Soamarat Vilaiyuk

The Localized Scleroderma Skin Severity Index and Physician Global Assessment of Disease Activity: A Work in Progress Toward Development of Localized Scleroderma Outcome Measures

Objective. To develop and evaluate a Localized Scleroderma (LS) Skin Severity Index (LoSSI) and global assessments’ clinimetric property and effect on quality of life (QOL). Methods. A 3-phase study was conducted. The first phase involved 15 patients with LS and 14 examiners who assessed LoSSI [surface area (SA), erythema (ER), skin thickness (ST), and new lesion/extension (N/E)] twice for inter/intrarater reliability. Patient global assessment of disease severity (PtGA-S) and Children’s Dermatology Life Quality Index (CDLQI) were collected for intrarater reliability evaluation. The second phase was aimed to develop clinical determinants for physician global assessment of disease activity (PhysGA-A) and to assess its content validity. The third phase involved 2 examiners assessing LoSSI and PhysGA-A on 27 patients. Effect of training on improving reliability/validity and sensitivity to change of the LoSSI and PhysGA-A was determined. Results. Interrater reliability was excellent for ER [intraclass correlation coefficient (ICC) 0.71], ST (ICC 0.70), LoSSI (ICC 0.80), and PhysGA-A (ICC 0.90) but poor for SA (ICC 0.35); thus, LoSSI was modified to mLoSSI. Examiners’ experience did not affect the scores, but training/practice improved reliability. Intrarater reliability was excellent for ER, ST, and LoSSI (Spearman’s rho = 0.71–0.89) and moderate for SA. PtGA-S and CDLQI showed good intrarater agreement (ICC 0.63 and 0.80). mLoSSI correlated moderately with PhysGA-A and PtGA-S. Both mLoSSI and PhysGA-A were sensitive to change following therapy. Conclusion. mLoSSI and PhysGA-A are reliable and valid tools for assessing LS disease severity and show high sensitivity to detect change over time. These tools are feasible for use in routine clinical practice. They should be considered for inclusion in a core set of LS outcome measures for clinical trials.

Development and initial validation of the Localized Scleroderma Skin Damage Index and Physician Global Assessment of disease Damage: a proof-of-concept study

OBJECTIVE To develop and assess the psychometric properties of the Localized Scleroderma (LS) Skin Damage Index (LoSDI) and Physician Global Assessment of disease Damage (PGA-D). METHODS Damage was defined as irreversible/persistent changes (>6 months) due to previous active disease/complications of therapy. Eight rheumatologists assessed the importance of 17 variables in formulating the PGA-D/LoSDI. LS patients were evaluated by two rheumatologists using both tools to assess their psychometric properties. LoSDI was calculated by summing three scores for cutaneous features of damage [dermal atrophy (DAT), subcutaneous atrophy (SAT) and dyspigmentation (DP)] measured at 18 anatomic sites. Patient GA of disease severity (PtGA-S), Childrens Dermatology Life Quality Index (CDLQI) and PGA-D were recorded at the time of each examination. RESULTS Thirty LS patients (112 lesions) and nine patient-visit pairs (18 lesions) were included for inter- and intra-rater reliability study. LoSDI and its domains DAT, SAT, DP and PGA-D demonstrated excellent inter- and intra-rater reliability (reliability coefficients 0.86-0.99 and 0.74-0.96, respectively). LoSDI correlated moderately with PGA-D and poorly with PtGA-S and CDLQI. PGA-D correlated moderately with PtGA-S, but poorly with CDLQI. CONCLUSIONS To complete the LS Cutaneous Assessment Tool (LoSCAT), we developed and evaluated the psychometric properties of the LoSDI and PGA-D in addition to the LS Skin Severity Index (LoSSI). These instruments will facilitate evaluation of LS patients for individual patient management and clinical trials. LoSDI and PGA-D demonstrated excellent reliability and high validity. LoSCAT provides an improved understanding of LS natural history. Further study in a larger group of patients is needed to confirm these preliminary findings.

Recurrent macrophage activation syndrome as the primary manifestation in systemic lupus erythematosus and the benefit of serial ferritin measurements: a case-based review

Macrophage activation syndrome (MAS) is a fatal complication in rheumatic diseases. It is characterized by prolonged fever, pancytopenia, and hepatosplenomegaly, which are consequences of uncontrolled macrophage activation. MAS in children is most commonly associated with systemic juvenile idiopathic arthritis. Its association with systemic lupus erythematosus (SLE) is relatively rare, so we report a Thai boy who initially presented with MAS and eventually was diagnosed as having SLE. He also had recurrent MAS during the course of therapy. Hyperferritinemia is one of the abnormal laboratory findings in MAS and it has been used as an inflammatory marker. However, its correlation with disease activity remains unclear. Therefore, a review of literature regarding MAS-associated SLE in children and ferritin level in this disease was carried out.

Phenobarbital‐induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children

Aromatic anticonvulsant–induced severe cutaneous adverse drug reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), are fatal immune‐mediated adverse drug reactions. CYP2C19, a cytochrome P450 isoform, plays a role in metabolic rate of aromatic anticonvulsant. HLA‐B*1502 has also been demonstrated to be associated with carbamazepine‐induced SJS‐TEN.

Cow's milk protein allergy: immunological response in children with cow's milk protein tolerance.

OBJECTIVE To study changes in immunological responses in patients with CMPA during symptomatic and asymptomatic episodes of cows milk protein tolerance status. METHODS 27 CMPA patients were enrolled and underwent diagnostic evaluation, including CM challenge test, skin prick test and specific IgE to CM. Blood samples were collected in two periods from those who became tolerant (n = 13) and those with persistent CMA (n = 14), in order to measure in vitro PBMC responses to cows milk protein (IL-10, IFN-γ, IL-5), IgG4 to β-lactoglobulin, casein, BLG-IgG4/IgE ratio and the CAS-IgG4/IgE ratio. RESULTS Seventy percent of CMPA patients in our study were male with a mean age at diagnosis of 8 months and mean age of onset of 3 months. The reaction time to CM ranged from within 7 minutes to within 14 days. Positive IgE-sensitization was defined as either a specific IgE to CM of more than 0.35 kUA/L (N=11) or SPTs positive for CM and/or fresh cows milk (N=20). Forty-eight percent of the patients (n = 13) could tolerate CM by 13.38 months (8-19 months). Mean specific-IgE levels to CM were 4.1 kUA/L (range 0.35-14.3 kUA/L). Determination of the cytokine (IL-10, IFN-γ, IL-5) response to BLG revealed significantly higher IL-10 levels during the tolerance phase (212.93 vs 142.46 pg/ml, P = .011). There was a significant increase in BLG-IgG4 and the BLG-IgG4/IgE ratio in the tolerance phase when compared to the symptomatic phase. CONCLUSIONS IL-10, BLG-IgG4 and the BLG-IgG4/IgE ratio were higher in CMPA patients during the tolerance phase compared to the symptomatic phase.

Pediatric anaphylaxis: triggers, clinical features, and treatment in a tertiary-care hospital

BACKGROUND Anaphylaxis is a life-threatening condition. There are limited data about its etiology and clinical characteristics in Asian children with anaphylaxis. OBJECTIVE To investigate triggers, presenting symptoms, treatment and clinical course of anaphylaxis in Thai children. METHOD Medical record of children who were diagnosed with anaphylaxis between 2004 and 2013 at Ramathibodi Hospital, Bangkok, Thailand were reviewed. RESULTS One hundred-seventy two episodes of anaphylaxis occurred in 160 children (91 boys, 69 girls) aged 3 months to 18 years. Anaphylaxis increased from 2.7 cases/1000 pediatric admission to 4.51 cases/1000 pediatric admission between 2004-2008 and 2009-2013. The main causes were food (34.92%), drug (33.1%), blood components (23.8%), insect sting (9%), and unidentified causes (2.8%). Allergy to the triggers was known prior to anaphylaxis in 42 episodes (24.6%). Treatment consisted of epinephrine intramuscularly (93.8%), corticosteroids (92.5%), H₁antihistamines (96%), H₂antihistamines (50%), and β₂agonists nebulization (35.1%). Biphasic anaphylaxis occurred in 8.7% of the documented episodes and severe anaphylaxis in 34.3% of the documented episodes. Biphasic anaphylaxis and severe anaphylaxis were associated with fewer administrations of intramuscular epinephrine (OR 0.08 [95% CI 0.014-0.43]; p =0.01 and OR 9.36 [95% CI 2.5-34.7]; p <0.001 respectively). There were no fatality cases. There were associations between triggers of anaphylaxis and atopic histories, patients with severe anaphylaxis and cardiovascular involvement (p <0.01). CONCLUSIONS The incidence of anaphylaxis in Thai children is increasing. Anaphylaxis in children commonly occurred without the histories of prior reaction to the causative agent. Less frequent treatment with intramuscular epinephrine was associated with biphasic and severe anaphylaxis. A better knowledge of patterns and causes of anaphylaxis might contribute to a better management.

Comparison of conjunctival and nasal provocation tests in allergic rhinitis children with Dermatophagoides pteronyssinus sensitization

BACKGROUND Nasal provocation tests (NPTs) are indicated in confirming the diagnosis of allergic rhinitis if the clinical history, skin tests or sIgE are inconclusive. NPTs are time- consuming, technically difficult and expensive to perform. Consequently, conjunctival provocation tests (CPTs), which are easier, cheaper and safer should be considered as an alternative method. No recent study has compared CPTs with NPTs in allergic rhinitis children. OBJECTIVE To compare CPTs with NPTs in allergic rhinitis children with house dust mite sensitization METHODS Fifty-five children with allergic rhinitis were included. Thirty-six children had positive skin prick tests (SPTs) to Dermatophagoides pteronyssinus (Dp). NPTs were performed by spraying 0.1 ml of Dp extract with concentrations of 50, 200 and 500 AU/ml to each nostril at 15 minute interval. The clinical symptom scores, anterior rhinomanometry results and nasal peak flow testing were performed to assess the responses. For CPTs, 0.1 ml of the same concentration of allergen extract was droppedinto one eye and the control solution was dropped into the other. The responses were assessed by clinical symptom scores. The tests were stopped when the subject reported a positive response, or continued to the maximum concentration. RESULTS The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CPT compared with NPT are 97.1% (84.7-99.9), 90.5% (69.6-98.8), 94.3% (80.8-99.3), 95% (75.1-99.9) and 94.5 (84.9-98.9), respectively in all patients. Among individual allergic rhinitis subjects the sensitivity, specificity, PPV and NPV are 100%. CONCLUSIONS CPT can be an alternative test for NPT in allergic rhinitis children with house dust mite sensitization, even if they do not have conjunctival symptoms.

Immunoglobulin values in healthy Thai children aged ≤ 24 months determined by nephelometry.

BACKGROUND Variation of normal immunoglobulin (Ig) levels between different genetic and environment factors has been studied. Although antibody deficiency diseases can start from infancy, data of Ig reference levels in children aged ≤24 months are still limited, especially in Asian children. PURPOSE The aim of this study was to determine serum IgG, IgA, IgM, and IgG subclasses in healthy Thai children from the newborn period to age 24 months. METHODS Serum samples were collected from healthy Thai children age <1-24 months to measured serum IgG, IgA, IgM, and IgG subclasses by nephelometry. RESULTS Of the 100 infants, 44% were female with a median (range) age of 13 (0.3-24) months. The geometric mean IgG was 803 mg/dL, IgA 36 mg/dL, and IgM 102 mg/dL. The mean IgG1 was 646 mg/dL, IgG2 127 mg/dL, IgG3 45 mg/dL, and IgG4 17 mg/dL. The average ratios of IgG subclass 1:2:3:4 were 77:15:6:2%. No significant differences in each immunoglobulin isotype between genders were found. Our mean IgG level was slightly lower than that in healthy Thai children, measured by radial diffusion method but not significant except 1-3 months (p = 0.016). However, the mean IgG level in our study was higher than that reported by radial diffusion in healthy US children (p <0.001). CONCLUSIONS This study illustrated the importance of having normal Ig values from age- and ethnically-matched controls by high precision nephelometric assay in order to appropriately diagnose immunologic disorders in Asian infants.

The comparisons between thermography and ultrasonography with physical examination for wrist joint assessment in juvenile idiopathic arthritis

OBJECTIVE This study aimed to assess infrared thermography (IRT) and ultrasonography (US) for detecting wrist arthritis in juvenile idiopathic arthritis (JIA) patients. Although IRT could help us in detecting joint inflammation, IRT studies in JIA patients with wrist arthritis are still limited. Currently, no validated US criteria exist for detecting arthritis, and the most useful parameters between gray-scale ultrasound (GSUS) or power Doppler ultrasound (PDUS) remain unclear. APPROACH Forty-six JIA patients were included in this study. Detecting wrist arthritis at varying degrees using IRT and US were compared with physical examination. MAIN RESULTS Sixteen patients had previous wrist arthritis that is currently inactive and 30 still had wrist arthritis. The median ages (IQR) were 7.7 (4.3) and 10.2 (4.8) years, respectively. Fifteen healthy participants were included, with a median age (IQR) of 9.2 (2.0) years. Using IRT, mean temperature (T mean) and maximum temperature (T max) at skin surface in the region of interest (ROI) in the arthritis group were higher than in the inactive group and the healthy controls with p  <  0.05. When patients with arthritis were subgroup analyzed by disease severity based on physical examination, the moderate to severe arthritis had T mean and T max higher than the mild arthritis group with statistical significance. The heat distribution index (HDI), two standard deviations of all pixel temperature values in the ROI, in the moderate to severe arthritis group was higher than in the healthy controls (p  =  0.027). The receiver operating characteristic analysis in arthritis detection revealed diagnostic sensitivity of 85.7% and 71.4% and specificity of 80.0% and 93.3% at cut-off points of T mean  ⩾  31.0 °C and T max  ⩾  32.3 °C, respectively. For US, GSUS and PDUS are useful in detecting arthritis, providing high sensitivity (83.3%) and specificity (81.3%). SIGNIFICANCE Our study demonstrated that both IRT and US were applicable tools for detecting wrist arthritis.

Henoch-Schönlein purpura from vasculitis to intestinal perforation: A case report and literature review

Henoch-Schönlein purpura (HSP) is generally a self-limited vasculitis disease and has a good prognosis. We report a 4-year-old Thai boy who presented with palpable purpura, abdominal colicky pain, seizure, and eventually developed intestinal ischemia and perforation despite adequate treatment, including corticosteroid and intravenous immunoglobulin therapy. Imaging modalities, including ultrasonography and contrast-enhanced computed tomography, could not detect intestinal ischemia prior to perforation. In this patient, we also postulated that vasculitis-induced mucosal ischemia was a cause of the ulcer, leading to intestinal perforation, and high-dose corticosteroid could have been a contributing factor since the histopathology revealed depletion of lymphoid follicles. Intestinal perforation in HSP is rare, but life-threatening. Close monitoring and thorough clinical evaluation are essential to detect bowel ischemia before perforation, particularly in HSP patients who have hematochezia, persistent localized abdominal tenderness and guarding. In highly suspicious cases, exploratory laparotomy may be needed for the definite diagnosis and prevention of further complications.