Rational Approach to Fever

Fever is a symptom of more than 300 diseases, a manifestation of man’s protest against the insults and intrusions to his system.

“There are ‘specialists’ for the heart, the brain, the nerves, the kidneys etc. But why is there no one for fever?”
– Conversation between two patients, overheard by a nurse.

Body temperature: The normal and the abnormal

Temperature 0 Centigrade 0 Fahrenheit
Normal 36.6 – 37.20 C 98 – 990 F
Pyrexia >37.20 C >990 F
Hyperpyrexia >41.60 C >1070 F
Subnormal <36.60 C <980 F
Hypothermia <350 C <950 F

The body temperature is lower in the morning and rises by evening, with a range of about half a degree. A morning temperature of >37.2ºC (>99.4ºF) or evening temperature of >37.7ºC (>99.9ºF) is considered as ‘fever’.

The Thermometer:

Thermometer is the most important tool in a clinician’s office. Small elevations in body temperature can be made out ONLY with the help of a thermometer and therefore, it should be a routine practice to record the temperature in ALL patients.

How to record the body temperature?

Body temperature is recorded with a thermometer inserted under the tongue. In some cases, especially in children and the infirm, the thermometer is inserted under the arm pit (axilla) or groin fold or into the rectum. Generally the temperature is recorded for 3 minutes. The rectal temperature represents the core temperature and is about half degree higher than the oral temperature. The axillary temperature is about half degree lower than the oral temperature.

Fallacies in recording the body temperature:

  1. Not keeping the thermometer properly
  2. Not keeping the thermometer for required length of time
  3. Recording the temperature soon after a hot or cold drink or food
  4. Faulty thermometer

Patterns of Fever

Fever takes a characteristic course in many diseases and the pattern of rise and fall of temperature may
itself be a clue for diagnosis.

Sustained: Persistent elevation in temperature with minimal diurnal variation (<10C)

Intermittent: Circadian rhythm is exaggerated, with wide variations; when the variation is extremely
large, it is called hectic or septic. If this occurs daily, it is called quotidian fever.

Remittent: Temperature variation is >20C, but does not touch normal. e.g.
Tuberculosis, viral fever, many bacterial infections etc.

Step – ladder fever is the one where the temperature rises gradually to a higher level with every spike.

Relapsing: Febrile episodes are separated by intervals of normal temperature. Examples are:

  • Tertian fever – fever occurs once in 3 days or 48 hours (vivax, falciparum malaria);
  • Quartan fever – fever occurs once in four days or 72 hours (P. malariae);
  • Pel Ebstein: fever occurs once in 7-20 days (Hodgkin’s and other lymphomas)
  • Saddle Back: Patient has fever for 1-2 days, followed by remission for 2-3 days and then relapse of fever
  • Double Quotidian: Patient gets two spikes of fever every day, generally once in the morning and once in the evening. May be a feature of miliary tuberculosis
  • Inverse fever: The temperature rises in the early hours of morning rather than in the evening, seen in some cases of miliary tuberculosis.

Evening rise in temperature or night sweats: In some diseases, the rise in body temperature s evident only
in the evening hours or the patient may be woken up at night with sweating. This pattern is seen when the elevation in the temperature is mild to moderate and added to the diurnal rise in the evening, the body temperature goes beyond the normal level. Common causes for evening rise of temperature are tuberculosis, leukemias, autoimmune disorders etc.

Approach to a febrile patient

History of the illness:

Like in any other illness, a detailed history plays a vital role in making a diagnosis. Attention should be paid to the following details:

  • Onset – Sudden / insidious / unnoticed
  • Type – Sustained / intermittent / remittent / relapsing
  • Duration
  • Associated complaints – head ache, body ache, running nose, rashes, sore throat, cough, chest pain, breathlessness, dysuria, frequency of micturition, diarrhoea, vomiting, abdominal pain, pain / redness of limbs, swellings, joint pains etc.
  • Weight loss
  • Contacts
  • Occupation
  • Travel – Trekking / endemic areas
  • Stay (hotel, hostel, ashram, hospital)
  • Habits
  • Past history
  • Treatment history – Transfusions, injections, allergies, medications, hospital interventions
  • Sexual practice

General Examination: Look for the following

Temperature Oral preferred; record for 3 minutes
Pulse For every 0 rise in temperature, pulse increases by 10. Pulse – temperature dissociation is seen in typhoid, brucellosis, leptospirosis, viral myocarditis, diphtheria, rheumatic carditis, bacterial
endocarditis etc
BP Hypotension signifies septic shock
Tachypnoea For every 0 rise in temp., respiratory rate rises by 4. Higher respiratory rate signifies pneumonia, bronchitis, pulmonary oedema
Breathlessness Bronchitis, pulmonary oedema, ARDS
Prostration Indicates severe infection
Sensorium Altered sensorium could be due to fever, metabolic disturbances, CNS involvement
Nails Look for anemia, jaundice, cyanosis, haemorrhages
Lymph nodes Cervical, axillary, inguinal node enlargement
Oral cavity Thrush, palatal haemorrhages, dental sepsis, oral hygiene, tonsils, pharynx, ulcers, pallor, jaundice
Skin Rashes – haemorrhagic/ non haemorrhagic, purpura, lymphangitis, cellulitis, pallor, jaundice
Eyes Injection of conjunctivae, jaundice, pallor, papilloedema

Fever – Systemic Examination

Careful and detailed systemic examination is very important in all cases of fever. All systems should be carefully
examined since the infection or the cause of fever could be lurking inside any system.

System What to look for Possibilities
Upper Respiratory Tract Oral cavity for tonsils,
pharynx, dental sepsis; sinuses for tenderness; ears for swollen membrane,
perforation, discharge
Tonsillitis, pharyngitis, sinusitis, ASOM, CSOM etc.
Respiratory System Tachypnoea, diminished breath sounds,
Bronchial breathing, crackles, wheezes, rub, dullness
Pneumonia, bronchitis, cavities, pleurisy, effusion, empyema
Abdomen Tenderness, organomegaly, free fluid, mass Hepatitis, splenomegaly in various infections, intra abdominal abscesses, peritonitis

Cardio Vascular System
Heart rate, murmurs, pericardial rub Endo /peri / myo carditis

Central Nervous System
Altered sensorium, neck stiffness,
ocular fundii, deficits
Meningitis, encephalitis, abscess
Musculo Skeletal Muscular tenderness in shoulders,
gluteals, calf; joint pain, swelling, tenderness; spine tenderness
Dengue, Leptospirosis; arthritis, myositis etc.
Genitalia Scrotum, testes, vagina, cervix Orchitis, pyocele, balanoposthitis, STDs, abscess
Per Rectal Perianal abscess, prostate & seminal vesicles Perianal abscess, prostatitis, seminal vesiculitis
Pelvic Examination PID

Duration of Fever and Approach:

Duration What is to be done Possibilities
<3 Days
It is the beginning!
If in a malarious area – Do MP test in ALL cases, and administer presumptive
antimalarial treatment to everybody
Fine rashes, runny nose, watering of eyes: Consider viral exanthematous fever.
Rashes, severe body ache, pain on moving the eye balls: Consider flaviviral fevers (dengue, chikungunya), leptospirosis etc.
Consider acute urinary infection in women and elderly men;
Consider respiratory infection in smokers, alcoholics, elderly
Look for common sites of infections: Pharynx/tonsils; sinuses; skin (cellulitis, commonly of legs)
Symptoms & signs of severe illness – admit & investigate
Investigations: Blood count; urine analysis, particularly in a female; MP test

Viral fever
Malaria
URTI
LRTI
UTI
Any other

3 days to 7 days
Case on follow-up: Look for new symptoms and signs – Chest pain (pleurisy), localised pain (focal infection), diarrhoea (enteric), head ache (meningitis, sinusitis), lymph nodes etc.
New case: Examine in detail
Symptoms & signs of severe illness – admit & investigate
Investigations: MP test (repeat), Blood count; urine analysis, cultures, Widal test
and other serological tests; chest x ray
All above
Enteric Fever

Fever – 7 days to 15 days

Symptom Possibilities
Head ache Sinusitis, Otitis, dental sepsis, malaria, subacute meningitis
Cough Tonsillitis, pneumonia, bronchitis, malaria, tuberculosis.
Chest pain Pleural effusion / empyema, pericarditis, liver abscess, root pain
Diarrhoea Enteric fever, colitis, drug induced
Pain abdomen Hepatitis, liver abscess, appendicitis, PID, other intra abdominal sepsis

Signs: Specifically look for lymph nodes, jaundice, anemia, chest signs, abdominal tenderness, organomegaly, free fluid, neck stiffness etc.

Consider: Prolonged viral fever (infectious mononucleosis, CMV, HIV, hepatitis); malaria; enteric fever; tuberculosis; partially treated or resistant infections

Investigations: Blood count, ESR, Urine analysis, MP test, Widal, serological tests for EBV, CMV, Leptospira, amebiasis, rickettsiae; Chest X ray, Ultra sound abdomen

Fever of Unknown Origin: Fever of Unknown Origin (FUO) is one of the most challenging and interesting problems
in clinical medicine

Definition of FUO:

Fever of >38.30 C (1010F) on several occasions

  • Classic: Fever for >2 weeks OR in hospital investigations for 3 days OR 3 out patient visits
  • Nosocomial: Hospitalized for 3 days, no fever on admission.
  • Neutropenic: Neutrophil count <500/mm3, in hospital investigations for 3 days
  • HIV associated: Proven HIV infection, 3 days in hospital or 4 weeks out patient

FUO – Common Causes:

Infections: Infections account for 40% of cases of FUO.

  • Localised: Appendicitis, cholangitis, cholecystitis, diverticulitis, dental sepsis, liver abscess, osteomyelitis (with
    prosthesis), P.I.D., prostatic abscess, sinusitis, intra-abdominal abscess, thrombophlebitis etc.
  • Intravascular: Endocarditis, aortitis
  • Systemic:
    • Bacterial – Tuberculosis, mainly extra pulmonary; Brucellosis, Leptospirosis, Salmonellosis, atypical mycobacteria, nocardia, actinomycosis
    • Rickettsial, mycopalsma
    • Fungal – Aspergillosis, candidiasis, cryptococcosis, P.carinii
    • Viral – Hepatitis A, B, C, D, E.; EBV, CMV, HIV
    • Parasitic – Malaria, Leishmania, Amebiasis

Other causes:

  • Neoplasms:
    • Malignant – Hodgkin’s and Non Hodgkin’s lymphoma, Immunoblastic lymphadenopathy, leukemia, renal cell carcinoma, hepatoma, sarcoma, pancreatic cancers.
    • Benign – Atrial myxoma, renal angiomyolipoma
  • Auto immune syndromes: Rheumatoid arthritis, SLE, PAN, MCTD etc.
  • Granulomatous diseases: Crohn’s disease, Idiopathic granulomatous hepatitis, Sarcoidosis
  • Miscellaneous: Drug fever, sub-acute thyroiditis, hematomas, gout, post MI, tissue infarction/ necrosis, cyclic neutropenia, adrenal insufficiency, brain tumor, hyperthyroidism, phaeochromocytoma, factitious fevers, habitual hyperthermia

FUO of more than > 6 months is less likely to be due to an infection

FUO – Investigations:

FUO may require a wide array of investigations to locate the cause of the fever. History, clinical findings and findings of routine investigations should guide the selection of these special investigations.

  • Hematological: Blood count, ESR, PS study, Malarial Parasite, Microfilaria, Leishmania
  • Biochemical: LFT, CSF study, analysis of pleural / peritoneal fluids
  • Serological: Widal, Brucellosis, Weil – Felix, Amebiasis, Hepatitis, HIV, EBV, CMV, Leptospira, Tuberculosis etc., Anti nuclear antibody, RA factor
  • Microbiological: Cultures of blood, body fluids, secretions; staining and examination of secretions
  • Pathological: Bone marrow aspiration, FNAC, examination of fluids and secretions, histopathology – Biopsy of liver, lymph nodes
  • Skin tests: Tuberculosis
  • Imaging: X – Ray of chest (PA, lateral, apical, under penetrated AP), sinuses, bones, joints, Barium Series etc.; Ultra sound studies, echocardiography (for vegetations) CT scan / MRI Scan
  • Invasive:
    • Biopsy of lymph nodes, liver, bone marrow; exploratory laparotomy; Ultra sound/CT guided aspiration/biopsy
    • Aspiration of fluids – pleural /peritoneal/Lumbar Puncture
  • Endoscopy: Gastroscopy/colonoscopy/cystoscopy/arthroscopy/laparoscopy etc.

FUO – Empirical Therapy:

Empirical therapy should be avoided as far as possible. However, on certain demanding situations, one may have to resort to empirical treatment. Some examples are given below:

Presumptive therapy for malaria: For ALL cases of fever in an malarious area or in a visitor to malarious area. Only the first full dose of chloroquine should be used for presumptive treatment and second line drugs should be avoided. In areas with known resistance to chloroquine, pyrimethamine/sulfadoxine can be added.

Empirical antimicrobial therapy:  Severe sepsis, shock, severe neutrophilic leukocytosis, immunocompromised
patients are indications to start empirical broad spectrum antibacterial therapy (to cover Gram positive, Gram negative and anaerobes). Examples include 3rd generation cephalosporins + Aminoglycosides + Metronidazole OR
Pseudomonas specific penicillins / cephalosporins + Metronidazole.

Empirical antitubercular therapy: This can be used when all investigations are negative and there is reasonable doubt about tuberculosis, particularly in areas where tuberculosis is common. Only INH and Ethambutol should be used in this therapeutic trial (other antitubercular drugs like rifampicin and streptomycin are effective against other bacterial infections as well). A fair trial for up to 8 weeks should be given and if the disease is indeed tuberculosis, the patient will show signs of recovery and may become apyrexial.

Empirical steroids: It can be tried only when all infections are ruled out and reasonable doubt of autoimmune syndromes exists.

See Antibiotics

Fever – Rational Approach

  • It can be the simplest to most difficult and challenging
  • Patient has only one consideration – fever, but the treating doctor has to consider hundreds of causes
  • Sometimes it may be difficult to convince the patient and relatives
  • Both patient and doctor should have ample patience
  • Better to avoid empirical therapy in the initial stages to avoid confusion later
  • It is important to know the natural history of common febrile illnesses to rationalize diagnosis and treatment
  • Review and second opinion are very useful. In cases of FUO, one has to retake the history, redo the examination and go through the available reports once again, as if in a new case. Such a review may itself provide a diagnosis.

Fever – Signs of severe illness and indications for admission

  • Prostration
  • Sick & toxic
  • Breathlessness
  • Hypotension
  • Severe head ache, severe body ache
  • Severe dehydration
  • Persistent vomiting & diarrhoea
  • Hyperpyrexia
  • UTI with fever
  • Haemoptyesis
  • Anemia &jaundice
  • Convulsions, altered sensorium
  • Immune compromised patients – Extremes of age, diabetes, patients on steroids and immuno suppressants, patients with HIV

When and How to Treat Fever?

The GOOD and BAD of FEVER

GOOD

  • Elevation of body temperature increases survival.
  • Growth and virulence of bacteria are impaired at high temperature.
  • Inhibiting fever is known to increase mortality in rabbits.
  • Temperature increases phagocytic and bactericidal activity of neutrophils and the cytotoxic effects of lymphocytes.

BAD

  • With 10C elevation in temperature, O2 consumption increases by 13%
  • Fluid and caloric requirements are increased
  • Stress of increased metabolic activity can be fatal to the growing fetus and for patients with end stage organ failure
  • Increase in IL – 1 and TNF accelerates muscle catabolism, resulting in weight loss and negative nitrogen balance
  • Fever reduces mental acquity, can cause delirium and stupor and can trigger convulsions
  • Single episode of fever doubles the risk of neural tube defects in the fetus.

Indications To Treat Fever:

  • Hyperpyrexia (41.60 C or 1070 F)
  • Pregnancy
  • Children with febrile seizures
  • Impaired cardiac, pulmonary, cerebral functions.

Adverse effects of unnecessary treatment of fever:

  • Adverse effects of drugs
  • (Reye’s syndrome with aspirin; gastritis etc.)
  • All NSAIDs inhibit inflammatory response – mask the localised infection, prevent its detection, and may even aid its spread
  • NSAIDs have anti platelet and anti phagocytic activity

How To Treat Fever:

  1. By resetting the hypothalamic set point
  2. By aiding heat loss – physical cooling

Resetting hypothalamic set point: Any antipyretic or NSAID can be used as antipyretic agent. Paracetamol, Aspirin, Ibuprofen or Mefenamic acid can be used.

See NSAIDs

Paracetamol is the safest with least side effects.

Physical cooling: Uncovering the body, tepid sponging, cooling blankets can be tried. Cold sponging may cause peripheral vasoconstriction and may result in the increase of core temperature and should therefore be avoided.

See Fever and Bathing

Prochlorperazine and chlorpromazine can be used to treat severe rigors.

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