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Rare Conditions of Great Importance in Differential Diagnoses

December 30, 2021
Jeffrey Szer, MBBS
Professor of Hematology, The Royal Melbourne Hospital, Australia

Hematologists are confronted by an array of complex and somewhat obscure conditions. As a follow-up to a popular session at the 2018 ASH Annual Meeting, this year's virtual meeting will include an Education Session titled, "Anxiety-Provoking Hematology Consults, Second Edition," in which several experts will present case-based examples of unusual or difficult-to-diagnose conditions.

Speakers include Kenneth L. McClain, MD, PhD, of Texas Children's Hospital, who will discuss histiocytic disorders including Langerhans cell histiocytosis (LCH) and Erdheim-Chester Disease (ECD); Michael Linenberger, MD, of the University of Washington and the Fred Hutchinson Cancer Research Center, who will provide an update on the diagnosis and management of the most common porphyrias; and Ari Zimran, MD, of Shaare Zedek Medical Center in Jerusalem, who will examine why Gaucher disease is so commonly overlooked and why diagnosis is often delayed.

Here, session chair Jeffrey Szer, MBBS, of The Royal Melbourne Hospital in Australia, and Dr. McClain preview the topics this session will address and discuss why these patient scenarios are "anxiety provoking."

Why was this an important topic to cover in this year's Education Program?

Dr. Szer: Last year, I approached the Education Committee organizers with concerns that some rare diseases with major hematologic consequences were underrepresented at the ASH Annual Meeting. My particular area of interest is Gaucher disease, a condition – at least in adult medicine – that is often diagnosed and managed by hematologists, but is so rare that most hematologists will never have seen a case. The consequences of delayed diagnosis can be devastating for patients, sometimes with the development of irreversible complications.

ASH decided to join this topic with two other frequently missed or misdiagnosed conditions – the hereditary porphyrias, and histiocytic disorders including LCH and ECD – in a session at this year's annual meeting about uncommon conditions hematologists may see in consultation. We invited three leading experts in these fields who not only understand the science, but also have substantial clinical expertise in the management of these patients.

Why are these conditions "anxiety provoking"?

Dr. McClain: With LCH and ECD, where I am focusing my presentation, the anxiety comes from the fact that many hematologists have little experience with these two diseases. They are challenged to know how to evaluate the patients and determine appropriate treatment.

Dr. Szer: These conditions are all characterized by having a very small pool of experts globally and of being underrecognized, and often forgotten, differential diagnoses when clinicians are confronted by complex patient scenarios. Patients with these conditions are commonly seen by hematologists at some point. The anxiety sets in when clinicians are unable to make a more usual diagnosis in a patient with confusing clinical and laboratory features.

Our brains (and PubMed) are challenged to come up with an appropriate plan for making a specific diagnosis. For example, most hematologists confronted by a patient with splenomegaly, thrombocytopenia, and bone pain will think of many differential diagnoses before, if ever, considering Gaucher disease. It is appropriate to consider more common diagnoses rather than conditions with an incidence of less than 5 cases per 1,000,000 people; however, inappropriate and often invasive investigations can be avoided if the "thought bubble" were a little wider.

"I hope [attendees] will take away a greater understanding of these conditions … that will reduce the anxiety around these types of clinical presentations."

—Jeffrey Szer, MBBS

Are these types of rare, obscure conditions something hematologists should be educated about? How can hematologists stay up to date about them?

Dr. Szer: Staying up to date about these disorders is challenging, but I perceive that one way – and possibly the best way – is to build educational aspects of the condition into more general hematology meetings. This way, at least the names and key features of these disorders are frequently put in front of our colleagues. In an increasingly subspecialized world, introductions like these could result in younger investigators becoming excited by a rare, complex condition, and assist in creating an ongoing and possibly growing pool of experts to drive advances and improve expertise in clinical care.

Dr. McClain: Not a whole lot is taught about these conditions in medical school. During residency, physicians may happen to see one or two patients with these diagnoses, which provides them with some background information. They are more often seeing patients with other diagnoses, so conditions such as LCH or ECD are left in the "zebra" category. While some hematologists have a little familiarity with these diseases, they are often left calling people like me, and others who are interested in these conditions, for advice.

What do hematologists need to know about the diagnosis and presentation of these disorders?

Dr. McClain: In LCH, I call the factors that should raise suspicion about an LCH diagnosis "the seven deadly sins." Clinicians should ask about chronic skin rashes, chronic sores in the mouth, chronic drainage from the ears, bone pain, chronic cough and respiratory difficulties, chronic diarrhea, and excessive thirst or urination. If there is a history of these, I would get a biopsy of any lesions.

The diagnosis of ECD is similar, except that a biopsy result does not nail down the diagnosis. You have to be aware that these patients have sclerotic changes in the femur and tibia, as seen by plain X-ray or a PET scan. They have tissues that wrap around the kidney or aorta, as seen on CT scans, and sometimes there are pituitary abnormalities, as seen on MRI.

What do you hope attendees will learn from this session?

Dr. Szer: Attendees will see case-based discussions of the latest advances in diagnosis and treatment of these three disease entities. Science will be intertwined with real clinical experience, and I hope they will take away a greater understanding of these conditions and an appropriate investigative pathway for their diagnosis that will reduce the anxiety around these types of clinical presentations.

Anxiety-Provoking Hematology Consults, Second Edition

Live Q&A: Saturday, December 5, 2020
12:00 noon – 12:45 p.m., Pacific time


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