Sheng-Chieh Lin

Hyper-IgM1 syndrome with interstitial pneumonia and diarrhea caused by coxsackievirus B4 in a 3-month-old infant.

BACKGROUND Hyper-IgM1 syndrome is a rare genetic primary immunodeficiency disease caused by mutations of the CD40 ligand gene. It is characterized by normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE levels. Patients with this syndrome often easily develop infections. During the past decade, it has become clear that enteroviral infections may also occur as a manifestation of hyper-IgM1 syndrome. OBJECTIVE To report a case of hyper-IgM1 syndrome in a 3-month-old boy who had interstitial pneumonia and intractable diarrhea. METHODS Chest radiography, bronchoscopy, immune studies, and open lung biopsy were performed. RESULTS Chest radiography revealed diffuse bilateral infiltrates. Immune studies revealed the following proportions of lymphocyte markers: CD3, 5,976/microL; CD4, 5,015/microL; CD8, 866/microL; CD19, 1,325/microL; CD16 + 56, 935/microL; and active T cells, 225/microL. The IgG level was 190 mg/dL; IgA, 2 mg/dL; IgM, 34 mg/dL; IgE, 1 IU/dL; and CH50, 23.8/mL. CD40L expression was less than 1%, and a Tyr 169 Asn (t526a) mutation in the exon 5 tumor necrosis factor domain of the CD40L gene was found. The patient was treated with intravenous immunoglobulin and had a dramatic improvement in symptoms. Open lung biopsy failed to demonstrate pneumocystis, and there was no evidence of cryptosporidium in the stool. However, coxsackievirus B4 was isolated by viral throat culture. CONCLUSION Interstitial pneumonia and diarrhea caused by coxsackievirus B4 may be a complication of hyper-IgM1 syndrome.

Recurrent acalculous cholecystitis and sclerosing cholangitis in a patient with X-linked hyper-immunoglobulin M syndrome

X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare genetic primary immunodeficiency disease caused by mutations of the CD40 ligand (CD40L) gene with normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE. Liver disease may occur as a clinical manifestation in XHIGM. This complication appears to increase with age. We report an 18-year-old male patient who had recurrent episodes of acalculous cholecystitis (AC) and sclerosing cholangitis (SC). The diagnosis of XHIGM was confirmed by the finding of CD40L expression < 1% of normal and a tyrosine 169 asparaginase (t526a) mutation in exon 5 (the tumor necrosis factor domain) of the CD40L gene. The patient had direct hyperbilirubinemia (direct bilirubin 5.5 mg/dL, total bilirubin 8.7 mg/dL), cholestasis (alkaline phosphatase 1133 U/L, gamma-glutamyl transferase 1019 U/L) and elevated transaminases (aspartate aminotransferase 70 U/L, alanine aminotransferase 101 U/L). Findings on abdominal ultrasound and abdominal computed tomography were compatible with AC. After the fourth episode of cholecystitis, cholecystectomy and liver biopsy were performed. Operative cholangiography revealed poor opacification of the hepatic duct and proximal common bile duct; the upstream intrahepatic bile ducts were not visualized. The biopsy specimen showed marked fibrosis of the portal areas. Enterococcus species was cultured from the bile. Children or adolescents with recurrent AC and SC should be evaluated for an underlying immunodeficiency syndrome such as XHIGM.

Prednisolone oral solution plus inhaled procaterol for acute asthma in children: a double-blind randomized controlled trial.

BACKGROUND To evaluate the efficacy of prednisolone sodium phosphate oral solution plus inhaled procaterol in the treatment of acute asthma in children. METHODS Forty-three patients aged 6 to 12 years with an acute exacerbation of asthma were double-blind randomized into one of two treatment groups in a 1:1 ratio:1) prednisolone oral solution +placebo tablets + procaterol MDI or 2) prednisolone tablets +placebo oral solution + procaterol MDI, all given three times daily for 7 days. Peak expiratory flow rate (PEFR), 24-hour reflective asthma symptom scores, spirometry and pulmonary index score (PIS) were recorded before and after treatment. Net changes in PEFR, symptom score, PIS, Forced Expiratory Volume in the first second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow between 25 and 75 percent of the forced vital capacity (FEF(25-75%)) (before and after treatment) and global assessment by the investigator and the subjects or their parents were analyzed. RESULTS The two groups were statistically similar at baseline values of these parameters. After a 7-day course of treatment, the net change of PEFR before and after treatment was significantly improved in both groups, but there was no significant difference in the net change of PEFR between the two groups (57.27+/-31.44 L/min vs. 54.29 +/-30.04 L/min, difference 2.99 +/-30.76 L/min, mean +/-SD, P=0.752). The net change in PIS and total symptom score did not differ between the two groups (P=0.091 and 0.827, respectively). Similarly, the FEV1, FEV1/FVC and FEF25-75% all improved with either treatment, and neither group was significantly superior to the other group (P=0.162, 0.48 and 0.081, respectively). Global assessment by the investigator and the subjects or their parents at the end of study indicated an essentially comparable result. CONCLUSIONS Prednisolone sodium phosphate oral solution plus inhaled procaterol is as efficacious as prednisolone tablets plus inhaled procaterol in the management of acute asthma in children.

Hyper-IgM syndrome: report of one case.

The hyper-IgM syndrome (HIM) is a rare primary immunodeficiency disorder caused by defects in the CD40 ligand (CD40L)/CD40-signaling pathway. It is characterized by recurrent infections with markedly decreased IgG, IgA and IgE levels but normal or elevated serum IgM levels. A 5-month-old boy presented with rapidly progressive pneumonia which responded poorly to antibiotics. High levels of IgM and very low levels of IgG, IgE and IgA were noted in his plasma specimen (IgM, 128 mg/dl; IgG, 18 mg/dl; IgE, 1 IU/ml; IgA, 4 mg/dl). The relative proportions of immune cells were CD3 24.6%, CD4 10.3%, CD8 2.2%, CD19 30.2%, CD57 1.0% and active T cells 1.1%. After IVIG treatment, the pneumonia improved. Repeat assessment at the age of 15 months showed IgM decreased to the normal range (32 mg/dl). Whole blood flow cytometry assay for CD40L expression confirmed the diagnosis of hyper-lgM syndrome when he was 21 months old. Only a small percentage (0.48%) of the patients in vitro activated CD4+ T cells expressed CD40L, compared with 33.54% from a healthy control. The patients father, mother and sister all had a normal CD40L expression activation patterns (43.52%, 40.78%, 34.11%, respectively). On a regimen of monthly IVIG infusion and oral trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) prophylaxis, the patient has had no recurrent infections.

Facial telangiectasia - An unusual complication of neonatal lupus erythematosus: Report of one case

Neonatal lupus erythematosus (NLE) is an uncommon passive autoimmune disease caused by transplacental passage of anti-Ro/SSA and/or anti-La/SSB or anti-U1RNP maternal autoantibodies. Common clinical manifestations include cutaneous lupus lesions, cardiac disease, notably congenital heart block, hematologic abnormalities, and hepatobiliary disease. The cutaneous lesions of NLE are usually transient, disappearing about six months after birth when maternal antibodies disappear from the infants circulation. Persistent telangiectasia is a rare complication of NLE. We report a 3-year-old female who had cutaneous lupus with persistent facial telangiectasias over the frontal area. She was diagnosed with NLE at 2 months of age. Her findings then included cutaneous lupus, hemolytic anemia, a high titer of antinuclear antibodies (1: 640) with a speckled pattern, positive anti-Ro/SSA and anti-La/SSB antibodies, and absence of anti-dsDNA antibodies. Her mother had systemic lupus erythematosus with the presence of high titer of antinuclear antibodies (1: 1260) with a speckled pattern and positive anti-Ro/SSA and anti-La/SSB antibodies. The childs cutaneous lupus and hemolytic anemia disappeared at 6 months of age, but the telangiectasia persisted.

Clinical Spectrum and Laboratory Characteristics of Neonatal Lupus Erythematosus in a Single Institute

Background: Neonatal lupus erythematosus (NLE) is a passive autoimmune disease in which maternal autoantibodies are transferred across the placenta. These anti-Ro/SSA and/or anti-La/SSB or anti-U1RNP antibodies can be detected in the affected infant for the first few months of life. Common clinical manifestations of NLE include cardiac disease, notably congenital heart block and cutaneous lupus lesions. The other features of NLE including hematologic abnormalities, hepatobiliary disease, and, rarely, CNS involvement are usually underestimated. We reviewed our experience with NLE and examined the relationship between the serology of the mothers and disease in their infants. Methods: We reviewed the records in 12 cases of NLE seen at Mackay Memorial Hospital from 1984 through 2003. Results: The female to male ratio was 1.4:1. Five of the 12 patients had congenital heart block, and 7 had cutaneous lesions. Other noncutaneous manifestations included thrombocytopenia in 2, anemia in 2, and elevated aminotransferases in 3, 1 of whom also had cholestasis without evidence of other metabolic, infectious or inherited causes. One infant had a right-sided focal seizure. Anti-SSA/Ro antibodies were detected in all 12 patients, a positive ANA in 10, and anti-SSB/La antibodies in 5. The last were among the 7 who had cutaneous NLE. Anti-SSB/La antibodies were not present in any of the infants with congenital heart block. Conclusions: In pregnant women with these antibodies, fetal echocardiographic screening is useful to look for atrioventricular heart block. Asymptomatic infants borne to these mothers should be followed carefully during the first 6 months of life, as babies with NLE may initially be asymptomatic. Pediatricians caring for such children should familiarize themselves with the typical features of the disease so that they can recognize it promptly if it occurs.