D.C. TRACTS FEATURE

ARTICLE

Differential Diagnosis

A Strategic Approach

Norman W. Kettner,D.C., D.A.C.B.R.

Dr. Norman W. Kettner graduated with honors from Logan College of Chiropractic in 1980, and after completing his residency training in radiology at Logan Health Centers, received his certification as a Diplomate of the American Chiropractic Board of Radiology in 1984. He is Associate Professor of Clinical Science and Chairman of the Department of Radiology at Logan College of Chiropractic. He received "Instructor of the Year" awards from Logan College of Chiropractic in 1984, 1987, and 1988, the Special Recognition Award for Chiropractic Education and Research in 1988, as well as numerous other awards. Dr Keitner's special areas of interest include MRI, electromagnetic imaging, clinical biomechanics, and chiropractic education.

ABSTRACT

Diagnosis is one of the cornerstones of patient management. Depending on the training and experience of the physician. This process tends to be speculative and, at the least, tentative. This outcome results in substandard patient care and poses the threat of liability. A systematic protocol is presented that outlines the differential diagnostic process. This approach enhances the clinical method as well as the subsequent therapeutic decisions.

INTRODUCTION

Patients seek the services of a physician for two fundamental reasons: to establish the correct diagnosis and to obtain the appropriate intervention, including prevention. Treatment provided for an incorrect diagnosis fails the patient to the same degree as does diagnosis without appropriate treatment. During the course of a patient's workup, the physician can encounter an often bewildering constellation of symptoms and signs. Usually these findings are nonspecific in nature (i.e., radiculopathy). The diagnosis is obtained only after considering a number of competitive etiologies (i.e., disc prolapse, neuroforaminal stenosis) and progressively eliminating them. This is the process of differential diagnosis. It demands both rational and intuitive skills and represents the essence of cost-effective health care.

This paper reviews a strategy for differential diagnosis that emphasizes an orderly approach to clinical diagnostic reasoning. The general approach to differential diagnosis includes data acquisition, analysis with ranking of positive findings, and the construction of the differential diagnosis, which is then narrowed by the testing strategy to a diagnosis. Therapeutic intervention is then designed and implemented.

ACQUISITION OF DATA

The history and physical exam are the most essential components of the differential diagnostic process. All of the subsequent diagnostic decisions are dependent upon the reliability of these data. The history and physical examination obtained by a combination of intuition and sensory input establish the clinical diagnosis. The examiner's intuitive skill is emphasized in the interview while the physical exam requires measurement of the patient's level of function. Both verbal and nonverbal clues (i.e., oversized clothing from weight loss) help formulate tentative diagnostic impressions.

The chief complaint should be thoroughly explored. The patient should review all the symptoms considered to be important. The interview also reveals the patient's level of expression and personality. As the patient's interview unfolds, associations with the natural course of one or more disorders are established. Some pitfalls in the interview process arise from cultural influences, attitudes, fears, ignorance, and memory loss altering the reliability of the historian. During the course of the history, specific branching questions may be posed with the intention of amplifying and distilling various diagnostic hypotheses or "hunches." Past medical, family, and social history may reveal additional clues. The review of systems provides additional value, in that clues such as urinary difficulty accompanying low back pain provide further diagnostic orientation.

The physical examination concentrates on the region of the chief complaint and any associated findings that are borne out in the review of systems. A general survey physical examination should always be conducted even failing the suspicion of abnormality. The vital signs are one of the most cost-effective tests in the clinical arena. An elevated temperature found in a patient with back pain may prevent a physician from mistaking a case of pyelonephritis for an acute facet syndrome.

It is important to describe thoroughly the abnormal findings in the course of the physical examination. The description of these abnormal findings must be independent of their specific anatomic location, as well as separate from the designation or diagnosis. There is no such physical finding as a "pinched nerve." Positive dual stretch tests, depressed deep tendon reflexes, and paresthesia are recorded and their specific spinal level is established before the diagnosis of a S1 root compression syndrome is advanced. The physical exam should also provide the physician with the answer to the question, "How sick or abnormal is this patient?” In addition, any evidence of segmental neurofacilitation should be sought in order to verify the presence of a somatovisceral reflex.

In the course of a physical examination, a finding that is abnormal will often trigger a subroutine of physical assessments, analogous to the branching used in the patient's history. The finding of a thoracic scoliosis in a tall patient would prompt a cardiac evaluation to exclude an aortic aneurysm, a finding associated with Marfan's syndrome. Finally, the patient's examination should be considered as an ongoing process and subsequent visits should allow for a brief review of the positive findings, as well as for identification of new findings or complications.

ANALYSIS AND RANKING OF POSITIVE fINDINGS

After the pertinent findings are obtained during the course of the history and physical examination, they are then listed in the order of apparent relevance. This "weighting" of positive findings in order of significance is often the point where diagnostic accuracy is compromised. Assigning improper significance results in either too much, or too little, consideration for a given finding. Time and the natural course of a disease may alter the frequency and significance of a given finding. Primary or key findings are valuable in that they demonstrate high sensitivity or specificity for a given pathophysiology. For example, weakness in all extremities or quadriparesis suggests a stenosis of the spinal cord, whereas other findings like constipation or vertigo are nonspecific. Some diagnostic findings provide such a high yield that they deserve cautious evaluation. Examples include headache, abdominal and chest pain, fever, and weight loss.

Common errors at this level of the differential process arise when insufficient data are available as a result of careless interview or examination techniques. It is also possible that the physician's knowledge is inadequate or simply lacking interpretive experience. Other sources of reasoning error in the analysis of findings include the "last-case bias." This is the influence on clinical reasoning generated by a recent diagnosis of some import. This influence biases similar cases for a variable period of time to follow. Lastly, avoid the tendency to force congruence of the history and physical findings with a diagnostic classification.

SYSTEM ASSIGNMENT

The positive findings that are delineated and ranked should next be assigned to one or more of the physiological systems. Most clinical findings associated with acute or chronic ambulatory pain syndromes arise in association with musculoskeletal and neurological systems. Examples of such findings would include radiculopathy, myelopathy, weakness, muscle atrophy, and spinal segmental fixation. The genitourinary system is the most common extraspinal source of referred pain to the lower thoracic and lumbar spine. The systems remaining for consideration include endocrine, cardiovascular, respiratory, gastrointestinal, and dermatological. For example, an elderly patient presenting with chronic progressive lumbosacral pain without associated neurological defects occurring in association with a long-standing history of hypertension would raise considerations of problems within the musculoskeletal, cardiovascular, and genitourinary systems. The association of physiological systems and clinical findings amplifies the anatomic designation and further augments or distills the diagnostic impression.

DIFFERENTIAL CATEGORIES

The priority, ranking, and assignment of positive findings to anatomic sites that are cross-referenced with physiological systems now prompts the consideration of one or more differential categories. The definition and diagnosis within these categories are, at times, variable and arbitrary. The categories include neoplasm, infection, vascular, trauma, arthritide, endocrine, and congenital.

Categorical diagnoses provide a classification of pathophysiology to which key clinical findings can be associated. Radiculopathy is assigned to arthritide but can cross into neoplasm or trauma if supported by appropriate findings.

An abbreviated overview of each category and examples of common pain syndromes and their clinical findings are presented below.

Neoplasm

The category of neoplasia should be considered the most life-threatening entity encountered in patient care. Malignant neoplasms of the primary or metastatic variety must be suspected in any adult patient presenting with progressive spinal or pelvic pain. Unfortunately, the average delay in the diagnosis of skeletal metastasis is 10 months. Findings that raise the index of suspicion include intractable skeletal pain or pain persisting day and night for a duration exceeding 5 days. A history, regardless of the remission interval of a bone-seeking neoplasm (i.e., bronchogenic or prostatic carcinoma), compels the suspicion of metastasis when a pain syndrome is refractory to treatment.

Physical findings of weakness₁unexplained fever, lymphadenopathy, organomegaly, or any progressive sensory or motor deficit are clues with important value. Laboratory findings including microcytic or macrocytic anemia, elevated erythrocyte sedimentation rate (ESR), hypercalcemia, elevated alkaline or acid phosphatase, proteinuria, and monoclonal gammopathy are common findings in association with skeletal malignancy. Negative lab tests and radiographs never exclude the possibility of skeletal malignancy.

Infection

The clinical manifestations of infection, like neoplasia, can mimic disorders of almost any etiology. The cardinal clinical manifestations of infection include acute onset of fever, chills, adenopathy, malaise, and myalgia. Joint infections in the appendicular skeleton are often suspected in the presence of a closed posttraumatic effusion that is warm. Spinal infections (discitis) should be considered when spinal or pelvic surgery is antecedent to progressive spinal pain and the patient is febrile.

Constitutional signs, including anorexia, weight loss, or malaise, may be noted. Intravenous drug abusers and other immunocompromised patients (i.e., patients with diabetes or patients taking immunosuppressive medications) are prone to bone and joint infections. Laboratory findings, including an elevation of the white blood cell count and ESR, may increase the index of suspicion for infection. The poor sensitivity of radiography limits its role in the early diagnosis of skeletal malignancy.

Vascular

This category is too often overlooked when acute pain evolves over hours or days following an abrupt onset. Headaches, especially occipital in location, which are sudden and severe in the presence of altered consciousness or neurological deficits, herald a transient ischemic attack, or stroke in evolution. Thromboemboli in the pulmonary or coronary circulation give rise to progressive chest pain, tachypnea, tachycardia, or shortness of breath. Findings of thrombophlebitis are often seen in the leg. Aneurysms of the abdominal aorta can erode the vertebral body giving rise to pain, often clinically indistinguishable from pathomechanical sources. Peripheral occlusive vascular disease should be considered when signs of claudication are noted. Unilateral edema in either extremity warrants consideration of vascular or lymphatic compression. Bilateral lower extremity edema is a sign of congestive failure.

Trauma

Trauma is a frequent source of ambulatory pain syndromes and often arises from vehicular or work-place accidents or from sports endeavors. Ligamentous injury, especially in the cervical spine, must be carefully sought. Atlantoaxial instability can be excluded by flexion-extension radiography. Occult fractures in the neural arches of the mid- and lower cervical spine should be considered if severe posttraumatic cervical spine pain persists beyond 7 to 10 days. Stress fractures can usually be suspected on the basis of a history disclosing that the skeletal pain is provoked by activity and relieved by rest. Fractures are usually accompanied by a history of trauma and pain with the exception of neurogenic arthropathy, which is only minimally painful, if at all. Pathological fractures are usually suspected after radiological evaluation reveals features of bone destruction and/or soft-tissue masses.

Arthritide

This category is probably the source of most patient diagnoses presenting with a pain syndrome. Often macrotrauma is the precipitating event of degeneratiye arthroses, although aggregate microtrauma from inefficient postural controls or work-place stresses may complicate the setting. Reproducible joint-based pain is the hallmark of a degenerative arthritide. The presence of provocable articular pain by an active, passive, or resistive maneuver almost certainly confirms the presence of an arthritide disorder.

The common complications of degenerative diseases of the vertebral column include disc degeneration and herniation, segmental instability, and spinal stenosis. Signs of these complications include altered joint mobility, radiculopathy, referred pain, reflex sympathetic dystrophy, atrophy, spasticity, weakness, or claudication. Myofascial trigger points are often located in neuro facilitated segments and should be recognized. This category also includes the inflammatory arthropathies such as rheumatoid arthritis and ankylosing spondylitis. Inflammatory arthropathies are characterized by a history of pain in multiple bilateral joints accompanied by swelling and morning stiffness. The metabolic arthropathies, such as pseudo-gout and gout, require laboratory diagnosis and joint aspiration for confirmation.

Endocrine

This category also includes metabolic and nutritional disorders. It is one of the most challenging diagnostic categories to evaluate since endocrine glands and metabolism govern physiological activities throughout the body. Often the history and physical exam, particularly inspection, raise a question of an endocrine-metabolic disorder. Most endocrine disorders arise as a result of an excess or deficiency of hormone secretion. Target receptor responsiveness may also be absent or elevated over normal. Common endocrinopathies may manifest by the presence of weakness, easy fatigability, growth abnormalities, hirsutism, weight loss or obesity, and altered reproductive function (impotence, menstrual irregularity). Among the disorders in this category are osteoporosis, which is the most common cause of spinal pain of metabolic origin, diabetes mellitus, hyper- and hypothyroidism, and hypoglycemia. Definitive diagnosis in this category is usually established by laboratory tests of specific hormone levels or by advanced imaging.

Congenital

This category is also grouped with dysplasias and genetic disorders. Among the most important clinical findings suggestive of this category are the short stature of dwarfism, the spider-like hands and feet of Marfan's syndrome, and the history of recurrent fractures in osteogenesis imperfecta. The most significant congenital spinal anomaly is that of an unstable os odontoidium. Without specific clinical features, it is diagnosed by flexion-extension radiography. This condition holds a potential for spinal cord injury if the cervical spine is exposed to significant traumatic forces.

DIFFERENTIAL DIAGNOSIS

After consideration of the various classifications or categories of disorders, a list of diagnoses is constructed in order of declining probability. This probability is influenced by a large number of factors, including age, gender, race, disease prevalence, and clinical features. Common sense, logic, and intuition are utilized to eliminate the diagnostic possibilities and advance the probabilities. These differential diagnoses are as specific as possible (i.e., spinal stenosis, myofascitis of gluteus maximus). Lacking adequate findings, it may be necessary to employ a nonspecific diagnosis. An example would be acute cephalgia or chronic low back pain. This is a working, and certainly a transient diagnosis. However, this is adequate since further resolution will be obtained by the next phase, the testing strategy.

It should be emphasized that the differential process employs significant negative or absent findings, as well as the presence of positive ones. In the case where all significant findings are not explained by a diagnosis, the question must then be raised as to the actual significance of those findings or the possibility of normal variation.

Lastly, always try to include treatable conditions in the differential diagnosis, since to overlook and fail to recognize them is nothing short of a tragedy.

TESTING STRATEGY

The physician is now faced with the decision of whether to proceed directly with treatment or employ testing procedures to eliminate further the differential diagnostic considerations. The outcome of this decision will be determined by the level of certainty or confidence operating over the differential, the presence of conditions capable of inflicting significant morbidity or mortality and the cost effectiveness of further testing. The first factor is a function of training, experience, and clinical intuition. When there is a differential containing morbid or potentially fatal conditions, the physician is compelled to pursue a testing strategy to rule out or confirm their presence. For example, a differential could contain spinal metastasis and spondylosis complicated by neuroforaminal stenosis. The suspicion of spinal metastasis dominates the differential and must be promptly eliminated by appropriate tests. The appropriate test in this case should have high sensitivity to skeletal metastasis. Magnetic resonance imaging (MRI) or radionuclide bone scanning would be obtained since negative plain radiographs demonstrate insufficient sensitivity to rule out metastasis. If the bone scan or MRI is positive, a more specific test will follow to confirm the diagnosis. Sensitive tests are able to detect a given disorder while specific tests confirm its presence.

Appropriate test selection, whether lab, imaging, or physiological (i.e., electrocardiography, spirometry), is necessary for diagnostic orientation, patient safety, and cost effectiveness. Battery, "shotgun," or routine testing is to be avoided. All tests selected in the strategy flow from the differential diagnosis, which, in turn, arises from the positive findings yielded by history and physical examination. This correspondence of the testing strategy with the differential diagnosis is essential in the justification of any ancillary testing procedure.

It must be emphasized that many patients will have the results of treatment modify the differential diagnosis. That is, treatment response is often of diagnostic value. One should not hesitate to employ a trial course of treatment as a testing strategy. In addition, I would emphasize that many patients do not require a testing strategy and may directly enter the treatment phase of management. There is little value in obtaining shoulder radiographs if a 25-year-old complains of occasional shoulder pain and your differential diagnosis suggests supraspinatous tendinitis or deltoid strain. I am reminded of a student who once raised a question regarding the definition of "cost beneficial," as follows: "Was the benefit side of the ratio directed at the physician or the patient?" The results of the appropriate testing strategy should be a working diagnosis that is consistent with all clinical information. An accurate diagnosis not only provides knowledge of a disorder but its natural history, course, and prognosis.

TREATMENT

The next phase of patient management is the use of appropriate therapeutic measures directed at one or more diagnoses. Since the natural course of a disorder is known and should be altered by appropriate treatment, the failure to alter the course implies that 1) treatment is inadequate, 2) other modes of treatment should be employed, or 3) the diagnosis needs revision. Diagnostic revision must be performed in a timely manner. The failure to arrive at a new diagnosis compels the physician to seek specialty consultation. The treatment of a chronic pain syndrome can induce "clinical hypesthesia." This term refers to the failure to discriminate between a benign etiology of pain and a newly superimposed life-threatening source of pain. It arises because the physician is lulled into an expectation of incurable chronic pain. Periodic exams can prevent this mistake.

The collection and analysis of clinical information is a dynamic process that begins with the patient's introduction and is ongoing with constant revision as new information from the interview, physical examination, test results, and treatment response is available. An outline of this approach to differential diagnosis is shown in Figure 1. Note that the process is illustrated in a loop configuration. This emphasizes the iterative nature of differential reasoning, which is a successive distillation of hypotheses that ultimately approximates the diagnosis.

CONCLUSIONS

Effective clinical decisions result from an orderly and strategic reasoning method. If employed, this method will provide cost-effective clinical management. The emergence of one or two diagnoses from a dozen or more differential considerations can be as satisfying a feature of patient care as a favorable response to treatment.