ß-Lactam allergy testing and delabeling-Experiences and lessons from Singapore.

BACKGROUND: ß-Lactam allergy is over-reported and this leads to greater healthcare costs. Allergy testing has inherent risks, yet patients who test negative may continue avoiding ß-lactams. OBJECTIVE: To evaluate the safety and diagnostic value of ß-lactams allergy testing locally and usage of antibiotics following negative testing. METHODS: We performed a retrospective medical record review and follow-up survey of patients who underwent ß-lactam testing between 2010 and 2016 at the National Skin Centre, Singapore. RESULTS: We reviewed the records of 166 patients, with a total of 173 ß-lactam allergy labels. Eighty (46.2%) labels were to penicillin, 75 (43.1%) to amoxicillin/amoxicillin-clavulanic acid, 11 (6.4%) to cephalexin, and 5 (2.9%) to others. Skin tests were performed in 142 patients and drug provocation tests (DPTs) in 141 patients. Eleven (6.6%) patients defaulted DPTs after skin testing. Out of 166 patients, 22 (13.3%) patients were proven allergic by either skin tests (16) or DPTs (6). Patients who tested positive had nonsevere reactions. Out of 155 patients who were conclusively evaluated, 133 (85.8%) were not allergic. Of these patients, 30 (22.6%) used the tested ß-lactam subsequently, with one reporting a mild reaction. Fifty-one (38.3%) patients were uncontactable or uncertain if they consumed a ß-lactam since testing negative. Fifty-two (39.1%) patients had no re-exposure (35 had no indication, 17 were fearful of reactions). CONCLUSION: Drug allergy testing was safe and removed inappropriate labels. CLINICAL IMPLICATION: Allergy testing is efficacious, but fears of subsequent rechallenge should be addressed to maximize the effectiveness of allergy delabeling.

Retrospective study on the characteristics and treatment of late-onset vitiligo.

BACKGROUND: Late-onset vitiligo, defined as being aged 50 years and above at the point of clinical onset, remains poorly characterized till now. AIM: This study aims to describe the clinical characteristics and treatment response of patients with late-onset vitiligo. METHODS: We retrospectively reviewed the case records of all patients diagnosed with late-onset vitiligo, from January 1, 2010 to December 31, 2014. Information obtained included patient demographics, characteristics of vitiligo and treatment responses. RESULTS: Of the 3128 patients diagnosed with vitiligo over the 5-year period, 461 (14.7%) had late-onset disease. The study had more females (n = 260, 56.4%) than males, with an average onset age of 59.4 ± 7.4 years. Majority of patients were Chinese (n = 308, 66.8%) and 45 (9.8%) patients had an associated autoimmune disease. Focal vitiligo, defined as the localized presence of depigmented patches, was most common (n = 209, 45.3%). Treatment response was evaluated in 359 patients, of which 216 received monotherapy (topical creams: n = 210, 97.2%; phototherapy: n = 6, 2.8%) and 143 received both modalities. Fifty six (15.6%) patients received oral steroids. Patients who were treated with both topical creams and phototherapy yielded better clinical responses compared to those on monotherapy (P < 0.001) with 56.6% (n = 81) of them achieving good epidermal repigmentation, defined as >50% return of pigmentation compared to baseline (vs. n = 66, 30.6% in the monotherapy group). The choice of phototherapy (targeted, narrowband ultraviolet B or psoralen + ultraviolet A) did not significantly affect clinical response (P = 0.774). LIMITATIONS: This study is limited by its retrospective nature, the nonstandardized documentation resulting in the inability to determine disease progression and associated metabolic comorbidities and also by the gradual loss to follow-up of patients. CONCLUSION: Late-onset vitiligo is not uncommon and tends to be of the focal vitiligo subtype. Nonsegmented vitiligo is more prevalent than segmental vitiligo. Combination therapy with topical medications and phototherapy is superior to monotherapy.

Twelve-month and sixty-month outcomes of noncultured cellular grafting for vitiligo.

BACKGROUND: Noncultured cellular grafting is a known surgical technique for vitiligo. OBJECTIVE: This study evaluated our center's 12-month repigmentation outcome and its maintenance up to 60 months, factors influencing repigmentation and safety data. METHODS: Clinicoepidemiologic and repigmentation data were reviewed for patients with vitiligo who had undergone noncultured cellular grafting from March 2006 to December 2012 at the National Skin Center, Singapore. RESULTS: All 177 patients who received noncultured cellular grafting during the study period were included. For those with available data, good to excellent repigmentation was present in 83% at 60 months. At 12 months, 88% of patients (n = 52) with segmental vitiligo achieved good to excellent repigmentation compared with 71% (n = 55) with nonsegmental vitiligo (P < .05). More patients on collagen dressings (82%) achieved good to excellent repigmentation compared with those who received hyaluronic acid (63%) (P < .05). Sites of lesions and postgrafting phototherapy did not significantly affect repigmentation outcome. Adverse reactions were uncommon and mild. LIMITATIONS: The study is limited by its retrospective nature, the progressive loss to follow-up of patients, the absence of blinding, and the lack of use of standardized assessment tools. CONCLUSION: Noncultured cellular grafting was successful in allowing more than 80% of patients to achieve good to excellent repigmentation for at least 60 months.

Retrospective Study on Autoimmune Blistering Disease in Paediatric Patients.

BACKGROUND: Autoimmune blistering diseases (AIBDs) are rare in children and their prevalence in Singapore is unclear. We aimed to investigate the clinical and immunopathologic characteristics of children diagnosed with AIBDs in Singapore. MATERIALS AND METHODS: The clinical and histology databases at the National Skin Centre in Singapore were searched to identify patients younger than 18 years old diagnosed with an AIBD from January 1, 1998, through December 31, 2012. Patient demographic characteristics, presentation, triggers, investigations, treatments, and disease course were analyzed. RESULTS: Twelve patients with AIBDs were identified; five (41.7%) had linear immunoglobulin A disease (LAD); two (16.7%) each had pemphigus vulgaris (PV), bullous pemphigoid, and bullous systemic lupus erythematosus; and one (8.3%) had pemphigus foliaceus. Four (33.3%) were female and eight (66.7%) male. The mean age of onset was 8.7 years (range 2-17 years). Most patients were treated with steroids and adjuvant immunosuppressants. Intravenous rituximab was used effectively in a patient with recalcitrant PV. The mean follow-up was 2.35 years (range 0.17-7.33 years). As of the last follow-up, four (33.3%) patients were in complete remission off therapy, two (16.7%) were in complete remission on therapy, four (33.3%) were in partial remission on therapy, and two (16.7%) were lost to follow-up. CONCLUSION: Consistent with the existing literature, our study shows that LAD is the most common cause of AIBDs in children. Although common in the West, dermatitis herpetiformis was not identified in the current study. Intravenous rituximab may be considered in recalcitrant childhood PV, but vigilant monitoring for side effects is crucial. Immunohistopathologic evaluation is important and repeat biopsies may be of value in patients with atypical disease courses.

Causes and features of erythroderma.

INTRODUCTION: Erythroderma is a generalised inflammatory reaction of the skin secondary to a variety of causes. This retrospective study aims to characterise the features of erythroderma and identify the associated causes of this condition in our population. MATERIALS AND METHODS: We reviewed the clinical, laboratory, histological and other disease-specific investigations of 225 inpatients and outpatients with erythroderma over a 7.5-year period between January 2005 and June 2012. RESULTS: The most common causative factors were underlying dermatoses (68.9%), idiopathic causes (14.2%), drug reactions (10.7%), and malignancies (4.0%). When drugs and underlying dermatoses were excluded, malignancy-associated cases constituted 19.6% of the cases. Fifty-five percent of malignancies were solid-organ malignancies, which is much higher than those previously reported (0.0% to 25%). Endogenous eczema was the most common dermatoses (69.0%), while traditional medications (20.8%) and anti-tuberculous medications (16.7%) were commonly implicated drugs. In patients with cutaneous T-cell lymphoma (CTCL), skin biopsy was suggestive or diagnostic in all cases. A total of 52.4% of patients with drug-related erythroderma had eosinophilia on skin biopsy. Electrolyte abnormalities and renal impairment were seen in 26.2% and 16.9% of patients respectively. Relapse rate at 1-year was 17.8%, with no associated mortality. CONCLUSION: Our study highlights the significant proportion of malignancy-related erythroderma in those whom common underlying causes such as dermatoses and drugs have been excluded. In cases of drug-related erythroderma, traditional medications and antituberculous medications are common causes in our population. Renal impairment and electrolyte abnormalities are commonly seen and should be monitored in patients with erythroderma.

Cutaneous angiosarcoma of the scalp mimicking a keratoacanthoma.

Cutaneous angiosarcoma (CA) has a wide range of clinical presentations. In this case report, we discuss a 78-year-old gentleman, who presented with a keratoacanthoma-like scalp lesion that turned out histologically to be a cutaneous angiosarcoma. A brief overview of CA, including its etiology, prognostic factors, clinical manifestations, and treatment options will also be discussed.

[Relationship between miR-218 and CDK6 expression and their biological impact on glioma cell proliferation and apoptosis].

OBJECTIVES: To investigate the relationship between the expression of miR-218 and CDK6 in glioma cells, and their biological impacts on the tumor cell proliferation and apoptosis. METHODS: Expression levels of miR-218 as well as CDK6 and Ki-67 proteins were analyzed in 60 cases of gliomas with various grades and 10 control brain tissue samples by tissue microarray, locked oligonucleotide probe in situ hybridization and immunohistochemistry. Glioblastoma multiform cell line (U87MG) was transfected with miR-218 mimics (mimics group) and a control sequence (control group), followed by qRT-PCR detection of miR-218 and immunocytochemical stain of CDK6 and Ki-67, respectively. Single cell gel electrophoresis was used to detect the presence of apoptotic cell. RESULTS: The miR-218 labeling indexes (LI) were statistically different (P<0.05) among all groups including control (22.45 +/- 0.59) and various glioma groups (grades I - II 4.00 +/- 1.07, grade III 1.87 +/- 1.06 and grade IV 0.94 +/- 0.78, respectively). The CDK6 LI of the four groups was 7.25 +/- 1.20, 16.71 +/- 0.80, 24.43 +/- 0.62 and 32.05 +/- 0.43, respectively. Significant differences existed between the control group and the glioma groups, and between grade IV and grades I - II glioma groups (P<0.01). Ki-67 positive cell densities of the above four groups (0.00 +/- 0.00, 9.30 +/- 3.48, 31.15 +/- 9.44 and 60.15 +/- 13.60) were significantly different from one and another (P<0.01). The expression of miR-218 negatively correlated with CDK-6 LI (r = -0.480, P<0. 01) and Ki-67 positive cell density (r = - 0.534, P<0.01), while the latter two positively correlated with each other (r = 0.530, P<0.01). U87MG transfection experiment showed that the miR-218 level of the mimics group was significantly higher than that of the control group (P<0.01). CDK6 and Ki-67 LI of the mimics group (14.74 +/- 1.19 and 30.88 +/- 3.31) were significantly lower than those of the control group (79.06 +/- 2.07 and 64.94 +/- 3.96, P<0.01), whilst its apoptotic index (AI) (68.44 +/- 7.05) was significantly higher than that of the control group (13.04 +/- 0.97, P<0.01). CONCLUSIONS: The expression level of miR-218 is an important reference indicator for the assessment of the grade of gliomas. An aberrant decrease of its expression may lead to an increase of the CDK6 expression and proliferative activity of giloma cells. Introducing exogenous miR-218 may effectively down-regulate the CDK6 expression, inhibit cell proliferation and induce apoptosis of malignant giloma cells. These findings imply that miR-218 may serve as a therapeutic agent against malignant glioma.