharski, LR, Kyle, RA. Significance of extreme elevation of erythrocyte sedimentation rate. JAMA 1967; 202:264
DIAGNOSIS OF FEVER OF UNKNOWN ORIGIN
CT scan of the chest/ abdomen/ pelvis
with IV/PO contrast
Needle biopsy/ Invasive testing
Radionuclide scanning procedures (67Ga scan, 111 In PMN scan)(to identify/ localize inflammatory processes)
Order appropriate follow up/diagnostic testingspecific therapy
Positive
NO
No diagnosis
positive
Empiric therapy (anti-TB / anti microbial)
Watchful waiting
DIAGNOSIS OF FEVER OF UNKNOWN ORIGINCT scan of abdomen/pelvis
With contrast
Assign to most likely category
29 years old male6 weeks intermittent fever Tmax 39.5
Treated as a case of typhoid feverCT Scan abdomen: renal cortical cyst
Cervical lymph node
CBC, ESR (77), CRP, urinalysis, liver function tests, electrolytes, blood culture, urine culture, monospot test, ANA, Lupus panel
CT scan of the chest - positive
AFB sputum smear negative x 3 days and AFB culture pending
Bone marrow biopsy for TB culture - pendingHIV test – negative
CD4 count-252
Positive
CASE 1 - SUMMARY
64 years old female3 weeks intermittent fever Tmax 38.8
abdominal pain and loose stoolsTreated as UTI and diverticulitis
Essentially normal PE
CBC (leukocytosis), ESR (125), CRP(1:16), urinalysis, liver function tests, electrolytes,
blood culture, urine culture, stool culture – no growthANA, Lupus panel - negative
CT scan of the chest – minimal fibrosis both apicesMRI of the abdomen – diverticulitis, complex fluid collections
t/c pelvic abscesses 20 to ruptured diverticulitis
CT scan of the abdomen- sigmoid diverticulitis with fistula formation
Exploratory laparotomy- phlegmon
Positive
CASE 2 - SUMMARY
Among infections, tuberculosis and abscesses are the most common etiologies.
Tuberculosis single most common infection in most FUO
series. Presentations of TB, which escape early
detection, are either extrapulmonary, miliary, or occur in the lungs of patients with significant preexisting pulmonary disease.
FEVER OF UNKNOWN ORIGIN
Abscess Usual location of occult abscesses -abdomen or pelvis
Underlying conditions which predispose to abscess formation –cirrhosis,steroid or immunosuppressive medications, recent surgery, and diabetes.
Abscesses arise when there has been disruption of a barrier such as the bowel wall in appendicitis or diverticulitis. The rupture often seals off spontaneously and local peritonitis is converted to an abscess by host defense mechanisms.
FEVER OF UNKNOWN ORIGIN
Therapeutic trials of antimicrobials or corticosteroids, rarely establish a diagnosis.
Antimicrobial agents could be expected to suppress, but not cure, an infectious process such as an occult abscess since adjunctive drainage would usually be required.
A trial of corticosteroids for an inflammatory process should not replace relevant biopsies for steroid responsive diseases; and a careful evaluation for infection should precede such a trial
FEVER OF UNKNOWN ORIGIN
SUMMARY
Fever of unknown origin (FUO) is defined as fever higher than 38.3ºC on several occasions lasting for at least three weeks without an established etiology despite intensive evaluation and diagnostic testing
Three general categories of illness account for the majority of "classic" FUO cases and have been consistent through the decades. These categories are infections, malignancies, and
collagen vascular diseases.
The most important aspects of the evaluation of a patient with FUO are to take a careful history, perform a detailed physical examination, and to reassess the patient frequently.
We recommend the following minimum diagnostic evaluation: blood cultures, erythrocyte sedimentation rate, lactate dehydrogenase, HIV antibody test and viral load, rheumatoid factor, heterophile antibody test, antinuclear antibodies, tuberculin skin test, and CT scan of abdomen and chest
SUMMARY
Diagnostic workup may fail to identify an etiology in as many as 30 to 50 percent of patients.
Most adults who remain undiagnosed have a good prognosis.
SUMMARY AND RECOMMENDATIONS
References De Kleijn, EM, Vandenbroucke, JP, van der, Meer JW. Fever of
unknown origin (FUO). I A. prospective multicenter study of 167 patients with FUO, using fixed epidemiologic entry criteria. The Netherlands FUO Study Group. Medicine (Baltimore) 1997; 76:392.
Knockaert, DC, Vanneste, LJ, Bobbaers, HJ. Fever of unknown origin in elderly patients. J Am Geriatr Soc 1993; 41:1187.
Miller, RF, Hingorami, AD, Foley, NM. Pyrexia of undetermined origin in patients with human immunodeficiency virus infection and AIDS. Int J STD AIDS 1996; 7:170.
Mourad, O, Palda, V, Detsky, AS. A comprehensive evidence-based approach to fever of unknown origin. Arch Intern Med 2003;163:545
Petersdorf, RG, Beeson, PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore) 1961; 40:1.2.
Vanderschueren, S, Knockaert, D, Adriaenssens, T, et al. From prolonged febrile illness to Fever of unknown origin: the challenge continues. Arch Intern Med 2003; 163:1033.12