Aulus Cornelius Celsus wrote his famous book ‘De Medicina’ approximately 2000 years ago. Living in the times of Caesar Augustus, little is known about his persona. We are not even sure whether he was a practicing physician. Many of his books were lost but Volume VIII was rediscovered in the early renaissance, around the year 1426 [1]. A few copies survived, mostly incomplete.
Celsus described tissue reactions to insults in terms of dolor, calor, rubor, and tumor, ie., pain, warmth, redness and swelling. This tetrad quite adequately describes the signs and symptoms of inflammation. Calor locally is warmth, and systemically would equal fever. The term ‘functio laesa’, or ‘functional impairment’, is often added.
Fast forward to 2026: The Biomarker Consortium, with contributions from FDA, NIH, CMS, FNIH and others, released a publication entitled ’20 years of advancing precision medicine’ [2],[3]. Among other therapeutic areas the Consortium worked on, were several infectious disease projects (ABSSSI, CABP, VABP) with the goal of developing PROs for these infections.
The Consortium developed 2 tools, called PNEUMO PRO© and SKINFECT PRO© which can be reviewed online [4].
Time and space do not allow us to dig into both tools; suffice it to introduce SKINFECT PRO© here, a PRO tool that allows patients to record symptoms every day using a 1-to-5 scoring system of symptoms. We no longer track 4 (four) but rather a whole slew of complaints:
- Local symptoms:
SORENESS – THROBBING – WARMTH – PRESSURE – TENDERNESS – ITCHINESS – HARDNESS TO TOUCH – BURNING – TIGHTNESS - Systemic symptoms:
TIREDNESS – LOW ENERGY – WEAKNESS – FEVER – CHILLS – SWEATING – HEADACHE – NAUSEA – DIZZINESS – FEELING ‘DOWN’ – FEELING ‘WORRIED’ – AVOIDANCE OF SOCIAL ACTIVITIES – DIFFICULTY SLEEPING – DIFFICULTY WORKING - Functional status:
DIFFICULTY WITH ACTIVITIES OF DAILY LIVING – DIFFICULTY WITH PHYSICAL ACTIVITIES
In a somewhat self-congratulatory tone, the Consortium states that FDA used this PRO to establish the ‘primary outcome measure’ for numerous ABSSSI drug approvals over the last decade.
Well, we truly have come a long way in the last 2000 years. What a marvelous achievement – chapeau! The task force came up with an elegant solution to a most vexing problem – how to assess antibiotic benefit without resorting to microbiology.
There is now a quantitative scoring system that replaces Celsus and his crude criteria with a more sophisticated multi-dimensional PRO that allows investigators and regulators to calculate a comprehensive symptom score. This new tool is patient-centric, relevant, and validated. It does away with the arbitrary assessment of doctors and caregivers. Using this catalogue of 25 well-considered criteria, assessment of antibiotic efficacy is now uniform and structured.
We cannot argue with this approach, but is this PRO truly a major milestone of regulatory science, or ultimately a wasted effort? Some may say there is no need for an ‘ABSSSI for Dummies’ approach while others point out its hidden value.
SKINFECT PRO provides a calculated sliding-scale symptom score The tool is objective, multi-dimensional, relevant, and validated It does away with the arguably arbitrary clinical assessment of doctors/investigators Antibiotic efficacy can now be measured using a expanded set of well-considered criteria in a uniform and structured fashion
The benefits of the new system become clearer when we consider all the factors included in the new PRO but not captured in the Celsus tetrad. Take this real-life example of a finger abscess:
- We can remember ‘feeling down’ when we developed the abscess, easily a ‘5’ on the PRO
- We got very anxious and had profuse sweating just thinking that someone would lance the pus collection; clearly a PRO ‘4’
- The finger throbbed badly, and the itch prevented us from falling asleep; make this a PRO ‘3-4’
- We got tired and felt handicapped; unable to work with the affected finger / hand, preventing us from filling out lengthy PRO questionnaires; make this a PRO ‘3’
- We finally relented and answered a few questions but selected ‘3’s and ‘4’s rather indiscriminately because we could not tell the difference between ‘Somewhat=3’ and ‘Quite a bit=4’
- After some time the throbbing stopped, thank goodness, but when it came back later that day, we realized that our PRO of ‘1’ rating was not the right answer
- Actually, we got worried (PRO=’4’) that we might have been assigned to the ‘Tylenol only’ placebo group
In summary, this tool captures a lot more than just Calor-Rubor-Dolor-Tumor. Nonetheless, we still have a nagging feeling that tells us that SKINFECT PRO will not replace Celsus De Medicina. You be the judge: Let us know what you think of SKINFECT PRO, on a scale of 1= not contributory to 5= essential. THANK YOU !
Come to think of it, as an afterthought, maybe the term ‘FUNCTIO LAESA’ was not transcribed properly by the monks that copied De Medicina in the Middle Ages. Could it be that they left out a small pronoun by mistake and the correct transcription should have been ‘PRO FUNCTIO LAESA’? It would have saved the Consortium a lot of work and settled the matter once and for all.
ABBREVIATIONS
ABSSSI skin / skin structure infection
CMS Centers of Medicare/Medicaid systems
FNIH Foundation for the NIH
PRO patient related outcome
REFERENCES
[1] https://www.historyofinformation.com/detail.php?entryid=2111
[2] Klein A. Comment. The Biomarkers Consortium: 20 years of advancing precision medicine. Nature Reviews Drug Discovery 25, 155-156 (2026)
[3] The Biomarkers Consortium: 20 years of advancing precision medicine. Supplementary information. Nature Rev Drug Discovery. 2026. https://doi.org/10.1038/d41573-025-00187-8
[4] https://eprovide.mapi-trust.org/instruments/acute-bacterial-skin-and-skin-structure-infections-symptom-diary
