Efficacy, safety, and pharmacokinetics of oral valganciclovir in patients with congenital cytomegalovirus infection.

OBJECTIVES: Valganciclovir (VGCV) has been shown to improve sensorineural hearing loss (SNHL) and neurological outcomes in patients with neonatal symptomatic congenital cytomegalovirus (cCMV) infection. However, reports on the pharmacokinetics, efficacy and safety of oral VGCV are limited. The aim of this study is to evaluate the pharmacokinetics of VGCV for use in the treatment of cCMV. METHODS: This was a single-center, retrospective observational study conducted at Saitama Children's Medical Center in Japan between 2012 and 2017. CMV DNA copy number, maximum plasma VGCV concentration (Cmax), and adverse events (ADEs) during treatment were evaluated. RESULTS: A total of 26 patients with cCMV who received VGCV were included in this study. The median age at VGCV initiation was 9.5 months (range 0-46). Twenty-one patients (81%) had SNHL at baseline. Of these, five patients (19%) presented with improved SNHL, and none experienced worsened SNHL during treatment. The mean VGCV Cmax was 3.5 µg/mL (range 2-5.3), with no significant variation among individual values, and the values were maintained during treatment. Furthermore, there were no correlations between the Cmax values and age, sex, SNHL improvement or ADEs. Neutropenia (<1000/mm3) was observed in six patients (23%); however, no serious ADEs occurred. CONCLUSIONS: VGCV prevented the progression of SNHL without serious ADEs due to its stable pharmacokinetics. This study provides safety and tolerability of VGCV for the treatment of cCMV patients.

Infected simple renal cyst due to Streptococcus pneumoniae rapidly diagnosed by the melting temperature mapping method: a case report.

BACKGROUND: Spontaneous infection of preexisting solitary renal cysts has been documented in adults but is extremely rare in children. To date, no cases of simple renal cysts infected with Streptococcus pneumoniae have been described. Recently, reports have described the diagnosis of bacterial infection using the 16 S rRNA gene as well as the accompanying antimicrobial stewardship for microorganisms that are difficult to culture and for culture-negative cases after preceding antibacterial administration. CASE PRESENTATION: A four-year-old Japanese girl who had a pleuroperitoneal shunt inserted to drain a right pleural effusion due to occlusion of the hepatic portion of the inferior vena cava at three years old visited our hospital due to fever and respiratory discomfort. She was incidentally found to have a right simple renal cyst 10 months before admission. The patient was suspected to have pneumonitis or catheter-related blood stream infection on chest X-ray, which showed right-side pleural effusion. She was diagnosed with invasive pneumococcal infection, as Streptococcus pneumoniae was detected from blood culture on admission. Transient improvements in her symptoms and decreases in the white blood cell count and C-reactive protein level were observed after effective antibiotic administration, but her respiratory condition deteriorated. Enhanced CT showed right renal cyst enlargement and enhancement and thickening of the surrounding wall. Using the melting temperature (Tm) mapping method, S. pneumoniae was rapidly detected directly from pus 4.5 hours after drainage. The specimen culture was negative, but the extracted 16 S rDNA sequence revealed 100 % identity for S. pneumoniae from the same specimen the subsequent day. We successfully performed optimal treatment and reduced medical cost based on the positive Tm mapping method result. CONCLUSIONS: We report the first case of a S. pneumoniae-infected simple renal cyst. The drainage culture was negative, but the Tm mapping method rapidly detected S. pneumoniae directly from the drainage. The Tm mapping method may have great impacts on rapid diagnosis and effective antimicrobial stewardship.

10-year follow-up of congenital cytomegalovirus infection complicated with severe neurological findings in infancy: a case report.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection leads to sensorineural hearing loss (SNHL) and neurodevelopmental delays. However, the long-term outcomes of cCMV infection with severe neurological manifestations in infancy remain unclear. CASE PRESENTATION: The patient was a one-month-old girl visited owing to abnormalities in neonatal hearing screening. Central nervous system involvement including intracranial calcification and extensive white matter abnormalities was identified. Right SNHL (50 dB) was detected by auditory brain response (ABR) testing. The cause of her hearing loss was determined to be cCMV infection by polymerase chain reaction (PCR) using a dried blood spot. At 1.5 months of age, the patient was treated with intravenous ganciclovir (GCV) for 5 weeks followed by oral valganciclovir (VGCV) for an additional 6 weeks. Cytomegalovirus (CMV) loads in her urine continued to be detected until she was 10 years old. Fortunately, during this time, her right hearing loss did not deteriorate, and her left hearing remained normal. Furthermore, the extensive abnormal areas of white matter observed at 1 month of age mostly disappeared by the time the patient was 9 years old. Her neurodevelopmental score was normal, and motor milestones were not delayed as of 10 years of age. CONCLUSIONS: Here, we report the 10-year follow-up of a patient with cCMV who showed normal neurodevelopment, no progression of hearing loss, and ameliorating magnetic resonance imaging (MRI) findings, despite having various complications and severe neurological findings during infancy.

Clinical analysis and outcome of interstitial lung disease complicated with juvenile dermatomyositis and juvenile polymyositis.

OBJECTIVES: The aim of this study was to determine the clinical phenotype and outcome of interstitial lung disease (ILD) complicated with juvenile dermatomyositis (JDM) or juvenile polymyositis (JPM). METHODS: This was a single-center retrospective study. From 1984 to 2015, we retrospectively reviewed 29 patients who were diagnosed with JDM/JPM, among whom eight cases were ILD and 21 were non-ILD. The clinical features and laboratory findings included chest computed tomography (CT) images that were compared between the patients with ILD and non-ILD. RESULTS: Eight cases (27.6%) were complicated with ILD. The mean age was 6.3 years, and 75% of the patients were women. We found that high fever, arthralgia, muscle weakness, and high serum Krebs von den Lungen-6 (KL-6) level were significantly associated with the presence of ILD (p < 0.05). Two patients were positive for the anti-Jo-1 antibody, and two other patients were positive for the anti-MDA5 antibody. Three cases were identified as rapidly progressive (RP)-ILD. The chest CT images of the ILD patients appeared to show ground glass opacity (GGO) with a lower lobe predominance, reticulation, and traction bronchiectasis consolidation. Three patients with RP-ILD showed random subpleural GGO with/without consolidation patterns. Further, three patients with RP-ILD died of respiratory failure (p < 0.01). CONCLUSION: ILD is one of the most serious complications of JDM/JPM. In the early phase of ILD, high levels of serum KL-6 can be detected, regardless of the respiratory symptoms. Additionally, RP-ILD can be predicted based on the presence of anti-MDA5 antibodies and the chest CT findings, including random subpleural GGO with/without consolidation patterns.

Thalidomide attenuates excessive inflammation without interrupting lipopolysaccharide-driven inflammatory cytokine production in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited disorder characterized by an inability to produce reactive oxygen species, resulting in recurrent life-threatening infections. Curiously, half of the patients with CGD suffer from aseptic bowel inflammation (CGD colitis) due to dysregulated inflammation induced by TNF-α and IL-1ß. Thus, developing therapies that regulate excessive inflammatory responses without interrupting antimicrobial immunity would benefit CGD colitis patients. Here, we show that thalidomide suppressed TNF-α-induced NF-κB activation and ATP-induced IL-1ß secretion, but did not interrupt the production of IL-1ß, IL-6, IL-8, and TNF-α in response to lipopolysaccharide in CGD monocytes. We report on a CGD colitis patient that showed decreased bowel inflammation characterized by reduced serum levels of inflammatory cytokines without evidence of progression of fungal and bacterial infections present at initiation of thalidomide therapy. Our results suggest that thalidomide could be an efficacious therapeutic option for patients with CGD colitis suffering from serious infections.

Rapid detection of intracellular p47phox and p67phox by flow cytometry; useful screening tests for chronic granulomatous disease.

Chronic granulomatous disease (CGD) is caused by defects of NADPH oxidase. The diagnosis of CGD can be made by analysis of NADPH oxidase activity, however, identification of the CGD subgroups is required before performing mutation analysis. The membrane-bound subunits, gp91phox and p22phox, can be quickly analyzed by flow cytometry, unlike the cytosolic components, p47phox and p67phox. We evaluated the feasibility of flow cytometric detection of p47phox and p67phox with specific monoclonal antibodies in two patients with p47phox deficiency and 7 patients with p67phox deficiency. Consistent with previous observations, p47phox and p67phox were expressed in phagocytes and B cells, but not in T or natural killer cells, from normal controls. In contrast, patients with p47phox and p67phox deficiency showed markedly reduced levels of p47phox and p67phox, respectively. These techniques will be useful to rapidly assess the expression of the cytosolic components, p47phox and p67phox, and represents important secondary screening tests for CGD.

Clinical and immunophenotypic features of atypical complete DiGeorge syndrome.

BACKGROUND: DiGeorge syndrome is a congenital malformation characterized by variable defects of the thymus, heart and parathyroid glands. Athymic patients are classified as exhibiting complete DiGeorge syndrome. Some of these patients may also exhibit oligoclonal T-cell expansion, generalized rash and lymphadenopathy at some point after birth. This rare condition is known as atypical complete DiGeorge syndrome, resembles Omenn syndrome, and has not been fully characterized. METHODS: The clinical and immunophenotypic features of atypical complete DiGeorge syndrome were assessed in two affected Japanese infants. T-cell receptor (TCR) Vß repertoire was analyzed on flow cytometry and complementarity-determining region 3 spectratyping. RESULTS: Both patients had no detectable thymus tissue and profound T-cell lymphopenia soon after birth. Progressive increase of activated T cells, however, as well as eosinophilia, high serum IgE level, generalized rash, and lymphadenopathy were observed during early infancy. A highly restricted TCR Vß repertoire was demonstrated both in CD4(+) and CD8(+) T cells. CONCLUSIONS: The Omenn syndrome-like manifestations might be associated with the oligoclonal proliferation of activated T cells. Analysis of the immunophenotype and TCR Vß repertoire is helpful to establish the early diagnosis of atypical complete DiGeorge syndrome.

Mycophenolate mofetil therapy for juvenile dermatomyositis with immune thrombocytopenic purpura.

A 6-year-old girl, who had received corticosteroid and cyclosporine on the diagnosis of interstitial pneumonitis related to juvenile dermatomyositis, developed severe thrombocytopenia. Her thrombocytopenia was resistant to repeated intravenous immunoglobulin administration and methylprednisolone pulse therapy. After additional treatment with mycophenolate mofetil (MMF), instead of cyclosporine, the thrombocytopenia improved, facilitating a reduction in the dose of corticosteroid without exacerbation of the interstitial pneumonitis. We propose MMF as effective option in the treatment of immune thrombocytopenic purpura with autoimmune disease.

[Severe aplastic anemia following living-donor liver transplantation for fluminant hepatitis].

We report a case of a 15-year-old girl with severe aplastic anemia who underwent orthotopic liver transplantation 5 years ago for fulminant hepatic failure during the course of immunodeficiency of unknown etiology. She previously exhibited similar immunodeficiency and experienced recurrent viral infections. She developed jaundice at 9 years of age and was diagnosed with fulminant hepatitis. One month later, she underwent living donor liver transplantation, with the donor being her father. Five years after the liver transplant, pancytopenia was noted; she did not respond to treatment with increasing doses of tacrolimus/prednisone and administration of granulocyte-colony stimulating factor. Bone marrow biopsy was performed, and severe aplastic anemia was diagnosed. Six years after the liver transplant, she underwent bone marrow transplantation (BMT), with the donor being her HLA-matched sibling. However, she developed liver dysfunction with recovery of white blood cells. She developed sepsis, which eventually led to her death on day 30 after BMT.

Purulent lymphadenitis due to Halomonas hamiltonii: a case report.

Halomonas hamiltonii is a gram-negative rod bacterium isolated from highly saline environments. H. hamiltonii has rarely been reported as a human pathogen. Herein, we present the first case report of a purulent lymphadenitis caused by H. hamiltonii worldwide. The patient was a previously healthy girl aged 1 year who was referred to our hospital for left axillary lymphadenitis. Although oral amoxicillin was administered, lymphadenitis did not improve, and an abscess developed. After incision and drainage, the abscess was reduced. No recurrence of lymphadenitis was observed. The pus culture was negative. However, the 16S ribosomal DNA was amplified by the melting temperature mapping method. The amplified 16S ribosomal DNA sequence revealed 99.7% identity of H. hamiltonii. To the best of our knowledge, this is the first case of H. hamiltonii infection in a lymph node. This pathogen should be considered when diagnosing purulent lymphadenitis in healthy patients with lymphadenopathy of unknown origin.

Genetic analysis of contiguous X-chromosome deletion syndrome encompassing the BTK and TIMM8A genes.

Patients with X-linked agammaglobulinemia (XLA) can present with sensorineural deafness. This can result from a gross deletion that not only involved the Bruton's tyrosine kinase (BTK) gene, but also TIMM8A, mutations in which underlie the Mohr-Tranebjærg syndrome (MTS). We analyzed the genomic break points observed in three XLA-MTS patients and compared these with deletions break points from XLA patients. Patient 1 had a 63-kb deletion with break points in intron 15 of BTK and 4 kb upstream of TAF7L. Patients 2 and 3 had 149.7 and 196 kb deletions comprising BTK, TIMM8A, TAF7L and DRP2. The break points in patients 1 and 3 were located in Alu and endogenous retrovirus (ERV) repeats, whereas the break points in patient 2 did not show involvement of transposable elements. Comparison of gross deletion sizes and involvement of transposable elements in XLA and XLA-MTS patients from the literature showed preferential involvement of Alu elements in smaller deletions (<10 kb). These results show further insights into the molecular mechanisms underlying gross deletions in patients with primary immunodeficiency.

Rituximab and cyclosporine therapy for accelerated phase Chediak-Higashi syndrome.

A 19-month-old male with Chediak-Higashi syndrome developed Epstein-Barr virus (EBV)-associated accelerated phase. Real-time polymerase chain reaction showed high EBV-DNA levels in plasma and peripheral blood mononuclear cells. His condition was refractory to conventional treatments for hemophagocytic lymphohistiocytosis, including corticosteroids, cyclosporine, and etoposide. In situ hybridization revealed higher proportion of EBER-1-positive cells in CD19+ cell fraction than in CD8+ cell fraction. Complete remission was achieved by combination therapy with rituximab and cyclosporine; subsequent bone marrow transplantation was successful. Combination therapy with rituximab and cyclosporine could be effective in patients with EBV-infected T and B cells.

Identification of severe combined immunodeficiency by T-cell receptor excision circles quantification using neonatal guthrie cards.

OBJECTIVE: To assess the feasibility of T-cell receptor excision circles (TRECs) quantification for neonatal mass screening of severe combined immunodeficiency (SCID). STUDY DESIGN: Real-time PCR based quantification of TRECs for 471 healthy control patients and 18 patients with SCID with various genetic abnormalities (IL2RG, JAK3, ADA, LIG4, RAG1) were performed, including patients with maternal T-cell engraftment (n = 4) and leaky T cells (n = 3). RESULTS: TRECs were detectable in all normal neonatal Guthrie cards (n = 326) at the levels of 10(4) to 10(5) copies/microg DNA. In contrast, TRECs were extremely low in all neonatal Guthrie cards (n = 15) and peripheral blood (n = 14) from patients with SCID, including those with maternal T-cell engraftment or leaky T cells with hypomorphic RAG1 mutations or LIG4 deficiency. There were no false-positive or negative results in this study. CONCLUSION: TRECs quantification can be used as a neonatal mass screening for patients with SCID.

[A case report of acute Q fever showing Kawasaki disease-like symptoms in a 9-year-old girl].

A 9-year-old girl developing fever and hyperemia of both bulbar conjunctiva 5 days before admission to the Saitama Children's Medical Center after antibiotics proved ineffective was found on admission to have general fatigue and a temperature of 39 degrees C. Physical examination showed hyperemia of the bulbar conjunctiva, fissures of the lips, redness of the pharynx, and swelling of the cervical lymph nodes. Laboratory tests detected neutrophilia (11,200/microL), mild anemia (11.4g/dL), thrombocytopenia (110,000/microL), and elevated serum aspartate aminotransferase (242IU/L), alanine aminotransferase (328IU/L), and C-rective protein (25.2 mg/dL). Autoantibodies such as anti-nuclear, anti-SS-A/Ro, and anti-Jo-1 were also found. Echocardiography showed no abnormality of the coronary arteries. She was diagnosed as having incomplete Kawasaki disease on day 7 of illness, necessitating that a high dose of immunoglobulin be given intravenously. Her temperature dropped temporarily to 37 degrees C, but she developed erythema of the cheek and fever. Intravenous immunoglobulin was restarted, and minocycline introduced because her daily contact with a pet cat indicated richettsial infection such as Q fever. Mild fever, muscle pain, and elevated C-reactive protein did not improve, but clinical signs and symptoms gradually lessened after ibuprofen was given, then disappeared. A definitive diagnosis of Q fever was made through an over 4-fold rise in phase II IgG antibody titers against Coxiella burnetii, titer of less than 1 : 16 on day 14 of illness, and titer of 1 : 256 on day 34. This case study describes on atypical case of Q fever with clinical manifestations mimicking Kawasaki disease.

Risk Factors for Thyroid Cancer in Systemic Lupus Erythematosus.

We studied 3 patients with systemic lupus erythematosus (SLE) who developed thyroid cancer (TC). Potential risk factors for TC development was explored. Fifty-three patients with a clinical diagnosis of rheumatic diseases including SLE at our hospital between July 2014 and December 2014 were enrolled. Demographic, clinical, and laboratory findings were retrospectively compared between TC-positive and TC-negative patients. Among rheumatic diseases, lymphadenopathy/splenomegaly at treatment commencement, and lymphadenopathy/splenomegaly, painless ulcer (oral, nasal, or mucosal), and weight loss during the entire study period were precipitating factors. Lower current values of hemoglobin and methylprednisolone pulse therapy favored TC development. In 29 SLE patients, lymphadenopathy/splenomegaly at treatment commencement, lymphadenopathy/splenomegaly and weight loss during the entire study period, urinary granular casts at treatment commencement, and a lower current value of hemoglobin predisposed patients to TC. Several risk factors of TC are present in pediatric SLE. Patients with SLE should be investigated vigorously for TC with ultrasound.

Screening for seemingly healthy newborns with congenital cytomegalovirus infection by quantitative real-time polymerase chain reaction using newborn urine: an observational study.

OBJECTIVE: Approximately 8-10% of newborns with asymptomatic congenital cytomegalovirus (cCMV) infection develop sensorineural hearing loss (SNHL). However, the relationship between CMV load, SNHL and central nervous system (CNS) damage in cCMV infection remains unclear. This study aimed to examine the relationship between urinary CMV load, SNHL and CNS damage in newborns with cCMV infection. STUDY DESIGN: The study included 23 368 newborns from two maternity hospitals in Saitama Prefecture, Japan. Urine screening for cCMV infection (quantitative real-time PCR) and newborn hearing screening (automated auditory brainstem response (AABR) testing) were conducted within 5 days of birth to examine the incidence of cCMV infection and SNHL, respectively. CNS damage was assessed by MRI of cCMV-infected newborns. RESULTS: The incidence of cCMV infection was 60/23 368 (0.257%; 95% CI 0.192% to 0.322%). The geometric mean urinary CMV DNA copy number in newborns with cCMV was 1.79×106 copies/mL (95% CI 7.97×105 to 4.02×106). AABR testing revealed abnormalities in 171 of the 22 229 (0.769%) newborns whose parents approved hearing screening. Of these 171 newborns, 22 had SNHL (12.9%), and 5 of these 22 were infected with cCMV (22.7%). Newborns with both cCMV and SNHL had a higher urinary CMV DNA copy number than newborns with cCMV without SNHL (p=0.036). MRI revealed CNS damage, including white matter abnormalities, in 83.0% of newborns with cCMV. Moreover, newborns with CNS damage had a significantly greater urinary CMV load than newborns without CNS damage (p=0.013). CONCLUSIONS: We determined the incidence of cCMV infection and urinary CMV DNA copy number in seemingly healthy newborns from two hospitals in Saitama Prefecture. SNHL and CNS damage were associated with urinary CMV DNA copy number. Quantification of urinary CMV load may effectively predict the incidence of late-onset SNHL and neurodevelopmental disorders.

[Thalidomide therapy for infantile-onset Crohn's disease].

A 6-month-old boy was diagnosed as having Crohn's disease (CD) by the endoscopic examination. Primary immunodeficiency syndrome was initially suspected due to a refractory infection that occurred just after birth and a family history that his older brother died at the age of 3 months of septicemia associated with perirectal abscess. Thalidomide was used because conventional medical treatment by steroids and immunosuppressives was ineffective. Thalidomide improved the symptoms of diarrhea, abdominal pain, high fever and fistula, and the PCDAI score decreased markedly from 45 to 15. Although thalidomide was discontinued after three months because of the onset of side effects, including edema, rash and the peripheral neuropathy, the effect on the fistula closure was maintained over a long period of time. Further studies will be necessary to determine the dosage of thalidomide that does not elicit side effects, but thalidomide seems to be effective in patients with refractory CD. Infantile CD is very rare and the diagnosis is often delayed. CD is generally resistant to medical treatment. More detailed information of infantile CD will be needed to elucidate the pathogenesis of this disease and progress of treatment. Recently the incidence of inflammatory bowel diseases has increased. CD should be suspected in any infant with the perianal lesion (fissures, fistula, skin tag and abscesses) especially when prolonged gastrointestinal symptoms, stomatitis or fever coexist.

[A case of Williams syndrome with p47-phox-deficient chronic granulomatous disease].

A 2-month-old boy with a characteristic elfin face was diagnosed as having Williams syndrome by means of specific fluorescence in situ hybridization (FISH) analysis for a chromosomal microdeletion located in 7q11.23. He was suspected to have immunodeficiency because of a persistent enlargement of axillary lymphnodes after immunization with Bacille Calmette-Guerin (BCG) vaccine since 7 month-old of age. The nitroblue tetrazolium test (NBT) and the chemiluminescence test revealed an absence of superoxide production. Western blotting and DNA sequence analysis confirmed the diagnosis of p47-phox-deficient autosomal recessive chronic granulomatous disease (CGD) (A47 degrees CGD). The predominant genetic defect in A47 degrees CGD was a GT deletion at the beginning of exon 2 in neutrophil cytosol factor 1 gene (NCF1) located in 7q11.23. It suggests that CGD in this patient resulted from the hemizygosity of recessive genetic mutation in NCF1 located at 7q11.23 associated with Williams syndrome. In such a disease with the chromosomal microdeletion like Williams syndrome, we should consider a combination with autosomal recessive diseases, the genes of which are located in the hemizygous region.

Copy number variations due to large genomic deletion in X-linked chronic granulomatous disease.

Mutations in genes for any of the six subunits of NADPH oxidase cause chronic granulomatous disease (CGD), but almost 2/3 of CGD cases are caused by mutations in the X-linked CYBB gene, also known as NAD (P) H oxidase 2. Approximately 260 patients with CGD have been reported in Japan, of whom 92 were shown to have mutations of the CYBB gene and 16 to have chromosomal deletions. However, there has been very little detailed analysis of the range of the deletion or close understanding of the disease based on this. We therefore analyzed genomic rearrangements in X-linked CGD using array comparative genomic hybridization analysis, revealing the extent and the types of the deletion genes. The subjects were five Japanese X-linked CGD patients estimated to have large base deletions of 1 kb or more in the CYBB gene (four male patients, one female patient) and the mothers of four of those patients. The five Japanese patients were found to range from a patient exhibiting deletions only of the CYBB gene to a female patient exhibiting an extensive DNA deletion and the DMD and CGD phenotype manifested. Of the other three patients, two exhibited CYBB, XK, and DYNLT3 gene deletions. The remaining patient exhibited both a deletion encompassing DNA subsequent to the CYBB region following intron 2 and the DYNLT3 gene and a complex copy number variation involving the insertion of an inverted duplication of a region from the centromere side of DYNLT3 into the deleted region.

Immunogenicity of influenza vaccine in children with pediatric rheumatic diseases receiving immunosuppressive agents.

BACKGROUND: Children with rheumatic diseases receiving immunosuppressive therapy are a high-risk group for influenza virus infection; however, few data are available regarding the efficacy and safety of influenza vaccine for those individuals. METHODS: This was a prospective study evaluating the immunogenicity and safety of influenza vaccine in 49 children (mean ± standard deviation: 12.1 ± 4.8 years, age range: 0-21 years) with pediatric rheumatic diseases including juvenile idiopathic arthritis (n = 23), systemic lupus erythematosus (n = 12), juvenile dermatomyositis (n = 6), and others (n = 8), who were receiving immunosuppressive therapies. A total of 36 healthy children were selected as a control. The influenza virus type-A and B antibody titers were measured using hemagglutinin inhibition before and after the vaccination. RESULTS: There were no significant differences in the percentage of vaccine recipients with an increase in the serum titers ≥ 4× after vaccination (H1N1, H3N2, and B strain) between the 2 groups (P = 0.49, P = 0.25, P = 0.56, respectively), demonstrating similar immunogenicity of the influenza vaccination between patients and control groups. There were no serious adverse effects related to the vaccine in either group. CONCLUSIONS: In the children with pediatric rheumatic diseases receiving immunosuppressive agents, influenza vaccination resulted in serum antibody titers similar to those in the controls without major adverse effects. Such children receiving immunosuppressive therapy are a high-risk group for influenza virus infection, therefore vaccine should be given.