Safety and efficacy of Pimecrolimus in atopic dermatitis among Chinese infants: a sub-group analysis of a five-year open-label study.

INTRODUCTION: Atopic dermatitis (AD) exhibits difference in immune polarization between Caucasians and Asian races due to which an evaluation of the efficacy and safety of Pimecrolimus (PIM) in Asian population is called for. The current study addresses the need via a sub-group analysis of the PETITE study (NCT00120523) to evaluate the safety and efficacy of PIM in Chinese infants. MATERIALS AND METHODS: Patients with AD (≥3 months-<12 months of age) were randomized in a 1:1 ratio to either PIM 1% cream or topical corticosteroids (TCS). The primary endpoint was safety. The secondary endpoint was efficacy. RESULTS: 120 patients were randomized to either PIM 1% or TCS (n = 61 for PIM, n = 59 for TCS). The most often reported adverse events were reported by similar proportions of patients treated with PIM or TCS. There was a progressive increase in overall IGA treatment success in infants treated with PIM (82.9%, p < .05, 95% CI: 70.4, 95.3) after 26 weeks which was comparable to the TCS group (88.5%, p < .05, 95% CI: 79.8, 97.1). CONCLUSION: PIM showed an early and sustained efficacy in the Chinese sub-population with a substantial corticosteroid-sparing effect in patients with AD.

HLA-A*02 alleles are associated with tetanus antitoxin-induced exanthematous drug eruptions in Chinese patients.

OBJECTIVE: Tetanus antitoxin (TAT) is an effective antitetanus medicine, but may sometimes cause adverse drug reactions such as rapid-onset anaphylactic shock and late-onset cutaneous adverse drug reactions, including exanthematous drug eruptions (EDE). Human leukocyte antigen (HLA) class I alleles are strongly associated with different types of cutaneous adverse drug reactions. This study aimed to assess whether there is an association between TAT-induced EDE and HLA-A, HLA-B, and HLA-C alleles in the Chinese Han population. PATIENTS AND METHODS: We carried out an association study in 15 patients with TAT-induced EDE and two groups of general Han Chinese patients. Allele-level genotypes of the HLA-A, HLA-B, and HLA-C genes of each patient were determined using the PCR-sequence-specific oligonucleotides method. RESULTS: The carrier frequency of HLA serotype A2 was significantly higher in the TAT-induced EDE patients than in the general Han Chinese study participants from the human major histocompatibility complex database [n=283, odds ratio (OR)=6.93; P=0.0061]. Particularly, the carrier frequency of three A2 alleles, including HLA-A*02:01, HLA-A*02:06, and HLA-A*02:07, is significantly higher than that of the control group (OR=14.40; P=2.4×10). Furthermore, HLA-B*39:01 was in complete linkage disequilibrium with HLA-A*02:06 in the case patients. Consequently, the distribution of the HLA-A*02:06/-B*39:01 haplotype was also significantly different in the cases and the controls (OR=105.00; P=0.0024). CONCLUSION: The HLA-A*02:06/-B*39:01 haplotype is a potential genetic marker for the TAT-induced EDE. Furthermore, the HLA-A2 serotype, especially three alleles A*02:01, A*02:06, and A*02:07, was identified to be associated with the TAT-induced EDE in the Han Chinese population for the first time.

New insights into CD4(+) T cell abnormalities in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that is characterized by vasculopathy and excessive deposition of extracellular matrix, which causes fibrosis of the skin and internal organs and eventually leads to multiorgan dysfunction. Studies have shown that CD4(+) T cell activation is a key factor in the pathogenesis of scleroderma because activated T cells can release various cytokines, resulting in inflammation, microvascular damage and fibrosis. T helper cell 17 (Th17) and regulatory T (Treg) cell activities are a hallmark SSc, as Th17-type cytokines can induce both inflammation and fibrosis. More recently, several studies have reported new T cell subsets, including Th9 and Th22 cells, along with their respective cytokines in the peripheral blood, serum and skin lesions of individuals with SSc. Herein, we review recent data on various CD4(+) T helper cell subsets in SSc, and discuss potential roles of these cells in promoting inflammation and fibrosis.

Research on Susceptible Genes and Immunological Pathogenesis of Cutaneous Adverse Drug Reactions in Chinese Hans.

Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthems (MPE), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). We used HLA high-resolution genotyping and genome wide association analysis (GWAS) to identify the genetic markers for cADRs induced by common culprit drugs in Han Chinese population. To further understand the immunopathogenesis of cADRs, and with the goal of developing treatment strategies, we compared the expression of cytoxic cytokines between the patients with cADRs and normal controls. Our data suggested that the carbamazepine induced SJS/TEN, allopurinol induced CADRs, methazolamide induced SJS/TEN and SASP induced DRESS were respectively strongly associated with HLA-B*15:02, HLA-B*58:01, HLA-B*59:01 and HLA-B*13:01. In addition, increased expression of cytotoxic cytokines in sera and tissues of cADRs patients were found, compared with healthy controls. Our findings may shed light on prediction and prevention of cADRs, provide clues to pathogenesis, and guide treatment strategies of these reactions.

[Clinicopathologic study of subependymal giant cell astrocytoma].

OBJECTIVE: To study the clinicopathologic features of subependymal giant cell astrocytoma. METHODS: The clinical and pathologic characteristics of 18 cases of subependymal giant cell astrocytoma were retrospectively analyzed. RESULTS: Amongst the 18 cases studied, there was a male predominance (male-to-female ratio = 2:1). The age of patients ranged from 7 to 54 years (mean age = 18.2 years). The tumor often occurred in the lateral ventricles (16/18, 88.9%). Most patients presented with headache and vomiting (11/18, 61.1%), followed by visual disturbance (3/18, 16.7%). Eleven patients (61.1%) had clinical features of tuberous sclerosis, usually in the form of facial angiofibroma (8/18, 44.4%). Computerized tomography was performed in 10 cases, in which 7 cases were of high density and 5 cases showed contrast enhancement. MRI revealed isointense mass lesion on T1WI (7/11, 63.6%), highly intense lesion on T2WI (10/11, 90.9%) and contrast enhancement in some cases (9/11, 81.8%). Four patients had follow-up information available and all of them were alive from 1 to 5 years (mean = 3.5 years). Histologically, there were bundles of spindle cells mixed with clusters of gemistocytes and ganglion-like cells. The spindle cells showed immunoreactivity for glial fibrillary acidic protein (18/18, 100%), while the gemistocytes and ganglion-like cells expressed synaptophysin (14/18, 77.8%). Most of the cases (16/18, 88.9%) had MIB-1 index

Cutaneous lesions and visceral involvement of tuberous sclerosis.

BACKGROUND: Tuberous sclerosis (TS) is an autosomal dominant disorder with a significant range of clinical expressions. The involvement of vital organs, such as the brain, kidney, heart and lung is the main cause of death in patients with TS. The aim of this study is to summarize the characteristic cutaneous features and common extracutaneous involvement of TS, which are helpful to the early detection of visceral involvement. METHODS: The analyzed clinical data from 78 patients with TS included those from detailed history, physical and dermatological examination, cranial computed tomography (CT) and magnetic resonance imaging (MRI), abdominal ultrasonography, chest roentgenography, hand and foot X-ray and ophthalmologic examination. RESULTS: The skin, brain and kidney were involved frequently in TS patients. Hypomelanotic macules were the most common and earliest cutaneous lesions. Their number was more than 3 in 81.5% of the patients. They were followed by facial angiofibromas and Shangreen's patch in a decreasing frequency. Forehead plaque, facial angiofibromas and Shagreen's patch appeared in patients at mean age of 2.6, 6.0 and 8.1 years respectively. Cranial CT showed a high positive rate in TS patients. CONCLUSIONS: Cutaneous features of TS are helpful in the early diagnosis of the disease. Hypomelanotic macules are especially important for patients with epilepsy or babies whose number of hypomelanotic macules is more than 3. Cranial CT is of great value in the diagnosis of TS. The involvement of visceral organs such as the brain and kidney should be examined in TS patients.