Classic clinical associations: findings that point to one disease

Medical students learn a great deal through associations: findings that are so characteristic of a disease that seeing them together brings it to mind at once. Clinicians call this pattern recognition. It is fast and often right, and it works best when you also know where the pattern breaks down.

This guide collects classic associations across the body systems, then looks at the findings that deliberately mislead.

Gastrointestinal

• Crohn's disease: patchy "skip" lesions anywhere from mouth to anus, most often at the end of the small bowel (terminal ileum); inflammation through the full thickness of the bowel wall; fistulas and abscesses, including around the anus (perianal fistulas); non-caseating granulomas on biopsy.
• Ulcerative colitis: bloody diarrhea; continuous inflammation that starts in the rectum and spreads up the colon; limited to the inner lining of the bowel; associated with primary sclerosing cholangitis, a disease of the bile ducts.
• Acute pancreatitis: severe epigastric pain radiating to the back; a lipase at least three times the upper limit of normal; gallstones and alcohol are the most common causes; low calcium can appear in severe cases.
• Acute appendicitis: pain that starts around the navel and moves to the right lower quadrant, near McBurney's point; loss of appetite; low-grade fever.
• Acute cholecystitis: right upper quadrant pain, fever and Murphy's sign, where deep breathing in stops short because the examiner's hand presses on the inflamed gallbladder.

Cardiovascular and respiratory

• Peripheral artery disease: intermittent claudication, a cramping pain in the calf on walking that eases with rest; weak or absent foot pulses such as the dorsalis pedis; a cool limb; an ankle-brachial index below 0.9.
• Heart failure: breathlessness when lying flat (orthopnea) or waking at night gasping (paroxysmal nocturnal dyspnea); raised jugular venous pressure; ankle swelling; a raised natriuretic peptide (BNP).
• Pulmonary embolism: sudden breathlessness, sharp chest pain on breathing in, a fast heart rate; risk factors such as recent surgery, immobility, cancer or pregnancy.
• Sarcoidosis: enlarged lymph nodes at both lung roots (bilateral hilar lymphadenopathy); non-caseating granulomas; tender red lumps on the shins (erythema nodosum); sometimes a high calcium.

Endocrine

• Graves' disease: an overactive thyroid (weight loss, heat intolerance, tremor, palpitations) together with bulging eyes and a diffusely enlarged thyroid.
• Hypothyroidism: tiredness, cold intolerance, weight gain, constipation, dry skin, a slow heart rate; a high TSH in the common primary form.
• Diabetic ketoacidosis: a high blood glucose, ketones, an acidic blood with a raised anion gap, deep rapid breathing (Kussmaul breathing) and a fruity smell on the breath.
• Addison's disease (adrenal insufficiency): tiredness, weight loss, low blood pressure, darkened skin, a low sodium and a high potassium.
• Cushing's syndrome: weight gain around the trunk, a rounded face, purple stretch marks, easy bruising, weak thigh and shoulder muscles and a high glucose.

Kidney

• Nephrotic syndrome: heavy protein in the urine (more than 3.5 g per day in adults), low blood albumin, swelling (edema) and high cholesterol.
• Nephritic syndrome: blood in the urine with red cell casts, high blood pressure and a reduced urine output.

Blood

• Iron deficiency anemia: small, pale red cells (microcytic anemia), a low ferritin, spoon-shaped nails and sometimes cravings for ice or non-food items (pica).
• Vitamin B12 deficiency: large red cells (macrocytic anemia), a sore smooth tongue and nerve damage that can affect sensation and balance.

Nervous system

• Parkinson's disease: a resting tremor, stiffness, slowness of movement and later unsteadiness.
• Myasthenia gravis: muscle weakness that gets worse with use, drooping eyelids and double vision.
• Multiple sclerosis: episodes of neurological symptoms separated in time and affecting different parts of the nervous system, often starting with painful blurred vision in one eye (optic neuritis).
• Bacterial meningitis: fever, headache, neck stiffness and confusion. The full classic triad is present in only a minority of patients, so its absence does not rule meningitis out.

Where patterns mislead

Many findings belong to more than one disease, and that is where pattern recognition gets into trouble.

• Bloody diarrhea fits ulcerative colitis, but also bacterial infections of the bowel and reduced blood supply to the colon (ischemic colitis).
• A raised troponin fits a heart attack, but also myocarditis, pulmonary embolism, sepsis and kidney disease.
• A low calcium fits severe pancreatitis, but also underactive parathyroid glands, vitamin D deficiency and chronic kidney disease.
• Erythema nodosum fits sarcoidosis, but also inflammatory bowel disease, streptococcal infection, tuberculosis and pregnancy.
• A red, painful eye can be inflammation inside the eye (anterior uveitis), which is linked to inflammatory bowel disease, ankylosing spondylitis and sarcoidosis, or an entirely separate eye problem such as acute glaucoma.

The way out is to look at combinations. Each finding on its own leaves several possibilities open, but each additional finding removes some of them. Bloody diarrhea plus perianal fistulas plus eye inflammation is a much narrower picture than bloody diarrhea alone.

How Associations uses this

Stat!'s Associations game is built on exactly this skill. You see sixteen findings, and four hidden diseases each claim four of them. In real medicine several of those findings could fit more than one of the diseases, but on the board each card belongs to exactly one group. The best approach is to find the group you are surest of first, then use the process of elimination on the rest. The Associations guide covers the rules and strategy.