A clear clinical question is often more useful than a larger test panel. This checklist helps organize an evaluation and handoff; it is not a diagnostic rule or a recommendation to order every investigation listed.
1. Establish the pattern and assess immediate risk
Document measured fever, episode duration and frequency, associated organ findings, age at onset, exposures, family history and the interval between episodes. Assess urgent illness on its own merits. A previous inflammatory diagnosis does not exclude infection or another new problem.
2. Keep the differential open
Consider infection, immune deficiency, autoimmune disease, inflammatory bowel disease, medication effects, malignancy and other causes according to the presentation. Distinguish patient-reported symptoms from documented findings without dismissing intermittent symptoms that are absent today.
3. Link each test to a question
Compare relevant results during illness and when well when that is clinically useful. Interpret inflammatory markers, blood counts and organ assessments with timing and treatment exposure. Choose investigations around the phenotype and avoid using a single negative result to close a complex evaluation.
4. Interpret genetics in context
| Finding | Question to resolve |
|---|---|
| Pathogenic or likely pathogenic variant | Does the phenotype and inheritance pattern fit? Is the report sufficient for this condition? |
| Variant of uncertain significance | What additional evidence or reinterpretation is appropriate? The result alone is not a diagnosis. |
| Negative panel | What was covered, with what sensitivity? Does the phenotype justify another approach? |
| Possible somatic disease | Was the relevant tissue and assay used, with adequate sensitivity for mosaicism? |
Use genetics expertise where needed. Do not turn classification criteria into mandatory diagnostic criteria or assume response to a medicine proves one disease.
5. Make follow-up and referral actionable
- Summarize episodes and objective findings on a timeline.
- Attach the actual genetic report, laboratory trends and relevant imaging/pathology.
- List treatment dose, duration, response, adverse effects and access problems.
- State the unresolved question and the urgency.
- Name who handles results, new episodes, prescriptions and the next appointment.
For established disease, consider inflammatory control, organ health, treatment safety and functional impact. The relevant guidance should inform the individual monitoring schedule.
Give the patient a useful companion
Offer the patient workbook and guide to diagnostic uncertainty. See VEXAS evaluation when acquired adult disease is a concern, and the clinical collection for condition-specific reading.
Sources and further reading
- ISSAID/EMQN best practice guidelines for genetic diagnosis (2020)
- EULAR/ACR guidance on CAPS, TRAPS, MKD and DIRA (2022)
General education, not a diagnosis or an individual treatment plan. Use these resources with your own care team. How this website is edited.