The Case for the Case Report
J. Jeffrey Malatack, MDPediatrics, Sidney Kimmel Medical School of Thomas Jefferson University and Division of Diagnostic Referral, Department of Pediatrics, Nemours Alfred I. duPont Hospital for Children, Wilmington, Delaware
DOI: https:// doi. org/ 10. 1542/ peds. 2018- 0328 Accepted for publication Feb 13, 2018
Address correspondence to J. Jeffrey Malatack, MD, Diagnostic Referral Department, Nemours Alfred I. duPont Hospital for Children, 1600 Rockland Rd, Wilmington, DE 19899. E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2018 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The author has indicated he has no financial relationships relevant to this article to disclose. FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: Dr Malatack is a member of the editorial board of Pediatrics and is the Case Reports section editor. Case reports at one time could be found in many if not most medical journals. I found that 40 years ago, the top 10 pediatric journals all published case reports (many with designated case report sections), and 30% of the articles published in the 10 journals collectively were case reports. Twenty years ago, these same journals had reduced their case report publications, averaging only 15% of their published articles, with many having dropped a case report section altogether. In 2016, case reports only accounted for 4% of articles published in this same group of journals, with
Pediatrics at 11% being the most committed to this format of medical publication. Pediatrics also is the only one of these publications with a designated section for case reports. Pediatrics’ recent decision to reduce the number of published case reports from a maximum of 8 an issue to 3 an issue is the latest in this long decline. It appears that 2 forces have had a role in the decline of the case report as a genre of medical publications. The 2 forces include the impact factor, created in the 1990s, and the inability to use statistical methodology to assess the data at hand.
The impact factor is a measure of the frequency with which the average article in a journal has been cited from a particular year. It is used to measure the importance or rank of a journal by calculating the times its articles are cited. A 2-year period is used and involves dividing the number of times articles that were cited in that 2-year period after publication by the number of articles that are potentially citable. Case reports are handled, for this purpose, as are original articles. Case Reports, for reasons outlined below, are invariably not going to be cited as often as original articles by the 2-year postpublication period that defines the impact factor.
WHAT WAS A CASE REPORT DURING ITS GOLDEN AGE?
Case reports at one time, when many more were published, included infrequently seen but well-described diagnoses as reminders of rare conditions one should not miss. The authors of other case reports described unexpected combinations of disease processes as an unlikely occurrence in a single patient. Still others reported on the diagnosis of a well-described condition from a geographical area not having reported the disease before. These kinds of case reports have all but disappeared from medical publication. Reminders of rare conditions or unusual presentations of common conditions are no longer necessary when the world’s literature is at everyone’s fingertips. Coincidence adds nothing to medical knowledge and the world has been so functionally reduced in size that isolated areas free of a given medical condition have nearly disappeared. As case report publications have dwindled, the definition of what makes up a publishable case report has evolved into something different.
WHAT IS A CASE REPORT NOW?
A case report at its best is a clever idea that arises from a physician-patient interaction. The authors may uncover an exception to the current paradigm, raising the proposition of “if 1, then some, ” and as such demanding a new paradigm able to incorporate these exceptions. A case report may be a starting point for hypothesis-testing research. The authors may suggest a new therapy or raise an early alert regarding untoward consequences of a new treatment, or they may raise the practice level of the reader. The articles in this supplement provide examples of some of these varied types of case reports.
Exceptions to a Current Paradigm
Many years ago, we published a report of cat scratch disease (CSD) in the absence of adenopathy.1 At the
time, before the identification of the putative organism of CSD, the dogma was that anyone suffering from CSD had to have adenopathy. A so-called sine qua non. However, an expert on CSD, after hearing the details of our case, including the child’s intimate contact with a kitten and despite the absence of adenopathy, sent us the then-only diagnostic test for CSD, a skin test (Hanger Rose test) that one applied by an intradermal injection.2
Sure enough, the test was positive. To add additional certainty to the diagnosis, we sent the tissue from a granulomatous lesion in our patient’s liver to Colonel Douglas Wear, MD. A few years earlier, Dr Wear et al, 3
while working at the Armed Forces Institute of Pathology, had reported a Warthin-Starry staining organism in the lymph node of a patient with CSD. Dr Wear identified those same silver staining organisms in our patient’s liver granuloma. Coincidentally, this identical finding was published in The Lancet shortly before our report appeared in The Journal of Pediatrics.4 The paradigm
changed. Since those 2 published reports, no one has performed a double-blind study to confirm the new paradigm. It has never been necessary. If CSD can occur without adenopathy, the possible spectrum of CSD became much wider than previously believed. In the ensuing years, the authors of a number of studies published as original articles about CSD took advantage of this increasing spectrum of disease. The authors of 1 study indicated how fever of unknown origin is frequently due to systemic CSD.5
Others identified how frequently a previously healthy child presenting to the emergency department with status epilepticus had systemic CSD without adenopathy but with CSD encephalitis.6 The authors of
yet another study identified the frequency at which a typical kitten harbors the CSD organism that is now called, after multiple names changes,
Bartonella henselae.7 The original
observation of CSD occurring without adenopathy remains the discovery published as a case report. It was years after that original observation before the studies mentioned were published. These studies added to the body of knowledge on CSD and emerged from the paradigm shift after the time it took to develop a study protocol, collect study data, analyze the data, and then publish the findings. Any reference to the 2 original case reports on CSD without lymphadenopathy were never credited to an impact factor because of the multiyear delay between these 2 case reports being published and subsequent studies years later.
A Starting Point for Hypothesis Testing Research
A case report also can be an observation that gives life to a novel idea (hypothesis). Although ideas derived from a single or even a few patient interactions might as easily be a misstep down the path to knowledge, they also can and have been the beginning of novel understanding. In these instances, case reports must be put to the test of the scientific method before the idea can take hold and be accepted. Ideas are precious and should never be squandered. It is perfectly acceptable to eliminate ideas that emerge from case reports that fail the test of scientific rigor so that those ideas that do emerge from that rigor unscathed can add to medical knowledge. Ideas are not science, but they are necessary at the beginning of a scientific advance no less than an acorn is necessary to allow an oak tree with the potential to be a giant, to burst into existence and begin to grow.
of propranolol as a treatment of expanding infantile hemangioma as case reports.8 These single cases
did not prove the effectiveness of propranolol itself or, more importantly, the effectiveness of propranolol as compared with the then-standard corticosteroid treatment. The finding of efficacy in a disease that spontaneously regresses is always a risky proposition. That the apparent clinical response (involution of the hemangioma) might be unrelated to the treatment was also possible, and it became necessary to clarify propranolol’s effectiveness or lack thereof. The authors of the case reports did not settle this issue but acted to stimulate controlled trials such that propranolol has now replaced corticosteroids as first-line treatment of infantile hemangioma.
Suggest New Therapy
The authors of case reports often raise questions regarding effectiveness of a new therapy when off-label treatment with a drug, sometimes recognized serendipitously, appears to impact outcome. Extending procedures outside of their intended purpose has also led to the identification of new treatments. A case report published early in the development of liver transplantation for end-stage liver disease in a patient with
α-1-antitrypsin deficiency led to recognition that the donor organs maintained the phenotype of the donor and corrected not only the complications of cirrhosis but also the enzyme deficiency state. Liver transplantation is now standard therapy for many liver-based inborn errors of metabolism, even in patients without a failing liver. The first case report in this supplement of the use of liver transplantation for pyruvate kinase deficiency is 1 such example.9 In the next 7 case
reports, novel therapies for difficult to manage conditions are suggested.
Treatments are offered to improve bronchopulmonary dysplasia with lung reduction surgery, 10 to manage
the consequences of an ATP1A2 gene mutation with an N-methyl-D-aspartate receptor antagonist, 11 to
treat neonatal hyperglycemia with insulin glargine, 12 and to improve
intestinal pseudo-obstruction with pyridostigmine.13 The authors of
3 other articles suggest a novel treatment of the erythroderma of Omenn Syndrome14 and discuss vagal
maneuver termination of ventricular tachycardia15 and an approach
to recanalizing a central vein in a total parental nutrition–dependent child with lost intravenous access.16 These approaches, as in
the use of propranolol for infantile hemangioma, will require study to confirm efficacy.
Early Alert Regarding Untoward Consequences
The authors of case reports have identified untoward consequences of new therapies acting as an early warning, a caution light, months or years before a blinded controlled study confirms the risk. The ninth and 10th case reports in this supplement do just that. Sirolimus use for management of complex vascular or lymphangiomatous lesions has raised great expectations and interest as management for conditions for which to date there have been few good options. The authors of these 2 reports warn of dire consequences when one uses sirolimus for management of complex vascular malformations, particularly in infants.17, 18 Because just a few
cases of these untoward outcomes with sirolimus exist, it is possible that the reports are misleading. However, the use of pneumocystis pneumonia prophylaxis in those who receive this new therapy until the definitive studies occur is a small price to pay even if it turns out that the apparent untoward effect had nothing to do with the use of sirolimus. Two other reports
also are warning case reports. One relates a vitamin B6 toxicity, 19 and
the other relates a drug reaction with eosinophilia and systemic symptoms to oxcarbazepine in a patient with a specific immunotype.20
Elevating Pediatric Practice Finally, case reports that can raise the level of practice of the pediatric community may also be worthy of publication, but in these instances, the bar needs to be set high. Vitamin A deficiency–induced blindness in autistic children because of peculiar diet self-restriction has been described repeatedly in case reports, but the 13th report in this supplement of a high-income child without autism and a self-restricted diet that led to symptomatic Vitamin A deficiency with blindness got over this high bar.21 Other articles in this
supplement similarly raise our level of practice. These include a report of craniosynostosis as the presenting feature of hypophosphotemic rickets, 22 autoimmune pancreatitis
and ulcerative colitis in a teen, 23
histoplasmosis myocarditis after a “mud run, ”24 recalcitrant
atopic conjunctivitis, 25 and the
development of hemophagocytic lymphohistiocytosis in a neonate due to adenovirus.26
is what is of consequence, and it has been described many years ago in peer-reviewed literature. If on the other hand the object retrieved is the first report of ingestion of something causing heretofore-unrecognized pathology, then it is case report material. This was the case with the then-new miniaturized button batteries some years ago. A more recent example are the packing balls that expand in the stomach or intestine as they take on fluid, leading to bowel obstruction.27 Likewise,
novel gene defects of a previously recognized mutation that lead to a specific phenotype only warrant a report if the novel mutation of that same gene is associated with a significant phenotype variation from the known mutation. Novel genotype mutations causing previously recognized phenotypes need to be cataloged but do not represent case report material. Case reports are not
“first reports” of a disease in a part of the world that had not previously reported this disease unless it is documenting the spread of an infectious disease outside its endemic area.
WHAT IS TO BE GAINED OR LOST BY ELIMINATING CASE REPORTS?
Some have raised concern that there is risk in publishing case reports that are yet to be proven as solid science. Another worry is that others will take a case report for fact and initiate treatments that are at best premature or at worst incorrect. In the supplement that follows, the authors of the final article that appears tested this concern. Bryan Sisk from Washington University in St Louis, while working as an editorial fellow for Pediatrics, decided with colleagues to study how case reports from Pediatrics are cited.28
He found that the majority provide a clear proviso that the citation is a case report and with appropriate caution, regarding its applicability,
only rarely have they been cited as scientific evidence.
The best case reports are written by authors who have a remarkable ability to see connections not previously appreciated as causal. In this supplement, you will find reports of a mutation of NALCN and its connection to disordered breathing, 29 hypospadias and its
relationship to a Wilms tumor 1 novel gene variant, 30
the association between a childhood immunodeficiency and panniculitis, 31 blue diaper syndrome
and PSCK1 mutations, 32 and
the association of neonatal
alloimmune thrombocytopenia with amegakaryocytosis, B lymphopenia, and villitis.33 These authors often
are not the same as those with aptitude to create study design, identify and control variables, and provide overall organizational skill to overcome obstacles in route to completing studies that eventually emerge as original articles. These 2 types of authors are “wired differently” as much as the left and the right of the political spectrum are wired differently.34
But they need each other. The case report writer who raises questions will never add anything to the scientific database unless those questions (hypotheses) are tested in controlled ways. The original article writer is always looking for ideas or hypotheses to be tested to advance the cutting edge of science. They are the yin and yang needed to complete the whole.
HOW DO WE SAVE THE CASE REPORT? If the arguments provided here have convinced you that there is lasting value in the case report, or if you needed no convincing in the first place, then what strategy needs to be applied if the case report is to remain a viable genre of medical literature? It is clear that case reports must not be handled as original articles with
regard to the impact factor. The pressure on managing editors to improve the “ranking” of the journal will trump the medical editor’s attempt to fulfill an academic mission every time. We need to recognize that there is a great deal of arbitrariness in the way impact factor is currently designed and in turn promoted as a sign of excellence when the impact factor is high. Why use a 2-year interval? Why not use a 3- or 4-year interval? Should Internet “hits” (not used in the impact factor) indicating how much an article is read have a role in the calculation? Does it matter who is citing the article and in what journals it is being cited? Because it is arbitrary, why not simply pull case reports out of articles counted in the impact factor or develop some alternate way for case reports to have an effect on the impact factor calculation different from original articles?
Each journal needs to allow its medical editors to focus on its academic mission, its raison d’etre. On the basis of its fit into the mosaic of medical publications, each journal must use or not use the case report to strengthen its message. Journal editors should not be focused on a flawed rating system that leads to false idolatry to a number, a number particularly ill-suited for the assessment of ideas.
We believe this supplement provides the argument for continued value of case reports. It demonstrates the important role that case reports have played and will continue to play in medical publications and in particular in
Pediatrics. We encourage readers to consider submitting their case reports to future issues of our journal.
ACKNOWLEDGMENTS
duPont Hospital for Children, for research performed in support of this work and Dr Deborah Consolini for editing work and suggestions to the article.
ABBREVIATION
CSD: cat scratch disease
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