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)

Abstract

BackgroundDeficiency of the interleukin (IL)−36 receptor antagonist (DITRA) is an autosomal recessive autoinflammatory syndrome caused by mutations in the IL36RN gene. Clinical manifestations of DITRA include recurrent episodes of generalised skin postulation, fever, systemic inflammation and leukocytosis. An uniformly effective treatment for DITRA has not yet been identified.ObjectivesWe present a case of a 5 year old patient with DITRA with prolonged response with tumour necrosis factor alfa inhibition with adalimumab.MethodsA five-year-old came to our dermatology clinic after worsening of a previous diagnosed plaque psoriasis, with an erythematous scaly dermatitis that extended throughout the trunk. Treatment with acitretin and cyclosporin were not effective and patient developed in few weeks a generalised erythroderma with pustules covering almost every part of his body, including palms and soles. He was admitted for the onset of fever and irritability due to painful rubbing of the skin. Family history of recurrent fevers or psoriasis were not revealed. Parents were not consanguineous.Complete blood count showed leukocytosis with neutrophilia and thrombocytosis, with an erythrocyte sedimentation rate (ESR) of 6 mm/hr and a C-reactive protein (CRP) of 8,4 mg/dl. Biochemistry panel revealed a mild elevation of liver enzymes without other abnormalities. Antinuclear antibody (ANA) and rheumatoid factor were negative with normal serum immunoglobulin and complement. Blood culture grew E. Coli, S. Maltophila and S. epidermidis. Skin biopsy showed acanthosis and papillomatosis with perivascular polymorphous inflammatory cells. Genetic analyses showed a homozygous mutation in the IL36RN gene (pSer113Leu). No mutations were detected in IL1RN and CARD 14 genes.ResultsTreatment was initiated with intravenous methylprednisolone 2 mg/kg/day and subcutaneous anakinra 2 mg/kg/day. Cefotaxime and co-trimoxazole were added until blood cultures were negative. Although skins lesions improved during the following days and patient was finally discharged, symptoms reappeared when decreasing the steroid dose. Three months later adalimumab and methotrexate were started, allowing the patient to end treatment with corticoids without evidence of activity of the disease.Abstract AB1087 – Figure 1ConclusionsAfter incomplete response with anakinra, inhibition of tumour necrosis factor alfa resulted in a prolonged response in our patient with deficiency of the interleukin (IL)−36 receptor antagonist (DITRA).Disclosure of InterestNone declared

Cutaneous findings and treatments in deficiency of interleukin‐36 receptor antagonist (DITRA): A review of the literature

“…12 Another case report described a 5-year-old girl with DITRA who was treated with adalimumab and cyclosporine. 21 This led to the complete remission of her skin lesions and the normalization of her laboratory parameters. Given the data are limited to use in case reports, more studies are warranted to evaluate the efficacy and safety of adalimumab in patients with DITRA.…”

“…Since the initial description of DITRA, which included 16 patients from nine families, 2,7,[10][11][12] only occasional cases of the disease in various age groups have been reported. 1,8,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Unfortunately, treatment options for DITRA are limited, especially in children. 30 However, there have been some more recent reports of success in managing disease symptoms with various biologics targeted at specific elements of the autoinflammatory cascade.…”

“…Emerging case reports suggest adalimumab may benefit DITRA patients, particularly in combination with other immunosuppressive agents like methotrexate or cyclosporine. 12,21,23,31,33 A case report describes an adolescent male with DITRA who was treated with subcutaneous secukinumab and methotrexate, significantly improving his skin lesions and systemic symptoms. 12 Another case report described a 5-year-old girl with DITRA who was treated with adalimumab and cyclosporine.…”

“…Adalimumab is a TNF‐α inhibitor used to treat various inflammatory diseases, including psoriasis. Emerging case reports suggest adalimumab may benefit DITRA patients, particularly in combination with other immunosuppressive agents like methotrexate or cyclosporine 12,21,23,31,33 . A case report describes an adolescent male with DITRA who was treated with subcutaneous secukinumab and methotrexate, significantly improving his skin lesions and systemic symptoms 12 .…”

“…Since the initial description of DITRA, which included 16 patients from nine families, 2,7,10–12 only occasional cases of the disease in various age groups have been reported 1,8,10–29 . Unfortunately, treatment options for DITRA are limited, especially in children 30 .…”