What could be causing sudden onset sweats, extreme fatigue, and a metallic taste in the mouth?

Sudden Onset Sweats, Extreme Fatigue, and Metallic Taste: Diagnostic Approach

You must immediately evaluate this patient for COVID-19 infection, tuberculosis, and hematologic malignancy, as this symptom triad—particularly the combination of metallic taste with constitutional symptoms—represents a potentially serious presentation requiring urgent workup. 1, 2, 3

Immediate Priority: COVID-19 Testing

• Perform COVID-19 testing immediately, as sudden-onset taste alterations (including metallic taste) combined with fatigue can be the sole presenting symptoms of SARS-CoV-2 infection. 1, 4
• In COVID-19 patients, anosmia and dysgeusia (altered taste) presented as early symptoms in 11.8-26.6% of cases, with one case series documenting an 85-year-old male who experienced sudden onset of anosmia and fatigue prior to admission and died on day 6. 1
• The metallic taste component is particularly concerning as it may represent dysgeusia associated with viral infection, which occurred in 59.4% of COVID-positive patients in one large survey. 1

Essential Laboratory Workup

Order the following tests immediately to rule out life-threatening conditions:

• Complete blood count with differential to evaluate for cytopenias, leukocytosis, or abnormal cells suggesting hematologic malignancy (sensitivity 70-80% for lymphoma). 2, 3
• Inflammatory markers (ESR and CRP) to assess for systemic inflammation from infection or malignancy. 2, 3
• Comprehensive metabolic panel including liver enzymes, alkaline phosphatase, LDH, and albumin to evaluate for organ dysfunction or malignancy. 2, 3
• Thyroid-stimulating hormone (TSH) to rule out hyperthyroidism, which can present with sweats and fatigue. 2
• HIV testing and tuberculosis screening (IGRA or TST) given the constitutional symptoms of sweats and fatigue, particularly if any risk factors exist. 2, 3

Critical History Elements to Obtain

Document the following specific details:

• Presence of B symptoms: drenching night sweats (requiring clothing/sheet changes), unexplained weight loss >10% over 6 months, and fever >37.5°C. 2, 3
• Timing and progression: whether symptoms began simultaneously or sequentially, and the exact duration of each symptom. 1
• Associated symptoms: cough, dyspnea, lymphadenopathy, pruritus, alcohol-induced pain, or any palpable masses. 2
• Medication history: numerous medications can cause metallic taste, including chemotherapy agents, targeted therapies, and even botulinum toxin. 1, 5, 6
• Recent dental procedures: inferior alveolar nerve blocks can cause taste disturbances through chorda tympani nerve injury. 7

Imaging Studies Based on Initial Findings

• Chest X-ray as initial screening for pulmonary pathology, tuberculosis, or mediastinal lymphadenopathy. 2, 3
• Contrast-enhanced CT of neck, chest, and abdomen if lymphadenopathy, organomegaly, or masses are suspected based on examination or laboratory abnormalities. 2, 3
• PET/CT scan if lymphoma is strongly suspected (sensitivity 90-95%), as it can guide biopsy and detect bone marrow involvement. 2, 3

Tuberculosis-Specific Considerations

Do not dismiss TB even without classic risk factors, as it can present atypically with night sweats, fatigue, and weight loss. 3

• If TST or IGRA is positive, rule out active TB with clinical history, physical examination, chest radiograph, and respiratory sampling. 2, 3
• Submit three sputum specimens for acid-fast bacilli smear, mycobacterial culture, and nucleic acid amplification testing if active TB is suspected. 2

Hematologic Malignancy Evaluation

If lymphoma is suspected based on lymphadenopathy or abnormal blood counts:

• Perform excisional or incisional lymph node biopsy (not fine-needle aspiration, which has only 50-60% positive predictive value) with fresh tissue sent for pathology, flow cytometry, and cytogenetics. 2, 3
• Consider bone marrow biopsy with fibrosis grading and molecular testing if blood counts are abnormal (sensitivity 80-90% for hematologic malignancy). 2, 3
• Assess for oncologic emergencies including superior vena cava syndrome, respiratory compromise, or spinal cord compression. 2

Metallic Taste-Specific Considerations

• While metallic taste can result from iron salt solutions creating retronasal smell through lipid oxidation reactions in the mouth 8, in the context of acute systemic symptoms, it more likely represents dysgeusia from viral infection or systemic illness.
• Metallic taste is reported by 34-46% of cancer patients receiving systemic therapy, but this typically occurs in the context of known malignancy and treatment. 6
• Neurological causes of taste disorders should be considered if other cranial nerve abnormalities are present, including Bell's palsy, skull base lesions, or cerebrovascular events. 9

Common Diagnostic Pitfalls to Avoid

• Do not rely on patient self-assessment of symptom severity; objective testing reveals much higher rates of dysfunction than patients report. 4
• Do not overlook HIV testing even in patients without obvious risk factors, as HIV significantly increases TB risk and changes management. 3
• Do not use fine-needle aspiration alone for lymph node evaluation when lymphoma is suspected; excisional biopsy is required for definitive diagnosis. 3
• Do not dismiss the metallic taste as benign without ruling out serious systemic illness, particularly in the context of acute constitutional symptoms. 1, 6

Follow-Up Protocol

• If COVID-19 is confirmed, monitor for progression and provide supportive care; recovery of taste typically occurs within 7.2 days (mean) but can persist longer. 1
• If initial workup is negative but symptoms persist, re-evaluate at 1 month and consider referral to appropriate specialists (infectious disease, hematology/oncology, or otolaryngology) based on predominant findings. 4, 2