Newborn-onset chronic urticaria as the first manifestation of NLRP3 mosaicism
Pediatric Dermatology
; 40(Supplement 2):20, 2023.
Article
in English
| EMBASE | ID: covidwho-20241213
ABSTRACT
Objectives:
A 7-month-old boy presented with generalized urticaria since the first week of life, without any other clinical manifestation. Cow's milk allergy was ruled out. His development was normal for his age. Maternal history was significant for COVID-19 infection in the third trimester of pregnancy with mild symptoms. Family history was significant for dermatographism in a maternal uncle. Hives were migratory with no single lesion persisting more than 24 h. There were no recognizable triggers and only relieved for 1-2 days after each vaccination. Patient was treated with optimal doses of antihistamines without improvement. Method(s) Laboratory tests and further studies were performedResults:
Laboratory tests were normal including complete blood testing, circulating autoantibodies and infectious studies. C-reactive protein level and erythrocyte sedimentation rate were elevated. Due to chronic urticaria of newborn onset unresponsive to antihistamines a monogenic autoinflammatory disease was suspected. A targeted gene panel covering causative genes revealed the unreported p.Gly307Ala variant in the NLRP3 gene with a variant allele frequency (VAF) of 3% compatible with gene mosaicism. NLRP3 variant was classified as "likely pathogenic" based on its location, where a different variant has been reported as causing a severe form of cryopyrin-associated periodic syndromes (CAPS), and bioinformatic analyses. As expected, the variant was absent in patient's parents supporting for its de novo nature. Vision and hearing exams were normal. Treatment with canakinumab will start soon. Discussion(s) CAPS are dominantly-inherited autoinflammatory diseases caused by gain-of-function NLRP3 variants. These variants are often germline, but in some reported cases the variants are postzygotic causing gene mosaicism as in the patient here described. We believe that the mild presentation in our patient, despite having a likely pathogenic variant, may be explained by the low VAF. The genetic diagnosis in our patient allowed early initiation of anti-IL-1 treatment, which probably will prevent the development of other CAPS manifestations.
allele; autoinflammatory disease; case report; chronic urticaria; clinical article; conference abstract; coronavirus disease 2019; cryopyrin-associated periodic syndrome; dermographism; drug therapy; erythrocyte sedimentation rate; family history; female; gene expression; gene frequency; germ line; hearing; human; human cell; laboratory test; male; maternal uncle; milk allergy; mosaicism; newborn; prevention; protein function; third trimester pregnancy; urticaria; vaccination; vision; antihistaminic agent; autoantibody; C reactive protein; canakinumab; cryopyrin; endogenous compound; interleukin 1
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Prognostic study
Topics:
Long Covid
/
Vaccines
/
Variants
Language:
English
Journal:
Pediatric Dermatology
Year:
2023
Document Type:
Article
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