Recently the Centers for Disease Control published the results of a fairly comprehensive study of what some call Morgellons disease (which Brian also blogged about last week). This is a controversial entity – not so much within scientific circles, but because of an active group of proponents. The claims that Morgellons is a distinct pathophysiological disease, and the recent study, raise some basic questions: How do we establish that a diagnosis really exists? How are psychogenic disorders diagnosed? These are a serious and complex questions in medicine.
First we have to recognize that the term “diagnosis” refers to various types of entities. A diagnosis is a label that we use to describe the signs, symptoms, natural history, and possible biological causes that we observe in more than one patient. There has to be some recurrent pattern, and that is what we are labeling. The term “disease” is similar, but more specific, referring to a specific pathophysiological entity – a specific malfunction or dysfunction of some biological process. For example, myasthenia gravis is a specific disease in which the immune system creates antibodies that attack the acetylcholine receptors on muscle cells, inhibiting muscle contraction and causing weakness and fatigue. In fact MG can be divided into several subtypes, depending on the presence and type of antibodies detected. It is a very specific pathophysiological entity, and diagnosis and treatment flows from our understanding of the disease process.
We do not always understand the details of what causes a specific medical entity, however. Often we start with a syndrome – a constellation of signs, symptoms, and natural history that occurs in more than one patient. It then may take years or decades to sort out the causes or causes of the syndrome, subtypes, prognosis and treatments. Knowledge of the cause is also not black or white. There are layers of depth and detail to our knowledge of various syndromes and diseases. We may know that a disease is an infectious disease, but not know much about the organism. Or we may know what body tissue is being affected and how that results in the symptoms, but not what is causing the damage.
Some labels are what we call a diagnosis of exclusion, but even here there is a range of what we mean by this. A diagnosis of exclusion is what you are left with once all the diagnoses we can rule out have been ruled out. This can be simply a placeholder for our ignorance, and sometimes the name reflects this, such as “fever of unknown origin.” Sometimes it is a “garbage pail diagnosis” – a label we throw into everything we don’t understand but with certain features in common. It think “chronic fatigue syndrome” is a good example of this. CFS is multiple entities that have in common chronic fatigue that is otherwise undiagnosed.
But sometimes a diagnosis of exclusion is a well-established pathophysiological entity, just not one we can practically diagnose with a laboratory study. Migraine headaches, for example, are very well understood (although not completely) pathophysiologically, yet there is no diagnostic test that positively establishes the diagnosis of migraine. It is diagnosed by having a number of typical symptoms and a negative workup for other causes.
With all this in mind – how do we establish that a previously unknown medical entity, such as Morgellons, exists? It’s tricky, but first we need to establish that there is a unique syndrome worthy of its own label. Those who suffer from “Morgellons” have a chronic sense of itching and tingling under their skin. This sensation leads to scratching. The dermatological manifestations include open sores, and there have been reports of strange fibers extruding from these sores. Sufferers also often exhibit psychiatric symptoms, such as anxiety.
There are two schools of thought about what is the true nature of Morgellons. One side, including the Morgellons Research Foundation, advocates the position that “Morgellons disease” is an infectious disease, primarily a skin infection. The infection leads to the itching sensation, the sores, and the strange fibers. The constant irritating sensation also leads secondarily to the psychiatric symptoms. They cite evidence linking Morgellons to Lyme disease, and note that sufferers often respond to prolonged antibiotic use.
The other side believes that the psychiatric symptoms are primary, a form of delusional parasitosis – or the belief that one is infected with parasites. The skin sensation is therefore a somatic (sensory) delusion, leading to chronic itching that causes the skin manifestations. The strange fibers are simply fibers from clothing worked into open sores, and sometimes even healed into healing sores. Analysis of the fibers has shown that they are often consistent with various textiles, and that they are not biological in nature. Any bacteria found in the sores are incidental and not causative, and response to antibiotics is incomplete which is more compatible with a placebo effect than a true antibiotic effect.
The history of Morgellons is relevant as well. The term and the belief that this is a distinct entity did not derive from the observations of physicians or scientists, or any study or new knowledge about biology. It was invented by a mother, Mary Leitao, who believed her son suffered from this entity, and was frustrated that she could not get a doctor to give him a diagnosis she found acceptable.
The presentation of Morgellons is indistinguishable from delusional parasitosis. This does not necessarily mean it does not exist as a separate entity. There are many syndromes in medicine that have more than one disease cause, but share a final common pathway of symptoms. But if we can know that there are distinct diseases under the same syndrome, there must be some evidence we can use to separate them out. With Morgellons there is no convincing evidence of any new or specific feature that distinguishes it as its own disease entity. Proponents make several claims – unidentified fibers and infectious agents mainly, but nothing proven.
This was the focus of the recently published CDC study. They set out to describe and examine those labeled with Morgellons to see if they could find any features that would distinguish Morgellons as a possible distinct pathophysiological entity. In short, their results were negative. The fibers that sufferers often find in the lesions were consistent with fibers from clothes and the environment, mostly cotton. The lesions themselves were consistent with scratching, and did not display any unusual features. No infectious agent was identified. Here are the results from the abstract:
We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17–93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants’ skin were composed of cellulose, likely of cotton origin.
Solar elastosis is essentially damage from sun exposure. The biopsies found no features new or unique to Morgellons. Clinical examination also failed to find anything that would imply a new pathophysiological entity. This was a descriptive study only, so there was no therapeutic intervention.
This study, essentially, is a formal and elaborate exercise in the diagnosis of exclusion – but really thoroughly ruling out known diseases or types of disease and also just looking for clues of a specific biological process. Basing conclusions on negative evidence or the absence of findings is always tricky, but not worthless and should not be dismissed. It’s also important to recognize that it is those who are claiming that a new disease exists that bear the burden of proof, and what this study showed is that every line of evidence in the argument that Morgellons exists as a distinct disease does not hold water. The fibers are not biological or mysterious – they are fibers from clothes. The skin lesions are bug bites and scratching (excoriations), and not some strange or suspicious process. There are no biopsy features that suggest a new process, and there is no evidence of an infectious process, an autoimmune process, a toxin, or anything else that was looked for.
There are features that are suggestive of a psychological entity, such as the presence of multiple somatic complaints and coexisting depression. It is always possible that these can be secondary to the illness, rather than the cause of the illness. This comes up in medicine all the time – are the physical symptoms causing anxiety, or is the anxiety causing the physical symptoms? How do we distinguish these two scenarios? Well, first we look for a biological cause of the symptoms. We may even treat for likely or common entities even if we cannot document them. But we also make a judgement based upon the nature of the psychological symptoms – do they seem out of proportion to the physical symptoms? Are the physical symptoms those that can plausibly be caused by a psychological cause?
In the case of Morgellons, we have a known psychological entity (delusional parasitosis) that fits well with the presentations, and now we have a thorough and complete lack of any findings to suggest that something else is going on.
What about response to treatment? This was not part of the study, and would be a good follow up. For example, when we think it is likely that a presentation is caused by a primary underlying anxiety disorder, we can treat the anxiety and see to what extent the physical symptoms resolve or improve. However, somatic disorders can be fairly difficult to treat (more difficult than anxiety or depression, which are not easy themselves). Further, it seems (although I am not aware of any specific studies on this) that the existence of a subculture that promotes the notion of a biological rather than psychological disorder invests sufferers in this conclusion, makes them hostile to a psychological diagnosis, and more resistant to treatment.
The authors of the study recommended that patients with self-diagnosed Morgellons might respond best to psychological treatments. No other specific treatment can be recommended based upon their study. This is not quite the same thing as concluding that Morgellons is a psychological entity. Medicine is an applied science, and we have to make decisions with incomplete information or tentative conclusions. I agree with the authors, who were very cautious throughout the paper, that the totality of evidence strongly suggests that a psychological cause of Morgellons is most likely, and there is no case to be made for any other alternative.
This still leaves open the possibility of an unknown – and believers will grasp onto this possibility. But there is always the possibility in science of a complete unknown. We have to keep this possibility in perspective, however. It is important to emphasize at this point that our knowledge of what is happening in a patient or with a disease is not black or white – we know everything or we know nothing. Even if there is an unknown entity at work, we are fairly good at finding signs that suggest what type of process is going on. We can see that the body is responding to some infection, or is having an inflammatory response, for example. We can rule out categories of disease by showing the absence of signs that should be present.
With this study, in my opinion, the evidence is now fairly solid that Morgellons is not a new pathophysiological entity. It is entirely consistent with delusional parasitosis. There is more than sufficient evidence to treat based upon this conclusion.