Fever

Fever often resolves spontaneously within 1–2 weeks, or the cause becomes clinically apparent without further investigation.

Normal body temperature varies between individuals, the time of day, environmental temperature, and the method of temperature measurement. At night, the temperature often decreases. In the afternoon, it is always slightly higher than in the morning and increases with physical activity.

Older individuals have lower body temperatures.

Women generally have a slightly higher temperature than men and may have approximately half a degree higher body temperature from ovulation until menstruation. The most important factor is not the temperature itself; what determines illness is how one feels overall.

In previous studies, unclear fever (fever of unknown origin, FUO) has typically been defined as documented body temperature above 38.3°C on several occasions, measured with a rectal thermometer over a period of at least three weeks. Others argue that fever should be considered as 1°C above what the individual has recorded as their normal temperature.

Most cases of unknown fever that remain undiagnosed despite extensive investigations tend to have a good prognosis and subside within a year.

How fever occurs?

When our body encounters something potentially harmful, like bacteria or viruses, a complex chain of events begins. Think of it like setting off a sophisticated alarm system in your house, but instead of sound, it produces heat.

First, our immune cells detect what we call “pyrogens.” These can come from two sources: either from outside our body (like bacterial toxins) or from inside (produced by our own immune cells). These pyrogens act as messengers, traveling through our bloodstream until they reach a special control center in our brain called the hypothalamus.

The hypothalamus works like our body’s thermostat. Normally, it keeps our body temperature around 37°C (98.6°F). However, when pyrogens arrive, they trigger the production of a substance called prostaglandin E2. This substance essentially “resets” our body’s thermostat to a higher temperature.

These pyrogens can be exogenous (from outside the body, such as bacterial toxins) or endogenous (produced by the body’s own cells, particularly cytokines like interleukin-1 and tumor necrosis factor). The resulting fever serves several immunological advantages: it enhances immune cell function, creates an unfavorable environment for many pathogens, and accelerates tissue repair processes.

Once the thermostat is reset, our body starts several processes to increase its temperature:

• Muscles begin to contract rapidly, creating heat (this is why we shiver)
• Our metabolism speeds up, generating more heat
• We might feel cold and seek warmth (like grabbing a blanket)

As these processes continue, our body temperature rises until it reaches the new, higher setpoint. This elevated temperature actually helps our body fight infection in several ways. It speeds up our immune system’s response, makes it harder for many bacteria and viruses to multiply, and accelerates our body’s repair processes.

When the infection or threat begins to clear, our body produces anti-inflammatory substances that gradually reset the hypothalamus back to its normal temperature setting. This is when we start feeling hot and sweating as our body works to cool back down to its usual temperature.

Classification of fever patterns

Medical professionals recognize several distinct fever patterns, each potentially indicating different underlying conditions:

• Continuous fever maintains an elevated temperature with minimal fluctuation (less than 1°C variation), often seen in lobar pneumonia or typhoid.
• Intermittent fever shows normal temperature periods alternating with fever spikes, common in malaria and sepsis.
• Remittent fever fluctuates daily but never returns to normal, characteristic of various viral infections.
• Hectic fever presents large daily fluctuations, often associated with severe infections or malignancies.

Clinical assessment

When evaluating fever, medical practitioners consider multiple factors beyond just temperature measurement. The pattern and timing of temperature elevation, associated symptoms, recent travel history, medication use, and underlying medical conditions all contribute to the diagnostic process. The presence of accompanying signs like rigors (severe shaking), sweating, or specific pain locations helps narrow down potential causes.

Temperature measurement methods vary in accuracy and appropriateness for different situations. While rectal temperature provides the most accurate core reading, oral and tympanic measurements offer practical alternatives in most clinical settings.

Medical professionals must look for following conditions, symptoms and status:

• Infections
• Non-infectious inflammations, such as autoimmune diseases
• Malignancies
• Medications
• Endocrine disorders
• Thromboembolic disease
• Factitious fever

Note: A thorough history is particularly important in cases of unclear fever!

• Travel history?
• Geographic upbringing?
• Family history?
• Occupation?
• Substance abuse?
• Infants in the household?
• Illnesses in the surrounding environment?
• Past illnesses, especially heart disease or autoimmune disease?
• Foreign body materials?
• Medications?
• Joint pain?
• Tachycardia?
• Weight loss?
• Night sweats?
• Focal symptoms? Runny nose? Cough? UTI symptoms? Diarrhea?

Status

• Does the patient actually have a fever?
• Oral cavity and throat normal? Pressure-sensitive teeth?
• Tenderness over the sinuses?
• Tenderness over the temporal artery?
• Heart murmur? Tachycardia?
• Normal lung auscultation?
• Lymph nodes? Resistance or tenderness in the abdomen?
• Tenderness over the thyroid?
• Tenderness on percussion over the kidney areas?
• Prostate tenderness? Normal rectal palpation?
• Skin changes? Redness in the nail beds?
• Joint swelling?
• Bone tenderness?
• Neurologically normal? Tremor?

Diagnostic approach

The diagnostic workup for fever follows a systematic approach. Initial evaluation includes detailed history taking and physical examination. Laboratory investigations typically begin with complete blood count, comprehensive metabolic panel, blood cultures, and urinalysis. Additional tests such as chest X-rays, inflammatory markers (ESR, CRP), or specific disease markers may be ordered based on clinical presentation.

Basic Investigation:

• Blood cultures
• Urine cultures
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
• White blood cell count (WBC)
• Differential white cell count
• Platelet count (PLT)
• Aspartate transaminase (AST/ASAT)
• Alanine transaminase (ALT/ALAT)
• Alkaline phosphatase (ALP)
• Bilirubin
• Sodium
• Potassium
• Creatinine
• Calcium
• Serum protein electrophoresis (SPEP)
• Serum lactate dehydrogenase (LDH/S-LD)
• Thyroid-stimulating hormone (TSH) / Free T4
• Urine dipstick test
• Chest X-ray

Extended or supplementary investigations that may be relevant depending on medical history, symptoms, findings on examination, and results of the above laboratory tests:

• CMV serology
• EBV serology
• Monospot test
• Thyroid function tests
• Temporal artery biopsy
• ANA (antinuclear antibody)
• Rheumatoid factor
• ANCA (antineutrophil cytoplasmic antibodies)
• CT scan of the abdomen
• Ultrasound of the liver and gallbladder
• Transesophageal echocardiogram
• PPD (tuberculin skin test)
• Gynecological examination
• Liver biopsy
• Bone marrow examination
• HIV antibodies
• Wasserman test (WR)
• Fecal occult blood (F-Hb)
• Serum uric acid (S-Urate)
• Angiotensin-converting enzyme (ACE)
• Malaria smear
• Mycobacterium cultures
• TNF receptor 1
• PET scan

Complications and special considerations

Extreme elevation in body temperature (hyperpyrexia, typically above 41.5°C or 106.7°F) can lead to serious complications including delirium, seizures, and organ damage. Certain patient populations require special attention: young children may experience febrile seizures, while elderly patients might not mount significant fever despite serious infection.

Neuroleptic malignant syndrome, malignant hyperthermia, and heat-related illnesses represent important differential diagnoses where elevated temperature occurs through mechanisms distinct from the typical fever pathway.

Infections

1. Infective Endocarditis
   • Listen for heart murmurs! Blood cultures are crucial. CRP and ESR can often be close to normal levels.
2. Deep Abscesses (e.g., Liver and Lung Abscesses)
   • Common in patients with poor general health or alcohol-related issues. Can sometimes mimic malignancy with gradual weight loss and low-grade fever.
3. Osteomyelitis and Septic Arthritis
   • Often present with focal symptoms from the affected area.
4. Cytomegalovirus (CMV)
   • Often seen in previously seronegative new fathers or grandparents infected via diaper changes from asymptomatic viral shedding in a child’s urine. Elevated transaminases. Positive IgM CMV.
5. Mononucleosis (Glandular Fever)
   • Can occur in a septic form without visible lymph node enlargement or throat symptoms. Diagnosed via Monospot, blood work, and potentially serology.
6. Tuberculosis (TB)
   • Primarily seen in immigrants (especially from Africa and Asia) and older Swedish individuals. Cultures from symptomatic sites and histopathological examination of lymph nodes confirm the diagnosis. Chest X-ray recommended.

Non-infectious auto-inflammatory and autoimmune diseases

1. Temporal Arteritis, Giant Cell Arteritis (GCA), and Polymyalgia Rheumatica (PMR)
   • Pain and stiffness in large muscle groups, especially in the morning. Elevated ESR, CRP, ALP, and platelet count. Temporal artery biopsy can confirm the diagnosis in temporal arteritis. Rapid and dramatic improvement is expected after initiating corticosteroids per treatment guidelines.
2. Systemic Lupus Erythematosus (SLE)
   • Often involves multiple organs, sometimes with butterfly-shaped rash.
3. Granulomatosis with Polyangiitis (Wegener’s Granulomatosis)
   • Often presents with lung symptoms or sinus involvement.
4. Adult-Onset Still’s Disease
   • Skin changes, often conjunctivitis, neutrophilia.
5. Sweet’s Syndrome (Febrile Neutrophilic Dermatosis)
   • Tender skin lesions.
6. Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
   • Very rare. Often presents with myalgia, peritonitis, and intermittent fever.
7. Periodic Fever with Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA)
   • A cause of fever in children.
8. Familial Mediterranean Fever
   • Often presents with myalgia, peritonitis, and intermittent fever.
9. Sarcoidosis
   • Often involves extrapulmonary manifestations in cases of unexplained fever.
10. Gout

• Commonly involves an inflamed big toe joint but can also affect other joints and organs. Elevated serum uric acid (S-Urate) is typically observed.

Malignancies

Malignant fever almost always has an inflammatory component (e.g., elevated ESR, haptoglobin, and platelet count), and S-LD is usually elevated as a sign of cell destruction.

• Hodgkin’s lymphoma
• Non-Hodgkin’s lymphoma
• Leukemia
• Renal cell carcinoma (hypernephroma)
• Multiple myeloma (myelomatosis)
• Ovarian cancer
• Lung cancer

Medications

Many medications can cause fever. The most common are:

• Angiotensin II receptor blockers
• ACE inhibitors
• Phenytoin
• Lamotrigine
• Rifampicin
• Hydralazine (Apresoline)
• Nitrofurantoin (Furadantin)
• Prolonged treatment with beta-lactam antibiotics
• Chemotherapy drugs (cytostatics)
• Interferon
• Antipsychotics (neuroleptics)

Endocrine diseases

• Hyperthyroidism
  Often associated with tachycardia, weight loss, and diarrhea. In subacute thyroiditis (de Quervain), there may be pain during swallowing and tenderness on palpation of the thyroid gland.

Thromboembolic disease

• Chronic Pulmonary Embolism
  Often presents with dyspnea.

Factitious fever

Self-induced fever is rare. Young, single women in healthcare-related professions are overrepresented. Blood cultures or cultures from abscesses may sometimes test positive for unusual mixed flora. Fever in children can sometimes be caused by parental behavior.

Treatment

Medical treatment

When doctors treat fever, they focus on two aspects: addressing the underlying cause and managing the symptoms. The choice of treatment depends on what’s causing the fever and how severe it is.

For bacterial infections, doctors prescribe appropriate antibiotics based on the likely causative organism or culture results. Viral infections generally don’t require specific medication since viruses typically resolve on their own, but certain cases might need antiviral medications.

The main medications used to reduce fever (antipyretics) include:

• Acetaminophen (Tylenol) works by affecting the temperature control center in the brain. It’s generally considered safe and effective, but doctors carefully monitor the daily dose to prevent liver damage.
• NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) like ibuprofen or naproxen not only reduce fever but also decrease inflammation. They work by blocking prostaglandin production, which helps reset the body’s temperature threshold. However, these medications require careful use as they can affect kidney function and stomach lining.

In hospital settings, severe cases might require additional interventions like intravenous fluids to prevent dehydration, cooling blankets for dangerously high temperatures, or specific treatments for underlying conditions.

Home treatment

Home care plays a crucial role in managing fever and supporting recovery. Here’s how you can effectively manage fever at home:

1. Hydration is absolutely essential. Fever increases fluid loss through sweating and faster breathing, so drinking plenty of water, clear broths, or electrolyte solutions helps prevent dehydration. Room temperature fluids often work better than very cold ones.
2. Keep cool. Keeping room temperature comfortable (around 70-74°F/21-23°C) and wearing light clothing allows proper heat release. A lukewarm bath or compress might help, but never use cold water as it can cause shivering and actually raise body temperature.
3. Take a rest. Your body needs extra energy to fight infection. Limiting physical activity and getting adequate sleep supports the immune system’s work.
4. Eat well. Proper nutrition, even if appetite is reduced, helps maintain strength. Light, easily digestible foods are usually best. If eating is difficult, liquid nutrition like broths or smoothies can help maintain energy levels.

Monitoring is important: check temperature regularly, watch for signs of dehydration (dark urine, decreased urination, dry mouth), and note any new or worsening symptoms.

When to seek medical care?

Understanding when to move beyond home treatment is crucial. Contact healthcare providers if:

• Temperature exceeds 103°F (39.4°C) in adults
• Fever lasts more than three days
• Severe headache or neck stiffness develops
• Confusion or excessive sleepiness occurs
• Difficulty breathing arises
• Signs of dehydration appear despite fluid intake
• New or severe symptoms develop

Different age groups require different approaches. Infants and elderly individuals need more careful monitoring and often lower thresholds for seeking medical care. People with certain medical conditions or taking specific medications might need modified treatment approaches.