fever of unknown origin in a 79 year old woman katy moran, md september 9, 2003

Fever of Unknown Origin Fever of Unknown Origin in a 79 year old womanin a 79 year old woman

Katy Moran, MDKaty Moran, MD

September 9, 2003September 9, 2003

HistoryHistory

79 yr old WF admitted to PHD 8/8/0379 yr old WF admitted to PHD 8/8/03 CC: intermittant high fevers x 2 weeksCC: intermittant high fevers x 2 weeks Pt has had approx 2 weeks with high spiking fever 102-Pt has had approx 2 weeks with high spiking fever 102-

104104° F, chills, drenching night sweats, malaise° F, chills, drenching night sweats, malaise Pt stopped taking methotrexate 3 weeks ago that she Pt stopped taking methotrexate 3 weeks ago that she

has been on for 4 months for rheumatoid arthritis – SE has been on for 4 months for rheumatoid arthritis – SE nausea, malaise.nausea, malaise.

Pt has decreased appetite, wt loss 5-10 lbs over 4 mo., Pt has decreased appetite, wt loss 5-10 lbs over 4 mo., fatigue, HA when temperature is high, occasional joint fatigue, HA when temperature is high, occasional joint pain and stiffness, nausea, weakness, constipation.pain and stiffness, nausea, weakness, constipation.

Denies cough, dyspnea, chest pain, abd pain, urinary sx, Denies cough, dyspnea, chest pain, abd pain, urinary sx, neck pain, visual change. neck pain, visual change.

PMHx: PMHx: RA dx 4/03, on MTX until 3 weeks agoRA dx 4/03, on MTX until 3 weeks ago COPD, spastic dysphonia, hypothyroidism, HTNCOPD, spastic dysphonia, hypothyroidism, HTN 1968 - TAH1968 - TAH 1981 – Non small cell lung CA s/p LUL resection and radiation1981 – Non small cell lung CA s/p LUL resection and radiation 1989 – Double mastectomy for “precancerous lesions,” s/p 1989 – Double mastectomy for “precancerous lesions,” s/p

bilateral breast implantsbilateral breast implants 1999 – CVA1999 – CVA

Meds: Meds: Synthroid 75 mcg qd, Advair Diskus bid, Folic acid, Norvasc 10 Synthroid 75 mcg qd, Advair Diskus bid, Folic acid, Norvasc 10

mg qd, Premarin .625 mg qd, Plavix 75 mg qd, Leukovorin 5 mg qd, Premarin .625 mg qd, Plavix 75 mg qd, Leukovorin 5 mg qd day 3/7. Recent d/c MTX 10 mg q weekmg qd day 3/7. Recent d/c MTX 10 mg q week

Allergies: codeine, ASA, PCNAllergies: codeine, ASA, PCN

SH: SH: Widowed, lives independently at Medistone apts, quit Widowed, lives independently at Medistone apts, quit

smoking in 1978- prior to that smoked heavily. No smoking in 1978- prior to that smoked heavily. No EtOH, no drugs.EtOH, no drugs.

FH: FH: Parents and siblings died of heart disease. Parents and siblings died of heart disease.

ROS:ROS: Occasional sore throat, dizziness. No congestion, Occasional sore throat, dizziness. No congestion,

diarrhea, rash, SOB, cough, sore throat, recent travel.diarrhea, rash, SOB, cough, sore throat, recent travel.

Physical ExamPhysical Exam Exam: Vitals Wt: 125 BP:132/69 P:112 R:20 T: 102.4Exam: Vitals Wt: 125 BP:132/69 P:112 R:20 T: 102.4 Gen: NAD, alert oriented x 3Gen: NAD, alert oriented x 3 HEENT: normocephalic, PERRLA, normal temporal artery, HEENT: normocephalic, PERRLA, normal temporal artery,

nontender. O/P -no lesions. Fundi with no AV nicking, nontender. O/P -no lesions. Fundi with no AV nicking, exudates, or hemorrhages. Disks clear.exudates, or hemorrhages. Disks clear.

Neck: Supple, no LAD, no JVD, no thyromegalyNeck: Supple, no LAD, no JVD, no thyromegaly Skin: no rash, no nail lesions. Faint erythematous changes, Skin: no rash, no nail lesions. Faint erythematous changes,

minimal warmth, minimal swelling left wrist and MCPs.minimal warmth, minimal swelling left wrist and MCPs. Chest: rales right lung base, no dullness to percussion Chest: rales right lung base, no dullness to percussion CVS: Tachycardic. No murmur, rubs, or gallops. CVS: Tachycardic. No murmur, rubs, or gallops. Abd: Soft, NT, ND. Bs present, no HSMAbd: Soft, NT, ND. Bs present, no HSM Neuro: grossly intact. Spastic dysphonia -hoarse voiceNeuro: grossly intact. Spastic dysphonia -hoarse voice Ext: no edemaExt: no edema

LabsLabs

CBC – W 7.8, 12.3/35.8, Plt 509CBC – W 7.8, 12.3/35.8, Plt 509 Chem 14 – Na 132, otherwise nl, LFTs nl, Chem 14 – Na 132, otherwise nl, LFTs nl,

ESR 128ESR 128 UA – 1.018/ pH 5.5/ trace prot/ mod blood/ UA – 1.018/ pH 5.5/ trace prot/ mod blood/

wbc neg/ rbc 7 hpfwbc neg/ rbc 7 hpf CXR CXR

Infiltrate right mid lungInfiltrate right mid lung Post surgical changes c/w prior surgery to LUL Post surgical changes c/w prior surgery to LUL

with slight mediastinal shiftwith slight mediastinal shift

Fever of Unknown OriginFever of Unknown Origin

CriteriaCriteria T> 38.3 on several occasions and lasting longer than T> 38.3 on several occasions and lasting longer than

3 weeks, with a diagnosis that remains uncertain after 3 weeks, with a diagnosis that remains uncertain after 1 wk of investigation1 wk of investigation

Prevalence of FUO in hospitalized pts is approx 2.9%Prevalence of FUO in hospitalized pts is approx 2.9% Spectrum of disease includes:Spectrum of disease includes:

Infection 28%Infection 28% Inflammatory diseases 21%Inflammatory diseases 21% Malignancy 17%Malignancy 17% DVT 3%DVT 3% Unknown 19%Unknown 19%

Differential DiagnosisDifferential Diagnosis

InfectionInfection TBTB Occult abscessOccult abscess Bacterial endocarditisBacterial endocarditis Other (osteomyelitis, Other (osteomyelitis,

tularemia, histoplasmosis)tularemia, histoplasmosis)

MalignancyMalignancy Lymphoma, leukemia, lung Lymphoma, leukemia, lung

cancer recurrence, renal cancer recurrence, renal cell ca, hepatoma, tumor cell ca, hepatoma, tumor metastatic to liver metastatic to liver

Collagen vascularCollagen vascular SLESLE AOSDAOSD RARA GCA/PMRGCA/PMR SarcoidosisSarcoidosis

DrugsDrugs Pulmonary embolusPulmonary embolus

Hospital CourseHospital Course

Day 1 Day 1 Admitted, dx = presumed right middle lobe pneumonia. Admitted, dx = presumed right middle lobe pneumonia.

Started on Levaquin.Started on Levaquin. Days 2 & 3Days 2 & 3

Continues to have fever, chills. Clindamycin addedContinues to have fever, chills. Clindamycin added Day 4 Day 4

ID consulted: No definite infection. Recommend d/c abx, ID consulted: No definite infection. Recommend d/c abx, observe. RF and ANA ordered. Tmax 101.observe. RF and ANA ordered. Tmax 101.

Day 5Day 5 Fever and chills continue off abx. Pt c/o pain and stiffness in Fever and chills continue off abx. Pt c/o pain and stiffness in

her hands. Rheumatology consulted. Review of old records her hands. Rheumatology consulted. Review of old records from Parkland show CXR with infiltrate v. old scar right mid from Parkland show CXR with infiltrate v. old scar right mid lung. CT Chest ordered.lung. CT Chest ordered.

Fever CurveFever Curve

Fever CurveFever Curve

Fever peaks at approx 4 pm each day and again at Fever peaks at approx 4 pm each day and again at midnight.midnight.

Rheum EvaluationRheum Evaluation On further questioning, pt states that since Jan 03 she has On further questioning, pt states that since Jan 03 she has

had several episodes of excruciating pain in her hands.had several episodes of excruciating pain in her hands. These “attacks” include pain, warmth, and swelling in her These “attacks” include pain, warmth, and swelling in her

MCPs and PIPs. The pain lasts approx 12 hours and is MCPs and PIPs. The pain lasts approx 12 hours and is somewhat relieved by Tylenol. Warmth and swelling somewhat relieved by Tylenol. Warmth and swelling decrease over a few days.decrease over a few days.

Two ER visits over the last few months when the pain Two ER visits over the last few months when the pain became unbearablebecame unbearable

Referred to a rheumatologist in the area where she lives, Referred to a rheumatologist in the area where she lives, was dx with RA and started MTX. RF was 1:160.was dx with RA and started MTX. RF was 1:160.

Joint symptoms have improved somewhat over the last Joint symptoms have improved somewhat over the last few months, but malaise, dyspnea, anorexia, and nausea few months, but malaise, dyspnea, anorexia, and nausea worsened. Also states she had “black stools” for one worsened. Also states she had “black stools” for one week.week.

Rheum EvaluationRheum Evaluation

Physical examPhysical exam Asymmetric oligoarticular joint swelling in left Asymmetric oligoarticular joint swelling in left

wrist, right shoulder, right first CMC and MCP, wrist, right shoulder, right first CMC and MCP, Heberden and Bouchard nodes present Heberden and Bouchard nodes present bilaterallybilaterally

More LabsMore Labs

RF 1:160, ANA negative, ESR 128, CRP RF 1:160, ANA negative, ESR 128, CRP 10.8 mg/dL 10.8 mg/dL

WBC now increased from 7 WBC now increased from 7 12 12 H/H decreased from 12/35 H/H decreased from 12/35 11/33 11/33 Ordered: ASO titer, ANCA, Ferritin, CPK, Ordered: ASO titer, ANCA, Ferritin, CPK,

Aldolase, urine histoplasma antigen, place Aldolase, urine histoplasma antigen, place PPD, GI consult to evaluate h/o “black PPD, GI consult to evaluate h/o “black stools”stools”

Hospital CourseHospital Course Day 6Day 6

Pt c/o increased pain left hip, right shoulder, and neck painPt c/o increased pain left hip, right shoulder, and neck pain CT Chest: nonspecific peripheral nodularity, interstitial CT Chest: nonspecific peripheral nodularity, interstitial

prominance R>L likely interstitial pneumonitis in setting of prior prominance R>L likely interstitial pneumonitis in setting of prior fibrosisfibrosis

GI – nl colon 99, h/o NSAIDS GI – nl colon 99, h/o NSAIDS EGDEGD X-ray hip, hands, shoulderX-ray hip, hands, shoulder

Day 7Day 7 EGDEGD gastritis but no UGIB gastritis but no UGIB Gallium scan – Diffuse activity left wrist, right knee. No evidence Gallium scan – Diffuse activity left wrist, right knee. No evidence

metastatic of infectious disease, no uptake in lungs by pulm metastatic of infectious disease, no uptake in lungs by pulm infiltrateinfiltrate

ANCA, CPK, ASO, ferritin, aldolase all negativeANCA, CPK, ASO, ferritin, aldolase all negative X-rays show degenerative changesX-rays show degenerative changes Therapy was initiatedTherapy was initiated

Differential Diagnosis revisitedDifferential Diagnosis revisited

InfectionInfection TBTB Occult abscessOccult abscess Bacterial endocarditisBacterial endocarditis Other (osteomyelitis, Other (osteomyelitis,

tularemia, histoplasmosis)tularemia, histoplasmosis)

MalignancyMalignancy Lymphoma, leukemia, lung Lymphoma, leukemia, lung

cancer recurrence, renal cancer recurrence, renal cell ca, hepatoma, tumor cell ca, hepatoma, tumor metastatic to liver metastatic to liver

Collagen vascularCollagen vascular SLESLE AOSDAOSD RARA GCA/PMRGCA/PMR

DrugsDrugs Pulmonary embolusPulmonary embolus

FUO: Rheumatologic CausesFUO: Rheumatologic Causes

Systemic Lupus ErythematosusSystemic Lupus Erythematosus Adult Onset Still’s DiseaseAdult Onset Still’s Disease Rheumatoid ArthritisRheumatoid Arthritis Polymyalgia Rheumatica / Giant Cell Polymyalgia Rheumatica / Giant Cell

ArteritisArteritis

Systemic Lupus ErythematosusSystemic Lupus Erythematosus

Clinical DiagnosisClinical Diagnosis CriteriaCriteria

Malar rashMalar rash Discoid rashDiscoid rash PhotosensitivityPhotosensitivity Oral ulcersOral ulcers ArthritisArthritis SerositisSerositis

Renal disorderRenal disorder Neurological disorderNeurological disorder Hematologic disorderHematologic disorder Immunologic disorderImmunologic disorder Antinuclear antibodyAntinuclear antibody

* Patient must have 4 or more of the 11 criteria, serially or simultaneously, during any interval of observation

Systemic Lupus ErythematosusSystemic Lupus Erythematosus

Demographics:Demographics: Peak incidence 15-40 yrsPeak incidence 15-40 yrs Female to male ratio 5:1Female to male ratio 5:1

ANA is positive in >95% of casesANA is positive in >95% of cases

Adult Onset Still’s DiseaseAdult Onset Still’s Disease

Definition: A systemic inflammatory disorder of Definition: A systemic inflammatory disorder of unknown cause that presents with a triad of unknown cause that presents with a triad of quotidian fever, evanescent rash, and quotidian fever, evanescent rash, and polyarthritis.polyarthritis.

Usually disease of younger population – 76% Usually disease of younger population – 76% onset b/w 16-35 yrs, 10% >50yrsonset b/w 16-35 yrs, 10% >50yrs

Symptoms: prodromal sore throat, arthralgia Symptoms: prodromal sore throat, arthralgia (knee 84%, wrist 74%, PIP 50%, MCP 33%, DIP (knee 84%, wrist 74%, PIP 50%, MCP 33%, DIP 20%), severe myalgia, rash, fever >102.2 20%), severe myalgia, rash, fever >102.2 spiking once daily, wt lossspiking once daily, wt loss

AOSDAOSD

DX: elevated ESR, leukocytosis with WBC DX: elevated ESR, leukocytosis with WBC 12,500-40,000, markedly elevated ferritin, 12,500-40,000, markedly elevated ferritin, thrombocytosis, elevated LFTs, anemia, thrombocytosis, elevated LFTs, anemia, ANA neg, RF neg or low titer, HSM, LADANA neg, RF neg or low titer, HSM, LAD

X-ray wrist nonspecific early with soft X-ray wrist nonspecific early with soft tissue swelling that progresses to tissue swelling that progresses to nonerosive joint space narrowing of nonerosive joint space narrowing of intercarpal joints intercarpal joints bony ankylosis bony ankylosis

AOSDAOSD

Most common rheumatologic cause of Most common rheumatologic cause of FUO according to several case seriesFUO according to several case series

Clin Rheumatology. 2003 May; 22(2): Clin Rheumatology. 2003 May; 22(2): 89-93.89-93.

Studied 130 pts with FUO, 36 had Studied 130 pts with FUO, 36 had collagen vascular disease, of these 36 collagen vascular disease, of these 36 patients 20 had AOSD according to patients 20 had AOSD according to criteria by Cush, et al.criteria by Cush, et al.

Intern Med. 1994 Feb; 33 (2): 65-66.Intern Med. 1994 Feb; 33 (2): 65-66.

Criteria for AOSDCriteria for AOSD

Rheumatoid ArthritisRheumatoid Arthritis

Definition: Chronic, systemic inflammatory Definition: Chronic, systemic inflammatory disease with persistent and progressive disease with persistent and progressive synovitis in peripheral jointssynovitis in peripheral joints

Peak incidence 4Peak incidence 4thth-6-6thth decades decades Associated with HLA DR 4Associated with HLA DR 4 Sx: Affects small joints of hands and feet. Sx: Affects small joints of hands and feet.

Pts c/o difficulty with tasks like buttoning Pts c/o difficulty with tasks like buttoning clothesclothes

Rheumatoid ArthritisRheumatoid Arthritis

Rheumatoid FactorRheumatoid Factor Autoantibody with specificity for Fc portion of Autoantibody with specificity for Fc portion of

Ig GIg G Associated with severe diseaseAssociated with severe disease Present in patients with extra articular Present in patients with extra articular

manifestations such as nodulesmanifestations such as nodules Not specific for RA - Detected in normal Not specific for RA - Detected in normal

individuals as well as pts with chronic individuals as well as pts with chronic inflammatory rheumatic diseases, chronic inflammatory rheumatic diseases, chronic bacterial infection, transplanted organsbacterial infection, transplanted organs

Criteria for Classification of Criteria for Classification of Rheumatoid ArthritisRheumatoid Arthritis

Morning StiffnessMorning Stiffness Arthritis of three or more joint areasArthritis of three or more joint areas Arthritis of hand jointsArthritis of hand joints Symmetric arthritisSymmetric arthritis Rheumatoid nodulesRheumatoid nodules Serum rheumatoid factorSerum rheumatoid factor Radiographic changesRadiographic changes

* Patient must have 4 of the 7 criteria and criteria 1-4 must be present for at least 6 weeks. Sensitivity, Specificity 90%

Advanced RAAdvanced RA

Polymyalgia RheumaticaPolymyalgia Rheumatica Definition: An inflammatory disorder of elderly w/ Definition: An inflammatory disorder of elderly w/

pain/stiffness in the proximal musculature.pain/stiffness in the proximal musculature. Strong association with HLA- DR4. Strong association with HLA- DR4. Approximately 85% of PMR patients are >60 yrs Approximately 85% of PMR patients are >60 yrs

of age. Very rare in non-Caucasians. of age. Very rare in non-Caucasians. Symptoms: pain, soreness, & stiffness in the Symptoms: pain, soreness, & stiffness in the

neck, hip/thigh and shoulder girdle. Sxs often neck, hip/thigh and shoulder girdle. Sxs often include anorexia, wt loss, and low-grade feversinclude anorexia, wt loss, and low-grade fevers

Dx: moderate-markedly elevated ESR, anemiaDx: moderate-markedly elevated ESR, anemia Rx: lower dose prednisone 10-20 mg/dayRx: lower dose prednisone 10-20 mg/day Note: PMR rarely evolves into GCANote: PMR rarely evolves into GCA

Polymyalgia RheumaticaPolymyalgia Rheumatica

Morning stiffnessMorning stiffness Prominent finding, lasting 1-4 hoursProminent finding, lasting 1-4 hours

Pain and stiffness in shoulder and hip girdlePain and stiffness in shoulder and hip girdle Problems getting out of bed, rising from a chair, Problems getting out of bed, rising from a chair,

combing haircombing hair In 33% of pts aching is so severe that self care In 33% of pts aching is so severe that self care

becomes difficultbecomes difficult Low grade fever is most frequent sx, then wt loss, fatigueLow grade fever is most frequent sx, then wt loss, fatigue If muscles of neck and shoulder are involved pts may be If muscles of neck and shoulder are involved pts may be

misdiagnosed with frozen shoulder or cervical misdiagnosed with frozen shoulder or cervical myelopathymyelopathy

Polymyalgia RheumaticaPolymyalgia Rheumatica

Clinical criteriaClinical criteria Pain, stiffness in at least 2 large muscle Pain, stiffness in at least 2 large muscle

groupsgroups Duration >2 weeks without clinical evidence of Duration >2 weeks without clinical evidence of

infection, RA, SLE, PAN, or malignancyinfection, RA, SLE, PAN, or malignancy Elevated ESRElevated ESR Age > 50Age > 50 Rapid, lasting relief of symptoms after Rapid, lasting relief of symptoms after

institution of corticosteroid therapyinstitution of corticosteroid therapy

Temporal ArteritisTemporal ArteritisGiant Cell (Cranial) ArteritisGiant Cell (Cranial) Arteritis

Large vessel granulomatous vasculitis affecting Large vessel granulomatous vasculitis affecting the branches of the external carotid artery.the branches of the external carotid artery.

Demographics: Whites >60yrs (DR4+). Rare in Demographics: Whites >60yrs (DR4+). Rare in non-whites. non-whites.

Sxs: profound constitutional Sxs (fever, wt loss, Sxs: profound constitutional Sxs (fever, wt loss, ++night sweats). + moderate-severe headache, night sweats). + moderate-severe headache, Scalp tenderness, diplopia, amaurosis fugax, Jaw Scalp tenderness, diplopia, amaurosis fugax, Jaw claudication. About ½ TA have sxs of PMRclaudication. About ½ TA have sxs of PMR

Labs: High ESR>100, anemia,Labs: High ESR>100, anemia, LFTs, LFTs, albumin albumin Dx: temporal arterty bx - granulomatous changesDx: temporal arterty bx - granulomatous changes Rx: high dose prednisone 60-80 mg/d 12-36 mos Rx: high dose prednisone 60-80 mg/d 12-36 mos

Criteria for Classification of GCACriteria for Classification of GCA

Age at disease onset > or = 50 yrsAge at disease onset > or = 50 yrs New HANew HA Temporal artery abnormalityTemporal artery abnormality Elevated ESR > 50Elevated ESR > 50 Abnormal artery biopsyAbnormal artery biopsy

For purposes of classification, dx of GCA requires 3/5 criteria. Presence of 3/5 criteria has a sensitivity of 93.5% and specificity of 91.2%.

Temporal ArteritisTemporal Arteritis

Optic Nerve Infarct secondary to Optic Nerve Infarct secondary to GCAGCA

GCA versus PMRGCA versus PMR

GCAGCA Biopsy proven vasculitisBiopsy proven vasculitis

PMRPMR Constitutional symptoms of GCA without Constitutional symptoms of GCA without

proven vasculitisproven vasculitis

Important because treatment variesImportant because treatment varies GCA GCA high dose prednisone >60 mg qd high dose prednisone >60 mg qd PMR PMR lower dose prednisone 10-20 mg qdlower dose prednisone 10-20 mg qd


Prospective study of 287 patients with Prospective study of 287 patients with PMR and GCA evaluating clinical and lab PMR and GCA evaluating clinical and lab manifestations at disease onset and at the manifestations at disease onset and at the time of diagnosistime of diagnosis Peripheral arthritis 24% of pts with PMR, none Peripheral arthritis 24% of pts with PMR, none

of the patients with GCAof the patients with GCA Random sample of 68 pts with “pure” PMR Random sample of 68 pts with “pure” PMR

temporal artery biopsy revealed inflammatory temporal artery biopsy revealed inflammatory changes in 3 pts (4.4%)changes in 3 pts (4.4%)

Br J Rheum 1996 Nov; 35(11): 1161-8.Br J Rheum 1996 Nov; 35(11): 1161-8.


About half of pts with PMR have distal About half of pts with PMR have distal manifestations in addition to the classic pain and manifestations in addition to the classic pain and soreness in the proximal joints and musclessoreness in the proximal joints and muscles

Included are the following: Included are the following: nonerosive, self-limited, asymmetric peripheral nonerosive, self-limited, asymmetric peripheral

arthritis, especially of the knees and wristsarthritis, especially of the knees and wrists Carpal tunnel syndromeCarpal tunnel syndrome Swelling and pitting edema of the dorsum of the Swelling and pitting edema of the dorsum of the

hands and wristshands and wrists

Rheumatologic ComparisonRheumatologic Comparison

PMRPMR RARA AOSDAOSD

AM stiffnessAM stiffness ++++++++ ++/+++++/+++ ++++

Proximal PainProximal Pain ++++++++ ++++ ++

Hand ArthritisHand Arthritis ++ ++++++ ++++++

SymmetricSymmetric painpain swellingswelling swellingswelling

ESR>80ESR>80 ++++++++ ++++ ++++++++

X-rayX-ray normalnormal abnormalabnormal abnormalabnormal

Prednisone 10 mg/dayPrednisone 10 mg/day ++++++++ ++++ + / -+ / -

Weight loss, anemiaWeight loss, anemia ++++++ ++ ++++++

Day 9Day 9 Pt started on Prednisone 20 mg po qd and Pt started on Prednisone 20 mg po qd and

had a rapid, dramatic improvement in her sxhad a rapid, dramatic improvement in her sx 48 hour gallium scan no uptake in lungs, PPD 48 hour gallium scan no uptake in lungs, PPD

negative, d/c home on Prednisone 20 mg qd negative, d/c home on Prednisone 20 mg qd with diagnosis of polymyalgia rheumaticawith diagnosis of polymyalgia rheumatica

TreatmentTreatment GCA Tx: Does adding MTX to prednisone reduce the GCA Tx: Does adding MTX to prednisone reduce the

incidence of GCA relapse? Does it diminish cumulative incidence of GCA relapse? Does it diminish cumulative steroid dose or decrease morbidity resulting from long steroid dose or decrease morbidity resulting from long term steroid therapy?term steroid therapy?

Evidence is conflicting depending on the studyEvidence is conflicting depending on the study

Annals of Int Med Jan 01 – Small trial that found MTX plus Annals of Int Med Jan 01 – Small trial that found MTX plus steroid as a safe alternative to prednisone alone with more steroid as a safe alternative to prednisone alone with more effective disease control. Double blind placebo controlledeffective disease control. Double blind placebo controlled

Arthritis Rheumatology April 02 – Larger trial, multicenter, Arthritis Rheumatology April 02 – Larger trial, multicenter, randomized, double blind, placebo controlled. Results did not randomized, double blind, placebo controlled. Results did not support the use of MTX as adjunct tx.support the use of MTX as adjunct tx.

ObjectivesObjectives

Rheumatologic causes of FUORheumatologic causes of FUO PMRPMR GCAGCA

ResourcesResources

Primer on Rheumatic Disease, Klippel et al.Primer on Rheumatic Disease, Klippel et al. Fever of unknown origin in elderly patients. J Fever of unknown origin in elderly patients. J

Am Geriatric Soc. 1993 Nov; 41 (11): 1187-92.Am Geriatric Soc. 1993 Nov; 41 (11): 1187-92. Fever of unknown origin in a 71 year old woman. Fever of unknown origin in a 71 year old woman.

Am J Med 1985 Sep; 79 (3): 373-84. Am J Med 1985 Sep; 79 (3): 373-84. Fever of unknown origin: a review of 20 patients Fever of unknown origin: a review of 20 patients

with AOSD. Clin Rheumatol. 2003 May; 22(2): with AOSD. Clin Rheumatol. 2003 May; 22(2): 89-93.89-93.

Fever of unknown origin: a review of 80 patients Fever of unknown origin: a review of 80 patients from the Sin’etsu area of Japan from 1986-1992. from the Sin’etsu area of Japan from 1986-1992. Intern Med. 1994 Feb; 33(2): 65-66. Intern Med. 1994 Feb; 33(2): 65-66.

ResourcesResources Fever of unknown origin: a changing diagnostic Fever of unknown origin: a changing diagnostic

spectrum. Intern Med 1994 Feb; 33(2): 65-6.spectrum. Intern Med 1994 Feb; 33(2): 65-6. Pyrexia of unknown origin. BMJ 1997 Feb; 314: 583-6.Pyrexia of unknown origin. BMJ 1997 Feb; 314: 583-6. A comprehensive evidence based approach to FUO. A comprehensive evidence based approach to FUO.

Arch Intern Med 2003 Mar 10; 163 (5): 545-51.Arch Intern Med 2003 Mar 10; 163 (5): 545-51. Clinical problem- solving. Diagnosis still in question. N Clinical problem- solving. Diagnosis still in question. N

Engl J Med 2002 Jun 6; 346 (23): 1813-6.Engl J Med 2002 Jun 6; 346 (23): 1813-6. Medium and Large Vessel Vasculitis. N Engl J Med Medium and Large Vessel Vasculitis. N Engl J Med

2003 July 10; 349 (2) : 160-9.2003 July 10; 349 (2) : 160-9. Medical Progress: PMR and GCA. N Engl J Med 2002 Medical Progress: PMR and GCA. N Engl J Med 2002

July 25; 347(4): 261-71.July 25; 347(4): 261-71. Approach to the pt with FUO. Br J Rheum 1996 Nov; Approach to the pt with FUO. Br J Rheum 1996 Nov;

35(11): 1161-8. 35(11): 1161-8.