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A 35-year-old man of Chinese ethnicity presented to the emergency department with fever, rash, mouth pain and visual impairment after two weeks of therapy with allopurinol. On examination, the patient had a generalized maculopapular rash, orolabial ulceration ([Figure 1][1]), keratoconjunctivitis

The P2X(7) receptor is a ligand-gated cation channel that is highly expressed on mononuclear leukocytes and that mediates ATP-induced apoptosis and killing of intracellular pathogens. There is a wide variation in P2X(7) receptor function between subjects, explained in part by four loss-of-function polymorphisms (R307Q, E496A, I568N, and a 5'-intronic splice site polymorphism), as well as rare mutations. In this study, we report the allele frequencies of 11 non-synonymous P2X(7) polymorphisms and describe a fifth loss-of-function polymorphism in the gene (1096C --> G), which changes Thr(357) to Ser (T357S) with an allele frequency of 0.08 in the Caucasian population. P2X(7) function was measured by ATP-induced ethidium(+) influx into peripheral blood lymphocytes and monocytes and, when compared with wild-type subjects, was reduced to 10-65% in heterozygotes, 1-18% in homozygotes, and 0-10% in compound heterozygotes carrying T357S and a second loss-of-function polymorphism. Overexpression of the T357S mutant P2X(7) in either HEK-293 cells or Xenopus oocytes gave P2X(7) function of approximately 50% that of wild-type constructs. Differentiation of monocytes to macrophages, which also up-regulates P2X(7), restored P2X(7) function to near normal in cells heterozygous for T357S and to a value 50-65% of wild-type in cells homozygous for T357S or compound heterozygous for T357S/E496A. However, macrophages from subjects that are compound heterozygous for either T357S/R307Q or T357S/stop codon had near-to-absent P2X(7) function. These functional deficits induced by T357S were paralleled by impaired ATP-induced apoptosis and mycobacteria killing in macrophages from these subjects. Lymphocytes, monocytes, and macrophages from subjects homozygous for T357S or compound heterozygous for T357S and a second loss-of-function allele have reduced or absent P2X(7) receptor function.

Protective immunity to mycobacterial infections requires activation of the antibacterial mechanisms of infected macrophages. It has previously been reported that ATP treatment of mycobacteria-infected macrophages induces apoptosis mediated via the P2X7 pathway and that this leads to the death of both the host cell and the internalized bacilli. We have recently identified a single nucleotide polymorphism in the P2X7 gene (1513A→C), with 1–2% prevalence in the homozygous state, which codes for a nonfunctional receptor. IFN-γ-primed, mycobacteria-infected macrophages from wild-type individuals were incubated with ATP and this induced apoptosis and reduced mycobacterial viability by 90%. Similar treatment of macrophages from individuals homozygous for the 1513C polymorphism failed to induce apoptosis and did not lead to mycobacterial killing via the P2X7-mediated pathway. These data demonstrate that a single nucleotide polymorphism in the P2X7 gene can allow survival of mycobacteria within infected host cells.

Background Neuromuscular blocking agents (NMBAs) are the most frequently reported causative agents in cases of anaesthetic related anaphylaxis. Assays for specific IgE (sIgE) to morphine and pholcodine are available as indicators of sIgE to the substituted ammonium groups on NMBAs. Chlorhexidine is an antiseptic also implicated in perioperative anaphylaxis. Aim To evaluate laboratory tests for sIgE to morphine, pholcodine and chlorhexidine in the investigation of perioperative anaphylaxis. Method This study included 140 patients referred to the Anaesthesia Allergy and Adverse Events clinic at Royal North Shore Hospital. Standardised skin tests were performed with all suspected agents to which patients had been exposed. Testing for sIgE to morphine, pholcodine and chlorhexidine was performed via the Phadia ImmunoCAP system. Results Using the recommended cut-off value sIgE tests for morphine, pholcodine and chlorhexidine all showed good sensitivity and specificity with reference to skin test results. ROC analysis suggested an alternative positive cut-off. Application of this lower threshold allowed for increased sensitivity without adversely affecting specificity. Conclusion Specific IgE testing to morphine, pholcodine and chlorhexidine is a reliable adjunct to skin testing in determining diagnosis of allergy to NMBAs and/or chlorhexidine. Additionally, adjustment of cut-off thresholds is able to increase test sensitivity.

To assess whether changes in mean cell volume (MCV) could be used as a surrogate marker of adherence, the percentage rise from the baseline MCV (%MCV rise) was compared to an independent marker of adherence, the number of days of medications dispensed in a 24-week period. Nucleoside analogues were found to differ in the extent to which they affect the MCV. The correlation between zidovudine (AZT) (30 subjects) and stavudine (D4T) (41 subjects) with adherence based on prescriptions was 0.82 ( P

Twenty-five patients living in a tick-endemic region of Sydney, New South Wales developed red meat allergy after experiencing large local reactions to tick bites. This represents a potentially novel cross-reaction between an arthropod and a food protein. (MJA 2009; 190: 510-511).

A female in her early 50s presented with a long-standing history of episodic urticaria and angioedema. She also reported urticarial reactions after ingestion of aspirin, prednisone and multiple antibiotics. These medications were all taken during upper respiratory tract infections. An elimination diet followed by a series of open challenges to food chemicals demonstrated an urticarial eruption following the ingestion of mints, which contain high levels of salicylates. A double-blinded placebo-controlled challenge to salicylate confirmed her sensitivity and explained her reaction to aspirin. The patient informed her treating physician of her copious ingestion of mints during upper respiratory tract infections. Drug hypersensitivity to antibiotics and prednisone was excluded on the basis of negative radioallergosorbent tests (RASTs) and/or absent skin-test responses and/or tolerance to oral challenges. This patient had a salicylate intolerance that caused her episodic urticaria and angioedema, and also masqueraded as a drug allergy due to the concurrent ingestion of mints.

A man in his 60s presented with dry eyes and progressive deterioration in vision bilaterally over a 2-year period. He was treated a number of times presumptively for conjunctivitis with topical antibiotics. Upon referral to an ophthalmologist, physical examination revealed the presence of conjunctival scarring with loss of the fornix, symblepharon (adhesion between conjunctival surfaces of the lid and globe), entropion (lid inversion due to conjunctival scarring) and …