Disseminated Mycobacterium avium complex infection in a child with partial dominant interferon gamma receptor 1 deficiency in India.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by clinical disease caused by weakly virulent mycobacteria. All genes mutated in MSMD patients are involved in IFN-γ immunity. Autosomal partial dominant (PD) interferon-γ receptor 1 (IFN-γR1) deficiency is the most frequent abnormality affecting the group of MSMD patients leading to impaired response of IFN-γ. We describe here a patient from India with disseminated infection due to Mycobacterium avium intracellulare (MAC) including multifocal osteomyelitis and BCG disease. A heterozygous mutation in exon 6 of IFNGR1 gene was identified, conferring an autosomal PD IFN-γR1 deficiency. Patient had recurrence of mycobacterial disease during antibiotic therapy for which subcutaneous IFN-γ was added as a modality of treatment for resistant MAC infection.

Gum pigmentation: an unusual adverse effect of sublingual immunotherapy.

Sublingual immunotherapy has gained acceptance amongst the paediatric community as it is very well tolerated and is safe. The adverse effects of this therapy is minimal consisting mainly of local side effects within the oral cavity such as itching of the mouth, swelling of the lips and less frequently abdominal pain, wheezing and urticaria has been described. This report is to highlight another local side effect of sublingual immunotherapy which has been observed in 3 of our patients. This is pigmentation of the gums which can occur anytime during the course of the immunotherapy. It resolves on stopping the immunotherapy and is likely due to a local inflammatory process occurring in the gums of these children. There is no associated pain or itching with the pigmentation. It can persist as long as the child is on the immunotherapy.

Mite component-specific IgE repertoire and phenotypes of allergic disease in childhood: the tropical perspective.

Sensitization to perennial aeroallergens correlates with the risk of persistent asthma (AS) in children. In tropical Singapore, multiple codominant species of mites abound in the indoor environment, and preferential species-specific sensitization has been associated with different phenotypes of allergic disease. We investigated the pattern of mite component-specific IgE (mcsIgE) in children with different phenotypes of clinical allergic disease in an environment with multiple mite species exposure. A prospective evaluation of newly diagnosed patients with clinical diagnosis of allergic rhinitis (AR), atopic dermatitis (AD), or AS and sensitization to one or more aeroallergens were performed. Sera were tested for specific IgE against an extensive panel of Dermatophagoides pteronyssinus and Blomia tropicalis allergens. A total of 253 children were included, mean age 7.3 yr, 79% fulfilled criteria for AR, 46% AS, 71% AD, and 31% for all three. Sensitization to one or both mites was observed in 91% of children, 89% were sensitized to D. pteronyssinus, and 70% to B. tropicalis. The most common mite allergens recognized by these atopic children were Der p 1 (64%), Der p 2 (71%), Blo t 5 (45%), Blo t 7 (44%), and Blo t 21 (56%). Specific IgE responses to an increased number of distinct mite allergens correlated with the complexity of the allergic phenotype. In multivariate analysis, an increased risk for the multi-systemic phenotype (AR + AS + AD) was associated with sensitization to an increased repertoire of mite components (three or more) (OR 4.3, 95% CI 2.1-8.8, p = 0.001) and a positive parental history of AS (OR 2.4, 95% CI 1.2-2.9, p = 0.013). A highly pleiomorphic IgE response to the prevalent indoor mites is associated with the presence of a multi-systemic allergic phenotype in childhood in a tropical environment.

Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort study.

OBJECTIVE: To describe the outcomes of clinical evaluation, skin testing, and vaccine challenge in adolescent schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine introduced in Australian schools in 2007. DESIGN: Retrospective cohort study. SETTING: Two tertiary paediatric allergy centres in Victoria and South Australia, Australia. PARTICIPANTS: 35 schoolgirls aged 12 to 18.9 years with suspected hypersensitivity reactions to the quadrivalent human papillomavirus vaccine. MAIN OUTCOME MEASURES: Clinical review and skin prick and intradermal testing with the quadrivalent vaccine and subsequent challenge with the vaccine. RESULTS: 35 schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine were notified to the specialised immunisation services in 2007, after more than 380 000 doses had been administered in schools. Of these 35 schoolgirls, 25 agreed to further evaluation. Twenty three (92%) experienced reactions after the first dose. Thirteen (52%) experienced urticaria or angio-oedema, and of these, two experienced anaphylaxis. Thirteen had generalised rash, one with angio-oedema. The median time to reaction was 90 minutes. Nineteen (76%) underwent skin testing with the quadrivalent vaccine: all were skin prick test negative and one was intradermal test positive. Eighteen (72%) were subsequently challenged with the quadrivalent vaccine and three (12%) elected to receive the bivalent vaccine. Seventeen tolerated the challenge and one reported limited urticaria four hours after the vaccine had been administered. Only three of the 25 schoolgirls were found to have probable hypersensitivity to the quadrivalent vaccine. CONCLUSION: True hypersensitivity to the quadrivalent human papillomavirus vaccine in Australian schoolgirls was uncommon and most tolerated subsequent doses.

Severe anaphylactic reaction to ibuprofen in a child with recurrent urticaria.

An acute anaphylactic reaction after a conventional antipyretic dose of ibuprofen was diagnosed in a child with allergic rhinitis, recurrent idiopathic urticaria, and nonimmunologic cross-reactive hypersensitivity to nonsteroidal antiinflammatory drugs and acetaminophen. The patient reported several previous, mild (isolated cutaneous) hypersensitivity reactions after exposure to acetaminophen or ibuprofen. There was no evidence of an underlying inflammatory disease except as described above. Patients with chronic or recurrent idiopathic urticaria and those with atopic disease represent groups at increased risk of nonsteroidal antiinflammatory drug hypersensitivity. Mild hypersensitivity reactions to acetaminophen and/or ibuprofen may precede subsequent, more-severe adverse reactions. Risks and benefits of continued use of nonsteroidal antiinflammatory drugs in these children should be carefully considered.

Nonsteroidal anti-inflammatory drug hypersensitivity in preschool children.

: Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA)-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX)-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.

Early presentation with angioedema and urticaria in cross-reactive hypersensitivity to nonsteroidal antiinflammatory drugs among young, Asian, atopic children.

OBJECTIVE: Nonsteroidal antiinflammatory drugs (NSAIDs), mainly ibuprofen, are used extensively among children as analgesic and antipyretic agents. Our initial survey in the Kendang Kerbau Children's Hospital in Singapore showed NSAIDs to be the second most common adverse drug reaction-causing medications among children of Asian descent. We attempted to characterize the clinical and epidemiologic profile of NSAID reactions in this group of patients. METHODS: A retrospective case series from a hospital-based pediatric drug allergy clinic was studied. A diagnosis of NSAID hypersensitivity was made with a modified oral provocation test. Atopy was evaluated clinically and tested with a standard panel of skin-prick tests. We excluded from analysis patients with any unprovoked episodes of urticaria and/or angioedema, patients < 1 year of age, and patients who refused a diagnostic challenge test. RESULTS: Between March 1, 2003, and February 28, 2004, 24 patients, including 14 male patients (58%) and 18 Chinese patients (75%), with a mean age of 7.4 years (range: 1.4-14.4 years), were diagnosed as having cross-reactive NSAID hypersensitivity. A family history consistent with NSAID hypersensitivity was elicited for 17% of patients. None of the patients reported any episodes of angioedema/urticaria unrelated to NSAIDs. The median cumulative reaction-eliciting dose was 7.1 mg/kg. Facial angioedema developed for all patients (100%) and generalized urticaria for 38% of challenged patients, irrespective of age. There was no circulatory compromise, but respiratory symptoms of tachypnea, wheezing, and/or cough were documented for 42% of patients. A cross-reactive hypersensitivity response to acetaminophen was documented for 46% of our patients through their history and for 25% through diagnostic challenge. Compared with patients with suspected adverse drug reactions to antibiotics, patients in the NSAID group were older (7.4 vs 4.8 years) and more likely to have a diagnosis of asthma (odds ratio: 7.5; 95% confidence interval: 3.1-19). CONCLUSIONS: Early presentations of facial angioedema and urticaria are key features of dose- and potency-dependent, cross-reactive reactions to NSAIDs in a subpopulation of young, Asian, atopic children. Significant overlap with acetaminophen hypersensitivity, especially among very young patients, for whom the use of a cyclooxygenase-2-specific medication may not be feasible, severely limits options for medical antipyretic treatment.