What are the possible causes of generalized myalgia and low‑grade fever in an otherwise healthy adult?

Causes of Body Aches and Low-Grade Fever

The most common causes of generalized body aches (myalgia) and low-grade fever in an otherwise healthy adult are viral infections—particularly influenza—followed by other infectious etiologies, rheumatologic conditions, and less commonly, drug reactions or early presentations of systemic inflammatory diseases.

Infectious Causes (Most Common)

Influenza and Viral Syndromes

• Influenza is the prototypical cause, presenting with fever (38-40°C), myalgia affecting mainly the back and limbs (53% of cases), malaise (80%), headache (65%), and cough (85%) 1.
• The incubation period is typically 2-4 days, with abrupt onset of symptoms and fever peaking within 24 hours 1.
• Myalgia is a hallmark feature of influenza, though arthralgia (joint pain) is NOT a typical influenza symptom—if severe polyarthralgia is present, consider alternative diagnoses such as arboviral infections (chikungunya, dengue) 2.
• Other viral infections can cause similar presentations but typically resolve within 3 months 3.

Bacterial Infections

• Focal bacterial infections are frequent causes of intermittent or low-grade fever, particularly infections in canals (urinary tract, biliary ducts, colon) or involving foreign materials 4.
• Infective endocarditis should be considered, especially if there are new cardiac findings, prolonged low-grade fever, and constitutional symptoms including arthralgias, myalgias, and fatigue 1.
• Tuberculosis remains an important consideration, particularly in high-risk populations or elderly patients 5.

Other Infectious Etiologies

• Q fever (Coxiella burnetii) presents with fever, myalgia, arthralgia, and often pneumonia—this closely matches the symptom constellation and should be considered especially with appropriate exposure history 6.
• Travel-related infections (malaria, dengue, enteric fever, rickettsial diseases) must be considered in anyone with recent travel to endemic areas 6.
• Epstein-Barr virus, though monospot may be negative in some cases, particularly in immunocompromised patients 6.

Rheumatologic and Inflammatory Causes

Adult-Onset Still's Disease (AOSD)

• AOSD is a critical consideration when fever is high-spiking (≥39°C, quotidian pattern), accompanied by arthralgia/myalgia (75-100% of cases) and systemic inflammation 6, 3.
• The classic triad includes high-spiking fever, evanescent salmon-pink rash on trunk/proximal limbs, and arthritis/arthralgia (93.5% sensitive) 3.
• Laboratory findings show marked neutrophilic leukocytosis, elevated ESR/CRP, and hyperferritinemia with low glycosylated fraction 6, 3.
• Critical pitfall: If pancytopenia develops, this signals macrophage activation syndrome (MAS), which requires urgent immunosuppressive treatment and carries significant mortality risk 6.

Acute Rheumatic Fever (ARF)

• Consider ARF if fever duration >5 days with migratory polyarthritis affecting large joints, particularly following streptococcal pharyngitis 1, 3.
• Polyarthralgia alone is a minor manifestation and highly nonspecific; it should not lead to overdiagnosis of ARF in low-risk populations 1.
• Requires evidence of preceding Group A Streptococcal infection PLUS either 2 major criteria OR 1 major + 2 minor criteria 3.

Polymyositis/Inflammatory Myopathies

• True myositis presents with proximal muscle weakness (difficulty standing, lifting arms) and elevated creatine kinase levels, distinguishing it from simple myalgia 6.

Drug-Related Fever

• Drug-related fever accounts for approximately 6% of low-grade fever cases and should be considered in the differential, particularly with recent medication changes 5.
• Critical pitfall: Do not start empiric corticosteroids before excluding infection and malignancy, as this can worsen outcomes in disseminated infections or mask leukemia 6.

Diagnostic Approach

Initial Clinical Assessment

• Document fever pattern: Quotidian high-spiking fever suggests AOSD; intermittent fever suggests focal bacterial infection 6, 3, 4.
• Characterize myalgia vs. arthralgia: True joint pain (arthralgia) versus muscle pain (myalgia) has different diagnostic implications 2.
• Assess for red flags: Weight loss and splenomegaly are significantly associated with organic causes of fever 7.
• Travel and exposure history: Essential for identifying Q fever, arboviral infections, and other geographically-restricted pathogens 6.

Laboratory Evaluation

First-line mandatory tests 6, 3:

• Complete blood count with differential (to identify leukocytosis, pancytopenia)
• ESR and CRP (elevated in inflammatory conditions)
• Blood cultures if septic process suspected
• Liver enzymes and creatine kinase

Second-line testing based on clinical suspicion 6, 3:

• Ferritin with glycosylated fraction (if AOSD suspected)
• ANA, rheumatoid factor, anti-CCP (if autoimmune disease suspected)
• Serologies for Q fever, EBV, other infections based on exposure history
• Chest radiography (for pneumonia, tuberculosis)

Advanced testing when diagnosis remains unclear 6:

• Bone marrow examination if pancytopenia present (to evaluate for hemophagocytosis, hematologic malignancy, disseminated infection)
• Echocardiography if endocarditis suspected
• Temporal artery biopsy in elderly patients (temporal arteritis is the most frequent specific diagnosis in elderly with FUO) 5

Key Clinical Pitfalls to Avoid

• Do not dismiss pancytopenia as part of a benign viral syndrome—it may signal MAS, hemophagocytic syndrome, or hematologic malignancy requiring urgent intervention 6, 8.
• Do not rely on negative monospot to exclude EBV, particularly in immunocompromised patients; use PCR instead 6.
• Do not assume lack of animal contact excludes Q fever—airborne transmission occurs 6.
• Absence of pathological signs on physical examination is significantly more frequent in habitual hyperthermia (non-organic fever) than organic causes 7.
• NSAIDs or salicylates taken before evaluation may mask the classic migratory pattern of polyarthritis in ARF, making careful history-taking essential 1.