A Case of Familial Cold Autoinflammatory Syndrome Type 2
Bibliographic record
Abstract
Background Systemic rheumatic diseases exist along a spectrum of autoimmune and autoinflammatory disorders. Autoinflammatory diseases (AID) result from errors of the innate immune system, which results in systemic inflammation. This differs from autoimmune syndromes which result from errors of the adaptive immune system when self-tolerance is broken and autoantibodies are generated. Case Mrs. X, a 46yo F, was referred for further evaluation and treatment of a possible cold autoinflammatory syndrome. She has a history of cold-induced episodes starting in her late childhood, which have worsened in severity since a SARS-CoV-2 infection in 2022. Her cold-induced episodes are marked by widespread hives and flushing, with associated arthralgias and myalgias, chest pain with concurrent tachycardia, and abdominal cramping with diarrhea. These episodes are self-limiting over the course of a day. She additionally has ongoing cyclic fevers, fatigue and headaches. Her physical examinations have always been unremarkable apart from these cold-induced episodes where she has widespread flushing of her skin and hives. Prior to this referral she has been evaluated by a number of other subspecialists whose investigations only revealed elevated serum amyloid A levels. She had genetic testing done looking for monogenic periodic fever syndromes, which revealed mutations of unknown significance in her NLRP12 gene, an area also mutated in her father’s testing. She has an extensive history of similar cold-induced episodes in other family members, which vary in severity, and follow an autosomal dominant pattern through her father’s family. No one in her family has received a formal diagnosis at this time. With this information, medical genetics agreed that this likely represents a cold autoinflammatory syndrome, familial cold autoinflammatory type 2, which is likely related to her NLRP12 mutation. Mrs. X has been using intermittent prednisone to treat these episodes with good effect previously. She was initiated on anakinra, an IL-1 receptor antagonist, which was effective at reducing the frequency and duration of her episodes, where she no longer uses prednisone. Conclusion Cold autoinflammatory syndromes have been described in literature, most often in pediatrics, with increasing frequency over the last decade. They are increasingly being studied which is revealing of genetic mutations as drivers of these diseases. This case highlights that adult presentations of these diseases exist and that the adult rheumatologist should have a working knowledge of these conditions and the genetics behind autoinflammatory disorders.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.003 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".