Top 10 Hard-to-Diagnose Diseases

Executive Summary

Many diseases are difficult to diagnose due to how and when they manifest in patients, which often leads to failures or delays in diagnosis. Diseases that are difficult to diagnose require consideration in the differential, as failures to diagnose and delays in diagnosis are common causes of medical liability claims.

Recommended Actions

• Document your consideration of diseases that are difficult to diagnose and your rationale for ruling out a disease given the patient’s symptoms.
• Evaluate when a disease is likely to occur and what makes it difficult to diagnose to be prepared when the situation arises.
• When possible, use prospectively studied decision tools to help defend your medical decision-making.
• Symptom-related macros in the EHR that include a complete differential diagnosis may provide a checklist of considerations for the physician.
• Attempt to avoid an anchoring bias that may lead you to ignore a specific diagnosis.

Failure to diagnose and delay in diagnosis are some of the most common allegations in medical liability claims that we see at MagMutual. There are a number of conditions that are difficult to diagnose either because they are rare and mimic milder, more common diseases, or the disease is common but presents in an atypical way. Frequently this delay or misdiagnosis can lead to devastating consequences. Following is a list of the top 10 diseases that can be difficult to diagnost.

1.     Pulmonary embolus

PE is associated with in-hospital mortality and it frequently occurs in post-op situations and after hospital discharges. There may be legitimate debate as to the extent of VTE prophylaxis required in a specific case. However, when adverse outcomes arise, your defense will be bolstered by your documentation showing that you considered the risks and benefits of the level of prophylaxis you chose. Aggressive attention to ambulation and drug intervention reduces PEs by 60 percent. So even if you are doing everything to prevent these diseases, they may occur. And it may be a masquerader, often misdiagnosed as a myocardial infarction, seizure or pneumonia.  Referencing UpToDate® or another respected source in your medical decision may help any claim defense.

2.     Necrotizing fasciitis

The “flesh-eating disease” is a rare infection of the skin and subcutaneous tissues, spreading along fascial planes. It progresses rapidly and has a greater risk of developing in the immunocompromised. It is of sudden onset and needs to be treated immediately with surgical debridement and intravenous antibiotics. At the outset it can look like a more routine cellulitis. Major clues can be pain out of proportion to history and exam and abnormal vital signs (toxic appearance) in the setting of musculoskeletal pain. A CT scan does not rule out this condition. Maintain a low threshold to consult surgery when necrotizing fasciitis is on the differential.

3.     Vascular pathology in the neck

Compromise of cerebral perfusion secondary to disruption of blood flow in the neck can lead to devastating neurologic injury. There are a range of insults to the vasculature that can occur including clotting, embolism, trauma and dissection. These manifest in various presentations. They can be silent, painful or show vague neurologic symptoms.

Investigation may require imaging that is not available in the necessary time at all institutions. Patients with neurologic symptoms, altered mental status or dizziness will likely benefit from a thorough neurological exam, including cranial nerve exam, strength and sensory testing of the extremities and cerebellar testing (and gait testing if safe to perform). Any patient with new-onset vertigo should have an assessment for cerebellar stroke including HINTS exam (Head Impulse Exam, Nystagmus Evaluation, and Skew Deviation) and gait testing. Neurology consulting, CT and CTA imaging and stroke alert should be considered when cerebrovascular accident is in the differential. 

4.     Compromise of the spinal cord

This includes epidural abscess and hemorrhage, spinal cord ischemi, and discitis. Any lesion around the spinal cord has a high risk of severe complications. Clinical presentations may be quite variable, and these rare conditions are imitated by many common conditions. The clinical triad of fever, back or neck pain, and neurologic deficit is only present in 13% of patients with epidural abscess or discitis, or may present when the time frame for intervention to prevent permanent deficits has passed.  Early presentations will likely be subtle and atypical.

A sequential evolution has been described, with localized spinal pain, radicular pain and paresthesia, muscular weakness, sensory loss, sphincter dysfunction and finally paralysis. It is important to really palpate the midline spine to evaluate for focal tenderness. Abscesses from hematogenous spread tend to progress rapidly, while the signs and symptoms of osteomyelitis or discitis may evolve over weeks or months. Frequently, the patient gives a history of back strain or mild injury, further confusing the ability to make these rare and serious diagnoses.

Risk factors, if present, may include IV drug use (IVDU), tattooing, acupuncture, indwelling catheters, recent infection and spinal surgery. It is important to consider epidural abscess when back pain presents with some other red flag: IVDU, fever, neurological findings, incontinence, immunocompromised, immunomodulating medication or TB. A heart murmur on exam may be helpful to pick up endocarditis as a primary source of bacterial emboli that seeded the spine. In traumatic back pain, it is helpful to document NEXUS or the Canadian C-spine rules in your medical decision-making. It is important to understand the limitations of the rules (e.g., not using them in the intoxicated or impaired patient and can provide a good neurologic exam) and understand the limitations of plain radiographs (only 70% sensitive).   

5.     Ischemic bowel

Intestinal ischemia is a condition in which inflammation and injury to the intestine results from inadequate blood supply. Intestinal ischemia can be acute or chronic and occurs with greater frequency in the elderly. Intestinal ischemia spans a wide spectrum of severity; most patients are treated supportively and recover fully, while a minority with very severe ischemia may develop sepsis and become critically ill. Diagnostic tests including CT can be normal in early disease, making it difficult to diagnose.  Abdominal pain out of proportion to abdominal exam should be a red flag to consider this diagnosis.

6.     Sleep apnea and post-op hypoventilation

Accompanying the obesity epidemic is an epidemic of sleep hypoventilation syndrome. Sleep apnea is a sleep disorder characterized by pauses in breathing or instances of shallow or infrequent breathing during sleep. In obstructive sleep apnea (OSA), breathing is interrupted by a physical block to airflow despite respiratory effort, and snoring is common. Post op, these patients can face particular difficulties. Giving opioids or other respiratory depressants may alter their typical sleep pattern and lead to aspiration and hypoventilation events.

7.     Compartment syndrome

Compartment syndrome is increased pressure within one of the body’s compartments that contains muscles and nerves. It most frequently occurs in the arms or legs. Crush injuries or long bone fractures can cause high pressure in a compartment, which results in insufficient blood supply to muscles and nerves. Acute compartment syndrome is a medical emergency that requires surgery to correct. If untreated, the lack of blood supply leads to permanent muscle and nerve damage and can result in the loss of function of the limb.

Classically, there are “5 Ps” associated with compartment syndrome: 1) pain 2) paresthesia 3) pallor 4) pulselessness and 5) paralysis. Pain on passive range of motion is one of the first signs of compartment syndrome. A high index of suspicion is essential for timely diagnosis. Nerve blocks and high-dose narcotics desensitize the patient and may contribute to a delay in diagnosis. Loss of function and decreased pulses, however, are late signs. According to an article in Trauma^[1], paresthesia in the distribution of the nerves traversing the affected compartment has also been described as a relatively early sign of compartment syndrome.

During the physical exam, unwrap dressings to fully expose the skin and examine full extremity. Obtain compartment pressures if there is concern. Document that compartment syndrome was a consideration, what factors led you to think it was more or less likely, rationale for including or excluding compartment pressures and orthopedic surgery consultation, and the content of the communication with an orthopedic surgeon if a consult was obtained (time, name, topics discussed, recommendations). Compartment syndrome also is seen when a hematoma occurs within a fascial compartment in an anticoagulated patient.

8.     Perforated or injured bowel post procedure

During patient consent, discuss and document the risk, symptoms and impact of bowel injury. Bowel injury may occur during surgery and is often occult. These injuries may be mechanical or thermal in nature. Methodically inspect abdomen at the end of the procedure and dissect tissue to assess bowel injury. Energy transmitting instruments, such as cautery or harmonic scalpel, should be kept away from the bowel and not left in the abdomen unless it is under direct vision and in active use. Maintain a high index of suspicion for bowel injury if the patient is not following normal course of recovery (fever, leukocytosis, tachycardia, tachypnea, persistent nausea/vomiting, prolonged ileus, greater than normal abdominal pain). Bowel injuries may take a few days to manifest and become apparent. Delayed diagnosis can lead to serious adverse outcomes, including death.

9.     Appendicitis

Appendicitis is a common clinical illness that is frequently missed in the ED or medical office. There are many descriptions of classical signs or symptoms, but atypical presentations are common. Consider CT in female with low abdominal pain, given that appendicits is missed in approximately 1/3 of non-pregnant women of childbearing age (and avoid anchor bias with a positive urinalysis and inconsistent presentation because an inflamed appendix can cause pyuria). Document the rationale for not obtaining a CT. Clear discharge instructions and reexamination within 24 hours when the diagnosis is not clear can be helpful.

10. Sepsis

Sepsis affects more than 750,000 people annually, with a prevalence of three cases per 1,000 people. Mortality rates remain between 25 to 30 percent for severe sepsis. Sepsis is responsible for 20 percent of all in-hospital deaths each year, which equals the number of annual deaths from acute myocardial infarction. Patients at the extremes of age are at higher risk of developing sepsis; for example, patients above age 65 are 13 times more likely to develop sepsis and have a twofold higher risk of death from sepsis.

Avoid prematurely ending consideration and investigation of bacterial illnesses by diagnosing a viral illness. Syndromes that mimic sepsis include hypovolemia, PE, acute myocardial infarction, acute pancreatitis, diabetic ketoacidosis and adrenal insufficiency. Patients with fever or altered mental status should trigger consideration of sepsis screening, including documenting vital signs, lactate, urinalysis and blood cultures. In patients who meet sepsis criteria, think about early empiric antibiotic therapy rather than waiting for a source confirmation. To diagnose sepsis, physicians must obtain historical, clinical and laboratory findings indicative of infection and organ dysfunction.

In summary:

1. Some of these illnesses are common such as PE and appendicitis. In frequent illnesses, it is often the atypical presentations that are the problem. Subtle or unusual presentations can mislead you.
2. In rarer conditions, there is a narrow window of opportunity to make the diagnosis before it may cause irreversible harm to the patient. You might be diagnosing a disease that you have not seen before. The pearl here is to revisit your differential diagnosis in patients who are seriously ill and evolving, and try to avoid the anchoring bias that may lead you to ignore the real diagnosis.
3. In confusing situations, always ask yourself, “What else could this be?” Consider the possibility that is “worst first.”
4. There can be instances in which there is practically no effective window of opportunity for the practitioner to change an outcome, and the defense of such an outcome rests greatly on our ability to recreate (from medical record documentation) what happened, what you thought and your reasonable efforts.

Lessons Learned

• Consider developing macros in the electronic health record (EHR) that include comprehensive differential diagnoses for common presenting symptoms to aid in diagnosis and demonstrate that you acknowledged potential illnesses.
• Consider discussing complex cases with other physicians for a holistic approach and supplemental opinions. Listen to your inner voice when the presentation seems unusual and review the differential diagnosis again.
• Stay up-to-date on current medical information. Podcasts are a great way to gain new information. This is particularly important as research continues to show increased complications the further removed physicians are from residency.

Potential Damages

Failure to diagnose or delays in diagnosis are common causes of lawsuits against physicians. A physician may be liable for the injuries or losses that were a result of the delay or failure to diagnose. Defending against such claims can be time intensive and costly.

[1]Trauma October 2006 vol. 8 no. 4 261-266