J. Jeffrey Malatack, MD The Case for the Case Report

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 Pediatrics15% of their published articles, with many having dropped a case report section altogether.Pediatrics 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. also is the only one of these publications with a designated section for case reports. 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. “ ’ The other force that has led to the decline of case reports is the inability to apply statistical analysis ” to strengthen the scientific merit of the report. In the words of one of my coeditors, You can t tell ’ anything from a single case. The error in this reasoning is the supposition that a case report and an original article have anything in common. They don t.

Pediatrics, 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.

Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 141, number s5, April 2018:e20180328 SUPPLEMENT ARTICLE WHAT WAS A CASE REPORT DURING ITS Exceptions to a Current Paradigm GOLDEN AGE? yet another study identified the frequency at which a typical kitten Many years ago, we published a Bartonellaharbors the henselae CSD organism that is now Case reports at one time, when many report of cat scratch disease1 (CSD) in called, after multiple7 names changes, more were published, included the absence of adenopathy. At the . The original infrequently seen but well-described time, before the identification of the observation of CSD occurring without diagnoses as reminders of rare putative organism of CSD, the dogma adenopathy remains the discovery conditions one should not miss. was that anyone suffering from CSD published as a case report. It was The authors of other case reports had to have adenopathy. A so-called years after that original observation sine qua non. However, an expert on before the studies mentioned were described unexpected combinations ’ of disease processes as an unlikely CSD, after hearing the details of our published. These studies added to occurrence in a single patient. Still case, including the child s intimate the body of knowledge on CSD and others reported on the diagnosis contact with a kitten and despite the emerged from the paradigm shift of a well-described condition from absence of adenopathy, sent us the after the time it took to develop a a geographical area not having then-only diagnostic test for CSD, a study protocol, collect study data, reported the disease before. skin test (Hanger Rose test) that one2 analyze the data, and then publish These kinds of case reports have applied by an intradermal injection. the findings. Any reference to the 2 all but disappeared from medical Sure enough, the test was positive. original case reports on CSD without To add additional certainty to the lymphadenopathy were never publication. Reminders of rare ’ conditions or unusual presentations diagnosis, we sent the tissue from a credited to an impact factor because ’ of common conditions are no granulomatous lesion in our patient s of the multiyear delay between these ’ longer necessary when the world s liver to Colonel Douglas Wear, MD.3 2 case reports being published and literature is at everyone s fingertips. A few years earlier, Dr Wear et al,​ Asubsequent Starting Point studies for years Hypothesis later. Coincidence adds nothing to medical while working at the Armed Forces Testing Research knowledge and the world has been Institute of Pathology, had reported so functionally reduced in size that a Warthin-Starry staining organism in the lymph node of a patient isolated areas free of a given medical A case report also can be an with CSD. Dr Wear identified those condition have nearly disappeared. ’ observation that gives life to a novel same silver staining organisms As case report publications have idea (hypothesis). Although ideas in our patient s liver granuloma. dwindled, the definition of what The Lancet derived from a single or even a Coincidentally, this identical finding makes up a publishable case report The few patient interactions might as was published in shortly has evolved into something different. Journal of Pediatrics easily be a misstep down the path before our report appeared in 4 to knowledge, they also can and WHAT IS A CASE REPORT NOW? . The paradigm have been the beginning of novel changed. Since those 2 published understanding. In these instances, reports, no one has performed a case reports must be put to the test double-blind study to confirm the of the scientific method before the A case report at its best is a clever new paradigm. It has never been idea can take hold and be accepted. idea that arises from a physician- necessary. If CSD can occur without Ideas are precious and should patient interaction. The authors may adenopathy, the possible spectrum never be squandered. It is perfectly uncover an exception to the current of CSD became much wider than “ ” acceptable to eliminate ideas that paradigm, raising the proposition previously believed. In the ensuing emerge from case reports that fail of if 1, then some,​ and as such years, the authors of a number of the test of scientific rigor so that demanding a new paradigm able studies published as original articles those ideas that do emerge from that to incorporate these exceptions. about CSD took advantage of this rigor unscathed can add to medical A case report may be a starting point increasing spectrum of disease. knowledge. Ideas are not science, but for hypothesis-testing research. The The authors of 1 study indicated they are necessary at the beginning authors may suggest a new therapy how fever of unknown origin is 5 of a scientific advance no less than or raise an early alert regarding frequently due to systemic CSD. an acorn is necessary to allow an oak untoward consequences of a new Others identified how frequently a tree with the potential to be a giant, treatment, or they may raise the previously healthy child presenting to burst into existence and begin to practice level of the reader. The to the emergency department with grow.Pediatrics articles in this supplement provide status epilepticus had systemic examples of some of these varied CSD without adenopathy6 but with published some of the first types of case reports. CSD encephalitis. The authors of reports of the use and effectiveness Downloaded from www.aappublications.org/news by guest on September 30, 2021 S380 MALATACK of propranolol as a treatment of Treatments are offered to improve also are warning case reports.19 One expanding infantile8 hemangioma bronchopulmonary dysplasia10 with relates a vitamin B6 toxicity,​ and as case reports. These single cases lung reduction surgery,​ to manage the other relates a drug reaction with did not prove the effectiveness the consequences of an ATP1A2 eosinophilia and systemic symptoms of propranolol itself or, more gene mutation with an N-methyl-D-11 to oxcarbazepine in a 20patient with a importantly, the effectiveness of aspartate receptor antagonist,​ to Elevatingspecific immunotype Pediatric Practice. propranolol as compared with treat neonatal hyperglycemia12 with the then-standard corticosteroid insulin glargine,​ and to improve treatment. The finding of efficacy in a intestinal pseudo-obstruction with 13 Finally, case reports that can raise disease that spontaneously regresses pyridostigmine. The authors of the level of practice of the pediatric is always a risky proposition. That 3 other articles suggest a novel community may also be worthy of the apparent clinical response treatment of the erythroderma of 14 publication, but in these instances, (involution of the hemangioma) Omenn Syndrome and discuss vagal – the bar needs to be set high. Vitamin might be unrelated to the treatment maneuver termination of ventricular ’ 15 A deficiency induced blindness was also possible, and it became tachycardia and an approach – in autistic children because of necessary to clarify propranolol s to recanalizing a central vein in a peculiar diet self-restriction has effectiveness or lack thereof. The total parental nutrition dependent been described repeatedly in case authors of the case reports did child with lost intravenous 16 reports, but the 13th report in this not settle this issue but acted to access. These approaches, as in supplement of a high-income child stimulate controlled trials such the use of propranolol for infantile without autism and a self-restricted that propranolol has now replaced hemangioma, will require study to diet that led to symptomatic Vitamin corticosteroids as first-line treatment confirmEarly Alert efficacy. Regarding Untoward A deficiency with blindness got over of infantile hemangioma. Consequences 21 Suggest New Therapy this high bar. Other articles in this supplement similarly raise our level of practice. These include a report of The authors of case reports have craniosynostosis as the presenting The authors of case reports identified untoward consequences feature of hypophosphotemic often raise questions regarding of new therapies acting as an early 22 rickets,​ autoimmune pancreatitis effectiveness of a new therapy warning, a caution light, months or 23 and ulcerative colitis in a teen,​ when off-label treatment with years before a blinded controlled “ ” histoplasmosis myocarditis a drug, sometimes recognized study confirms the risk. The ninth 24 after a mud run,​ ‍ recalcitrant serendipitously, appears to impact and 10th case reports in this 25 atopic conjunctivitis,​ and the outcome. Extending procedures supplement do just that. Sirolimus development of hemophagocytic outside of their intended purpose use for management of complex lymphohistiocytosis in a neonate due has also led to the identification vascular or lymphangiomatous 26 to adenovirus. of new treatments. A case report lesions has raised great expectations published early in the development and interest as management for WHAT A CASE REPORT SHOULD NOT BE of liver transplantation for end- conditions for which to date there α stage liver disease in a patient with have been few good options. The -1-antitrypsin deficiency led to authors of these 2 reports warn of Case reports also have had a long recognition that the donor organs dire consequences when one uses history of being an entry pathway maintained the phenotype of the sirolimus for management of complex for young physicians into the world donor and corrected not only the vascular malformations,17,18​ particularly of medical publication. It is a potent complications of cirrhosis but also in infants. ‍ Because just a few argument for continuing the place the enzyme deficiency state. Liver cases of these untoward outcomes of case reports in medical literature. transplantation is now standard with sirolimus exist, it is possible Yet even in this role, the case report therapy for many liver-based inborn that the reports are misleading. must remain a genre that lives in errors of metabolism, even in However, the use of pneumocystis the realm of new ideas. Case reports patients without a failing liver. The pneumonia prophylaxis in those should not be recognition of a rare first case report in this supplement who receive this new therapy until disease already well described but of the use of liver transplantation the definitive studies occur is a exciting to the clinician who made a for pyruvate kinase9 deficiency is 1 small price to pay even if it turns rare diagnosis. It is not a finding from such example. In the next 7 case out that the apparent untoward a well-oiled procedure (foreign body ’ reports, novel therapies for difficult effect had nothing to do with the retrieval) of the newest ingested to manage conditions are suggested. use of sirolimus. Two other reports children s toy. The retrieval process Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 141, number s5, April 2018 S381 is what is of consequence, and it has only rarely have they been cited as regard to the impact factor. The “ ” been described many years ago in scientific evidence. pressure on managing editors to ’ peer-reviewed literature. If on the improve the ranking of the journal The best case reports are written other hand the object retrieved is the will trump the medical editor s by authors who have a remarkable first report of ingestion of something attempt to fulfill an academic mission ability to see connections not causing heretofore-unrecognized every time. We need to recognize that previously appreciated as causal. pathology, then it is case report there is a great deal of arbitrariness In this supplement, you will find material. This was the case with in the way impact factor is currently reports of a mutation of NALCN the then-new miniaturized button designed and in turn promoted as a and its connection to disordered batteries some years ago. A more 29 sign of excellence when the impact breathing,​ hypospadias and its recent example are the packing factor is high. Why use a 2-year relationship to a Wilms “ ” balls that expand in the stomach or 30 interval? Why not use a 3- or 4-year tumor 1 novel gene variant,​ intestine as they take on fluid, leading interval? Should Internet hits (not 27 the association between a to bowel obstruction. Likewise, used in the impact factor) indicating childhood immunodeficiency and novel gene defects of a previously 31 how much an article is read have a panniculitis,​ blue diaper syndrome recognized mutation that lead to 32 role in the calculation? Does it matter and PSCK1 mutations,​ and a specific phenotype only warrant who is citing the article and in what the association of neonatal a report if the novel mutation of journals it is being cited? Because alloimmune thrombocytopenia with that same gene is associated with a it is arbitrary, why not simply pull amegakaryocytosis, B lymphopenia, significant phenotype variation from 33 case reports out of articles counted and villitis. These authors often the known mutation. Novel genotype in the impact factor or develop some are not the same as those with mutations causing previously alternate way for case reports to aptitude to create study design, recognized phenotypes need to be have an effect on the impact factor identify and control variables, and cataloged but do not represent case calculation different from original “ ” provide overall organizational report material. Case reports are not articles? skill to overcome obstacles in first reports of a disease in a part route to completing studies that Each journal needs to allow its of the world that had not previously ’ eventually emerge as original reported this disease unless it “ ” medical editors to focus on its articles. These 2 types of authors is documenting the spread of an academic mission, its raison d etre. are wired differently as much as infectious disease outside its endemic On the basis of its fit into the mosaic the left and the right of the political area. 34 of medical publications, each journal spectrum are wired differently. must use or not use the case report WHAT IS TO BE GAINED OR LOST BY But they need each other. The case to strengthen its message. Journal ELIMINATING CASE REPORTS? report writer who raises questions editors should not be focused on will never add anything to the a flawed rating system that leads scientific database unless those to false idolatry to a number, a questions (hypotheses) are tested in Some have raised concern that there number particularly ill-suited for the controlled ways. The original article is risk in publishing case reports assessment of ideas. writer is always looking for ideas or that are yet to be proven as solid hypotheses to be tested to advance We believe this supplement science. Another worry is that others the cutting edge of science. They are provides the argument for will take a case report for fact and the yin and yang needed to complete continued value of case reports. It initiate treatments that are at best the whole. demonstrates the important role premature or at worst incorrect. that case reports have played and In the supplement that follows, HOW DO WE SAVE THE CASE REPORT? Pediatricswill continue to play in medical the authors of the final article that publications and in particular in appears tested this concern. Bryan . We encourage readers Sisk from WashingtonPediatrics University If the arguments provided here have to consider submitting their case in St Louis, while working as an convinced you that there is lasting reports to future issues of our editorial fellowPediatrics for , decided value in the case report, or if you journal. with colleagues to study how case needed no convincing in the first 28 ACKNOWLEDGMENTS reports from are cited. place, then what strategy needs to be He found that the majority provide applied if the case report is to remain a clear proviso that the citation is a viable genre of medical literature? a case report and with appropriate It is clear that case reports must not I acknowledge Ms Kristina Flathers, caution, regarding its applicability, be handled as original articles with MLIS, medical librarian at Alfred I. Downloaded from www.aappublications.org/news by guest on September 30, 2021 S382 MALATACK 9. Char tier ME, Hart L, Paganelli M, et al. 20. Kim H, Chadwick L, Alzardi Y, et al. HLA- Successful liver transplants for liver A* 31:01 and oxcarbazepine-induced duPont Hospital for Children, for failure associated with pyruvate kinase DRESS in a patient with seizures and research performed in support of this deficiency. Pediatrics. 2018;141(suppl complete DCX deletion. Pediatrics. work and Dr Deborah Consolini for 5):e20163896 2018;141(suppl 5):e20171361 editing work and suggestions to the 10. Sohn B, Park S, Park IK, et al. 21. Mar tini S, Rizzello A, Corsini I, et al. article. Lung volume reduction surgery Vitamin A deficiency due to selective ABBREVIATION for respiratory failure in infants eating as a cause of blindness in with bronchopulmonary dysplasia. a high income setting. Pediatrics. Pediatrics. 2018;141(suppl 2018;141(suppl 5):e20162628 5):e20163901 CSD: cat scratch disease 22. Vakharia J, Matlock K, Taylor H, et al. 11. Ueda K, Serejee F. 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