Fever

fever

1. 1.FEVER 2.FEVER OF UNKNOWN ORIGIN 3.FEVER WITH NEUTROPENIA 4.FEVER WITH RASH

2. FEVER Definition : Fever is an elevation of body temperature above the normal physiological variation as a result of the change in the thermoregulatory center, located in the hypothalamus At oral site fever is defined as temp:-. Am >98.9 F Pm > 99.9 F

3. Pathophysiology of Fever

4. DIFFERENT METHODS OF TAKING TEMPRETURE Digital thermometer Mercury thermometer- TYMPANIC MEMBRANE THERMOMETER Rectal Thermometer with different bulb design then oral thermometer

5. Site of measuring Tempreature Oral cavity-sub lingual Axilla Rectum . Tympanic Membrane based thermometer . Rectal temp is 1 .F higher then then Oral which is 1.F higher then Temp recorded in Axilla Rectal temp mos accurate for core body temp.

6. VARIATION Hypothermia = rectal temperature <35 °C (<95 °F). Body temperature °F (oral site) Normal Febrile 98.6–99.9 >100 Mild/low grade fever 100.5–102.2 Moderate grade fever 102.2–104.0 High grade fever 104.1–106.0 Hyperpyrexia >106.0

7. VARIOUS RELATIONSHIPS Every one degree rise of core body temp above 100.F – Pulse >10 , RR by 4 Fever increases o2 demand This law when not followed in respect of pulse, for some diseases , called RELATIVE BRAYCARDIA ( Faget sign), reported in typhoid fever, typhus, leptospirosis, malaria etc.

8. PATTERNS OF FEVER 1.Continuous Fever : Constant above baseline Variation <1°F e.g. lobar pneumonia, infective endocarditis, enteric fever.

9. Remittent Fever The temperature fluctuation exceeds 0.6°C (1°F), but without touching the baseline eg :- Brucellosis , Typhoid fever , Infective Endocarditis .

10. Intermittent Fever The elevated temperature touches the baseline in between diurnal variation is extremely large 3-4 .F associated with septicemia .

11. Relapsing Fevers Febrile episodes are separated by normal temperature for more than one day, various types described a. Tertian fever--- , e.g. Plasmodium vivax, ovale , falciparum. b. Quartan fever ----- , e.g. Plasmodium malariae . c. Pel-Ebstein -----e.g. Hodgkins and other lymphomas. d. Saddle back fever/Bi-Phasic fever:---- e.g. Dengue fever. e f )cyclic neutropenia ---- every 21 days

12. Drug induced fever It begins 1–3 weeks after the start persists 2–3 days after withdrawal Rash, arthralgia, Hypotension Relative bradycardia CBC –Eosinophilia Any drug but most notorious are Sulphonamide Procainamide Penicillins Propylthiouracil Iodides Methyldopa Anti-TB drugs Anticonvulsants

13. Hyperpyrexia core body temperature, above 41°C (106°F) Medical emergency, Causes 1. Severe infection & septicemia 2 CNS haemorrages eg Pontine haemorrhage 3. Rheumatic fever 4. Meningococcal meningitis 5. Cerebral malaria. Treatment emergency: physical cooling later treat the cause

14. APPROACH TO THE PATIENT Fever Documentation & Same site. Chronology with other symp ? , Age , Duration, Events before fever ? Exposure, immune status , underlying Renal or Liver conditions? LABORATORY TESTS The workup must include CBC and PS Urine Analysis, naked eye and laboratory CXR C-reactive protein (CRP) level and the ESR Further -- case by case basis. Fever must be relived by anti- pyretics,as no evidence has been found that its reduction hampers disease recovery in any way.

15. Nacked Eye Urine Examination Turbid urine – sign of UTI and infection Reddish/pink Urine – s/o Gross Hematurea ? renal./urethral stones,? Cystitis / Ca bladder Cola coloured Urine(dark/brown urine) – Choluria is a common symptom of liver diseases, when serum bilirubin is higher than 1.5 mg/dL. Black coloured – Black water fever , P. Falcifarum inf not adequately treated ? Black water fever sudden and severe intravascular haemolysis leading to haemoglobinaemia and haemoglobinuria and clinically manifested by anaemia , passage of dark urine and often oliguric renal failure Black Water Urine choluria

16. TPR RECORDS FROM WARDS FOR TEMP, PULSE CHARTING We keep on sos

17. Pyrexia of Unknown Origin

18. Pyrexia /Fever of Unknown Origin FUO is defined as follows: 1. Fever ≥38.3°C (≥101°F) on at least two occasions 2. Illness duration of ≥3 weeks 3. No known immunocompromised state 4. Diagnosis that remains uncertain after a thorough history-taking, physical examination, and the following obligatory investigations

19. Obligatory Investigations for workup HIV serology , CBC with PS, ESR, CRP, electrolytes, creatinine, total protein, alkaline phosphatase(ALP), alanine aminotransferase(ALT/SGPT), aspartate aminotransferase(AST/SGOT), lactate dehydrogenase, creatine kinase, ferritin, antinuclear antibodies, and rheumatoid factor; protein electrophoresis; urinalysis; blood cultures ( n = 3); urine culture; chest x-ray; abdominal ultrasonography; and tuberculin skin test (TST) or interferon γ release assay (IGRA For Indian scenarios , three blood smears for malarial parasites, urine microscopy, typhi dot also recommended

20. Differential diagnosis of PUO DIFFERENTIAL DIAGNOSIS The differential diagnosis for FUO is extensive. It is important to remember that FUO is far more often caused by an atypical presentation of a rather common disease than by a very rare disease .

21. DIAGNOSTIC APPROCH AND INITIAL WORKUP Fever Documentation ‘Detailed History and Physical Examination

22. DIAGNOSTIC APPROACH

23. If the patient is not in multi-organ system failure, previous antibiotics/drugs should be stopped, the patient observed for at least 72 hours, at which point multiple blood (and fluid, if indicated) cultures should be taken. A second tier of investigations, depending on the constellation of symptoms like CSF Examination, bone marrow aspiration with a biopsy and routine, mycobacterial and fungal cultures and specific radiological investigations like CT, MRI is undertaken PUO if further categorized as :- 1)Classic 2) Nocosomial and with Neutropenia

24. Classical PUO The three major categories include infections, neoplasms and non-infectious inflammatory diseases (collagen vascular diseases and sarcoidosis). Other minor category include drug fever.

25. In a large series of classic FUO from Eastern India, infections were the most dominant cause seen in 53% (half of these were tuberculosis), neoplasms in 17% and collagen vascular diseases in 11%.

26. Infectious Causes The most common infectious causes of FUO include the following: Tuberculosis (TB) Subacute bacterial endocarditis (SBE), Discitis Enteric (typhoid) fever, Malaria, Extrapulmonary TB Less-common infectious causes of FUO include the following: HIV infection Abdominopelvic abscesses Epstein-Barr virus (EBV) infection Cytomegalovirus (CMV) infection Toxoplasmosis

27. Non-infective causes of pyrexia of unknown origin common noninfectious inflammatory causes of FUO include the following: Giant cell (temporal) arteritis Systemic lupus erythematosus (SLE) Periarteritis nodosa/microscopic polyangiitis (PAN/MPA) Rheumatoid arthritis (RA) Antiphospholipid syndrome (APS) Gout Pseudogout Behçet disease Sarcoidosis Felty syndrome Takayasu arteritis

28. Malignant and Neoplastic Causes of FUO Malignant and neoplastic causes of FUO are as follows: Most common: Lymphoma, renal cell carcinoma Less common: Myeloproliferative disorder, acute myelogenous leukemia Multiple myeloma, breast/liver/pancreatic/colon cancer, atrial myxoma, metastases to brain/liver

29. Nosocomial PUO In Nosocomial origin fever when uncertain diagnosis despite 1 week of inpatient evaluation. About 50% of nosocomial fever is due to infections. Non-infectious causes include drug fever, deep venous thrombosis, cholecystitis, pancreatitis and pulmonary embolism .

30. Nosocomial Approch

31. HIV associated FUO In India, tuberculosis accounts for about 70% of cases of prolonged fever, followed by disseminated cryptococcosis (10%), Pneumocystis jiroveci pneumonia (7%), community acquired pneumonia (2%) and liver abscess (2%). In the initial 6 months after the start of ART, immune reconstitution inflammatory syndrome (IRIS), drug fever are common whereas after 6 months, causes of prolonged fever include various forms of tuberculosis, neoplasms and non-infectious inflammatory diseases similar to a classic FUO.

32. APPROCH

33. Miscellaneous Causes of FUO Most common: Cirrhosis (due to portal endotoxins), drug fever Less common: Thyroiditis, Crohn disease Least common: Pulmonary emboli, hypothalamic syndrome, familial periodic fever syndromes, cyclic neutropenia, factitious fever (especially in those experienced with the healthcare field)

34. World Wide - Increasing early use of positron emission tomography–computed tomography (PET-CT) and the development of new molecular and serological tests for infection have improved diagnostic capability, but up to 50% of patients still have no cause found despite adequate investigations. Reassuringly, the cohort of undiagnosed patients has a good prognosis.

35. Neutropenic Fever Causes of Neutropenia are divided as Decreased production – These conditions are either a ) Drug Induced b)Infections and others . At least 50% of neutropaenic patients who become febrile have an established or occult infection

36. Drug fever with the drugs may be presented with neutropenia like, drug induced fever with Alkylating agents , Antimetabolites eg MTX , Non Cytotoxic agents like antibiotics Chloroquin , Penicilline , Sulphonamides , anticonvulsant like carbamazepine , antipsycotics like clozapine , and many others . some infections like Tuberculosis , Typhoid fever, Brucellosis , Tularemia , Measels , Infectious Mononucleosis , Malaria , Viral Hepatitis, Leishmaniasis and AIDS may present with neutropenic puicture . Conditions with Increase peripheral pooling may present with Transient Neutropenuia e.g. Overwhelming Bacterial Infections Conditions with inc destructions like Autoimmune Disorders , Rheumatoid arthritis , Lupus erythrematosis , Feltys syndrome may also present eith febrile illness with neutropenia

37. Approach After Excluding drug fever and noninfectious causes

38. Fever with Rash

39. Fever and Rash Fever with rash is a common presentation of many infectious and non infectious diseases that range from benign to life threatening.

40. DIAGNOSTIC APPROACH  

41. Clinical features

42. Appropriate laboratory testing includes Non specific tests like CBC, Urine Analysis etc. Serological and Antigen testing where appropiate

43. CENTRALLY DISTRIBUTED MACULOPAPULAR ERUPTIONS Diseases with fever and rash may be classified by type of eruption: centrally distributed maculopapular & peripheral Centrally distributed rashes , in which lesions are primarily truncal, are the most common type of eruption.

44. Measels The rash of rubeola (measles) starts at the hairline 4th days into the illness and moves down the body, typically sparing the palms and soles . MaculoPapular Rash Causative agent is Measels Virus or ParaMyxoVirus Mgt- Symptomatic & supportive Complication– Associated Pneumonia, encephlitis and Subacute sclerosing panencephalitis (late n rare)

45. Rubella German Measels Causative Agent- Rubella Virus Ip- 18 days Pink maculopapular , develops on forehead spread to extremities , fades by third day . Forchheimer sign small red papule on area of soft palate in 20% of cases Mgt- supportive and symptomatic

46.  Epidemic typhus  Epidemic typhus is due to  Rickettsia prowazekii   spread by  body lice , no vaccine is commercially available Treatment – Tab Doxy 100 mg Bd x 14 days

47. SCRUB TYPHUS AGENT – O.tutugamosi Harvest mites  on

48. Dengue Fever Diffuse flushing Maculopapular rash begins on trunk and spread to extremities and face , petechial on extremities , pruritic during recovery t/t- Supportive with Carefull attention to fluid management

49. Tornuque test Aedes Mosquito

50. Typhoid Fever Rose spots on chest and abdomen on 1 st week , small pale red macule blanchable . Last 2-3 days

51. Bacterial endocarditis Rash – Janeway lesions – Painless erythematous macules usually on palms or soles Osler Nodes – Tender pink nodules on finger or toe pads Petechial rash on skin mucosa Splinter hemorrhage on Nails

52. Chikungunya fever Vector – Aedes aegypti , Aedes albopictus . IP- 2-4 days Rash Transient between 1-4 days , Maculopapular mostly on face , trunk , extremities

53. Erythema marginatum (Rheumatic fever ) Cause– Gp A streptococcous , in patient with Rheumatic fever Rash- Erythematous annular papule and plaque over trunk and proximal extremities . Evolving and resolving within hours. (evanescent rash )

54. Systemic Lupus erythematosus (SLE) Rash – Malar rash , butterfly rash,-- fixed erythema over malar eminence Discoid rash –Erythematous raised patches with adherent keratotic scaling, a/w photosensitivity

55. NODULAR ERUPTIONS

56. Erythema Nodusum Due to inflammation of fat cells under the skin ( strepto , fungal , mycobacterial , yersinal ), Drugs 9 sulfa , penicillin ,OCP ) , sarcoidosis or idiopathic Delayed hypersensitivity . Immune complex mediated Rash- Large Violaceous , non ulcerative , tender, subcutaneous nodules self limiting and reolves in 3-6 weeks , treat the cause , NSAIDS

57. SS is reactive

58. Purpuric Eruptions N.meningitidis and Meningicoccoal pneumonia – Multilobular evolving pneumonuia Rash- Erythematous Maculopapular rash initially petechial or frankly purpuric over hours . Large Purpuric lesions in severe cases

59. Vesiculobulbur or Pustular Eruptions

60. Primary Herpes Infection

61. Herpes Zoster Herpes zoster  is viral infection that occurs with reactivation of the  varicella - zoster  virus. It is usually a painful but self-limited dermatomal vasicular rash Reactivation of varicella-zoster virus (VZV) that has remained dormant within dorsal root ganglia

62. Drug Indused Rash Mild , mostly disappear with 2-3 days and rarely upto 14 days , when offending drug is withdrawn In CBC – Eosinophilia may be present Macular eruptions ,a/w itching , arthralgia , mild fever Some drugs are more notorious :

63. SJS  is defined as skin involvement of < 10%,  TEN  is defined as skin involvement of > 30%, and  SJS / TEN  overlap as 10-30% skin involvement.

64. Ebola Hemorragic Viral fever Virus appeared in South sudan   Ebola  is a nonspecific maculopapular  rash  that appears between day four and six of disease. , Dark-red pinpoint papules arise on the face, arms, legs, buttocks, and around the hair roots with subsequent spread to the rest of the body. Ebola treatment is largely supportive and symptoimatic , VACCINE is available

65. Waterhouse- Friderichsen syndrome meningococcal septicemia but may complicate sepsis caused by other organisms Waterhouse- Friderichsen syndrome is characterized by the abrupt onset of fever, petechiae, arthralgia, weakness, and myalgias, Acute adrenal insufficiency due to adrenal gland hemorrhage

66. CLINICAL SCENARIOS A RECENTLY DIAGNOSED PLHA BY ROUTINE INCIDENTAL EXAMINATION ,AFEBRILE ERLIER HAS BEEN STARTED ART , AFTER `12 DAYS HE PRESENTEED AGAIN WITH C/O INTERMITTENT FEVER , ALL DIAGNOISTIC TEST HAS FOUND TO BE NEGATIVE . WHAT IS MOST PROBABLE CAUSE OF FEVER ? OPTION ????? ??1) IMMUNE RECONSTITUTION SYNDEOME ??2) DRUG FEVER

67. ANS- DRUG FEVER, DUE TO ONE OF ART COMPONENT IS ,MOST LIKEKY AS IT APPERED BEFORE < 6 WEEK OF STARTING OF ART AND ALL DIAGNOSTIC TESTS WERE NEGATIVE

68. Clinical scenario 2 A 60ye old female with a H/o CAD and on regular medications , presented with she h/o mild intermittent fever since 15 days Gross ascites, on ascitic fluid exam cell count 384/Cum, 92% lymphocytes and 8% PMN were found , further ESR was 42 mm in 1 hr. SAAG ratio of ascitic fluid was 1 . On P/e JVP was not raised chest was clear. BP was 100/60 and pulse 80/min . s.Amlyase was normal and s.create was 0.7 , her Mantoux was negative , what is most probable cause of her recently developed ascitis >? Option 1 CHF 2 abdominal Koch 3 CRF

69. Ans- Here SAAG Ratio 1 indiacate infective causes , in that mononuclear cells being 90 % with abundant cellularity and 42 esr indicate toward chronic indolent infection , all most consistence with Abdominal Koch Q2 – For confirmation what further workup as tier 3 investigation should be done ?

70. Ans – USG W/A and CECT Abdomen for evidence of enlargement of Mesenteric nodes is most likely step forward .

71. Take home message Fever is commonly encountered in OPD and IPD patients , Red flag sign which should alert clinician Fever with Hypotension , Visual disturbences , Severe Headache, Neck rigidity, H/o Significant weight loss, Aneamia , Cr. Jaundice , Anuira / Oligurea , Toxic look, S/o Multi-Organ Involvement , Unintentional weight loss, seizures, dark coloured urine , h/o drenching night sweats , new cardiac murmer , splinter hemorrhage Fever with Hemoptysis or ahematoemesis These are associated with disease with severe outcomes and should not be taken casualy

72. Thanks to Everyone References Harrison 20 th edition API book of medicine 10 th Edition Alagappan 6 th edition