Autoimmune Hemolytic Anemia Due to Spondyloenchondrodysplasia with Spastic Paraparesis and Intracranial Calcification due to Mutation in ACP5.

Spondyloenchondrodysplasia (SPENCD) is a rare spondylometaphyseal skeletal dysplasia with characteristic lesions mimicking enchondromatosis and resulting in short stature. A large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders. SPENCD is caused by loss of tartrate-resistant acid phosphatase activity, due to homozygous mutations in ACP5 , playing a role in nonnucleic-acid-related stimulation/regulation of the type I interferon pathway. In this article, we presented a 19-year-old boy with SPENCD, presenting with recurrent autoimmune hemolytic anemia episodes since he was 5 years old. He had short stature, platyspondyly, metaphyseal changes, intracranial calcification, spastic paraparesis, and mild intellectual disability. He also had recurrent pneumonia attacks. The clinical diagnosis of SPENCD was confirmed by sequencing of the ACP5 gene, and a homozygous c.155A > C (p.K52T) variation was found, which was reported before as pathogenic. In conclusion, in early onset chronic autoimmune cytopenias an immune dysregulation may often have a role in the etiology. Associating findings and immunologic functions should be carefully evaluated in such patients in the light of the literature. The present case shows the importance of multisystemic evaluation for the detection of SPENCD that has a monogenic etiology.

Angioedema-like presentation as the presenting finding of juvenile myositis and juvenile dermatomyositis in 2 patients.

BACKGROUND: Juvenile dermatomyositis (JDM) is the most common subtype of idiopathic inflammatory myopathies in childhood. Gottron's papules, shawl sign, periorbital heliotrope rash, and periungual telengiectasis are characteristic skin findings of the disease. Besides characteristic skin involvement, some other skin findings, such as angioedema, may be seen prior or in the course of the disease. The presence of angioedema in JDM is emphasized in this report. CASE PRESENTATIONS: We present 2 unrelated girls, aged 2 (case 1) and 12 years (case 2), who had developed symmetrical weakness in the proximal muscles, muscle pain, elevated muscle enzymes and angioedema. Both cases had abnormal muscle magnetic resonance imaging findings, suggestive of inflammatory myositis. Muscle biopsy was performed only in case 1, and major histocompatibility complex-1 expression on myofibers was shown consistent with JDM. Cases were diagnosed as probable and definite JDM, respectively. Angioedema was prominent, particularly in the lips and extremities of both cases, without laboratory evidence of C1 inhibitor deficiency or capillary leak syndrome, and absence of family history. Mast cell-mediated, acquired angioedema was the most likely diagnosis. In both cases, skin and muscle findings improved significantly with steroid treatment. CONCLUSION: We suggest that angioedema may be among the characteristic skin findings in JDM, and may be included in subsequent definitions.

Proven Food-Induced Acute Urticaria and Predictive Factors for Definitive Diagnosis in Childhood.

BACKGROUND: Urticaria can be the only sign of a food allergy or can be seen together with other signs and symptoms of a food allergy. OBJECTIVE: To determine the demographic, etiologic, and clinical features of food-induced acute urticaria in childhood. METHODS: Patients suspected of food-induced acute urticaria were included in this prospective cross-sectional multicenter study. RESULTS: Two hundred twenty-nine urticaria cases were included in this study. Seventeen patients who did not meet the inclusion criteria of the study were excluded. Of the 212 included cases, 179 (84.4%) were diagnosed with definitive food-induced acute urticaria. The most common foods causing acute urticaria were cow's milk, hen's eggs, and nuts in 56.4, 35.2, and 19% of cases, respectively. The positive predictive value of a history of milk-induced acute urticaria together with a milk-specific IgE >5 kU/L for cow's milk-induced acute urticaria was 92% (95% CI: 81-96%). A history of cow's milk-induced and/or hen's egg-induced acute urticaria was consistent with a definitive diagnosis of food-induced urticaria (Chen's kappa: 0.664 and 0.627 for milk and eggs, respectively). Urticaria activity scores were higher in patients with food-induced acute urticaria (p = 0.002). CONCLUSION: Cow's milk, hen's eggs, and nuts were the most common allergens in the etiology of childhood food-induced acute urticaria. Although the urticaria activity score provides guidance for diagnosis, an oral food challenge is often essential for the definitive diagnosis of a patient with a history of food-induced acute urticaria.

Utility of fresh egg skin prick test and egg yolk specific immunoglobulin E for outgrowth.

BACKGROUND: In children younger than 2 years, studies evaluating the value of skin prick tests (SPTs) and specific immunoglobulin E (sIgE) results to predict persistence or resolution of egg allergy (EA) are limited. In addition, the value of egg yolk (EY) sIgE and fresh egg (FE) SPTs has not been well characterized. OBJECTIVE: To investigate the optimal decision points (ODPs) for outgrowing allergy with SPTs and sIgE tests for egg allergen preparations. METHODS: SPTs for FE, egg white (EW), and EY, sIgE tests for EW and EY, and oral food challenges (OFCs) were performed in children with suspected EA. Reactive patients strictly avoided all dietary egg. After 1 year, EA was reevaluated with addition OFCs, SPTs, and sIgE tests. RESULTS: A total of 81 children (median age, 7 months; age range, 2-24 months) were enrolled. Notably, 4 children with a history of anaphylaxis and 60 of 77 children with a positive challenge result underwent egg elimination. The 1-year follow-up OFC test was performed on 59 children. A total of 27 reacted to egg. No persistent patient had a follow-up SPT result for FE of 4 mm or less (positive predictive values of 100% and negative predictive value of 56% for outgrowth). The diameters of the initial SPT for FE decreased 50% or more in half of the patients who outgrew EA. The ODPs for outgrowing allergy for follow-up sIgE tests for EY and EW were 2.1 kU/L or less (positive predictive value of 86.2%) and 4.0 kU/L or less (positive predictive value of 84.6%), respectively. CONCLUSION: A SPT diameter for FE of 4 mm or less and sIgE values of 2.1 kU/L or less for EY and 4.0 kU/L or less for EW have a good positive predictive value for outgrowth of EA in children younger than 2 years.

Two approaches for diagnosis of nonsteroidal anti-inflammatory drug hypersensitivity in children.

BACKGROUND: The oral provocation test (OPT) with culprit drug is the gold standard in the diagnosis of nonsteroidal anti-inflammatory drug hypersensitivity (NSAID-H). Some authors have proposed that the total number of OPTs required to diagnose NSAID-H is much lower with acetyl salicylic acid (ASA) provocations, regardless of patients' reaction history, and less time consuming. OBJECTIVE: This study aims to evaluate the total number of OPTs required to confirm NSAID-H according to the drugs (ASA or culprit NSAID) used in the initial OPT. METHODS: The study included patients with a history of NSAID-H. Data on the demographic and clinical features, coexisting chronic or allergic disease, and laboratory results were collected from medical records. The drug used for the initial OPT (ASA or culprit NSAID), results of the OPT, and the total number of OPTs were reviewed. RESULTS: We included 56 children with suspected hypersensitivity reaction to NSAIDs. NSAID-H was confirmed in 21 children (37.5%). We calculated that if all OPTs were performed with culprit drugs as an initial choice, the number of OPTs required for diagnosis would be 3 or more in 85.7% of positive cases. The number of episodes was an independent risk factor for NSAID-H by multiple logistic regression analysis (odds ratio, 4.3; 95% confidence interval, 1.48-12.24; P = .007). CONCLUSION: Performing an initial OPT with ASA regardless of patients' reaction history can result in much lower numbers of OPT to diagnose NSAID-H and can improve patient compliance.

Suspected Reaction with Cephalosporin May Be a Predictive Factor for ß-Lactam Allergy in Children.

BACKGROUND: Most children diagnosed with ß-lactam allergy based only on history are not truly allergic, and mislabeling leads to use of less effective and more costly alternative broader-spectrum antibiotics, significantly increasing drug resistance. OBJECTIVE: To determine the frequency and risk factors of confirmed allergy in patients with ß-lactam allergy reported by parents or their doctors and evaluate cross-reactivity between ß-lactams in children with confirmed allergy. METHOD: Sixty-seven children with suspected ß-lactam allergy were evaluated via history, sIgE measurements, skin tests, and drug provocation tests over a period of 5 years. RESULTS: ß-Lactam allergy was confirmed in 10 (14.9%) patients. Six patients had a positive intradermal test result to one or more of the penicillin skin test materials or ceftriaxone, 4 patients with negative skin test results had positive test results with suspected drugs. Age, gender, time interval between evaluation and the initial reaction, personal history of atopy, parental history of drug allergy, reaction type, and multiple drug allergy history were not significantly different between allergic and tolerant patients. For culprit drugs, there was a significant different between the 2 groups; the rate of confirmed diagnosis was significantly higher for cephalosporins such as ceftriaxone, cefuroxime, and cefprozil (p = 0.03). Three patients with allergy to penicillin tolerated cefuroxime; in 4 patients with selective allergy to ceftriaxone tolerated cephalosporins with a dissimilar side chain (cefadroxil, cefuroxime, cefaclor, and cefdinir). CONCLUSION: Our study indicates that most patients with a suspected ß-lactam allergy tolerated this drug. An appropriate diagnostic allergy workup may prevent the use of less effective and more expensive alternatives.