The efficacy and safety of systemic corticosteroids as first line treatment for granulomatous lymphocytic interstitial lung disease.

BACKGROUND: Granulomatous and lymphocytic interstitial lung disease (gl-ILD) is a major cause of morbidity and mortality among patients with common variable immunodeficiency. Corticosteroids are recommended as first-line treatment for gl-ILD, but evidence for their efficacy is lacking. OBJECTIVES: This study analyzed the effect of high-dose corticosteroids (≥0.3 mg/kg prednisone equivalent) on gl-ILD, measured by high-resolution computed tomography (HRCT) scans, and pulmonary function test (PFT) results. METHODS: Patients who had received high-dose corticosteroids but no other immunosuppressive therapy at the time (n = 56) and who underwent repeated HRCT scanning or PFT (n = 39) during the retrospective and/or prospective phase of the Study of Interstitial Lung Disease in Primary Antibody Deficiency (STILPAD) were included in the analysis. Patients without any immunosuppressive treatment were selected as controls (n = 23). HRCT scans were blinded, randomized, and scored using the Hartman score. Differences between the baseline and follow-up HRCT scans and PFT were analyzed. RESULTS: Treatment with high-dose corticosteroids significantly improved HRCT scores and forced vital capacity. Carbon monoxide diffusion capacity significantly improved in both groups. Of 18 patients, for whom extended follow-up data was available, 13 achieved a long-term, maintenance therapy independent remission. All patients with relapse were retreated with corticosteroids, but only one-fifth of them responded. Two opportunistic infections were found in the corticosteroid treatment group, while overall infection rate was similar between cohorts. CONCLUSIONS: Induction therapy with high-dose corticosteroids improved HRCT scans and PFT results of patients with gl-ILD and achieved long-term remission in 42% of patients. It was not associated with major side effects. Low-dose maintenance therapy provided no benefit and efficacy was poor in relapsing disease.

Idiopathic anaphylaxis.

Idiopathic anaphylaxis (IA) or spontaneous anaphylaxis is a diagnosis of exclusion when no cause can be identified. The exact incidence and prevalence of IA are not known. The clinical manifestations of IA are similar to other known causes of anaphylaxis. A typical attack is usually acute in onset and can worsen over minutes to a few hours. The pathophysiology of IA has not yet been fully elucidated, although an IgE-mediated pathway by hitherto unidentified trigger/s might be the main underlying mechanism. Elevated concentrations of urinary histamine and its metabolite, methylimidazole acetic acid, plasma histamine and serum tryptase have been reported, consistent with mast cell activation. There is some evidence that corticosteroids reduce the frequency and severity of episodes of IA, consistent with a steroid-responsive condition. Important differential diagnoses of IA include galactose alpha-1,3 galactose (a carbohydrate contained in red meat) allergy, pigeon tick bite (Argax reflexus), wheat-dependent exercise-induced anaphylaxis, Anisakis simplex allergy and mast cell disorders. Other differential diagnoses include "allergy-mimics" such as asthma masquerading as anaphylaxis, undifferentiated somatoform disorder, panic attacks, globus hystericus, vocal cord dysfunction, scombroid poisoning, vasoactive amine intolerance, carcinoid syndrome and phaeochromocytoma. Acute treatment of IA is the same as for other forms of anaphylaxis. Long-term management is individualized and dictated by frequency and severity of symptoms and involves treatment with H1 and H2 receptor blockers, leukotriene receptor antagonist and consideration for prolonged reducing courses of oral corticosteroids. Patients should possess an epinephrine autoinjector with an anaphylaxis self-management plan. There are anecdotal reports regarding the use of omalizumab. For reasons that remain unclear, the prognosis of IA is generally favourable with appropriate treatment and patient education. If remission cannot be achieved, the diagnosis should be reconsidered.

Isolating polysaccharide IgG pneumococcal antibody responses by pre-adsorption of conjugate vaccine serotypes: A modified approach for the conjugate vaccine era.

BACKGROUND: Assessment of pure polysaccharide response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) can be biased by previous exposure to the conjugate vaccine (PCV). We applied pre-analytical modification to the existing ELISA by pre-incubating serum with PCV. METHODS: PCV-adsorbed and non-adsorbed sera were prepared before measuring the concentration of anti-pneumococcal capsular polysaccharide (PCP) IgG antibodies by the whole pneumococcal ELISA. Paired pre and post-pneumococcal vaccination sera from 73 subjects were analyzed and the baseline anti-PCP IgG for each sample was subtracted from the post-vaccination value to measure vaccine responses. Absolute change in titers and fold changes were then compared between both methods. RESULTS: In the PCV-vaccinated group (n = 28), pre-adsorption with PCV significantly reduced the vaccine responses compared to non-adsorbed sera [median increase in anti-PCP titers: 27.55 mg/l and 45.98 mg/l, respectively]. In addition, the median fold change dropped significantly from 3.026 to 2.313. In PPV23-vaccinated immunocompetent subjects (n = 28) there was a significant difference in anti-PCP responses with PCV adsorption [median values: 73.71 mg/l without and 51.04 mg/l with adsorption]. All the antibody deficiency patients (n = 17) displayed poor PPV23 responses. Although PPV23 responsiveness was not statistically different between both methods, we have observed a trend for lower anti-PCP IgG titers in PCV-adsorbed sera compared to non-adsorbed ones. Serotype-specific IgG analysis using a multiplexed bead-based immunoassay performed on 10 paired samples confirmed that the adsorption observed is specific to PCV serotypes. CONCLUSION: Pre-analytical modification to the conventional ELISA by removing the PCV-specific serotypes may differentiate true polysaccharide response from recall response induced by previous PCV vaccination.

Empty mast cell syndrome: fallacy or fact?

Post-anaphylaxis mast cell anergy (PAMA), commonly referred to as 'empty mast cell (MC) syndrome', is a state of temporary loss of cutaneous MC reactivity in the immediate aftermath of anaphylaxis. Data relating to this condition are sparse and the incidence rate is currently unknown. PAMA has been described only in a few published case reports in the context of hymenoptera venom allergy and perioperative anaphylaxis. Best practice guidelines regarding optimal timing for performing skin tests postanaphylaxis are largely based on expert opinion, and allergy work-up has been recommended after 4-6 weeks postanaphylaxis to avoid false-negative results.This article provides a review of clinical literature surrounding PAMA, critically evaluates intracellular events in MCs from in vitro data and hypothesises regarding plausible immune mechanisms. There are no published data to directly explain molecular mechanisms underlying this phenomenon. Although not evidence based, PAMA has been attributed to depletion of MC granules following anaphylaxis. It is also plausible that exposure to high allergen concentrations in anaphylaxis can induce a temporary shift in MCs towards dominance of inhibitory signalling pathways, thus contributing to a state of transient hyporesponsiveness observed in some patients. Other potential contributory factors for reduced MC reactivity include downregulation of FcεRI expression, cross-linking of FcεRI to the inhibitory, low-affinity IgG receptors and administration of pharmacotherapeutic agents for anaphylaxis treatment. It is likely that this interesting phenomenon can be explained by a combination of these proposed mechanisms in addition to other genetic/host factors that have not yet been identified.

A Retrospective Critical Analysis and Risk Stratification of Penicillin Allergy Delabeling in a UK Specialist Regional Allergy Service.

BACKGROUND: A spurious label of penicillin allergy (Pen-A) negatively impacts on antibiotic stewardship and health care costs. Recent studies have proposed a guideline-steered direct penicillin challenge without undertaking allergy tests when "true allergy" is unlikely. OBJECTIVE: To critically analyze Pen-A clinical presentation, perform risk stratification, and determine clinical predictors for "true allergy." METHOD: Data were extracted retrospectively from clinical and electronic patient records. RESULTS: A total of 231 patients (M = 82; F =149; mean age 51.22 [standard deviation ± 18.07] years) were analyzed. Based on clinical history, patients were categorized as likely type I hypersensitivity reaction (HSR) (n = 27), likely type IV HSR (n = 65), indeterminate (n = 111), and HSR unlikely (n = 28). Based on an index reaction and comorbidities, patients were classified into "low risk" (n = 143) and "high risk" (n = 78). Pen-A was excluded in 74% of patients assessed having likely type I HSR, 91% with likely type IV HSR, 93% of indeterminate, and 100% of HSR unlikely patients. The negative predictive value for successful delabeling in the "low risk" group was 94% (odds ratio [OR] = 2.9; P = .02). Predictors for "true Pen-A" were history of anaphylaxis (OR = 30.6; P < .001), hospitalization (OR = 7; P < .001), ≤5 years since the index reaction (OR = 3; P = .04). CONCLUSIONS: Systematic clinical characterization and risk stratification has an important role in Pen-A delabeling. These data provide proof of concept for a guideline-based selection of patients labeled with Pen-A for a direct penicillin challenge. Patients in the "low risk" group seem suitable for this intervention, although a rigorous prospective evaluation is needed in a multicenter study.

Unexplained abnormal liver function in patients with primary antibody deficiency: could it be chronic hepatitis E infection?

Data from recent studies suggest rising incidence rate of hepatitis E virus (HEV) infection in the UK. HEV infection may take a severe and persistent course in immunocompromised patients, including transplant recipients on immunosuppressives, patients with HIV, haematological malignancies and in idiopathic CD4+ T lymphocytopenia. The prevalence of HEV in primary antibody deficiency (PAD) disorders is still unknown. The aim of this study was to investigate HEV infection in 27 patients with PAD with unexplained, persistently elevated liver enzymes. Although all the 27 patients tested negative for HEV-RNA, we would still strongly recommend that HEV should be considered in any immunodeficient patient with impaired liver function.

Acute-phase proteins in pregnant Sudanese women with severe Plasmodium falciparum malaria.

A case-control study was carried out in Kassala and Medani Maternity Hospitals in Sudan to investigate acute-phase proteins [haptoglobin, C-reactive protein (CRP), ferritin and albumin] in three groups of pregnant women (32 in each arm) comprising those with severe Plasmodium falciparum malaria or uncomplicated P. falciparum malaria and healthy controls. Whilst there was no significant difference in the levels of albumin and haptoglobin, ferritin and CRP levels were significantly higher in pregnant women with severe P. falciparum malaria. There were significant positive correlations between parasite count and haptoglobin, and medium positive correlations between parasite count and CRP.