How to Diagnose and Treat a Rare Disease: A Case of Mycobacterium Tuberculosis
Case Report Insights are in-depth interviews that take you inside the diagnosis with clinicians who recently published a Consultant case report.
In this Consultant Case Report Insights, Matthew Nemoy, DO, speaks about his team’s study, “Supraclavicular Lymphadenopathy as the Presenting Feature of Disseminated Mycobacterium Tuberculosis.” Dr Nemoy discusses how the multidisciplinary care of the patient influenced their treatment decision-making, how they navigated the treatment of the rare disease, and what he learned from this case.
Additional Reference:
Nemoy M, Damani J, Backous C. Supraclavicular Lymphadenopathy as the Presenting Feature of Disseminated Mycobacterium Tuberculosis. Consultant. 2023;63(6):e5. doi:10.25270/con.2023.05.000001
To read the full case report, visit the Photoclinic.
TRANSCRIPTION:
Matthew Nemoy, DO: Hi, my name is Matthew Nemoy. I am a second-year pulmonary critical care fellow at Swedish Hospital in Chicago, Illinois. I'm very excited to be here today to discuss a recent case that I helped to take care of along with a couple of other physicians at our hospital.
Consultant360: How did you approach this case and did your approach change during the patient’s continuum of care?
Dr Nemoy: To discuss that a little bit, as with most pulmonary consultations, our initial approach when taking care of the patient was aimed at maintaining a very wide differential regarding the patient's lymphadenopathy and scattered pulmonary nodules for which we were consulted. We wanted to make sure that initially, we excluded aggressive life-threatening diagnoses, specifically things like malignancies or really aggressive infections.
Tuberculosis (TB) was included in this differential as the patient had been born in Mexico and was actually receiving biologic therapy for rheumatologic disease and did show some systemic symptoms consistent with infection, things like fevers, rigors, and night sweats. One other key point that we kind of wanted to hone in on when addressing the symptoms initially was that the biologic therapy has a tendency to weaken her immune system, so she was on CIMZIA, which would leave her more prone to infection. So until the underlying cause of the patient's lymphadenopathy could be uncovered, we wanted to make sure that we maintained appropriate airborne isolation precautions while continuing to work up the underlying cause. The extent to which these isolation precautions needed to be maintained was really based on the patient's results, which would later confirm a diagnosis of mycobacterium tuberculosis [MTB] infection.
C360: Several tests were performed to reach the patient’s diagnosis. How did multidisciplinary care influence the decision on what tests to perform?
Dr Nemoy: As a pulmonary critical care fellow, I often find that patients really get the most comprehensive care when their providers work together as part of a multidisciplinary team. So each step in the diagnostic workup for this individual patient was the result of ongoing discussion between primarily the internal medicine service taking care of the patient in the hospital, but also the pulmonary service that was consulted. So both services agreed that malignancy and infection, particularly pneumonia, whether it be viral, bacterial or of other etiology, as well as tuberculosis should be ruled out as part of the patient's initial evaluation.
Once this kind of differential was agreed upon, it became clear that there would need to be a wide variety of diagnostic evaluations that would be included in the patient's workup. These were things that included sputum cultures, serum, amino acids as well as a lymph node biopsy as the patient had a palpable supraclavicular lymph node that was appreciated on physical exam and then could be visualized on ultrasound as well. Once the decision was agreed upon between the internal medicine service and the pulmonary service, that biopsy should be pursued, interventional radiology was looped in as well to the discussion just to make sure that they felt that the lymph node was amenable to be accessed safely via ultrasound-guided biopsy.
But in the meantime, while all these discussions were going on in the background, we also went ahead and repeated a QuantiFERON assay. From the case presentation, the patient had actually had a negative QuantiFERON assay performed previously as an outpatient by a rheumatologist before she was started on the CIMZIA. And so we just wanted to repeat that to make sure that nothing had changed over the last 6 months since that initial QuantiFERON assay was obtained. So we repeated the QuantiFERON assay and then also obtained some sputum [acid-fast bacilli] AFB cultures that we felt would be helpful in ruling in or out tuberculosis while awaiting these biopsy results. We did get in contact with the patient's outpatient rheumatologist just because they were part of a different healthcare network, and the rheumatologist did recommend that the CIMZIA be held until a diagnosis was confirmed.
C360: What was the key piece of information or data point that confirmed your diagnosis and how did this indicate you reached the diagnosis?
Dr Nemoy: Ultimately, the determining factor in making the patient's diagnosis was a positive AFB culture that we received about 4 weeks after the sputum sample had been submitted to the lab. Initially, the culture had been negative growth to date, but after having some time to grow, it did come back positive for mycobacterium tuberculosis after about 4 weeks. Now, in the meantime, there were some other kind of key lab findings that were pointing us in that direction while we were awaiting the finalization of that culture. Those included epitheloid granulomas that came back on the pathology report from the supraclavicular lymph node biopsy, as well as an indeterminate QuantiFERON Gold assay that was obtained as a repeat test from the patient's initial QuantiFERON Gold assay that was done six months prior with her outpatient rheumatologist.
C360: There was hesitation by the patient to initiate empiric therapy without confirmatory testing, and it appears that she was very mindful of her health care coverage. Can you please speak about this and how you approached the patient’s hesitation?
Dr Nemoy: Honestly, it was one of the best learning points from taking care of this patient, so it's true. Initially, she was hesitant to start any sort of ripe therapy when her QuantiFERON Gold assay came back indeterminate while we were awaiting finalization of the AFB culture as it was initially negative growth to date following the first few weeks in the lab. We thoroughly explained the risks and benefits of going ahead and initiating TB therapy while awaiting a confirmatory diagnosis and encouraged her to start therapy. We think that the patient's hesitancy really was kind of rooted in establishing a long-term treatment plan with us in our particular healthcare network as she was in the process of establishing care with other subspecialists at an outside network, and she was afraid that there would end up being gaps in her care and inconsistent follow-up.
Naturally, this was pretty concerning from a provider standpoint because our gut was kind of telling us that she would be best suited to go ahead and start therapy even while awaiting finalization of that AFB culture. But once that culture result came to us and the diagnosis of mycobacterium tuberculosis was confirmed, it became abundantly clear that she needed to start therapy even while in the process of establishing care with an outside health care network. So therapy was started and then she established care with other specialists, and then we believe that the Department of Public Health likely followed up with the patient's new provider as in the state of Illinois, the Department of Public Health is heavily involved with the treatment of any reported cases of tuberculosis, and we weren't in contact with them specifically. So we believe that they probably followed up with her new providers.
C360: You note in the case that MTB, despite its low prevalence in the United States, is one of the deadliest diseases in the world. What is your approach to treating a rare disease? Are you trying to find the cause of the disease or simply trying to get the patient as healthy as possible?
Dr Nemoy: While the overall prevalence of TB is quite low in the United States, one of the unique things about Swedish Hospital is that it's actually located in one of the most diverse zip codes in the entire country. So we have a very large immigrant and refugee population that we help to take care of here at our hospital, which therefore kind of increases the local prevalence of tuberculosis amongst the patients that we see on a daily basis. So our geographic location kind of makes TB a diagnosis that we do frequently think about when presented with the appropriate clinical findings and imaging.
However, with common things being common, our workups typically follow a pretty stepwise fashion to eliminate other possible etiologies. Things that are at the top of our list typically include bacterial and viral pneumonias, complications of other previously established diagnoses, so in this case, the patient's underlying rheumatologic disorders, malignancies, and other things that are frequently encountered in a pulmonary clinic and in the inpatient setting. It kind of becomes a fine balancing act for us when trying to secure a diagnosis of a rare disease.
While we do gear our efforts towards treating symptoms and trying to keep patients as comfortable as possible, we do so while simultaneously trying to find the underlying cause of the disorder in order to prevent symptoms from recurring and trying to minimize the risk of having any long-term complications. What did become clear as we continued to work through the differential diagnosis and ultimately land on this diagnosis of mycobacterium tuberculosis causing this lymphadenopathy is that the patient's current biologic therapy would be difficult to re-initiate going forward, given that it probably did increase her risk of contracting disease.
C360: What did you learn from this case and what can other clinicians take away from it?
Dr Nemoy: There were so many things that we learned honestly from start to finish and being involved in the patient's care. I think one of the biggest things that we learned is not to let your guard down. So even if you have a negative or an indeterminant QuantiFERON assay, further workup for mycobacterial infections is really warranted, including AFB cultures, particularly in patients that are on TNF alpha inhibitors such as CIMZIA and those with other kind of immunocompromised states or taking medications that can lower the immune system's ability to fight infections. Another thing that kind of became clear and evident in this case is that you really have to allow for adequate time for AFB cultures to grow, as in this case, it may initially be negative, but then eventually turn positive, which ultimately shifts the final diagnosis and the approach to treatment for these patients that you're taking care of.
I felt like we did a pretty good job of keeping a wide differential for the lymphadenopathy, really maintaining an objective stepwise approach while trying to keep the rare diagnoses in mind, but ruling out the common things that we often see that cause lymphadenopathy like the pneumonias and the malignancies that we frequently encounter. And then I think working with patients and really always listening to them that the answer can often line the history. So making sure that you're getting good details about patient's fevers, is there any weight loss, night sweats, kind of those common buzzwords that often patients are the ones to really provide for you and kind of help key you into making sure that you're not leaving out any of those rare diagnoses from your differential.
Ultimately, I think this case really reinforces something that's important for all trainees and coming to the realization that it really takes a full team to provide adequate and sufficient patient care. This was not by any means, an individual effort by the pulmonary service at the hospital. It was very much a multidisciplinary team that ultimately came together to find a diagnosis and help change the life of one individual and their family. I think staying grounded and knowing that it really takes a team to get results is one of the best lessons you can learn, not only as a trainee but also as any provider in medicine.
Dr Nemoy: Thank you so much for taking the time to speak with me today. It was truly a privilege to get to be here. We hope that everyone can kind of take some good learning points from our involvement in this patient's care and recognize some of the challenges that come with making a diagnosis of mycobacterium tuberculosis and ultimately initiating treatment. We certainly learned a lot ourselves, and it was a great case to be involved with.