Insulin Allergy to Detemir Followed by Rapid Onset of Diabetic Ketoacidosis: A Case Report and Literature Review.

The management of diabetes mellitus in an insulin-dependent patient is challenging in the setting of concomitant antibody-mediated-insulin hypersensitivity. We report a case of a 62-year-old woman with pre-existing type 2 diabetes mellitus of 10 years duration who developed type 3 hypersensitivity reaction to insulin analogue detemir, and subsequently, severe diabetic ketoacidosis (DKA). She was C-peptide negative and was diagnosed with insulin-dependent diabetes. Despite increasing dose adjustments, insulin-meal matching, and compliance with insulin, she experienced episodes of unexpected hyperglycaemia and hypoglycaemia. The development of rash after detemir initiation and rapid progression to DKA suggests an aberrant immune response leading to the insulin allergy and antibody-induced interference with insulin analogues. Glycaemic control in the patient initially improved after being started on subcutaneous insulin infusion pump with reduced insulin requirements. However, after a year on pump therapy, localised insulin hypersensitivity reactions started, and glycaemic control gradually deteriorated.

A novel NSDHL variant in CHILD syndrome with gastrointestinal manifestations and localized skin involvement.

BACKGROUND: CHILD syndrome is an X-linked dominant disorder associated with pathogenic mutations in the NSDHL gene. The condition is predominantly found in females as it is lethal in males. Most cases present at birth with extensive unilateral ichthyosiform erythroderma involving the trunk and limbs. Milder and less extensive presentations have been reported, leading to misdiagnosis especially during early childhood. METHODS AND RESULTS: We report an adult female of Malay ancestry who presented with minimal skin and limb involvement. She was only diagnosed in adulthood when she presented with gastrointestinal symptoms and worsening of skin manifestations. The clinical diagnosis was suspected after a combination of clinical, pathological and immunohistochemistry correlation, and molecularly confirmed with the discovery of a frameshift variant in NSDHL. The novel variant was inherited from her mother who had some linear hypopigmented patches over the medial aspects of both her arms and right forearm. CONCLUSION: We uncovered a novel frameshift variant associated with presentations that cast a new light on the clinical features of CHILD syndrome.

Epidemiology, risk factors, and outcomes of adult cutaneous non-tuberculous mycobacterial infection over a 10-year period in Singapore.

BACKGROUND: Unfamiliarity with the presentation, diagnostic process, and treatment of cutaneous non-tuberculous mycobacterium (NTM) infection leads to poorer outcomes. We describe our experience with managing cutaneous NTM infection in a regional hospital in Singapore from 2005 to 2014. METHODS: Adult patients with cutaneous NTM infections were identified through positive skin tissue cultures in this retrospective case series. We excluded patients younger than 21 years of age, patients whose care was transferred to another hospital, and patients with catheter-related infections. Data including demographic variables, as well as disease and treatment outcomes, were collected. We compared the data between patients with and without risk factors for immunosuppression to look for any significant difference. RESULTS: Fifty-eight cases were reviewed. Mycobacterium abscessus was the commonest organism isolated (51.7%), and abscesses or inflamed cysts were the most common presentation. Nineteen specimens (57.6%) showed suppurative or necrotizing granulomatous dermatitis on biopsy and acid-fast bacilli were identified in 2 of 21 histologic specimens (9.5%) stained for mycobacterium. Treatment included systemic antibiotics, surgery, or both. In total, 33 cases had clinical resolution while 25 cases were lost to follow-up. Our study was limited by the under-reporting of cases, bias due to data from a single center, and high dropout rates, thereby precluding a detailed assessment of treatment outcomes. CONCLUSIONS: A high index of suspicion is required to diagnose cutaneous NTM infection. Education of both patients and physicians will help to raise the level of awareness and reduce treatment delays.

Tailoring of recommendations to reduce serious cutaneous adverse drug reactions: a pharmacogenomics approach.

The Health Sciences Authority launched a pharmacogenetics initiative in 2008 to facilitate evaluation of pharmacogenetics associations pertinent for Chinese, Malays and Indians in Singapore. The aim was to reduce the incidence and unpredictability of serious adverse drug reactions, with a focus on serious skin adverse drug reactions. This paper describes the gathering of evidence and weighing of factors that led to different genotyping recommendations for HLA-B*15:02 with carbamazepine and HLA-B*58:01 with allopurinol, despite both having strong genetic associations. Translation of pharmacogenomics at a national level requires careful deliberation of the prevalence of at-risk allele, strength of genetic associations, positive predictive value, cost-effectiveness and availability of alternative therapies. Our experience provides a perspective on translating genomic discoveries in advancing drug safety.

The profile of adult onset Henoch-Schönlein purpura in an Asian population.

BACKGROUND: Henoch-Schönlein purpura (HSP) is less common in adults and has been linked with a more severe clinical syndrome as well as a higher frequency of renal disease and internal malignancy. Renal involvement in adult HSP has been significantly associated with antecedent infections, pyrexia at time of first presentation, and purpura above the waist. We aim to evaluate the frequency of cutaneous and extra-cutaneous features and identify the predictive factors for renal involvement in Asian adults with HSP. METHODS: We performed a retrospective study of 48 adult Asian patients diagnosed with HSP based on the European League Against Rheumatism (EULAR) criteria at a tertiary hospital in Singapore between January 2000 and December 2011. RESULTS: The most common cutaneous manifestations were palpable purpura (73%), papules (31%), and petechiae (27%). Forty-percent had cutaneous lesions extending above the waist. Fifteen patients (31%) had gastrointestinal symptoms, 21 (44%) had joint involvement, and 27 (56%) had renal disease. Seventy-percent of patients with pyrexia at presentation experienced renal disease, whereas only 30% without pyrexia had renal involvement (P = 0.018). Sixty-six percent of patients with purpura had renal involvement as compared to 31% in those without purpura (P = 0.049). The frequency of renal involvement in patients with purpura above the waist (52%) was similar to those with purpura below the waist (55%). CONCLUSIONS: Our study confirms that HSP in adults tends to be more severe with a high incidence of extracutaneous manifestations, especially renal disease. Pyrexia at presentation and the presence of purpura were significant predictive factors for renal involvement.

Relationship between exhaled nitric oxide and atopy in Asian young adults.

OBJECTIVES: The relationship between exhaled nitric oxide and atopy is controversial. The aim of this study was to determine the relationship between exhaled nitric oxide (FE(NO)) and atopy in Asian young adults. METHODOLOGY: Subjects were assessed by: (i) the International Study of Asthma and Allergies in Childhood questionnaire to differentiate asthmatic from nonasthmatic and rhinitis from non-rhinitis subjects; (ii) skin prick testing to 10 allergens; and (iii) FE(NO) measurements performed online at a flow rate of 50 mL/s. RESULTS: Complete results were available for 84 subjects. FE(NO) values were highest in atopic asthmatics (n = 34; median FE(NO), 59.8 p.p.b.; interquartile range, 30.4-85.5 p.p.b), followed by atopic nonasthmatics (n = 34; median, 38.4 p.p.b.; range, 16.7-49.3 p.p.b), nonatopic asthmatics (n = 5; median, 19.1 p.p.b.; range, 17.9-33.4 p.p.b), and lowest in nonatopic nonasthmatics (n = 11; median, 15.7 p.p.b.; range, 11.5-21.7 p.p.b). FE(NO) values were significantly higher in atopic (n = 68; median, 44.7 p.p.b.; range, 27.3-75.2 p.p.b) compared to nonatopic subjects (n = 16; median, 17.0 p.p.b.; range, 11.7-23.8 p.p.b.; P < 0.0001), regardless of asthma and rhinitis status. FE(NO) levels correlated with the severity of atopy (wheal size) for both asthmatic (r = 0.44, P = 0.005) and nonasthmatic subjects (r = 0.48, P = 0.001). There was no significant difference in FE(NO) levels between nonatopic asthmatics and nonatopic nonasthmatic subjects (P = 0.25). CONCLUSIONS: Increased FE(NO) levels are more reflective of atopy rather than asthma, and increased nitric oxide production may be predominantly a feature of atopy in asthmatics.