Case reports

A case report describes the course of an illness or a response to treatment in one patient, or a few, and analyses what was observed, so that other clinicians can use the observation or learn from it. Writing one well turns on whether the case adds anything, which readers it should reach, and the parts that journals and reporting guidelines expect, for human and veterinary patients alike.

What a case report is

Wikipedia's definition describes a case report as a detailed report of the symptoms, signs, diagnosis, treatment and follow-up of an individual patient. ¹ Signs and symptoms form one category, so the definition names at least four parts. ² A case report should also serve a medical, scientific or educational purpose and be evidence-based. ² The EQUATOR Network's page for case reports defines one as a narrative describing, for medical, scientific or educational purposes, a medical problem experienced by one or more patients. ³

The case report, sometimes called the clinical vignette, is probably the oldest model of written medical communication, and many worthwhile clinical observations that do not lend themselves to controlled or scientific study still deserve recording and contribute to medical advance. ⁴ The urge to report a case usually comes from a disease manifestation, a therapeutic outcome or a cluster of oddities so far outside the writer's familiar experience that they feel compelled to share it. ⁴ A case report cannot be written without a case: it needs a patient with a disease, and the sense that something observed in or perhaps done to that patient is unusual. ⁴ In a sense it is a focused review article, set apart by its emphasis on one or more actual cases, a rationale for why the findings are being reported, and an evidence-based analysis of what was found. ⁴ For most clinicians the likeliest route to a published case report is an unusual disease manifestation in a single patient, and such a report must derive its value from the novelty of the finding and the perception that other physicians should be aware of the case. ⁵

A case report can also rest on an unusual twist to the story. ⁴ One report opens on the chief complaint of a 47-year-old woman with Huntington disease, misdiagnosed by a folk healer as the victim of a magic spell: "No puedo quedarme quieta" ("I can't stay still"). ⁴ Another describes a husband and his pregnant wife bitten by the same snake, where, contrary to popular belief, the husband, bitten second, was the more seriously affected. ⁴ Some reports combine the vignette with a literature review, as one on shunt-induced chorea does with 22 references. ⁴

What case reports contribute and why they are written

A medical case report describes and discusses the course of an illness or a response to treatment, and serves two functions: sharing information, and supporting teaching or learning in clinical care. ⁶ In evidence-based practice it can seem that only the well-designed randomised controlled trial has merit, but case reports still have an important role in advancing knowledge, and new diseases and unexpected effects of drugs and procedures may first emerge as case reports. ⁶ This is particularly true of drugs: the patients selected for clinical trials often do not represent the patients treated once a drug is launched, and there are many examples of new information on a drug's actions emerging after it was licensed. ⁶

Case reports are considered the lowest level of evidence, and their findings usually require formal verification through robust epidemiological studies. ⁷ Even so, they can represent the emergence of new issues and key ideas, and can provide important information for patient care that is not detected in clinical trials or in other studies seen as more robust in design. ⁷ They usually describe in detail an individual clinical case showing one of six things: a rare variation of a condition, an unexpected drug adverse event, clues to the pathogenesis of a disease, an unexpected association between factors, a unique therapy, or a unique anatomical variation. ⁷

The reason for writing a particular case up defines its writing style and the information it should contain, and more than one reason may apply. ⁸ The writer should be clear about why the case is being written up. ⁹ The most common reason to write one is to add to the evidence about a disease, drug or procedure: an unusual presentation of a recognised disease, unexpected drug efficacy or, more likely, unusual side effects or interactions, or findings that shed new light on how to recognise or manage unusual patients. ⁸ Another reason to write one is to add to a list of publications, which is less bad than it sounds: for a writer trying to establish a reputation in an area of patient care, published case reports are one way of signalling experience and specialist knowledge. ⁸

A general veterinary journal's author instructions ask that a case report carry veterinary knowledge that makes sense and have educational value, and say it could offer a change in clinical practice, in a diagnostic or prognostic approach, or a new therapeutic approach. ² The same instructions welcome case reports on unusual side effects or adverse interactions, unusual presentations of a disease, new associations or variations in disease processes, a new diagnosis, new management of a disease, a disease never described before, new associations between diseases and symptoms, and new knowledge of a possible pathogenesis. ¹⁰

A first case report

Case reports are interesting to write as well as to read, are based on a real patient the writer was involved with, should make it relatively easy to communicate the enthusiasm felt while investigating the patient, and are usually short enough not to be daunting, which makes them a good way to get started in medical writing. ¹¹

One veterinary journal devoted entirely to case reports supplies a downloadable Word template for a full case report with explanatory guidance written into it, and points authors at an example it considers well presented. ^{12, 13} One veterinarian finds that this helps even an inexperienced author to write a case report, and holds that neither a veterinary nor a human case report is rocket science. ^{13, 14} A medical writer who is also a pet owner can encourage their own vet to think about publishing interesting cases and sharing them with the scientific community. ^{14, 15}

Novelty and the literature search

The first task when considering a case report is a literature review. What the writer has found may be far less uncommon than they believed: a first encounter with an unexpected side effect of a drug does not mean several others have not seen and reported it. ^{4, 16} Prior reports that validate the observation need not prevent writing the report; what makes a great case report is the case-related analysis that advances collective medical knowledge. ⁴ If the search finds one or two similar cases, the case may still be worth documenting, because it adds to the information already reported; if it finds many, acceptance by a worthwhile journal is unlikely, and the better course may be a review article that pulls the reported experience together with the writer's own, or abandoning the exercise. ¹⁶

A claim to be the first report of something can be justified. ¹⁷ For a report that claimed the first case of sensorineural hearing loss after sildenafil, one clinician-author's search of PubMed and Google Scholar found no earlier report, so the claim may be justified. ¹⁷ A new and unexpected side effect of a popular drug of that kind is not extremely rare, and later case reports of such effects are valuable additions to the literature. ¹⁷ A newly discovered syndrome is another matter: a writer should think twice before claiming one, since such a claim may be severely criticised, and if the writer has in fact found the first case ever of something, colleagues rather than the writer should record that primacy. ¹⁷ A report that says no similar case was found should explain where and how the search was made. ¹⁸

A journal can make the search part of the report rather than a preliminary to it. ² Wikipedia's definition of a case report says nothing about reviewing previous cases, while the general veterinary journal's author instructions say the report should include an up-to-date review of all previous cases in the field. ^{1, 2}

Signals of harm or benefit, and the duty to report them

A published case can be the first indication of a new benefit of a treatment in an unexpected patient group, as with anticonvulsants for neuropathic pain or rituximab for rheumatoid arthritis, or the first warning of a side effect that may at worst lead to a drug or procedure being withdrawn, as with rhabdomyolysis and cerivastatin or hepatotoxicity and troglitazone. ⁶ Either way, publication can prompt clinicians to look for similar effects in their own patients, adding to the body of evidence and informing future practice, or to think laterally about a product and its potential. ⁶ A case written to share such information should ideally be written up promptly and published with as short a time lag as possible, particularly where it highlights a side effect or disadvantage of treatment in a particular patient group. ¹⁹

In one clinician-author's view, the highest accolades go to case reports that change what clinicians do in practice. ⁴ An example is a 2001 report of a 38-year-old patient with schizophrenia who suddenly developed diabetes mellitus and ketoacidosis 12 months after starting the atypical antipsychotic olanzapine, one of 30 such reports in the literature including theirs. ⁴ On 10 November 2003, two years after the report was published, a manufacturer's "Dear Healthcare Provider" letter stated that the FDA had asked all manufacturers of atypical antipsychotics to add a warning on hyperglycaemia and diabetes mellitus to their labelling, and this report and others on the topic appear to have prompted the action. ⁴

A veterinarian who meets a very unexpected reaction that need not be notified to any authority should still consider preparing a manuscript when the case is interesting because it is so unusual. ²⁰ One veterinary journal's author instructions, for example, list the case report among the manuscript types it accepts. ²⁰

Off-label use can mean giving an animal a human pharmaceutical because no other pharmaceutical is available. ²¹ One veterinarian, who had not thought it through in detail, holds that an adverse event observed with a product used off-label is certainly worth considering for a case report. ²¹ Whether there is also a mandatory obligation to report it is a separate question. ²¹ One veterinarian sees no reason not to seek publication of an interesting benefit of off-label use, such as an off-label treatment that anecdotally seemed to help a troublesome condition with no established therapy, like a sarcoid. ^{15, 22, 23}

Choosing the journal

Where the case adds to the evidence in a way that may influence patient care, the report should reach the clinicians who care for similar patients. ²⁴ A report is usually fairly easy to publish in the writer's own professional journal, or in a widely distributed free journal, but it may then not reach the clinicians best able to put it to use or to add similar patients of their own. ²⁴ A pharmacist reporting a side effect of a new drug for, say, rheumatoid arthritis should aim at a journal read by the relevant prescribers, not just by pharmacists. ²⁴ The journal should ideally be indexed by a database such as Medline or EmBase, so that a literature search on the topic finds the report. ²⁴ The writer should weigh whether the material merits a national or an international audience, since sticking to the journals they know and read may limit the audience, look at less familiar journals to see whether they routinely publish case reports of the planned type, and ask the colleagues involved in the case which journal they would expect to see it in. ²⁴

A case can also be published as a letter to the editor. ^{4, 24} A single-patient case report can be hard to place in a peer-reviewed journal indexed by health-related search engines, and the chosen journal may take the material as a letter instead. ²⁴ One such letter-style case report, in the correspondence section of the New England Journal of Medicine, describes acetazolamide used to treat lithium-induced diabetes insipidus. ⁴ The veterinary case-report journal also invites shorter contributions: an interesting photograph with a very short description and a short educational message, and an optional image quiz, which it highly encourages, in which the author sends a photograph and asks the reader what they see. ²⁵

Once the journal is chosen, the writer should read back issues that contain case reports and study the guide to authors, because a report written in the style the editors require has a much better chance of being accepted and published fairly promptly. ^{26, 9} The writer should note the recommended word count for a case report or, where there is none, the length of recently published reports, and follow the journal's reference style to the letter. ²⁶ Case reports are generally succinct, and are not meant to be a full or state-of-the-art review of the literature on their topic. ^{26, 17} A report that exceeds 12 double-spaced manuscript pages should be considered for cutting. ¹⁷

Title and key words

A good title encourages people to read the report. ²⁷ It should be snappy but descriptive, so that it is clear what the content will cover. ²⁷ Its level of detail depends partly on the publication, but in general "Liver failure in a 13-year-old following Bordilox therapy" is more likely to catch a reader's attention than "Bordilox therapy as a possible cause of liver failure: a case report in a 13-year-old admitted for appendicitis". ²⁷ Some readers search for key words only in the title of a publication to narrow their literature search, so the key words crucial to the case belong in the title or, where that proves impossible and the journal asks for a list of key words for indexing, in that list. ²⁸ One single-patient report bolstered by a catchy but descriptive title and a literature review is "Risking life and limb: a case of spontaneous muscle infarction (diabetic myonecrosis)". ⁵

The 2013 CARE guidelines for clinical case reporting ask instead for the words "case report" or "case study" in the title beside the phenomenon of greatest interest, and for two to five key words identifying the areas the report covers. ^{29, 30}

The veterinary case-report journal tells its authors otherwise. ¹³ Because every article in it is a case report, its template guidance says there is no need to put "case report" in the title, and adds that authors may be cryptic if they wish. ¹³

Introduction, case description, discussion and conclusion

Once the title is settled, the material the report needs is fairly similar whatever the journal chosen. ²⁸ A report of a 77-year-old woman who developed pseudomembranous colitis without taking antibiotics presents the classic format for a case report: an introduction saying why the case is unusual, since almost all cases reported over the previous three decades had been associated with antimicrobial use; a case description with medical history, physical findings, results of tests and procedures, and treatment; a literature review that found nine non-antibiotic instances; a discussion of intestinal flora and other possible causes; a conclusion that the condition should be considered in persistent diarrhoea once more common causes are ruled out, even without antibiotic use; and sixteen references, a number one clinician-author judges about right. ¹⁷

The introduction usually starts the report by briefly explaining why the case is worth reporting, and aims to show why it is unique or adds to previous literature. ³¹ For a suspected first case of hepatotoxicity linked to a drug, it might set the scene with any current links between hepatic abnormalities and that drug or its class, leaving the full review of the topic to the discussion. ³¹

The case description must include only relevant material, set out in a clear and succinct format, and generally covers the presentation, medical history including relevant family and social history, medication history, physical examination, test results, diagnosis, treatment and outcomes. ³² It need not include every detail or every laboratory result measured, but it must include any relevant information that guided the conclusions, such as investigations that ruled out alternative diagnoses or explain the findings. ³² Every reported test should carry its laboratory reference values, because ranges vary between laboratories and clinicians unused to an uncommon test are unlikely to remember its normal range, which leads to frustration or to the implications of the results being missed. ³³ Where laboratory results are crucial to the case, the writer should consider whether a table or graph expresses them better. ³³ Where photographs, X-rays, scans or microscopic evidence add to the understanding of the case, the writer should consider reproducing them as figures for readers to view rather than just describing them. ³⁴ Diagnostic images greatly enhance a single-patient report, as excellent colour photographs do in one report of an unusual finger lesion in a 53-year-old man. ⁵

The discussion should relate back to the introduction, consider and evaluate every other possible explanation of the findings, and reference its comments wherever possible in the style the journal requests. ¹⁸ All the relevant literature should be reviewed to support the report's comments and conclusions. ⁹ While writing the discussion, the writer should check that any main theme of the case is covered adequately and that it meets the needs of the specialist audience the report is aimed at. ¹⁸ A conclusion may close the report, usually as a succinct summary of the case that includes any implications for future patient care. ³⁵

Whatever the reason for writing it, it is very helpful to have colleagues read and comment on the draft before it goes to a journal, or to a book or manual used for teaching. ³⁶ An objective view from others who were involved in the case, or who have expertise in that type of patient, may save a painful rejection or rewrite, catch missing elements in the flow of the case or its reasoning, and help confirm that it is written at the right level for its readers, which matters most for an unfamiliar journal or one read by clinicians outside the writer's own profession. ³⁶

The CARE checklist and animal patients

The CARE checklist spells out the parts of a case report item by item: ²⁹

• Abstract: what the case adds to the medical literature; the main symptoms, clinical findings, diagnoses, interventions and outcomes; and the main takeaway lessons.
• Introduction: a brief background summary of the case, referencing the relevant medical literature.
• Patient information: demographics; the main symptoms; and medical, family and psychosocial history, including diet, lifestyle and genetic information whenever possible, and relevant comorbidities with their past interventions and outcomes.
• Clinical findings: the relevant physical examination.
• Timeline: the important dates and times in the case, in a table or figure.
• Diagnostic assessment: diagnostic methods; diagnostic challenges, such as financial or cultural ones; diagnostic reasoning, including the other diagnoses considered; and prognostic characteristics, such as staging, where applicable.
• Therapeutic intervention: the types of intervention and how they were administered, including dosage, strength and duration.
• Follow-up and outcomes: outcomes as assessed by clinician and patient, and a summary of the clinical course of all follow-up visits, including important positive or negative follow-up test results, adherence and tolerability, and adverse and unanticipated events.
• Discussion: the strengths and limitations of the case's management; the relevant medical literature; the rationale for the conclusions, including the assessment of cause and effect; and the main takeaway lessons.

^{29, 30}

The EQUATOR Network hosts the CARE guidance for case reports. ³ It is written more for human patients than for veterinary ones, but it is always worth checking for a veterinary case. ³ Its patient-information item does not fit a veterinary patient: demographic details and medical, family and psychosocial history do not transfer to an animal. ³⁷ Of its other items, some are much the same for a veterinary case and some do not fully fit. ³⁸

Adverse-event case reports

The guidelines for submitting adverse-event reports for publication sort what to include into what is required, what is highly desirable and what is needed only if relevant. ³⁹

Part	Required	Highly desirable	If relevant
Title	Consistent with the content of the report
Patient	Age group and sex; the disease or symptoms being treated with the suspect drug; medical history relevant to the adverse event; abnormal physical or laboratory findings; disposition: the presence or absence of death, a life-threatening circumstance, hospitalisation or prolonged hospitalisation, or significant disability	Exact age; body weight; duration of illness; prior exposure to the drug or its class; baseline laboratory findings with the laboratory's normal ranges; status several months after the event	Height; race and ethnicity; severity of the disease or symptoms; previous therapy of the active disease; alcohol, tobacco and substance abuse history; family history; drugs taken by household members; pertinent negative physical findings
Drug	Generic name; approximate dosage; duration of therapy; duration of therapy before the event	Brand name with strength; exact dosage; start and stop dates; route; first and last dose-event intervals	Product formulation; serum or other fluid drug concentrations; restart dates; patient adherence; last dose-resolution interval
Herbal or manufactured product	For a herbal product, the Latin binomial of its herbal ingredients, the plant parts and the type of preparation; for a manufactured product, its proprietary name and producer	For a herbal extract, the type and concentration of the extraction solvent; for a herbal product, whether it is authorised or licensed and whether samples were retained for analysis, with any results	For a manufactured herbal product, whether it was standardised, for which constituents and at what concentrations; for an extract, the drug-to-extract ratio
Concomitant therapies	An assessment of whether they may have contributed	A description of them, including nonprescription, herbal or complementary therapies	Their start and stop doses
Adverse event	Its description and severity against established definitions, using consensus conference criteria whenever possible; its outcome	Onset date; duration	A case definition where more than one patient is involved; any specific treatment of the event
Discussion	The presence or absence of evidence for a causal link, including timing, dechallenge and rechallenge, or why these were not possible; previous reports of the event in biomedical journals and in the product labelling	The diagnostic procedures that confirmed the final diagnosis; biological plausibility; an assessment of competing explanations; prior reports to regulatory agencies	The progress of any planned clinical trials of the event; for a series of such cases, its own reporting recommendations

^{39, 40, 41}

Consent and confidentiality

The patient should always be referred to by an identifier, such as Mr A, to preserve confidentiality. ³² The CARE checklist asks whether the patient gave informed consent, to be provided if requested, and asks that patients share their perspective or experiences whenever possible. ³⁰

Signed consent from the patient is mandatory to publish any case report, and more than one case report has caused distress to the family of a deceased patient. ⁴² In one, a case study in a respiratory journal reported that a bagpipe musician had died from inhaling mould and fungi from his instrument. ⁴² His family had been told that he had a fatal condition called pulmonary fibrosis and that a heart condition had caused his death, so they learned the cause from the published report, and their distress was extensively covered in the UK's mainstream media. ⁴² The paper stated that the patient had given consent, and the journal's co-editor-in-chief said consent had been sought from the family, but the patient's daughter told a retraction-tracking site that neither the next of kin nor the patient had been approached for consent. ⁴² The hospital apologised, but, as of late 2016, the journal had not issued a retraction. ⁴²

The veterinary counterpart of patient consent is informed owner consent: agreement from the owner of the pet or other animal that a case report may be written about it. ^{37, 38}

Case series, herds and flocks

Beside the single-patient report, a second type of case report includes more than one observation: several patients with an uncommon disease, such as an increased incidence of leukaemia in a single neighbourhood, three young adults with argyria, or a cluster of blastomycosis in a rural community. ⁵ A case written to add to the evidence may describe a single patient's experience or a few patients who illustrate the same point. ⁸

Kempen's 2011 checklist for reporting an uncontrolled case series asks the writer to: ³⁰

1. State the hypotheses explicitly.
2. Give the eligibility criteria for subjects explicitly.
3. Describe precisely how treatments were administered or potential risk factors defined.
4. Compare the results with an appropriate external comparison group, and discuss the biases that comparison may bring.
5. Use appropriate statistics whose assumptions are reasonable in the setting.
6. Discuss the biological plausibility of the hypothesis in light of the report's observations.
7. Discuss the report's limitations explicitly, and how future studies could overcome them.

³⁰

The veterinary case is not always one animal. ⁴³ The veterinary journal devoted entirely to case reports asks for a clinically valuable lesson from any field of veterinary practice and accepts the story of a single animal or of a herd, flock or other group managed together. ⁴³ Where chickens are kept in managed groups of thousands, reporting on a single animal does not always make sense, and a report on the entire herd or flock is still one case report. ^{43, 12} The same journal welcomes small case series, and the story should carry clinical interest and educational value rather than resting on novelty or rarity alone. ¹²

For a veterinary case series, the American Veterinary Medical Association's author instructions carry their own guidance for reporting retrospective and prospective case series, somewhat more sophisticated than the single-case checklist. ^{38, 44}

Veterinary worked examples

In one veterinary case report, a pet cockatiel was hospitalised urgently after three drops of tea tree oil were applied directly to the skin of its wing. ^{45, 46} The bird became completely apathetic, and the diagnosis was systemic intoxication by transdermal uptake of the oil. ⁴⁶ A 0.8 mL blood sample from the jugular vein showed severe liver damage and renal involvement on serum biochemistry. ⁴⁷ Treatment was fluid injection and vitamin B12, after which the bird improved within eight hours and was discharged in stable condition after a further 48 hours of hospitalisation. ⁴⁷

The authors' review found reports of intoxication in cockatiels with other substances, such as heavy metals and toxic plants, and nothing on tea tree oil. ⁴⁸ At follow-up the bird came back two weeks later for a second blood sample, and creatine kinase, aspartate transaminase and lactate dehydrogenase had been tenfold, twofold and fivefold higher at the first visit than in that sample. ⁴⁸ The take-home message was not to use tea tree oil on cockatiels, probably not on parakeets, and generally not on parrots. ^{48, 43}

The well-presented example that the case-report journal points its authors to concerns a 19-year-old cat in south-east England with pruritus, hair loss, scaling, crusts and papules, whose owner had developed skin changes and pruritus too. ⁴⁹ The cat had outdoor access, foxes are frequent visitors to gardens in that region, and the cat slept during the day in a presumed fox den and spent the evening on the owner's lap. ^{49, 50} Skin scrapes found round-bodied, short-legged burrowing mites, identified anatomically as Sarcoptes scabiei by their terminal anus and the spikes on their surface. ⁵⁰ The authors' review found no case of feline notoedric mange reported in the UK since the 1960s, and only very infrequent reports of this mite infesting cats worldwide. ⁵⁰ Treatment was selamectin twice, four weeks apart; the owner's pruritic rash resolved within two to four weeks of the cat's first treatment without the owner being treated, and the crusts resolved completely after the second application. ⁵¹ The suspected chain of transmission was fox to cat to human. ⁵¹

A case report in the Journal of the American Veterinary Medical Association concerns a 12-year-old, 10 kg female shusui koi with a swelling on the left body wall, reduced appetite and reduced activity. ⁵² Anaesthetic was added to the water, whole-body computed tomography showed a fat-opaque mass within the muscle, and a biopsy examined histologically identified a lipoma. ^{52, 53} The mass was excised surgically, and the fish was kept for three weeks afterwards in salt-containing water, with no antimicrobials and no analgesics. ⁵³ Appetite and activity improved immediately after surgery with no sign of discomfort, and a five-week follow-up found the incision healed and a repeat scan showing no regrowth. ^{53, 54}