What are the causes of night fevers?

Causes of Night Fevers

Night fevers can result from infectious diseases (most commonly tuberculosis, endocarditis, and abscesses), non-infectious inflammatory conditions (including drug reactions, malignancies, and autoimmune diseases), or specific syndromes like post-Q fever fatigue syndrome that characteristically present with night sweats.

Infectious Causes

Tuberculosis and Chronic Infections

• Tuberculosis is a classic cause of night fevers and should be investigated in patients with upper zone infiltrates on chest X-ray, particularly in travelers from endemic areas 1
• Chronic Q fever can manifest with night sweats as part of post-Q fever fatigue syndrome, occurring in up to 20% of patients after acute infection 1
• Endocarditis presents with fever patterns that may be more prominent at night, and is the most common form of chronic Q fever which is generally fatal if untreated 1
• Brucellosis, chronic meningococcemia, and rat-bite fever can cause intermittent fevers including nocturnal patterns 2

Localized Bacterial Infections

• Focal bacterial infections in canals (urinary ducts, biliary ducts, colon) frequently cause intermittent fever patterns 2
• Abscesses and infections of foreign materials commonly present with intermittent fevers 2
• Osteomyelitis, particularly in children with chronic Q fever, can cause recurrent fever episodes 1

Tropical and Travel-Related Infections

• Malaria should be considered in all patients who visited tropical countries within 1 year, as it can cause characteristic fever patterns 3
• Rickettsial infections (African tick bite fever, Mediterranean spotted fever) cause fever with night sweats in travelers from endemic areas 1
• Visceral leishmaniasis can cause double quotidian fever patterns 4

Non-Infectious Causes

Drug-Induced Fever

• Beta-lactam antibiotics are the most common medication cause, typically occurring after a mean of 21 days (median 8 days) of administration 5
• Drug fever persists as long as the medication is continued and resolves within 1-3 days after discontinuation 5
• Drug withdrawal from alcohol, opiates, barbiturates, or benzodiazepines causes fever with tachycardia, diaphoresis, and hyperreflexia 1, 5
• Antipsychotic medications can cause neuroleptic malignant syndrome with fever and muscle rigidity 1

Rheumatologic and Autoimmune Diseases

• Juvenile rheumatoid arthritis (JRA) and adult Still's disease can present with double quotidian fever patterns and night sweats 4
• In 30% of fever of unknown origin cases, the cause is eventually found to be a rheumatologic disease 6
• Autoinflammatory diseases frequently present with repetitive fever attacks that may be nocturnal 7, 8

Malignancies

• Lymphomas and leukemias commonly cause night fevers and sweats 4
• Neoplastic etiologies are a preponderant cause of fever of unknown origin, particularly in elderly patients 4

Other Non-Infectious Causes

• Acute myocardial infarction and Dressler syndrome 5
• Venous thrombosis and pulmonary infarction 5
• Thyroid storm and adrenal insufficiency 5
• Gout and other inflammatory conditions 5

Diagnostic Approach

Initial Evaluation

• Obtain detailed history including medication use (mean lag time 21 days for drug fever), travel history, and pattern of fever episodes 5, 3
• Perform comprehensive physical examination focusing on skin lesions (eschars in rickettsial disease), lymphadenopathy, hepatosplenomegaly, and muscle rigidity 1, 3
• Order blood cultures (at least two sets during fever), complete blood count, liver function tests, and urinalysis 3, 9

Advanced Testing When Initial Workup is Unrevealing

• Serum procalcitonin levels and endotoxin activity assay can discriminate infection from non-infectious causes 1, 3
• Chest radiography or high-resolution CT to evaluate for tuberculosis, bronchiectasis, or occult infection 9
• Abdominal ultrasound or CT for intra-abdominal abscess or malignancy 9
• Echocardiogram if endocarditis is suspected 9
• FDG-PET/CT in absence of diagnostic clues 6

Critical Management Principles

When to Treat Empirically

• When clinical evaluation suggests infection as the cause, administer empirical antimicrobial therapy as soon as possible after cultures are obtained, especially if the patient is seriously ill 1, 3
• Delay of effective antimicrobial therapy increases mortality from infection and sepsis 1

Drug Fever Management

• Immediately discontinue the suspected medication—this is the primary management 5
• Fever typically resolves within 1-3 days after drug discontinuation 5
• Never rechallenge patients who experienced anaphylaxis or toxic epidermal necrolysis 5

Important Pitfalls to Avoid

• Do not delay antibiotics in potentially septic patients; when uncertain, treat empirically for infection first as mortality increases with delayed treatment 5, 3
• Consider drug fever when fever persists despite appropriate antibiotic therapy—the temporal relationship averages 21 days from drug initiation 5
• Do not overlook tuberculosis in patients with night fevers and respiratory symptoms, particularly with upper zone infiltrates 1
• Remember that post-Q fever fatigue syndrome causes night sweats lasting beyond one year and requires exclusion of chronic Q fever with organ involvement 1