Early Clinical Signs and the Evolution of Diagnosis in Wilson Disease

This episode, titled 'Early Clinical Signs and the Evolution of Diagnosis in Wilson Disease,' features panelists discussing the standard and evolving protocols for identifying Wilson disease in various patient populations. Dr. Rima Fawaz explains that while elevated alanine aminotransferase (ALT) remains the most common signal for a pediatric workup, the medical community is entering a new era shaped by preconception genetic testing and advanced screening. The discussion highlights a pilot neonatal screening program in Washington state that measures ATP7B protein peptides. Although this testing offers the potential to catch patients before they become symptomatic, the experts note current limitations, including false positives and the need for more robust data.

The conversation also addresses how age influences the clinical profile of the disease. While younger children primarily present with hepatic symptoms, neurological manifestations such as tremors and hyperkinetic movements typically emerge in pre-teen years or young adulthood. Dr. Peter Hedera notes that as patients age, they may trend toward hypokinetic movements, though the disease remains highly heterogeneous.

To differentiate Wilson disease from other movement disorders like Parkinson’s, the panel emphasizes a multi-modal diagnostic approach. Because clinical signs alone are often nonspecific, experts rely on a suite of confirmatory tests, including ceruloplasmin levels, 24-hour urine copper, and non-ceruloplasmin copper (NCC) assays. They also discuss the utility of neuroimaging for detecting T2 signal changes in the basal ganglia and the importance of ophthalmological exams to identify Kayser-Fleischer rings. The episode concludes by reinforcing that because Wilson disease is such a persistent masquerader, clinicians must maintain a low threshold for laboratory evaluation to avoid missing a diagnosis.

In the next episode, 'Multidisciplinary Collaboration and Diagnostic Frameworks in Wilson Disease,' panelists will continue their discussion on Wilson disease and highlight the importance of a team-based approach involving hepatologists, neurologists, and psychiatrists. The conversation covers the practical application of the Leipzig score and the growing role of next-generation sequencing in identifying preclinical cases.

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Learn how subtle liver enzyme changes and age-specific movement symptoms signal Wilson disease, plus the latest on newborn screening and tests.

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Mark G. Lebwohl, MD, the dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai,

Zasocitinib in Plaque Psoriasis from the LATITUDE Trials

This episode, titled ‘Zasocitinib in Plaque Psoriasis from the LATITUDE Trials,’ features Dr. Tina Bhutani-Jacques and Dr. Mark Lebwohl as they analyze breakthrough data recently presented at the 2026 American Academy of Dermatology annual meeting. The experts focus on the efficacy of zasocitinib, a selective TYK2 inhibitor that demonstrated significant results in a difficult to treat patient cohort. Dr. Lebwohl notes that the study population included many individuals who were near the obesity threshold or had previously failed biologic therapies. Despite these challenges, the trial results showed that a quarter to a third of patients achieved total skin clearance, or PASI 100, within the first 16 weeks of treatment.

The discussion highlights that zasocitinib offers a level of efficacy previously reserved for injectable medications. Dr. Lebwohl points out that the drug shows an incremental benefit over time, with PASI 100 rates climbing as high as 42% by week 24. This trajectory suggests that while the drug may not peak as rapidly as some IL-17 blockers, its long term performance rivals many of the leading biologics currently on the market. Dr. Bhutani-Jacques emphasizes that these findings are a game changer for patients who desire the convenience of a pill without sacrificing the high clinical standards of modern psoriasis care. The experts conclude that zasocitinib effectively addresses a major unmet need by providing biologic level results in an oral format, offering a promising new direction for real world psoriasis management.

In the next episode, ‘Patient-Reported Outcomes and Safety of TYK2 Inhibitors in Psoriasis’, panelists will discuss the correlation between skin clearance and improvements in itch and quality of life. The experts also evaluate the safety distinctions between TYK2 and JAK inhibitors and the advocacy efforts to update tuberculosis screening requirements for modern psoriasis therapies.

Psoriasis care shifts beyond skin: treat-to-target goals, heart risk reduction, and new oral TYK2 pills with strong safety data.

Who Diagnoses EPI? Defining Roles Across the Care Team

With symptoms and presentations now established, this episode explores who in the healthcare system is best positioned to make an EPI diagnosis. Dr. Kaul frames the discussion: while gastroenterologists and specialty practices handle referrals, the initial contact is often a primary care provider, surgeon, or endocrinologist who may not routinely order EPI-specific tests.

Jennifer Geremia advocates for widespread awareness across specialties, proposing a multi-modal, collaborative approach. The key expectation is not that every provider must know how to order and interpret every test, but that they should have a sufficient index of suspicion to recognize when referral to gastroenterology is appropriate. She cautions against the assumption that "someone else" will pick it up—diagnosing and acting on EPI is a shared responsibility.

Sarah Enslin echoes this, noting that with the evolving healthcare landscape, NPs and PAs are increasingly managing complex patients in both subspecialty and primary care settings. This further distributes the responsibility for EPI recognition. The growing volume of primary care practices makes platforms like this peer exchange especially critical for disseminating knowledge efficiently.

Dr. Kaul reinforces that this is a disease state touchable by virtually every specialty—and that national conferences, regional courses, and educational programs are essential vehicles for spreading that message. He closes the episode by reminding viewers that every provider who encounters a patient with relevant symptoms or risk factors has a role in moving toward a diagnosis or appropriate referral.

EPI Testing Strategies: What to Order and When

," the panel conducts a practical deep dive into the diagnostic tools available for EPI, from fecal elastase to EUS, covering when to use each and how to avoid common testing pitfalls.

Clinicians across specialties spot red flags, refer early to GI, and follow guidelines to improve diagnosis and management.

Understanding Pathophysiology and Copper Transport in Wilson Disease

In 'Understanding Pathophysiology and Copper Transport in Wilson Disease,' our experts delve into the underlying biological drivers of this autosomal recessive metabolic disorder. Dr. Peter Hedera provides a technical overview of the ATP7B gene, a critical copper transporter located primarily in the liver, kidneys, and brain. Under normal physiological conditions, this protein facilitates the transfer of copper to ceruloplasmin for transport and manages the excretion of excess dietary copper into the bile. However, a loss of function in ATP7B leads to chronic copper overload, causing a shift toward what is known as non-ceruloplasmin copper or biologically active copper.

The panel discusses how this "free" copper becomes highly toxic when it exceeds the body's buffering capacity. Historically referred to as hepatolenticular degeneration, the disease specifically targets the liver and the basal ganglia of the brain due to the high metabolic activity in these areas. Dr. Hedera explains that while patients are born with this genetic deficiency, clinical presentation typically peaks in the second and third decades of life, though rare cases appear much later.

The experts also explore the multi-system defects caused by abnormal copper metabolism. They highlight that the disruption of oxidative systems and subsequent mitochondrial dysfunction are primary drivers of cellular damage. This process leads to hepatic cell death and neurodegeneration, illustrating why copper, though an essential trace element, becomes a destructive force when regulation is broken. The episode concludes by emphasizing the importance of understanding these cellular pathways to better recognize the diverse clinical manifestations seen in practice.

Our next episode, 'Early Clinical Signs and the Evolution of Diagnosis in Wilson Disease,' further explores Wilson disease, highlighting the critical role of elevated liver enzymes as a primary clinical trigger for evaluation. The panelists discuss the emerging era of neonatal screening and the necessity of combining laboratory testing with clinical suspicion to identify this master masquerader.

Wilson disease mimics tremor, dystonia, Parkinsonism or psychosis; watch for subtle liver signs and screen early to avoid delay.

The Role of TYK2 Inhibitors in Modern Psoriasis Care

In ‘The Role of TYK2 Inhibitors in Modern Psoriasis Care,’ our panel explores the scientific advancements of TYK2 inhibition and its place as a bridge between traditional oral therapies and injectable biologics. Dr. Tina Bhutani-Jacques explains that TYK2 is a member of the Janus kinase family that facilitates signaling for key cytokines involved in psoriasis pathogenesis, such as IL-12, IL-23, and type 1 interferons. Dr. Mark Lebwohl describes how blocking these signals at the intracellular level prevents the rapid cell multiplication and epidermal thickening characteristic of the disease. He emphasizes that unlike older systemic treatments like methotrexate, which broadly suppress the immune system, TYK2 inhibitors offer a more targeted approach with fewer systemic side effects.

The experts specifically compare the first FDA approved TYK2 inhibitor, deucravacitinib, with the emerging agent zasocitinib. Dr. Lebwohl highlights that because these drugs target the regulatory domain of the TYK2 enzyme, they avoid the significant safety warnings associated with broader JAK inhibitors, such as clotting, heart attacks, and malignancy. He notes that zasocitinib shows even higher selectivity and affinity, potentially offering enhanced efficacy. Dr. Lebwohl also reflects on long term data and real-world studies presented at recent American Academy of Dermatology meetings, which confirm the effectiveness of TYK2 inhibition even in difficult to treat, overweight populations. With five years of safety data showing no significant signals for serious infections or cancers, the experts express high confidence in using these oral agents to achieve stable, long term disease control.

Our next episode, ‘Zasocitinib in Plaque Psoriasis from the LATITUDE Trials,’ features the panelists reviewing the top line results of a novel oral TYK2 inhibitor. The experts discuss how this agent achieves PASI 100 clearance rates that are comparable to injectable biologics even in refractory patient populations.

Discover how oral TYK2 inhibitors deliver targeted psoriasis control with strong safety data and biologic-like clearance, including insights on deucravacitinib and zasocitinib.

Patrick Campbell is the editorial director of HCPLive. Patrick has spent years spearheading coverage surrounding cardiometabolic health and rheumatic disease for MJH Life Sciences. Before joining MJH Life Sciences in 2019, he spent time as a beat reporter and/or multimedia specialist with the Pocono Record, Star News Group, and NJ Advance Media. He is the executive producer for multiple HCPLive podcasts, including Diabetes Dialogue, Don't Miss a Beat, Kidney Compass, Medical Ethics Unpacked, The Medical Sisterhood, and Skin of Color Savvy. 


Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

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FDA Accepts Delgocitinib sNDA for Chronic Hand Eczema in Adolescents Aged 12–17

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Latest News

Early Clinical Signs and the Evolution of Diagnosis in Wilson Disease

Zasocitinib in Plaque Psoriasis from the LATITUDE Trials

Who Diagnoses EPI? Defining Roles Across the Care Team

Understanding Pathophysiology and Copper Transport in Wilson Disease

The Role of TYK2 Inhibitors in Modern Psoriasis Care