What labs are recommended for this differential diagnosis?

Laboratory Tests for Differential Diagnosis

For patients with a broad differential diagnosis, laboratory testing should focus on high-yield tests that can identify common and serious conditions, including complete blood count (CBC) with differential, comprehensive metabolic panel, and specific tests targeting suspected conditions based on clinical presentation.

Core Laboratory Tests

First-Line Tests (For All Patients)

• Complete blood count (CBC) with differential 1

  • Evaluates for leukocytosis/leukopenia, thrombocytopenia, and anemia
  • Particularly important for detecting neutrophilia (bacterial infection) or lymphopenia (viral infections)
  • Presence of band neutrophils may indicate acute infection

• Comprehensive metabolic panel 1

  • Electrolytes (sodium, potassium, chloride, bicarbonate)
  • Renal function (BUN, creatinine)
  • Liver function tests (AST, ALT, alkaline phosphatase, bilirubin)
  • Glucose (to evaluate for diabetes or hypoglycemia)

Condition-Specific Tests

For Suspected Tick-Borne Diseases

• Serologic testing for:
  • Rocky Mountain Spotted Fever (RMSF)
  • Ehrlichiosis
  • Anaplasmosis
  • PCR testing for these conditions if available 1

For Suspected Encephalitis/Meningitis

• Lumbar puncture with: 1
  • Opening pressure
  • Cell count with differential
  • Protein and glucose
  • Gram stain and bacterial culture
  • HSV-1/2 PCR
  • VZV PCR
  • Enterovirus PCR
  • Cryptococcal antigen
  • Oligoclonal bands and IgG index
  • VDRL

For Suspected Metabolic Disorders

• Glucose tolerance test (if diabetes or pre-diabetes suspected) 1
• HbA1c (for evaluation of long-term glucose control) 1

For Suspected Polyneuropathy

• Serum B12 with metabolites (methylmalonic acid with or without homocysteine)
• Serum protein immunofixation electrophoresis (IFE) 1

For Suspected Multiple Myeloma

• FISH panel including: 1
  • TP53 deletion (17p)
  • 1p deletion
  • 1q gain/amplification
  • IGH rearrangements

For Suspected Clostridium difficile Infection

• Nucleic acid amplification tests (NAAT) for C. difficile toxin genes
• Glutamate dehydrogenase (GDH) screening with toxin A/B enzyme immunoassays 1

Decision Algorithm Based on Clinical Presentation

For Fever with Rash

1. CBC with differential
2. Comprehensive metabolic panel
3. Blood cultures
4. Serologic testing for tick-borne diseases (if relevant exposure)

For Altered Mental Status

1. CBC with differential
2. Comprehensive metabolic panel
3. Lumbar puncture with CSF analysis
4. Blood glucose (urgent)
5. Toxicology screen
6. Blood cultures

For Polyneuropathy Symptoms

1. Glucose/HbA1c
2. Serum B12 with metabolites
3. Serum protein immunofixation electrophoresis
4. Consider genetic testing if family history suggests hereditary neuropathy 1

Important Considerations

• Timing is critical: For tick-borne diseases, acute and convalescent sera should be collected 10-14 days apart 1

• Sample collection: For CSF analysis, collect at least 20cc of fluid when possible and freeze 5-10cc for additional testing if needed 1

• False negatives: Be aware that early testing for tick-borne diseases may be negative; clinical suspicion should guide empiric treatment decisions 1

• Avoid unnecessary testing: Laboratory testing should be guided by clinical presentation rather than ordered as extensive panels without clear indications 1

The laboratory evaluation should be tailored based on the patient's presentation, with consideration of epidemiological factors such as season, geographic location, and potential exposures to guide the selection of appropriate tests.