Body temperature is controlled by the hypothalamus. Neurons in both the preoptic anterior hypothalamus and the posterior hypothalamus receive two kinds of signals: one from peripheral nerves that reflect warmth/cold receptors and the other from the temperature of the blood bathing the region. These two types of signals are integrated by the thermoregulatory center of the hypothalamus to maintain normal temperature. Human metabolic processes are temperature dependent, and an individual’s body temperature rarely varies by more than 1C from baseline. The peripheral effector mechanisms are sweating (to reduce temp.), shivering (to raise temperature by muscle activity) and vasoregulation (constriction and dilatation). The central thermostat is situated in the hypothalamus. Heat and cold sensitive neurons are located in the anterior hypothalamus and pre-optic areas. Temperature information from peripheral receptors is integrated in the hypothalamus , allowing modulation of the body’s heat production, conservation and loss. This is controlled by neuronal mechanisms involving the limbic system, lower brain stem, spinal cord and autonomic nerves. Temperature in healthy adults is tightly controlled at a mean of 36.8C; there is however a physiological diurnal variation of approx 0.5C, with the maximum occurring btw 4 and 8pm and the minimum btw 2 and 6am.
IFN-gamma is produced mainly by T-cells and natural killer cells activated by antigens, mitogens, or alloantigens. It is produced by lymphocytes expressing the surface antigens CD4 and CD8.
Vasculitis (plural: vasculitides) refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected.
HPC- history of presenting complaintPMH- Past medical history
Macule – A macule is a change in surface color, without elevation or depression and, therefore, nonpalpable, well or ill-defined, variously sized, but generally considered less than either 5 or 10 mm in diameter at the widest point.Vesicle – A vesicle is a circumscribed, fluid-containing, epidermal elevation generally considered less than either 5 or 10 mm in diameter at the widest pointNodule – A nodule is morphologically similar to a papule, but is greater than either 5 or 10 mm in both width and depth, and most frequently centered in the dermis or subcutaneous fat. The depth of involvement is what differentiates a nodule from a papulePapule-A papule is a circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than either 5 or 10 mm in diameter at the widest point
Living conditionsIf in squatter’s area-reflect on the lifestyle of Pt, easy transmissibility of other infections due overpopulation within the area, hygiene and cleanlinessIf living near a body of water-especially stagnant water, may bring about the possibility of contracting the disease from vectors for example: mosquitoes (Dengue) Source of water-may indicate if water-borne pathogens have a role in the disease (Typhoid, Cholera)Geographic area of living-Malaria-Saudi (malaria area)/Africa/IndiaBrucella-Saudi/Gulf AreaTyphoid-India/Pakistan/Egypt/IndonesiaHistoplasmosis-USA (West Coast)Tuberculosis, Liver Abscess, AIDS- All over the world
Which countries and regions were visited, arrival and departure datesDetails of living hx including living and sleeping conditions, whether bed nets were used, what type of food and water was consumed and whether there was any contact with animals, hospitals or fresh water.Sexual hx-Unprotected sexual intercourse with a commercial sex worker
Approach to history taking in a patient with fever
2012School of Clinical Medicine Clinical Skills NRMSM UKZN Dr RM Abraham
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
INTRODUCTIONFEVER(Pyrexia) Is an elevation of body temperature above the normal circadian range (daily variation) as a result of a change in the thermoregulatory center located in the anterior hypothalamus and pre-optic area (i.e. an increase in the hypothalamic set point of 37 C) due to infection, metabolic derangements or increased cell destruction.
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 ± 0.5°C, as required to preserve normal function of many enzymes and other metabolic processes.
THERMOREGULATIONIn a hot environment sweating is the main mechanism for increasing heat loss. This usually occurs when the ambient temperature rises above 32.5°C or during exercise
PATHOPHYSIOLOGY OF FEVERThe initiation of fever begins: when exogenous or endogenous stimuli are presented to specialized host cells, principally monocytes and macrophages ,they will then stimulate the synthesis and release of various pyrogenic cytokines including : 1)interleukin-1, interleukin-6 2)TNF-α, and 3)IFN-γ.
PATHOPHYSIOLOGY OF FEVERExogenous pyrogens: stimuli from outside the host like : microorganism, their products, or toxins and it is called EndotoxinEndotoxin : lipopolysaccharide ( LPS) LPS: is found in the outer membrane of all gram negative organismsAction : 1) through stimulation of monocytes and macrophages 2) direct on endothelial cell of the brain to produce fever
PATHOPHYSIOLOGY OF FEVEREndogenous pyrogens: polypeptides that are produced by the body ( by monocytes and macrophages ) in response to stimuli that is usually triggered by infection or inflammation stimuli
PATHOPHYSIOLOGY OF FEVERPyrogens: Substances that cause fever are called pyrogensCytokines : Cytokines are regulatory polypeptides that are produced by 1) monocytes / macrophages 2) lymphocytes 3) endothelial and epithelial cell and hepatocytes
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
PATHOPHYSIOLOGY OF FEVER Cytokine-receptor interactions in the pre-optic region of the anterior hypothalamus activate phospholipase A. This enzyme liberates plasma membrane arachidonic acid as substrate for the cyclo-oxygenase pathway. The resulting mediator, prostaglandin E2, then modifies the responsiveness of thermosensitive neurons in the thermoregulatory centre. The PGE2 in the brain then stimulates the rapid release of cAMP from glial cells, this release then induces the release of neurotransmitters that raises the thermoregulatory set point in the hypothalamus. These events then lead to increased body heat content and fever.
FEVERnfection, microbial toxins,mediators of inflammation, Microbial toxins immune reactions Cyclic Heat conservation, AMP heat production nocytes/macrophages, dothelial cells, others PGE₂ Elevated thermoregulatory set point genic cytokines IL-1, IL- Hypothalamic 6, TNF, IFN endothelium Circulation 26
INFECTION Monocytes, macrophages Endogenous pyrogens (IL-1,TNF, IL-6) Hypothalamus: ↑ temperature setpoint Skeletal muscle Skin arterioles ↑ vasoconstriction shivering Curl up/add clothes↑ heat production ↓ heat loss Heat production > Heat loss Heat retention ↑ Body temperature Human Physiology 5th edition 1990
TYPES OF FEVERThe pattern of temperature changes may occasionally hint at the diagnosis: Continuous fever: Temperature remains above normal throughout the day and 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 Plasmodium falciparum malaria Tertian fever (48 hour periodicity), typical of Plasmodium vivax or Plasmodium ovale malaria Quartan fever (72 hour periodicity), typical of Plasmodium malariae malaria.
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.
PYREXIA OF UNKNOWN ORIGIN (PUO) A common presenting problem. Defined as a consistently elevated body temperature of more than 37.5 C persisting for more than 2 weeks with no diagnosis despite one week of initial investigations. The commonest cause of PUO is a common disease presenting atypically. As the duration of fever increases the likelihood of an infectious cause decreases. Among children, infections are the most common causes.
Aetiology and Epidemiology ofPUO in developed countriesInfections (30%) Sepsis- Abscess at any site; Cholecystitis/ Cholangitis Urinary 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)
FACTITIOUS FEVER This is defined as fever engineered by the patient by manipulating the thermometer and/or temperature chart apparently to obtain medical care. uncommon and typically presents in young women with a medical and nursing background. Examples include The dipping of thermometers into hot drinks to fake a fever. The factitious disorder is usually medical but may relate to a psychiatric illness with reports of depressive illness.
FACTITIOUS FEVERCLUES TO THE DIAGNOSIS OF FACTITIOUS FEVER A patient who looks well Absence of temperature-related changes in pulse rate Temperature > 41°C Absence of sweating during the period of fever Normal ESR and CRP despite high fever Useful methods for the detection of factitious fever include 1) Supervised (observed) temperature measurement 2) Measuring the temperature of freshly voided urine
HISTORY TAKING IN FEBRILEPATIENTS Using the Calgary Cambridge guide as a framework to interviewing patients. The most important step is taking a meticulous detailed history to explore the patients problems from three perspectives. Biomedical perspective- to understand the chronology of symptoms, analyse each symptom and review each system to localize the source of the fever. Contextual history- very important Patients perspective- to understand the patients interpretation of the illness. Systems review- This is a guide not to miss anything. Any significant finding should be moved to HPC or PMH depending upon where you think it belongs.
Initiating the session preparation establishing initial rapport identifying the reasons for the consultationProviding Gathering information Building thestructure exploration of the patient’s problems to discover the: relationship biomedical perspective the patient’s perspectivemakingorganisation background information - context usingovert appropriate Physical examination non-verbalattending to behaviourflow Explanation and planning developing providing the correct type and amount of information rapport aiding accurate recall and understanding involving achieving a shared understanding: incorporating the the patient patient’s illness framework planning: shared decision making Closing the session ensuring appropriate point of closure forward planning a
The content of the medical interviewPatient’s problem list1.2.3.Exploration of patient’s problems:Biomedical perspectivesequence of events, symptom analysis, relevant systems reviewPatient’s perspectiveideas, concerns, expectations, effects on life, feelings ICEBackground information - contextPast medical historyFamily historyPersonal and social historyDrug and allergy historySystems review b
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 teeth and severe shivering, implies a rapid rise in body temperature. Can be produced by : 1) brucellosis and malaria 2) sepsis with abscess 3) lymphoma Excessive sweating. Night sweats are characteristic of tuberculosis, but sweating from any cause is usually worse at night.
BIOMEDICAL PERSPECTIVE Recurrent fever. Source is often a focus of bacterial infection such as cholecystitis or cholangitis or urinary tract infection especially associated with an obstruction or calculi. Headache. Fever from any cause may provoke headache. Severe headache and photophobia, may suggests meningitis. Delirium. Mental confusion during fever is well described and relatively more common in young children and in old age. Muscle pain. Myalgia is characteristic of viral infections such as influenza, Malaria and brucellosis.
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 intermittent ask 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 may indicate the source of fever.
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-suggesting a) Urinary tract infection, b) Pelvic inflammatory disease and c) Sexually transmitted infection (STI)
BIOMEDICAL PERSPECTIVE Abdominal symptoms: diarrhea, with or without blood, weight loss and abdominal 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
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 : fleeting 1) infective arthritis- oligoarthritis 2) collagen vascular disease-fleeting 3) reactive arthritis
BIOMEDICAL PERSPECTIVEConstitutional symptoms: Weakness Fatigue Anorexia Change of weight Fever/chills Lumps Night sweats
CONTEXTUAL HISTORYPast Medical /Surgical HistoryStart by asking the patient if they have any medical problems IHD/DM/Asthma/HT/RHD, TB/Jaundice/Fits e.g. if diabetic- mention time of diagnosis/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 these procedures. Patient known to have rheumatic heart disease is at risk to develop infective endocarditis if not given prophylaxis Any minor operations or procedures including endoscopies, dental interventions, biopsies.History of trauma/accidents E.g. time/place/ and what type of accident History of tattoo piercing
CONTEXTUAL HISTORYDrug and allergy History dosage, timing &how long. Drug fever is uncommon and therefore easily missed-The culprits include : penicillin and cephalosporin sulphonamide anti tuberculous agents anticonvulsants particularly phenytoin OCT/Vitamins/Traditional /Herbal medicine & alternative medicine such as acupuncture. Blood transfusion. Immunization against Hepatitis A &B, Typhoid fever. Malaria prophylaxis
CONTEXTUAL HISTORYFamily History Any familial disease/running in families e.g. breast cancer, IHD, DM, Asthma, Arthritis Infections running in families as TB, Leprosy. Cholera, typhoid in case of epidemics.
CONTEXTUAL HISTORYPersonal and Social History Smoking history - amount, duration & type- strong risk factor for IHD Alcohol history - amount, duration & type-Unhealthy alcohol use is associated with cardiomyopathy, CVA, liver cirrhosis, alcoholic hepatitis, 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) or animals (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-septic arthritis, ilio-psoas abscess)
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
PATIENTS PERSPECTIVEAlways ask the patient how he/she feels/thinks about the illness by analysing Ideas Concerns Feelings Expectations Effects on daily living
SYSTEMS REVIEW General• Weakness• Fatigue• Anorexia• Change of weight• Fever/chills• Lumps• Night sweats
SYSTEMS REVIEWCardiovascular• Chest pain• Paroxysmal Nocturnal Dyspnoea• Orthopnoea• Short Of Breath(SOB)• Cough/sputum (pinkish/frank blood)• Swelling of ankle(SOA)• Palpitations• Cyanosis
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
SYSTEMS REVIEWUrinary System• Frequency• Dysuria• Urgency• Hesitancy• Terminal dribbling• Nocturia• Back/loin pain• Incontinence• Character of urine: color/ amount (polyuria) & timing• Fever
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.
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