Lindsay S. Ackerman, MD, FAAD

 (EPP) remains among dermatology's most under-recognized diagnoses, often mistaken for solar urticaria or polymorphic light eruption for years before clinicians identify its hallmark feature: severe burning pain after sun exposure with little or no visible skin change.

, hosts Lindsay Ackerman, MD, and Christopher Bunick, MD, PhD, spoke with Angelika Erwin, MD, PhD, founder and director of the Porphyria Center at Cleveland Clinic, about diagnosing and managing EPP and its X-linked counterpart, XLP.

On this episode of ABCs in Dermatology, Angelika Erwin, MD, PhD, founder and director of the Porphyria Center at Cleveland Clinic, joins hosts Lindsay Ackerman, MD, and Christopher Bunick, MD, PhD, to discuss a rare, often-missed photosensitivity disorder and how care for it is evolving.

ABCs in Dermatology: Updates in Erythropoietic Protoporphyria Management for 2026

EPP results from ferrochelatase deficiency, causing free protoporphyrin IX to accumulate in red blood cells, plasma, and skin. Pain typically strikes within minutes of sun exposure, most often on the backs of the hands, and can precede any visible finding. Onset usually occurs between ages 1 and 4, and diagnosis is frequently delayed for years because symptoms resolve before a clinician examines the skin. About 5% of patients develop protoporphyric hepatopathy, which in rare cases progresses to fulminant liver failure requiring transplantation paired with bone marrow transplant, since liver transplant alone is not curative.

Erwin outlined a diagnostic pathway starting with plasma total porphyrins, available through standard commercial labs, followed by erythrocyte protoporphyrin testing at specialized centers such as Mayo Clinic or ARUP to distinguish EPP from XLP based on the ratio of free to zinc-bound protoporphyrin. Urine porphyrins remain normal in both conditions and should not be used for screening. Genetic testing targets the FECH gene in EPP, an autosomal recessive condition typically involving a common low-expression allele paired with a disease-causing mutation, and the ALAS2 gene on the X chromosome in XLP.

Before afamelanotide's 2019 approval, management relied on physical sun avoidance, zinc oxide and titanium dioxide sunscreens, and UV-filtering window films, with limited benefit from oral beta-carotene. Afamelanotide, a subcutaneous implant given every 60 days, increased pain-free sun exposure by a mean of 69 hours over 6 months versus placebo in the US phase 3 trial

, though it is not approved in pediatric patients. Bitopertin, an oral glycine transporter 1 inhibitor now in phase 3 testing, reduces porphyrin production upstream in the heme biosynthetic pathway and has shown promise in patients as young as 12 years in earlier trials

Erwin also pointed to earlier-stage candidates, including an ABCG2 inhibitor, ex vivo FECH gene replacement, mRNA-based delivery, and dersimelagon, an oral melanocortin receptor agonist in phase 3 testing. She emphasized that suspected EPP warrants erythrocyte protoporphyrin or plasma porphyrin testing rather than urine studies, and that confirmed cases require coordinated monitoring of liver function and vitamin D levels alongside referral to a specialized porphyria center.

Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria. N Engl J Med. 2015;373(1):48-59. doi:

Yeung AK, Bonkovsky HL, Balwani M, et al. Bitopertin shows efficacy in patients with erythropoietic protoporphyria: results from the randomized, double-blind, placebo-controlled AURORA trial. J Am Acad Dermatol. 2025. doi:

Articles

Erythropoietic protoporphyria and X-linked protoporphyria present in early childhood with rapid-onset, severe phototoxic burning pain and minimal visible erythema, leading to frequent misdiagnosis and prolonged diagnostic delay. Pathobiology centers on excess protoporphyrin IX from ferrochelatase deficiency (EPP) or ALAS2 gain-of-function (XLP), with rare but serious protoporphyric hepatopathy. Diagnosis hinges on plasma porphyrins and specialized erythrocyte protoporphyrin fractionation, not urine testing. Management has shifted from strict photoprotection to melanocortin-based and heme-pathway–targeted therapies.

Angelika Erwin, MD, PhD, joins the podcast to discuss diagnosing and managing EPP and XLP on ABCs in Dermatology.

 to clear or almost clear skin, rather than partial improvement, is emerging as the standard clinicians should hold themselves to across every affected body site, including the scalp, nails, and genitals. Special sites carry a disproportionate quality-of-life burden relative to their body surface area (BSA) and are increasingly recognized by clinical guidelines as sufficient grounds for systemic therapy on their own.

, Lindsay Ackerman, MD, and Christopher Bunick, MD, PhD, discussed data supporting transformational care in psoriasis, with a focus on risankizumab and the underappreciated burden of special-site disease.

Hosts discuss the latest updates in psoriasis management for 2026, including new data on risankizumab and changes in management for difficult-to-treat areas.

ABCs in Dermatology: Updates in Psoriasis Management for 2026

International Psoriasis Council guidelines now define systemic eligibility using 3 criteria: 

Disease in hard-to-treat areas such as the scalp, nails, palms, soles, or genitals

Failure of 2 topical therapies used for at least 4 weeks each 

Special-site involvement matters beyond symptom burden: scalp disease confers a fourfold higher risk of psoriatic arthritis, and nail disease a 3-fold higher risk, against a baseline lifetime psoriatic arthritis risk of roughly 30% to 35% across the psoriasis population.

In the phase 3 UltIMMa-1 and UltIMMa-2 trials, risankizumab, an IL-23 p19 inhibitor dosed every 12 weeks, achieved PASI 90 in about 75% of patients by week 16. In the head-to-head IMMerge trial, risankizumab sustained superiority over secukinumab through week 52. Long-term LIMMitless extension data showed durability, with response curves for modified non-responder imputation and as-observed analyses nearly superimposed, and roughly 54% of patients reaching PASI 100 by week 304. In the phase 3b IMMprint trial, risankizumab also demonstrated efficacy in palmoplantar psoriasis, an area with thicker epidermis that is traditionally difficult to clear.

The speakers noted structural differences among IL-23 p19 inhibitors, including epitope binding surface area and dissociation rate, may help explain efficacy differences observed across the class. Risankizumab has also shown a 10% to 20% efficacy advantage over the oral IL-23 receptor blocker icotrolimod in indirect comparisons, alongside evidence that IL-23 inhibition may delay psoriatic arthritis onset more effectively than other mechanisms.

Collectively, the data support a shift in benchmark thinking, from PASI 75 toward PASI 90 and 100, and reinforce special-site and nail involvement as legitimate, guideline-recognized triggers for systemic therapy rather than exceptions to standard BSA-based criteria.

Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650-661. doi:10.1016/S0140-6736(18)31713-6

Warren RB, Blauvelt A, Poulin Y, et al. Efficacy and safety of risankizumab vs. secukinumab in patients with moderate-to-severe plaque psoriasis (IMMerge): results from a phase III, randomized, open-label, efficacy-assessor-blinded clinical trial. Br J Dermatol. 2021;184(1):50-59. doi:10.1111/bjd.19341

Papp KA, et al. Long-Term Safety and Efficacy of Risankizumab to Treat Moderate-to-Severe Plaque Psoriasis: Final LIMMitless Phase 3, Open-Label Extension Trial Results. Am J Clin Dermatol. 2025. doi:10.1007/s40257-025-00964-6

Lebwohl M, Bukhalo M, Bissonnette R, et al. A randomized phase 3b study evaluating the safety and efficacy of risankizumab in adult patients with moderate-to-severe plaque psoriasis with non-pustular palmoplantar involvement. J Am Acad Dermatol. 2024. doi:10.1016/j.jaad.2024.07.1521

Podcasts

Hosts discuss the latest data in psoriasis and the case for treating scalp, nail, and genital psoriasis as systemic-eligible disease.

Live podcast episode of ABCs in Dermatology recorded at Revolutionizing Atopic Dermatitis 2026

 ABCs in Dermatology: Updates in Atopic Dermatitis at RAD 2026

New analyses are adding momentum to early systemic intervention in moderate-to-severe 

, with growth outcomes emerging as a previously underappreciated marker of disease control in children. The findings reinforce a broader shift across the AD biologic class toward measuring success beyond skin clearance alone.

, co-hosts Christopher Bunick, MD, PhD, and Lindsay Ackerman, MD, FAAD, discussed the maturing interleukin-4 (IL-4)/interleukin-13 (IL-13) biologic landscape in AD. The conversation, recorded live at the 

Revolutionizing Atopic Dermatitis (RAD) 2026 meeting

 in Nashville, Tennessee, spanned dupilumab (Dupixent), tralokinumab (Adbry), and lebrikizumab (Ebglyss).Because no head-to-head trials exist among the 3 agents, comparative efficacy data rely on indirect network meta-analyses. 

Roughly 30% of patients reach Eczema Area and Severity Index (EASI) 90 or Investigator Global Assessment (IGA) 0/1 by week 16, with response rates continuing to climb well beyond this early window. In dupilumab's long-term extension trial, more than 90% of patients who had not reached EASI 75 by week 16 achieved it by week 100. 

None of the 6 FDA-approved advanced AD therapies require routine laboratory monitoring, and tralokinumab and dupilumab have each published 5-year safety data showing predominantly mild to moderate adverse events without new safety signals. 

By contrast, around 1 in 5 patients with moderate to severe AD still receive oral corticosteroids. Even a 6-day prednisone dose pack raises the risk of sepsis, bone fracture, and venous thromboembolism for 30 days afterward.Pediatric growth emerged as a focal point. Extension data from the Liberty AD PS trial showed children treated early with dupilumab had a 3.7- to 4.2-fold greater likelihood of meaningful growth improvement versus peers on no systemic therapy, independent of corticosteroid exposure. Bunick described the underlying mechanism as likely multifactorial, reflecting reduced inflammation, lower corticosteroid use, and improved sleep.

Itch tracks closely with quality of life: registry data show quality of life drops sharply unless itch reaches a 0 or 1 on a 10-point scale. This prompted both hosts to counsel patients toward this stricter target rather than partial relief. Collectively, the data point to a biologic class no longer competing only on skin clearance, but increasingly on durability, safety, and capacity to address the systemic burden of AD across the lifespan.

Relevant disclosures for Bunick include AbbVie, South Beach Symposium, Almirall, Apogee Therapeutics, Arcutis Biotherapeutics, Daiichi Sankyo, Eli Lilly, LEO Pharma, US, Novan, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Timber Pharmaceuticals, and UCB. Relevant disclosures for Ackerman include AbbVie, Alumis, Amgen, Arcutis, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, L'Oréal, Novartis, Sun Pharmaceutical, and UCB.

New AD biologic data highlight early systemic treatment, durable itch control, and improved pediatric growth—shifting goals beyond skin clearance.

ABCs in Dermatology: Updates in Atopic Dermatitis Live at RAD 2026

What Is Next for OX40 Ligand Inhibition in Atopic Dermatitis?

 explored the future potential of amlitelimab in atopic dermatitis, with hosts Christopher Bunick, MD, PhD, and Lindsay Ackerman, MD, emphasizing the importance of maintaining scientific curiosity and clinical perspective as more data emerge regarding OX40 ligand-targeted therapy.

The discussion centered on balancing enthusiasm for a novel therapeutic mechanism with the need for continued investigation into safety signals and patient selection. Bunick argued the field should remain optimistic about amlitelimab’s future, noting that a better understanding of patient-specific risk factors could ultimately help clinicians identify individuals most appropriate for treatment. He compared this approach to the risk stratification strategies dermatologists have already adopted for JAK inhibitors, where clinicians routinely evaluate patients for factors that may increase the likelihood of adverse events before initiating therapy.

Rather than viewing emerging questions about the therapy as a reason to abandon the pathway, Bunick suggested that dermatology should focus on generating more data and demanding greater scientific transparency. In his view, understanding the underlying biology behind observed safety findings will allow clinicians to make more informed, patient-centered decisions while preserving access to potentially valuable treatment options.

Ackerman agreed, describing the OX40-OX40 ligand pathway as an example of why dermatology remains one of the most rapidly evolving areas of medicine. She highlighted the complexity of inflammatory disease biology and suggested that upstream immune modulation may ultimately have implications extending beyond atopic dermatitis. According to Ackerman, the pathway’s broad immunologic relevance could make it important not only for eczema but also for other chronic inflammatory disorders that continue to present therapeutic challenges.

The hosts also discussed the ongoing unmet need in atopic dermatitis despite an expanding therapeutic landscape. Ackerman noted that the disease remains highly heterogeneous, with significant variability in clinical presentation and treatment response. As a result, she argued that continued investment in new mechanisms of action remains essential, even as effective therapies already exist. She pointed to the continued development of amlitelimab as evidence of an ongoing commitment to addressing gaps in care for patients whose disease remains difficult to control.

The conversation then shifted to Ackerman’s firsthand experience as a clinical trial investigator. Drawing on her participation in amlitelimab studies, Ackerman described seeing several patients achieve substantial improvements despite having previously failed multiple therapies. Although she acknowledged that these observations represent only a small number of patients, she noted that some individuals continued to do well even after completing the interventional portion of the study. Ackerman said she had anticipated needing to rapidly transition certain participants to additional treatments after trial completion because of the severity and recalcitrance of their disease, but some had yet to experience significant flares.

Bunick cautioned against drawing broad conclusions from individual cases but viewed those experiences as further reason to remain open-minded. Both hosts ultimately stressed that advancing patient care requires careful scientific investigation, patience, and a willingness to evaluate new therapeutic pathways on the basis of evolving evidence. They concluded that maintaining a patient-centered approach while pursuing deeper mechanistic understanding will be critical as the role of OX40 ligand inhibition continues to develop within atopic dermatitis and potentially other inflammatory diseases.

Editor’s note: This segment was summarized with the help of AI tools.

Sanofi. Press Release: AAD: new results from Sanofi’s amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. Sanofi.com. Published March 28, 2026. Accessed June 1, 2026. 

https://www.sanofi.com/en/media-room/press-releases/2026/2026-03-28-15-00-00-3264184

Kyowa Kirin. Kyowa Kirin Announces Discontinuation of Rocatinlimab Clinical Trials - Kyowa Kirin. Kyowakirin.com. Published March 3, 2026. Accessed June 1, 2026. 

https://www.kyowakirin.com/media_center/news_releases/2026/e20260303_01.html

Videos

The latest ABCs of Dermatology explored the future potential of amlitelimab in atopic dermatitis and the potential of OX40 ligand-targeted therapy.