A guide to the new ichthyosis and palmoplantar keratoderma naming system - Epidermal Differentiation Disorders (EDDs)

This article explains the recent changes in how we name some inherited skin conditions. This includes conditions like the ichthyoses and palmoplantar keratodermas. These changes may seem confusing at first, but we hope with time and support they will become widely used and understandable. We hope that they will lead to improvements in patient care. They will be essential for future targeted treatments.

Currently, people with inherited skin conditions may know their condition by different names. This can depend on when they were diagnosed. For example, if someone has an ichthyosis, there may be many different names for it. Some people just say ichthyosis, which may not be specific enough to help understand all the associated clinical features. Others might use names like lamellar  ichthyosis or ARCI. Some even refer to the gene involved, like TGM1 or ALOXE3.

What are Epidermal Differentiation Disorders (EDDs)?

EDD is a new name which includes three groups: ichthyosis (dry, scaly skin with varying amounts of redness), palmoplantar keratoderma (thickening of the skin affecting the palms and/or the soles) and syndromes which affect the skin as well as other organs.

A simple way to explain EDDs is to compare the skin to a protective shield. Our skin has many layers, and as new skin cells grow, they move upward to the surface. This forms a strong barrier that protects us from things like infections, allergens and injuries. In people with an epidermal differentiation disorder, this process doesn't work properly. Their skin cells might not form or work the way they should. This makes the skin weaker and more fragile, leading to problems like painful blisters. To overcome the problem, the skin may often also be thicker and/or scaly. This again can lead to blisters or cracks. An abnormal barrier also leads to an increased risk of inflammation (redness) and infections.

Why change the names?

There have been many previous attempts to classify and name these conditions. Older terms often described the skin's appearance and have led to some offensive names. For example, ‘ichthyosis’ likens the skin to fish scales. 'Hystrix' compares it to a porcupine, while ‘harlequin’ refers to a historic entertainer’s outfit.

Names based on appearance can also be inaccurate. This can limit research and treatment of these conditions. Older names can be based on an outdated understanding of a disease. For example, the name pachyonychia congenita makes it sound like all patients have thickened nails, but we now know this is not always the case.

This new classification, developed by experts and patient representatives, aims to:

• Create more precise names: Link the condition directly to the specific genetic change causing it.
• Guide treatment: Help doctors understand what causes your condition. This can lead to better and more focused treatments.
• Remove stigmatising or outdated terms: Remove names that are considered offensive.
• Support research: Make it easier to conduct research and advance new treatments.

How does the new naming system work?

The new names have two parts:

• The gene that is affected
• The type of EDD, divided into three main groups:

New name	Old name	Description
nEDD (Non-syndromic Epidermal Differentiation Disorders)	Ichthyoses	These conditions mainly affect the skin
pEDD (Palmoplantar Epidermal Differentiation Disorders)	Palmoplantar keratodermas	These conditions mainly affect skin on the palms and soles
sEDD (Syndromic Epidermal Differentiation Disorders)	Syndromic ichthyoses	These conditions involve the skin but also affect other organs

Examples of New Names:

What was called ‘ichthyosis vulgaris’ is caused by changes in the FLG gene. If it mainly affects the skin, it is a nEDD. Its new name would combine FLG and nEDD to become: FLG-nEDD. In some patients with changes in FLG, it mainly affects skin on the palms and soles (pEDD), and the new name will combine FLG and pEDD to become FLG-pEDD.

Other examples include:

• ABCA12-nEDD, ALOX12B-nEDD, ALOXE3-nEDD, CYP4F22-nEDD, NIPAL4-nEDD, TGM1-nEDD, and PNPLA1-nEDD: formerly Congenital Ichthyosiform Erythroderma/Lamellar Ichthyosis or Autosomal Recessive Congenital Ichthyosis
• ABCA12-nEDD: formerly Harlequin ichthyosis
• KRT1-nEDD and KRT10-nEDD: formerly Epidermolytic Ichthyosis, Bullous Ichthyosiform Erythroderma (also known as bullous ichthyosis), Epidermolytic Hyperkeratosis. Note: if a patient with a KRT1 variant has mainly palmoplantar involvement with very little other skin involved they will be KRT1-pEDD
• KRT2-nEDD: formerly Ichthyosis Bullosa of Siemens or Superficial Epidermolytic Ichthyosis
• SPINK5-sEDD: formerly Netherton syndrome
• STS-sEDD: formerly X-linked ichthyosis
• SLURP1-pEDD: formerly Mal de Meleda
• KRT16-pEDD: formerly Pachyonychia Congenita (PC- K16)

What if I do not know what my affected gene is?

Genetic testing is crucial. It helps with an accurate diagnosis, treatment, future pregnancy planning, and joining clinical trials. Although genetic testing has improved, in about 10% of cases, we do not find the affected gene. This may be because it is a gene that has not yet been found or because the abnormality in the gene is difficult to find. Sometimes genetic testing may not be available. In these cases, dermatologists have been given guidance on making a diagnosis based on your skin's appearance and whether you have problems in other organs. This helps them make an EDD clinical diagnosis, even without genetic information.

The term "unspecified-nEDD" (or -sEDD or -pEDD) can be used until genetic confirmation is possible, sometimes followed by the suspected cause in parentheses/brackets.

What Does This Mean for You?

This new classification is a step forward. Knowing the genetic cause of your disease and the effects on your skin can help improve diagnoses and create targeted treatments. The new classification might worry patients and carers. Older names can be part of a person's identity or their role in the community. Patients who have an existing diagnosis can continue to use this together with the new name. We expect a transition period, with both names used in healthcare records. For patients who have a new diagnosis, the change will be easier as they will use the new name from the beginning. 

Where Can You Find More Information?

The Ichthyosis Support Group should be able to support you with this change. Your dermatologist will also be able to discuss the new classification with you or refer you to an expert centre.

All academic articles on the new classification system are free to access:

Hernandez-Martin A, Paller AS, Sprecher E et al. A proposal for a new pathogenesis-guided classification for inherited epidermal differentiation disorders. Br J Dermatol 2025; https://doi.org/10.1093/bjd/ljaf065

Akiyama M, Choate K, Hernandez-Martin A et al. Nonsyndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy. Br J Dermatol 2025; https://doi.org/10.1093/bjd/ljaf154

Paller AS, Teng J, Mazereeuw-Hautier J et al. Syndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy. Br J Dermatol 2025; https://doi.org/10.1093/bjd/ljaf123

Sprecher E. Ishida-Yamamoto A, Schwartz J et al. Palmoplantar epidermal differentiation disorders: a new classification toward pathogenesis-based therapy. Br J Dermatol 2025; https://doi.org/10.1093/bjd/ljaf054

This article's first draft was written by Mark Eisner with input from Edel A O’Toole, Neil Rajan, Mandy Aldwin-Easton.  Additional input from the Reclassifying Epidermal Differentiation Disorders Initiative group: Ángela Hernández-Martín, Amy S Paller, Eli Sprecher, Masashi Akiyama, Céline Granier Tournier, Christine Bodemer, Keith Choate,  Judith Fischer,  Antoni Gostynski, Alain Hovnanian, Akemi Ishida-Yamamoto, Matthias Schmuth, Janice Schwartz, Gianluca Tadini, Joyce Teng and Juliette Mazereeuw-Hautier.