Drug-Induced Pyrexia - Causes, Diagnosis, and Treatment

What Is Pyrexia?

Pyrexia, also known as fever, is called raised body temperature; elevated body temperature up to 100.4 Fahrenheit can be diagnosed as fever. Body temperature can be measured with the help of a thermometer device, which indicates the alteration in temperature by a change in the levels of mercury. Pyrexia is considered an immune response of the body to foreign bacteria or other agents considered potential threats to the body. 98.6 ᵒF is considered normal body temperature, but this temperature varies according to the recording site. The following are the most common sites where the temperature is recorded and the normal temperature of the respective sites:

• Rectal Temperature - 37.5 – 38.3 °C.

• Oral Temperature - 37.7 °C.

• Axillary or Otic Temperature - 37.2 °C.

The rectal site is considered to record the most accurate temperature among the sites mentioned above, as it records the core temperature.

What Are the Types of Fever?

Based on the Pattern of Occurrence, Fever Is Categorized As:

• Continuous Fever: The constant temperature for 24 hours without any fluctuation of more than one degree

• Intermittent Fever. The temperature elevation was noted for a short duration; the temperature fluctuated between very high and normal.

• Remittent Fever. This type of fever is similar to continuous fever with the difference that the temperature fluctuation is more than one degree within 24 hours. The temperature never returns to normal till the person is completely recovered.

• Hectic Fever. Fever with high fluctuations, the temperature difference in this type of fever is always more than 1.4 degree Celsius between the highest and lowest temperature.

• Relapsing Fever. This is a type of intermittent fever where the temperature is again elevated after being normal for a few days or weeks, this type of fever is commonly seen in cases of malaria or infections.

What Are the Signs and Symptoms of Pyrexia?

Fever, along with elevated body temperature, is accompanied by sickness behaviors like:

• Lethargy.

• Depression.

• Anorexia.

• Sleepiness.

• Hyperalgesia.

• Inability to concentrate.

• Weakness.

• Dehydration.

• Headache.

• Bodyache.

What Are the Causes of Pyrexia?

Pyrexia can result from various foreign bacteria or substances considered foreign and a threat to the body. In such situations, the body elevates its temperature to prevent the growth of these invaders or as a defense mechanism for the body to fight against foreign bodies. Various causes of fever can be segregated as infectious and non-infectious causes, which include:

Infectious Causes:

• Lower respiratory tract infections like bronchitis.

• A bacterial lung infection is called tuberculosis.

• Complicated urinary tract infections.

• Bone infections like osteomyelitis.

• A bacterial infection of the cardiac tissue is called endocarditis.

• Viral infections like HIV (Human-Immunodeficiency syndrome) and Cytomegalovirus.

Non-infectious Causes:

• Neurological conditions like brain fever or hemorrhages.

• Malignant conditions like leukaemia and renal cell carcinoma.

• Reactions to drugs.

• Bowel or bladder-related problems.

• Reactions to blood transfusion.

What Is Drug-Induced Pyrexia?

Drug-induced fever is a reaction of the body to new medications in the form of elevated body temperature; this is seen after a few days or weeks of starting new medications. Medications commonly known to cause fever include antimicrobials, anticonvulsants, antibiotics, sympathomimetics, and sulfonamides. The risk of drug-induced fever increases with the number of medications taken, particularly in older adults and in those with active Human Immunodeficiency Virus infection.

Patients with cystic fibrosis have a high incidence of drug-induced fever, most commonly from parenteral beta-lactams, piperacillin, and imipenem or cilastatin. This type of fever is often misdiagnosed, as very few cases have been reported. Therefore every physician needs to consider it as a possible cause of fever in every case with a history of being on medications. It is difficult to diagnose as the diagnosis is made as an exclusion or by eliminating all other possible reasons. The fever pattern can be continuous, remittent, or intermittent, the most common being the hectic fever. The temperature range varies from 38.8 °C to 40 °C, with the highest reported 42.8 °C.

Which Drugs Have the Potential to Cause Pyrexia?

Following are the drugs that have been reported to induce fever in some cases:

• Hypersensitivity – Anticonvulsants, penicillin, minocycline, sulfonamide, allopurinol

• Altered Thermoregulatory Mechanisms – Thyroxine, anticholinergics, amphetamines, cocaine

• Directly Related to Administration – Paraldehyde, pentazocine, amphotericin B, bleomycin

• Direct Extension of Pharmacologic Action – Chemotherapy.

• Idiosyncratic – Succinylcholine, haloperidol, serotonergic.

• Antibiotics - Beta-lactams and Sulfonamides.

• Antineoplastics - The onset of fever is quickest when the person is on antineoplastics compared to other medications. A person on antineoplastics can have a temperature elevated within half a day from the onset of the medications.

• Anticonvulsants - Phenytoin and Carbamazepine.

• Antiarrhythmics - Quinidine and Procainamide.

• Cardiac medications - Methyldopa induces fever at a very slow rate. Fever in such cases is presented around the 16th day from the start of the medications.

• Antimicrobials - Onset of fever is expected around six days after starting the doses of medications.

How Long Does Drug-Induced Pyrexia Last?

Drug pyrexia can last until the medications are continued. Therefore the causative agents must be immediately discontinued. After discontinuation of medications, a patient might feel relief and be fine after 3-4 days. But the patient must not face any medical emergency or complications after discontinuation of medications; it can be prevented by slowing the causative drugs.

How Is Drug-Induced Pyrexia Diagnosed?

The diagnosis is confirmed when:

• The resolution of the fever occurs within 48 hours after the discontinuation of medications.

• The fever relapses within a few hours of restarting the same medication again.

• Fever occurs within 7-10 days after starting the medication.

• The patient presents clinically healthy and unaware of pyrexia.

• The diagnostic key in cases with drug-induced pyrexia is relative bradycardia, a condition where the heart rate is increased but not more than 110 beats per minute, which is less than what is observed in other cases of pyrexia with similar temperature elevation.

• Cutaneous manifestation of hypersensitivity makes it easier to find the possible cause of fever.

• Blood investigations might complicate the diagnosis as the findings in cases with drug-induced pyrexia are similar to infectious fever.

In cases with recurrence after a month or years, the fever appears within a few hours of drug administration.

How Is Drug-Induced Pyrexia Treated?

The treatment in cases with drug-induced pyrexia depends on treating the fever, but care is also taken to prevent any medical complication or emergency by discontinuing the medications. The first step in treatment includes discontinuation of medications, and a patient is advised to rest and have adequate fluid intake. Inform your doctor if any symptoms like headache, stiff neck, shortness of breath, or any discomfort are present; Tylenol or Ibuprofen can be taken with the advice of your physician. Regular or sponge bath with lukewarm water is advised. A healthy balanced diet helps in faster recovery.

Conclusion:

Drug-induced pyrexia is fever due to certain medications. It appears a few days after the medications are started, and the body returns to normal temperature after discontinuation; this helps confirm the diagnosis of the condition. The type of fever is most commonly hectic but, depending on the causative drug, can also be of any other nature. In most cases, the patient is asymptomatic and unaware of pyrexia; a diagnosis is made when the patient presents with bradycardia, which is different from that observed in cases with a fever of other origins. Treatment includes discontinuing medications with adequate rest and fluid intake to prevent dehydration.