Hypertension - Clinical and Historical Significance for Psychiatry

 

 

I have written about hypertension in the past on this blog. During the treatment and ongoing care of the many patients I have seen over the years it is always present. The prevalence of hypertension increases with age and other comorbidities. The case of the patients I have seen alcohol and other substance use, obesity, smoking, stress, and prescribed medications are all risk factors. As a psychiatrist following blood pressures, I have to be more compulsive than the average physician. I have rarely been in an outpatient clinic where blood pressures were routinely checked. On the inpatient units where I have worked, blood pressure monitoring could also be a problem. I am reminded of teaching in services on blood pressure monitoring. In inpatient settings is also fairly common to see patients admitted who have discontinued antihypertensive therapy and developed dangerously high blood pressures. In many of those cases they continued to refuse the medication. I was put in the uneasy position of having to follow extremely high blood pressures until a probate court judge could convince the patient it was in their best interest to take those medications.

I have also seen the long-term consequences of uncontrolled hypertension in the form of acute hemorrhagic strokes, subarachnoid hemorrhages, aortic aneurysms, hypertensive cardiomyopathy, and the variations of hypertension related dementia. Many of these findings were in the context of an acute emergency. Several were more of an unexpected finding such as the likely long-term consequences of eclampsia and a brain imaging study done 30 years later.

In the day-to-day care of patients, knowing whether or not they may have hypertension is a critical aspect of care. That is true whether you are considering a medication that can elevate or decrease blood pressure, advising the patient on lifestyle changes to improve their health, or discussing their current exercise program. Most people are unaware of the acute effects of exercise on blood pressure and why strenuous exercise may be contraindicated until they have adequate control of blood pressure.

For all of these reasons, I am always interested in when new guidelines come out or blood pressure screening. Over the years that I have been practicing the suggested cutoffs demarcating hypertension and ranged anywhere from 120/80 to [Age + 100]/90. The [Age + 100]/90 cutoff was a guideline we used when I was an intern in the 1980s. That meant that if you are treating a 70-year-old their acceptable blood pressure was a maximum of 170/90. Over the years extensive research has examined blood pressure dependent outcomes and determined that systolic blood pressures that high are problematic. The question is always-where is the cutoff? Specifically at what point are we maximizing the gains and reducing the risks from overtreatment and using excessive diagnostics. 

The question is one that the US Preventive Services Task Force (USPSTF) seeks to answer. They published their comprehensive look at the issue recently (1).  Hypertension prevalence of 45% of all adults in the US is noted as well as the morbidity and mortality associated with untreated hypertension.  The quoted range of cutoffs is from 130/80 to 140/90. The technical considerations of blood pressure determinations are discussed. Suggested sensitivity of 0.8 and specificity 0.55 for office blood pressure measurement (OBPM) and 0.84 and 0.6 for home blood pressure measurement (HBPM).  Review of 13 study showed that the harms of blood pressure screening are minimal. 

The standard online medical text in the US is UpToDate and it defines hypertension as <120 mmHg systolic and <80 mmHg diastolic with Stage 1 hypertension being 130-139 mmHg systolic and 80-89 mmHg diastolic.  Stage 2 hypertension is defined as systolic of 140 mmHg and diastolic of 90 mmHg. UpToDate also defines a category of treated hypertension for any patient taking antihypertensive medication irrespective of their blood pressure reading. 

The USPSTF paper had an interesting section called How Does Evidence Fit with Biological Understanding? This did not involve a discussion of pathophysiology, but the description of subtypes and what the implications might be.  Sustained hypertension was defined as elevated blood pressure determine both in the office and outside of office settings. Whitecoat hypertension was defined as elevated blood pressure in the office but not in ambulatory settings. Masked hypertension was defined as elevated blood pressure outside of the office but not in office settings. For the purposes of the document, sustained hypertension is considered the entity that the recommendations are based on and the overall risk of cardiovascular disease is sustained hypertension > masked hypertension > whitecoat hypertension.  The diagnosis of white coat hypertension is made by comparing OBPM with HBPM or ABPM (ambulatory blood pressure measurement).  No specific biological mechanisms are discussed. The document points out that even though masked hypertension and whitecoat hypertension are associated with adverse cardiovascular outcomes there is no current evidence that treatment improves as outcomes and they consider that to be a knowledge gap.

UpToDate take a more detailed look at primary and secondary hypertension but does not elaborate much more on the pathogenesis and biology of hypertension. For example, it outlines the autonomic nervous system, the renin aldosterone system, and total plasma volume as being the main systems involved in hypertension. Secondary causes and screening for these causes is suggested but there are no confirmatory tests for essential hypertension.  Interestingly atypical antipsychotics and antidepressants are on a list of medications thought to contribute to hypertension but in personal correspondence with a hypertension specialist – he considered even the most likely medications in that category (bupropion and venlafaxine) to be rare causes.  Empirical treatment and how to treat more resistant forms of hypertension are reviewed. The medications typically address a purported mechanism of hypertension but there is no suggestion to determine the underlying physiology and match it with a medication effect.

Monitoring is another role that psychiatrists can fill. I see the same patient ranging from 6 to 24 visits per year and ideally those would all be heart rate and blood pressure data points. With many of those patients I also discuss home monitoring since approved devices are now very affordable and many of them are being treated often intermittently for hypertension. It is also critical that some patients are able to do HBPM if they are treated with medications that can clearly affect blood pressure such as beta-blockers, prazosin, and clonidine. For subgroup of people who have sustained tachycardia who need close monitoring I also recommend HBPM.

Every psychiatrist should be aware of both the USPSTF screening guideline and either the UpToDate chapter or a similar comprehensive book chapter or review.  Making sure that the patients in question get adequate screening, evaluation, and treatment is as critical as the treatment for their psychiatric disorder.  Comorbidities that are the direct result of end organ damage from hypertension also need to be addressed. I have been able to advise patients on dietary changes, exercise programs, and accepting treatment for obstructive sleep apnea when it was ignored from other sources.

Apart from the medical and clinical considerations of hypertension – are there any other lessons for psychiatry?  It turns out there are and they were first noted in 1960 and since forgotten.  Until that year there was a predominance of the view that diseases are caused by discrete pathological lesions. That view was advanced by Virchow and Koch and was the predominant view of the day. A corollary is that there are always qualitative differences between health and disease.  If a person has the required lesion, they have the disease and if not, they are healthy. That theory was disrupted by a paper by Oldham, et al (3) on the nature of essential hypertension. At that time, the dominant theory of hypertension was that it was an autosomal dominant determined disease that “separately sharply” from the normotensive population. The authors looked at collected data on families and showed that the percentage of families in previous generations with hypertension was too low for Mendelian inheritance.  The authors looked at data on the blood pressure ranges of first-degree relatives of their index hypertensives. The graphical data was interpreted as bimodal distribution of blood pressures consistent with a clear demarcation between elevated blood pressure and normotension.  However, re-examination of the data and a further trial showed that the frequency distribution of blood pressures was not consistent with a bimodal distribution or as the author’s state:

 “seems to illustrate once again that it is not hypertension that is inherited but the degree of hypertension.”

The authors use this data to reject a dominant gene and qualitative differences between disease and non-disease state.  They go on to describe the biological implausibility:

“The alternative hypothesis-that arterial pressure is inherited polygenically over the whole range, and that the inheritance is of the same kind and degree in the so-called normal range as in that characteristic of essential hypertension-is in general conformity with biological theory and with the facts of observation. Just as stature, the classical human example of polygenic inheritance, is the sum of a number of separate bones and tissues, so is the arterial pressure the resultant of a number of discrete components of the cardiovascular system. One need only mention the radii of different parts of the vascular system, the lengths of the vessels constituting the resistance, their elasticity, the chemical composition.”  p. 1092.

As I read that passage, I was reminded of current work looking at the tens to hundreds of network genes activated across the genotypes of millions of unique individuals as a basis for the polygene events that occur in polygenic disorders including psychiatric disorders.

Once the polygene quantitative model was accepted over the single dominant gene qualitative model, it led to a broader application including the obvious one to psychiatric disorders.  Psychiatric disorders have been demonstrated to have familial patterns and some have a very high degree of heritability, but they also do not follow single dominant gene inheritance.  To recap, Oldham, et al basically blew the single gene, qualitative difference between disease state and normality, single pathological mechanism out of the water for complex disorders and they did it in 1960! No philosophy or rhetoric – just good old science. At one point the authors point out that “no student of genetics” had explained the dips in the hypertension frequency graphs.

The psychiatric significance of these authors’ work occurs when Kendell (4) highlighted it 15 years later to illustrate why the single pathological mechanism as “proof” of psychiatric disease is a failure.  Hypertension is a complex polygenic disorder that all psychiatrists must concern themselves with if they are actively treating patients.  It is also a useful comparison model for the psychiatric disorders that we treat,

 the body fluids, the action of the heart, and the

 George Dawson, MD, DFAPA

 

References:

1:  US Preventive Services Task Force, Krist AH, Davidson KW, Mangione CM, Cabana M, Caughey AB, Davis EM, Donahue KE, Doubeni CA, Kubik M, Li L, Ogedegbe G, Pbert L, Silverstein M, Stevermer J, Tseng CW, Wong JB. Screening for Hypertension in Adults: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2021 Apr 27;325(16):1650-1656. doi: 10.1001/jama.2021.4987. PMID: 33904861.

2:  Basile JM, Bloch MJ. (2021) Overview of Hypertension in Adults. In GL Bakris, WG White, GP Forman, L Kunins, UpToDate (Accessed 4/28/2021) from:  https://www.uptodate.com/contents/overview-of-hypertension-in-adults

3:  Oldham PD, Pickering G, Fraser Roberts JA, Sowry GS. The nature of essential hypertension. Lancet. 1960 May 21;1(7134):1085-93. doi: 10.1016/s0140-6736(60)90982-x. PMID: 14428616.

4:  Kendell RE. The concept of disease and its implications for psychiatry. Br J Psychiatry. 1975 Oct;127:305-15. doi: 10.1192/bjp.127.4.305. PMID: 1182384.

5:  Breu AC, Axon RN. Acute Treatment of Hypertensive Urgency. J Hosp Med. 2018 Dec 1;13(12):860-862. doi: 10.12788/jhm.3086. Epub 2018 Oct 31. PMID: 30379139.

6:  Rossi GP, Rossitto G, Maifredini C, Barchitta A, Bettella A, Latella R, Ruzza L, Sabini B, Seccia TM. Management of hypertensive emergencies: a practical approach. Blood Press. 2021 May 8:1-12. doi: 10.1080/08037051.2021.1917983. Epub ahead of print. PMID: 33966560.

 

Graphics Credit:

The image at the top of this blog is for Shutterstock per their standard licensing agreement. I picked it based on the fact that it reminded me of a patient I saw in the emergency department when I was an intern.  He had a large left basal ganglia cerebral hemorrhage that was most likely due to sustained hypertension.

Apologies:

Editing this post was tough. For some reason my Word processer switched to Polish language and stopped automatically checking my grammar and spelling. That was compounded by the fact that I was dictating in Dragon and sound alike words that were spelled correctly were substituted.  I ended up proofing everything on my phone and just finished tonight (4/29).   

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.