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Have Pain? Are You Crazy? Rare Diseases Pt. 2

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Wretched - Piers Nye

“It’s all in your head,” patients with unexplained pain or unexpected symptoms often hear.

My recent post on rare diseases and pediatric pain clearly resonated with a number of people, prompting my immersion in the medical literature and speaking with some experts and patients about these topics and about the difficulties patients with atypical symptoms face.

Rare Diseases

“Rare” diseases cover a variety of illnesses—about 6,800 different ones, according to NIH, each affecting fewer than 200,000 in the U.S. While each disease alone is rare, together they affect almost 30 million, or about 1 in 10 people, just in the U.S. Globally, estimates are that 350 million people have rare diseases. Most of these diseases have a genetic basis; 95% have no approved treatment. Although the Orphan Drug Act was passed in 1983 to stimulate drug development by providing hefty financial benefits, only 326 new drugs have been marketed for these conditions since then, as they are generally not a profitable enough pursuit. (For an exception, please see here on how a drug for Gaucher’s disease was exploited by Genzyme).

Some of the diseases you may have heard of are connective tissue diseases or cystic fibrosis, or phenylketonuria (PKU), because newborns are screened for those. Others are the more recently recognized mitochondrial diseases and pain syndromes of complex regional pain syndrome (CRPS, previously known as reflex sympathetic dystrophy, or RSD). There are more than 50,000 new cases of CRPS annually in the United States, making it a more frequently occurring condition than multiple sclerosis and comparable to Parkinson’s disease, yet receiving a fraction of the attention.

The lack of recognition of many diseases has huge consequences. For example, in one survey, it took patients in the US an average of 7.6 years to be properly diagnosed, after visits to 8 physicians. During that process, they received 2-3 misdiagnoses. Two thirds had to get financial help from charities or public assistance, among other financial difficulties. Unsurprisingly, 75% complained of depression, and 86% of anxiety and stress.

Pain

Each of the teens I wrote about last month has conditions that can cause severe pain. This is commonly misdiagnosed as a “somatoform” or “conversion” disease—symptoms unexplained by medical diagnoses—causing further damage to the patient. For example, as I mentioned last month, Justina Pelletier was taken away from her family and kept in Boston Children’sHospital psychiatric ward for almost a year, because the hospital reportedly thought her symptoms were psychiatric rather than “real.” Justina’s family and physicians are under a gag order by the court, so we can’t learn more now.

Sick Chick's feet

Since writing about Justina and Rose, I’ve spoken with “Sick Chick,” a teen with chronic pain that was also misdiagnosed for some time. At age 11, Chick developed severe, incapacitating knee pain abruptly, without a prior injury, which is a common precipitant. Then she developed patchy loss of sensation. Her foot turned blue and cold. She saw multiple doctors trying to find out what was wrong, including a pediatrician who said “it didn’t make sense so it must be in her head.” When asked how she could make her feet different temperatures and colors, he replied “There are Swamis in India who can do that.” After being diagnosed by multiple doctor’s with CRPS, she saw a neurologist, who immediately said she didn’t have CRPS and, in only a 30 minute appointment, diagnosed her with a conversion disorder (where symptoms are thought to have a psychological, rather than physical or medical cause). Chick says, “It made me very scared that it could be” this, “but I knew this was real and I wasn’t imagining the pain…Now I’m really angry [about that].”

Sick Chick"s Pain - location and type

Since then, Chick has traveled cross-country for care. She went to one inpatient rehabilitation unit where she says the therapist initially took her crutches, threw them across the room, and told her to go get them. Surprisingly, she seems less angry with them than I might have expected, as the intensive physical therapy did result in her regaining her ability to walk. The following year, the RSD spread to her other knee, and she was hospitalized again at a different rehab center. By this point, she had also developed symptoms of postural orthostatic dizziness and tachycardia (POTS, or Postural Orthostatic Tachycardia Syndrome) and dysautonomia (a malfunction of the autonomic nervous system that can cause unstable pulse and blood pressure, leading to fainting spells and GI symptoms, among other). ). These symptoms were explained away as anxiety and the possibility of conversion disorder was again raised, rather than their looking for a medical explanation.

Hearing Sick Chick’s story, I wondered if, had she ended up at Boston Children’s, she would have ended up on the locked psych ward because her parents, too, could have been accused of “doctor shopping” and medical child abuse.

Instead, Chick finally kissed the right frog, and found her prince—a caring, observant physician, who made the correct diagnoses, finding that she has Ehlers-Danlos syndrome (EDS), historically viewed as a connective tissue disease causing extremely hypermobile joints, but now known to be far more complex. She is now getting appropriate therapy for her CRPS, EDS, and other associated syndromes.

Conversion Disorder and CRPS

Hearing these and other similar stories, I studied these syndromes further. I first turned, as I frequently do, to UpToDate, an on-line subscription resource. The chapter on pediatric CRPS is written by Dr. David Sherry, a professor of pediatrics at University of Pennsylvania. Dr. Sherry has recategorized Complex regional pain syndrome (CRPS) as an “amplified musculoskeletal pain syndrome (AMPS).” He states that CRPS “is characterized by extreme pain in a limb out of proportion to the history and physical findings, accompanied by one or more signs of autonomic dysfunction.” He adds that conversion symptoms are “not uncommon.” Yet CRPS is characterized by severe pain, induced by normally non-noxious stimuli (allodynia), edema, cyanosis (bluish purple discoloration typically seen with poor circulation), and excessive sweating. Skin and nail changes are common. In adults, CRPS frequently follows injuries such as fractures (1-2%), especially in women; precipitating injuries are less common in kids. CRPS is one of the few pain conditions that can be diagnosed with objective signs (temperature asymmetry, color asymmetry, abnormal hair and nail changes).

Sherry recommends intensive physical therapy for hours daily daily without offering these children any pain relief. “The treatment starts at the first visit with confirming the diagnosis, discontinuing further medical evaluations, stopping medications for pain (these 2 steps are sometimes much harder on the doctor than the child)…It is important that the team is confident in its ability to cure these children, tolerate the child's pain, be genuinely interested in these children, and understand each other's roles and positions because both the child and parents are prone to try to split the team by playing one member off another.” When asked about not providing pain meds, Sherry responded, "There is no good data that medications work. The most recent Cochrane analysis do not support the use of medications...Most children do not do well with medications, have a lot of side effects and they are expensive."

I also learned more about conversion disorders. These are said to occur when there is some sort of unconscious psychological conflict which can’t be adequately expressed, and becomes “converted” to a physical symptom. By definition, it is unconscious, rather than deliberately factitious or malingering.

Sherry lists conversion symptoms his clinic commonly sees, including in them involuntary muscle spasms and “Fainting and lightheadedness, often called postural orthostatic tachycardia syndrome (POTS) or dysautonomia.” He says “Up to 40 percent of children with AMPS will have at least one conversion symptom.” Sherry adds, “The vast majority of these symptoms need to be ignored since calling attention to them tends to make them worse.” Of note, POTS and dysautonomia are well recognized medical conditions that can be objectively tested (e.g., Tilt Table Test, orthostatic vital signs). These conditions are often treated by cardiologists and neurologists.

The Psychiatric Association definition, such as it is, of conversion disorder, in DSM-4, states “The symptom or deficit, after appropriate investigation, cannot be explained fully by a general medical condition.” Yet Sherry has said, “Once the clinical diagnosis of CRPS is made, it is counterproductive to do further studies, as they delay treatment and put doubts about the diagnosis in the mind of the patient and family.” But if you don’t do a thorough medical evaluation, and base a diagnosis on subjective impression by a clinician, how do you know that there is no underlying physiologic explanation?

A review of studies on conversion symptoms found a misdiagnosis rate of 29% in the 1950s, 17% in the ’60s, and 4% since the ‘70s. While the decline is reassuring, it still a substantial number and leaves considerable room to wonder how many unrecognized medical or genetic illnesses causing odd symptoms are still missed.

The new definition of somatic symptom disorder is similarly troubling:

1. One or more somatic symptoms that is distressing or results in disruption of everyday life

2. High level of anxiety about health or symptoms

3. Excessive time or energy devoted to these symptoms or health concerns

4. Symptoms persisting for 6 months.

Even the physician who chaired the DSM-IV and DSM-IV-TR committees on Pain Disorders, Stephen King, is troubled that the criteria risk mislabeling many people as mentally ill when, in fact, more likely they are suffering from mismanagement of their pain.

A different perspective on CRPS and pediatric pain

On the one hand, we have the focus on psychiatric interpretation of complex symptoms. After having been immersed in the Markingson case over the past year, and the abuses by psychiatrists in schizophrenia drug trials, I am perhaps a little cynical here. I am reminded, too, of the creation of osteopenia to market more drugs (see Drugs in Search of a Disease).

Not all physicians believe in the psychiatric explanation for CRPS or pediatric pain commonly being due to conversion disorder. There is a non-profit organization I have become familiar with called The Coalition Against Pediatric Pain (TCAAP). They have a number of videos on their site (and YouTube) from an interdisciplinary conference last year focusing on Ehlers-Danlos syndrome. While this used to be viewed primarily as a problem of loose joints, EDS now has many overlaps with CRPS, as well as associated with neuropathies, POTS, and migraine. Dr. Pradeep Chopra, a Harvard trained pain specialist and Assistant Professor at Brown University's Medical School, and head of TCAPP’s medical advisory board, told me that there is a “huge component” of autoimmune diseases and that the “joint problem is the least of the issues” in EDS. Many of the children he sees with Ehlers-Danlos present with CRPS. Most notably, he observed, “I’ve never seen a child with conversion disorder.”

Similarly, Dr. Richard Barnum, a child and adolescent forensic psychiatrist formerly with U. Mass and Harvard Medical Schools, spoke at the TCAAP Think Tank. He, too, believes that conversion disorder, if it does exist, is very uncommon. He noted there that patients experience a “diagnosis” of conversion disorder as an accusation of dishonesty, and that it leaves the real problem untreated. Further, such labeling doesn’t ever lead to effective treatment and is very destructive, driving kids away from seeking further medical or psychiatric care.

I am troubled by other aspects of Dr. Sherry’s “boot camp” approach to treating children, particularly in not allowing children to receive any pain meds despite hours of intensive physical therapy. As a parent and occasional patient, myself, I find such an approach unconscionable. I worry, too, that as his approach is more widely adopted, it will lead to more children being taken from their parents as happened at Boston Children’s Hospital. Frighteningly, what happened to Justina is not unique.

Dr. Pradeep Chopra

In contrast, Dr. Chopra recently received the Compassionate Caregiver of the Year award from the Schwartz Center for Compassionate Healthcare, based at Massachusetts General Hospital in Boston. Regarding his award, Chopra said, “I’m providing these patients with a sense of hope. [Telling them] you’re not alone. I’m not going to send you out with a piece of paper, I’m going to send you out with something more precious than that and that’s hope.”… “These are powerful “medicines” that we don’t use. Spiritual validity, love, providing hope. A smart physician can always say, I don’t know what you have, but I’m going to find out, or I know what you have but I don’t know how to help you but I’m going to try. Whether you come up with an answer or not, a patient leaves the office thinking ‘I have someone smart who is there to care for me.’ That is what compassionate care is all about.

As a physician, I understand the frustration of dealing with patients with chronic, unexplained symptoms. They are often angry and unpleasant, not without some justification. I know we don’t have answers for many symptoms. I have no problem admitting my lack of knowledge to patients, looking things up, or referring them elsewhere. Sometimes you know that a diagnosis will likely become clearer over time, like multiple sclerosis or many autoimmune illnesses, and you can explain that. Other times, making a diagnosis is very much like the story of the Elephant and the Blind Men. You see things or look for things with which you are the most familiar or feel are most probable. We have a limited fund of knowledge, and often too little time or opportunity to discuss difficult-to-diagnose symptoms with our colleagues. Often, we have no one to consult with.

And as a person who herself gets weird illnesses and the parent of a child who does the same, I share the frustrations my patients. Sometimes you have to persist in seeking other opinions—a search that is expensive and exhausting, financially and emotionally. It is discouraging. But, as I remind myself and my patients, some times you have to kiss a lot of frogs until you find the prince. Just like Sick Chick did.

Further reading, resources:

A Patient's Story - the story behind the founding of The Schwartz Center for Compassionate Care

A Lack of Data - Julie Maher The tragic and moving story of Dr. Maher's death from a rare cancer

JAMA. 2012;308:1331-1332.

A special thanks to "Rose" for introducing me to these education and advocacy organizations:

The Coalition Against Pediatric Pain www.tcaap.org

Making the Connection

Sick Chick's avatar

Surviving the Rabbit Hole

Sick Chick's Blog

 

Reflex Sympathetic Dystrophy Syndrome Association

Dysautonomia International

MitoAction

The Coalition for Diagnostic Rights

The Global Genes Project

Credits:

"Wretched" - Piers Nye/Flickr

Pradeep Chopra, courtesy Mark Ostow, Schwartz Center for Compassionate Care

Sick Chick's avi and feet, and pain map - courtesy of her and her mom

"Molecules to Medicine" banner © Michele Banks

The views expressed are those of the author and are not necessarily those of Scientific American.

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