1.1. Gaps, Restrictiveness, and Deficiencies in the Healthcare Systems
Many physicians find it challenging when making a diagnosis involving the interface between general medical and psychiatric illnesses, and diagnostic errors harm patients. Historically, there has been a bias in which poorly understood illnesses are often considered to have a psychiatric origin until the pathophysiology is better understood and explained on some other basis. There is a broad spectrum of opinion regarding how to approach a diagnosis when there is a general medical and psychiatric differential diagnosis [1
In recent years, medicine has gravitated towards a pressure to comply with third party guidelines and computerized algorithms, and there has been a trend towards super specialization with limited training in non-specialty fields. The combination of these issues has collectively contributed to a silo mentality and a fragmentation of knowledge [2
]. Restrictive, third-party guidelines, time constraints, and restrictive, computerized algorithms have often limited the thoroughness of a physician’s evaluation. In one study, in 67% of encounters in which clinicians elicited patient concerns, the clinician interrupted the patient after a median of only 11 seconds [3
]. These limitations impede the adequacy of the clinical assessment of complex diseases.
Knowledge gaps can be associated with several issues: (1) a lack of knowledge in either psychiatry or medicine, (2) gaps between clinical expertise and research knowledge, (3) difficulties converting research results derived from groups of subjects to the uniqueness of individual patients, and (4) the improper application of guidelines.
The average physician who practices in an internal medicine specialty, including many who write guidelines that others follow, may have a very limited basic background in psychiatry, often consisting of a one-month rotation through a state hospital while in medical school, and little continuing medical education in psychiatry or psychosomatic medicine since then. Although psychiatrists have a strong foundation in general medicine, not all psychiatrists keep current in general medicine, and many other mental health professionals have very limited training in general medicine. With specialization and fragmentation in healthcare systems, there are many healthcare providers lacking capability in both psychiatry and general medicine. As a result, the understanding of the interface between mental and somatic disorders falls into a gap between psychiatry and medicine. It is a concern when thought leaders lacking adequate knowledge in both psychiatry and general medicine write and promote diagnostic and treatment guidelines that others may then follow rigidly on subjects such as somatoform disorder, somatic symptom disorder, medically unexplained symptoms, bodily distress disorder, and multisystem illnesses.
Another gap exists between clinical expertise and medical research. This can result in difficulty reconciling differences between clinical observation and clinician experience vs. research performed by bench scientists and academicians who often have limited clinical capabilities. This is referred to as translational research, in which there is a unidirectional continuum where research findings are moved from the researcher’s bench to the patient’s bedside [4
]. However, more effective progress is achieved when there is also a bidirectional process in which clinical observations and wisdom also inform basic science research.
Many who write United States Centers for Diseases Control and Prevention’s guidelines are epidemiologists, microbiologists, and other researchers rather than practicing clinicians who have the long-term responsibility for treating patients. For example, the Second National Conference on Serological diagnosis of Lyme Disease in Dearborn, Michigan, USA in 1994 resulted in the Association of State and Territorial Public Health Laboratory Director’s (ASTPHLD)’s criteria for the diagnosis of Lyme disease. Most who attended this meeting were not physicians, and the few physicians who attended were academicians and researchers rather than physicians practicing in the community which had higher levels of clinical experience and expertise [5
Another limitation occurs when research is performed on groups of individuals, which generate statistics for groups of patients that are then translated into a specific treatment for the individual patient. Patients with unique presentations are being compromised by an emphasis upon population-based standards of care rather than their individual patient needs and experiences. It is far better for physicians to rely less upon clinical guidelines based upon group statistics for managing single diseases and instead rely more on their own clinical judgment to create treatment plans that are tailored to meet the needs of individual patients [6
]. Diseases involving brain and body interaction are particularly challenging. In view of the uniqueness of individuals, biological heterogeneity, the complexity of some illnesses, and individual differences in treatment tolerance, safety, and efficacy, any treatment based upon rigid adherence to treatment guidelines derived from groups and applied to individual patients without exercising clinical judgment is clearly below the standard of care [7
]. As a result of these multiple issues, patients with complex illnesses can feel lost and abandoned by the healthcare system.
1.2. Consequences of Diagnostic Errors
Complex brain–body differential diagnoses are challenging to payers, physicians, and affected patients.
Patients often describe going to many different physicians before they acquire an accurate diagnosis. One survey of over 12,000 participants found the average patient with Lyme disease was seen by five physicians before they were properly diagnosed [10
]. When the time allowed for a more thorough assessment is limited by healthcare reimbursement policies, physicians often respond by ordering an excessive amount of testing. Healthcare financial resources are strained, since these patients may not fit well into current diagnostic and treatment algorithms, and the evaluations of these patients may result in multiple tests and consultations of limited cost effectiveness [11
]. Diagnostic delays also result in increased costs from disability, lost productivity, and caretaker burden. The payers who assume these financial burdens may include insurance companies, government healthcare systems, employers, patients, and patient’s families. Many insurance companies have barriers and limitations of what they cover, and patients with complex, chronic, and costly diseases incur significant out-of-pocket costs. A significant number of medical bankruptcies occur among both insured and uninsured individuals [12
]. When dealing with these challenging cases, some physicians view these patients as being difficult, frustrating, and demanding [14
]. In addition, some physicians react to these difficult cases by becoming highly stressed [15
]. However, the greatest stress is endured by the patients who report feeling dissatisfied, disbelieved, and dismissed by clinicians [16
Brain–body diagnostic errors are common in these patients, and these errors receive considerable attention in both the media and in the medical literature. Most of the cases receive this attention in books, media, and journal articles and involve erroneous psychiatric diagnoses rather than medical diagnoses [17
Females are more often given an incorrect psychosomatic diagnosis, indicating gender-based bias and lack of research/understanding on how the female body responds to biological illness [19
]. A recent book explored the systemic problems of women’s experiences of being dismissed by the medical providers. This included being discharged from a hospital emergency department mid-heart attack with a prescription for anti-anxiety meds, having autoimmune diseases and being labeled “chronic complainers” for years before being properly diagnosed, and having endometriosis and being told they are just overreacting to “normal” menstrual cramps [19
]. Illnesses such as chronic fatigue syndrome and fibromyalgia are “contested” illnesses. They are considered psychosomatic and not “real” illnesses. They are given labels such as “hysteria”, “hypochondriacal”, or “all in their head” [19
There are many reported cases of misdiagnosis and treatment delays in the media. One case that drew considerable media attention was the case of Julia, who was in a wheelchair from Lyme disease and was blessed by the Pope when he visited Philadelphia. Two psychiatrists independently cleared Julia of any psychological cause for her symptoms. The attending pediatrician refused to accept either report. To rule out her suspicion of malingering, she had the physical therapist purposely drop Julia on the concrete floor [20
]. Another case drawing considerable attention was a woman in the United Kingdom who was told her symptoms were “all in her head” and was diagnosed with somatization disorder, which resulted in a 20-year treatment delay [23
An example of misdiagnosis reported in the medical literature is the case of a 57-year-old woman with pain and discomfort in multiple sites on her upper body. She was diagnosed with somatic symptom disorder after a partial examination turned out to be negative. Falsely diagnosed as having somatic symptom disorder for six months, she was then correctly diagnosed as having multiple myeloma [24
]. Another example of diagnostic errors and improper treatment is gastroenterological patients whose symptoms were of unclear etiology and were most commonly treated with antipsychotics [25
One interesting study found in the Dutch General Practice Registry showed patients with a diagnosis of somatoform disorders had a higher infection load compared to matched controls preceding their diagnosis. The results of the study demonstrated a somatopsychic process. However, the authors concluded the opposite by stating the infection caused somatoform disorders, which instead would be viewed as psychological symptoms causing physical symptoms [26
]. Other similar studies conclude a strong causal association between infections and psychiatric illness [27
Difficult-to-diagnose cases are often viewed as invisible illnesses, since there may be no outward appearance of illness by a superficial examination. Many people suffering from these chronic, invisible illnesses such as myalgic encephalomyeletis/chronic fatigue syndrome, fibromyalgia, Lyme disease, and postural orthostatic tachycardia syndrome (POTS) are frequently misdiagnosed. They are tired of being unheard and told symptoms are imaginary, self-inflicted, and psychosomatic. As a result of this, they often describe feelings of abandonment from physicians and the healthcare system, which results in increased risks of suicidal ideation, suicide attempts, and suicide compared with the general population [29
All guidelines have limitations and disclaimers that individualized judgment is necessary. Different guidelines have different levels of reliance upon randomized, controlled studies, which have two major limitations: (1) Once a certain level of knowledge is achieved by doing these studies, it is no longer ethical to continue further placebo-controlled studies. (2) Any given research may not be relevant to the uniqueness of any particular individual. Because of these and other limitations, guidelines are useful but cannot be universally applied [30
Flawed guidelines have resulted from flawed research and bias. This problem is further compounded when well-intentioned physicians follow these guidelines assuming they are trustworthy. Examples of this have occurred with myalgic encephalomyelitis/chronic fatigue syndrome, Lyme disease, and “medically unexplained symptoms.”
A lack of understanding of myalgic encephalomyelitis/chronic fatigue syndrome both prior to and after the Institute of Medicine Report on this disorder has contributed to many patients feeling maligned, blamed, untreated, and undertreated. Some patients stated that they felt belittled, dismissed, and ignored by their health care professionals who followed some of the commonly disseminated guidelines. More than 80% of patients with myalgic encephalomyelitis/chronic fatigue syndrome (CFS) go undiagnosed, while 65% of patients spend more than a year seeking the correct diagnosis [31
]. Treatment recommendations based upon a graded activity and a cognitive behavioral therapy (PACE) trial were previously adopted by many healthcare organizations. However, the research was highly flawed and never supported the belief that ignoring symptoms would lead to recovery [35
]. The inaccurate treatment recommendations based upon the PACE trial recommended patients should ignore symptoms. In addition, patients were given a form of cognitive behavior therapy that challenged their beliefs of their having any physiological illness limiting their ability to exercise. Instead, to become more active—and possibly fully recover—they only needed to ignore their symptoms [37
]. Many patients failed to respond to this treatment, and the research supporting the concept that exercise can treat chronic fatigue syndrome was subsequently rejected by Cochrane stating that the work does not meet the organization’s “quality standards.” [38
]. After the PACE study was found to be invalid, there have been further advances in the field, and many guidelines have since been revised [39
Another set of guidelines that failed to adequately address brain–body interactions is The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) [40
]. These guidelines gave excessive credibility to flawed testing, failed to recognize the psychiatric symptoms caused by Lyme and other tick-borne diseases, and instead discounted many of the late stage symptoms as being ”the aches and pains of daily living”, subjective and non-specific, and medically unexplained symptoms. The IDSA Lyme disease guidelines have had multiple criticisms, including being highly biased and lacking objectivity, since the day they were published [41
]. The Institute of Medicine’s report, Clinical Practice Guidelines We Can Trust [48
], uses the example of the IDSA Lyme disease guidelines to illustrate issues associated with untrustworthiness, including problems of conflicts of interests, lack of transparency, and scientific bias in guidelines development—“Unfortunately, patients cannot put their chronic illness on hold until the medical scientists come to a consensus on whether the evidence suggesting infectious causation is or is not close enough to ‘definitive.’ Making wise decisions in an uncertain environment requires balanced reasoning, critical thinking, compassion, and common sense… Some players in the Lyme controversy seem to pride themselves in their acceptance of a conclusion only when the evidence overwhelmingly supports it…” [49
]. The IDSA is in the process of revising these guidelines in 2019, and a draft of its guidelines was posted briefly for public comment. The revised guidelines showed little change in most of the areas of controversy, and attention to some of the flaws in the proposed guidelines has been addressed
A guideline called Medically Unexplained Symptoms (MUS) in Children and Young People: A Guide to Assessing and Managing Patients Under the Age of 18 Who Are Referred to Secondary Care
was endorsed by the Royal College of Psychiatrists and the Paediatric Mental Health Association and gives a clear appearance of a bias to benefit third parties and physicians rather than patients [53
]. In this guideline, the authors attempt to revive the concept of medically unexplained symptoms (MUS), even though it has been considered an invalid concept since the 2013 publication of the 5th edition of the American Psychiatric Association’s (APA) Diagnostic and Statistical Manual of Mental disorders 5th Edition
]. This guideline encouraged doctors to consider a diagnosis of MUS if: “(1) Your patient has undergone an unusual level of investigations and/or been to a significant number of hospital specialists relative to their diagnosis. (2) You experience a high level of anxiety when seeing the patient and their family, and/or feel pressured into referring for investigations or to other specialists in a way that you don’t experience with other patients in a similar clinic setting. (3) You feel irritated with the patient or their family for not ‘getting better.’ (4) There is a family history of MUS. (5) There is significant absence from school as a result of symptoms that appear ‘out of proportion’ to physical investigations. (6) You have an experience of a parent who appears overly-invested in their child’s illness and loss of function” [53
2. Materials and Methods
Two case presentations are given to demonstrate some of the relevant issues when differentiating between psychosomatic, somatopsychic, and multisystem illnesses, and they are discussed herein. The patients’ identities are concealed, and written consent for publication was acquired. To help make a differential diagnosis, relevant brain–body diagnostic terms used in making a differential diagnosis and terms in which there is confusion, controversy, debate, misdiagnoses, and abuse are then identified. Some of these are terms the first author has encountered while doing consultation-liaison psychiatry. Additional terms are considered for inclusion using searches of PubMed, Google Scholar, and the author’s archives. The terms are then defined and discussed. Some of these terms are identified and defined in formalized diagnostic references, which include the APA DSM-5 [54
] and the International Classification of Diseases
(ICD), which are considered standards for diagnosis [54
]. Other terms may be included in only one or neither of these references. The terms that are defined include APA DSM-5 diagnostic categories, mental health, mental illness, psychosomatic disorders, somatopsychic disorders, multisystem disorders, medical uncertainty, somatoform disorders, medically unexplained symptoms, functional disorders, psychogenic disorders, compensation neurosis, psychogenic seizures, psychogenic pain, psychogenic fatigue, delusional parasitosis, subjective vs. objective, non-specific and vague symptoms, bodily distress disorder, and bodily distress syndrome. Relevant terms in the DSM-5 are followed by the DSM-5 diagnostic code with the associated International Classification of Diseases
(ICD) codes following in parentheses [54
]. Articles relevant to defining and differentiating psychosomatic, somatopsychic, and multisystem illnesses are reviewed. Terms with the greatest potential for misuse and abuse are discussed in greater detail. Significant issues relevant to accurate diagnosis and diagnostic errors are discussed. Conclusions are drawn to aid the clinician in differentiating psychosomatic, somatopsychic, multisystem illnesses, and medical uncertainty.
Historically, there has been a tendency to label physical symptoms that could not be explained as being of a psychiatric origin. As a result, many patients with complex, confusing symptoms and poorly understood diseases who receive an inadequate assessment for their condition are often referred to psychiatrists until the time when the disease is better understood and defined. Limited integration between psychiatry and general medicine, silo mentality, restrictive diagnostic criteria, and erroneous guidelines currently contribute to diagnostic errors. Uncommon, complex, and multisystem diseases such as Lyme disease ME/CFS more often misdiagnosed as having a psychogenic etiology to their symptoms. As more sophisticated technologies emerge to visualize the brain, to demonstrate brain pathophysiology, and to quantitate mental functioning, and the causes of mental illness become better understood, the validity of many of the previously used phrases that were based upon the absence of physical findings, such as psychogenic and functional disorders, are becoming less valid. There is now an increasing amount of literature demonstrating somatopsychic and multisystem processes and the accompanying pathophysiology [57
The diagnosis of any medical or psychiatric syndrome requires the presence of clearly defined signs and symptoms consistent with each diagnostic category. Reliance upon the total clinical exam, including an adequate history, review of systems, psychiatric assessment, and clinical judgment, is more valid than reliance upon any single laboratory or diagnostic test. When using diagnostic testing, absence of proof is never proof of absence. Although the absence of a finding in a diagnostic test may raise the suspicion of a psychiatric illness, the absence of a finding alone can never confirm the presence of a psychiatric illness. The diagnosis of a psychosomatic condition requires a causal psychodynamic explanation, and it is never a diagnosis of exclusion based upon a failure to confirm some other diagnosis. A more thorough psychiatric assessment can determine whether there is a psychodynamic and/or psychiatric pathophysiological process that would explain a symptom. The onset of a multisystem illness is rarely, if ever, associated with a psychogenic etiology. The presence of a psychiatric diagnosis does not eliminate the possibility of a comorbid, somatic diagnosis or a comorbid somatic diagnosis causing psychiatric symptoms. Many complex conditions once described as “all in your head” are immune mediated infections. These conditions may—more probably and accurately—be in the immune system and/or the microbiome [117
We can learn from history. Syphilis was once a difficult to understand multisystem illness with periods of latency and a broad spectrum of presentations including both psychiatric and somatic and symptoms. Now, we are attempting to understand other multisystem, complex, interactive infectious diseases that are far more complex than syphilis. Treponema pallidum
(syphilis) has only 22 genes. In contrast, Borrelia burgdorferi
(the bacterium responsible for Lyme disease) has 132 genes with plasmids that allow for rapid genetic changes and interactions with other tickborne and opportunistic infections [143
]. There are over one hundred other infectious agents that cause mental illnesses [57
We always need to be alert to new and emerging diseases. We must recognize there is always some degree of medical uncertainty with any condition. Not everything is well understood or categorized. Complex diseases require complex explanations, and there needs to be recognition of varying degrees of medical uncertainty. Everything is caused by something. Nothing is caused by nothing. When clinical findings are puzzling, the ethical approach is to continue attempting to explain the symptom, search for its cause, and admit that we do not have the required knowledge to provide a cure or even complete symptom relief.
Medically unexplained symptoms, somatoform disorder, and compensation neurosis are outdated and/or inaccurate terms. Qualitative terms such as subjective, vague, and nonspecific can be used inaccurately. Conversion disorders, functional disorders, psychogenic illness, factitious disorder imposed upon another (Munchausen’s by proxy), somatic symptom disorder, psychogenic seizures, psychogenic pain, psychogenic fatigue, and delusional parasitosis can be over-diagnosed. Bodily distress disorder is highly subjective and is a scientifically unsupported and inaccurate term. Bodily distress syndrome is also highly subjective. It is dependent upon the flawed concept of medically unexplained symptoms and is a scientifically unsupported and inaccurate term. A common diagnostic pitfall with all of these terms is the risk that something unexamined or not adequately understood can result in an improper diagnosis, inadequate treatment, and inadequate financial coverage by third party payers.
To properly understand the mind/body connection, adequate training and knowledge of general medicine, psychiatry, and the systems that link the soma and the brain are required. No one has complete knowledge of all fields of medical sciences. Not all diseases have been discovered or are properly understood, and much remains to be learned. Better education concerning the interface between medicine and psychiatry and the associated diagnostic nomenclature as well as utilizing clinical judgment and thorough assessment, exercising humility, and maintaining our roots in traditional medicine will help improve diagnostic accuracy and move both science and medicine forward.