Deficiency of interleukin-36 receptor antagonist (DITRA)

DITRA is an autosomal recessive (hereditary) autoinflammatory disease caused by mutations in the IL36RN gene. It is a rare, life-threatening auto-inflammatory disease characterized by repeated episodes of high fever and the sudden onset of generalized pustular psoriasis GPP).

In most cases, symptoms develop during childhood. However, the age of onset can vary considerably. Neonatal onset has also been reported.

Differential diagnosis (distinguishing a particular disease or condition from others that present similar clinical features) includes other causes of GPP, mainly DIRA, in cases where symptoms appear during the first weeks of life.

 

Symptoms

Patients suffering from this syndrome often present the following symptoms:

  • flares of acute generalised skin pustulation (raised bumps filled with pus)

  • fever

  • systemic inflammation

  • general malaise

  • marked leukocytosis (increased number of white cells) during flares

  • elevated CRP (C-reactive protein) levels

 

It can also cause:

  • geographic tongue

  • nail dystrophy

  • failure to thrive

 

Other phenotypes of the IL36RN mutation may include:

  • related pustular disorders

  • palmoplantar pustulosis (of palms and soles)

  • acrodermatitis continua of Hallopeau (abbr. ACH, a rare inflammatory disease characterised by pustular eruptions beginning in the tips of fingers and toes)

  • acute generalized exanthematous pustulosis (a sudden skin eruption, also known as pustular drug eruption).

 

Treatment

There is no established treatment. Topical and oral steroids, vitamin D3, acitretin and anti-TNF-α are effective.

These other treatments have been successful depending on the case:

  • intravenous methylprednisolone

  • Cefotaxime and co-trimoxazole

  • Anakinra

  • Adalimumab and methotrexate

 

 

References:

Edward W. Cowen and Raphaela Goldbach-Mansky. DIRA, DITRA, and New Insights Into Pathways of Skin Inflammation. Arch Dermatol. 2012 Mar; 148(3): 381–384. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464919/

Davide Martorana et al. Monogenic Autoinflammatory Diseases with Mendelian Inheritance: Genes, Mutations, and Genotype/Phenotype Correlations. Front Immunol. 2017; 8: 344.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376573/

Clemente D, López Robledillo J, Torrelo A, et al AB1087 Prolonged response with tumour necrosis factor alfa inhibition in a 5 year old boy with severe manifestations of il-36 receptor antagonist deficiency (DITRA) Annals of the Rheumatic Diseases 2018;77:1653. https://ard.bmj.com/content/77/Suppl_2/1653.1

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