Gout - Another Comparison Illness

The word gout in the above opening sentence from the chapter in UpToDate (1) can be replaced with any one of the major psychiatric disorders.  Gout is an extremely painful arthritis affecting one or more joints during an acute attack.  The arthritis is caused by the deposition of monosodium urate (MSU) crystals in the joint.  In a recent survey gout sufferers describe the pain as the worst pain they have ever experienced in their life - worse than childbirth or a heart attack (2).  Unlike psychiatric disorders gout has a gold standard diagnosis of the direct observation of uric acid crystals as being birefringent in a polarizing microscope, but only about 10% of gout sufferers ever has this test done.  The epidemiology of gout in the USA suggests that the prevalence is increasing to about 3.9% of the population or about 8.3 million people.  It is more common in men (5.9%) than women (2.0%).  There is an expected increase associated with obesity, hypertension, metabolic syndrome and aging.  Certain medication like diuretics can also cause increases in uric acid levels. but most people with hyperuricemia do not have gout.  The misdiagnosis of gout is common with gout sufferers being diagnosed with sprains and other forms of arthritis.  The inflammatory response is so striking that a misdiagnosis of cellulitis can also occur.  Searching Medline, I could not find a single study on the rate of misdiagnosis of gout.  Common biases that affect misdiagnoses include the over reliance on uric acid levels and demographic factors like age and sex of the patient.  Some earlier guidelines suggested an empirical trial of medication to lower uric acid levels and if that was ineffective to consider other diagnoses.

The pathophysiology of gout is interesting because it has been historically viewed as a disorder of uric acid intake, overproduction or undersecretion.  Intake is from dietary sources and there are numerous  resources that examine the purine content of foods.  Alcohol intake also directly increases uric acid production through increased metabolic demands by the liver.  The dietary approach is not uniformly accepted by physicians as a useful approach to treatment.  Many consider it to be a minor contributor to serum uric acid levels.  There is some data to support the use of low fat dairy products as a protein source and Vitamin C as a way to decrease the frequency of acute attacks.  Common claims include the use of grape and tart cherry juice as ways to decrease uric acid levels.  Internet information suggest that grape juice transiently lowers level but tart cherry juice provide more permanent decreases.  The only medical reference that I could find on grape juice was dated (4), but the references on tart cherries and cherry juice seemed excellent (5,6).  One group of authors (5) suggested that after 4 months of ingesting cherry juice there was a 50% reduction in gout attacks and patients were able to stop regular intake of non-steroidal anti-inflammatory after 60 days.  Cherry juice intake also protected patients with elevated uric acid levels from attacks.  In another study they used pomegranate juice as a comparator and it had no effect on the frequency of gout attacks.  Apart from the cherry juice evidence there is also some controversy about whether high purine content vegetables are as likely to precipitate a gout attack as meat products with high purine content.

Xanthine metabolism is intimately liked to glycolysis, so that increased metabolic demands can lead to increased uric acid production.  Common examples of how these pathways are activated in gout include excessive alcohol intake with increased metabolic demand and excessive intake of sugar sweetened beverages.

Uric acid secretion and reabsorption is captured in this graphic that attempts to address both the transport mechanisms as the uric acid transportasome and the expectedly complex genetics.  Thinking about the proteins coded for in uric acid metabolism and the transportasome,  this is clearly another complex polygenic disorder.  The diagram depicts uric acid transport in the proximal renal tubule.  The complexity of the involved mechanisms has increased significantly in the past decade.  Sodium dependent monocarboxylate transporters SLC5A8, SLC5A12 and SLC13A3 allow uric acid to accumulate in the cell.  A number of transporters allow for uric acid secretion.  In the case of OAT1 and OAT3 the direction of uric acid transportation is not clear.  PDZK1 is involved in assembling the transporter complex.  Genetic variants at all of these levels are associated with gout.

From: Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015 Apr 10. (reference 7)

Merriman's review of the genetics of gout emphasizes how the complexity of the disorder is not appreciated.  Preliminary genetic studies for example indicate that there are hundreds of potential genotypes affecting the involved proteins as well as epigenetic factors to explain the environment influence on the genomics, but they would only account for about 10% of gout patient with elevated levels of uric acid.

The lack of a complete explanation for gout based historical precedence has led some innovative researchers to look for an explanation in the inflammatory arm of the illness rather than the deposition of MSU crystals.  Gout is a highly inflammatory condition in the acute phase and there has been scant attention paid to potential phenotypes.  Some patients will get very localized pain and swelling in a clearly demarcated joint space.  Other will get marked swelling, edema, erythema, in multiple joints of the ankle and foot.  In some cases there is inflammation and swelling of the surrounding tendons and connective tissue.  In other extreme cases there is blistering of the skin surface over the affected joint.  Gout gives meaning the to the term "hot joint".  The most straightforward explanation for the inflammatory response was initial complement protein activation at the surface of the MSU crystals.  That leads to phagocytosis of the crystals by macrophages and generation of pro-inflammatory cytokines (IL-6, IL-8, IL-1β, and TNFα).  Neutrophils are recruited and superoxide and IL-8 are generated.  Macrophages eventually take up MSU crystals and apoptotic neutrophils and generate transforming growth factor (TGFβ).  MSU crystals are coated with apolipoprotein B (ApoB)  and ApoE blocks further activation of complement proteins.  The inflammation resolves and the joint is reset back to baseline.

There are alternate mechanisms proposed  that involved the NLRP3 inflammasome.  That leads to caspase-1 activation and secretion of IL-1β, IL-18 and other proinflammatory cytokines (IL-6, IL-8 and TNF).  That leads to neutrophil infiltration of the joint and periarticular tissues.   The  authors in reference 8, emphasize the importance of the IL-33/1RL1 axis and polymorphisms in genes that code for IL-33, IL-1RL1, IL-23R and STAT4 as candidate genes for the inflammatory response in gout.  They determined that the IL-23R rs10889677 AC or CC genotypes were much more likely to develop gout than the AA genotype.  Other research groups have determined associations with inflammatory candidate genes and rheumatoid arthritis, asthma, Alzheimer's disease and Crohn's disease.  

What  are the implications for psychiatry and why is a psychiatrist interested in the details of the inflammatory response?  The first reason is the diagnostic process in medicine and the myth the gold standard or some kind of biological test.  In the case of gout a biological test exists, but hardly anyone uses it.  There are good reasons for that.  It takes a considerable amount of skill to successfully aspirate an inflamed joint.  If there is significant inflammation around the joint that means pushing a needle through all of that inflammation to get to the joint.  Physicians vary significantly in their ability to insert needles into joints and based on that skill level - it may be good idea to avoid a test even if it is the gold standard.  There is also a likelihood that even when the gold standard test is done, the test misinterpretation rates are high - maybe close to 50% according to a poster session mentioned in one of the references.  The second reason is that there is a diagnostic feature here that is almost pathognomonic of the illness, even without that feature.  A person with acute onset of joint pain, in the absence of other conditions is highly likely to have gout.  The Agency for Healthcare Research and Quality and the American College of Rheumatology/European League Against Rheumatism collaborative initiative have taken two different approaches in providing assessments of gout diagnosis algorithms with and without a gold standard test and assessed their accuracy based on available data.  Third, inflammation has current and historical importance in psychiatry both as a treatment and potential etiology for psychiatric illness and there may come a time when psychiatrists need to know more about it on a routine basis for refining diagnosis and treatment methods.  Finally, complex polygenic illnesses are difficult to diagnose and treat.  That is becoming more apparent as molecular biology shows us that the first efforts at determining the pathophysiology of these disorders may have been grossly correct - but that the diagnosis requires a lot of refinement in order to capture the full range of pathophysiology that may account for the illness.     



George Dawson, MD, DFAPA




1:  Becker MA.  Clinical manifestations of gout.  In: UpToDate,  Schumacher HR, Romain PL (Eds), UpToDate, Waltham, MA.  (accessed on July 10, 2016).

2:  Liddle J, Roddy E, Mallen CD, Hider SL, Prinjha S, Ziebland S, Richardson JC. Mapping patients' experiences from initial symptoms to gout diagnosis: a qualitative exploration. BMJ Open. 2015 Sep 14;5(9):e008323. doi: 10.1136/bmjopen-2015-008323. PubMed PMID: 26369796; PubMed Central PMCID: PMC4577947.

3: Newberry SJ, FitzGerald J, Maglione MA, O'Hanlon CE, Han D, Booth M, Motala A,Tariq A, Dudley W, Shanman R, Shekelle PG. Diagnosis of Gout [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2016 Feb. Available from http://www.ncbi.nlm.nih.gov/books/NBK350137/ PubMed PMID: 26985540.

4:  LOEPER J, TISSEYRE JC. [Contribution to the uricosuric property of grape juice]. Prog Med (Paris). 1960 Nov 24;88:384 passim. French. PubMed PMID: 13763105.

5:  Schlesinger N, Schlesinger M. Previously reported prior studies of cherry juice concentrate for gout flare prophylaxis: comment on the article by Zhang et al. Arthritis Rheum. 2013 Apr;65(4):1135-6. doi: 10.1002/art.37864. PubMed PMID: 23334899.

6:  Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi HK. Cherry consumption and decreased risk of recurrent gout attacks. Arthritis Rheum. 2012 Dec;64(12):4004-11. doi: 10.1002/art.34677. PubMed PMID: 23023818; PubMed Central PMCID: PMC3510330.

7:  Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015 Apr 10;17:98. doi: 10.1186/s13075-015-0609-2. Review. PubMed PMID: 25889045; PubMed Central PMCID: PMC4392805.

8: Liu S, Zhou Z, Wang C, Guo M, Chu N, Li C. Associations between interleukin and interleukin receptor gene polymorphisms and risk of gout. Sci Rep. 2015 Sep 24;5:13887. doi: 10.1038/srep13887. PubMed PMID: 26399911.

9: Neogi T, Jansen TL, Dalbeth N, Fransen J, Schumacher HR, Berendsen D, Brown M,Choi H, Edwards NL, Janssens HJ, Lioté F, Naden RP, Nuki G, Ogdie A, Perez-Ruiz F, Saag K, Singh JA, Sundy JS, Tausche AK, Vaquez-Mellado J, Yarows SA, Taylor WJ. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2015 Oct;74(10):1789-98. doi: 10.1136/annrheumdis-2015-208237. Erratum in: Ann Rheum Dis. 2016 Feb;75(2):473. PubMed PMID: 26359487; PubMed Central PMCID: PMC4602275.

Supplementary 1:

Disclaimer - this is not medical advice on how to treat gout, but my personal experience.  See your personal physician if you think that you may have gout or any type of arthritis.

I have had a lot of personal experience with gout since medical school. That is where I experienced my first gout attack.  I was up cramming for a Pathology test, eventually went to bed and was awakened at 3AM with intense left ankle pain. People have various descriptions for gout pain.  The one I have settled on is that it feels like your foot is being burned off with a blowtorch. The pain and inflammation are so intense that I end up feeling physically ill for days until the acute episode resolves. That first time I went the ED of the county hospital affiliated with my medical school. I was there for about 8 hours and at some point, the Orthopedic surgery team came by and aspirated my ankle joint between trauma surgeries.  They also asked my wife to leave the room and asked me if there was any chance that I had contracted gonorrhea -  another cause of acute arthritis.  I was given a prescription for acetaminophen with codeine and discharged home. Acetaminophen with codeine is not an anti-inflammatory medication and it does not treat gout – so the acute episode basically resolved on its own after a few days.

I was lucky enough to have gone to a medical school where the head of Medicine was a Rheumatologist who ran a lab that analyzed joint aspirates. I got in to see one of his associates and the diagnosis was confirmed based on that sample. That was after several visits to the Orthopedic surgery clinic where may leg had been casted in a splint for a presumed traumatic injury that I could not recall.

Over the intervening 30+ years, I would estimate that I have had about 20 attacks, 5 of them severe. In that time, I saw one excellent Rheumatologist who told me that given the fact that I do not have hyperuricemia or secondary manifestations of gout (tophi, nephrolithiasis) – I could treat the episodes symptomatically as they occur. Over the years that has been a moving target. A few of the regimens have been:

1. Indomethacin 50 mg TID for acute attacks.

2. Prednisone 60 mg/day x 5 days.

3. Prednisone 40 mg/day x 5 days.

4. Prednisone 40 mg/day x 5 days then 20 mg/day x 5 days then 10 mg/day x 5 days then 5 mg/day x 5 days.

5. Naproxen 250-500 mg BID for acute attacks

6. Vioxx (rofecoxib) 25-50 mg/day for acute attacks. Vioxx was taken off the market for cardiovascular and cerebrovascular side effects.

7. Colchicine – tried briefly and could not tolerate.

It should be apparent that seeing 10 different doctors for gout results in 10 different prescriptions. I can say that in my case, I do not tolerate high dose prednisone very well for even brief periods of time and that 20 mg will terminate an acute attack of gout within hours. The short course of prednisone always result in a flare-up of the primary attack and a tapering course of 15-20 days is usually needed, especially if that physician advises to not use prednisone and NSAIDS at the same time. My current goal is to get off of prednisone as soon as possible and on to naproxen.

The diagnostic problems with gout have also led to several misadventures. I recall being seen by a primary care MD who I had never seen before for acute wrist pain that was probable gout.  He insisted on inserting a needle into my right radiocarpal joint, even though I told him I had a diagnosis of gout by one of the top experts in the world at the time.  He ended up aspirating a piece of the joint capsule, instead. I have also had gout of the wrist and ankle misdiagnosed as cellulitis, even though I told that physician this was gout and I had a longstanding diagnosis of gout.

People tend to attribute the tremendous physician variation in diagnostic processes and treatments in complex polygenic illnesses to the “art of medicine.” I have always considered that an inaccurate phrase. I don’t consider anything about medicine to be artsy. Medicine including psychiatry is a technical field and physicians need to know technical details. The variation is accounted for in biological complexity that adds to the varied presentations of illness and the selection of treatments along a continuum from being very effective to not so effective for a particular person.

I also wanted to add a bit about the genetic approaches to illnesses especially the one mentioned in reference 8.  Today it is possible to search your own DNA for genotypes that are found in the literature to correlate with illnesses.  When I did that for the candidate gene for gout mentioned in the paper,  I found that I have the rs10889677 SNP with a C/C genotype on the IL23R gene on Chromosome 1.   According to this paper that may better explain why I am bothered with gout than the steady state of uric acid flux in my body.  My uric acid levels are always normal.

So much for what you learn in medical school.


Supplementary 2:

Total ICD-10 Gout Diagnoses

Total ICD-10 Mood Disorder Diagnoses

And you thought the DSM had too many diagnoses?


Attribution:

1:  The diagram on factors affecting the reabsorption and secretion of uric acid is form: Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015 Apr 10. (reference 7) and posted here per the conditions of their open access license.

Schizoaffective Disorder and Surfing Music

I will disclose my biases on schizoaffective disorder from the outset.  My decades of acute care experience suggests that it is a lot less common than suggested by medical records.  Reflecting on the unique experience of seeing people hospitalized many times over the course of 20 years, the most frequent pattern I observed was clear cut bipolar disorder turning into a diagnosis of schizoaffective disorder or in some cases "bipolar disorder and schizophrenia".  Since I worked at this hospital long enough and had the memories of my enthusiastic young psychiatrist self and my compulsive documentation to count on, I can say that the most frequent pattern was patients presenting with manic episodes turning to the less specific diagnosis.  Most of these people were in their 20s or 30s when they experienced a clear cut manic episode.  There was no doubt about it because of the rapid onset and mood congruent psychotic symptoms.  They responded well to treatment and I discharged them from the hospital.  They would be rehospitalized from time to time, either on my inpatient service or another.  I would eventually see them in more detail after another 5 - 20 hospitalizations, look at the chart and notice that for some time, the diagnosis had become schizoaffective disorder.  Some would ask me about the diagnosis and some recalled the original diagnosis.  If they asked my opinion, I would always tell them what I considered to be the best answer: "As far as I am concerned, your diagnosis is still bipolar disorder.  I am basing that answer on your first hospitalization and your response to treatment.  You don't have any residual symptoms.  Having episodes of bipolar disorder for various reasons does not change the diagnosis."

One of the biases that exists about this diagnosis is that it tends to be more chronic and difficult to treat than bipolar disorder.  The reality is that bipolar disorder can be associated with a significant number of losses in terms of social network, net worth, and in some cases functional capacity.   There are frequently problems with alcohol and use of other intoxicants. Primary psychiatric disorders are always made more complicated by addictions. Like schizophrenia and depression, psychiatric research has not done a good job of defining the cognitive problems associated with bipolar disorder or coming up with successful treatment approaches. Although some rehabilitative approaches are in place for people in Assertive Community Treatment (ACT) programs, successful treatment is usually based on getting the mood symptoms in remission and the prevention of rehospitalization and suicide.  I have treated people on an outpatient basis with chronic mood disturbance and a diagnosis of schizoaffective disorder - bipolar type who work and function at an excellent level.  If they ask me what the diagnosis is - I tell them that it is probably bipolar disorder, even if they have episodic hallucinations.  I tell them "probably" because I know how the diagnosis of schizoaffective disorder is made.  And also because they are functioning well and I don't think that there is a lot of good information on the prognosis of that disorder.  At some level I am also probably biased by the idea that bipolar disorder has a better diagnosis.

My experience with the schizoaffective disorder diagnosis is a necessary backdrop for the following comments from the screenwriter Oren Moverman on whether composer Brian Wilson has a mental disorder:  "Yes, and it's public knowledge. It's called schizoaffective disorder, and it's really a combination of some schizophrenia symptoms, like hallucinations, and mood disorder, such as depression." (see transcript for reference 1).  Moverman is the screenwriter for the Brian Wilson biopic Love and Mercy.  For younger people reading this, Brian Wilson is the founder and composer for the rock and roll group The Beach Boys.  When I was in middle school in the 1960s, people of my generation started dancing to this group.  Their early genre was known as surfing music, based on that culture in southern California.  In these interviews Wilson talks about how he got started writing surfing music.   During the broadcast one of the early songs was Catch a Wave and that immediately brought me back to this time:





The Beach Boys were very successful in that type of music and made a significant comeback in the 1970s and 1980s with different types of music.  Behind all of that was Brian Wilson, a widely acknowledged musical genius who also performed live with the group in its early days.  Wilson is also known for his mental illness and substance use problems as well as his involvement with a highly controversial therapist.  The therapy methods included exerting total control over Wilson, by living with him 24/7 and having him under constant supervision by several case managers.  Wikipedia states that the cost of these services was about $20,000/month.  There was an initial 14 month episode of involvement followed by dismissal due to a dispute over fees and then another episode of involvement prior to permanent dismissal and placement of a restraining order.  Although that therapist seems to be credited in many ways with saving Wilson's life and getting him back to composing music, he was also reported to his California psychology licensing board for violations of professional conduct and according to Wikipedia resulted in a loss of license.  That same source points out that Wilson developed tardive dyskinesia and impaired functional capacity from prescriptions from this therapist's "staff".  I did not see any reference to prescribing psychiatrists or physicians.

This brings me to the inspiration for this post.  Once again it is Fresh Air's longtime interviewer for this program - Terry Gross.  In this series of interviews, Gross starts out with a story about the release of a new film about the life of Brian Wilson titled Love and Mercy.  She has two interviews that she conducted with Wilson from the past and a current interview with the screenwriter of the current film. One of the full length interviews is available on the Fresh Air web site from 2002, but I could not find the one from the 1990s.  There are also excerpts of earlier interviews played in the current interview.  The author starts out describing the focus on three discrete periods in Wilson's life and how that proved to be too much and how the focus had to be narrowed to two periods in the 1960s and 1980s.  Because of those time frames, Wilson is played by two different actors Paul Dano in the 1960s and John Cusack in the 1980s.  Moverman comments on the technical aspects of the film, like the reason for focusing on the musicians.  He also comments on the therapy controversy and states that Wilson was misdiagnosed and overmedicated.  At that point Terry Gross comments that the California Board of Medical Quality Assurance was investigating the therapist because medications were being prescribed and he was not licensed to prescribe them.

One of the most interesting aspects of Gross's work is the historical context.  She has commentary from Brian Wilson in an earlier interview commenting on the therapist controversy:

WILSON: "He's been performing a health operation on my head. He's done something that's impossible that nobody could do."

GROSS: "What do you think he's done that's really worked for you?"

WILSON: "Well, what he's done that worked for me was he's taken my body and transformed not only my physical shape, but he's transformed the chemistry within my blood, you know, from dirty to clean. And when you go through those transformation periods, you go through a little hell, you know what I mean? It's a little bit of hell to have to come through all that, all right?......."

Moverman thought that Wilson was referring to getting him off of intoxicants when he refers to blood chemistry.  Listen or read the complete transcript but in this section Wilson emphasizes the need for moving ahead rather than focusing on revenge for something that happened in the past.  I encourage anyone interested in this particular story or recovery from mental illness to listen to Brian Wilson's spoken words in these interviews with Terry Gross. 

Any acute care psychiatrist will probably be interested in this story.  For me it highlighted a number of issues.  Whenever I see a story like this, the usual way it is handled in the media is to get an expert and try to make diagnosis.  This is exactly the wrong thing to do at many levels.  One of the main concerns is the interplay between substance use and psychosis and mood symptoms.  In my experience, 95% of people seen in acute care and addiction settings are misdiagnosed with bipolar disorder, schizophrenia, depression, and even attention deficit hyperactivity disorder when they have a clear substance use problem that is responsible for those symptoms.  That does not mean that medical treatment is not necessary, but it probably means that it will be temporary.  I am not prepared to say that was an issue in this case, only that when you have seen that problem as often as I have that is one way to approach the issue.  The other dimension here is how difficult it is to effect changes and help people get back on path when they are clearly engaged in high risk and what is described in these transcripts as destructive behavior.  There are really very few options left for people with problems as severe as the ones that Brian Wilson was going through.  In most cases, it is a number of emergency department visits and brief admissions to psychiatric units.  I can say without a doubt that problems this severe are not reversible by those interventions or outpatient visits for twenty minutes to see a psychiatrist every one to three months or seeing a therapist every week for an hour.  Most people stop seeing the therapist after a visit or two.  They may have the thought that they are seeing the therapist because it is somebody else's idea.  

I certainly do not condone the therapy methods used Wilson's case, but fully acknowledge that our current systems of care are not likely to produce a positive result for persons with severe disabilities.  Above everything else this is a story of recovery.  Brian Wilson endured acute symptoms and significant disability and came out the other side.  He continues to write and produce music and that music inspires millions of people.  


George Dawson, MD, DFAPA


References:

1:  Fresh Air with Terry Gross.  'Love & Mercy' Brings The Life Of Brian Wilson To The Big Screen'.  June 18, 2015.

2:  Fresh Air with Terry Gross.  Producer And Arranger Brian Wilson, A Genius Of Rock.  August 27, 2002.

Supplementary:

I have not seen Love and Mercy yet but will probably add a few comments here when I have.

Attribution:

By Brocken Inaglory (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

kappa statistic rhetoric

This post was inspired by a post on the Neuroskeptic.  The impression I get from that blog is that the average reader thinks that psychiatrists are a bunch of chuckleheads who know very little and that is probably why they are so ignorant of science.  The Neuroskeptic himself seems to be slighlty more tolerant but like most bloggers he has to stir the pot.  The focus of this post was to take a look at kappa statistics given in the article by Freedman on DSM5 field trials and a graphic supplied by the boringoldman blog and conclude that DSM5 reliabilities were not good, they were not as good as DSM-IV, and thankfully psychiatrists could just ignore the DSM if they wanted to.

On the face of it all this seems like damning criticism.  Is there any defense from the neuroscientific opinion?  It turns out that there is and it comes from two sources.  The first is the common experience that most people have had who have any medical diagnosis in their lifetime.  Were you ever misdiagnosed?  Did you ever get a second opinion and find that the diagnoses by both doctors were so far apart that it was difficult to make a plan to address the problem?  I can give you one of many examples from my lifetime.  When I was a second year medical student I had several incidents of ankle pain.  I was assessed and ended up at an orthopedics clinic.   I had my ankle casted a couple of times, even though I had no history of trauma.  I finally woke up one night with excruciating left ankle pain and went to the emergency department.  I saw orthopedics again and they aspirated the joint.  They also asked my  wife to leave and asked me if I had possibly contracted gonorrhea somewhere.  I was given acetaminophen with codeine and discharged after about 8 hours.  A couple more weeks of pain and I finally got in to see one of the top experts in Rheumatology who finally made the diagnosis of gout.  At that point I had seen 4 or 5 other doctors and none of them had been able to correctly diagnose the cause of my ankle pain.  Calculating a kappa statistic for a comparison between the expert and the previous physicians would have resulted in a very low number.

But the story doesn't end there.  As anyone with gout knows, it has varied presentations including inflammation that often seems to extend outside of the joint.  During my residency training a few years later I had acute right wrist pain.  The internist I saw decided he needed to aspirate my wrist joint and ended up aspirating a piece of the wrist joint into the syringe.  No diagnosis despite this procedure.  I demanded treatment for gout and of course it worked.  Several recurrences of wrist pain have resulted in misdiagnoses of cellulitis.  Keep in mind that I am not testing these doctors.  I am presenting to them and telling them I have gout and I think my wrist pain is an acute gout attack.  They are saying: "Well gout doesn't usually affect the wrist. I think this is cellulitis."  I have walked out of clinics and thrown the prescription for antibiotic away as I walked out the door.  I finally just got a supply of the anti-inflammatory medication that I need and treat these episodes myself rather than risk misdiagnosis by a physician who does not know much about gout.

You could say this is all anecdotal.  I have more anecdotes about how I have been personally misdiagnosed and the anecdotes of an additional thousand people at this time.  I heard Ben Stein say: "At some point the anecdotal becomes the statistical" and this is a good example from medicine.  But what does the literature say about the reliability of diagnoses.  The diagnostic criteria for gout have been around longer than the DSM.  Another frequent criticism of psychiatric diagnosis is that there are no confirmatory tests for the diagnosis.  Numerous confirmatory tests for gout did not prevent misdiagnosis in my case.  

That brings us to the second line of defense - kappa values that are documented in the medical literature.  Let me preface that by saying that compared to psychiatry, there are literally a smattering of kappas from other specialties.  The following table is a sample from this literature search:
  

observation	kappa	reference
Scaphoid bone fractures diagnosed by radiologists	0.51	de Zwart AD, et al.  Interobserver variability among radiologists for diagnosis of scaphoid fractures by computed tomography. J Hand Surg Am. 2012 Nov;37(11
Reproducibility of serrated polyp diagnosis by pathologists	0.38-0.557	Ensari A, et al. Serrated polyps of the colon: how reproducible is their classification? Virchows Arch. 2012 Nov;461(5):495-504. doi: 10.1007/s00428-012-1319-7.
Detection of anomalous origin of coronary arteries by CT	0.65	Jappar IA, et al. Diagnosis of anomalous origin and course of coronary arteries using non-contrast cardiac CT scan and detection features. J Cardiovasc Comput Tomogr. 2012 Sep-Oct;6(5):335-45.
Skeletal muscle CT to idenitify various muscular dystrophies	Overall 0.27 but in some cases 0.51 and 0.59	ten Dam L, et al.  Reliability and accuracy of skeletal muscle imaging in limb-girdle muscular dystrophies. Neurology. 2012 Oct 16;79(16):1716-23.
Criteria standards to diagnose CHF	0.59-0.74	Collins SP, et al. A comparison of criterion standard methods to diagnose acute heart failure. Congest Heart Fail. 2012 Sep-Oct;18(5):262-71.
Spoke sign for otitis media	0.21 (residents) 0.24 (staff) 0.61 (ENT residents)	Sridhara SK, Brietzke SE. The "Spoke Sign": An Otoscopic Diagnostic Aid for Detecting Otitis Media With Effusion. Arch Otolaryngol Head Neck Surg. 2012 Oct 15:1-5.
Pediatric residents diagnosis of otitis media compared to ENT experts	0.3	Steinbach WJ, etal. Pediatric residents' clinical diagnostic accuracy of otitis media. Pediatrics. 2002 Jun;109(6):993-8.
Abnormal cardiac exam during sports screening	0.1 (cardiology fellows) 0 (fellows compared to staff)	O'Connor FG, et al. A pilot study of clinical agreement in cardiovascular preparticipation examinations: how good is the standard of care? Clin J Sport Med. 2005 May;15(3):177-9

What jumps out at you from the table?  The kappas from other specialties are widely variable and certainly no better than criticized values from psychiatry.  The fact that some of these kappas are based on interpretations of more uniform test data (radiology images or pathology specimens) seems to make little difference.

Low interobserver consensus seems to be the rule rather than the exception in medicine.  Psychiatry is the only specialty that openly admits this.  Misdiagnosis is a universal phenomenon and I would argue that it is a basic element in the process of medical diagnosis.  Some have referred to it as the "art" of medicine, but I prefer a more scientific explanation.   From a neurobiological standpoint there is certainly the phenomenon of significant variability between people.  Medicine from the outset has always presented itself to practitioners as a field where rational analysis produces a logical result.  With the degrees of freedom inherent in biological systems that degree of certainty is an illusion at best.   Pretending that psychiatry is less reliable than any other field is an equally problematic illusion, but I guess it makes for good rhetoric.

George Dawson, MD, DFAPA

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