Novel use of Autoinflammatory Diseases Activity Index (AIDAI) captures skin and extracutaneous features to help manage pediatric DITRA: A case report and a proposal for a modified disease activity index in autoinflammatory keratinization disorders

Abstract

Generalized pustular psoriasis (GPP) is a severe form of psoriasis, which is rare in pediatric and adult patients. It is characterized by sterile pustular lesions that appear on erythematous skin, associated with systemic features. A recent identification of mutations in the IL36RN gene in some GPP patients has led to a diagnosis of new autoinflammatory disease, interleukin‐36‐receptor antagonist deficiency (DITRA). DITRA represents an emerging group of autoinflammatory diseases with hyperkeratotic skin involvement, called autoinflammatory keratinization diseases (AIKD). DITRA diagnosis and management are challenging as neither DITRA‐specific clinical assessment tools nor treatment trials exist. Autoinflammatory Diseases Activity Index (AIDAI) is a validated tool originally developed to evaluate disease activity and treatment response in other inherited autoinflammatory diseases with systemic and skin involvement. We report the first use of AIDAI in a pediatric DITRA patient with the following goals: (a) to describe the contribution of AIDAI to our patient's management; (b) to identify potential limitations of AIDAI in DITRA; (c) to review literature for current psoriasis assessment tools; and (d) to propose a preliminary DITRA/AIKD disease activity index (DITRA/AIDAI) to be validated in future studies.

Clinical Disease Measures in Generalized Pustular Psoriasis

“…The Autoinflammatory Diseases Activity Index (AIDAI), a validated tool originally developed to evaluate disease activity and treatment response in inherited autoinflammatory diseases that involve skin and systemic symptoms, was recently implemented in the assessment and monitoring of disease activity in a patient with deficiency of IL-36-receptor antagonist (DITRA) [ 25 ]. The AIDAI measures 12 items including fever ≥ 38.5 °C, overall symptoms, abdominal pain, nausea/vomiting, diarrhea, headaches, chest pain, painful nodes, arthralgia or myalgia, swelling of the joints, eye manifestations, and skin rash.…”

“…The AIDAI measures 12 items including fever ≥ 38.5 °C, overall symptoms, abdominal pain, nausea/vomiting, diarrhea, headaches, chest pain, painful nodes, arthralgia or myalgia, swelling of the joints, eye manifestations, and skin rash. In a 4-year-old Caucasian boy with GPP, the AIDAI was used to monitor disease activity; however, several limitations were identified [ 25 ]. The systemic symptoms associated with DITRA are usually acute and require immediate intervention, which makes it difficult to obtain a baseline assessment.…”

Generalized pustular psoriasis—Dawn of a new era in targeted immunotherapy

“…Stephenson (DITRA/AIKD-AI), which consists of AIDAI and additionally particularizes "skin rash" into pustular, plaque-type with keratinization or unspecified and adds geographic tongue as a single criterion. 24 With further future validation, this specified assessment tool could be used not only to monitor disease activity but also provide a way to measure treatment response in multiple organs.…”

“…Stephenson et al allude to this topic on reporting on a 4‐year‐old Caucasian boy with an underlying mutation in IL36RN, who developed pustular lesions with systemic symptoms at the age of 2. They suggest to assess the severe extracutaneous manifestations of this autoinflammatory DITRA disease via the autoinflammatory disease activity index (AIDAI) due to its symptom overlap to other autoinflammatory diseases 24 …”

“…AIDAI was originally developed for other inherited autoinflammatory diseases such as familial Mediterranean fever (FMF) and consists of 12 items (fever, overall symptoms, abdominal pain, nausea/vomiting, diarrhoea, headaches, chest pain, painful nodes, arthralgia or myalgia, swelling of the joints, eye manifestations and skin rash) which are scored every day with 0 (no symptoms present) or 1 (symptoms present). A monthly score ≥9 out of 372 maximum points is described as an “active disease.” For the scoring of skin focussed autoinflammatory diseases, the authors propose the 15‐item DITRA/Autoinflammatory Keratinization Diseases Activity Index (DITRA/AIKD‐AI), which consists of AIDAI and additionally particularizes “skin rash” into pustular, plaque‐type with keratinization or unspecified and adds geographic tongue as a single criterion 24 . With further future validation, this specified assessment tool could be used not only to monitor disease activity but also provide a way to measure treatment response in multiple organs.…”