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Rona Marie Leonor, M.D. November 12, /F Ledesma Hall

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1 Rona Marie Leonor, M.D. November 12, 2009 9/F Ledesma Hall
The Great Pretender Rona Marie Leonor, M.D. November 12, 2009 9/F Ledesma Hall

2 OBJECTIVES To present a case of a patient with persistent fever.
To discuss the approach and management in patient with persistence of fever.

3 GENERAL DATA R.B, 58-year-old male, married, Filipino
Farmer from Tuguegarao, admitted on July 5,2009

4 CHIEF COMPLAINT FEVER

5 HISTORY OF PRESENT ILLNESS
3 WEEKS PTA fever, undocumented right upper quadrant pain No change in bowel movement

6 HISTORY OF PRESENT ILLNESS
local Institution in Tuguegarao. A> enteric fever Cotrimoxazole and Metronidazole. A> Malaria Chloroquine started as an empiric treatment. opted to go home , and was lost to follow up

7 HISTORY OF PRESENT ILLNESS
2 WEEKS PTA Fever and Right upper quadrant pain Dyspnea No cough, chest pain

8 HISTORY OF PRESENT ILLNESS
local institution Tuguegarao. Abdominal Ultrasound: Cholesterolosis Chest xray and Chest Ultrasound : pleural effusion on the right. Thoracentesis 1 liter

9 HISTORY OF PRESENT ILLNESS
Empirically treated with Ceftriaxone, Ciprofloxacin and eventually Anti koch’s medication Opted to go home Pleural fluid Culture and histopath results unknown to patient consult in MMC for further management

10 REVIEW OF SYSTEMS generalized weakness weight loss Loss of appetite
no headache no palpitations No signs of bleeding no dysuria/ frequency/ hematuria no joint stiffness/ weakness

11 PAST MEDICAL HISTORY No Diabetes Mellitus No hypertension No Asthma
No Pulmonary Tuberculosis No history of accidents or injuries No history of blood transfusion No history of hepatitis No previous surgeries

12 PERSONAL & SOCIAL HISTORY
Non smoker Non alcoholic beverage drinker No illicit drug use Denies exposure to a PTB patient

13 FAMILY HISTORY No Hypertension No Cancer No Diabetes Mellitus
No asthma No PTB

14 PHYSICAL EXAMINATION Conscious, coherent, ambulatory, Not in cardio respiratory distress weight: 61 Kg Height: cm BMI 22.5 100/70 HR : 92/min RR 20 cycles/min Temp 38.0 C Skin: no jaundice, good turgor, no lesions. Pink palpebral conjunctivae, anicteric sclerae, no neck mass, no cervical lymphadenopathy, no oral mass or ulcers Adynamic precordium, no heaves, no thrills, Normal rate, regular rhythm, no murmurs

15 PHYSICAL EXAMINATION Asymmetrical chest expansion (Right chest lag), no rib retractions, decreased tactile fremitus, dull on percussion and decreased breath sounds - mid to lower right lung field, no crackles, no wheezes Left lung field: resonant, clear breath sounds Flat abdomen, normoactive bowel sound, soft, direct tenderness, RUQ, no masses Full & equal peripheral pulses. No cyanosis. no edema

16 SALIENT FEATURES Febrile ( 38C), RR- 20 58 year old male R chest lag
decreased tactile fremitus, dull on percussion,mid-lower right lung field decreased breath sounds- mid to lower right lung field no crackles, no wheezes Flat abdomen, normoactive bowel sound, soft, direct tenderness, RUQ 58 year old male FEVER x 3 weeks right lower quadrant pain Dyspnea UTZ: Cholesterolosis CXR & Chest UTZ: Pleural Effusion

17 ADMITTING IMPRESSION Fever secondary to Pulmonary Tuberculosis vs. Pneumonia r/o malignancy Pleural effusion, right Cholesterolosis

18 COURSE IN THE WARDS On Admission
CBC Chest radiograph Serum electrolytes sputum smear for acid fast bacilli Paracetamol 500mg Tramadol 50mg

19 COURSE IN THE WARDS 3rd Hospital day
febrile Tmax 39.3 ; abdominal pain Patient referred to IDS Impression: Hepatic abcess. Parapneumonic Effusion, right. CT scan of the chest and abdomen Chest tube thoracostomy, right (300ml of serous fluid)

20 COURSE IN THE WARDS repeat Chest radiograph
Acid fast bacilli sputum smear Ampicillin-Sulbactam 1.5g, q6

21 Fever Pattern 3rd hospital day D1 AMPICILLIN

22 COURSE IN THE WARDS 4th hospital day
Pleural fluid gram staining Ampicillin-Sulbactam was shifted to Cefepime 1g, every 12 hrs.

23 Fever Pattern 4th Hospital day D1 CEFEPIME

24 COURSE IN THE WARDS 6th Hospital day
Febrile Tmax 39.1 CBC Blood culture Acid fast bacilli smear of pleural fluid Acid fast bacilli culture HRZE (Myrin P forte) 4 tablets, once a day.

25 Fever Pattern 6th hospital day D1 ANTI KOCH’S

26 COURSE IN THE WARDS 8th hospital day
febrile Tmax 39C loss of appetite Dizziness loose bowel movement Pleural fluid cytology Myrin P Forte discontinued

27 COURSE IN THE WARDS INH 300mg,1 tab, before breakfast
Rifampicin 600mg,1 tab, before breakfast; Ethambutol 400mg,3 tabs, after breakfast PZA 500mg,4 tablets, after lunch

28 COURSE IN THE WARDS 10th hospital day
Febrile Tmax 38.9 Headache, vomiting, dizziness and tinnitus Impresssion: Drug induced vs central cause R/O Connective tissue disease

29 COURSE IN THE WARDS Lupus Panel Plan: Cranial CT scan & Lumbar Tap
Anti Koch’s, Tramadol were discontinued Betahistine was started

30 Fever Pattern 10th hospital day ANTI KOCH’S 4th Hospital day
D1 CEFEPIME 10th hospital day ANTI KOCH’S

31 COURSE IN THE WARDS 12th hospital day
Fever secondary to Infection vs. Malignancy Naproxen 375mg, BID and later decreased to mg, BID Cefepime discontinued

32 Fever Pattern 12th hospital day CEFEPIME

33 12th hospital day NAPROXEN
Fever Pattern 12th hospital day NAPROXEN

34 COURSE IN THE WARDS 18th Hospital day
Fever Pleural fluid cytology CYTOSPIN Chest tube thoracostomy drainage (24ml for 24 hrs) Contrast chest CT scan done. Chest tube removed. Video- assisted Thoracoscopic surgery.

35 Fever Pattern 18th hospital day 24ml x 24hrs

36 COURSE IN THE WARDS 25th Hospital day
Post MINI thoracostomy, Decortication with pleural and lung biopsy Isoniazid 300mg,1 tab, after dinner (Aug 1) Rifampicin 600mg,1 tab,before dinner (Aug 2) Ethambutol,400mg,3 tabs,after dinner (Aug 4

37 Fever Pattern 25th hospital day S/P VATS

38 COURSE IN THE WARDS 32nd hospital Day
Afebrile Chest x-ray no recurrence of fever noted

39 Fever Pattern DAY 28-30 RE CHALLENGE ANTI KOCH’S

40 FINAL DIAGNOSIS PLEURAL EFFUSION, RIGHT SECONDARY TO PULMONARY TUBERCULOSIS S/P CHEST TUBE INSERTION, RIGHT S/P MINI THORACOSTOMY, DECORTICATION WITH PLEURAL AND LUNG BIOPSY

41 FEVER OF UNKOWN ORIGIN (FUO)
Temp of >38.3 on several occasions >3 weeks Failure to reach a diagnosis despite 1 week of inpatient investigation Approach to the adult with fever of Unknown Origin UpToDate®www.uptodate.com AuthorDavid H Bor, MDSection EditorPeter F Weller, MD, FACPDeputy EditorAnna R Thorner, MD Last literature review version 17.2: May 2009 T| his topic last updated: September 22, 200(8M ore)

42 FEVER OF UNKOWN ORIGIN (FUO)
CLASSIC NOSOCOMIAL NEUTROPENIC HIV

43 DIFFERENTIAL DIAGNOSIS
58 year old male FEVER x 3 wks RUQ pain Dyspnea Decreased tactile fremitus dull on percussion decreased breath sounds- mid to lower right lung field no crackles no wheezes INFECTIONS NEOPLASMS MISCELLANEOUS CONDITION COLLAGEN VASCULAR DISEASES

44 FEVER OF UNKNOWN ORIGIN (FUO)
Temp of >38.3 on several occasions X >3 weeks; Failure to reach a diagnosis despite 1 week of inpatient investigation PHYSICAL EXAM & HISTORY CBC, DIFF SMEAR, ESR,CRP, URINALYSIS, LFT, MUSCLE ENZYMES,VDRL,HIV,CMV,EBV,ANA,RF,SPEP,PPD,CONTROL SKIN TESTS, CREATININE,ELECTROLYTES, Ca, Fe, TRANSFERRIN, TIBC, VIT B12, BLOOD CULTURE, URINE, SPUTUM,FLUIDS

45 Chest CT, abdomen, pelvis. Colonoscopy
CBC, DIFF SMEAR, ESR,CRP, URINALYSIS, LFT, MUSCLE ENZYMES, VDRL, HIV, CMV, EBV, ANA, RF, SPEP, PPD, CONTROL SKIN TESTS, CREATININE,ELECTROLYTES, Ca, Fe, TRANSFERRIN, TIBC, VIT B12, BLOOD CULTURE, URINE, SPUTUM,FLUIDS Diagnostic clues Directed exam Positive Negative No diagnostic clues Chest CT, abdomen, pelvis. Colonoscopy

46 PULMONARY TUBERCULOSIS
leading diagnosable cause of FUO 6th leading cause of morbidity and mortality Diagnosis, Treatment, Prevention and Control of Tuberculosis: 2006 Update CLINICAL PRACTICE GUIDELINES

47 PULMONARY TUBERCULOSIS
When should one suspect that patient may have PTB? Cough of two weeks or more Cough with or without the ff: night sweats, weight loss, anorexia, unexplained fever and chills, chest pain, fatigue and body malaise Cough x 2 weeks or more with or without accompanying symptoms TB SYMPTOMATIC

48 PULMONARY TUBERCULOSIS
CATEGORIES DEFINITION NEW A patient who has never had treatment for TB or, if with previous anti TB medications, taken for less than 4 weeks. RELAPSE Declared cured of any form of TB in the past by a physician after one full course of anti TB medications, & now has become sputum smear (+) RETURN TO TREATMENT AFTER DEFAULT Stops medications for 2 months or more and comes back to the clinic smear (+)

49 PULMONARY TUBERCULOSIS
CATEGORIES DEFINITION FAILURE While on treatment, remained or become smear (+) again at the fifth month of anti TB treatment or later; or a patient who was smear (-) at the start of treatment and becomes smear (+) at the 2nd month TRANSFER –IN Management was started from another area and now transferred to a new clinic CHRONIC CASE Became or remained smear (+) after completing fully a supervised re-treatment regimen

50 PULMONARY TUBERCULOSIS
What is the initial work up for a TB symptomatic? Sputum microscopy (preferably 3 should be sent) Collected first thing in the morning for 3 consecutive days

51 PULMONARY TUBERCULOSIS
INTERPRETATION OF RESULTS: SMEAR POSITIVE: If at least two sputum specimens are AFB (+) SMEAR NEGATIVE: If none of the specimens are AFB (+)

52 PULMONARY TUBERCULOSIS
DOUBTFUL: When only one of the 3 sputum specimens is (+) When results are doubtful, a second set of the three must be collected One of the second three is (+): SMEAR POSITIVE All of the second three are (-): SMEAR NEGATIVE

53 PULMONARY TUBERCULOSIS
What additional tests should be done after a TB symptomatic has been found to be SMEAR POSITIVE? No further tests are required

54 PULMONARY TUBERCULOSIS
Chest radiographs are not routinely necessary in the management of a TB symptomatic patient who is smear positive PPD (Purified Protein derivative) testing will not add additional information

55 PULMONARY TUBERCULOSIS
Blood/serum tests maybe taken when specific risks for possible adverse events during treatment are present

56 PULMONARY TUBERCULOSIS
All adults suspected to have PTB should have TB culture Drug susceptibility testing is recommended: Retreatment Treatment failure Smear positive patients suspected to have one or multi-drug resistant TB (MDR-TB)

57 PULMONARY TUBERCULOSIS
What tests are recommended for TB symtomatics who are smear negative? TB culture with Drug susceptibilty Chest Radiograph

58 PULMONARY TUBERCULOSIS
RECOMMENDED TREATMENT FOR NEWLY DIAGNOSED SMEAR POSITIVE Short course chemotherapy (SCC) regimen 2 months isonoazid, rifampicin, pyrazinamide and ethambutol

59 PULMONARY TUBERCULOSIS
4 moths isoniazid and rifampicin Given daily as initial phase followed by daily or thrice weekly administration of isoniazid and rifampicin during the continuation phase

60 PULMONARY TUBERCULOSIS
The recommended dosages for daily and thrice –weekly administration in mg/kg body weight are as follows: DRUGS DAILY (RANGE) THRICE-WEEKLY (RANGE) ISONIAZID RIFAMPICIN PYRAZINAMIDE ETHAMBUTOL STREPTOMYCIN 10 25 15 35 30

61 PULMONARY TUBERCULOSIS
RECOMMENDED TREATMENT FOR NEWLY DIAGNOSED SMEAR NEGATIVE 2HRZE/4HR (WITHOUT HIV OR WITH AN UNKNOWN HIV)

62 PULMONARY TUBERCULOSIS
How can one reliably diagnose extrapulmonary tuberculosis (EPTB)? High degree of suspicion in a patient at risk Appropriate specimen should be processed for microbiologic, both microscopy, culture and histopathologic examinations

63 PULMONARY TUBERCULOSIS
What is the effective treatment regimen for EXTRAPULMONARY TUBERCULOSIS? 6-9 month regimen consisting of 2 months Isoniazid, Rifampicin, Pyrazinamide and Ethambutol (Initial Phase) 4-7 months Isoniazid and Rifampicin (Continuation Phase)

64 PULMONARY TUBERCULOSIS
TUBERCULOUS PLEURAL EFFUSION Microscopic examination detecs acid fast bacilli in about 5-10% of cases

65 PULMONARY TUBERCULOSIS
TREATMENT ADMINISTRATION FIXED DOSE COMBINATION Recommended for newly diagnosed TB patients: Minimize the risk of monotherapy Minimize drug resistance Improve adherence with lesser number of pills to swallow Reduce prescription errors

66 PULMONARY TUBERCULOSIS
ADVERSE REACTIONS DRUG MANAGEMENT MINOR Gastro intestinal intolerance Rifampicin/INH Meds at bedtime/ small meals Mild skin reaction Any kind of drugs Anti histamine Orange/ red colored urine Rifampicin Reassure patients Pain at the Injection site streptomycin Warm compress

67 PULMONARY TUBERCULOSIS
ADVERSE REACTIONS DRUG MANAGEMENT Peripheral neuropathy Isoniazid Pyridoxine ng, daily (Treatment) 100mg prevention Arthralgia due to Hyperurecemia Pyrazinamide NSAID Flu-like symptoms Rifampicin Anti pyretics

68 PULMONARY TUBERCULOSIS
ADVERSE REACTIONS DRUGS MANAGEMENT MAJOR Severe skin rash Any kinds of drugs (Streptomycin) Discontinue anti TB drugs, refer to DOTS Jaundice (Isoniazid, Rifampicin, Pyrazinamide) Discontinue anti TB drugs, refer to DOTS; If symptoms subside, resume treatment & monitor clinically Impaired visual acuity Ethambutol

69 PULMONARY TUBERCULOSIS
ADVERSE REACTIONS DRUGS MANAGEMENT Psychosis Isoniazid Discontinue anti TB drugs, refer to DOTS Hearing impairment Streptomycin Thrombocytopenia, anemia, shock Rifampicin Oliguria Streptomycin/Rifampicin

70 PULMONARY TUBERCULOSIS
SINGLE DOSE PREPARATION Adverse reactions Co morbid conditions requiring dose adjustments Disease conditions where treatment is expected to have significant drug interactions with Anti TB drugs At risk for adverse reactions

71 PULMONARY TUBERCULOSIS
The 2000 Philippine TB Consensus found no studies correlating the resolution of clinical signs and symptoms with bacterial response to treatment Teo SK. Four month chemotherapy in the treatment of smear negative PTB: results at months. Ann Acad Med Singapore 2002;31: (CLINICAL PRACTICE GUIDELINES)

72 PULMONARY TUBERCULOSIS
MONITORING OF OUTCOMES AND RESPONSE DURING TREATMENT Defervesence occurred within 2 weeks in 78% of patients with drug susceptible organisms while only 9% of patients with multi drug resistance became afebrile Teo SK. Four month chemotherapy in the treatment of smear negative PTB: results at months. Ann Acad Med Singapore 2002;31:

73 BMJ 1996;313:1543-1545 (14 December) Education and debate
“Possible causes of persistent fever in pulmonary tuberculosis (once non-compliance and supra-added infections have been excluded) include cytokine release, drug induced fever, drug resistance, and drug malabsorption.” BMJ 1996;313: (14 December) Education and debate Grand Rounds--Hammersmith Hospital: Persistent fever in pulmonary tuberculosis Hammersmith Hospital, London W12 0HS Case presented by: Maha T Barakat, senior house officer in respiratory medicine Chairman: J Scott, director of medicine.

74 “Naproxen test” as a clinical tool in the differential diagnosis of fever of undetermined origin (FUO) Patients with cancer in a study conducted at the Oncology Unit of the Good Samaritan Hospital in Dayton, Ohio. Patients with FUO and suspected or diagnosed malignancy Naproxen 250 mg twice a day orally at 12-hourly intervals for at least 3 days Validity was not established because of the lack of an independent, blind comparison with a reference standard Correlation of the final diagnoses of FUO in all patients with their response to antibiotics and naproxen

75 Recommendation: More appropriate reference standard would be the absence of infection after extensive and thorough laboratory work-up coupled with the absence of any clinical deterioration without administration of any antibiotics on continued follow-up for at least a period of 2 weeks. Utility of Naproxen in the Differential Diagnosis of Fever of Undetermined Origin in Patients with Cancer: A Commentary Marissa M. Alejandria, M.D.* (*Infectious Disease Fellow, UP-PGH, Taft Avenue, Manila) (Phil J Microbiol Infect Dis 1999; 28(2):73-74)

76 RECHALLENGE Restart each anti koch’s one by one.
To determine which the drug that the patient had allergic reaction

77 LABORATORIES AND ANCILARIES
CBC JULY 5 JULY 10 JULY 27 HEMOGLOBIN 11.6 12.0 12 HEMATOCRIT 33 34.4 36 WBC 3.94 6.79 11.7 SEGMENTER 69 66 76 LYMPHOCYTE 18 17 13 MONOCYTE 9 11 PLATELETS 493,00 401,000 349,000

78 LABORATORIES AND ANCILARIES
7/5 7/6 7/15 7/23 7/30 8/4 Sodium 139 137 Potassium 3.8 4.3 Creatinine 0.90 1.0 0.9 BUN 75.9 Glucose Calcium 8.3 albumin 2.7 Alkaline phosphatase 152 AST 28 21 ALT 42 34

79 LABORATORIES AND ANCILARIES
Pleural fluid analysis: MICROSCOPY: RBC 1219 U/L WBC 115 U/L SEGMENTER 0.05 LYMPHOCYTE 0.95 Fungal elements: negative AFB smear: negative Gram stain: pus cell 0-2

80 LABORATORIES AND ANCILARIES
Pleural Fluid culture (July 8): no growth Pleural Fluid Cytology: negative for malignant cells Cytospin: Chronic Inflammatory process

81 LABORATORIES AND ANCILARIES
Pleural Tissue and Lung Biopsy CHRONIC GRANULOMATOUS INFLAMMATION, CONSISTENT WITH TUBERCULOSIS, RIGHT PLEURAL BIOPSY Congestion and atelectasis, adjacent lung tissue

82 LABORATORIES AND ANCILARIES
Lupus panel : negative

83 LABORATORIES AND ANCILARIES
AFB Sputum x 3 days (July 5-7, 2009): Negative AFB sputum culture July 8,2009: no growth Blood Culture July 6,09: No growth after 5 days

84 LABORATORIES AND ANCILARIES
Chest x-ray July 6, 2009 Decreased in the pleural density at the right mid-lower outer lung with blunting of the costophrenic sulcus. No layering seen in the right lateral decubitus view. Loculated pleural effusion and /or thickening considered. Underlying parenchymal pathology not ruled out. The heart is not enlarged.

85 JUNE 27,09

86 JULY 6,09

87 JULY 6,09

88 JULY 6,09

89 LABORATORIES AND ANCILARIES
July There is decreased in the pleural fluid seen in the right Hemithorax. Right Chest tube is noted July 29, 2009 There is partial evacuation of the pleural effusion in the right. The visualized lung appear clear

90 JULY 8.09

91 LABORATORIES AND ANCILARIES
July There is decreased in the pleural fluid seen in the right Hemithorax. Right Chest tube is noted July 29, 2009 There is partial evacuation of the pleural effusion in the right. The visualized lung appear clear

92 JULY29,09

93 LABORATORIES AND ANCILARIES
CT SCAN OF THE CHEST July 7,2009: Consider Pneumonia vs PTB, right upper lobe. Moderate pleural effusion, right passive atelectasis of the posterior basal segment of the right lower lobe prominent paratracheal lymph nodes, not enlarged by CT criteria Subcentimeter cyst, right kidney, Bosniak I Category Normal contrast enhanced CT scan of the rest of the abdominal organs

94 LABORATORIES AND ANCILARIES
CT SCAN OF THE CHEST July 23,2009: Interval placement of the right thoracostomy tube with residual pleural effusion Possibilty of loculation is entertained No interval change in the right pulmonary infiltrates since the previous examination Present note of focal atelectasis in the right lower lobe seen Prominent pretracheal and precarinal lymph node, relatively unchanged.

95 POSITIVE DIRECTED EXAM Needle biopsy, invasive testing
NO DIAGNOSIS EMPIRICAL THERAPY Anti TB therapy Colchicine/ NSAID Steroids WATCHFUL WAITING DIAGNOSIS Specific therapy

96 NEGATIVE DIRECTED EXAM GA Scan, PMN scan, PET scan NEGATIVE POSITIVE
Needle biopsy, invasive testing NO DIAGNOSIS EMPIRICAL THERAPY Anti TB therapy Colchicine/ NSAID Steroids WATCHFUL WAITING

97 NEGATIVE CT chest, abdomen, pelvis and colonoscopy
GA Scan, PMN scan, PET scan NEGATIVE POSITIVE Needle biopsy, invasive testing No diagnosis Empirical therapy Anti TB therapy Colchicine/ NSAID Steroids Watchful waiting

98 POSITIVE CT chest, abdomen, pelvis and colonoscopy
Needle biopsy, invasive testing NO DIAGNOSIS Empirical therapy Anti TB therapy Colchicine/ NSAID Steroids Watchful waiting DIAGNOSIS Specific therapy

99 SUMMARY PTB leading diagnosable cause of FUO
Defervesence occurred within 2 weeks in 78% of patients with drug susceptible organisms while only 9% of patients with multi drug resistance became afebrile Validty is not established in Naproxen test Should be treated accordingly

100 Thank you!!!


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