Li-Hsin Huang

Systemic anaphylaxis after the ingestion of pancake contaminated with the storage mite Blomia freemani

BACKGROUND Systemic anaphylaxis after the ingestion of mite-contaminated food has rarely been reported. OBJECTIVE To describe an 8-year-old boy in whom systemic anaphylaxis developed shortly after the ingestion of pancakes prepared with commercial pancake flour. METHODS The patient underwent skin prick testing for house dust mites and with uncontaminated and mite-contaminated pancake flour. Specific IgE for mites and the main ingredients of the pancake flour were also evaluated, with titers for Der p 1, Der f 1, and Blo t 5 quantitated using immunochemical methods. A sample of pancake flour was examined microscopically for mites. RESULTS The patient had positive skin prick test results to contaminated pancake flour extract (1 g/5 mL), Dermatophagoides pteronyssinus, and Dermatophagoides farinae but a negative skin test response to uncontaminated pancake flour. The patients serum specific IgE analysis was positive for antibodies to dust and storage mite allergens. There was no response, however, to the main ingredients of the pancake mix. Microscopic examination of the pancake flour revealed the storage mite Blomia freemani. Using an immunochemical assay, we found that the contaminated flour contained 5.4 microg/g of the allergen Blo t 5 but no Der p 1 or Der f 1. CONCLUSIONS This patients anaphylactic episode was the result of ingestion of the storage mite B. freemani. To our knowledge, this is the first reported systemic hypersensitivity reaction caused by this mite anywhere in the world.

De novo mutation in the BTK gene of atypical X-linked agammaglobulinemia in a patient with recurrent pyoderma

BACKGROUND X-linked agammaglobulinemia (XLA), characterized by a profound deficiency of all immunoglobulins and the absence of mature B cells, is caused by mutations in the gene encoding Bruton tyrosine kinase (BTK). Most patients have recurrent sinopulmonary infection. Infections usually occur in multiple locations across time, but single infection may be limited to one anatomic location. OBJECTIVES To report a case of atypical XLA with recurrent pyoderma and to observe the immunologic changes in the patient in 10 years. METHODS Immunologic investigations, skin wound culture, and molecular study with DNA sequencing were performed. RESULTS The patient was originally diagnosed as having common variable immunodeficiency disease because of the presence of circulating B cells (CD19+ B cells: 7%) at 11 years old. On further evaluation at the age of 20 years, flow cytometric analysis of lymphocytes showed only 0.4% B cells. The molecular study with DNA sequencing of the patient showed a point mutation in complementary DNA 1630 A>G(p.R544G) in the BTK gene, indicating that the patient has XLA. The mutation analysis of the BTK gene revealed a normal DNA sequence in the other family members. CONCLUSIONS This case is an important example of a possible presentation of XLA with a predominant skin manifestation, and it demonstrates that maintaining a high level of clinical suspicion is essential for the diagnosis of XLA in a child with recurrent pyoderma.

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.

X-linked hyper-immunoglobulin M syndrome: Molecular genetic study and long-time follow-up of three generations of a Chinese family

Background: X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare immunodeficiency disease caused by mutations of the CD40 ligand gene. Patients are subject to recurrent infections and have normal or elevated levels of IgM but markedly decreased serum IgG. Objective: We describe molecular genetic studies and clinical manifestations in three generations of one family, as well as results of long-term treatment of 2 young men with the disorder. Methods: Of 37 living family members, mutational analysis of the CD40 ligand gene was performed in 36 members. Laboratory data for patients and carriers were reviewed. Results: Four male family members had died of unexplained causes. The 3 patients with XHIGM syndrome and the 5 carriers all had a novel mutation located at Tyr 169 Asn (T526A) in exon 5, the tumor necrosis factor domain of the CD40 ligand gene. In the 3 patients, CD40 ligand expression in activated CD4+ T cells was below 1%. In the carriers, about half of activated CD4+ cells expressed CD40 ligand. One carrier had malignant lymphoma. Long-term (>20 years) intravenous immunoglobulin therapy in 2 patients improved IgG levels but did not fully suppress the high levels of IgM, nor did it prevent late complications (bronchiectasis and sclerosing cholangitis). Conclusions: Diagnosis of a genetic immunodeficiency, especially an X-linked disease such as XHIGM syndrome, should prompt a survey of the entire family.

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.

Paternal mosaicism and hereditary angioedema in a Taiwanese family

BACKGROUND Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of localized subcutaneous or submucosal edema. It is inherited in an autosomal dominant fashion and caused by a deficiency of C1 inhibitor (C1 INH). Most patients with HAE have an absolute deficiency of C1 INH (type I HAE), whereas the rest (approximately 15%) synthesize a dysfunctional C1 INH protein (type II HAE). Mosaicism is rare in HAE. OBJECTIVE To describe the clinical manifestations, laboratory findings, and molecular genetic studies in a Taiwanese family with type I HAE with paternal mosaicism. METHODS A family that included a 34-year-old man (index patient) and his 25-year-old brother who both had recurrent peripheral angioedema was evaluated. A younger sister had died of an unexplained cause at 18 years of age. We analyzed blood levels of C3, C4, and C1 INH and sequenced the SERPING] (C1NH) gene that codes for C1 INH in 5 family members, including the parents and 3 brothers. RESULTS The 4 men in the family had a novel mutation c.3_73del, p.N1fsX34 in exon 3 of the C1INH gene, resulting in C1 INH deficiency. Although the father carried this mutant gene, he had normal serum levels of C1 INH. Based on quantitative analysis of allele dosage by DNA fragment analysis (GeneScan), the father was determined to have genetic mosaicism. CONCLUSION Parental mosaicism is a possible explanation for normal C1 INH plasma concentrations in both parents despite clinically apparent HAE in the children.

Chlamydia Trachomatis Pneumonia: Experience in a Medical Center

Chlamydia trachomatis is one of the important causes of afebrile pneumonia in infants. The purpose of this study was to evaluate the demographic features, clinical manifestations, and outcome of C. trachomatis pneumonia patients seen during the past 10 years in one medical center. We reviewed the records on 30 patients with a diagnosis of C. trachomatis pneumonia. The diagnosis was based on characteristic clinical features and confirmed by culture, serologic testing, or polymerase chain reaction (PCR). Clinical features including age, sex, symptoms at the time of admission, laboratory data, and treatment were analyzed. Of the 30 patients (17 males and 13 females), 29 (96%) were less than 4 months old (range 10 days to 5 months). All patients had productive cough followed by tachypnea. Three patients (10%) presented with apnea. Four (13%) had conjunctivitis. Fever was present in only 3 (10%), of whom 2 also had concurrent respiratory syncytial virus infection. Peripheral eosinophilia (eosinophils > or = 400/mm3) was present in 14 (47%) patients. Hyperinflation was seen on chest x-ray in 15 patients. All infants were treated with erythromycin and responded well. The mean time to clinical improvement was 3.53 days after the start of treatment. The mean duration of hospitalization was 8.97 days (range, 3 to 17 days). No patients died. Pediatricians and general practitioners must have a high index of suspicion for chlamydial infection in afebrile infants presenting with tachypnea, peripheral eosinophilia, and hyperinflation on chest x- ray during the first four months of life.

Pachydermodactyly: Three new cases in Taiwan

Pachydermodactyly (PDD), Greek for thick-skin-finger, is an infrequently recognized benign disorder characterized by painless fusiform swelling of the soft tissues around the proximal interphalangeal joints of the hands. Histopathologic features include increased dermal accumulation of collagen fibers. Young males are predominantly affected. PDD is quite rare with approximately 90 cumulative cases reported worldwide. We report three new cases of PDD in Taiwan, including two female patients. Except for patient 1 having the habit of cracking the knuckles, and patient 2 having a history of patent ductus ateriosus post catheterization, the histories of all three patients were unremarkable. X-ray of bilateral hands revealed no abnormal finding except for soft tissue swelling around proximal interphalangeal joints. Laboratory examinations all showed negative results. No local or systemic treatment was given to these patients to treat PDD, with the exception of non-steroidal anti-inflammatory drugs prescribed to one patient for a short period. Skin care with local irritation avoidance was explained to all three patients. The long-term outcome of PDD was benign.

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.