1.2012School of Clinical MedicineClinical SkillsNRMSM UKZN Dr RM Abraham

2. OVERVIEW Introduction Thermoregulation Pathophysiology of fever Aetiology /Differential diagnosis of fever Types of fever Pyrexia of Unknown origin(PUO) Factitious fever History taking in a febrile patient 3. INTRODUCTIONFEVER(Pyrexia) Is an elevation of body temperature above the normalcircadian range (daily variation) as a result of a changein the thermoregulatory center located in the anteriorhypothalamus and pre-optic area (i.e. an increase inthe hypothalamic set point of 37 C) due to infection,metabolic derangements or increased cell destruction. 4. THERMOREGULATION Body temperature is controlled in the hypothalamus, which is directly sensitive to changes in core temperature The normal set-point of core temperature is tightly regulated within 37 0.5C, as required to preserve normal function of many enzymes and other metabolic processes. 5. THERMOREGULATIONIn a hot environment sweating is the main mechanism for increasing heatloss. This usually occurs when the ambient temperature rises above 32.5C or during exercise 6. PATHOPHYSIOLOGY OF FEVERThe initiation of fever begins: when exogenous or endogenous stimuli are presentedto specialized host cells, principally monocytes andmacrophages ,they will then stimulate the synthesisand release of various pyrogenic cytokines including :1)interleukin-1, interleukin-62)TNF-, and3)IFN-. 7. PATHOPHYSIOLOGY OF FEVERExogenous pyrogens: stimuli from outside the hostlike : microorganism, their products, or toxins and it iscalled EndotoxinEndotoxin : lipopolysaccharide ( LPS) LPS: is found in the outer membrane of all gramnegative organismsAction : 1) through stimulation of monocytes and macrophages 2) direct on endothelial cell of the brain to producefever 8. PATHOPHYSIOLOGY OF FEVEREndogenous pyrogens: polypeptides that are produced by the body ( bymonocytes and macrophages ) in response to stimulithat is usually triggered by infection or inflammationstimuli 9. PATHOPHYSIOLOGY OF FEVERPyrogens:Substances that cause fever are called pyrogensCytokines : Cytokines are regulatory polypeptides that areproduced by 1) monocytes / macrophages 2) lymphocytes 3) endothelial and epithelial cell and hepatocytes 10. PATHOPHYSIOLOGY OF FEVER The most important cytokines are : Interleukin 1 and 1 (The most pyrogenic) Tumor necrosis factor Interferon gamma Interleukin 6 (The least pyrogenic)cytokines>fever develop within 1hr of infection 11. PATHOPHYSIOLOGY OF FEVER Cytokine-receptor interactions in the pre-optic region ofthe anterior hypothalamus activate phospholipase A. This enzyme liberates plasma membrane arachidonic acidas substrate for the cyclo-oxygenase pathway. The resultingmediator, prostaglandin E2, then modifies theresponsiveness of thermosensitive neurons in thethermoregulatory centre. The PGE2 in the brain then stimulates the rapid release ofcAMP from glial cells, this release then induces the releaseof neurotransmitters that raises the thermoregulatory setpoint in the hypothalamus. These events then lead to increased body heat content andfever. 12. FEVERnfection, microbial toxins,mediators of inflammation, Microbial toxinsimmune reactions CyclicHeat conservation,AMP heat production nocytes/macrophages, dothelial cells, othersPGEElevated thermoregulatory setpoint genic cytokines IL-1, IL- Hypothalamic 6, TNF, IFN endothelium Circulation26 13. INFECTIONMonocytes, macrophagesEndogenous pyrogens (IL-1,TNF, IL-6)Hypothalamus: temperature setpoint Skeletal muscle Skin arterioles vasoconstrictionshivering Curl up/add clothes heat production heat loss Heat production > Heat lossHeat retention Body temperature Human Physiology 5th edition 1990 14. INFECTIONSMALIGNANCIES AUTOIMMUNE OTHERSTyphoid FeverCONDITIONS-LeukemiaHepatitis A & BJOINT/CONNECT Drug-inducedLymphomaLeptospirosisIVE TISSUEfeverTuberculosis DISEASEMalariaRheumatoid arthritisRheumatic feverSystemic lupuserythematosus 14 15. TYPES OF FEVERThe pattern of temperature changes may occasionally hint at the diagnosis: Continuous fever: Temperature remains above normal throughout the dayand does not fluctuate more than 1 C in 24 hours, e.g. lobar pneumonia,typhoid fever, urinary tract infection, brucellosis Intermittent fever: The temperature elevation is present only for a certain period, later cycling back to normal(i.e. Normal temp. between fever episodes), e.g. malaria, pyaemia, or septicemia.Following are its types Quotidian fever, with a periodicity of 24 hours, typical of Plasmodiumfalciparum malaria Tertian fever (48 hour periodicity), typical of Plasmodium vivax or Plasmodiumovale malaria Quartan fever (72 hour periodicity), typical of Plasmodium malariae malaria. 16. TYPES OF FEVER Remittent fever: Temperature remains above normal throughout the day and fluctuates more than 1 C in 24 hours, e.g., infective endocarditis. Pel-Ebstein fever: A specific kind of fever associated with Hodgkins lymphoma, being high for one week and low for the next week and so on. However, there is some debate as to whether this pattern truly exists. 17. PYREXIA OF UNKNOWN ORIGIN (PUO) A common presenting problem. Defined as a consistently elevated body temperature ofmore than 37.5 C persisting for more than 2 weekswith no diagnosis despite one week of initialinvestigations. The commonest cause of PUO is a common diseasepresenting atypically. As the duration of fever increases the likelihood of aninfectious cause decreases. Among children, infections are the most commoncauses. 18. Aetiology and Epidemiology ofPUO in developed countriesInfections (30%) Sepsis- Abscess at any site; Cholecystitis/ CholangitisUrinary tract infection Dental and sinus infection Bone and joint infections Imported infections, e.g. Malaria, Dengue, Brucellosis Enteric or Typhoid fever Infective endocarditis Tuberculosis (particularly extrapulmonary) Viral infections (cytomegalovirus-CMV, Ebstein-Barr virus-EBV, human immunodeficiency virus-HIV), Hepatitis A and B and toxoplasmosis Fungal infectionsMalignancy (20%) Lymphoma and myeloma Leukaemia Solid tumours (renal, liver, colon, stomach, pancreas) 19. Connective tissue disorders (15%)Vasculitic disorders (including polyarteritis nodosaand rheumatoid disease with vasculitis)Systemic lupus erythematosis (SLE)Rheumatoid arthritisRheumatoid feverTemporal arteritisPolymyositisMiscellaneous (20%)Inflammatory bowel diseaseLiver disease: Cirrhosis and granulomatous hepatitisSarcoidosisDrug reactionsThyrotoxicosisHypothalamic lesionsFamilial meditaranean feverNo diagnosis or resolves spontaneously (15%) 20. FACTITIOUS FEVER This is defined as fever engineered by the patient bymanipulating the thermometer and/or temperaturechart apparently to obtain medical care. uncommon and typically presents in young womenwith a medical and nursing background. Examples include The dipping of thermometers intohot drinks to fake a fever. The factitious disorder is usually medical but mayrelate to a psychiatric illness with reports ofdepressive illness. 21. FACTITIOUS FEVERCLUES TO THE DIAGNOSIS OF FACTITIOUS FEVER A patient who looks well Absence of temperature-related changes in pulse rate Temperature > 41C Absence of sweating during the period of fever Normal ESR and CRP despite high fever Useful methods for the detection of factitious feverinclude1) Supervised (observed) temperature measurement2) Measuring the temperature of freshly voided urine 22. HISTORY TAKING IN FEBRILEPATIENTS Using the Calgary Cambridge guide as a framework tointerviewing patients. The most important step is taking a meticulous detailed historyto explore the patients problems from three perspectives. Biomedical perspective- to understand the chronology ofsymptoms, analyse each symptom and review each system tolocalize the source of the fever. Contextual history- very important Patients perspective- to understand the patients interpretationof the illness. Systems review- This is a guide not to miss anything. Anysignificant finding should be moved to HPC or PMH dependingupon where you think it belongs. 23. Initiating the sessionpreparationestablishing initial rapportidentifying the reasons for the consultationProviding Gathering information Building thestructure exploration of the patients problems to discover the: relationship biomedical perspective the patients perspectivemakingorganisation background information - contextusingovertappropriate Physical examinationnon-verbalattending to behaviourflowExplanation and planning developingproviding the correct type and amount of information rapportaiding accurate recall and understanding involvingachieving a shared understanding: incorporating thethe patientpatients illness frameworkplanning: shared decision makingClosing the sessionensuring appropriate point of closureforward planninga 24. The content of the medical interviewPatients problem list1.2.3.Exploration of patients problems:Biomedical perspectivesequence of events, symptom analysis, relevant systems reviewPatients perspectiveideas, concerns, expectations, effects on life, feelings ICEBackground information - contextPast medical historyFamily historyPersonal and social historyDrug and allergy historySystems reviewb 25. BIOMEDICAL PERSPECTIVEPresenting complaints of a patient with fever Feeling hot A feeling of heat does not necessarily imply fever Rigors.profound chills accompanied by chattering of the teethand severe shivering, implies a rapid rise in bodytemperature. Can be produced by :1) brucellosis and malaria2) sepsis with abscess3) lymphoma Excessive sweating.Night sweats are characteristic of tuberculosis, butsweating from any cause is usually worse at night. 26. BIOMEDICAL PERSPECTIVE Recurrent fever. Source is often a focus of bacterial infection such ascholecystitis or cholangitis or urinary tract infectionespecially associated with an obstruction or calculi. Headache.Fever from any cause may provoke headache.Severe headache and photophobia, may suggestsmeningitis. Delirium. Mental confusion during fever is well described andrelatively more common in young children and in old age. Muscle pain. Myalgia is characteristic of viral infectionssuch as influenza, Malaria and brucellosis. 27. BIOMEDICAL PERSPECTIVESymptom analysis for fever Verify presence of fever- True or factitious fever Duration- Acute or chronic Mode of onset- Abrupt or gradual Progression- Continuous or intermittent. If intermittentask about frequency to determine the pattern. Severity- how it affects daily work/physical activities. Relieving and aggravating factors Treatment received or/and outcome Associated symptoms- Localizing symptoms mayindicate the source of fever. 28. BIOMEDICAL PERSPECTIVE Respiratory tract symptoms:1) Sore throat, nasal discharge, sneezing-URTI2) Sinus pain and headache-suggests sinusitis3) cough, sputum, wheeze or breathlessness-suggests a LRTI Genitourinary symptoms:1) Frequency of micturition, dysuria, loin pain, and vaginal or urethral discharge-suggestinga) Urinary tract infection,b) Pelvic inflammatory disease andc) Sexually transmitted infection (STI) 29. BIOMEDICAL PERSPECTIVE Abdominal symptoms: diarrhea, with or without blood, weight loss andabdominal pain -suggesting a) Gastroenteritis, b) Intra-abdominal sepsis, c) Inflammatory bowel disease, d) Malignancy Skin rash: enquire about appearance and distribution as it may provide clues to the diagnosis-1)Macular- Measles,Rubella,toxoplasmosis2)Haemorrhagic- Meningococcal infections, viral haemorrhagic fever.3)Vesicular- Chickenpox, Shingles, herpes simplex4) Nodular- Erythema nodosum( TB and Leprosy)5)Erythematous- Drug rashes, Dengue fever 30. BIOMEDICAL PERSPECTIVE Joint symptoms: joint pain, swelling or limitation of movement is suggestive of active arthritis. A) distribution : mono , oligo or poly arthritis B) appearance : fleeting1) infective arthritis- oligoarthritis2) collagen vascular disease-fleeting3) reactive arthritis 31. BIOMEDICAL PERSPECTIVEConstitutional symptoms: Weakness Fatigue Anorexia Change of weight Fever/chills Lumps Night sweats 32. CONTEXTUAL HISTORYPast Medical /Surgical HistoryStart by asking the patient if they have any medicalproblems IHD/DM/Asthma/HT/RHD, TB/Jaundice/Fits e.g. if diabetic- mention time ofdiagnosis/current medication/clinic check upPast surgical/operation history E.g. time/place/ what type of operation. Note any blood transfusion / blood grouping. H/O dental extractions/circumcision & any excessive bleeding during theseprocedures.Patient known to have rheumatic heart disease is at risk to develop infectiveendocarditis if not given prophylaxis Any minor operations or procedures including endoscopies, dentalinterventions, biopsies.History of trauma/accidents E.g. time/place/ and what type of accident History of tattoo piercing 33. CONTEXTUAL HISTORYDrug and allergy History dosage, timing &how long. Drug fever is uncommon and therefore easily missed-Theculprits include : penicillin and cephalosporin sulphonamide anti tuberculous agents anticonvulsants particularly phenytoin OCT/Vitamins/Traditional /Herbal medicine & alternativemedicine such as acupuncture. Blood transfusion. Immunization against Hepatitis A &B, Typhoid fever. Malaria prophylaxis 34. CONTEXTUAL HISTORYFamily History Any familial disease/running in families e.g. breastcancer, IHD, DM, Asthma, Arthritis Infections running in families as TB, Leprosy. Cholera, typhoid in case of epidemics. 35. CONTEXTUAL HISTORYPersonal and Social History Smoking history - amount, duration & type- strong risk factor for IHD Alcohol history - amount, duration & type-Unhealthy alcohol use isassociated with cardiomyopathy, CVA, liver cirrhosis, alcoholichepatitis, hepatocellular carcinoma. Occupation, social & education background, family social support&financial situation, Social class. Home conditions-Water supply, Sanitation status in his home &surrounding, Geographic area of living, fresh-water swimming. Animals / birds in his/her house- exposure to birds (psittacosis) oranimals (toxoplasmosis, brucellosis, leptospirosis) Consumption of unpasteurized milk or milk products (tuberculosis,brucellosis and Q fever). Sexual History- Unprotected exposure to sexual partner with STI, HIV Illicit drug usage- injections and sharing of needles (HIV, hepatitis B&C, infective endocarditis), site of injection (e.g Femoral vein-septicarthritis, ilio-psoas abscess) 36. CONTEXTUAL HISTORYTravel HistoryTravel to an area known to be endemic for certain disease: Name of the area, duration of stay Onset of illness- (incubation period) 1 10 Days- Malaria, Dengue, Salmonella 10 21Days-Malaria,Typhoid,Brucella,HepatitisA Weeks-Months- Amoebiasis, HIV, HepatitisVital questions-(Always ask about foreign travel). a) Where have you been? Endemic area or not ? b) What have you done? C) How long were you there? d) Did you have insect bites or contact with animals? e) Did you take precautions/prophylaxis against malaria?If the patient has been in an endemic area The most common diagnoses :Malaria, Typhoid fever, Viral hepatitis, Dengue fever Malaria must be excluded whatever the presenting symptoms 37. PATIENTS PERSPECTIVEAlways ask the patient how he/she feels/thinks aboutthe illness by analysing Ideas Concerns Feelings Expectations Effects on daily living 38. SYSTEMS REVIEW General Weakness Fatigue Anorexia Change of weight Fever/chills Lumps Night sweats 39. SYSTEMS REVIEWCardiovascular Chest pain Paroxysmal Nocturnal Dyspnoea Orthopnoea Short Of Breath(SOB) Cough/sputum (pinkish/frank blood) Swelling of ankle(SOA) Palpitations Cyanosis 40. SYSTEMS REVIEWGastrointestinal Appetite (anorexia/weight change) Diet Nausea/vomiting Regurgitation/heart burn/flatulence Difficulty in swallowing Abdominal pain/distension Change of bowel habit Haematemesis, melaena Jaundice 41. SYSTEMS REVIEWRespiratory System Cough(productive/dry) Sputum (colour, amount, smell) Haemoptysis Chest pain SOB/Dyspnoea Tachypnoea Hoarseness Wheezing 42. SYSTEMS REVIEWUrinary System Frequency Dysuria Urgency Hesitancy Terminal dribbling Nocturia Back/loin pain Incontinence Character of urine: color/ amount (polyuria) & timing Fever 43. SYSTEMS REVIEWNervous System Visual/Smell/Taste/Hearing/Speech problem Head ache Fits/Faints/Black outs/loss of consciousness(LOC) Muscle weakness/numbness/paralysis Abnormal sensation Tremor Change of behaviour or psyche. Paresis. 44. SYSTEMS REVIEWGenital system Pain/ discomfort/ itching Discharge Unusual bleeding Sexual history Menstrual history menarche/ LMP/ duration &amount of cycle/ Contraception Obstetric history Para/ gravida/abortion 45. SYSTEMS REVIEWMusculoskeletal System Pain muscle, bone, joint Swelling Weakness/movement Deformities Gait 46. THE END: REFERENCES Guytons Textbook of Medical Physiology Davidsons Principles & Practice of Medicine Hutchinsons Clinical Methods Harrisons Principles of Internal Medicine Google images