The mission of the fourth edition of Differential Diagnosis in Primary Care is twofold. The first part of the mission is to provide a quick reference for the busy physician who needs a list of common diseases that will explain the patient's symptoms and signs. To accomplish this, the author has listed symptoms and signs alphabetically so that they can be found without searching through the index. Then, as the clinician locates the symptoms and signs, he will find an illustration of the differential diagnosis for the symptom or sign. Also, in most cases, he will find a table listing many diseases that should be considered in the differential. Then, in the text associated with each symptom and sign, the clinician will find the laboratory tests and other diagnostic procedures that will be included in the workup of that symptom and sign. In the appendix, he will find the workup of specific diseases in the differential. The clinician can sharpen his skills by reading the case histories in each section and developing a differential diagnosis. The answers will be found in Appendix B.
The second part of the mission is to teach the clinician or student of differential diagnosis how to arrive at a list of diagnostic possibilities without referring to a textbook of differential diagnosis. After all, in the course of a busy practice, it is not usually practical to look up a differential diagnosis while interviewing or working up the patient. There has to be another way, and the author believes he has found it.
The first step is to group symptoms and signs into one or more of the following categories:
1. Pain
2. Mass
3. Bloody discharge
4. Nonbloody discharge
5. Functional changes
6. Abnormal laboratory results
Now, the basic sciences of anatomy, physiology, histology, biochemistry, and pathophysiology can be applied to each of these categories to develop a differential diagnosis. This is done as follows.
Pain
Developing a list of causes of pain anywhere in the body is best achieved by first visualizing the anatomy of the area. For example, a 50-year-old man presents with chest pain of 2 hours duration. The physician visualizes the chest and sees the lung, the heart, the esophagus, the mediastinum, the aorta, ribs, and spine. With his knowledge of what is common, the physician can develop a useful list of the causes of the patient's acute chest pain as follows:
1. Lungs: Pulmonary infarction, pneumothorax
2. Heart: Myocardial infarct, coronary insufficiency, pericarditis
3. Esophagus: Reflux esophagitis or Mallory–Weiss syndrome
4. Mediastinum: Mediastinitis
5. Aorta: Dissecting aneurysm
6. Ribs: Fracture, costochondritis
7. Spine: Osteoarthritis, herniated disc, fracture
The astute clinician who is not in a hurry may want to go to a second step. This involves a more thorough consideration of the etiologies that may affect each organ. It is helpful to have a mnemonic to help recall the etiologic categories. Any one will do, but the author has found the mnemonic VINDICATE very useful in the differential diagnosis of pain. Applying this mnemonic to the causes of acute chest pain will provide the following possibilities:
· V—Vascular suggests myocardial infarction, coronary insufficiency, pulmonary infarct, or dissecting aneurysm.
· I—Inflammation suggests pericarditis or pleurisy.
· N—Neoplasm might prompt the recall of a neoplasm affecting the pleura or pericardium such as mesenthelioma, carcinoma of the lung, or carcinoma of the esophagus.
· D—Degenerative diseases do not usually cause pain so this would not suggest any possibilities.
· I—Intoxication might suggest uremic pericarditis.
· C—Congenital anomalies are not usually associated with pain in the chest either; however, Marfan syndrome is associated with a dissecting aneurysm.
· A—Autoimmune diseases would prompt the diagnosis of lupus pleuritis.
· T—Trauma would suggest contusion or hemorrhage of the chest wall or pericardium or fracture of the spine.
· E—Endocrinopathies would bring to mind a substernal thyroiditis.
Now, by combining the first and second steps in this process, one can make a very useful table of the differential diagnosis of chest pain. This is the system. Although it may seem cumbersome at first, it can become automatic and second nature with use. The benefit of this system is that one can develop this list of possibilities while interviewing the patient and begin asking meaningful questions to eliminate some of these possibilities prior to the workup. That makes it cost effective.
Mass
With few exceptions, anatomy and histology are the basic sciences that are most useful in developing a differential diagnosis of a mass or swelling. It works as follows:
A 38-year-old white woman presents with a history of a right upper quadrant mass. Visualizing the anatomy in the right upper quadrant, we see the gallbladder, colon, liver, duodenum, pancreas, and kidney.
By simply thinking of what is common, one can arrive at the following list of possibilities:
1. Gallbladder: Carcinoma, hydrops
2. Colon: Carcinoma
3. Liver: Hepatoma, metastatic neoplasm, cirrhosis, hepatitis
4. Duodenum: A neoplasm of the ampulla of Vater would rarely present as a right upper quadrant mass
5. Pancreas: Pancreatic neoplasm, pseudocyst of the pancreas
6. Kidney: Hypernephroma, hydronephrosis, or polycystic kidney
By visualizing the histology of each of these organs, one can broaden the list of possibilities. For example, the liver is made up of a capsule, parenchyma, fibrous tissue, ducts, arteries, and veins. Considering the capsule, one would think hematoma or subdiaphragmatic abscess; considering the parenchyma brings to mind hepatoma; the fibrous tissue suggests alcoholic cirrhosis while the duct suggests biliary cirrhosis; the veins would prompt consideration of hepatic vein thrombosis or pyelophlebitis.
Applying the second step, as was done under the category of pain, one can develop a list of possibilities using a mnemonic. In this instance, it is helpful to use the mnemonic MINT.Here is how that works:
· M—Malformation suggests hepatic or renal cysts.
· I—Inflammation or intoxication suggests hepatitis, alcoholic cirrhosis, pancreatitis with a pseudocyst, cholecystitis, subdiaphragmatic abscess, liver abscess, perinephric abscess, or diverticular abscess.
· N—Neoplasm suggests hematoma, metastatic neoplasm, cholangiocarcinoma, carcinoma of the pancreas, hypernephroma, or colon carcinoma.
· T—Trauma would bring to mind laceration, contusion, or hematoma of any one of these organs.
Once again, by putting the anatomy and/or histology together with the etiologic classification, one can develop a very useful table (see page 5).
Now the clinician has a list of possibilities that will help him ask the right questions in the interview with the patient. It will also help the clinician to determine which tests to order in the workup.
Bloody Discharge
Any body orifice may be the site of a bloody discharge. It usually is the cause of great alarm, as it should be in most cases. That is because a bloody discharge often signifies malignancy. In most cases, a bloody discharge should be considered malignant until proven otherwise.
What basic science should be used to develop the differential diagnosis of a bloody discharge? The answer is anatomy, of course. For example, a 56-year-old woman complains of hematuria for several hours. The clinician knows the site of bleeding may be anywhere along the urinary tract. Starting from the bottom up, he can visualize the urethra, bladder, ureters, and kidneys. By simply applying one's knowledge of what is common, it is possible to develop a useful list of diagnoses as follows:
1. Urethra: Urethritis, stone
2. Bladder: Cystitis, stone, neoplasm
3. Ureter: Stone
4. Kidney: Stone, glomerulonephritis, neoplasm, polycystic kidney
The astute clinician will want a more exacting and extensive list of diagnostic possibilities. To obtain this, he can proceed to the second step: Recalling the etiologic possibilities by using a mnemonic such as VANISH as follows:
· V—Vascular suggests embolism, thrombosis, or subacute bacterial endocarditis.
· A—Anomaly suggests polycystic kidney, double ureter, horseshoe kidney, hereditary nephritis, and medullary sponge kidney.
· N—Neoplasm suggests hypernephroma, Wilm tumor, or carcinoma of the bladder or prostate.
· I—Inflammation suggests cystitis, pyelonephritis, glomerulonephritis, or tuberculosis.
· S—Stones can be found in the kidney, ureter, bladder, or urethra and are a common cause of hematuria.
· H—Hemorrhage should bring to mind trauma anywhere along the urinary tract as well as hematologic disorders such as Henoch–Schönlein purpura, disseminated intravascular coagulation (DIC), and hypo-prothrombinemia.
Here again, one can combine steps one and two to make a very useful table of the diagnostic possibilities (see page 217). Now having a list of possible causes of the patient's symptoms makes the interview and workup more meaningful.
Nonbloody Discharge
The differential diagnosis of a nonbloody discharge, like that of a bloody discharge, begins with the basic science of anatomy. Visualizing where the discharge could come from means visualizing the anatomic “tree” or tract of the organ system involved. Unlike a bloody discharge, a nonbloody discharge is most likely due to inflammation. For example, a 48-year-old black man presents with a productive cough of 2 weeks duration. Visualizing the respiratory tree, we find the nasopharynx, larynx, trachea, bronchi, and alveoli. Now, translating each structure into common inflammatory diseases that may involve each of them, we can develop a useful list of diagnostic possibilities as follows:
1. Nasopharynx: Rhinitis, sinusitis
2. Larynx: Laryngitis
3. Trachea: Tracheobronchitis
4. Bronchi: Bronchitis, bronchiectasis, foreign body, bronchial asthma
5. Alveoli: Pneumonia, lung abscess, pneumoconiosis, congestive heart failure
Proceeding to the second step, we can develop a list of causes of productive sputum further by recalling the etiologic categories of respiratory diseases with the help of the mnemonic MINT. This would translate into a list of diagnoses as follows:
· M—Malformations do not lead to a nonbloody discharge of themselves but predispose to infection. Bronchiectasis and lung cysts are examples of malformations in the lung that can cause productive sputum.
· I—Inflammation would bring to mind rhinitis, sinusitis, pharyngitis, laryngitis, tracheobronchitis and abscess, or pneumonia. Hay fever and asthma should be included here.
· N—Neoplasms predispose to infection. Thus a bronchogenic carcinoma or bronchial adenoma may cause pneumonia or bronchitis with productive sputum.
· T—Toxins would be suggested by this category and should bring to mind pneumoconiosis, foreign body, and lipoid pneumonia as causes of a nonbloody discharge.
As with the other symptom categories, a differential diagnosis table can be constructed by combining the first and second steps in this process (see page 410).
One can develop inflammation further by thinking of the smallest organism to the largest. Considering the alveoli or lung would prompt recall of viral pneumonia, mycoplasma, psittacosis, bacterial pneumonia or tuberculosis, fungal pneumonia such as histoplasmosis, and parasitic infestation such as Pneumocystis carinii or Echinococcus.
Now, with these diagnostic possibilities in mind, one can proceed with the interview asking meaningful questions that will help pinpoint the diagnosis.
Functional Changes
Functional changes take place because of an alteration in the physiology or biochemistry of an organ system. Consequently, a differential diagnosis can be best developed by using physiology or biochemistry. For example, a 24-year-old black woman presents with a 2-day history of jaundice and anorexia. Jaundice results from an elevation in the bilirubin level in the blood. Using pathophysiology, one can appreciate that an increased serum bilirubin may result from increased production of bilirubin as occurs in hemolytic anemia or decreased excretion of bilirubin by a diseased liver or obstructed biliary tree. Now one can translate these categories into a list of possibilities using common causes as follows:
1. Increased production: Sickle cell anemia, hereditary spherocytosis, acquired hemolytic anemia
2. Decreased excretion by a diseased liver: Viral hepatitis, toxic hepatitis, cirrhosis
3. Decreased excretion due to bile duct obstruction: Biliary cirrhosis, common duct stone, neoplasm
This list may be abbreviated, but it would provide the clinician with a basis for a meaningful interview of the patient and a logical laboratory workup. Thinking of increased production, one would ask about other symptoms of sickle-cell anemia, such as joint pain, cramps, and the fever of sickle-cell crisis. Thinking of bile duct obstruction, one would ask about previous attacks of right upper quadrant pain with fever and nausea or vomiting to substantiate a diagnosis of cholecystitis or common duct stone.
In the workup, one would not forget to order a serum haptoglobin level to exclude hemolytic anemia or sickle-cell preparation. One would also consider a gallbladder sonogram if the hepatitis profile were normal.
Now, for a more extensive list of possibilities, a second step can be taken to develop functional changes like jaundice using etiologic categories. The mnemonic MINT can be applied as follows:
· M—Malformation would help recall congenital bile duct atresia and hereditary hemolytic anemias.
· I—Inflammation would bring to mind viral hepatitis, amebic abscess, lupoid hepatitis, and acquired hemolytic anemia.
· N—Neoplasm would suggest hepatoma, carcinoma anywhere along the biliary tree, and metastatic carcinoma.
· T—Toxins would remind one of chlorpromazine, carbon tetrachloride, alcoholic cirrhosis, and so on.
A third step can be taken to develop a table as has been done in the other categories of symptoms or signs previously discussed.
Abnormal Laboratory Values
As with functional changes, the principal basic sciences used to develop the differential diagnosis of abnormal laboratory values will be physiology and biochemistry.
For example, the clinician has just received a complete blood cell count showing a reduction of the hemoglobin and hematocrit. Using physiology, he or she can recall that anemia may develop from a decreased intake or absorption of iron, B12 or folic acid, a decreased production of red cells in the bone marrow, or increased destruction of red cells in the spleen or blood circulation. Now the clinician can prepare a simple list of possibilities using common etiologies as follows:
1. Decreased intake: Iron deficiency anemia, starvation, folic acid deficiency
2. Decreased absorption: Pernicious anemia, malabsorption syndrome
3. Decreased production: Aplastic anemia, myelophthisic anemia
4. Increased destruction: Hemolytic anemia, DIC, malaria, etc.
The list of possibilities can be expanded by taking this sign to the second and third steps, as demonstrated above.
A unique feature of this fourth edition are the case histories in each section. This allows the student to test his or her ability to apply what's been learned. The correct answers are in Appendix B.
The methods outlined in this introduction now will be applied to each symptom and sign in the rest of this book. It is the hope of the author that the reader will eventually be able to apply these methods smoothly and efficiently in his or her daily practice of medicine.
One other method that has assisted the author immensely in his quest for a diagnosis is prayer. The Bible says, “the Lord will give wisdom to anyone who asks for it” (James 1:5). It is highly recommended that this method be applied in the daily practice of medicine also.