I co-opted the title above from last week's New England Journal of Medicine perspective article by Dr. Anthony Fauci. It's 3 pages, read it if you have a chance. Mostly by virtue of working in the same infectious diseases community as Fauci for the past few decades, I've been privileged to interact with him on a number of occasions both formal and informal. He is a true genius but also a warm and caring person.
His timeline of emerging infectious diseases, copied below, particularly spoke to me as it coincided with my entry into the pediatric infectious diseases subspecialty. Because my practice was located in an area of high international travel, I had to respond very quickly to possibilities of new infectious diseases. Each time I felt exhilaration with a tinge of fear.
I also note that, of the 21 infectious diseases listed, I've only directly cared for children who truly had 10 of them. However, I was prepared and did evaluate children for all of them. I suspect all infectious diseases clinicians are accustomed to working in hyperdrive at the slightest hint of something new appearing.
Overdiagnosis of Penicillin Allergy
Most healthcare providers know that penicillin and other drug allergies are over-diagnosed. Also, drug allergy is not a lifelong condition but rather is very dynamic. That amoxicillin "allergy" in an infant, even if a true type 1 hypersensitivity reaction, often resolves in later life. Penicillin allergy is a real problem in pediatric healthcare; I long ago lost track of the number of children I've seen who were hospitalized with a serious infection and treated with broad spectrum antibiotics chosen because of a penicillin allergy history. With further probing, it was readily clear that the original so-called allergic event was poorly documented, making it difficult to remove that label in real time. Virtually none of the children had ever been referred to an allergist to sort out the penicillin allergy label. The unnecessary use of broad spectrum therapy contributes to antimicrobial resistance.
This brings us to a recent systematic review and meta-analysis of studies of adult and pediatric patients referred to non-allergists for de-labelling of penicillin allergy. After an extensive systematic literature review of over 11,000 articles, the authors from the UK selected 69 that were of sufficient quality to include in the analysis based on pre-established quality criteria. [Note, this winnowing of articles from 11,000 down to 69 isn't unusual. It's another way of saying that most published articles add little to our understanding of medical management, probably a by-product of "publish or perish" pressure in academic medicine that sometimes rewards quantity over quality.]
Meta-analyses require some of the most sophisticated statistical evaluation in all of medicine; these authors did follow fairly standard methodology in their approach. What's interesting to me are the bottom line numbers. Looking at just the studies that had complete data listed for the proportion of patients tested who were de-labelled, 5072 were tested of which 4698 (92.6%) were de-labelled and 76 (1.5%) were harmed. None of those harmed had serious reactions. Digging a little deeper, 14% of 4350 patients assessed by history alone, 98% of 4207 patients assessed by drug provocation, and 41% of 2890 assessed by skin testing followed by drug provocation were de-labelled.
The take-home points I see from this study are: 1) most subjects labelled as penicillin-allergic aren't truly allergic; 2) front-line healthcare providers need to carefully document possible drug reactions, i.e. don't just record "rash" but rather a complete description of the event in the patient's medical record; 3) for those with possible type-1 hypersensitivity reactions, re-evaluate those patients at the next well visit and consider referral to a provider who can assess for true allergy if needed; and 4) don't let that patient languish for years with a penicillin (or other drug allergy) label. Reassess at every well-child visit and consider a de-labelling process before many years have passed.
COVID-19 Cutaneous Findings
Another group of primarily UK researchers reported findings of cutaneous symptoms from 348,691 participants in an ongoing self-reporting system for COVID-19 symptoms. This is essentially a retrospective case series study. The time period covers both delta and omicron variant waves. They found that skin findings were reported more commonly during the delta time period, 17% versus 11% during omicron, and that cutaneous findings rarely (<2%) were the initial or only findings of infection. The most prominent cutaneous features were unusual hair loss and rashes described as burning, acral, erythematopapular, or urticarial. Skin findings lasted slightly longer in the delta period compared to omicron, and both were shorter than what was reported from the onset of the pandemic with the ancestral strain. Vaccination status didn't seem to have a bearing on cutaneous findings with the exception that vaccinated individuals were less likely to report a burning rash.
Last year some of these same authors developed a nice website to view these cutaneous findings of COVID-19 illness. I look forward to seeing updates of this study as we see new variants and waves.
The Doctor's Dilemma
Fauci referred to an older article by Robert Petersdorf, an early infectious diseases giant, titled The Doctor's Dilemma. That in turn referred to the play by George Bernard Shaw which has been one of my favorites for many years. It is a satire and critique of the medical profession and expresses strong anti-vivisectionist viewpoints. I strongly disagree with some of the tenets presented while agreeing with others, but overall it is very entertaining. If you're looking for some high-quality escapist reading, try it!