Background Deficiency of interleukin-36 receptor antagonist (DITRA) is a life threatening monogenic autoinflammatory disease caused by loss of function mutations in the IL36RN gene. Affected patients develop recurrent episodes of generalized pustular psoriasis (GPP) with systemic inflammation and fever. We here review and analyze the literature on pediatric DITRA patients who have been treated by biologicals targeting inflammatory cytokines. Method A database research was performed to identify all relevant articles on pediatric DITRA patients treated with biologicals. According to defined response criteria therapeutic efficacy was analyzed. Results Our literature research revealed 12 pediatric patients with DITRA who have received treatment with biologicals and we add a further not yet reported patient. Out of these 13 patients 10 were homozygous including 6 with the p.Leu27Pro, 3 with the p.Arg10 Argfs* and 1 with the p.Thr123Met mutation. 3 patients were compound heterozygous. In total 28 flares were treated with biological agents- targeting IL-1, IL-17, IL-12/23 and TNF-α. Complete response was achieved in 16 flares (57%), a partial reponse was seen in 2 flares (7%), and no response was observed in 10 flares (36%). Response rates were heterogeneous among the different agents. While complete/partial/no response with inhibition of TNF-alpha could be achieved in 7 (58%)/1 (8%)/4 (33%), the inhibition of IL-17 and of IL-12/23 led in each 4 flares to a 100% complete response. IL-1 inhibition led to complete/partial response in each 1 (13%) and was not effective in 6 (76%) flares. Of note, the novel patient was successfully treated with weekly dosed adalimumab. Conclusions DITRA is a rare disease that has to be considered in GPP with systemic inflammation and fever. It can be effectively treated with specific biological inhibition of TNF-alpha, IL-12/23 and IL- 17, while anti-IL-1 treatment seems less effective. Weekly dosed adalimumab appears to be a treatment option for pediatric patients. Further reports and studies of biological treated pediatric DITRA patients are warranted for evaluation of optimal treatment.

d-Lactic acidosis with associated encephalopathy caused by overgrowth of intestinal lactic acid bacteria is a rarely diagnosed neurological complication of patients with short bowel syndrome. Here, we report the draft genome sequence of Lactobacillus delbrueckii strain #22 isolated from a patient with short bowel syndrome and previous d-lactic acidosis/encephalopathy.

BackgroundDeficiency of interleukin-36 receptor antagonist (DITRA) is a life threatening autoinflammatory disease caused by autosomal recessive mutations of the IL36RN gene leading to recurrent episodes of generalized pustular psoriasis with systemic inflammation and fever. The disease is rare and no standardized treatment guidelines existObjectivesTo systematically review and analyze the literature on biologically treated pediatric DITRA patientsMethodsA NCBI pubmed database research was performed to identify all relevant articles on pediatric DITRA patients treated with biologicals. According to defined response criteria therapeutic efficacy was analyzed.ResultsOur literature research revealed 13 pediatric patients with DITRA and biolocial treatment. Ten patients were homozygous including six with the p.Leu27Pro, three with the p.Arg10 Argfs* and one with the p.Thr123Met mutation and three were compound heterozygous. We add an unreported DITRA patient with a compound heterozygous IL36RN p.Pro76Leu/pSer113Leu mutation. In total 29 flares in 14 patients were treated with biological agents- targeting IL-1/R, IL-17, IL-12/23 and TNF-α. Complete response was achieved in 15 (52%), partial in 4 (14%), and no response in 10 (34%) of the flares. Response rates were heterogeneous among the different agents. While complete/partial/no response with inhibition of TNF-alpha could be achieved in 6 (46%)/3 (23%)/4 (31%), the inhibition of IL-17 and of IL-12/23 led in each 4 flares to a 100% complete response. IL-1/R inhibition led to complete/partial response in each 1 (13%) and was not effective in 6 (75%) flares. Of note, the unreported patient was successfully treated with weekly dosed adalimumab.ConclusionDITRA is a rare disease that has to be considered in patients with generalized pustular psoriasis with systemic inflammation and fever. It can be effectively treated with specific biological inhibition of TNF-alpha, IL-12/23 and IL- 17, while anti-IL-1/R treatment seems less effective. Weekly dosed adalimumab appears to be a novel treatment option for pediatric patients. Further reports and studies of biological treated pediatric DITRA patients are warranted for evaluation of optimal treatment.Reference[1] Marrakchi, S., P. Guigue, et al. (2011). “Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis.” N Engl J Med 365(7): 620-628.Disclosure of InterestsToni Hospach Speakers bureau: Chugai, Roche, Novartis, Fabian Glowatzki: None declared, Friederike Blankenburg: None declared, Dennis Conzelmann: None declared, Christian Strinkorb: None declared, Chris Sandra Muellerschoen: None declared, Peter Driesch von den: None declared, Lisa Koehler: None declared, Meino Rohlfs: None declared, Christoph Klein: None declared, Fabian Hauck: None declared