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 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.

Extensively hydrolyzed formula (MA-mi) induced exacerbation of food protein-induced enterocolitis syndrome (FPIES) in a male infant.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a severe, cell-mediated food allergy in which digestive symptoms such as severe vomiting and diarrhea are induced by cow's milk and/or soy protein in infants. Generally, a food-specific IgE is not detected, and FPIES may be caused by inadvertent exposure to allergenic foods. CASE SUMMARY: The patient in our case was a male infant in whom vomiting had been induced by ingestion of a cow's milk-based formula and bloody diarrhea had been caused by ingestion of breast milk during the neonatal period. Accidental ingestion of a new and extensively hydrolyzed casein/whey formula, MA-mi, caused watery diarrhea at 8 months of age, and FPIES was diagnosed based on these symptoms. In antigen-specific lymphocyte stimulation tests, New MA-1 was negative, but MA-mi and cow's milk antigens were positive. The only causative antigens were derived from cow's milk, and the symptoms were not induced by another extensively hydrolyzed casein formula, New MA-1. The patient grew and developed normally thereafter, and no symptoms were induced by solid food during the course of the condition. DISCUSSION: MA-mi is likely to be used increasingly for allergic infants, but it is not necessarily a substitute for other hydrolyzed milk formulae in all cases, and care should be taken regarding its use and possible misuse.

Juvenile dermatomyositis: clinical characteristics and the relatively high risk of interstitial lung disease.

To clarify the clinical features of juvenile dermatomyositis (JDM) in Japanese cases, we retrospectively evaluated the characteristics of 16 children with JDM that were treated at Saitama Children's Medical Center between 1985 and 2004. The age at disease onset ranged from 3.5 to 14.1 years old (7 boys, mean age 7.9 years; 9 girls, mean age 9.2 years). In 14 patients more than two muscle enzymes were elevated at diagnosis. The antinuclear antibody at diagnosis was positive in all girls but one, while it was positive in only two boys (2/7; P<0.01). Three patients were complicated with interstitial lung disease (ILD) (18.8%) and their serum KL-6 levels were already elevated on admission. Our findings suggest that serum KL-6 levels seemed to be sensitive to the detection of ILD in an early phase, and the relatively high frequency of JDM-associated ILD indicated that a careful evaluation of the lungs was therefore required in any individuals with JDM. Of 16 patients, two boys showed a favorable improvement and prognosis without relapse for over 9 years after the termination of treatment. Overall, in girls, there is a tendency to be a delay in the diagnosis/treatment for JDM, and this disease also demonstrated a severe course.

New sequence polymorphisms in the outer loops of the JC polyomavirus major capsid protein (VP1) possibly associated with progressive multifocal leukoencephalopathy.

JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML) in patients with decreased immune competence. To elucidate genetic changes in JCPyV associated with the pathogenesis of PML, multiple complete JCPyV DNA clones originating from the brains of three PML cases were established and sequenced. Although unique rearranged control regions occurred in all clones, a low level of nucleotide variation was also found in the coding region. In each case, a parental coding sequence was identified, from which variant coding sequences with nucleotide substitutions would have been generated. A comparison between the parental and variant coding sequences demonstrated that all 12 detected nucleotide substitutions gave rise to amino acid changes. Interestingly, seven of these changes were located in the surface loops of the major capsid protein (VP1). Finally, 16 reported VP1 sequences of PML-type JCPyV (i.e. derived from the brain or cerebrospinal fluid of PML patients) were compared with their genotypic prototypes, generated as consensus sequences of representative archetypal isolates belonging to the same genotypes; 13 VP1 proteins had amino acid changes in the surface loops. In contrast, VP1 proteins from isolates from the urine of immunocompetent and immunosuppressed patients rarely underwent mutations in the VP1 loops. The present findings suggest that PML-type JCPyV frequently undergoes amino acid substitutions in the VP1 loops. These polymorphisms should serve as a new marker for the identification of JCPyV isolates associated with PML. The biological significance of these mutations, however, remains unclear.