What are the steps involved in a diagnostic workup?

Diagnostic Workup: A Systematic Approach

The diagnostic workup should follow a structured, algorithmic approach that includes thorough history, targeted physical examination, appropriate laboratory testing, imaging studies, and specialized procedures based on the suspected condition to ensure accurate diagnosis and guide effective treatment.

Initial Assessment

• Begin with a comprehensive medical history including a three-generation family history with pedigree analysis to identify hereditary conditions and risk factors 1
• Perform a thorough physical examination focusing on organ systems relevant to presenting symptoms 1
• Document chief complaints, symptom duration, aggravating/alleviating factors, and associated symptoms 1
• Review any available patient photo documentation or imaging from previous evaluations 1

Basic Laboratory Studies

• Complete blood count (CBC) with differential and platelet counts to assess for cytopenias, infections, or malignancies 1, 2
• Examination of peripheral blood smear to confirm abnormalities and identify morphological changes 1, 2
• Basic chemistry panel including blood urea nitrogen, serum creatinine, electrolytes, liver function tests, calcium, albumin, and lactate dehydrogenase 1, 2
• Inflammatory markers such as C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) 1
• Urinalysis with urine protein electrophoresis when indicated 1, 3

Disease-Specific Testing

• For suspected hematologic disorders:

  • Bone marrow aspiration and biopsy when unexplained cytopenias are present 2
  • Flow cytometry of peripheral blood and/or bone marrow to identify leukemia or lymphoma 2
  • Cytogenetic analysis and molecular studies to detect genetic abnormalities 2

• For suspected infectious diseases:

  • Microbiological cultures of relevant specimens 1
  • Serological testing for specific pathogens based on clinical suspicion 1
  • Molecular diagnostic tests such as PCR for rapid pathogen identification 1

• For suspected genetic or developmental disorders:

  • Chromosomal microarray (CMA) as a first-tier test for unexplained developmental disorders 1
  • Exome or genome sequencing for undiagnosed conditions with suspected genetic etiology 1
  • Targeted genetic testing when a specific syndrome is suspected 1

Imaging Studies

• Choose appropriate imaging modalities based on suspected pathology:
  • CT scans of relevant body regions to evaluate for structural abnormalities or masses 1
  • MRI for detailed soft tissue evaluation, particularly for neurological conditions 1
  • PET/CT for suspected malignancies or when whole-body assessment is needed 1
  • Ultrasound for initial evaluation of specific organs or guided procedures 1

Specialized Procedures

• Endoscopic procedures (e.g., esophagogastroduodenoscopy, colonoscopy) when gastrointestinal pathology is suspected 1
• Tissue biopsy for definitive diagnosis of suspected malignancies or inflammatory conditions 1
• Lumbar puncture for evaluation of central nervous system disorders 1
• Specialized functional tests based on organ system involvement 1

Diagnostic Algorithm Refinement

• Use a stepwise approach, starting with less invasive tests before proceeding to more invasive procedures 1, 2
• Interpret test results in the context of pre-test probability based on history and physical examination 4
• Consider the "7 Cs" approach to diagnostic workup: confirm diagnosis, identify causes, recognize cofactors, check for comorbidities, assess consequences, evaluate components, and monitor course 1
• Re-evaluate diagnosis if treatment response is inadequate or if new symptoms develop 1

Common Pitfalls to Avoid

• Avoid assuming that multiple abnormalities are due to the same cause, as multiple pathologies may coexist 2
• Don't delay essential diagnostic procedures (like bone marrow examination) when clinical suspicion for serious conditions is high 2
• Be cautious about over-testing, which can lead to false positives and unnecessary interventions 4
• Remember that some conditions require observation over time for accurate diagnosis 1

Documentation and Follow-up

• Document all diagnostic findings systematically 1
• Establish a clear follow-up plan to monitor disease progression or treatment response 1
• Consider consultation with specialists when findings are complex or diagnosis remains unclear 2
• Use validated assessment tools to monitor disease activity and treatment response when available 1