From Fever to Fatigue: A Guide to Systemic Symptomatology
Arthralgia
Arthralgia refers to joint pain, a common symptom in various infectious, autoimmune, and inflammatory conditions. It can present alone or alongside systemic symptoms depending on the underlying cause.
Fatigue and Weakness
Fatigue, weakness, lassitude, prostration, and lethargy describe a generalized sense of tiredness or exhaustion. These symptoms are non-neurological and often associated with infections, chronic illnesses, or systemic inflammation. For neuromuscular involvement, see also "muscular weakness."
Fever
Fever is a hallmark symptom in many acute and chronic conditions. In hospitalized patients, causes of fever less than 102°F include:
- Acute cholecystitis
- Myocardial infarction (MI)
- Phlebitis
- Pulmonary embolism (PE)
- Viral hepatitis
- Wound infections
- Cystitis
In contrast, fevers greater than 102°F may suggest more severe infections such as:
- Cholangitis
- Pericarditis
- Suppurative thrombophlebitis
- Septic pulmonary emboli
- Non-viral hepatitis
- Deep abscesses
- Bowel infarction
- Pyelonephritis
Fever may also accompany rheumatologic diseases (e.g., systemic lupus erythematosus, gout), sarcoidosis, hyperthyroidism, and various cancers. For more detailed reference, see Table 129-1 (Causes of Acute Fever) and Table 129-2 (Causes of FUO) in standard infectious disease texts.
Biphasic or Relapsing Fever
A biphasic fever occurs when the fever resolves temporarily and then returns. Diseases associated with this pattern include:
- Colorado tick fever
- Dengue fever
- Leptospirosis
- Brucellosis
- Lymphocytic choriomeningitis
- Yellow fever
- Poliomyelitis
- Smallpox
- Rat-bite fever (Spirillum minus)
- Chikungunya fever
- Rift Valley fever
- Ebola and Marburg viruses
- Lassa fever
- Echovirus 9
Remittent or intermittent fevers may be found in:
- Upper respiratory viral infections
- Malaria
- Acute rheumatic fever
- Legionellosis
- Mycoplasma infections
- Tuberculosis
- Infective endocarditis
- Visceral leishmaniasis
- Adult Still’s disease
- Intra-abdominal abscesses
- Kawasaki disease
- Peritonitis
- Gram-negative sepsis
- Toxic shock syndrome
The differential diagnosis for relapsing or biphasic fever should include Bartonella, echoviruses, and organisms causing chronic meningococcemia, among others.
Myalgia
Myalgia refers to muscle aches or pains, commonly seen in viral infections (like influenza or dengue), inflammatory syndromes, and autoimmune diseases. It often accompanies systemic symptoms such as fever and fatigue.
Recognizing Gastrointestinal and Upper Respiratory Symptoms in Infectious Diseases
Relative Bradycardia
Relative bradycardia refers to an unexpectedly slow heart rate relative to the degree of fever. Typically, the pulse increases by about 10 beats per minute for every 1°F rise in temperature. When this expected increase is absent, it is termed temperature–pulse dissociation. This phenomenon has been observed in illnesses such as typhoid fever, leptospirosis, rickettsiosis, dengue, legionellosis, and babesiosis, although the exact mechanisms remain unclear.
ENT and Oral Symptoms
Dysphagia
Dysphagia is defined as difficulty swallowing. This may result from local causes such as injury to the mouth, throat, or esophagus, or may originate from neurological disorders affecting the central nervous system.
Epistaxis
Epistaxis, or nosebleed, is most frequently due to local trauma, which may include nose blowing, picking, or dryness of the nasal mucosa. While usually benign, recurrent or severe cases warrant further investigation.
Nasal Ulcers
Nasal ulcers are sores in the nasal cavity, which may be caused by local infection, trauma, or systemic diseases such as autoimmune disorders.
Pharyngitis
Pharyngitis refers to a sore throat, often caused by viral or bacterial infections. It is a common symptom in upper respiratory tract infections.
Rhinitis
Rhinitis manifests as runny nose or rhinorrhea. The common cold is most often caused by rhinoviruses (30–50%), followed by other viruses such as coronaviruses, influenza, parainfluenza, RSV, and enteroviruses. Despite extensive studies, the cause remains unidentified in about half of all cases.
Stomatitis
Stomatitis describes inflammation or sores in the mouth. Up to 30% of adults experience recurrent aphthous ulcers, often with an unknown etiology. Viral causes include Epstein-Barr virus, influenza, CMV, and HIV. Additionally, acute necrotizing ulcerative gingivitis, a severe form of stomatitis, is caused by fusospirochetal bacteria.
Gastrointestinal Signs and Symptoms
Abdominal Mass
An abdominal mass may indicate an enlarged organ, tumor, cyst, or intra-abdominal abscess. The cause depends on the location and clinical context.
Abdominal Pain
Abdominal pain is a nonspecific but common symptom in gastrointestinal, infectious, and systemic diseases.
Blood in Stool
Blood in stool may present as hematochezia (bright red blood) or melena (black, tarry stool). These findings suggest gastrointestinal bleeding and can be associated with infections, ulcers, or malignancies.
Constipation
Constipation is the infrequent or difficult passage of stool, often influenced by diet, medication, or underlying pathology.
Diarrhea
Diarrhea is the frequent passage of loose or watery stools, which may be non-inflammatory or inflammatory in origin.
Fecal Leukocytes
The presence of pus or white blood cells in stool indicates inflammatory diarrhea. Common causes include Campylobacter jejuni, Clostridioides difficile, Salmonella, and Shigella. Detection is more reliable with fecal lactoferrin than a Gram stain. Elevated lactoferrin levels help determine if C. difficile toxin testing is warranted, even if fecal leukocytes are absent due to destruction by the pathogen.
Hematemesis
Hematemesis is the vomiting of blood, usually originating from bleeding in the upper gastrointestinal tract. It may appear red or resemble coffee grounds, depending on the duration of gastric exposure.
Hepatomegaly
Hepatomegaly refers to enlargement of the liver. It is seen in a wide range of infectious diseases such as amebic liver abscess, brucellosis, malaria, histoplasmosis, viral hepatitis, tuberculosis, typhoid fever, visceral leishmaniasis, and more. In acute viral hepatitis, hepatomegaly is reported in up to 85% of cases.