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Pneumocystis carinii infection is rare in infants, and raises strong concerns of immune deficiency. This report describes the unusual case of a male infant with concurrent chest infections caused by [...]

*The UK incidence of anaphylactic reactions is increasing. *Patients who have an anaphylactic reaction have life-threatening airway and, or breathing and, or circulation problems usually associated with skin or mucosal changes. *Patients having an anaphylactic reaction should be treated using the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. *Anaphylactic reactions are not easy to study with randomised controlled trials. There are, however, systematic reviews of the available evidence and a wealth of clinical experience to help formulate guidelines. *The exact treatment will depend on the patient's location, the equipment and drugs available, and the skills of those treating the anaphylactic reaction. *Early treatment with intramuscular adrenaline is the treatment of choice for patients having an anaphylactic reaction. *Despite previous guidelines, there is still confusion about the indications, dose and route of adrenaline. *Intravenous adrenaline must only be used in certain specialist settings and only by those skilled and experienced in its use. *All those who are suspected of having had an anaphylactic reaction should be referred to a specialist in allergy. *Individuals who are at high risk of an anaphylactic reaction should carry an adrenaline auto-injector and receive training and support in its use. *There is a need for further research about the diagnosis, treatment and prevention of anaphylactic reactions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether online resources developed to educate people about the risks associated with experimental stem cell (SC) treatments influence stroke survivors' attitudes about the safety and effectiveness of these treatments., Methods: Adult stroke survivors who had not previously received SC treatments (N = 112) were recruited from international stroke advocacy/support groups for a prospective, parallel-group randomized controlled trial. Participants indicated whether they were considering SC treatments (yes/no) prior to, immediately following, and 30-days after reading/viewing the International Society for Stem Cell Research booklet or Stem Cell Network video. Participant attitudes regarding the safety, effectiveness, accessibility and affordability of SC treatments were examined on each occasion, and compared to those of a waitlist control group., Results: Significantly fewer participants were considering SC treatments immediately after reading the SC research booklet (p =.031), although neither intervention had any impact after 30-days (p >.05). Waitlist and intervention groups reported positive attitudes toward SC treatments at each assessment., Conclusions: Stroke survivor attitudes toward SC treatments were initially influenced by the patient booklet, however these changes were not maintained., Practical Implications: Clinicians are encouraged to initiate discussions about experimental SC treatments during inpatient rehabilitation and to reinforce the risks throughout subsequent care., Competing Interests: Declaration of Competing Interest The authors declare no interests., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Purpose: Interest in stem cell treatments is increasing among some patient groups, but it is unclear whether this holds true for stroke survivors. This study examined stroke survivor attitudes toward stem cell treatments and identified a number of variables that may increase the likelihood that patients will consider these treatments. Methods: Adult stroke survivors ( N  = 183) were recruited (stroke advocacy/support groups, outpatient register) for a cross-sectional study. Attitudes to stem cell treatments were surveyed, guided by the Theory of Planned Behavior. Demographic information was collected, and a number of self-report medical, cognitive and psychological measures completed. Results: Twenty-five percent ( n  = 46) of respondents indicated they were considering undergoing stem cell treatments, although most were unsure about the safety/effectiveness and accessibility/affordability. Stroke survivors with positive attitudes toward stem cell treatments, longer post-stroke intervals, poorer physical functioning, younger age, and greater perceived caregiver burden were more likely to be considered experimental treatments (odds ratios = 1.22, 1.08, 0.95, 0.96, 1.07; respectively). Conclusions: Stroke survivors may consider undergoing experimental stem cell treatments despite uncertainty regarding the risks/benefits. Clinicians should be mindful of the factors that may increase the likelihood of patients considering these treatments and intervene, where appropriate, to clarify any misconceptions regarding the medical/financial risks.IMPLICATION FOR REHABILITATIONStem cell treatments offer a new focus for reducing stroke-related disability, although their safety and effectiveness have yet to be established.Despite uncertainty regarding the medical risks and benefits associated with stem cell injections, stroke survivors may still consider undergoing treatment in private, unregulated clinics.A number of factors, including younger age, longer post-stroke interval, poorer physical functioning, and perceived caregiver burden may place stroke survivors at an increased risk of considering these treatments.Clinicians should endeavor to educate stroke survivors regarding the risks and benefits of these experimental treatments and clarify any misconceptions, in order to reduce the likelihood that they will consider these as-yet unproven treatments.

Goal: Depression and anxiety are important complications of stroke but are underdiagnosed in community settings. The current study identified which patients were at increased risk of developing either disorder more than1 year poststroke to assist in targeted screening., Methods: Crosssectional survey of 147 adults who had a stroke more than 1 year ago were recruited from stroke advocacy/support groups and an outpatient register. Participants completed the Hospital Anxiety and Depression Scale (HADS) and reported whether they had emotional problems as a stroke inpatient (single item: yes/no). Standardized self-report measures evaluated medical (physical independence, health-related quality of life), cognitive (memory, executive functioning), and psychological (social support) variables. Demographic and stroke-related (stroke type, year) information were also recorded., Findings: Between 53% and 80% of respondents (n = 117) screened positive for depressed mood and/or anxiety (HADS subscale cut-offs: ≥8 or ≥4). Logistic regression analyses indicated that stroke survivors who reported having emotional problems as inpatients (odds ratio [OR]: 0.23), were female (OR: 3.42), and had poor health-related quality of life (OR: 0.45-0.53) and cognitive problems (OR: 0.68-0.74), were more likely to screen positive for either disorder. Models based on these variables predicted screening outcomes with 91% accuracy., Conclusions: Community-based stroke survivors who reported experiencing emotional problems as inpatients, were female, or had poor health-related quality of life (chronic pain, disturbed sleep, communication difficulties) and/or cognitive issues were at greater risk of being depressed/anxious. Targeted screening of these patients may help to identify those who are most in need of more comprehensive clinical assessments and evidence-based interventions., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Alcohol and substance (drugs and/or alcohol) abuse are major risk factors for traumatic brain injury (TBI); however, it remains unclear whether outcomes differ for those with and without a history of preinjury abuse. A meta-analysis was performed to examine this issue. The PubMed, Embase, and PsycINFO databases were searched for research that compared the neuroradiological, cognitive, or psychological outcomes of adults with and without a documented history of alcohol and/or substance abuse who sustained nonpenetrating TBIs. Data from 22 studies were analyzed using a random-effects model: Hedges's g effect sizes measured the mean difference in outcomes of individuals with/without a history of preinjury abuse, and Bayes factors assessed the probability that the outcomes differed. Patients with a history of alcohol and/or substance abuse had poorer neuroradiological outcomes, including reduced hippocampal (g = -0.82) and gray matter volumes (g = -0.46 to -0.82), and enlarged cerebral ventricles (g = -0.73 to -0.80). There were limited differences in cognitive outcomes: Executive functioning (g = -0.51) and memory (g = -0.39 to -0.43) were moderately affected, but attention and reasoning were not. The findings for fine motor ability, construction, perception, general cognition, and language were inconclusive. Postinjury substance and alcohol use (g = -0.97 to -1.07) and emotional functioning (g = -0.29 to -0.44) were worse in those with a history of alcohol and/or substance abuse (psychological outcomes). This study highlighted the type and extent of post-TBI differences between persons with and without a history of alcohol or substance abuse, many of which may hamper recovery. However, variation in the criteria for premorbid abuse, limited information regarding the history of abuse, and an absence of preinjury baseline data prevented an assessment of whether the differences predated the TBI, occurred as a result of ongoing alcohol/substance abuse, or reflected the cumulative impact of alcohol/substance abuse and TBI.

Aim: To assess the safety and efficacy of cell therapies for chronic stroke., Methodology: Five databases were searched for treatments administered >90 days post-stroke. Reporting quality, adherence to research guidelines, treatment safety (risk ratios/pooled incidence rates) and neurological/functional efficacy (Hedge's g) were all evaluated., Results: Twenty-three studies examined 17 treatments. Reporting quality scores were medium to high, but adherence to recommended guidelines was lower. Three treatments resulted in serious adverse events; four improved outcomes more than standard care. However, many studies were under-powered and individual patients varied in their response to some treatments., Conclusion: Preliminary findings suggest that some cell therapies may be relatively safe and effective, but larger double-blinded placebo-controlled studies are needed to establish the long-term risks and benefits.

Aims: To evaluate the safety and efficacy of cell therapies administered acutely/sub-acutely after stroke., Methods: Five databases were searched for studies examining the safety/efficacy of cell therapies administered ≤90 days post-stroke. Reporting quality and adherence to research guidelines were evaluated. Safety and efficacy were assessed using risk ratios/pooled incidence rates and Hedge's g, respectively., Results: 11 therapies (Nstudies= 28) were trialed: reporting quality was high, but adherence to guidelines low. Serious adverse events were observed following five treatments; six improved outcomes. There was a trend toward larger treatment effects in non-blinded studies, younger participants, and higher dosages., Conclusion: Although a number of therapies appear effective, many studies did not control for normal recovery (standard-care). Long-term safety also needs to be established.

Therapeutic immunoglobulin G (IgG) products are produced from numerous plasma donations, and are infused in many medical conditions. The serological testing of patients who have received IgG infusions may well produce falsely positive and misleading results from this infused IgG, rather than endogenously produced IgG. We present two example cases of clinical situations where this could cause concern. We tested multiple IgG products with a range of serological tests performed in infective or autoimmune conditions, including hepatitis B, syphilis, human immunodeficiency virus, human T-lymphotropic virus, anti-neutrophil cytoplasmic antibody (ANCA), anti-nuclear antibody (ANA), anti-cardiolipin antibodies and anti-double stranded DNA (dsDNA) antibody. We found positivity within these products for hepatitis B surface and core antibody, syphilis, ANCA, ANA, anti-cardiolipin IgG and dsDNA antibody, which may result from specific or non-specific reactivity. The serological testing of patients who have received IgG treatment detects the administered IgG in addition to IgG produced by the patient., (© 2015 Royal College of Physicians.)

Suspected adverse drug reactions may be subdivided on the basis of mechanism e.g. immunological (requiring sensitisation by previous exposure) versus nonimmunological; timing (e.g. immediate or delayed), or whether the phenomenon is dose dependent or not. In the NICE guideline the main approach is to classify the event according to whether it: is immediate (within an hour of drug administration) or delayed (hours or days); affects a single or multiple systems; is clinically severe/life threatening or not. An immediate, immunologically mediated, multisystem, life-threatening reaction would for example include anaphylaxis (type 1 or typically IgE- mediated hypersensitivity) especially if the clinical features (e.g. bronchospasm, hypotension) are suggestive. Serum mast cell tryptase should be tested ideally within two hours and certainly before four hours post reaction. Detailed investigation of suspected cases in a specialist clinic is ideally delayed for 4-6 weeks after the event. Adverse drug reactions need to be meticulously recorded and the patient fully informed. Documentation should include: date of reaction; drug name (chemical and generic); route of administration; time interval between first dose and event; and nature and severity of symptoms. Written guidance should be provided on which other chemically related drugs also need to be avoided. Specialist referral is indicated for: suspected anaphylaxis; severe/life- threatening episodes e.g. Stevens-Johnson syndrome; severe NSAID reactions with ongoing need for NSAID therapy; suspected penicillin allergy (if alternative antibiotics are not available); and problems related to general and local anaesthesia.

Background: Anaphylaxis is increasing in incidence. This potentially fatal condition requires immediate intramuscular adrenaline as a vital part of early treatment. A 2002 survey of UK Senior House Officers showed a lack of knowledge regarding the recognition and management of anaphylaxis. Since then major changes in medical education and updated national guidelines have aimed to ensure that doctors can recognise and treat anaphylaxis appropriately., Objectives: To determine current knowledge concerning the recognition and management of anaphylaxis among junior doctors compared to their predecessors., Methods: Using the same methodology as in 2002, we asked 68 Foundation doctors to read five clinical scenarios potentially suggesting anaphylaxis and indicate how they would respond to each case. Their results were compared to those of Senior House Officers in 2002., Results: 68 of 107 (64%) junior doctors completed the questionnaire. All recognised the need for adrenaline in anaphylaxis, but only 74% selected the correct intramuscular route, and 34% the correct route and dose. 82% of junior doctors would inappropriately give adrenaline to the patient who had inhaled a foreign body (case 2). A higher percentage of the 2013 cohort indicated the correct route and dose of adrenaline in anaphylaxis than their 2002 colleagues. However, a greater percentage also selected adrenaline treatment inappropriately in non-anaphylactic case scenarios., Conclusions: Despite updated guidelines, junior doctors continue to have poor knowledge about the recognition and management of anaphylaxis, with some still considering inappropriate intravenous adrenaline. More effort should be given to the recognition of anaphylaxis in early medical training., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Primary immunodeficiency is seen in an estimated one in 1200 people, and secondary immunodeficiency is increasingly common, particularly with the use of immunosuppresion, cancer therapies and the newer biological therapies such as rituximab. Delays in the diagnosis of immunodeficiency predictably lead to preventable organ damage. Examples of abnormal pathology tests that suggest immunodeficiency from all laboratory specialities are given, where vigilant interpretation of abnormal results may prompt earlier diagnosis. If immunodeficiency is suspected, suggested directed testing could include measuring immunoglobulins, a lymphocyte count and T-cell and B-cell subsets., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Complement dysregulation from an uncontrolled activation of the alternate pathway can be mediated by C3 Nephritic Factor and results in C3 glomerulopathy. Identification of C3 degradation products C3c and C3d in patient serum provides evidence of uncontrolled complement activation. It is possible to detect C3c and C3d in patient serum by an immunofixation assay which induces in vitro C3 degradation. The clinical performance of the immunofixation assay has been assessed by comparing the assay results with findings from immunostaining of kidney biopsies. The immunofixation assay is a simple and reliable technique for detection of C3 degradation on a widely available platform and can be used to provide corroborative evidence of acquired complement dysregulation in patients with C3 glomerulopathy., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Food allergy (IgE-mediated hypersensitivity) is a common clinical problem affecting approximately 15% of children in the Western world. These hypersensitivity reactions tend to be "immediate" (typically within minutes of food exposure), and clinical features may range from mild to life threatening (anaphylaxis). Detailed clinical history is critical to correct diagnosis. Available laboratory tests have limitations not least poor positive predictive value and limited repertoire. Laboratory tests should support clinical diagno sis not vice versa.

Aims: A review of practice to determine whether serum-free light chain (SFLC) assays are helpful in detecting underlying clonal B-cell disorders or amyloidosis in patients with primary antibody deficiency (PAD) and recurrent infection., Methods: SFLC were assayed by nephelometry (BN2 nephelometer, Siemens; FREELITE assay, Binding Site). We reviewed SFLC test results recorded in our regional laboratory over a 4-year time period; 20 adults with PAD were identified as having been tested on at least two occasions., Results: Of 20 patients, 4 with PAD had abnormal serum-free kappa/lambda (K/L) ratios but no evidence of B-cell clonality. We also found extremely low levels of kappa and or lambda (below the limits of reliable detection) in 19/20 PAD cases (mostly common variable immunodeficiency), such that in many, ratios were not calculable., Conclusions: The data suggest that the abnormal ratios are generated by an inability to produce and/or secrete SFLCs, particularly kappa FLC. In this small initial study, we seek to highlight PAD cases where a suspicious K/L ratio, typically with very low absolute quantities of SFLCs, most likely points to B-cell dysfunction, rather than to B lymphocyte clonality.

We present a serendipitous case of clinically significant pan-hypogammaglobulinaemia, diagnosed after routine serological testing for possible coeliac disease led first to identification of IgA deficiency (discovered as a low background in IgA-based routine serological screening), and subsequently to confirmed pan-hypogammaglobulinaemia (antibody immunodeficiency). Hypogammaglobulinaemia is a relatively rare diagnosis (estimated at 1 in 36,000), in which delayed diagnosis and treatment are associated with chronic organ damage including bronchiectasis. Routine serological testing for coeliac disease using the IgA anti-tissue transglutaminase (IgA TTG) test is in widespread use and provides an opportunity for early diagnosis of hypogammaglobulinaemia. Routine serological screening for coeliac disease may uncover IgA deficiency, and we suggest that all IgA-deficient cases identified should also be checked for antibody deficiency by quantifying the other immunoglobulins (IgG, IgM).

Anaphylaxis is defined as a severe, life-threatening, generalised or systemic hypersensitivity reaction. Diagnosis is based on the presenting symptoms and signs which classically develop rapidly, typically evolving over minutes but in some cases hours. Various combinations of airway and/or breathing and/or circulatory problems are possible, as well as urticaria, and hypotension. Skin and/or mucosal changes (typically urticaria and/or angioedema) are seen in around 75% of cases, but importantly these features alone are insufficient for a diagnosis of anaphylaxis. As soon as possible after successful emergency treatment, timed blood samples should be taken for the mast cell tryptase (MCT) test. Serum samples need to be taken within 1-2 hours but no later than 4 hours from the onset of symptoms. It is important to document the acute clinical features (record BP, respiratory rate etc) and the time course of the onset of symptoms/signs and their resolution. Because of the risk of relapse patients should be observed for 6-12 hours after the onset of symptoms. Children under 16 years should be admitted and supervised by a paediatrician. An adrenaline injector device for intramuscular use only, should be prescribed as an interim measure before referral to a specialist allergy clinic. Referral to a specialist allergy service (or specialist paediatric service), is strongly recommended. Diagnosis can be confirmed, and further investigations organised.

Resolution of egg allergy occurs in the majority of egg allergic children. Positive specific IgE antibodies to ovomucoid (OVM) have been suggested to be of greater predictive value for persistent egg allergy than specific IgE to egg white. The performance of OVM-specific IgE antibody levels in a cohort of children referred for a routine egg challenge was compared with egg white specific IgE levels in predicting a positive egg challenge. 24/47 subjects had persistent egg allergy. Receiver operating characteristic analysis showed that OVM-specific IgE testing was the most useful test for the diagnosis of persistent egg allergy. The optimal decision points for the prediction of persistent egg allergy were >0.35 kUA/L for specific IgE levels to both EW and OVM, and ≥3 mm for SPT. Children with specific IgE levels suggestive of persistent egg allergy need not be subject to an egg provocation challenge, reducing both costs and risks to the child.

Background: Patients with primary antibody deficiency often have delayed diagnosis. Very low IgE, found during investigations for allergy, may be a marker for other immunodeficiency., Methods: We introduced a new laboratory policy of testing cases with very low IgE levels for possible linked antibody deficiency. The data represent an audit of routine results collected over two years., Results: Very low IgE (≤2 IU/mL) was identified in 85/2622 (3.2%) routine patient samples. Two children and four adult patients were found to have one or more classes of immunoglobulin below the reference range for age. In 2/6, the initiative of the laboratory led to a new unsuspected diagnosis of antibody immunodeficiency., Conclusions: Common variable immunodeficiency continues to be overlooked as a primary cause of lung disease in adults. Very low serum IgE should trigger appropriate investigation (immunoglobulin quantification and serum electrophoresis).

Adverse reactions to foods may arise by a variety of mechanisms, both immune (IgE and non-IgE) and non-immune mediated. This article considers those assays useful in the diagnosis of Type 1 hypersensitivity to foods (IgE-based) and, importantly, discusses those assays where evidence is lacking for their use. In all cases of suspected food allergy, a full clinical history is indispensable in facilitating diagnosis. Total serum IgE is not a suitable screen for food allergy. Suspect allergens may be confirmed by either skin prick testing or serological assays for specific IgE. Several studies suggest concentrations of food-specific IgE at which there is a high probability of reaction on food challenge. These cut-off levels are now being used by physicians to direct clinical advice. However, it is important to note that not all studies agree on these limits and the chosen cut-off is dependent on the population studied and the assay used.

This article focuses on the immunogenetics, immunology, rejection and immunosuppression in kidney transplantation. HLA matching still affects outcome data, and HLA matching improves graft survival. Graft sources and related outcomes are discussed.

A broad overview, with examples, of the potential pitfalls encountered in the clinical immunology laboratory is presented. Illustrative examples and case scenarios are provided from autoimmunity, immunochemistry and cellular immunology, looking at both technical and interpretative pitfalls.

There are approximately 30 serum complement proteins (15% of the globulin fraction), excluding cell surface receptors, and regulatory proteins. Many are manufactured in the liver, and reduced complement is a feature of severe liver failure. Complement proteins contribute to the acute phase response, and high levels are seen in chronic untreated inflammation (eg, rheumatoid arthritis). Once activated, complement is strongly pro-inflammatory. Indeed, almost half of the complement system proteins/receptors play regulatory roles, reflecting the importance of controlling inappropriate activation. This review focuses on disease states arising as a direct consequence of complement deficiency or dysfunction.

Background: Streptococcal throat infections and HLA Cw6 (Cw*06) have been implicated in the pathogenesis of psoriasis, particularly in the guttate form., Objectives: To study 105 Irish patients with psoriasis to investigate the relationship between streptococcal infections and Cw*06., Methods: The patients were divided into two groups: those with guttate psoriasis or guttate flare (guttate group, GG, n=64) and those with chronic plaque psoriasis (chronic plaque group, CPG, n=41)., Results: The incidence of Cw*06 was 86% in the GG and 73% in the CPG, which was not significantly different (P=0.1725) but the incidence in both groups was significantly higher than in an Irish control group (18%) (P<0.0001 vs. GG and P<0.0001 vs. CPG). Evidence for streptococcal infection was higher in the GG (56%) than in the CPG (32%) (P=0.0231). Of those patients with evidence of streptococcal infection, 30 of 36 GG (83%) and nine of 13 CPG (69%) patients possessed the Cw*06 genotype., Conclusions: Thus, not all patients with streptococcal-related psoriasis carry Cw*06. The role of Cw*06 in psoriasis, if any, has yet to be determined.

"Gluten sensitive" neurological syndromes (ataxia, peripheral neuropathy, and other conditions) have been hypothesised in patients with various idiopathic neuropathologies, detectable anti-gliadin antibodies and HLA-DQ2 or DQ7. Further investigation of these cases has suggested a high incidence of anti-neuronal antibodies (anti-Purkinje, anti- neuronal nuclear, anti-GAD). This study investigates this contentious area. Over a two-year period, from a local UK population base of two million, seeing over 5000 general neurology referrals per year, we collected 20 cases with idiopathic ataxia, and 32 with idiopathic peripheral neuropathy, and referred them all for blinded antibody testing. 30 adult healthy blood donors, and 7 cases of hereditary ataxia were used as control subjects. Anti-gliadin antibodies (IgG and or IgA) were found in 40% of cases with idiopathic ataxia, 34% with idiopathic peripheral neuropathy, 17% healthy blood donors and 43% with hereditary ataxia. None was positive for antiPurkinje cell or anti-neuronal nuclear antibodies. Only two patients with idiopathic ataxia were positive for antiGAD antibodies (one also being anti-gliadin positive). We were unable to confirm the findings of other groups. First, cases of so-called "gluten sensitive" neurological syndromes were extremely rare in our centre. Second, our idiopathic cases, whether they be gliadin antibody seropositive or not (i.e. "gluten sensitive" or not) were rarely neuronal autoantibody positive.

Some authors contend that patients with idiopathic neurological disease who are also anti-gliadin antibody seropositive are gluten sensitive. However, anti-gliadin antibodies lack disease specificity being found in 10% of healthy blood donors. We report a study comparing anti-gliadin antibody with other food antibodies in patients with idiopathic ataxia (20), hereditary ataxias (seven), or idiopathic peripheral neuropathy (32). Patients were HLA typed. IgA anti-tissue transglutaminase antibodies (tTG) were measured. No case was positive for IgA anti-tTG making occult coeliac disease unlikely. HLA DQ2 and HLA DQ8 were found distributed equally across all patient groups and unrelated to gliadin antibody status. HLA DQ2 expressing, anti-gliadin antibody positive cases (so called "gluten ataxia") were rare in our clinics (four cases in 2 years from a population of 2 million). We conclude that coeliac disease per se is not commonly associated with either idiopathic ataxia or idiopathic peripheral neuropathy. Our study also casts doubt on the nosological status of "gluten ataxia" as a discreet disease entity. All food antibodies tested, particularly IgG, were a common finding in both ataxia and peripheral neuropathy groups. No particular food antibody was associated with any patient group. Food antibodies were equally common in hereditary ataxias. We conclude they are a non-specific finding.

We describe a woman with primary Sjögren's syndrome who presented with an acute pulmonary-renal syndrome resulting from cryoglobulinaemic vasculitis. Pulmonary manifestations of Sjögren's syndrome are relatively common, whereas overt pulmonary complications of cryoglobulinaemia are rare. Pulmonary haemorrhage is rare in either disorder. The combination of Sjögren's syndrome, cryoglobulinaemia, and acute pulmonary haemorrhage has not been previously reported.

Objectives: In developed countries, small bowel histology in coeliac disease is a spectrum, ranging from normal with increased intraepithelial lymphocytes to the classic flat mucosa. In developing countries, mild to moderate enteropathies in children with chronic diarrhea and growth failure are assumed to be caused by tropical sprue, persistent infections, or malnutrition with bacterial overgrowth. We report the prevalence and histology of coeliac disease in children with chronic diarrhea at a tertiary referral hospital in North India., Methods: Two hundred fifty-nine children with symptoms indicating coeliac disease attended the All India Institute of Medical Sciences. Histology was graded after a modified Marsh classification. Serum immunoglobulin A anti-endomysial antibodies (AEA) were assayed using indirect immunofluorescence. Subjects with abnormal histology and positive AEA were put on a gluten free diet (GFD). Coeliac disease was diagnosed on small intestinal biopsy changes and a clinical response to a GFD., Results: Severe enteropathies were present in 63 (24%) subjects, and 58 (92%) responded to a GFD. Sixty-six (25%) had moderate histologic changes, 61 responding to a GFD. AEA was positive in 56 of 63 patients with severe and 65 of 66 with moderate enteropathies. Fifty-seven children had mild enteropathies, and 19 of 20 with positive AEA responded clinically to a GFD., Conclusions: Coeliac disease is more common than previously believed. It presents a variable histology, and diagnoses may be missed or delayed if based only on severe enteropathies. Serology is a useful adjunct to diagnosis, and diagnostic criteria need to be developed appropriately for coeliac disease in developing countries despite limited facilities.

An understanding of the possible causes of dysgammaglobulinaemia in the elderly helps to direct further investigation to establish a diagnosis. In this review we provide brief case studies to illustrate some of the disorders associated with dysgammaglobulinaemia in the elderly. We consider both hypergammaglobulinaemia (polyclonal, characteristic of chronic inflammatory disorders or autoimmunity, and monoclonal, often with an associated malignant disorder) and hypogammaglobulinaemia (including immunodeficiency, immune paresis secondary to malignancy and protein loss). Where dysgammaglobulinaemia is noted in the elderly the most useful laboratory tools to help discern the pathogenesis are serum and urine electrophoresis, autoantibody investigations and measurement of liver and renal function.

Two atypical patients with a multiple sclerosis (MS)-like illness and evidence of occult celiac disease (CD) were managed by the authors. This prompted screening of a further 49 unselected MS cases for serologic evidence of CD. IgA anti-endomysial antibody was found in one case (2%). IgG anti-gliadin antibody was found in 12% of patients and 13% of blood donors. Anti-gliadin antibody (especially IgG isotype) can be a nonspecific finding.

Background: Anti-tissue transglutaminase (tTG) antibody is being used increasingly as a diagnostic tool in the serological investigation of coeliac disease. However, positive predictive values of immunoglobulin A anti-tTG for coeliac disease in prospective studies have been disappointing., Objective: To determine whether anti-tTG can arise as a non-specific consequence of abnormal gut permeability., Patients: A cohort from routine investigation for possible gluten-sensitive enteropathy, with 44 cases selected based on whether permeability studies had been performed., Methods: The cohort was assessed for anti-tTG by enzyme-linked immunosorbent assay, small-bowel biopsy and C-mannitol absorbency., Results: Eighteen of the 44 patients had biopsy-proven coeliac disease and 23 showed abnormal permeability. There was poor correlation between the level of anti-tTG and gut permeability., Conclusions: These data confirm an association between anti-tTG and coeliac disease but no clear relationship with other forms of increased gut permeability.

Background: Anti-tissue transglutaminase (tTG) antibody is being used increasingly as a diagnostic tool in the serological investigation of coeliac disease. However, positive predictive values of immunoglobulin A (IgA) anti-tTG for coeliac disease in prospective studies have been disappointing and false-positive results are reported., Objective: To assess the clinical utility of cascade testing for anti-tTG and anti-endomysium antibody (AEA)., Patients: Two unselected retrospective cohorts from routine diagnostic investigation for possible gluten sensitive enteropathy: group 1 comprised 57 cases seropositive for anti-tTG and group 2 comprised 52 cases seronegative for anti-tTG. In both groups, all cases had also undergone small-intestinal biopsy., Methods: Patients were assessed for the presence of IgA anti-tTG by enzyme-linked immunosorbent assay and for IgA AEA by immunofluorescence., Results: The positive predictive value of IgA anti-tTG for biopsy-confirmed coeliac disease was 54%. The positive predictive value of dual positivity for anti-tTG and AEA was 97%. The negative predictive value of IgA anti-tTG was 100%., Conclusions: The data presented here support the use of IgA anti-tTG as an initial screen for coeliac disease. Coeliac disease is unlikely when IgA anti-tTG is absent. However, many false-positive results are seen, and clinical utility and diagnostic efficiency are improved markedly if positive results are confirmed with the more accurate, but labour-intensive, AEA assay.

Objective: To document cardiac abnormalities secondary to pulmonary disease in primary antibody deficiency., Patients and Methods: A cross sectional audit study of patients from a regional immunology centre. Subjects undergoing two dimensional and Doppler transthoracic echocardiography were reviewed. Ventricular dimensions and function, valvular competence, and estimated pulmonary artery pressure were recorded. Data were compared with clinical variables, pulmonary function tests, and thoracic computed tomography data., Results: Nineteen patients with common variable immunodeficiency and one with IgG(2) subclass deficiency were included, mean age at diagnosis 37.5 years, mean estimated diagnostic delay 10.94 years. Left ventricular impairment was found in 15% and right heart dilatation in 20%. Pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg) was found in 45% (9/20), graded as moderate (40-60 mm Hg) in 44% of cases. Pulmonary function was obstructive in 47% (9/19). Fifty five percent of the patients with computed tomography data within the last five years (10/18) had confirmed bronchiectasis. Patients with right heart dilatation and/or moderate pulmonary hypertension (n = 6) had a more prolonged diagnostic delay (p = 0.04) and more severe lung disease., Conclusion: Echocardiographic abnormalities are common in primary antibody deficiency, associated with diagnostic delay and pulmonary complications. Pulmonary hypertension should be considered in those with severe lung disease and can be confirmed by echocardiography.