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The real malady of Marcel Proust and what it reveals about diagnostic errors in medicine
Medical Hypotheses 90 (2016) 14–18
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Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
The real malady of Marcel Proust and what it reveals about diagnostic errors in medicine Yellowlees Douglas ⇑ Clinical and Translational Science Institute, University of Florida, Gainesville, FL 32611-7150, USA
a r t i c l e
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Article history: Received 13 January 2016 Accepted 27 February 2016
a b s t r a c t Marcel Proust, author of À La Recherche du Temps Perdu, was considered a hypochondriac not only by the numerous specialists he consulted during his lifetime but also by every literary critic who ventured an opinion on his health, among them several clinicians. However, Proust’s voluminous correspondence, as detailed in its attention to his every symptom as his novel, provides valuable clues to Proust’s real, organic, and rare illness. Proust, in fact, was not only genuinely ill but far sicker than he even he believed, most likely suffering from the vascular subtype of Ehlers–Danlos Syndrome. Ironically, Proust’s own doctors and his clinician-critics replicated the same kinds of diagnostic errors clinicians still routinely make today, shedding light on the plight of patients with rare illnesses. Ó 2016 Elsevier Ltd. All rights reserved.
Introduction
Hypothesis
Literary history teems with hypochondriacs, but none as famous or prolix as Marcel Proust, who lovingly documented his every ache, fever and bout of dyspepsia in a correspondence nearly as voluminous as the pages of his novel À La Recherche du Temps Perdu. No commentary on Proust is complete without mention of his hypochondria, evidenced most recently in Alain de Botton’s How Proust Can Save Your Life, [1] just as no history of famous hypochondriacs is complete without mention of Proust, who cropped up most recently in Brian Dillon’s recent Nine Hypochondriacs [2]. The ranks of commentators on Proust’s hypochondria even include several clinicians [3,4], one of whom dedicated an entire monograph to Proust’s morbid preoccupation with his own ill health which, every commentator agrees, amounted to little more than relatively mild asthma exacerbated by peculiar dietary, sleep, and living habits. This picture of Proust has only a single, but rather substantial problem, lurking in it. The same loving catalogue of aches and fevers also reveals that Proust was suffering from an organic and visceral illness. In fact, if one reads Proust’s correspondence with an eye not toward branding him a self-obsessed neurasthenic but toward understanding what afflicted him, one understands that Proust was not only genuinely ill—but almost certainly more seriously ill than even he imagined himself to be.
The more one considers Proust’s case, the more striking and puzzling the unanimous agreement about his hypochondria. However, the explanation for his literary critics’ reactions is simple. No one who complained of ill health at such length and in such detail could be genuinely ill and still manage an output of three million published words in a career begun relatively late in life. In contrast, the response of the clinicians requires more unraveling and sheds some light on diagnostic errors in medicine—and on the fate of patients with rare, multi-systemic diseases. Proust, as a differential diagnosis of his extensively-chronicled symptoms reveals, most likely suffered from Ehlers–Danlos Syndrome, the somatic disorder that accounts comprehensively for every one of his multi-factorial and multi-systemic symptoms that so puzzled his doctors.
⇑ Tel.: +1 (352) 273 3215. E-mail addresses: [email protected], yellowleesdouglas@icloud. com http://dx.doi.org/10.1016/j.mehy.2016.02.024 0306-9877/Ó 2016 Elsevier Ltd. All rights reserved.
Evidence What ailed Proust: a differential diagnosis On one point, Proust’s commentators all agree: the writer suffered from asthma, evident from his first attack at age ten. If we disregard the belief, held by clinicians in Proust’s day through the fifties, that asthma resulted from a morbid craving for maternal affection [5], what is most striking about Proust’s symptoms is that complaints about his breathing account for less than half his reports on his bodily afflictions. The rest concern the state of his stomach and bowels, with a small proportion dedicated to bodily aches and pains, as well as intermittent fevers departing as mysteriously as they arrive. Nor were these complaints due to either
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Proust’s predilection for self-medicating or to the bizarre practices he adopted to avoid what he believed were triggers for his asthma. These practices included seldom venturing outdoors in daylight and remaining shut in a sealed bedroom, burning fumigation powders, lying swaddled in blankets and coats before a fire that blazed year-round. On the contrary, his complaints about his sinuses, stomach, bowels, and joints long pre-date his attempts to accommodate them, as evidenced in early letters to his mother during a period in which he was living and eating normally. Most significantly, Proust’s letters chronicle a long history of gastrointestinal complaints, including bloating, stomach pain, diarrhea and what gastroenterologists would recognize as early satiety. If he drank more than a quarter-glass of Vichy water prior to bedtime, nine or ten hours after consuming his evening meal [6], he reported feeling full. By his late twenties, Proust complained of being unable even to lie down, let alone sleep, within eight hours of eating. These same symptoms also afflicted his father’s sister, Élisabeth Amiot, the model for Tante Leonie in À La Recherche du Temps Perdu and an invalid for much of her life [6]. While some of the digestive problems Proust describes could be caused by dyspepsia, his early satiety and feeling full for prolonged periods after eating point to a single possibility: gastroparesis or significantly delayed gastric emptying. While standards vary among gastroenterologists in classifying the length of the delays in gastroparesis, most agree that any patient with more than 10% of a meal retained after four hours exhibits some degree of gastroparesis with severe cases involving delays of anywhere from five to sixteen hours [7]. Gastroparesis results in bloating, abdominal discomfort, refractory gastroesophageal reflux or GERD, and chronic nausea with vomiting and occasional diarrhea stemming from the stomach simply dumping its contents, largely undigested, after hours of gastric inactivity [8]. In his correspondence, Proust complains of every one of these symptoms associated with gastroparesis, in addition to numerous sore throats, most likely the product of GERD. Proust’s gastroparesis was also responsible for his celebrated abstemious diet, widely reported in his correspondence and confirmed by his housekeeper to have consisted during the last decades of his life of a croissant and two bowls of café au lait [9]. If Proust’s gastric emptying were delayed for anything approaching the six to eight hours he reports, his gastroparesis was both severe and far from imaginary. But his gastroparesis also holds the key to what really ailed the writer, as gastroparesis can be symptomatic of serious, multi-systemic disorders. While 8% of patients contract gastroparesis through viral infection [10], Proust, a scrupulous reporter of sniffles, aches, and bloating, never reports anything approaching the symptoms of a gastrointestinal infection. Nor does he report symptoms congruent with the other common causes of gastroparesis, which include diabetes or the use of opiods [11] like the heroin he once asked his mother to procure for him [12]. While the use of opiods can cause both gastroparesis and the constipation Proust occasionally reported, he only reported taking trional and heroin years after he first mentioned symptoms of gastroparesis [12]. Ironically, the sedatives and painkillers Proust used to dampen the discomfort caused by his gastroparesis ended up exacerbating the very symptoms he was attempting to alleviate [13]. During his last months, Proust suffered from edema and also reported results of an earlier urinalysis that found glucose in his urine, which could have resulted from diabetes. But, given Proust’s complaint that he urinated very little for years [6], his symptoms are hardly congruent with the excessive thirst, frequent urination, and complications that would have accompanied diabetes, especially given a diet consisting almost solely of carbohydrates that would have exacerbated the disease. Proust is equally unlikely to have suffered from the other diseases most likely to have caused his gastroparesis, which include
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lupus and hypothyroidism, as well as infections such as tuberculosis and syphilis. Contemporaries described Proust as ‘‘wraithlike” even during the years when he was attempting to eat robust meals [12], exhibiting the pallor, loss of appetite, and weight loss consistent with tuberculosis [14]. Proust, of course, had a prolonged cough, also consistent with a diagnosis of TB. However, the writer’s cough was notably non-productive, even during his final weeks, when his brother, clinician Robert Proust, was certain the writer suffered from a lung abscess [9]. Moreover, if tuberculosis were the source of Proust’s cough, not asthma, giving rise to the fatigue, weight loss, and gastroparesis that afflicted Proust from his childhood onward, the disease would have progressed during the writer’s adulthood, with the secondary TB lesions spreading to other parts of the body, most commonly the kidneys, lymph nodes, brain, and bones. However, Proust neither exhibited evidence of any other symptoms of TB, nor did his brother or the veritable army of other specialists he saw ever diagnose him with TB. Proust’s malaise, fatigue, and gastroparesis are also symptomatic of hypothyroid disease, which could also have caused his alternating bouts of diarrhea and constipation [10,15]. Proust’s sensitivity to cold is also consistent with a diagnosis of hypothyroidism [16]. However, Proust never reports any of the other symptoms hypothyroidism would have also caused, particularly the hoarse voice and dry skin that are most commonly linked to the condition, which also tends to affect women far more commonly than men [16]. Similarly, Proust, who had his symptoms and even his urine scrutinized by clinicians throughout his life, also never exhibited signs of syphilis, which in its primary stage, would have resulted in a chancre, albeit one on the writer’s penis or rectum, a place he was unlikely to have invited a clinician to inspect. Moreover, Proust, in his a letter to his brother, written in his thirties, asks his brother whether he should be taking calomel and sugar or mercury enemas, ostensibly for the worms he believes are causing his asthma [12]. Mercury had been long used as a cure for syphilis, which doctors had discovered was poorly absorbed by the bowel but worked best when administered orally as mercurous chloride—known as calomel [17]. Moreover, metallic mercury was also commonly used as treatment for syphilis, administered via fumigation [17], and Proust was notorious for burning fumigation powders throughout his adult life. However, throughout the nineteenth and early twentieth century, calomel was also used widely as both a cathartic and diuretic. In addition, fumigation powders were commonly employed as treatment for asthma. Maimonides was the first to counsel patients with asthma to raise the temperatures of their sick rooms through the burning of herbs, and the practice continued intro Proust’s day [18]. Furthermore, by the late 1880 s, bismuth had largely replaced calomel as treatment of syphilis, with bismuth itself being replaced by the end of World War I by salvarsan [17]. If the evidence is mixed whether Proust suffered from syphilis, however, syphilis is unlikely to have caused Proust’s gastroparesis, as he failed to exhibit the most common symptom of secondary or tertiary syphilis, the macular rash found on nearly 90% of syphilis patients [19], despite exhibiting the sore throat, malaise, weight loss, anorexia, and ocular complaints also common to secondary syphilis. Moreover, stomach and bowel dysfunction are symptomatic of tabes dorsalis, a development of late neurosyphilis, which is accompanied by sensory ataxia. Had Proust’s neurosyphilis caused his gastroparesis, it would also have caused ataxia, first becoming evident by making Proust unsteady while walking in the dark, then developing into worsening balance and difficulty maintaining a normal gait [20]. As Proust never exhibited any difficulties with his balance or walking and confined his social calls during the latter part of his life to late-night hours, he is highly unlikely to have suffered from neurosyphilis.
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Proust certainly had symptoms consistent with another disease that could have caused his gastroparesis: lupus. Systemic lupus erythematosus has multiple symptoms congruent with Proust’s complaints about his ill-health [21], particularly the joint soreness he reported sporadically from his twenties until his death [6,12]. He also reported the fatigue that afflicts patients with lupus [22], fevers [23], and protein in his urine [6], as well as what might easily have been pleurisy rather than pneumonia during his final, fatal illness [9,24], all of which point toward lupus, known to rheumatologists for its ability to mimic multiple diseases. According to the criteria developed by the American College of Rheumatology, any four of the eleven criteria established for lupus is sufficient to suggest a high probability a patient might have lupus [25]—making Proust’s symptoms consistent with a diagnosis of lupus. However, lupus disproportionately strikes women of childbearing age [25], involving over 90% of cases [26]. Proust moreover reported his first asthma attack having occurred when he was ten, a very young age for onset of the disease that would have made Proust’s survival into adulthood—even if he had received today’s standard of care—highly unlikely. Furthermore, while lupus can inflame the lining of the lungs, resulting in pleurisy, Proust’s pulmonary symptoms were definitely asthmatic, causing him to wheeze painfully, rather than struggle with the chest pain and shortness of breath caused by pleurisy or by lesions in the lungs that simulate pneumonia, commonly experienced by lupus patients [25], which Proust would likely have experienced long before his last months. Lupus also seldom causes the symptoms of acute sinusitis and asthma suffered by Proust. Although Proust might conceivably have suffered from lupus, lupus patients rarely go a lifetime, particularly one stocked with so many symptoms of a profound systemic disorder, without exhibiting at least once the classic ‘‘butterfly” or malar rash that is one of the most identifiable characteristics of a disease that can often evade ready diagnosis. Proust, for all his painstaking notes on his fevers, aches, and even itches, never once mentions a rash, let alone the alopecia, hyperor hypopigmentation, deep nodules, or blisters characteristic of lupus [25]. Proust’s gastroparesis could also have been caused by sarcoidosis, a rare disorder with a familial origin indicative of inherited predispositions to the disease, which tends to occur more frequently in people in African or Ashkenazi descent [27]. Since Proust’s maternal grandmother was an Ashkenazi Jew, and the disease, while rare, affects about one in every 10–20,000 people [27], Proust may have suffered from sarcoidosis, a condition thought to occur from an auto-immune reaction to infection that causes lumps of inflammatory cells, called granulomas, that occur throughout the body [28]. Proust’s ostensible asthma would thus have stemmed from scarring in his lungs [29], caused by the same sarcoidosis that compromised the action of his digestive tract and also prompted the fatigue, fever, and weakness reported so frequently by Proust. However, Proust displayed difficulty breathing during his first decade, a rare occurrence if he suffered from sarcoidosis, which usually develops during the third or fourth decades of life [28]. And sarcoidosis is similarly unlikely to have accounted for his gastroparesis, as sarcoidosis has gastric effects in less than 1% of cases [30]. Even in this rare subset of patients, sarcoidosis granulomas generally cause abdominal discomfort, nausea, vomiting, diarrhea, and weight loss—but not the early satiety reported so frequently by Proust. In the end, Proust’s gastroparesis is most likely to have been caused by a profoundly multi-systemic disorder like Marfan or Ehlers–Danlos syndromes, both of which can cause delayed gastric emptying. Resulting from an inherited tendency to overproduce fibrillin, as in Marfan Syndrome, or from a hereditary predisposition to overproduce collagen in Ehlers–Danlos Syndrome, either
disorder could account for not only Proust’s gastroparesis and alternating bouts of constipation and diarrhea but also his catalogue of aching joints, the vision problems he complained of during his last decade, and both his sinus and pulmonary issues. However, Marfan patients tend to have marked physical characteristics that include scoliosis, flat feet, crowded teeth, long, thin fingers, and the tall, thin build similar to that of famous Marfan case Abraham Lincoln [31]. Proust also did not report other classic Marfan characteristics, including an unusual growth spurt during early puberty or myopia in childhood, although Marfan patients may have only one or more of these physical characteristics [32]. Proust’s symptoms seem more closely allied with one of the types of Ehlers–Danlos Syndrome (EDS), which could account for the transitory joint pain that moved from wrist to elbow to knee and then mysteriously resolved in a way markedly unlike arthritis. EDS could also account for Proust’s poor sinus and lung motility, which resulted in chronic sinusitis and asthma, for his low-grade fevers, and for the sporadic fatigue about which he complained for much of his life. Had Proust suffered from EDS, both his fatigue and his celebrated inability to keep warm—which caused Proust to attend formal functions swaddled in coats and to maintain a blazing fire year-round in his Paris bedroom—would have stemmed from an excess of collagen affecting the ability to his endothelium to constrict [33]. Instead, lacking in tone, his endothelium would have been unable to constrict or dilate in reaction to the demands of gravity and the temperature of Proust’s environment, giving him orthostatic hypotension and a profound sensitivity to cold. Tellingly, Proust was able to maintain a voluminous correspondence on top of an outpouring of three million words of published prose during a career begun late in life—mostly by remaining in bed and thus avoiding the fatiguing effects of his orthostatic hypotension. And Proust also notably complained of being cold all over, rather than exclusively in his hands or just his extremities, which would have made his condition similar to Raynaud phenomenon and thus congruent with mixed connective tissue disease (MCTD), which shares clinical symptoms similar to Proust’s with both lupus and EDS [34]. Strikingly, Proust reacted to his symptoms by taking to his bed as a lifelong invalid, imitating his father’s sister, who also suffered from the same fatigue, fevers, and symptoms of gastroparesis, suggesting a hereditable disorder. Ultimately, Proust’s symptoms match closely with those suffered by patients diagnosed with EDS—and thus also suggest several factors responsible for his demise at the comparatively early age of 51. Less than a month before the writer’s death, his brother, a clinician like their father, breezily reported that Marcel was suffering from a treatable and easily cured pneumococcal infection. After his brother’s rapid decline, Robert Proust declared that Marcel had died from a ruptured lung abscess, even though no autopsy was ever performed and no diagnostic tool more sophisticated than a stethoscope ever used on the writer. According to the writer’s housekeeper, Robert Proust believed that his brother’s abscess ruptured, and septicemia ultimately killed Marcel. However, housekeeper Céleste Albaret, insisted that the writer had a nonproductive cough, producing no sputum whatever [9], let alone the hemoptysis that accompanies lung abscesses. Furthermore, recent studies have debunked clinicians’ abilities to detect either pneumonia or lung abscesses based on breath sounds alone [35], and lung abscesses are notoriously difficulty to diagnose, even with sophisticated imaging technologies like CT scans first used a halfcentury after Proust’s demise. Although Proust never reported any of the joint instability consistent with the hypermobility type of EDS or the tendon or ligament herniation typical of the deadlier vascular type, the syndrome is a spectrum disorder, with even patients with vascular type EDS displaying none of its typical hallmarks [35]. However, patients with either type of EDS display a tendency toward arterial
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tears, dissections, aneurysms, pulmonary cysts, and pneumothorax. If Proust suffered from EDS, pulmonary cysts or pneumothorax could explain his rapid and seemingly inexplicable decline, especially if Proust had vascular type EDS. Ironically, even if Proust had been diagnosed today with vascular type EDS, which can be identified through genetic testing, his demise at fifty-one is congruent with the life expectancy for these patients, even given the vast improvement in diagnostics and treatments available eighty years after Proust’s death [36]. Proust, however, might also have died from complications resulting from his severe gastroparesis, which could have led to his having aspirated food particles while laying down due to overwhelming reflux, developing the pneumonia sometimes seen in gastroparesis patients [37]. Or his worsening dyspepsia and early satiety, which limited his diet to coffee and the purée one friend begged him to eat, could have resulted in malnutrition. Had his malnutrition been profound, Proust would have experienced a selenium deficiency—certainly possible, given the extremities of his diet—resulting in congestive heart failure, a compromised immune system, and the development of pneumonia from a mild upper respiratory infection [38]. No matter what initially ailed Proust, whatever caused his gastroparesis most likely lies at the root of what killed him. And, as this differential diagnosis of his extensively-reported symptoms reveals, Ehlers–Danlos Syndrome remains the most likely cause of his gastroparesis. Proust was a zebra: availability and Sutton’s Law None of his critics has considered the possibility that Proust, far from shamming, was genuinely ill. However, a genuinely ill Proust fosters an entirely different understanding of his work. In this view, the exquisitely attuned sensibilities on display throughout his masterpiece are of a piece with the attention Proust displayed toward his health in his correspondence. Proust might well have observed the world as he did, alive to every shifting sensation, because nothing in his body quite behaved as it should. Proust himself would have been acutely aware of the irony in producing a masterpiece while genuinely ill, while the rest of the world believed his illness the product of an overactive imagination and a lifelong bid for sympathy. He might even have completed his novel not in spite of his genuine illness but because of it, his perspective shaped intensely by his awareness of his body’s own susceptibility. In fact, studies have established the role of the insula in the perception of pain, demonstrating both that the insular cortex also registers pain and irregular symptoms in patients who routinely experience pain [39], at the same time researchers have established the insula’s key role in establishing our sense of both bodily pereption and agency [40]. Ironically, the same affliction that merely made his Tante Élisabeth take to her bed could well have made Proust an intent observer of his own body, minutely aware of its functions in a way that the truly healthy can never know. Perhaps, in the end, Proust was able to write À La Recherche du Temps Perdu not in spite of but expressly because of the malady with which he was born and which ultimately ended his life. What is particularly compelling about Proust’s case is the unanimity in his critics’ verdict that he suffered from little more than a mild case of asthma and profound hypochondria. Even to the clinicians among his critics, his catalogue of symptoms were interpreted as merely neurasthenic bids for attention, just as they were by the well-regarded clinicians in Proust’s own family, his father and brother. Nevertheless, a close reading of his critics’ verdicts also sheds light on diagnostic errors in medicine, explaining why at least four seasoned clinicians, all with experience in multiple areas in medicine, read Proust’s somatic illness as purely imaginary.
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In fact, Proust’s misdiagnoses, some of them arrived at by modern clinicians with considerably more diagnostic resources to hand than Proust’s own doctors or brother, illustrate common diagnostic errors in medicine. These clinicians were all influenced by availability [41], a bias toward the diseases they encountered most frequently, like the neurasthenia clinicians saw so frequently in the late nineteenth and early twentieth centuries [9,12]. The earlier diagnoses, in turn, influenced the judgments of the late twentieth-century clinicians who examined Proust’s case [3,4]. In this instance, the clinicians were partially influenced by the initial diagnoses, which can lead to an error first identified by the behavioral economists who classified some of the errors that decisionmakers of all kinds, including clinicians, fall prey to. That error, anchoring, occurs when clinicians fail to revise an initial diagnosis, even when potentially conflicting information becomes available [42]. In the clinicians considering Proust’s case, anchoring also served to bestow on the diagnoses of Proust’s own doctors and his brother greater validity than they deserved, especially given the late-twentieth century clinicians’ awareness of just how incomplete medical knowledge was during an era before the discovery of antibiotics. But the availability bias has a complement that might have also made clinicians less likely to identify the rare disorder which really afflicted Proust. Sutton’s Law is a diagnostic dictum that cautions young doctors, ‘‘When you hear hoof beats, think horses, not zebras” [43]. Supposedly named for the bank robber Willie Sutton, who said he robbed banks because that was where the money was, Sutton’s Law might well have taken shape to counter the availability biases of medical students. Exposed to an encyclopedic range of conditions and diseases, many of them rare, medical students endure testing that focuses less on common diseases than on syndromes they are infinitely more likely to encounter in a textbook than in clinic. During their initial consults with patients, Sutton’s Law reminds residents and young clinicians to diagnose wheezing and shortness of breath as asthma, probably exacerbated by sleeping in a smoky room. Useful for the average patient, Sutton’s Law also increases the likelihood that a zebra like Proust today would have received no more accurate medical treatment than he had eighty years ago. Today, patients with rare disorders—Sutton’s zebras—typically require years of persistent visits to clinics, demands for referrals, and both the financial means and selfconfidence to persist in the process of repeated consults and misdiagnoses.
Conclusions Ironically, even if Proust were correctly diagnosed—after the years required by most patients with rare diseases to obtain correct diagnoses—he would not necessarily receive much better care today than he did in the early twentieth century. Today, modern medicine, balkanised into specializations with minimal interaction between them, poses a particular dilemma for patients with profoundly multi-systemic disorders like Ehlers–Danlos and Marfan syndromes, schleroderma, lupus, sarcoidosis, and mixed connective tissue disease. Currently, these multi-systemic disorders are typically treated by rheumatologists, who tend to administer pain management and focus on issues involving patients’ soft tissues. But these disorders can affect virtually every system in the body, requiring not only follow-up from nearly every specialization from ophthalmology to gastroenterology but patients sufficiently well educated to understand how they need to manage their own wellbeing. We like to think that, with the advances medicine has made over the past eighty years, Proust would have enjoyed a correct diagnosis, sympathy, and a life span considerably longer than the fifty-one years he enjoyed. But, the more closely one examines
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Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
The real malady of Marcel Proust and what it reveals about diagnostic errors in medicine Yellowlees Douglas ⇑ Clinical and Translational Science Institute, University of Florida, Gainesville, FL 32611-7150, USA
a r t i c l e
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Article history: Received 13 January 2016 Accepted 27 February 2016
a b s t r a c t Marcel Proust, author of À La Recherche du Temps Perdu, was considered a hypochondriac not only by the numerous specialists he consulted during his lifetime but also by every literary critic who ventured an opinion on his health, among them several clinicians. However, Proust’s voluminous correspondence, as detailed in its attention to his every symptom as his novel, provides valuable clues to Proust’s real, organic, and rare illness. Proust, in fact, was not only genuinely ill but far sicker than he even he believed, most likely suffering from the vascular subtype of Ehlers–Danlos Syndrome. Ironically, Proust’s own doctors and his clinician-critics replicated the same kinds of diagnostic errors clinicians still routinely make today, shedding light on the plight of patients with rare illnesses. Ó 2016 Elsevier Ltd. All rights reserved.
Introduction
Hypothesis
Literary history teems with hypochondriacs, but none as famous or prolix as Marcel Proust, who lovingly documented his every ache, fever and bout of dyspepsia in a correspondence nearly as voluminous as the pages of his novel À La Recherche du Temps Perdu. No commentary on Proust is complete without mention of his hypochondria, evidenced most recently in Alain de Botton’s How Proust Can Save Your Life, [1] just as no history of famous hypochondriacs is complete without mention of Proust, who cropped up most recently in Brian Dillon’s recent Nine Hypochondriacs [2]. The ranks of commentators on Proust’s hypochondria even include several clinicians [3,4], one of whom dedicated an entire monograph to Proust’s morbid preoccupation with his own ill health which, every commentator agrees, amounted to little more than relatively mild asthma exacerbated by peculiar dietary, sleep, and living habits. This picture of Proust has only a single, but rather substantial problem, lurking in it. The same loving catalogue of aches and fevers also reveals that Proust was suffering from an organic and visceral illness. In fact, if one reads Proust’s correspondence with an eye not toward branding him a self-obsessed neurasthenic but toward understanding what afflicted him, one understands that Proust was not only genuinely ill—but almost certainly more seriously ill than even he imagined himself to be.
The more one considers Proust’s case, the more striking and puzzling the unanimous agreement about his hypochondria. However, the explanation for his literary critics’ reactions is simple. No one who complained of ill health at such length and in such detail could be genuinely ill and still manage an output of three million published words in a career begun relatively late in life. In contrast, the response of the clinicians requires more unraveling and sheds some light on diagnostic errors in medicine—and on the fate of patients with rare, multi-systemic diseases. Proust, as a differential diagnosis of his extensively-chronicled symptoms reveals, most likely suffered from Ehlers–Danlos Syndrome, the somatic disorder that accounts comprehensively for every one of his multi-factorial and multi-systemic symptoms that so puzzled his doctors.
⇑ Tel.: +1 (352) 273 3215. E-mail addresses: [email protected], yellowleesdouglas@icloud. com http://dx.doi.org/10.1016/j.mehy.2016.02.024 0306-9877/Ó 2016 Elsevier Ltd. All rights reserved.
Evidence What ailed Proust: a differential diagnosis On one point, Proust’s commentators all agree: the writer suffered from asthma, evident from his first attack at age ten. If we disregard the belief, held by clinicians in Proust’s day through the fifties, that asthma resulted from a morbid craving for maternal affection [5], what is most striking about Proust’s symptoms is that complaints about his breathing account for less than half his reports on his bodily afflictions. The rest concern the state of his stomach and bowels, with a small proportion dedicated to bodily aches and pains, as well as intermittent fevers departing as mysteriously as they arrive. Nor were these complaints due to either
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Proust’s predilection for self-medicating or to the bizarre practices he adopted to avoid what he believed were triggers for his asthma. These practices included seldom venturing outdoors in daylight and remaining shut in a sealed bedroom, burning fumigation powders, lying swaddled in blankets and coats before a fire that blazed year-round. On the contrary, his complaints about his sinuses, stomach, bowels, and joints long pre-date his attempts to accommodate them, as evidenced in early letters to his mother during a period in which he was living and eating normally. Most significantly, Proust’s letters chronicle a long history of gastrointestinal complaints, including bloating, stomach pain, diarrhea and what gastroenterologists would recognize as early satiety. If he drank more than a quarter-glass of Vichy water prior to bedtime, nine or ten hours after consuming his evening meal [6], he reported feeling full. By his late twenties, Proust complained of being unable even to lie down, let alone sleep, within eight hours of eating. These same symptoms also afflicted his father’s sister, Élisabeth Amiot, the model for Tante Leonie in À La Recherche du Temps Perdu and an invalid for much of her life [6]. While some of the digestive problems Proust describes could be caused by dyspepsia, his early satiety and feeling full for prolonged periods after eating point to a single possibility: gastroparesis or significantly delayed gastric emptying. While standards vary among gastroenterologists in classifying the length of the delays in gastroparesis, most agree that any patient with more than 10% of a meal retained after four hours exhibits some degree of gastroparesis with severe cases involving delays of anywhere from five to sixteen hours [7]. Gastroparesis results in bloating, abdominal discomfort, refractory gastroesophageal reflux or GERD, and chronic nausea with vomiting and occasional diarrhea stemming from the stomach simply dumping its contents, largely undigested, after hours of gastric inactivity [8]. In his correspondence, Proust complains of every one of these symptoms associated with gastroparesis, in addition to numerous sore throats, most likely the product of GERD. Proust’s gastroparesis was also responsible for his celebrated abstemious diet, widely reported in his correspondence and confirmed by his housekeeper to have consisted during the last decades of his life of a croissant and two bowls of café au lait [9]. If Proust’s gastric emptying were delayed for anything approaching the six to eight hours he reports, his gastroparesis was both severe and far from imaginary. But his gastroparesis also holds the key to what really ailed the writer, as gastroparesis can be symptomatic of serious, multi-systemic disorders. While 8% of patients contract gastroparesis through viral infection [10], Proust, a scrupulous reporter of sniffles, aches, and bloating, never reports anything approaching the symptoms of a gastrointestinal infection. Nor does he report symptoms congruent with the other common causes of gastroparesis, which include diabetes or the use of opiods [11] like the heroin he once asked his mother to procure for him [12]. While the use of opiods can cause both gastroparesis and the constipation Proust occasionally reported, he only reported taking trional and heroin years after he first mentioned symptoms of gastroparesis [12]. Ironically, the sedatives and painkillers Proust used to dampen the discomfort caused by his gastroparesis ended up exacerbating the very symptoms he was attempting to alleviate [13]. During his last months, Proust suffered from edema and also reported results of an earlier urinalysis that found glucose in his urine, which could have resulted from diabetes. But, given Proust’s complaint that he urinated very little for years [6], his symptoms are hardly congruent with the excessive thirst, frequent urination, and complications that would have accompanied diabetes, especially given a diet consisting almost solely of carbohydrates that would have exacerbated the disease. Proust is equally unlikely to have suffered from the other diseases most likely to have caused his gastroparesis, which include
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lupus and hypothyroidism, as well as infections such as tuberculosis and syphilis. Contemporaries described Proust as ‘‘wraithlike” even during the years when he was attempting to eat robust meals [12], exhibiting the pallor, loss of appetite, and weight loss consistent with tuberculosis [14]. Proust, of course, had a prolonged cough, also consistent with a diagnosis of TB. However, the writer’s cough was notably non-productive, even during his final weeks, when his brother, clinician Robert Proust, was certain the writer suffered from a lung abscess [9]. Moreover, if tuberculosis were the source of Proust’s cough, not asthma, giving rise to the fatigue, weight loss, and gastroparesis that afflicted Proust from his childhood onward, the disease would have progressed during the writer’s adulthood, with the secondary TB lesions spreading to other parts of the body, most commonly the kidneys, lymph nodes, brain, and bones. However, Proust neither exhibited evidence of any other symptoms of TB, nor did his brother or the veritable army of other specialists he saw ever diagnose him with TB. Proust’s malaise, fatigue, and gastroparesis are also symptomatic of hypothyroid disease, which could also have caused his alternating bouts of diarrhea and constipation [10,15]. Proust’s sensitivity to cold is also consistent with a diagnosis of hypothyroidism [16]. However, Proust never reports any of the other symptoms hypothyroidism would have also caused, particularly the hoarse voice and dry skin that are most commonly linked to the condition, which also tends to affect women far more commonly than men [16]. Similarly, Proust, who had his symptoms and even his urine scrutinized by clinicians throughout his life, also never exhibited signs of syphilis, which in its primary stage, would have resulted in a chancre, albeit one on the writer’s penis or rectum, a place he was unlikely to have invited a clinician to inspect. Moreover, Proust, in his a letter to his brother, written in his thirties, asks his brother whether he should be taking calomel and sugar or mercury enemas, ostensibly for the worms he believes are causing his asthma [12]. Mercury had been long used as a cure for syphilis, which doctors had discovered was poorly absorbed by the bowel but worked best when administered orally as mercurous chloride—known as calomel [17]. Moreover, metallic mercury was also commonly used as treatment for syphilis, administered via fumigation [17], and Proust was notorious for burning fumigation powders throughout his adult life. However, throughout the nineteenth and early twentieth century, calomel was also used widely as both a cathartic and diuretic. In addition, fumigation powders were commonly employed as treatment for asthma. Maimonides was the first to counsel patients with asthma to raise the temperatures of their sick rooms through the burning of herbs, and the practice continued intro Proust’s day [18]. Furthermore, by the late 1880 s, bismuth had largely replaced calomel as treatment of syphilis, with bismuth itself being replaced by the end of World War I by salvarsan [17]. If the evidence is mixed whether Proust suffered from syphilis, however, syphilis is unlikely to have caused Proust’s gastroparesis, as he failed to exhibit the most common symptom of secondary or tertiary syphilis, the macular rash found on nearly 90% of syphilis patients [19], despite exhibiting the sore throat, malaise, weight loss, anorexia, and ocular complaints also common to secondary syphilis. Moreover, stomach and bowel dysfunction are symptomatic of tabes dorsalis, a development of late neurosyphilis, which is accompanied by sensory ataxia. Had Proust’s neurosyphilis caused his gastroparesis, it would also have caused ataxia, first becoming evident by making Proust unsteady while walking in the dark, then developing into worsening balance and difficulty maintaining a normal gait [20]. As Proust never exhibited any difficulties with his balance or walking and confined his social calls during the latter part of his life to late-night hours, he is highly unlikely to have suffered from neurosyphilis.
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Proust certainly had symptoms consistent with another disease that could have caused his gastroparesis: lupus. Systemic lupus erythematosus has multiple symptoms congruent with Proust’s complaints about his ill-health [21], particularly the joint soreness he reported sporadically from his twenties until his death [6,12]. He also reported the fatigue that afflicts patients with lupus [22], fevers [23], and protein in his urine [6], as well as what might easily have been pleurisy rather than pneumonia during his final, fatal illness [9,24], all of which point toward lupus, known to rheumatologists for its ability to mimic multiple diseases. According to the criteria developed by the American College of Rheumatology, any four of the eleven criteria established for lupus is sufficient to suggest a high probability a patient might have lupus [25]—making Proust’s symptoms consistent with a diagnosis of lupus. However, lupus disproportionately strikes women of childbearing age [25], involving over 90% of cases [26]. Proust moreover reported his first asthma attack having occurred when he was ten, a very young age for onset of the disease that would have made Proust’s survival into adulthood—even if he had received today’s standard of care—highly unlikely. Furthermore, while lupus can inflame the lining of the lungs, resulting in pleurisy, Proust’s pulmonary symptoms were definitely asthmatic, causing him to wheeze painfully, rather than struggle with the chest pain and shortness of breath caused by pleurisy or by lesions in the lungs that simulate pneumonia, commonly experienced by lupus patients [25], which Proust would likely have experienced long before his last months. Lupus also seldom causes the symptoms of acute sinusitis and asthma suffered by Proust. Although Proust might conceivably have suffered from lupus, lupus patients rarely go a lifetime, particularly one stocked with so many symptoms of a profound systemic disorder, without exhibiting at least once the classic ‘‘butterfly” or malar rash that is one of the most identifiable characteristics of a disease that can often evade ready diagnosis. Proust, for all his painstaking notes on his fevers, aches, and even itches, never once mentions a rash, let alone the alopecia, hyperor hypopigmentation, deep nodules, or blisters characteristic of lupus [25]. Proust’s gastroparesis could also have been caused by sarcoidosis, a rare disorder with a familial origin indicative of inherited predispositions to the disease, which tends to occur more frequently in people in African or Ashkenazi descent [27]. Since Proust’s maternal grandmother was an Ashkenazi Jew, and the disease, while rare, affects about one in every 10–20,000 people [27], Proust may have suffered from sarcoidosis, a condition thought to occur from an auto-immune reaction to infection that causes lumps of inflammatory cells, called granulomas, that occur throughout the body [28]. Proust’s ostensible asthma would thus have stemmed from scarring in his lungs [29], caused by the same sarcoidosis that compromised the action of his digestive tract and also prompted the fatigue, fever, and weakness reported so frequently by Proust. However, Proust displayed difficulty breathing during his first decade, a rare occurrence if he suffered from sarcoidosis, which usually develops during the third or fourth decades of life [28]. And sarcoidosis is similarly unlikely to have accounted for his gastroparesis, as sarcoidosis has gastric effects in less than 1% of cases [30]. Even in this rare subset of patients, sarcoidosis granulomas generally cause abdominal discomfort, nausea, vomiting, diarrhea, and weight loss—but not the early satiety reported so frequently by Proust. In the end, Proust’s gastroparesis is most likely to have been caused by a profoundly multi-systemic disorder like Marfan or Ehlers–Danlos syndromes, both of which can cause delayed gastric emptying. Resulting from an inherited tendency to overproduce fibrillin, as in Marfan Syndrome, or from a hereditary predisposition to overproduce collagen in Ehlers–Danlos Syndrome, either
disorder could account for not only Proust’s gastroparesis and alternating bouts of constipation and diarrhea but also his catalogue of aching joints, the vision problems he complained of during his last decade, and both his sinus and pulmonary issues. However, Marfan patients tend to have marked physical characteristics that include scoliosis, flat feet, crowded teeth, long, thin fingers, and the tall, thin build similar to that of famous Marfan case Abraham Lincoln [31]. Proust also did not report other classic Marfan characteristics, including an unusual growth spurt during early puberty or myopia in childhood, although Marfan patients may have only one or more of these physical characteristics [32]. Proust’s symptoms seem more closely allied with one of the types of Ehlers–Danlos Syndrome (EDS), which could account for the transitory joint pain that moved from wrist to elbow to knee and then mysteriously resolved in a way markedly unlike arthritis. EDS could also account for Proust’s poor sinus and lung motility, which resulted in chronic sinusitis and asthma, for his low-grade fevers, and for the sporadic fatigue about which he complained for much of his life. Had Proust suffered from EDS, both his fatigue and his celebrated inability to keep warm—which caused Proust to attend formal functions swaddled in coats and to maintain a blazing fire year-round in his Paris bedroom—would have stemmed from an excess of collagen affecting the ability to his endothelium to constrict [33]. Instead, lacking in tone, his endothelium would have been unable to constrict or dilate in reaction to the demands of gravity and the temperature of Proust’s environment, giving him orthostatic hypotension and a profound sensitivity to cold. Tellingly, Proust was able to maintain a voluminous correspondence on top of an outpouring of three million words of published prose during a career begun late in life—mostly by remaining in bed and thus avoiding the fatiguing effects of his orthostatic hypotension. And Proust also notably complained of being cold all over, rather than exclusively in his hands or just his extremities, which would have made his condition similar to Raynaud phenomenon and thus congruent with mixed connective tissue disease (MCTD), which shares clinical symptoms similar to Proust’s with both lupus and EDS [34]. Strikingly, Proust reacted to his symptoms by taking to his bed as a lifelong invalid, imitating his father’s sister, who also suffered from the same fatigue, fevers, and symptoms of gastroparesis, suggesting a hereditable disorder. Ultimately, Proust’s symptoms match closely with those suffered by patients diagnosed with EDS—and thus also suggest several factors responsible for his demise at the comparatively early age of 51. Less than a month before the writer’s death, his brother, a clinician like their father, breezily reported that Marcel was suffering from a treatable and easily cured pneumococcal infection. After his brother’s rapid decline, Robert Proust declared that Marcel had died from a ruptured lung abscess, even though no autopsy was ever performed and no diagnostic tool more sophisticated than a stethoscope ever used on the writer. According to the writer’s housekeeper, Robert Proust believed that his brother’s abscess ruptured, and septicemia ultimately killed Marcel. However, housekeeper Céleste Albaret, insisted that the writer had a nonproductive cough, producing no sputum whatever [9], let alone the hemoptysis that accompanies lung abscesses. Furthermore, recent studies have debunked clinicians’ abilities to detect either pneumonia or lung abscesses based on breath sounds alone [35], and lung abscesses are notoriously difficulty to diagnose, even with sophisticated imaging technologies like CT scans first used a halfcentury after Proust’s demise. Although Proust never reported any of the joint instability consistent with the hypermobility type of EDS or the tendon or ligament herniation typical of the deadlier vascular type, the syndrome is a spectrum disorder, with even patients with vascular type EDS displaying none of its typical hallmarks [35]. However, patients with either type of EDS display a tendency toward arterial
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tears, dissections, aneurysms, pulmonary cysts, and pneumothorax. If Proust suffered from EDS, pulmonary cysts or pneumothorax could explain his rapid and seemingly inexplicable decline, especially if Proust had vascular type EDS. Ironically, even if Proust had been diagnosed today with vascular type EDS, which can be identified through genetic testing, his demise at fifty-one is congruent with the life expectancy for these patients, even given the vast improvement in diagnostics and treatments available eighty years after Proust’s death [36]. Proust, however, might also have died from complications resulting from his severe gastroparesis, which could have led to his having aspirated food particles while laying down due to overwhelming reflux, developing the pneumonia sometimes seen in gastroparesis patients [37]. Or his worsening dyspepsia and early satiety, which limited his diet to coffee and the purée one friend begged him to eat, could have resulted in malnutrition. Had his malnutrition been profound, Proust would have experienced a selenium deficiency—certainly possible, given the extremities of his diet—resulting in congestive heart failure, a compromised immune system, and the development of pneumonia from a mild upper respiratory infection [38]. No matter what initially ailed Proust, whatever caused his gastroparesis most likely lies at the root of what killed him. And, as this differential diagnosis of his extensively-reported symptoms reveals, Ehlers–Danlos Syndrome remains the most likely cause of his gastroparesis. Proust was a zebra: availability and Sutton’s Law None of his critics has considered the possibility that Proust, far from shamming, was genuinely ill. However, a genuinely ill Proust fosters an entirely different understanding of his work. In this view, the exquisitely attuned sensibilities on display throughout his masterpiece are of a piece with the attention Proust displayed toward his health in his correspondence. Proust might well have observed the world as he did, alive to every shifting sensation, because nothing in his body quite behaved as it should. Proust himself would have been acutely aware of the irony in producing a masterpiece while genuinely ill, while the rest of the world believed his illness the product of an overactive imagination and a lifelong bid for sympathy. He might even have completed his novel not in spite of his genuine illness but because of it, his perspective shaped intensely by his awareness of his body’s own susceptibility. In fact, studies have established the role of the insula in the perception of pain, demonstrating both that the insular cortex also registers pain and irregular symptoms in patients who routinely experience pain [39], at the same time researchers have established the insula’s key role in establishing our sense of both bodily pereption and agency [40]. Ironically, the same affliction that merely made his Tante Élisabeth take to her bed could well have made Proust an intent observer of his own body, minutely aware of its functions in a way that the truly healthy can never know. Perhaps, in the end, Proust was able to write À La Recherche du Temps Perdu not in spite of but expressly because of the malady with which he was born and which ultimately ended his life. What is particularly compelling about Proust’s case is the unanimity in his critics’ verdict that he suffered from little more than a mild case of asthma and profound hypochondria. Even to the clinicians among his critics, his catalogue of symptoms were interpreted as merely neurasthenic bids for attention, just as they were by the well-regarded clinicians in Proust’s own family, his father and brother. Nevertheless, a close reading of his critics’ verdicts also sheds light on diagnostic errors in medicine, explaining why at least four seasoned clinicians, all with experience in multiple areas in medicine, read Proust’s somatic illness as purely imaginary.
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In fact, Proust’s misdiagnoses, some of them arrived at by modern clinicians with considerably more diagnostic resources to hand than Proust’s own doctors or brother, illustrate common diagnostic errors in medicine. These clinicians were all influenced by availability [41], a bias toward the diseases they encountered most frequently, like the neurasthenia clinicians saw so frequently in the late nineteenth and early twentieth centuries [9,12]. The earlier diagnoses, in turn, influenced the judgments of the late twentieth-century clinicians who examined Proust’s case [3,4]. In this instance, the clinicians were partially influenced by the initial diagnoses, which can lead to an error first identified by the behavioral economists who classified some of the errors that decisionmakers of all kinds, including clinicians, fall prey to. That error, anchoring, occurs when clinicians fail to revise an initial diagnosis, even when potentially conflicting information becomes available [42]. In the clinicians considering Proust’s case, anchoring also served to bestow on the diagnoses of Proust’s own doctors and his brother greater validity than they deserved, especially given the late-twentieth century clinicians’ awareness of just how incomplete medical knowledge was during an era before the discovery of antibiotics. But the availability bias has a complement that might have also made clinicians less likely to identify the rare disorder which really afflicted Proust. Sutton’s Law is a diagnostic dictum that cautions young doctors, ‘‘When you hear hoof beats, think horses, not zebras” [43]. Supposedly named for the bank robber Willie Sutton, who said he robbed banks because that was where the money was, Sutton’s Law might well have taken shape to counter the availability biases of medical students. Exposed to an encyclopedic range of conditions and diseases, many of them rare, medical students endure testing that focuses less on common diseases than on syndromes they are infinitely more likely to encounter in a textbook than in clinic. During their initial consults with patients, Sutton’s Law reminds residents and young clinicians to diagnose wheezing and shortness of breath as asthma, probably exacerbated by sleeping in a smoky room. Useful for the average patient, Sutton’s Law also increases the likelihood that a zebra like Proust today would have received no more accurate medical treatment than he had eighty years ago. Today, patients with rare disorders—Sutton’s zebras—typically require years of persistent visits to clinics, demands for referrals, and both the financial means and selfconfidence to persist in the process of repeated consults and misdiagnoses.
Conclusions Ironically, even if Proust were correctly diagnosed—after the years required by most patients with rare diseases to obtain correct diagnoses—he would not necessarily receive much better care today than he did in the early twentieth century. Today, modern medicine, balkanised into specializations with minimal interaction between them, poses a particular dilemma for patients with profoundly multi-systemic disorders like Ehlers–Danlos and Marfan syndromes, schleroderma, lupus, sarcoidosis, and mixed connective tissue disease. Currently, these multi-systemic disorders are typically treated by rheumatologists, who tend to administer pain management and focus on issues involving patients’ soft tissues. But these disorders can affect virtually every system in the body, requiring not only follow-up from nearly every specialization from ophthalmology to gastroenterology but patients sufficiently well educated to understand how they need to manage their own wellbeing. We like to think that, with the advances medicine has made over the past eighty years, Proust would have enjoyed a correct diagnosis, sympathy, and a life span considerably longer than the fifty-one years he enjoyed. But, the more closely one examines
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