New Antifibrotics Are Changing the Treatment Calculus in ILD

 (ILD) has been largely static since 2014, when nintedanib and pirfenidone became the first approved agents for idiopathic pulmonary fibrosis (IPF). Effective at slowing fibrosis progression, both drugs carried a tolerability burden that shaped clinical decision-making in a particular way: in patients who were clinically stable or early in their disease course, many providers opted to wait before initiating therapy, weighing the risk of side effects against the uncertain benefit in a patient who felt well. 

That calculus is now shifting, according to Jessica Glennie, MSN, APRN, of the Cleveland Clinic ILD Center in Cleveland, Ohio, who presented as part of the multidisciplinary ILD bootcamp series at the 

Association of Pulmonary Advanced Practice Providers (APAPP) National Conference, held June 28-20 in Colorado Springs

The catalyst is nerandomilast (Jascayd), a first-in-class preferential phosphodiesterase 4B (PDE4B) inhibitor approved by the United States Food and Drug Administration (US FDA) in October 2025 for IPF and subsequently for progressive pulmonary fibrosis (PPF) — the first new antifibrotic mechanism in more than a decade.

 In the FIBRONEER phase 3 trials, nerandomilast significantly reduced the annual rate of forced vital capacity decline versus placebo, with a tolerability profile meaningfully better than existing agents: no requirement for liver function monitoring, no food requirement for administration, and substantially lower rates of gastrointestinal adverse effects.

"Now I can put a patient on a medication that they're potentially going to tolerate a lot better, not have these side effects and feel worse — so why not try to get them on something that's potentially going to slow the progression of their disease?" Glennie said. She described offering nerandomilast upfront to antifibrotic-naïve patients, switching patients intolerant of nintedanib, and using it as add-on dual therapy in patients who are tolerating their existing antifibrotic but continuing to show functional decline. Insurance coverage remains an obstacle in some cases, but when it is accessible, patient preference has consistently favored nerandomilast given its tolerability advantages.

The evolution in prescribing approach reflects a broader shift: when side effects were the dominant limiting factor, the rational strategy was to withhold therapy until progression was clear. When a well-tolerated option exists, the equation tips toward earlier intervention — preserving function before irreversible fibrosis accrues, rather than waiting for measurable deterioration to justify treatment.

Glennie J. Bridging specialties in ILD: a multidisciplinary bootcamp series for early recognition and targeted treatment; ILD 102. Presented at: Association of Pulmonary Advanced Practice Providers Annual Meeting (APAP 2026); Las Vegas, NV.

Richeldi L, Azuma A, Cottin V, et al. Nerandomilast in patients with idiopathic pulmonary fibrosis. 

 2025;392:2193–2202. doi:10.1056/NEJMoa2414108

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With nerandomilast offering a more tolerable alternative to nintedanib and pirfenidone, Jessica Glennie, MSN, APRN, says the threshold for initiating antifibrotic therapy in early or stable disease is moving up.

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Donna Culton, MD, PhD, is professor of dermatology at the University of North Carolina at Chapel Hill

When Blisters Don't Look Like Blisters: Diagnosing Pemphigus, Pemphigoid

 are among the most diagnostically challenging conditions in dermatology, and not just because they are rare. At 

in Colorado Springs, Donna Culton, MD, PhD, professor of dermatology and director of the Immunofluorescence Service at the University of North Carolina School of Medicine, led an interactive case-based session titled “Blistering Diseases: What's the Diagnosis?”

 The session addressed conditions that do not frequently present the way textbooks suggest they will.

Chronicity and Oral Involvement as Early Clues

For clinicians encountering a patient with suspected autoimmune blistering disease, Culton emphasized that the clinical picture is often more nuanced than the classic tense blister of bullous pemphigoid or the flaccid erosions of pemphigus vulgaris. Chronicity is a key historical feature, as is the distribution of involvement, particularly oral disease in pemphigus.

"For a pemphigus patient, a lot of times it's the chronicity of the disease, accompanying not only cutaneous features but also, and sometimes only, oral disease, so oral ulcers, sores, erosions, [and] bleeding,” Culton said. “That should tip you off to maybe this [being] pemphigus.”

For pemphigoid, the diagnostic challenge is somewhat different. Clinicians should be aware that many patients experience a prodromal phase that may resemble urticaria, eczematous dermatitis, or prurigo nodularis, none of which immediately suggest a blistering disease. For some patients, this non-bullous phenotype is not a prodrome at all. It is simply how their disease manifests.

While blisters and erosions are the classic hallmarks of autoimmune blistering diseases, lesions may present in highly variable forms, including erythematous, urticarial, prurigo-like, or eczematous manifestations.

 This heterogeneity is a primary reason these diagnoses are missed or delayed.

Culton offered a practical rule of thumb for NPs and PAs working in general dermatology: any patient > 65 years old presenting with a pruritic disorder that is not responding to topical steroids or other first-line treatment should prompt consideration of a non-bullous form of pemphigoid.

During the meeting, Culton presented 2 cases chosen specifically to illustrate atypical presentations. The first involved a younger-than-expected patient with pemphigus herpetiformis: a clinical variant with an annular morphology that does not resemble the flaccid blisters most clinicians associate with pemphigus.

"It just trips people up because they're not expecting pemphigus in a younger patient, and they're not expecting it to look more classic in the flaccid blisters," Culton said.

The diagnostic stakes here are high. Culton noted that data increasingly support earlier initiation of B cell depletion therapy in pemphigus, with earlier treatment correlating with better odds of achieving clinical remission. A delayed or missed diagnosis translates directly into a delayed start on rituximab and a worse long-term prognosis.

The second common pitfall she addressed involves serological testing. Indirect immunofluorescence and ELISA can return low-titer or negative results even in pathologically confirmed disease, particularly in atypical presentations. Newer forms of pemphigoid, including anti-p200 pemphigoid, do not produce antibodies to BP180 or BP230, the targets of standard ELISA panels. When the serology is negative but the clinical picture fits, Culton said that clinicians should not abandon the diagnosis.

For NPs and PAs considering how to work up a suspected case before or alongside referral, Culton underscored 2 practical prerequisites: knowing where to biopsy and having a reliable lab capable of processing specimens for direct immunofluorescence. Perilesional tissue, not the lesion itself, is the appropriate site for direct immunofluorescence biopsy, Culton explained.

Referral Thresholds and the Role of Dupilumab

For pemphigus, Culton recommended prompt specialist referral once a diagnosis is biopsy-confirmed, given that rituximab initiation typically requires specialist involvement and that earlier B cell depletion confers a durable benefit.

For pemphigoid, the treatment calculus has shifted considerably following the June 2025 FDA approval of dupilumab (Dupixent), the first targeted therapy to receive approval for bullous pemphigoid and the 8th indication for the biologic in diseases driven by type 2 inflammation.

 Because many NPs and PAs are already experienced prescribers of dupilumab, Culton suggested this approval creates an opportunity for earlier intervention without immediate specialist escalation. Referral becomes most pressing when a patient is failing dupilumab or when the diagnosis remains uncertain.

"A referral is more necessary if the patient is failing [dupilumab]," she said. "[That would be a reason] to prompt a referral to a specialist."

Editor’s note: Reported disclosures for Culton include GENZYME CORPORATION, ARGENX US, and Regeneron Pharmaceuticals.

Culton D. Blistering Diseases: What's the Diagnosis? – Interactive Format. Session presented at Maui Derm Summer 2026 in Colorado Springs on June 27.

van Beek N, Holtsche MM, Atefi I, et al. State-of-the-art diagnosis of autoimmune blistering diseases. 

https://doi.org/10.3389/fimmu.2024.1363032

Smith T. FDA Approves Dupilumab (Dupixent) for Bullous Pemphigoid in Adult Patients. 

 Published June 20, 2025. Accessed June 25, 2026. 

https://www.hcplive.com/view/fda-approves-dupilumab-dupixent-for-bullous-pemphigoid-in-adult-patients

Donna Culton, MD, PhD, explains why autoimmune blistering diseases often look nothing like the textbook and how to pursue the diagnosis anyway.

Dermatology

The HCPLive dermatology page is a resource for medical news and expert insights on skin disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for dermatologic conditions, and more.

When Blisters Don't Look Like Blisters: Diagnosing Pemphigus, Pemphigoid 

Daria Igudesman, PhD, MS, is a postdoctoral research fellow at AdventHealth.

Lifestyle Interventions and the AIM Framework in Type 1 Diabetes, With Daria Igudesman, PhD, MS

Shifting understanding and technological advancements have led to a significant change in how 

 is addressed and treated, according to a recent presentation.

Endocrine Society (ENDO) Annual Meeting 2026

 in Chicago, Illinois, by Daria Igudesman, PhD, MS, a postdoctoral research fellow at AdventHealth, this statement addresses the gradual paradigm shift towards 

 and overweight in patients with T1D, as well as the development of multiple monitoring and insulin-delivery devices to minimize treatment burden for these patients.

Igudesman has been at the helm of several studies evaluating the effects and efficacy of new methods of managing aspects of T1D; in particular, a 2022 paper focused on the effects of dietary changes on the conflicting aspects of weight and glycemia. This earlier publication emphasizes the impact that non-pharmacological interventions can have on this disease.

“I think the real issue is having tools to address the rising prevalence of obesity in patients with type 1 diabetes,” Igudesman told 

in an exclusive interview. “I think that goes back to not really having a robust evidence base of weight loss interventions, including lifestyle, diet, and exercise interventions, that are effective and safe in T1D, as well as in relevant subgroups.”

In her presentation at ENDO, Igudesman highlighted multiple gaps across the spectrum of T1D knowledge, from lifestyle interventions to long-term management. She discussed the framework she had created to encapsulate these issues, titled AIM.

The A in this framework stands for adding diet interventions, as well as other lifestyle interventions focused on weight management. In Igudesman’s previous publications, she and a team of investigators implemented interventions such as hypocaloric low carbohydrate, hypocaloric moderate low fat, and Mediterranean diets without calorie restrictions to determine their effects on weight loss in T1D. These strategies resulted in substantial weight loss and HbA1c maintenance or improvement without boosting hypoglycemia among included patients.

The I in the AIM framework stands for integrating cardiometabolic risk factors beyond weight. Igudesman specifically highlights fat distribution and insulin resistance, as these individual factors can directly impact organ health outside of T1D and bring about comorbid diseases. Additionally, blood lipids and cholesterol levels can influence cardiometabolic risk.

The M in this framework stands for measuring diet, which Igudesman identifies as an increasingly critical factor in managing obesity. While medications like GLP-1 receptor agonists are growing more and more prevalent, their effects are often reversed after treatment discontinuation if patients fail to maintain lifestyle interventions in both diet and exercise. Additionally, Igudesman highlights the historically well-supported knowledge that diet quality has a direct effect on both weight and cardiometabolic risk, making it a central component of not only obesity care, but all cardiometabolic disease.

Igudesman also acknowledges the technological advancements that have been made in T1D management and care in recent years. Continuous ketone monitors and automated insulin delivery systems have optimized care access and simplified treatment, addressing both possible extremes of T1D between hypoglycemia and ketosis. Igudesman believes that these devices may support future research into the more behavioral methods of managing the disease, as the more dire risks are now more easily averted.

“These new technologies like continuous ketone monitors are priming the field to prescribe adjunctive pharmacotherapies like SGLT2 inhibitors more safely, because the converse of hypoglycemia is an increased risk of ketosis,” Igudesman said. “Those are the two sides of the coin that I think we need to be thinking about, and I believe new tools are coming to market that are going to help in those efforts.”

Editors’ Note: Igudesman reports no relevant disclosures.

Igudesman D. Weight Management in T1D: Current Challenges and Novel Perspectives. Presented at the Endocrine Society (ENDO) Annual Meeting 2026, Chicago, IL. June 13-15, 2026.

Igudesman D, Crandell J, Corbin KD, et al. Weight management in young adults with type 1 diabetes: The advancing care for type 1 diabetes and obesity network sequential multiple assignment randomized trial pilot results. 

Igudesman discusses her presentation at ENDO 2026, during which she covered the importance of managing obesity with lifestyle changes in patients with T1D.

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Type 1 Diabetes

Stefan Weiss, MD, a dermatologist at Trillium Clinic and adjunct professor of dermatology at Brown University School of Medicine.

Why Dermatologists Should Add Serum Tryptase to the Workup for Chronic Itch

Mast cell disorders have historically landed in the hands of hematology, but newer targeted therapies and a growing recognition of their 

 are creating an opening for dermatologists to play a more active role in both diagnosis and treatment. That was the central argument Stefan Weiss, MD, a dermatologist at Trillium Clinic and adjunct professor of dermatology at Brown University School of Medicine, made during his session at 

“It's one of those diseases that if we don't look for it, we don't see it," Weiss said, "and now there's an opportunity to really begin to consider a mast cell disorder as the cause of the itching before we jump necessarily to one of the new great anti-itch therapeutics that we have."

Weiss framed chronic itch as the most underutilized clinical cue for suspecting mast cell disease. As itch becomes an increasingly prominent presenting complaint in dermatology, he argued that the workup should routinely include a serum tryptase level before defaulting to atopic dermatitis, pruritus of unknown origin, or other diagnoses.

“You have some skin findings, you have the sensation of itch, and now we really want to add tryptase into the mix of our laboratory evaluation,” he said.

Systemic and cutaneous mastocytosis remain rare conditions, Weiss acknowledged, but they may be more prevalent than current diagnosis rates suggest, particularly in adult and geriatric patients where the disorder is less commonly considered. He noted that dermatology training has historically emphasized mastocytosis as a predominantly pediatric and cutaneous condition, which contributes to underrecognition in older adults who more often present with systemic involvement.

“It's not something that's going to present every day, like psoriasis or atopic dermatitis, but we do want to keep it on our differential,” he said.

Weiss described mast cell activation disorder as an umbrella encompassing a spectrum from IgE-mediated allergic disease to clonal disorders such as systemic mastocytosis to mast cell activation syndrome. When patients present with overlapping features, he emphasized that history, physical exam findings, and laboratory results, including genetic testing, are what allow clinicians to sort between categories.

If an elevated tryptase is identified and the clinical picture is consistent with mast cell disease, both in skin and non-skin findings, he recommends proceeding to genetic blood testing through a reference laboratory such as LabCorp to evaluate for the KIT D816V mutation.

For patients with a confirmed KIT D816V mutation and both cutaneous and non-cutaneous findings consistent with systemic mast cell disease, Weiss pointed to avapritinib as a targeted option now available to dermatologists to consider.

In the PIONEER trial, patients with moderate to severe indolent systemic mastocytosis randomized to avapritinib 25 mg once daily achieved a decrease of 15.6 points in total symptom score from baseline to week 24, compared to 9.2 points in the placebo group.

 Significantly more avapritinib-treated patients also achieved ≥ 50% reductions in serum tryptase, bone marrow mast cell aggregates, and KIT D816V variant allele fraction compared with placebo.

For patients who do not qualify for targeted therapy or for whom access is a barrier, Weiss noted that supportive care options include antihistamines and omalizumab, which he described as older but potentially more accessible given insurance approval rates.

"By ordering that tryptase level, if you do identify one of these individuals to have mast cell disease, then that's the individual who is now being helped based on [this] lecture," he said.

Editor’s note: Reported disclosures for Weiss include Galderma Laboratories, ABBVIE, Arcutis Biotherapeutics, Incyte Corporation, SUN PHARMACEUTICAL INDUSTRIES, LEO Pharma, Novartis Pharmaceuticals Corporation, and more.

Weiss S. A New Tack on Mast Cell Disorders. Session presented at Maui Derm NP+PA Summer 2026 in Colorado Springs on June 26.

Gotlib J, Castells M, Elberink HO, et al. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. 

Stefan Weiss, MD, on recognizing mast cell disorders in the dermatology clinic and how avapritinib is reshaping treatment for indolent systemic mastocytosis.

Christopher G. Bunick, MD, PhD, is an associate professor of dermatology at Yale University School of Medicine.

What Will Precision Dermatology Look Like in Atopic Dermatitis?

In another segment of his latest interview, Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine, described his views on the future of precision medicine in the atopic dermatitis space, speaking with 

2026 Revolutionizing Atopic Dermatitis (RAD) Conference

Bunick noted both the progress made so far toward this future and the scientific challenges that will continue to be seen before clinicians can reliably predict which medications will be best for individuals. He explained while atopic dermatitis therapy has entered an era of unprecedented therapeutic expansion, a true precision medicine future remains a work in progress.

“It's going to take a lot more understanding of what drives atopic dermatitis,” Bunick explained. “For example, understanding how OX40 ligand-targeted drugs, or any other drug, whether it's JAK inhibitors or the other biologics that are currently approved, may or may not cause disease modification requires us to actually study how are memory T-cells affected over short and long courses of therapy.”

He described current research efforts, including gene expression profiling, as having begun to provide key findings on how individuals may respond to different therapeutic classes, such as biologics and Janus kinase (JAK) inhibitors. However, Bunick also emphasized the field as not having yet attained a level whereby clinicians can confidently implement molecular signatures alone with the aim of matching patients with the optimal course of therapy.

According to Bunick, attaining that goal will involve gaining a much deeper understanding of the immunologic mechanisms known to drive atopic dermatitis. While cytokines such as IL-4, IL-13, and others have become important targets, he described researchers in this space as increasingly looking upstream in the disease process. Emerging investigations are assessing how immune cells contribute to disease activity and long-term disease control.

Bunick further explored the concept of disease modification, noting the increasing prominence of the topic as new therapeutic targets begin clinical development. The growing interest in drugs targeting pathways such as OX40/OX40 ligand, STAT6, and other immune regulators that may influence the underlying biology of the disease was highlighted by Bunick. An awareness of how these medications impact immune memory and long-term inflammatory responses may ultimately help determine whether durable disease modification is a potential aim for the future.

In his interview, Bunick additionally pointed to advances in transcriptomics, proteomics, and cellular immunology as areas that could potentially play a major role in the future of therapy prediction. Through the integration of molecular profiling with a deeper understanding of immune system behavior, those conducting such research may eventually be able to identify which patients will be most likely to see positive results from specific drugs prior to initiation of treatment.

Bunick has reported receiving consultant fees or serving as an investigator for AbbVie, Incyte, LEO Pharma and Pfizer.

Nguyen H, Bunick C, Cotter D, Shahriari M. Medical Crossfire and Clinical Case Challenge. Session presented at: 2026 Revolutionizing Atopic Dermatitis Conference; June 17-19, 2026; Nashville, TN.

Bunick C. Highlighting FDA-Approved Therapies in Atopic Dermatitis, With Chris Bunick, MD, PhD. HCPLive. June 25, 2026. 

https://www.hcplive.com/view/highlighting-fda-approved-therapies-atopic-dermatitis-chris-bunick-md-phd

The topic of precision medicine in dermatology is explored in this segment of Bunick's interview at RAD 2026.

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Dawn Eichenfield, MD, PhD, is a dermatologist at Rady Children's Hospital-San Diego and an assistant clinical professor of dermatology at UC San Diego School of Medicine.

Articles

Dawn Eichenfield, MD, PhD, discusses differential diagnosis, off-label treatment rationale, and multidisciplinary care for rare and atypical skin conditions in children.

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Diagnosing Uncommon Dermatoses in Children: LCH, Psoriasis, and More

Keisha Gibson, MD, MPH, is a pediatric nephrologist and Division Chief of the Pediatric Nephrology Division at the UNC School of Medicine.

Keisha Gibson, MD, MPH, discusses what an FDA approval of obinutuzumab (Gazyva) would mean for patients with the rare disease INS. 

Obinutuzumab Achieves 95.5% Remission in INS, May Shift Steroid-Sparing Treatment Strategies

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This interview at RAD highlights FDA-approved therapies in the atopic dermatitis treatment armamentarium.

Highlighting FDA-Approved Therapies in Atopic Dermatitis, With Chris Bunick, MD, PhD

John Giacona, PhD, PA-C, says identifying pulmonary hypertension early, distinguishing its type, and engaging critically with clinical evidence are paramount.

Cardiology

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Rishi Wadhera, MD, MPP, MPhil, is a cardiologist, health policy researcher, and associate professor at Harvard Medical School and the Harvard T.H. Chan School of Public Health.

Rishi Wadhera, MD, MPP, MPhil, addresses performance metrics, cross-specialty prescribing, and the policy forces reshaping the cardiometabolic care cascade.

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Type 2 Diabetes

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Victoria Johnson joined MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and is now an assistant managing editor for HCPLive and RheumatologyLive. She doesn’t have enough time for her numerous hobbies. You can reach her at vjohnson@mjhlifesciences.com.

The US FDA has approved olezarsen as an adjunct to diet to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia.

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Matthew Zirwas, MD, explains why topical JAK inhibitors represent a clinical turning point for hand eczema.

Latest News

New Antifibrotics Are Changing the Treatment Calculus in ILD

When Blisters Don't Look Like Blisters: Diagnosing Pemphigus, Pemphigoid

Lifestyle Interventions and the AIM Framework in Type 1 Diabetes, With Daria Igudesman, PhD, MS

Why Dermatologists Should Add Serum Tryptase to the Workup for Chronic Itch

What Will Precision Dermatology Look Like in Atopic Dermatitis?