Hickam's Victims: Misdiagnosis & Treatment of an Incidentaloma in Guillain-Barre Syndrome and Careless Citation Practices

I'm following citations to our paper explicating Hickam's Dictum (HD) and Ockham's Razor (OR) as applied to diagnostic decision making, published two years ago. It was my hope that this paper would lead to a more thoughtful consideration of these allegedly conflicting clinical saws, but alas I was too sanguine about that prospect. It would seem that most people citing our paper are not even reading it. Rather, it appears that they conclude that they have identified a case of HD, write a case report about it, then seek supporting references and cite our paper without reading it or applying its insights to their case.

Nonetheless, I'm happy to have our paper cited for any perspicatious and curious readers of these case reports. And, the problem of careless citation practices is rampant. Often when I check citations to see if they support the referenced statements, I'm gobsmacked: not only do many citations fail to support the authors' statements, sometimes they directly undermine them. Commonly, an author makes claims as though starting from truth rather than uncertainty, then searches for supporting references, but does not carefully evaluate the references or their relation to his claim -- or even read the papers he's referencing. Rather, he reads the title or abstract ingenuously and cites the paper. This is not scholarship, this is confirmation bias and motivated reasoning in action. It is abetted and exacerbated by the tendency of authors to overextend themselves in their abstracts, arriving at conclusions that are broader and firmer than warranted by the data. This phenomenon has a tendency to magnify and replicate flimsy claims, so we wind up with wholly unsupported concepts that persist for decades, viz, immune dysregulation in sepsis. (Just think about this for a second and decide if it makes sense:"Some people die of sepsis; therefore, evolution of mamallian immunology stalled, failed, or overshot, and the immune system is dysregulated.") Yet this concept accompanies almost every single article about sepsis for going on a generation; you gotta reference it in your sepsis paper. So, you go to pubmed, type it in, find the latest abstract that mentions  it, import it into EndNote, cite it. Done. Specious concept propagated yet again.

In this case report alleging the simultaneous presentation of Guillain-Barre Syndrome (GBS) and a pancreaticoduodenal artery aneurysm PDAA with "impending rupture," the author invokes Hickam's dictum becaues the patient has two diseases that were discovered at the same time. The schema outlined in Figure 3 of our paper shows that there are four possibilities for the relations between two (or more) disease: incidentalomas, pre-existing diseases, diseases causally connected to the principal diagnosis, and lastly, two symptomatic, independent, temporally coincident diseases. This last possibility is decidecly the least common, but it's what the author settled upon.

The patient had a preceeding viral illness (setting the stage for GBS) and a week later developed numbness and back pain, two common symptoms of GBS. She went to an ER and because of the back pain, had a CT of the abdomen, and a PDAA was discovered. The case report describes it as having an "impending rupture," but we are not told how this determination was made. (Can it be made?) It was embolized and her back pain (maybe? kinda?) resolved. Days after the embolization, they discovered the true cause of her numbness and back pain: GBS.

Not described in the report is the well-established fact that the vast majority of unruptured PDAA are totally asymptomatic and discovered incidentally on imaging as in this case. Furthermore, when they are symptomatic they cause epigastric and abdominal pain, not back pain. Risk of rupture is not clearly correlated with size, so size alone cannot be used to infer "impending rupture." Just that background knowledge is enough to establish that this is an incidentaloma. 

In real time, considering that these aneurysms take years to form and are mostly incidentally discovered and don't cause back pain should lead the wary clinician to question whether this is an incidentaloma and the real disease is still lurking in the background. Her symptoms should be more carefully explored, information about the patient and the diagnostic possibilities further investigated and synthesized.

If we find incidentalomas and treat them with invasive therapies without careful consideration, we are liable to cause iatrogenic problems. Though PDAAs warrant embolization because of a high risk of later rupture, we may not want to place it high on the list of management priorities depending on the acute disease (here, GBS) we're dealing with. Imagine that this lady had presented just a bit later when she had respiratory muscle weakness, and had been taken for urgent embolization, and then she coded during conscious sedation for the procedure. Or, imagine if, as almost happened in this case, that the principal diagnosis (the one which explains the chief complaint: GBS) was missed and she had respiratory arrest because PDAA with "impending rupture" was misidentified as the principal problem and her weakness was misattributed to residual sedation effects.

Analysis of this case report makes clear that this is not a purely pedagogical or pedantic exercise. Knowledge structured according to our Figure 3 heightens awareness that we can always be chasing incidentalomas or anchoring on known diseases, missing the true principal diagnosis, or failing to make connections between causally related facets of the presenting illness, invoking multiple diagnoses --sometimes highly unlikely combinations of rare diseases -- rather than a unifying one.

Some of these case reports alleging HD are downright embarrassing. They expose fundamental errors of diagnostic logic that persist even after the effort to write up the case for full publication has been undertaken. As we showed in our paper -- the one that apparently nobody reads -- most of the time when you invoke HD it means you missed the big picture and were surprised by an unsurprising set of multiple diagnoses because of incomplete or flawed understanding of the case. 

Medicine is hard.

Hickam's Victims: An M&M of an MM misdiagnosis

In this case report, the authors describe the case of a 42-year-old-woman who presented with abdominal pain, rash, fever, loose stools and anorexia. Her serum eosinophil count was 2.07x10^9 (25%), and she had increased light chains - both kappa and lambda. Bone marrow biopsy showed lots of eosinophils and immature plasma cells. I will leave it to the oncology nerds to reference the report for details, but just note that the presence of both kappa and lambda is a red flag, and so are the eosinophils if you're going to call this multiple myeloma (MM). And the presenting symptoms are another red flag because they're not consistent with MM.

Nonetheless, the patient was diagnosed with MM and underwent treatment for it for seven years. The treatments included bortezomib, and she developed peripheral neuropathy. The treatment did not relieve her symptoms including asthma, rash, diarrhea, etc., and her eosinophils and kappa and lambda levels were unchanged. Never deterred, her oncologists changed her chemotherapy regimen several times, and performed over a dozen bone marrow biopsies, all showing persistent eosinophilia.

After these seven years of misdiagnosis and status iatrogenicus, she sought a second opinion, and the correct diagnosis was made: EGPA. She was treated for EGPA, and her symptoms resolved (except for the bortezomib-induced peripheral neuropathy).

One pivotal error the oncologists made was to assign a disease based on laboratory findings suggesting a disease that is an unlikely (even preposterous) explanation for the clinical presentation. This is all too common. The coronavirus is positive? The diagnosis is coronavirus, despite an incompatible clinical and radiographic picture. The PJP PCR is positive? It's PJP despite no symptoms and natural history to suggest this, and a negative 1,3-beta-D glucan. I recently conferred with a colleague talking about very odd sputum culture results, in a patient whose "pneumonia would not clear". I looked up the unfamiliar to me bugs: they are not human pathogens. Nonetheless, they are being treated. I looked at the CT: cystic disease pathognomonic of lymphangioleiomyomatosis (LAM). But it need not be microbiology results as the current case makes clear.

Hickam Tricked 'em with the 'ol Red Herring Ruse (Hickam's Victims series)

One of my favorite Charlie Munger quotes goes something like this:

"Warren, over the years you and I have appreciated the great value in learning from mistakes; Another thing we realized is that it's a lot more pleasurable to learn from other people's mistakes."

In light of that sage advice, here's another recent case report invoking Hickam's dictum. In this case, a 38-year-old man from Pakistan who has sex with men presents with uveitis and a rash on his palms and soles. He has a positive interferon-gamma release assay. This caused diagnostic confusion which resulted in the unnecessary invocation of Hickam's dictum. There is, after all, a simple explanation for the two findings, as I explicated in an online comment:

"This is an interesting case. Neither Ockham's razor, nor Hickam's dictum, nor Crabtree’s bludgeon need be invoked to sort it out.

The annual incidence of syphilis in men who have sex with men in the USA is a whopping 309 cases per 100,000 persons per year - almost as common as community acquired pneumonia in unselected adults. Compare that to 2.9 syphilis cases/100,000 person-years in men who have sex only with women. A risk factor that increases the incidence of disease over 100-fold should point even the novice diagnostician straight to the diagnosis. Combined with a rash on the palms and soles? The diagnosis is all but made. Positive RPR? We’re finished here! For guidance on using incidence/disease frequency as a surrogate for disease probability, see: https://pubmed.ncbi.nlm.nih.gov/34854514/

Next, IGRA (e.g., quantiferon Gold) is NOT a diagnostic test for active tuberculosis infection (indeed, active infection is a cause of false negative IGRA), it is used clinically as a marker of prior tuberculosis exposure. In Pakistan, the annual incidence of tuberculosis is 230 cases per 100,000 persons per year, so it is hardly surprising that this patient has a positive quantiferon-gold. This is a red herring rather than an instantiation of Hickam’s dictum. Likewise, the dermatologist consultation was a false negative test for secondary syphilis. It is unbelievable that they attributed this rash to psoriasis, but this highlights that we should not put too much credence into any single piece of data or consultation if it flies in the face of the totality of the evidence. Similarly, angiotensin converting enzyme (ACE) levels are notoriously both insensitive and non-specific.

In the end, there is a simple unifying (and unsurprising) diagnosis in this case: syphilitic rash and uveitis in a man who has sex with men. For an explication of Ockhams razor and Hickams dictum (and the limits of their inferential powers), see: https://pubmed.ncbi.nlm.nih.gov/39467949/

Interestingly, Hickam started in the Boston hospital system, went to Emory, then to Duke, and finally to Indiana. Though not formally specialty trained, he did pioneering work in ophthalmology research, as well as cardiopulmonary research. An entire edition of the Archives of Internal medicine was dedicated to him after his death by reprinting seven of his original papers – the entire issue of the journal."

Hickam's Victims: The Unwary Diagnostician

In this case report, the authors describe a woman, some 82 years of age who had immigrated from Korea 30 years prior to presenting with syncope and dehydration, which was soon discovered to be Salmonella enterica subspecies typhi. Despite urine culture growing gram negative rods, 

"CT of chest, abdomen, and pelvis without contrast was ordered to better characterize the source of her sepsis."

Ignoring that we already have a source for her sepsis (indeed the most common source: urosepsis), and that gram negative sepsis almost never originates from the chest, we will move on after noting that they found multiple cavitary lesions in the upper lobes of the lungs. The authors state that they tried to link the cavitary lung disease with the urinary tract infection (staghorn calculi were found too!) and Salmonella bacteremia, because of an inclination towards Ockham's razor, but alas learned that the chest disease was tuberculosis (who knew!?) so they invoke Hickam's dictum. I rather think that this is a case of Crabtree's bludgeon which states that:

"No set of mutually inconsistent observations can exist for which some human intellect canno t conceive a coherent explanation, however complicated."

Alas, much about the epidemiology and natural history of both Salmonella and tuberculosis in this case report was neglected, so I penned this letter to the editor, below. I did not receive confirmation of my submission, and this journal's website is a bit inchoate, so I assume my letter was lost....

Added on 10/6/2025: Actually, my letter was not lost, as I received an acceptance letter today, but only after the invoice charging me $1530.00 USD as a publication fee for a letter to the editor! But let me tell you, the reviews, wherever they came from, were over the moon with my "clinical acumen" and "insightful analysis".

I replied saying nevermind, I can't afford that charge to publish a *letter* They replied saying "how much can you afford?" I offered $200 and it was immediately accepted. Never overlook the value of flattery, or the cold hard dollar. 

So I will link the letter, after it is published. In the meantime, comment below if you have your own insights about the case.

Added 10/21/2025: Published letter linked here. Text below:

Letter to the Editor: Guo and Liu reported an interesting case of a woman who presented with Salmonella enterica serovar typhi bacteremia and was also concurrently diagnosed with pulmonary tuberculosis [1]. Readers of this report may appreciate two additional perspectives beyond those discussed by the authors. First, humans are the only reservoir for S. enterica serotype typhi; all disease results from human shedding of the bacterium and it is not endemic in the U.S [2]. Because the patient was a Korean resident 30 years ago when it was endemic there [3], it is most likely that she acquired the infection prior to immigration to the U.S., and the reported infection arose from a chronic carrier state. The source of carriage is usually the gallbladder, which was not mentioned in the report, but could have been the source of seeding the urinary tract. Second, as was recently reported [4], the juxtaposition of Hickam’s dictum and Ockham’s razor as conflicting clinical maxims oversimplifies their application to the diagnostic process. Multiple diseases in the same patient are commonplace, and concurrent diagnosis must consider timing of symptoms, probability, and causal connections between diseases in addition to the much rarer situation where two independent diseases present with nearly simultaneous symptoms [4]. The only plausible causal connection between Salmonella and tuberculosis in the case reported is that they were probably both acquired in Korea – a common cause that would seem to satisfy Ockham’s razor. But because the symptoms the patient sought care for are directly attributable to Salmonella bacteremia, the tuberculosis infection likely represents a chronic infection, or an incidentaloma, albeit a consequential one. Within a framework that considers symptom timing as a non-arbitrary marker of disease onset, physicians are alerted to the omnipresent possibility of discovering asymptomatic diseases such as incidentalomas if causal connections between two diseases discovered concurrently cannot be made. This framework obviates the impossible task of discerning which of two allegedly conflicting clinical axioms – Hickam’s dictum or Ockham’s razor – applies in a given case, since diagnosticians can never know, a priori, which one to invoke. In the final analysis, this patient had chronic, asymptomatic tuberculosis reactivation, which was accidentally discovered during her acute illness with Salmonella, both of which were acquired remotely in Korea.

1. Guo S, Liu M. A rare concurrent presentation of typhoid fever with bacteremia and pulmonary tuberculosis. Arch Clin Biomed Res 9 (2025): 226-228. 

2. Tagg KA, Kim JY, Henderson B, et al. Azithromycin-resistantpositive Salmonella enterica serovar Typhi in the United States. J Glob Antimicrob Resist 39 (2024): 69-72. 

3. Yoo S, Pai H, Byeon JH, et al. Epidemiology of Salmonella enterica serotype Typhi infections in Korea for recent 9 years: trends of antimicrobial resistance. J Korean Med Sci 19 (2004): 15-20.

4. Aberegg SK, Poole BR, Locke BW. Hickam’s dictum: an analysis of multiple diagnoses. J Gen Intern Med 39 (2024): 1-4.