Myelitis and Rheumatological Syndromes: Diagnostic Challenges and the Need for Research
Julius Birnbaum, MD
Johns Hopkins Clinic for Neurological Rheumatic Disease

I.  Introduction

Although myelitis can occur in the context of isolated neurologic syndromes (i.e., multiple sclerosis, Devic’s syndrome), it is less appreciated that myelitis can emerge in the context of rheumatologic diseases.  Systemic rheumatic syndromes - lupus, Sjogren’s syndrome, scleroderma - are diseases characterized by deleterious inflammation directed against any organ.   Therefore, a crucial diagnostic challenge in the evaluation of myelitis is the elucidation of symptoms suggestive of systemic rheumatic syndromes.   When rheumatic disease goes undetected, flares or progression of myelitis can worsen, and ongoing inflammation can damage other organs.  A central theme of this article is that myelitis patients who are not adequately and comprehensively screened for rheumatological syndromes are being incompletely evaluated, especially as rheumatic disease is a risk factor for new flares of myelitis. 

Unfortunately, neurologists lack the specialized training to detect subtler manifestations of rheumatic disease.  In July, 2007, under the aegis of the Johns Hopkins Transverse Myelitis Center, I will be starting a unique Clinic wholly dedicated to evaluating myelitis or other neurological syndromes in the context of rheumatic disease.  I have completed full Residency training in Neurology, and am currently completing a Rheumatology Fellowship.  Below, I discuss why my dual training in Neurology and Rheumatology has afforded me a unique diagnostic and prognostic perch to optimize care of patients with neurologic rheumatic disease. 

For purposes of this article, myelitis refers to an inflammatory syndrome affecting the spinal cord, causing weakness, pain, and/or bowel or bladder difficulties.  Within the past years, the term “myelitis” has been further subcategorized by the longitudinal extent of spinal cord inflammation.  Specifically, “transverse” myelitis refers to inflammation limited to less than 3 vertebral segments on MRI (the vertebral segments are bones encasing the spinal cord); in contrast, “longitudinal” myelitis (or “longitudinal extensive myelitis”) refers to inflammation spanning 3 or more vertebral segments.  The term “mylelitis” will be used to encompass both diagnostic entities of “transverse,” as well as “longitudinal” myelitis.   Both “transverse” and “longitudinal” myelitis can occur in the context of rheumatic disease.  An ongoing research interest is whether for patients with rheumatic disease, the pattern of “longitudinal” versus “transverse” myelitis has important mechanistic or prognostic differences.  A paradigmatic approach to both types of myelitis occurring in the context of rheumatic disease is discussed below. 

II. The diagnosis of rheumatic disease -- the premium of a patient-physician dialogue

As indicated above, most neurologists are familiar with the diagnostic criteria of multiple sclerosis (MS) and Devic’s syndrome.  These criteria emphasize that myelitis or other neurological syndromes are consistent with MS only if there is no better diagnostic explanation.  One of the ironies and weaknesses of updated diagnostic criteria of MS is that it does not elaborate on the specific steps needed for the evaluation of alternative diagnostic explanations.  In the context of this diagnostic vacuum, neurologists who are not trained in the evaluation of rheumatic disease can improperly screen patients for rheumatic disease.  For example, neurologists may perform blood tests checking for ANA antibodies, which are antibodies which can be seen in lupus disease.  However, these antibodies can also be seen in the general, unaffected population.  Therefore, there is no specific blood test which can irreducibly establish a diagnosis of rheumatic disease.  Ultimately, the diagnosis of any rheumatic syndrome tilts on the interpretation of blood tests in the context of a careful history and physical examination.  This premium on patient-physician dialogue is one of the pleasures of Rheumatology.  However, when blood tests are divorced from such a dialogue, then potential treatment or diagnostic workup can be misappropriated.  

At this unique Clinic, my training in Rheumatology will enable me to elicit timely and crucial symptoms which might point towards a systemic autoimmune disease.  

III. Example of a “rheumatological review-of-symptoms”
           
In medical parlance, a “review-of-symptoms” refers to an exhaustive list of diagnostic questions poised to detect and weave seemingly discrepant symptoms into a diagnostic story.  A neurologist’s review of symptoms will include questions relating to decreased vision, clumsiness, confusion or cognitive impairment, motor or sensory symptoms.  However, all patients with myelitis or other neurologic syndromes similarly require and deserve a rheumatologist’s review of symptoms.
           
Lupus poses a formidable diagnostic challenge, as it can affect the skin, heart, lungs, kidneys, as well as the neurologic system.  When I screen patients for the presence of lupus, I need to consider the potential involvement of all of these organs.  This leads to an exhaustive list of questions not usually encountered in the neurologist’s review of symptoms: Has there been any joint pains/joint swelling/joint warmth?  Any morning stiffness?  Any episodes of fingers or toes turning blue in cold weather?  Any hair loss?  Any rashes?  Any oral or genital ulcers?  Any history of shortness of breath, any pain on deep inspiration?  Any history of dry eyes or dry mouth?  Any problem swallowing?  Any worsening of rashes or fatigue on exposure to sunlight?  Any burning in the fingertip or toes?        

Frequently, patients can be initially overwhelmed by the number of questions.  What can difficulties with swallowing have to do with sudden paralysis and incontinence?  They often demur that prior neurologist evaluations have never led to this cavalcade of questions.  A critical goal is to explain the hidden unrelatedness of these questions; part of the elusiveness and complexity of any rheumatic disease is that the pathophysiologic process is as seemingly arbitrary and undiscriminating as the breadth of the rheumatologist’s review of systems.  Because any organ can be attacked in rheumatic disease, questions need to comprehensively delve into the most subtle symptoms suggestive of systemic inflammation.  Without such information, any “screening” tests which are commonly performed by neurologists are incomplete.  In a sense, this is the redemptive aspect of the rheumatologist’s review of systems - the narrative of the patient remains the most important part of the diagnostic process.  By the time I have completed a rheumatological review-of-systems, the likelihood of underlying rheumatic disease has crystallized, and awaits confirmation or repudiation by the physical examination. 

IV. Example of the rheumatolgist’s physical examination

Any myelitis patient is familiar with the rhythm and detail of the neurologic examination.  However, the rheumatological examination has a similarly meticulous sensitivity for subtle findings.  Sjogren’s syndrome is characterized by inflammation of the glands causing salivary production in the mouth.  I therefore spend time looking under the tongue, looking for any deficiencies of salivary production.  I palpate the cheeks, feeling for any swelling or nodularity of the salivary glands.  All of the rheumatic disorders can cause inflammation of the smallest blood vessels.  Such capillaries are clustered around the nailbeds, and I often spend minutes looking at nails, looking for any corkscrewing, twisting, or other abnormalities of nailbed blood vessels.  The scalp is examined for patchy hair loss.  The joints are maneuvered, palpated, ranged, felt for heat, examined for structural deformities.  The edge of finger tips are examined for ulcers, pitting, or loss of digital pulp, skeletal signs that can signify scarring.  

V. Formulation of the diagnostic impression

Recently, I encountered a patient with myelitis, who for years had been complaining of being thirsty.  Her neurologists, aware that the impaired salivary production in Sjogren’s syndrome can produce symptoms of thirst, had considered this diagnosis, but improperly terminated diagnostic investigation on the basis of blood work.  When I examined her, her lips were chapped, there were no saliva bubbles under the tongue.  A small biopsy of the lip confirmed the diagnosis of Sjogren’s syndrome, and she was started on appropriate therapy.

By the conclusion of the history and physical examination, I might have a reasonable suspicion about whether myelitis or other neurological syndromes are manifested in the context of rheumatic disease.  I might then order specific blood tests to further corroborate or repudiate my diagnostic impression.  A key point worth emphasizing is that such blood tests only serve to enhance or blunt my clinical diagnostic impression, but never subvert the saliency of the history or physical examination.  In effect, there are no blood tests for lupus, Sjogren’s syndrome, or other autoimmune disease.  Any rheumatologic disease, like multiple sclerosis or Devic’s syndrome, is a clinical diagnosis, imbued by the hierarchy and impact of a patient’s symptoms.  Therefore, any myelitis patient who undergoes blood screening tests as an exclusive diagnostic step for rheumatic disease is being shortchanged, as each symptom needs to be chronicled and rigorously investigated.  

VI. The prognosis and therapeutic implications of detecting underlying rheumatic disease

When should a patient with myelitis be concerned for underlying rheumatic disease?   Here is my simple answer: Every single time.  Any new diagnosis of myelitis deserves a thorough clinical and physical examination for detecting underlying rheumatic disease.   Any new flare of myelitis, or any example of myelitis becoming intractable or less responsive to previous adequate therapy also deserves a more intensive evaluation for underlying rheumatic disease.  Diagnoses of multiple sclerosis are unsatisfactory and invalidated in the absence of considering alternative rheumatological explanations.  As illustrated above, the most seemingly mundane and seemingly incidental symptoms are often crucial in elucidating subtle symptoms of systemic inflammation. 

Detection of underlying rheumatic disease is important, especially as recent work has illustrated that syndromes, such as lupus and Sjogren’s syndrome are risk factors for underlying rheumatic disease.  Although distinguishing myelitis occurring in demyelinating disease (i.e., multiple sclerosis, Devic’s syndrome) from rheumatological syndromes can pose a diagnostic challenge, this distinction is crucial.  In some cases, the treatment for multiple sclerosis (i.e., the interferons) may cause relapse of underlying rheumatic disease.  Additionally, the treatment for the myelitis of rheumatic disease are immunosuppressant drugs, such as Cyclosphosphamide, Methotrexate, and Imuran, which are not usually the first-line agents for multiple sclerosis. 

VII. Whom should be evaluated at the Neurological Clinic for Rheumatic Disease

In my experience, patients with potential neurological rheumatic disease are fatigued by the process of being separately evaluated by individual Neurologists and Rheumatologists.  Inevitably, each specialist approaches symptoms by a restricted diagnostic lens.  For the patient, this leads to the confusing and apprehensive process of reciting similar symptoms, and receiving discrepant or even conflicting interpretations.  By bridging the gap between the disciplines of Neurology and Rheumatology, the convenience offered by a cross-disciplinary evaluation in a single diagnostic center will hopefully alleviate patient concerns.  We anticipate evaluating the following group of patients:

 (1) Patients with a diagnosis of multiple sclerosis, but who have symptoms or signs of rheumatological disease.   
(2) Patients with relapsing myelitis, or a history of Devic’s syndrome, since these syndromes have a higher risk of underlying rheumatological disease. 
(3) Patients with possible “antiphospholipid antibody syndrome.”  This is a syndrome characterized by clots in the arteries or veins, and is associated with specific antibodies on blood tests.  Antiphospholipid antibody syndrome can be associated with all rheumatic diseases, and can sometimes occur independently. 

In the next TMA Newsletter, I will elaborate on proposed research studies which will be conducted based on the clinical experience of the Johns Hopkins Clinic for Neurological Rheumatic Disease. 

In summary, I want to emphasize that my goal is to continue interacting with patients and Neurology/Rheumatology Colleagues.  As such, I welcome any inquiries or questions.   Please do not hesitate to contact me by email at jbirnba2@jhmi.edu for any clinical or personal concerns.