Wall Street Journal coverage

A great article appeared in the Wall Street Journal today entitled "When Disease Can't be Diagnosed". It further points out the challenge associated with complex diagnosis and the need to improve diagnostic processes and tools. This is great mainstream validation of what we have been talking about, punctuated by the fact that the author clearly read this blog in her research. It's great to get some recognition, even if it isn't cited : )

Healthcare pushing online

A recent article in the New York Times highlights the emerging practice of online consultations in cosmetic surgery. While many patients and physicians find this to be a useful way to efficiently find the right provider and discuss treatment options, others object that such "diagnosis" can't be made online via videoconferencing. These activities are likely to challenge laws about the interstate practice of medicine, benefiting all of those who seek to develop new, innovative health tools online. While we must always keep patient safety in mind, the market is reminding us that there are many health applications for which virtual meetings can substitute for face to face interactions. As technology and attitudes evolve, so must the laws that govern them.

Service to assist with complex diagnosis seeking seed investors and web developers

Berkeley, CA: ComplexDx, a startup that is building a marketplace to facilitate the resolution of complex diagnoses, is seeking seed investors and web developers to help complete product development and launch their innovative service. The company believes that this service could offer a revolutionary way to help the innumerable patients who are unable to find a diagnosis for an extended period of time (see previous posts and links on Hyoumanity.com) due to the complexity or rarity of their cases. The company believes that this issue comes down to a matching problem, with a successful diagnosis requiring a patient with a complex or rare condition to find the doctor with the unique expertise, experience, and insight to recognized and diagnose it. ComplexDx would essentially reverse the diagnostic search by allowing patients to post detailed cases and giving doctors both the mechanism and incentive to find the patients they are uniquely able to diagnose. This will more rapidly and effectively foster the appropriate patient-doctor match for successful diagnoses in complex cases, leading to lower medical costs, better health outcomes, and reduced pain and suffering.

The company is seeking strategic seed-stage investors who have experience with and insight into the challenges faced by patients seeking a difficult diagnosis. One co-founder has an MBA/MPH from UC Berkeley with a background in strategy consulting while the other is an MD with an MBA from UC Berkeley who has experience implementing EMRs. This opportunity has the potential to be highly profitable while helping thousands of patients in need. Please contact brad@complexdx.com to request more information.

Desperately Seeking Diagnosis

This message was sent to me by a reader desperately seeking a diagnosis for her daughter. I re-posted it with her permission to show the challenging situation these patients are in as well as see if anyone may have suggestions to help her.

I just heard about you from a co worker and I have a story about my 23 year old daughter. She became ill 26 months ago after being a very healthy child and young adult.

At age 17, she was diagnosed with ulcerative colitis, after about 12 months of various stomach issues. The gastroenterologist put her on Asacol and the disease was controlled with the medication and food choices. 26 months ago she came down with what appeared to be a severe sinus infection, with horrible headaches, facial swelling, eye irritation, rashes on her hands and various parts of her body, persistent cough and excessive phlegm. Kaiser treated her symptoms separately and nothing helped. In the course of routine blood testing we found some very disturbing numbers in her white blood counts. Platelets were very high – they started in about August of 2007 in the 800,000’s and by February 2008, were close to 1.5 million. Her other white counts also high. Inflammatory markers were also off the charts.

We had seen approximately 30 doctors within Kaiser system and it wasn’t getting us anywhere. They did rule out cancer, a primary blood disorder as well as a number of diseases. But no diagnosis. In February of 2008 I took her to the Mayo Clinic in Arizona, to see if we could get any diagnosis. When they found out her platelets were at 1.5 million they immediately admitted her to the hospital and performed plasmapheresis – had I realized how invasive this process was – we never would have consented since we had already ruled out a primary blood disease. Unfortunately, they didn’t tell us what they were going to do. After spending 6 days in the hospital with an array of specialists, they decided that this was most likely attributable to her ulcerative colitis – though it was a rare occurrence. Extra gastrointestinal manifestations of ulcerative colitis. Mayo put her on 60mg of prednisone in February 2008 and within about 30 days, some of the symptoms subsided. Since that time during her tapering process the headaches returned with a vengeance for about 4 months this past January and the light sensitivity came back.

Her Kaiser docs want to put her on Remicade or Humiera for the inflammation, but we still don’t have a real diagnosis and the side effects of these drug are not worth experimenting with. She has tapered down to 5 mg of prednisone and is still experiencing the excessive phlegm, occasional cough, eye irritation and terrible light sensitivity. Her platelets hover around 800,000.

We have since turned to alternative therapies trying to heal her naturally. This poor young woman with a recent college degree is unable to work, move out of our house and rarely able to drive due to the sensitivity to the light. We are at our witts end, trying to figure out what is really going on. We need a Dr. House and his team!

I am going thru money that we don’t have and cannot get back from Kaiser and I am at a loss trying to help my only child come back from this. Emotionally, I don’t know how much longer she will hang on.

If anyone has any thoughts – they would be greatly appreciated. Thank you so much.

Telemedicine and the Need for a Federal Medical License

For years now, proponents have been talking about the potential for telemedicine to improve health care by expanding access to services. There are a number of examples of this working extremely well, including the UC Davis telemedicine center and the Mass General's Telestroke center. The California Health Care Foundation, Robert Wood Johnson Foundation, and many others have also discussed extensive benefits available from telemedicine and increasing broadband penetration and web-based tools make it increasingly feasible. Nonetheless, we have been much slower to adopt telemedicine than many had hoped. It’s time to get beyond outdated worries and protectionist fears and realize the benefits that telemedicine offers.

Traditionally, we have always conceived of a patient consult as necessarily being face to face. After all, doctors gather significant information from a patient’s nonverbal cues and from physical examination. But, it seems that we are slowly realizing that for many healthcare services, knowledge and experience, rather than proximity, are the most important factors in delivering the best care (particularly if well supported locally). Telemedicine can allow for increased specialization and for experts to deliver their services to a geographically broader, yet medically more focused group of patients.

Complex diagnosis is a clear example of this. In many tough cases, successfully determining a diagnosis becomes a matching problem. For example, consider a patient who has developed the symptoms of Behcet Disease, but who does not yet have a diagnosis. Because this disease affects less than 1 in 300,000 per year in the US, it is often difficult to diagnose and many doctors are likely to miss it. But, a handful of doctors specialize in Behcet and could recognize it immediately. As the patient, would you rather be consulting face to face with a doctor who has never seen Behcet but can do a physical exam, or on a teleconference with the expert who sees 5 cases a day?

Medicine is about knowledge, experience, and insight. Co-location with a patient is preferred, but given the highly fragmented nature of medical knowledge, it is not always possible. For many conditions, the value that can be added by connecting patients with the best person to treat them, regardless of location, by far outweighs what is given up by not being face to face.

Despite these opportunities to dramatically improve care (not to mention reduce costs to patient, payer, and provider), telemedicine has seen slow adoption. Why? One major reason is opposition from physicians and state regulators citing patient safety. I am of course a proponent of patient safety and appropriate oversight, but in this case, I believe that this is largely a deflection of the true motivation. My opinion is that many physicians are concerned that telemedicine will take away business from them and have pushed for tight state licensing and telemedicine laws as a protectionist measure to ensure that doctors from other states cannot take their patients. This only inhibits the advancement of medicine and patient care by limiting the benefit we can realize from a growing arsenal of telemedicine tools and applications.

What can we do? It is time for a federal medical license that allows doctors to practice in any state. Allowing consultations and treatments to cross state lines and to foster the appropriate connections between patients and doctors regardless of location will dramatically improve care for many conditions. Of course this needs to be done with caution, patient protection, and appropriate oversight, but it must be done if we are to realize the benefits of health IT.

Diagnostic Breakthroughs

''I never even heard of that disease before I got it -- and to tell you the truth, I don't think my doctor had, either.”

Many patients who face persistent nondiagnosis or misdiagnosis begin to lose faith that they will ever find a solution to their case. After seeing so many doctors, undertaking so many tests, and trying so many treatments, they no longer want to ride the emotional roller coaster of hope and disappointment and resign themselves to the possibility that they may never find an answer. At the same time, many doctors have the perception that a large portion of patients in this situation are hypochondriacs, have somatization disorders, or suffer from conditions which are beyond current medical understanding – in short, that these cases are “unsolveable.”

While there has been no scientific study of this phenomenon, an abundance of anecdotal evidence suggests that many of these prolonged and difficult cases are in fact solveable. It is not uncommon to hear stories of patients whose diagnsosis evaded numerous doctors, only to be quickly recognized by a later doctor with the right insight and experience to diagnose the condition. Some of the drivers behind this phenomenon are well detailed in Dr. Gurpreet Dhaliwal’s posting “The Distributed Knowledge of Medicine” on this blog. This underlines the need for patients to keep trying to find an answer and to not give up hope. At the same time, doctors must remind themselves that while these cases can be frustrating and it may be difficult to discern between those that are and are not solveable, many of these patients are in fact suffering from conditions that are defined, understood, and diagnoseable.

Narratives of patient cases which presented in a mystifying manner, eluded diagnosis, and were eventually resolved are widely available in The New York Times’ “Diagnosis” column, Discovery Channel’s “Mystery Diagnosis”, and the New England Journal of Medicine’s “Clinical Problem Solving” feature. A small sample of the difficult but solveable cases discussed in these features include Salmonella Choleraesuis, Teratoma, Jamaican Vomiting Sickness, Lemierre's disease, Meckel’s diverticulum, Quinine allergy, Carnitine Palmitoyltransferase Deficiency, Aortic Dissection, Addison's disease, Hodgkin's lymphoma, Idiopathic Diabetes Insipidus, Familial Mediterranean Fever, Tic Douloureux, Coarctation, Thoracic Outlet Syndrome, Ehrlichiosis, Sarcoidosis, Gout, Jimson Weed Poisoning, Hereditary Angioedema, Scurvy, Adrenal Carcinoma, Eosinophilic Pneumonia, Rocky Mountain Spotted Fever, Leptospirosis, and Adult Still's Disease, among many others.

Thankfully, the patients described in these columns had largely positive outcomes. But, given the challenges in diagnosing them we must think about those who were not so lucky. For each of these success stories, there must be many other patients who were unable to find their answer and suffered needlessly. Two autopsy studies (Lundberg 1998, American College of Chest Physicians 2001) show that about 40% of cases examined after death had been misdiagnosed and that a correct diagnosis would have resulted in a different treatment in approximated half of these cases (admittedly, these studies were performed on intensive care patients, so they may not be entirely representative of the broader patient population). We cannot overestimate the need for and value of a correct diagnosis.

The important takeaway is that patients facing complex and difficult diagnoses should not be dismissed as nuisances as many of these cases are in fact solveable. Diagnosis is as much art as science, requiring determined and proactive patients working with resourceful and empathetic doctors. The process can be long and frustrating, but both sides should draw inspiration from the widely available evidence that for many of these patients, an answer is out there.

The Distributed Knowledge of Medicine

The recent entry “A doctor’s view on diagnosis” reveals the challenges that physicians and their patients experience in the face of an unknown diagnosis. John’s situation is regrettably common: being sent to multiple doctors with none able to render a convincing or actionable diagnosis. This leaves the physician and patient emotionally drained and despondent, feeling as if there is no one who can help.

A counterbalance to complete despair is every physician’s first hand or anecdotal knowledge of a seemingly unsolvable case spanning months or years of evaluations, testing, and treatment that is suddenly and unexpectedly diagnosed. Frequently this change of fortune comes about by crossing paths with a single doctor. Fans of Fox’s House will recognize this as a weekly phenomenon. The opening chapter of Jerome Groopman’s How Doctors Think vividly outlines this occurrence, highlighting the weariness on the part of both the patient and the physician in perusing yet another referral and culminating in the diagnosis of celiac sprue, a prevalent but perpetually under-recognized illness. Recently, a young woman suffered from hearing loss, urticaria, and arthritis for decades until she walked into the office of my colleague who recognized the very rare Muckel Well’s syndrome. Relief from a lifetime of pain came within days by instituting treatment with an interleukin-1 receptor antagonist.

In the New England Journal of Medicine weekly case report, expert diagnostic discussions of challenging cases are presented. The point is made on multiple occasions (see June 26, July 3, and August 14, 2008) -- and with refreshing honesty -- that the case was solved on account of the consulting physician’s experience with the disease in question. After 9 years of thirst, insomnia, fatigue, arthralgias, and endocrine abnormalities followed by the development of radiographic abnormalities in the pituitary gland, cerebellum, and aorta, Dr. John A. Mills of the Rheumatology, Allergy, and Immunology Division of Massachusetts General Hospital made the very rare diagnosis of Erdheim–Chester disease (a type of histiocytosis) (http://content.nejm.org/cgi/content/full/359/7/736).

At the conclusion, the following exchange occurs between the physicians at the conference:

Dr. Harris: This patient saw internists, neurologists, and ophthalmologists in his home town, and at [Harvard University’s Massachusetts General Hospital] he saw two neuro-oncologists, a neuro-endocrinologist, and a hematologic oncologist. He also saw another rheumatologist after the biopsy results were available and before seeing Dr. Mills. Experienced pathologists did not consider this diagnosis when the biopsy specimen was first seen. In retrospect, the lesions seen on radiography that suggested the diagnosis to Dr. Mills had been present for several years, but their significance was not appreciated….This experience tells us that the diagnosis of histiocytoses can be remarkably difficult, even with all our available expertise and technology.

A Physician: It seems that this case has lessons for radiologists, pathologists, and internists. Dr. Mills, since most of us here are internists, what lessons should we draw from this case to make us better able to recognize this type of disorder sooner?

Dr. Mills: I was aware of this condition because I have been interested in vasculitis and particularly in aortitis…I have seen several patients with Erdheim–Chester disease who were referred to me with a diagnosis of aortitis, as this patient was. If you had not read literature on this disease, it is unlikely that you could have arrived at the diagnosis.


Whenever I observe this type of insight (and the circumstances that bring together the patient with that particular physician), I recall my challenging cases and think to myself that there must be somebody who recognizes the collection of signs and symptoms that evades diagnosis by me, my network of colleagues, and even Google. I am reminded that there is often a physician whose specific knowledge and experience -- which may derive from a single patient seen years ago or from their lifetime’s work -- holds the key for an undiagnosed patient.

The collective knowledge of human medicine and the experiences and insights of the worldwide medical community are vast. Medical science can be described as a distributed knowledge (http://en.wikipedia.org/wiki/Distributed_knowledge): it is the union of all the knowledge of individuals in a community, which is far more than any one physician, hospital, university, or geographic locale can possess.

A great challenge is determining how to harness this knowledge and make it accessible for physicians who are faced with diagnostic dilemmas. Isabel (http://www.isabelhealthcare.com/) and other diagnostic support systems are one way to connect to this distributed knowledge network. Physician interaction through the internet, essentially replicating the familiar curbside consultation many times over, is another promising way to connect a patient’s case with the appropriate physician. If these sorts of efforts were undertaken with regularity, it is possible that the solutions to difficult cases would come about not by serendipity, as in the instances described above, but rather by systematic and deliberate access to the global medical community’s knowledge and talent.