The clinical spectrum of omega-5-gliadin allergy.

BACKGROUND: IgE-mediated allergy to the wheat protein omega-5-gliadin (O5G) is associated with wheat-dependent exercise-induced anaphylaxis (WDEIA), where exercise acts as a cofactor, triggering anaphylaxis after wheat ingestion. The wider application of O5G-specific IgE (sIgE) testing has revealed that the manifestations of O5G allergy extend beyond WDEIA. AIMS: This study documents clinical manifestations in a large series of patients with sIgE to O5G. METHODS: A retrospective clinical audit was performed on adult patients with a positive O5G sIgE (>0.35kU/L) between 2007 and 2013 compared with a group who had negative O5G sIgE. Clinical characteristics and skin prick test (SPT) results were examined. RESULTS: Sixty-seven patients were characterised, 26 of whom presented with food-dependent exercise-induced allergy, whilst others presented with exercise-induced symptoms without apparent food association (16/67), idiopathic anaphylaxis (10/67), food-induced allergic symptoms without exercise (10/67) or recurrent acute urticaria (5/67). Specific IgE to O5G had 91% sensitivity and 92% specificity for wheat-related allergic symptoms. SPT had sensitivity of 92% and specificity of 84%. CONCLUSION: WDEIA is the most common manifestation of O5G allergy, but patients may present with a variety of allergic manifestations, and wheat allergy is not always obvious on history. Non-exercise cofactors or a lack of cofactors were identified in many patients. A distinctive feature of this allergy is that despite regular wheat ingestion, allergic reactions to wheat occur infrequently. Testing for sIgE to O5G should be considered in patients presenting with exercise-induced urticaria/anaphylaxis, idiopathic anaphylaxis and recurrent acute (but not chronic) urticaria.

Clinical and laboratory characteristics of 19 patients with Churg-Strauss syndrome from a single South Australian centre.

BACKGROUND: Churg-Strauss syndrome (CSS) is a rare, idiopathic systemic vasculitis. There is emerging evidence of an association between the presence or absence of antineutrophil cytoplasmic antibodies (ANCA) and clinical phenotype. Thromboembolism is an increasingly recognised complication of the disease. AIMS: Given the paucity of Australian data, the aim of this study was to examine the clinical and laboratory features of CSS in a single Australian centre. METHODS: We performed a retrospective review of all patients who fulfilled the American College of Rheumatology classification criteria for CSS managed at the Department of Immunology, Royal Adelaide Hospital between 2002 and 2008. RESULTS: Nineteen patients were included. All patients had asthma and most had upper airway involvement. Peripheral nerve, musculoskeletal, gastrointestinal and cutaneous involvement was common. Renal and cardiac involvement was uncommon in this series. Histological confirmation was obtained in 15 patients (78.9%). Ten patients (52.6%) were ANCA+, and these were more likely to have musculoskeletal involvement, such as arthralgia or myalgia (odds ratio 57, P = 0.005). Thrombosis was a feature at diagnosis in six patients (31.6%); two of these recurred with relapse. Sixteen patients (84.2%) were followed up; five died, and mean survival was 8.9 years. CONCLUSIONS: This is the first Australian study to focus on CSS. Our results demonstrate similar presentation and prognosis of CSS to previous descriptions; however, we noted that musculoskeletal involvement was more common in ANCA+ patients. In our series, thrombosis was a significant complication and we suggest that thromboprophylaxis may be warranted.

Efficacy of rituximab in refractory antisynthetase syndrome.

We report the successful use of repeated administration of rituximab in a patient with antisynthetase syndrome refractory to conventional immunosuppressive medications. A literature review revealed that previous experience with rituximab in this condition has been sparse. The rationale for the use of B-cell depleting therapies in antisynthetase syndrome has been explored in light of the current understanding of the pathogenesis of this condition.

Utility of peripheral blood B cell subsets analysis in common variable immunodeficiency.

Abnormalities in peripheral blood B cell subsets have been identified in common variable immunodeficiency (CVID) patients and classification systems based upon their numbers have been proposed to predict the clinical features. We analysed B lymphocyte subsets by multi-colour flow cytometry (MFC) in a cohort of well-characterized CVID patients to look at their clinical relevance and validate the published association of different classification criteria (Freiburg, Paris and Euroclass) with clinical manifestations. CVID patients had a reduced proportion of total and switched memory B cells (MBC, swMBC) compared to normal controls (P < 0·0006). Patients classified in Freiburg Ia had a higher prevalence of granulomatous diseases (P = 0·0034). The previously published associations with autoimmune diseases could not be confirmed. The Euroclass classification was not predictive of clinical phenotypes. The absolute numbers of all B cell subsets were reduced in CVID patients compared to controls. There was a significant linear correlation between low absolute total B cells and MBC with granulomatous disease (P < 0·05) and a trend towards lower B cells in patients with autoimmune diseases (P = 0·07). Absolute number of different B cell subsets may be more meaningful than their relative percentages in assessing the risk of granulomatous diseases and possibly autoimmunity.

Pharmacokinetics and safety of Intragam 10 NF, the next generation 10% liquid intravenous immunoglobulin, in patients with primary antibody deficiencies.

BACKGROUND AND AIMS: Intragam® 10 NF is the next generation 10% intravenous immunoglobulin with three pathogen reduction steps and a noncarbohydrate stabiliser. This open label, cross-over study in patients with primary immunodeficiency was designed to evaluate whether Intragam 10 NF differed in its pharmacokinetics (PK) compared with Intragam P and to assess Intragam 10 NF safety and tolerability. METHODS: Nineteen primary immunodeficiency patients were administered one cycle of their existing Intragam P dose (0.2-0.8 g/kg 3-4 weekly), followed by seven cycles of Intragam 10 NF administered at the same dosing schedule as Intragam P. The primary objective was to compare serum immunoglobulin G (IgG) trough levels. Secondary endpoints were PK variables, safety and tolerability. RESULTS: There was no significant within-patient difference in the average trough immunoglobulin G concentration between Intragam P and Intragam 10 NF (8.76 g/L, 8.55 g/L respectively) (geometrical mean ratio 1.034; 95% confidence interval 0.996-1.073; P = 0.079). Mean PK parameters for both products were similar, with all 95% confidence interval encompassing 1.0 except for time to maximum concentration. Time to maximum concentration occurred earlier with Intragam 10 NF compared with Intragam P, with a shorter infusion time (mean 1.75 h vs 2.52 h respectively; P < 0.05). Headache was the most frequent treatment-related event following both products. There were no study withdrawals, deaths, or notable changes in laboratory values or vital signs. CONCLUSION: Intragam 10 NF was well tolerated and exhibited similar PK to Intragam P, with the advantage of a 45 min shorter infusion time.

Oral drug challenges in non-steroidal anti-inflammatory drug-induced urticaria, angioedema and anaphylaxis.

BACKGROUND: Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). AIM: To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. METHODS: Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. RESULTS: Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. CONCLUSION: In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAID-induced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs.

Survival in scleroderma: results from the population-based South Australian Register.

AIM: To ascertain the mortality risk and investigate clinical and serological factors influencing survival of patients listed on the South Australian Scleroderma Register (SASR). METHODS: The SASR is a population-based register, which was commenced in 1993 and has actively sought to recruit all scleroderma patients diagnosed in SA over a 15-year period. Clinical and serological details have been accessed from questionnaires or from clinical and laboratory files. Standardized mortality ratio (SMR) was calculated and survival analyses performed on all living and deceased patients listed on this SASR (n = 786). RESULTS: Patients with scleroderma had increased mortality compared with the general SA population (SMR 1.46 (95% confidence interval (CI) 1.28-1.69)). Factors that adversely altered survival included older age at onset, male gender, diffuse skin involvement, presence of scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer and anti-topoisomerase (Scl-70) and anti-U1 RNP antibodies, while a trend was observed with increased nailfold capillary dropout. Mean age of death for patients with limited scleroderma was 74.1 years (95% CI 72.5-75.7), diffuse scleroderma 62.9 years (95% CI 59.4-66.4) and overlap disease 57.8 years (95% CI 48.7-66.9). Survival improved over the 15-year study period. CONCLUSIONS: Scleroderma substantially reduces life expectancy. Survival is influenced by age at onset, gender, diffuse involvement of skin fibrosis, visceral involvement, development of cancer, extent of microvascular capillary damage and by the presence of scleroderma-associated antibodies, Scl-70 and RNP. Scleroderma renal crisis continues to carry high mortality. Survival improved over the 15-year study period.

The presence of leukaemia-associated phenotypes is an independent predictor of induction failure in acute myeloid leukaemia.

Immunophenotyping of acute myeloid leukaemia (AML) has controversial implications with regards to prognosis. The aims of the present study were to determine the frequency of leukaemia-associated phenotypes (LAP) in AML and to correlate their presence with response to induction chemotherapy. We analysed bone marrow samples at diagnosis from 84 AML patients using triple staining flow cytometry with routine standard panel of monoclonal antibodies. The association of LAP and response to induction chemotherapy was evaluated retrospectively. LAP were observed in 54 (64%) patients: lineage infidelity in 19 (35%), asynchronous antigen expression in 28 (52%), and lack of expected lineage specific antigens in 19 (35%). Significant correlation was found between LAP and responses to induction chemotherapy. Response to induction chemotherapy was more frequent in the absence of LAP (P < 0.05, estimated risk ratio of 1.6, 95%CI, 1.0-2.6) in a multivariate analysis. In conclusion, our data show the presence of LAP in AML is an independent predictor for response to induction chemotherapy and risk of relapse and should be considered for counselling patients and planning therapy.

Wegener's granulomatosis: epidemiological and clinical features in a South Australian study.

BACKGROUND: The epidemiology of Wegener's granulomatosis (WG) has shown a latitude-dependent predisposition in Northern Hemisphere and in New Zealand. There are no studies describing epidemiology or long-term follow up of WG reported from Australia. The aims of this study were to describe the epidemiological and clinical features of WG in South Australia (SA). METHODS: The 5-year incidence of WG in SA over the period 2001-2005 was determined using the International Classification of Diseases classification (M313) of the discharge diagnosis using the Integrated South Australian Activity Collection. A retrospective case record analysis of 30 patients fulfilling the American College of Rheumatology criteria for WG and managed at two regional hospitals over a 20-year period (1985-2004) was carried out. RESULTS: The 5-year incidence of WG in SA was 56 per 10(6) (95% confidence interval 44.1-68.4 per 10(6)). There were no regional or seasonal variations in disease occurrence. The demographic, clinical and serological features in the clinical study were similar to previously published studies. Significant treatment-related morbidity was noted with 50% of patients having atherosclerotic vascular complications. The median survival was 12 years. There were two important periods with greater risk of dying -- in the first 5 years and after 10 years. CONCLUSION: The 5-year incidence of WG in SA is higher than that in the same latitudinal region in New Zealand ( approximately 34 degrees S). Atherosclerotic vascular disease was a major long-term morbidity. There is increased incidence of early mortality, warranting the need for earlier diagnosis and better therapies. Further studies from Southern Hemisphere are required for better epidemiological description of this disease.

Chronic urticaria: the autoimmune paradigm.

Chronic urticaria is a disease consisting of spontaneous pruritic welts, present on all or most days for more than 6 weeks. It is commonly supposed to be allergic in origin, although allergy is not the cause in the majority of cases, and it has therefore been termed 'chronic idiopathic urticaria'. Recent evidence indicates that at least a subset of patients in whom no extrinsic or internal cause can be identified are in fact autoimmune in origin. This is based mainly on the detection of pathogenic autoantibodies to the high-affinity immunoglobulin E receptor FcepsilonR1, which are thought to activate cutaneous mast cells. In this article, we review the evidence that has given rise to this autoimmune 'paradigm' and its impact on diagnosis and management.

Angioedema, lymphoproliferative disorder and angiotensin-converting enzyme inhibitors: masking of diagnosis by corticosteroids.

Angioedema is a relatively common clinical disorder. Although most cases are idiopathic, the use of angiotensin-converting enzyme inhibitors is a well recognized cause of angioedema and a further rare but important diagnostic consideration is acquired C1 inhibitor deficiency. We discuss the diagnosis of C1 inhibitor deficiency in angioedema, with reference to a case in which the diagnosis was initially masked by the use of corticosteroids, which normalized the C1 inhibitor level.

Rituximab use in systemic lupus erythematosus pneumonitis and a review of current reports.

Rituximab is a chimeric monoclonal antibody specific for human CD20 that causes selective transient depletion of the CD20+ B-cell subpopulation. We report the first case of systemic lupus erythematosus (SLE) pneumonitis resistant to conventional treatments that responded well to rituximab and review current reports on the use of rituximab in SLE.

Primary Sjogren's syndrome: rarity in India.

OBJECTIVE: Primary Sjogren's syndrome (SS) is rarely reported from India. We have studied the clinical spectrum and immunological profile of patients with primary SS. METHODS: A prospective analysis of patients with primary Sjogren's syndrome fulfilling San Francisco criteria, seen at our clinic in the last 10 years was carried out. RESULTS: The study included 26 patients, 21 being women. The presenting symptoms included dry eyes, dry mouth, and arthritis/arthralgia. Extra-glandular manifestations were glomerulonephritis, vasculitis, renal tubular acidosis and peripheral neuropathy. The important laboratory abnormalities were hypergammaglobulinaemia (16/20), antinuclear antibodies (18/26), anti-La (11/19) and anti-Ro (10/19). Minor salivary gland provided a definitive diagnosis in 16/26 (60%). CONCLUSION: The prevalence of primary Sjogren's syndrome is rare even in tertiary care rheumatology clinics. The clinical and immunological profile as seen here is similar to that reported in Western countries.