Netherton Syndrome

Netherton Syndrome is a severe, ultra-rare multisystem disorder which has a life-altering impact across a person’s life.¹

Illustration of a man with the skin scaling

Symptoms of Netherton Syndrome:

Netherton Syndrome is classified as an autosomal recessive congenital ichthyosis (ARCI).² It is caused by a mutation in the SPINK5 gene, resulting in a loss of skin barrier function and excess immune system activation^1,3

In addition to symptoms affecting the skin it also can cause non-skin manifestations and these symptoms can differ between people living with Netherton Syndrome.¹ Netherton Syndrome symptoms can appear from birth and may continue into adulthood.⁴

The key symptoms affecting the skin are:^1,4,5

Scaling including circular scaly rashes and peeling
Erythema/redness
Persistent itch
Pain
Thin, fragile hair (bamboo hair), hair loss and other abnormalities

As a multisystemic condition, the impact of Netherton Syndrome goes beyond the skin. The non-skin related symptoms of Netherton Syndrome include:^1,4,5

Immune related problems such as asthma, rhinitis, conjunctivitis, angioedema and food allergies
Recurrent infections and sepsis
Sleep disorders
Severe impact on organs resulting in Rickets, pancreatitis and esophagitis

Overview of Netherton Syndrome by Dr Amy Paller (Chair, Department of Dermatology; Director, Skin Biology and Diseases Resource-Based Center; Walter J. Hamlin Professor of Dermatology; Feinberg School of Medicine, Northwestern University, Chicago, Illinois, US)

What causes Netherton syndrome:

Netherton Syndrome is caused by a mutation in the SPINK5 gene, inherited from each parent, which plays an important role in everyday skin renewal.^1,3 A mutation in this gene leads to the loss of skin barrier function and excess immune system activation.^1,3.

Illustration of Netherton Syndrome symptoms and the caption "Up to 9 people per million live with NS"

Netherton Syndrome is estimated to affect 1 to 9 people per million in the population.⁶ However, the prevalence of Netherton Syndrome may be underestimated because of early mortality in newborns and difficulty in its diagnosis due to symptoms often resembling those of other conditions.^5,7

Diagnosing Netherton Syndrome is often challenging as it is very rare, symptoms can change over time and can differ between people living with Netherton Syndrome.¹

Netherton Syndrome in newborns can be life-threatening because of severe water loss and the risk of infections.^8,9 Prognosis is poor due to high mortality in the first years of life, with mortality rates ranging from 10% to 20%.^10,11 Infants with this condition tend to grow slowly and have poor weight gain.⁴

Netherton Syndrome: Unmet Needs for Treatment by Dr Amy Paller (Chair, Department of Dermatology; Director, Skin Biology and Diseases Resource-Based Center; Walter J. Hamlin Professor of Dermatology; Feinberg School of Medicine, Northwestern University, Chicago, Illinois, US)

How Netherton Syndrome affects the quality of life of people living with the condition:

Netherton Syndrome has a significant impact on quality of life.¹² People may experience extreme tiredness and pain, sleeping problems, financial burden due to fewer career opportunities, and compromised performance in school.¹² They may also have emotional problems, including anxiety, and depression.¹²

Current treatment strategies leave patients of all ages with considerable unmet needs, highlighting the importance of new and improved management options for Netherton Syndrome.^5,13

IL-36 signaling appears to be a key driver in Netherton Syndrome with abnormal IL-36 signatures seen in both lesion skin and blood in people with Netherton Syndrome. An increased expression of IL-36 in Netherton Syndrome correlates with disease severity^14,15

Boehringer Ingelheim is investigating the IL-36 receptor (IL-36R) inhibitor spesolimab for the treatment of Netherton Syndrome.¹⁶

You can find a link to the clinical study to test whether Boehringer Ingelheim’s IL-36R inhibitor spesolimab helps people with Netherton Syndrome here.

Netherton Syndrome: Impact on Quality of Life by Dr Amy Paller (Chair, Department of Dermatology; Director, Skin Biology and Diseases Resource-Based Center; Walter J. Hamlin Professor of Dermatology; Feinberg School of Medicine, Northwestern University, Chicago, Illinois, US)

References:

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Netherton syndrome: A patient’s perspective. https://www.firstskinfoundation.org/types-of-ichthyosis/netherton-syndrome (Accessed September 2023).
Netherton syndrome. https://rarediseases.info.nih.gov/diseases/7182/netherton-syndrome (Accessed September 2023).
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Orpha.Net. Netherton syndrome. https://www.orpha.net/consor/cgi-bin/Disease_Search.php (Accessed September 2023).
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Versteegh JJ, et al. J Health Psychol. 2020;25:2296-2316.
DermNet NZ. https://dermnetnz.org/topics/netherton-syndrome (Accessed September 2023).
Barbieux C, et al. J Allergy Clin Immunol. 2021;149:1358-1372.
Malik K, et al. J Allergy Clin Immunol. 2019;143(2):604–618.
ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT05856526 (Accessed September 2023).