Perspectives in Medicine: Diagnostic Challenges

Chris Cirino

About the Author, Dr. Christopher Cirino has been a physician for more than 20 years. His specialties include internal medicine, infectious diseases, and public health. Dr Cirino believes that majority of health problems in a presenting patient a physician sees in the clinic are linked to behavior. I quickly learned how feeble available medications are for these health problems compared to the effectiveness of health empowerment and working toward behavior. The average clinic visit doesn’t afford much time to delve into these areas. As a result of this, I explored the option of reaching out to patients more directly through direct patient coaching and volunteerism. You can find the original post and other interesting posts published by Chris at Find the original post at {{original_post_url}}.

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The last perspectives in medicine was about sudden changes.  This post is on more insidious changes and the diagnostic challenge.

There is an interesting challenge that I notice in clinical medicine.  It is a situation when someone’s health is not quite right but the diagnostic test and the clinical condition has not yet materialized to allow the physician to make a diagnosis.  There is certainly a sweet spot in timing of the diagnosis: long enough to discern one cause from another and confirm it;  not too long that a person is left with discomfort or a health risk.

In the inpatient setting, a patient may come in with a nonspecific series of complaints:  fatigue, chills, jaundice.  There may be nonspecific test results: elevated liver tests, a low white blood cell count, low platelets and a high bilirubin.  This very circumstance happened in a patient that I evaluated.  This series of findings is described as a mononucleosis syndrome.    The challenge is that there are many things, infectious, rheumatologic, and neoplastic, that can cause these findings besides Epstein Barr Virus (EBV), the virus that causes “mono”.

The patient developed the symptoms over a period of three weeks.  She noticed jaundice and increased fatigue.  She had no flu-like symptoms, sore throat, lymph node swelling, or sick contacts.  A battery of infectious diseases tests were performed, but none of them singled out one process.  She may have had a positive antibody for EBV, but so does 80% of the population.  The EBV DNA Polymerase chain reaction test (PCR), a marker of active infection, did not detect any copies.  A CT scan showed an enlarged liver and spleen.  Over a period of several days, she improved to the point that she was able to be discharged – without a diagnosis.

We discussed the next steps, which included a liver biopsy.  The pathology of the liver sample suggested a process that is a result of many possible causes.  It suggested a rare finding known as hemophagocytic lymphohistiocytosis (HLH), which is caused by autoimmune, neoplastic, or infectious causes.  No telling findings otherwise were seen.  Fortunately, she was feeling better.

We had a discussion about the results.  I brought up strategy to address diagnostic challenges.

In medicine, seldom is a condition diagnosed on the spot.  An astute physician can evoke a diagnosis like they are conjuring up magic.  One of my mentors in infectious diseases, while rounding with us on a particularly vexing patient, walked in the room, looked at the patient face and skin (he had some ulcers on his lips and a generalized rash), and almost immediately said “he has Mycoplasma.  And that is what he had.  All other tests were negative, but he had the typical X-ray finding of Mycoplasma, a cause of “walking pneumonia,” and all his tests HIV, syphilis, etc were otherwise negative.  We were spellbound, as we reviewed about this less common presentation of Mycoplasma.

A disease process sometimes takes time to present, time to grow and enable a safe way to diagnose it.  Some diseases can be diagnosed fairly reliably by looking at the skin, our bodies largest organ.  In fact, there is an app for that.  The skin houses a network of vessels that mirror what is going on the in the entire body.  Occasionally, systemic diseases can present with skin findings, that facilitate a less invasive way of making a diagnosis.  This includes conditions such as sarcoidosis, T-cell lymphoma, malignant melanoma, metastatic squamous cell carcinoma of the lung, and lupus vasculitis.

When the disease is confined to the deeper vessels and lymphatic system, often there will be nonspecific changes in the GI tract.  The tests may be nonspecific, such as elevated liver enzymes, white blood cell changes, and anemia.  Since there are a multitude of infections that can present similarly, a shot-gun approach isn’t always high-yield or cost-effective.  The radiologic imaging may also be nonspecific, such as a large liver and spleen, and mildly enlarged lymph nodes.  At that point, the next step becomes a decision between watchful waiting or more aggressive, invasive testing.

The imaging and tests can only hint at the possibilities.  Sometimes, there is a need of tissue, and sometimes there is a need to treat while not being completely sure.  It reminds me of a patient that I saw from Africa who presented in the US with peritoneal fluid, lymph nodes, and thickening changes of the peritoneal lining.  These changes usually occur when there is inflammation.  The pathology report of the peritoneal biopsy was that of non-caseating granulomas, a feature of sarcoidosis but certainly not exclusive to it.  She was from a part of Africa, where an article was published on cases of sarcoidosis.

noncaseating granuloma
Noncaseating Granuloma of Sarcoidosis (Ref:  Wickepedia)

It was also a high prevalence country for tuberculosis, which can present as non-caseating granulomas (though are more known for caseating changes).  Her blood test (quantiferon) was positive for tuberculosis, but it wasn’t clear if it was latent infection (and had sarcoidosis) or if this was peritoneal tuberculosis.  I saw her in the hospital; a different one from where she was being seen.  She just had a biopsy there.  I called the pathologist told him that I found it worrisome for tuberculosis.  He looked at the smears before (tuberculosis stains with acid fast stain) and did not find anything.  My call was enough to get him to go back and look.  He called me a few hours later saying that he found “one acid fast bacillus.”  We started her on four drug tuberculosis and after about one week, she had already felt better.  None of the cultures ever grew; none of the genetic tests were ever positive.  Yet, she had peritoneal tuberculosis.

Although ultimately it goes back to the service that physicians provide to the patient, a vague but concerning presentation can get a physician concerned about whether something is missing, and even if he or she is skilled enough.  Hovering around is a concern of malpractice.  As many as 39% of medical malpractice lawsuits come from failure to make a diagnosis, missed diagnosis, or delay.   There is a point when the nonspecific, mild symptoms start to escalate to more specific, acute symptoms.  Ideally, the time to diagnose a disease is before it can cause a threat on health.

Photo by Pixabay on

Fortunately, there are some important aspects to addressing a challenging diagnosis, for patient and doctor alike.  I approached the patient with the diagnostic dilemma with these points in mind:

  •  Go back to the History and Physical Exam

This is one of the physician’s most important tool.  Whenever I get into a situation of a diagnostic challenge, I go back to the patient and really listen to his/her words and determine the development of symptoms.  A dying art in the era of advanced medical technology, a good history can still assist greatly in making a diagnosis; from some estimates, 70-90% of the time.

A follow-up physical examination while reviewing the history is critical.  I often find that the best exam includes a second visit.  It gives clarity on the history:   the patient may have had a chance to think about the symptoms or questions more; the exam may have been changed or a physician may have missed something on the prior exam. There was a time that after a fourth genital exam, in my stubborn fashion, I found the source of the patient’s fever – a penile abscess.

  • Communication

It is important to keep the channels open and to feel comfortable to discuss any questions or concerns.  I like to reassure the patient that I will continue to search for a the person can contact me and inform me of their health.  We can keep visits at closer intervals to review progress.

  • Go toward the place where there is the greatest change

A blood test can sometimes show changes, for instance in the white blood count or the liver tests.  A patient may have localizing symptoms, for instance, localized abdominal pain.  If there is a concern, an imaging test may be ordered, such as a CT scan.  Where an abnormality is encountered is the place that a more invasive test can be used to assist in the diagnosis.  This often requires a scope or interventional radiology to take a sample.

  • Watchful waiting requires diligence

If a person is not suffering from severe symptoms, they may be safe enough to monitor over time.  This requires careful planning and setting goals.  This could be ensuring that the patient is seen frequently or receives additional testing, such as an imaging study or diagnostic test, in a timely fashion.  In the infectious diseases clinic, I once diagnosed a patient with atrial fibrillation, but needed to confirm it on an ECG, which we didn’t have.  I sent him to the cardiovascular lab; it was closed.  He wasn’t able to get the test for one week, which confirmed the clinical exam.  Was that too long to wait?  Maybe.

  •   Consider collaborative discussions and second opinions

Occasionally bias can obfuscate the ability to draw objective conclusions.  There are always going to be knowledge gaps, as well.  I used to think that being a specialist would have a more confined and manageable knowledge foundation than a generalist.  I though wrong.   It is just as complex and ever-changing.

It’s common that a patient’s information is discussed by multiple providers involved.  In fact, it is a disservice to not have this collaboration otherwise.  It isn’t unusual and sometimes helpful to walk down to the radiology reading rooms, review slides in microbiology or the biopsies with a pathologist, or to scrub in on a surgery.  These perspectives enhance care.

I discuss cases with other infectious diseases specialist as well, if I can’t find a satisfactory answer from my knowledge base or from a brief literature review.  Sometimes, one can be treated while closely watching and considering other causes.  Other times, it is necessary to wait until a definitive diagnosis is made.  It all depends on the acuity.