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.

Omission Bias in Therapeutic Medical Decision Making

Having studied so-called heuristics and biases, aka cognitive biases and System 1 & System 2 processes in medical decision making on and off for 25 years, and thinking constantly about them in the full-time practice of clinical medicine, I have come to the conclusion that they are hard to spot in the wild. Except one: Omission Bias.

Omission bias represents a preference for inaction that preserves the status quo over action which changes it, and it is insidious because each day we encounter countless status quo states in medicine, established earlier and perhaps by different providers, but often by ourselves. The status quo inures us to what is, obscuring the question of what ought to be.

In this recent paper, and an accompanying editorial, omission bias is (partly) explained and several recurring examples in the ICU are discussed. But this is the tip of the iceberg. I venture a guess that every day, there is a decision that is made, or not made, that instantiates this bias. In addition to those discussed in the linked papers, here I will point out some common scenarios outside of the ICU where this bias lurks, preying on the desultory physician.

The patient presented to the ER (or elsewhere) for pneumonia, and was started on Zosyn (or cefepime) and vancomycin. Despite having no risk factors for pseudomonas, anaerobes, or MRSA, the team continues those antibiotics rather than change them to standard CAP coverage. The prospect of not covering something, always nagging at the physician, now looms larger because if the patient does unexpectedly have a resistant organism causing pneumonia, the anticipatory regret of not leaving things as they were deters the change.

The patient was started on unfractionated heparin for intermediate (or low) risk DVT/PE, when LMWH is the preferred drug, because of the misguided worry that "an intervention may be needed." Even if that were a legitimate concern at the outset, the patient has made it through the night and has improved, yet UFH is continued, requiring those pesky aPTT checks and the unpredictable pharmacokinetics of the drug.

Aortic Aneurysm Mimicking Recurrent Achalasia after Mediastinitis Complicating Botulinum Toxin Injections.......for Achalasia (Hickam's Victims series)

In this case report, the authors describe a case of a young woman with achalasia who got repeated episodes of mediastinitis complicating botulinum toxin injection. Later she presented with "pseudoachalasia" or presumed recurrence of achalasia, but imaging showed that, lo and behold, she had developed a complication of her mediastinitis, viz an aortic arch aneurysm that required surgical repair. The authors claim that Ockham's razor suggested recurrent achalasia, whereas Hickam's dictum prevailed because the patient had more than one disease. They would have benefited from reading our paper elaborating and operationalizing both clinical saws. The case is easily synthesized into a unifying diagnosis -- a unifying causal pathway -- which obviates invoking multiple diagnoses. The symptoms of the aortic aneurysm mimicked achalasia because they are in the same anatomic location as the mediastinitis causing them, which was in turn caused by the botulinum injections treating the original achalasia. A coauthor and I wrote a letter to the editor, which was not published, but is pasted below. While this critique may seem punctilious or pedantic, there are tangible consequences of this failure of synthesis: the patient went unnecessary testing for Marfan's syndrome and other genetic conditions of the vasculature, and case reports of this very condition (aneurysm after botulism injection induced mediastinitis) were apparently ignored, an omission that may have compromised surgical planning.

Goodrich et al¹ present an interesting case of a young woman with achalasia who developed pseudoachalasia mimicking recurrence of achalasia. The pseudoachalasia was caused by an aneurysm of the posterior aortic arch, and Hickam’s dictum is invoked to remind readers that new symptoms ought not to be reflexively attributed to recurrences of known diseases, an approach they suggest is encouraged by Ockham’s razor. A recent paper operationalized the application of Hickam’s dictum and Ockham’s razor to the problem of multiple diagnoses². According to this framework, multiple diagnoses are almost always due to a primary diagnosis that explains the chief complaint and one or more of: incidentalomas, known pre-existing diseases, or phenomena causally connected to the primary diagnosis. This latter category comprises Occam’s razor which, rather than suggesting a simple or single diagnosis, is better understood as favoring a single causal pathway that links findings together into a unifying diagnosis. When viewed through this lens, the posterior aortic aneurysm was caused by mediastinitis episodes that in turn were caused by treatment of achalasia -- a single, unifying diagnosis. While patients indeed may “have as many diseases as they damn well please” it is prudent to first try to link phenomena into a unifying causal pathway. Such an approach would have led to multiple case reports of aortic aneurysms associated with botulinum toxin injection for achalsaia,^3-5 informed operative planning (e.g., presaging adhesions), and obviated searches for unlikely genetic diseases (e.g., Marfan’s syndrome) in a patient without other features of these conditions.

1.           Goodrich HWF, Muniraj T, Masoud AE. Pseudoachalasia in an Achalasia Patient: A Ticking Time Bomb. ACG Case Rep J. Dec 2025;12(12):e01927. doi:10.14309/crj.0000000000001927

2.           Aberegg SK, Poole BR, Locke BW. Hickam's Dictum: An Analysis of Multiple Diagnoses. J Gen Intern Med. Oct 28 2024;doi:10.1007/s11606-024-09120-y

3.           Berman SS, Sabat JS. Mycotic aneurysm of the distal thoracic aorta after botulinum toxin injection for esophageal dysmotility. J Vasc Surg Cases Innov Tech. Sep 2020;6(3):388-391. doi:10.1016/j.jvscit.2020.04.005

4.           Chao CY, Raj A, Saad N, Hourigan L, Holtmann G. Esophageal perforation, inflammatory mediastinitis and pseudoaneurysm of the thoracic aorta as potential complications of botulinum toxin injection for achalasia. Dig Endosc. Jul 2015;27(5):618-21. doi:10.1111/den.12392

5.           Tan MZ, Whitgift J, Warren H. Mediastinitis, pseudo-aneurysm formation, aortic bleed, and death from endoscopic botulinum toxin injection. Endoscopy. 2016;48 Suppl 1:E186-7. doi:10.1055/s-0042-107074