Clinical features of the 7 subjects with SAD included rhinosinusitis (n = 6), otitis media (n = 5), warts (n = 3), malignancies (n = 3; lymphoma, basal cell carcinoma, uterus carcinoma), severe ...varicella requiring hospitalization (n = 2), and recurrent herpes simplex virus infection (n = 1). Because mortality due to infections and malignancies is increased in CHH,4 patients surviving into adulthood represent individuals with milder disease. Worldwide, of the 30 subjects with CHH and hematopoietic stem cell transplantation (HSCT) whose genotype has been reported, only 6 patients were homozygous for g.70A>G mutation.6-9 Only 1 Finnish child with CHH, homozygote for g.70A>G mutation, has required HSCT for severe hypoplastic anemia, not for immunodeficiency. ...selection of patients who would benefit from HSCT based on routinely available laboratory parameters is highly cumbersome in a cohort carrying predominantly RMRP g.70A>G mutations. Laboratory parameter Children <18 y (n = 15)∗ Adults 18-45 y (n = 23)∗ Adults >45 y (n = 18)∗ Patients with symptoms of CID∗ Patients without symptoms of CID∗ P value Neutrophils 2.45‡ 3.91 4.36‡ .005 Naive thymic T cells† 0.009 0.036 .022 CD3+ cells 0.66 0.93 .048 CD4+ cells 0.514 0.487‡ 0.699‡ .038 CD8+ cells 0.22 0.33 .018 CD19+ cells 0.150‡ 0.085‡ 0.120 .014 IgA 1.42‡ 1.80 2.75‡ .006 IgG 9.2‡ 10.5 11.7‡ .027 IgG2 1.25‡ 1.98 2.19‡ .034 Antibodies to tetanus toxoid (IU/mL) 0.35‡ 3.50‡ 1.50 .002 1 M.A. de la Fuente, M. Recher, N.L. Rider, K.A. Strauss, D.H. Morton, M. Adair, Reduced thymic output, cell cycle abnormalities,...
In patients with immunodeficiency, lung disease such as BE or parenchymal changes contribute to poorer prognosis.6 Out of 8 previously reported patients with BE, 1 died from pneumonia at 58 years; ...others had significant respiratory symptoms and 6 suffered from pneumonia.1 BE was progressive in all those with longitudinal follow-up extending to adulthood.1 Another report described a young adult with CHH, frequent infectious exacerbations and rapid progression of BE, leading to fatal septicemic pneumonia within 2 years.9 We previously reported higher IgG levels in infection-prone patients with CHH.2 Here, we find the same trend, as well as higher white blood cells, total lymphocyte, and CD16/56+ cell counts in CHH patients with BE. Supplementary data Online Repository textFig E1 Characteristics Normal values for adultslow * Patients with BE Patients without BE P value Median age (y) (range)  59.5 (29-68) 36.5 (13-68) .023dagger Sex  F 70% (7 of 10)M 30% (3 of 10) F 88% (21 of 24)M 12% (3 of 24) .328 History of chronic cough  50% (5 of 10) 17% (4 of 24) .085 History of sinusitis  90% (9 of 10) 63% (15 of 24) .215 History of otitis media  70% (7 of 10) 75% (18 of 24) 1 History of pneumoniadouble dagger  30% (3 of 10) 21% (5 of 24) .666 History of physician-diagnosed asthma  30% (3 of 10) 29% (7 of 24) 1 History of allergic rhinitis  60% (6 of 10) 38% (9 of 24) .276 History of smoking  40% (4 of 10) 8% (2 of 24) .048 Previous or ongoing IVIG substitution  0% (0 of 10) 17% (4 of 24) .296 IgG (g/L) 6.8-15.0 13.0 (10.1-15.7) 10.6 (6.2-15.9) .013 IgG2 (g/L) 1.50-6.40 2.03 (0.27-4.01) 2.00 (0.55-4.52) .755 IgG3 (g/L) 0.20-1.10 0.43 (0.17-1.17) 0.45 (0.12-1.20) .724 IgG4 (g/L) 0.08-1.40 0.09 (0.00-0.82) 0.08 (0.00-0.47) .724 IgA (g/L) M 0.88-4.84F 0.52-4.02 2.82 (1.24-4.95) 1.83 (0.00-7.49) .086 IgM (g/L) M 0.36-2.59F 0.47-2.84 0.89 (0.28-2.47) 0.99 (0.20-3.06) .512 IgE (kU/L) 0-100 34 (10-98) 13 (2-254) .205 WBC (x109 cells/L) 3.4-8.2 6.8 (4.7-12.0) 4.8 (1.2-11.1) .034 Neutrophil count (x109 cells/L) 1.5-6.7 4.26 (2.22-8.40) 3.31 (0.28-7.88) .137 Total lymphocyte count (x109 cells/L) 1.3-3.6 1.76 (1.16-3.25) 1.21 (0.26-2.22) .008 CD3+ cell count (x109 cells/L) 0.85-2.28 1.24 (0.57-3.01) 0.90 (0.16-1.91) .051 CD4+ cell count (x109 cells/L) 0.458-1.406 0.711 (0.353-1.287) 0.524 (0.118-1.312) .123 CD8+ cell count (x109 cells/L) 0.24-0.98 0.52 (0.15-1.72) 0.30 (0.04-0.76) .068 CD3/CD4/CD45RA/CD31+ cell count (x109 cells/L) 0.05-2.4 0.011 (0.003-0.171) 0.030 (0.000-0.247) .269 CD16/56+ cell count (x109 cells/L) 0.08-0.57 0.25 (0.11-0.55) 0.14 (0.07-0.36) .008 CD19+ cell count (x109 cells/L) 0.12-0.43 0.11 (0.04-0.22) 0.11 (0.00-0.28) .524 CD27+ IgD+ B-cell count (cells/μL) 9-88 5,9 (2.9-13.3) 6.5 (0.0-20.9) .603 CD27+ IgD- B-cell count (cells/μL) 13-122 12.8 (3.9-59.6) 10.6 (0.0-63.8) .269 Antibodies to tetanus toxoid (IU/mL) >0.1 2.85 (0.07-4.60) 2.35 (0.05-8.90) .621 Good response to immunization with PPV (no. of serotypes)§ 7 4 (3-5) 6 (1-7) .773 Table I Comparison of clinical and laboratory characteristics of patients with and without BE Values for laboratory parameters are presented as median (range).
Hyperimmunoglobulinemia D syndrome (HIDS) is an autoinflammatory disorder that is caused by mevalonate kinase deficiency (MKD). Recent advances in the pathogenesis of MKD, including the proposed ...mechanisms of inflammasome activation, provide the basis for the development of new treatment modalities. So far, feedback on the treatment of HIDS with biological medicines has come from case reports with limited numbers of patients. In this review, we summarize the data that is currently available on the treatment of HIDS in children, with the emphasis on new therapies, and present three Finnish pediatric cases treated with anakinra. Case reports have been published on 33 pediatric HIDS patients who have been treated with biological medicines, and in some cases, they were treated with more than one drug. Of these patients, 21 were treated with anakinra and 16 with etanercept, resulting in complete or partial responses in 90 and 50 % of cases, respectively. A further five patients were treated with canakinumab, with complete or partial responses.
Conclusion
: The accumulating evidence on the efficacy and safety of biological drugs in pediatric HIDS suggests that the anti-interleukin-1 agent anakinra is the drug of choice for HIDS in children.
What is Known:
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Various biologic drugs have been tried for the treatment of HIDS
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What is New:
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Based on the 90 % response rate, anakinra seems to be the drug of choice for HIDS in children
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BackgroundCartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia caused by RMRP (RNA component of mitochondrial RNA processing endoribonuclease) gene mutations. Manifestations ...include short stature, variable immunodeficiency, anaemia and increased risk of malignancies, all of which have been described also in telomere biology disorders. RMRP interacts with the telomerase RT (TERT) subunit, but the influence of RMRP mutations on telomere length is unknown. We measured relative telomere length (RTL) in patients with CHH, their first-degree relatives and healthy controls and correlated RTL with clinical and laboratory features.MethodsThe study cohort included 48 patients with CHH with homozygous (n=36) or compound heterozygous RMRP mutations (median age 38.2 years, range 6.0–70.8 years), 86 relatives (74 with a heterozygous RMRP mutation) and 94 unrelated healthy controls. We extracted DNA from peripheral blood, sequenced the RMRP gene and measured RTL by qPCR.ResultsCompared with age-matched and sex-matched healthy controls, median RTL was significantly shorter in patients with CHH (n=40 pairs, 1.05 vs 1.21, p=0.017), but not in mutation carriers (n=48 pairs, 1.16 vs 1.10, p=0.224). RTL correlated significantly with age in RMRP mutation carriers (r=−0.482, p<0.001) and non-carriers (r=−0.498, p<0.001), but not in patients (r=−0.236, p=0.107). In particular children (<18 years) with CHH had shorter telomeres than controls (median RTL 1.12 vs 1.26, p=0.008). In patients with CHH, RTL showed no correlation with genotype, clinical or laboratory characteristics.ConclusionsTelomere length was decreased in children with CHH. We found no correlation between RTL and clinical or laboratory parameters.
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