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Mast cells and basophils degranulate upon activation, releasing preformed mediators from intracellular granules into the extracellular environment, of which tryptase and histamine are the two most common and best characterized mediators. Despite the large number of mediators synthesized by mast cells, the non-tryptase biomarkers used to evaluate systemic mastocytosis and mast cell activation syndrome do not include the metabolites of the prestored amine histamine and the de novo synthesized phospholipids prostaglandin D2 and leukotriene C4. Currently, these markers are not used as criteria for the diagnosis of mastocytosis and mast cell activation syndrome. However, consensus groups foster the use of increases in measured baseline levels of these metabolites as potential diagnostic criteria. Metabolites of arachidonic acid such as prostaglandin D2 or leukotriene C4 play a role in the development of symptoms in systemic mastocytosis and mast cell activation syndrome. In this review, the metabolites of arachidonic acid and the detection of the metabolites of leukotrienes and prostaglandins in mastocytosis are highlighted. Measurement of these metabolites remains a major challenge because they are not widely available in daily clinical practice. However, new insights have been gained in recent years, and their application in the clinic has progressed.

Zusammenfassung. Die Impfung von Patenten mit Immundefekten stellt eine Herausforderung dar. Ein fehlender Anstieg von Impfantikörpertitern oder impfinduzierte Infektionen können auf einen primären Immundefekt hinweisen. Alle in der Schweiz zugelassenen Impfstoffe gegen SARS-CoV-2 können auch bei immungeschwächten Patienten verabreicht werden.

Zusammenfassung. Die Primären Immundefekte (PID) werden durch eine genetisch bedingte Fehlentwicklung/Funktionsstörung des Immunsystems verursacht. Leitsymptome sind neben Infektanfälligkeit, Autoimmunerkrankungen, lymphoproliferative, allergische als auch malige Erkrankungen. Sie können in zehn Hauptgruppen unterteilt werden, worunter die primären Antikörpermangelsyndrome (PAD) bei den Erwachsenen dominieren. Zu den bekanntesten PAD gehören das variable Immundefektsyndrom (CVID), die Brutonsche Agammaglobulinämie, die IgG-Subklassendefekte, der Immunglobulin-A-Mangel, der spezifische Antikörpermangel und die transiente Hypogammaglobulinämie im Kindesalter. Sekundäre bedingte Hypogammaglobulinämien durch Medikamente, hämatologische Erkrankungen, Malignome und Infektionen sollten ausgeschlossen werden. Bei Diagnoseverzögerungen der CVID konnte eine signifikante Erhöhung der Morbidität und Zunahme der Mortalität nachgewiesen werden. Therapeutisch erfolgt neben Impfungen auch eine Immunglobulin-Ersatztherapie.

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Background: X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency disease caused by XIAP gene mutations. A broad range of phenotype, severity, and age at onset present challenges for patient management.Objective: We sought to characterize the phenotype, treatment, and survival outcomes of XIAP deficiency and to assess parameters influencing prognosis.Methods: Data published from 2006 to 2020 were retrospectively analyzed.Results: A total of 167 patients from 117 families with XIAP deficiency were reported with 90 different mutations. A wide spectrum of clinical features were seen, of which hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease were the most common. Patients frequently developed multiple features with no clear genotype-phenotype correlation. A total of 117 patients were managed conservatively and 50 underwent hematopoietic stem-cell transplantation (HSCT), with respective overall survival probabilities of 90% and 53% at age 16 years. The predominant indication for HSCT was early-onset HLH. Active HLH and myeloablative conditioning regimens increased HSCT-related mortality, although HSCT outcome was much better after 2015 than before. For conservatively managed patients reaching adulthood, survival probabilities were 86% at age 30 years and 37% by age 52 years, with worse outcomes for patients developing the disease before the age of 5 years or with new disease features in adulthood. Nine asymptomatic mutation carriers with a median age of 13.5 years were identified.Conclusions: Our study demonstrates the variable nature of XIAP deficiency, which evolves over life for individual patients. Better therapeutic strategies and prospective studies are required to reduce morbidity and mortality and improve decision making and long-term outcomes for patients with XIAP deficiency. (J Allergy Clin Immunol 2022;150:456-66.)

Antibodydeficiencies Epidemiology, Clinical manifestation, Diagnostics and Therapy

Vaccination and Vaccination Response in Immunodeficiency

Mesalazine is often used as first-line therapy for ulcerative colitis. Several reports have pointed to systemic adverse reactions associated with this drug. Most have evoked a drug-induced hypersensitivity syndrome, while some have described lupus syndromes but with limited clinical and varied biological features. A 75-year-old man presented with fever, dyspnoea, chest pain, polyarthralgia, and myalgia, following mesalazine introduction. Clinical symptoms and low-titre positive antihistone antibodies disappeared after mesalazine withdrawal without recourse to steroids. Pericardial effusion and 8F-fluorodeoxyglucose uptake on positron emission tomography/CT scan, and glomerular haematuria and proteinuria also disappeared. Cytokine-lymphocyte transformation tests showed a strong sensitisation pattern with interleukin-5 production. This case advances our knowledge of the mechanism of mesalazine-induced adverse effects, namely via drug-induced hypersensitivity with lupus manifestations, which we are the first to report.

NSAID-Exacerbated respiratory disease (also known as Samter's or Widal's triad, aspirin-exacerbated respiratory disease) is characte- rized by asthma, nasal polyposis and hypersensitivity to NSAIDs. The pathogenesis of this chronic inflammation arises from an imbalance in arachidonic acid metabolism, leading to an increase in pro- inflammatory cysteinyl-leukotrienes. The treatment is based on drug management of asthma and polyps and, in advanced situations, surgical management of polyposis. Monoclonal antibodies have shown promising results in the further medical treatment of this entity.Le syndrome de Widal (SW) (également connu sous le nom de triade de Samter, maladie respiratoire exacerbée par l’Aspirine) est une entité clinique caractérisée par la triade comprenant un asthme, une polypose nasale et une intolérance aux AINS. La physiopathologie de cette maladie, bien qu’incomplètement élucidée, est caractérisée par un déséquilibre dans le métabolisme de l’acide arachidonique (AA) en faveur de la voie des cystéinyl- leucotriènes (cysLT). Son traitement repose sur une prise en charge médicamenteuse agressive de l’asthme et des polypes et, dans des situations avancées, la prise en charge chirurgicale de la polypose. L’avènement des traitements par anticorps monoclo- naux a montré des résultats encourageants pour les alternatives thérapeutiques futures.

The diagnosis of anaphylaxis relies on a suggestive clinical history after exposure to a potential triggering factor. Serum tryptase concentrations increase on degranulation of mast cells and therefore serum tryptase levels are measured to diagnose anaphylaxis. There is no standardized method for assessing total serum mast cell tryptase (MCT) in anaphylaxis. The Working Conference in 2010 proposed a consensus equation (peak MCT should be > 1.2x baseline tryptase + 2 ng/L) to diagnose acute mast cell activation (aMCA). Our objective was to narratively review the literature since the Working Conference in 2010, examining the use of the consensus equation and other equations comparing baseline and peak serum tryptase during anaphylaxis. Computerized bibliographic searches of PUBMED and EMBASE were supplemented with a manual search of reference lists. English-language studies were included. Eleven studies met our inclusion criteria with a total of 4551 participants. However, only four studies with 653 participants used the consensus equation. The other seven studies used other methods to compare peak and baseline serum tryptase concentrations. Measuring serum tryptase levels is valuable in the diagnosis of anaphylaxis but is unable to detect all anaphylactic reactions. Based on our current literature review, the consensus equation is underused in the diagnosis of anaphylaxis. There is also a need for exploration of other biomarkers which could be used in parallel to peak and baseline serum tryptase measurements for further diagnostic certainty. Serum tryptase is the most studied biomarker in anaphylaxis but is still far from being the ideal biomarker for this. There is a need to identify new potential useful biomarkers. Serum tryptase levels are valuable in the diagnosis of anaphylaxis, but are unable to detect all anaphylactic reactions. Additionally serial tryptase measurements are laborious in daily clinical practice.

« Penicillin allergy » is a common finding in patient's medical files (up to 10 %). Although it is important not to neglect such records (due to the serious and life-threatening reactions an allergic patient may suffer from), most of the time these reported notions of allergy are wrong and lead to the unfortunate avoidance of all betalactamins. This in turn leads to increased risks of antibiotic resistance and increased health costs. This review aims to summarize the current knowledge on penicillin allergy epidemiologic data and proposes a first-line guide for general practitioners to the evaluation of the patient with a history of « penicillin allergy ».La « notion d’allergie à la pénicilline » dans les dossiers des patients est une trouvaille assez fréquente (jusqu’à 10 %) et généralement erronée. Cette dernière peut mener à une sous-utilisation des bêtalactamines avec des conséquences négatives sur l’émergence de germes résistants, la prise en charge et les coûts médicaux. D’un autre côté, il s’agit néanmoins d’un diagnostic à ne pas ignorer ni à banaliser (notamment devant une anamnèse incomplète) étant donné la sévérité des réactions qu’une exposition pourrait occasionner. Cet article propose un résumé des connaissances actuelles des données épidémiologiques sur le sujet, et un algorithme de prise en charge en première intention des « notions d’allergie à la pénicilline ».

Background: Patients with mastocytosis often suffer from a variety of symptoms caused by mast cell mediators where treatments remain difficult, showing various success rates. Omalizumab, a monoclonal anti-IgE antibody, has been postulated to have a positive impact on mastocytosis-associated symptoms such as flush, vertigo, gastrointestinal problems, or anaphylaxis. Objective: To investigate the efficacy and safety of omalizumab in systemic mastocytosis. Methods: Patients with histologically proven mastocytosis were investigated in a multicenter prospective double-blind placebo-controlled trial to receive either omalizumab or placebo, dosed according to IgE and body weight. The primary endpoint was change in the AFIRMM activity score after 6 months of treatment. Different laboratory parameters were analyzed. Results: Sixteen patients were analyzed: 7 to omalizumab and 9 to placebo (mean age 47.7 ± 13.8 vs. 45.4 ± 8.8 years; 66.6 vs. 85.7% were female; mean disease duration 10.0 ± 5.1 vs. 4.5 ± 2.9 years, respectively). After 6 months the median AFIRMM score decreased 50% from 52.0 to 26.0 in the omalizumab group versus 104.0–102.0 in the placebo group (p = 0.286); however, the difference was not significant (p = 0.941). Secondary endpoints, including the number of allergic reactions, changes in major complaints, wheal-and-flare reaction due to mechanical irritation (Darier’s sign), and frequency of the use of mastocytosis-specific drugs improved in the omalizumab group, but not significantly. Adverse events like urticaria, bronchospasm, and anaphylactic shock showed no significant difference between the groups. No severe adverse events occurred. FcεRI (Fc-epsilon receptor) expression on basophils decreased after receiving omalizumab versus placebo. Conclusion: Omalizumab was safe and showed a tendency to improve mastocytosis-related symptoms, in particular diarrhea, dizziness, flush, and anaphylactic reactions, including the AFIRMM score and secondary endpoints; however, the difference was not significant. Due to the small study size and difference at baseline between the study groups, further studies are required to confirm our findings.

« Penicillin allergy » is a common finding in patient's medical files (up to 10 %). Although it is important not to neglect such records (due to the serious and life-threatening reactions an allergic patient may suffer from), most of the time these reported notions of allergy are wrong and lead to the unfortunate avoidance of all betalactamins. This in turn leads to increased risks of antibiotic resistance and increased health costs. This review aims to summarize the current knowledge on penicillin allergy epidemiologic data and proposes a first-line guide for general practitioners to the evaluation of the patient with a history of « penicillin allergy ». La « notion d’allergie à la pénicilline » dans les dossiers des patients est une trouvaille assez fréquente (jusqu’à 10 %) et généralement erronée. Cette dernière peut mener à une sous-utilisation des bêtalactamines avec des conséquences négatives sur l’émergence de germes résistants, la prise en charge et les coûts médicaux. D’un autre côté, il s’agit néanmoins d’un diagnostic à ne pas ignorer ni à banaliser (notamment devant une anamnèse incomplète) étant donné la sévérité des réactions qu’une exposition pourrait occasionner. Cet article propose un résumé des connaissances actuelles des données épidémiologiques sur le sujet, et un algorithme de prise en charge en première intention des « notions d’allergie à la pénicilline ».

Helper innate lymphoid cells (ILCs), the most recently identified population of the ILC family, play a fundamental role in the restoration of tissue integrity, in the protection against infiltrating pathogens as well as in tumor immune-surveillance. ILCs have been divided into three main subsets, ILC1, ILC2, and ILC3, that can be specifically activated by different signals coming either indirectly from pathogens or from other cell populations, including cancer cells. Following activation, ILCs are in turn able to promptly secrete a wide range of soluble mediators that modulate effector cell functions. The discovery and the study of these immune cells is now offering important opportunities for innovative therapies of allergic airway diseases, inflammatory disorders and might be crucial for the discovery of new targets for the therapy of cancer. It is therefore fundamental that the scientific community establishes harmonized guidelines to obtain a consensus in the identification and phenotypical and functional characterization of ILCs. © 2018 International Clinical Cytometry Society.

We report two rare cases of inflammatory reactions with multiple subcutaneous facial painful collections after Hyaluronic acid injections, expose their management and discuss aetiologic hypothesis. Due to unfavourable evolution despite antibiotic treatment, surgical drainage was performed. Immune-mediated delayed hypersensitivity reactions were the most probable cause.

Enthesitis-related arthritis (ERA) necessitates presence of arthritis and/or enthesitis for at least 6 weeks in a child under 16 years of age In the presence of enthesitis or arthritis alone, at least two of the following should be present to make a diagnosis of ERA: sacroiliac tenderness or inflammatory spinal pain, HLA-B27 positivity, onset of arthritis in boys aged >6 years, anterior uveitis associated with pain, redness, or photophobia, or a family history of HLA-B27-associated disease NSAIDs are traditionally used as initial treatment of ERA Methotrexate and biologic agents are reserved for patients who are refractory to NSAIDS

Nasal polyposis is a specific phenotype of chronic rhinosinusitis (CRS). Some cases can be managed with topical and infrequent use of systemic steroids, while many patients require surgery. Despite postoperative, regular steroid administration, recurrences may be found especially in patients suffering from Aspirin exacerbated respiratory disease (AERD), a particularly severe form of CRS with polyps, asthma and non-steroid-anti-inflammatory-drug (NSAID) intolerance. We report two cases of difficult-to-treat AERD patients following revision surgery, treated with monoclonal anti-IgE antibody (omalizumab) and successful control of the disease and symptoms. Omalizumab may be a promising alternative in selected cases of CRS with nasal polyps to avoid overuse of systemic steroids and frustrating repetition of paranasal sinus surgeries.La rhinosinusite chronique (RSC) touche 15 % de la population et se caractérise par l’obstruction et l’écoulement nasaux pendant plus de trois mois. Les formes sévères de la RSC sont associées à la présence de polypes nasaux. Le traitement de première ligne sont des corticoïdes topiques, qui ne sont pas toujours efficaces et certains patients ont besoin de plusieurs cures de stéroïdes per os et chirurgies nasales répétitives pour stabiliser la maladie. Ce cercle vicieux s’observe souvent dans le syndrome de Widal (polypes, asthme et intolérance aux AINS). On rapporte deux cas de Widal avec interruption de cette boucle, obtenue par l’application de l’anticorps monoclonal anti-IgE omalizumab. L’omalizumab pourrait être une alternative dans certains cas de RSC pour limiter la surutilisation de stéroïdes et la répétition frustrante de chirurgie nasale.

Primary immunodeficiencies (PID) constitute a heterogeneous group of genetic disorders caused by defects in the development and/or function of the immune system resulting in an increased susceptibility to recurrent infections. In addition to a predisposition to infections, PID patients present an increased vulnerability to autoimmunity, lymphoproliferation, allergies and malignancies. Studies performed in the past decade revealed that the prevalence of PID in adults was largely underestimated. These have also demonstrated that the disease burden of PID is not less than in children. PID is more common than generally thought.Les immunodéficiences primaires (IDP) constituent un groupe hétérogène génétique, causées par des défauts de développement et/ou de fonctionnement du système immunitaire, entraînant une susceptibilité aux infections récurrentes. Les patients atteints d’une IDP présentent une prédisposition au développement de pathologies auto-immunes, lymphoprolifératives, allergiques ou malignes. Les études réalisées au cours de la dernière décennie ont corrigé les sous-estimations de la prévalence des IDP adultes et ont montré que la morbidité n’est pas moins lourde chez les adultes que chez les enfants. Les IDP sont en effet plus fréquentes qu’on ne le pense.

Acquired hypogammaglobulinemia should always be considered during the evaluation of a patient with a suspected antibody deficiency Chronic corticosteroid use, antiepileptic drugs, and rituximab therapy, malignancies such as chronic lymphocytic leukemia, or lymphomas, nephrotic syndrome, protein-losing enteropathy and congenital lymphangiectasis, as well as HIV infection are considered as common causes of secondary hypogammaglobulinemia Headaches are a typically associated with intravenous immunoglobulin infusions Slowing or stopping the infusion for 15–30 minutes can reverse most of the acute reactions associated with IVIG infusion Adequate hydration or prescribing acetaminophen or NSAIDs are among options to prevent headaches during IVIG treatment

Immune system failure in primary antibody deficiencies (PADs) has been linked to recurrent infections, autoimmunity, and cancer, yet clinical judgment is often based on the reactivity to a restricted panel of antigens. Previously, we demonstrated that the human repertoire of carbohydrate-specific immunoglobulin G (IgG) exhibits modular organization related to glycan epitope structure. The current study compares the glycan-specific IgG repertoires between different PAD entities. Distinct repertoire profiles with extensive qualitative glycan-recognition defects were observed, which are characterized by the common loss of Galα and GalNAc reactivity and disease-specific recognition of microbial antigens, self-antigens, and tumor-associated carbohydrate antigens. Antibody repertoire analysis may provide a useful tool to elucidate the degree and the clinical implications of immune system failure in individual patients.

An understanding of natural killer (NK) cell physiology in acute myeloid leukemia (AML) has led to the use of NK cell transfer in patients, demonstrating promising clinical results. However, AML is still characterized by a high relapse rate and poor overall survival. In addition to conventional NKs that can be considered the innate counterparts of CD8 T cells, another family of innate lymphocytes has been recently described with phenotypes and functions mirroring those of helper CD4 T cells. Here, in blood and tissues, we identified a CD56(+) innate cell population harboring mixed transcriptional and phenotypic attributes of conventional helper innate lymphoid cells (ILCs) and lytic NK cells. These CD56(+) ILC1-like cells possess strong cytotoxic capacities that are impaired in AML patients at diagnosis but are restored upon remission. Their cytotoxicity is KIR independent and relies on the expression of TRAIL, NKp30, NKp80, and NKG2A. However, the presence of leukemic blasts, HLA-E–positive cells, and/or transforming growth factor-β1 (TGF-β1) strongly affect their cytotoxic potential, at least partially by reducing the expression of cytotoxic-related molecules. Notably, CD56(+) ILC1-like cells are also present in the NK cell preparations used in NK transfer–based clinical trials. Overall, we identified an NK cell–related CD56(+) ILC population involved in tumor immunosurveillance in humans, and we propose that restoring their functions with anti-NKG2A antibodies and/or small molecules inhibiting TGF-β1 might represent a novel strategy for improving current immunotherapies.

Mast cell activation syndrome (MCAS) encompasses a heterogeneous group of pathologies, which are characterized by the existence of clinical symptoms secondary to the systemic effects of mediators released by activated mast cells. MCAS-related symptoms may be mild, moderate, severe, or even life-threatening. Detailed knowledge of the pathogenesis and complexity of MCAS can help in the management and treatment of these patients.Le syndrome d’activation mastocytaire (MCAS) englobe un groupe hétérogène de pathologies qui sont caractérisées par la présentation des symptômes cliniques secondaires aux effets systémiques des médiateurs libérés par les mastocytes activés. Les symptômes liés au MCAS peuvent être légers, modérés, graves ou même mortels. Une connaissance détaillée de la pathogenèse et de la complexité du MCAS peut aider dans la prise en charge et le traitement de ces patients.

Hereditary angioedema (HA) is a disabling and potentially fatal condition. The management of HA includes treatment of acute attacks, short-term prophylaxis to prevent an attack, and long-term prophylaxis to minimize the frequency and severity of recurrent attacks. In this article, we will present new therapeutic alternatives for long term prophylaxis. Glucocorticoids (GC) usage leads to a number of severe side-effects. In giant cell arteritis, the use of tocilizumab in conjunction with low doses of GC reduces the number of relapses. In ANCA-associated vasculitis the use of an anti-C5R (avacopan) alone or in conjunction with low doses of GC results in similar remission rates to those induced by high dose GC.L’angiœdème héréditaire (AH) est une maladie invalidante et potentiellement mortelle. La prise en charge de l’AH comprend le traitement des crises aiguës, la prophylaxie à court terme pour prévenir une attaque et la prophylaxie à long terme pour minimiser la fréquence et la gravité des crises récurrentes. Nous discutons les nouvelles alternatives thérapeutiques pour la prophylaxie à long terme. L’utilisation des glucocorticoïdes (GC) est grevée d’effets secondaires multiples et graves. Dans l’artérite gigantocellulaire l’adjonction d’un anti-IL6 à des doses faibles de GC a permis de réduire le nombre de rechutes. Dans les vascularites à ANCA, un anti-C5R (avacopan) a permis de réduire la quantité de GC nécessaire pour atteindrela rémission.

Helper innate lymphoid cells (ILCs), the most recently identified population of the ILC family, play a fundamental role in the restoration of tissue integrity, in the protection against infiltrating pathogens as well as in tumor immune-surveillance. ILCs have been divided into three main subsets, ILC1, ILC2, and ILC3, that can be specifically activated by different signals coming either indirectly from pathogens or from other cell populations, including cancer cells. Following activation, ILCs are in turn able to promptly secrete a wide range of soluble mediators that modulate effector cell functions. The discovery and the study of these immune cells is now offering important opportunities for innovative therapies of allergic airway diseases, inflammatory disorders and might be crucial for the discovery of new targets for the therapy of cancer. It is therefore fundamental that the scientific community establishes harmonized guidelines to obtain a consensus in the identification and phenotypical and functional characterization of ILCs. © 2018 International Clinical Cytometry Society.

Hereditary angioedema (HA) is a disabling and potentially fatal condition. The management of HA includes treatment of acute attacks, short-term prophylaxis to prevent an attack, and long-term prophylaxis to minimize the frequency and severity of recurrent attacks. In this article, we will present new therapeutic alternatives for long term prophylaxis. Glucocorticoids (GC) usage leads to a number of severe side-effects. In giant cell arteritis, the use of tocilizumab in conjunction with low doses of GC reduces the number of relapses. In ANCA-associated vasculitis the use of an anti-C5R (avacopan) alone or in conjunction with low doses of GC results in similar remission rates to those induced by high dose GC.

Background The castor bean plant, Ricinus communis, is known to have allergenic and toxic properties. Castor bean allergy has been described mainly as an occupational inhalation allergy in laboratory workers, in persons working in oil processing mills or in agricultural industry. So far, only one case of anaphylactic reaction due to castor bean sensitization confirmed by specific IgE has been described in literature. Case presentation A 30-year-old woman presented to the emergency room with severe angioedema followed by urticaria, hypotension and tachycardia. She recovered after treatment with antihistamines, corticosteroids, nebulized adrenaline and intravenous fluids. Food induced anaphylaxis was excluded by allergological investigations. After repeated thorough history, the patient mentioned having bitten into a castor bean just before the reaction. Cutaneous test (prick-to-prick) and specific IgE for castor bean were highly positive. Conclusions We report the second case of a severe anaphylactic reaction to castor beans, confirmed by IgE testing, reported in the literature. It underlines the importance of a meticulous history in allergology and highlights the fact, that castor beans may cause potentially fatal anaphylaxis.

A 30-year-old male smoker presented to the emergency department with anterior ST-segment elevation myocardial infarction. Primary percutaneous coronary intervention performed via the right radial artery showed an ostial thrombotic subocclusion of the left anterior descending artery ([Figure 1A][1

Concise overview of the field of anticytokine autoantibodies with a focus on recent developments.Advances in particular in the analysis of autoantibodies to IFNγ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and type I IFN are presented. The target epitope for anti-IFNγ autoantibodies has been found to have high homology to a protein from Aspergillus suggesting molecular mimicry as a mechanism of breaking self-tolerance. A treatment strategy using a recombinant, epitope-depleted version of IFNγ is suggested. Autoantibodies to GM-CSF are associated with disseminated Crytococcus and Nocardia infections thus expanding the spectrum of associated diseases beyond pulmonary alveolar proteinosis. Detailed analysis of anti-GM-CSF autoantibody clones derived from pulmonary alveolar proteinosis patients show evidence of high somatic mutation suggesting T cell-dependent affinity maturation; full GM-CSF neutralization is achieved by synergistic binding of antibodies targeting various distinct noncross-reactive epitopes and leading to antigen sequestration and Fc-mediated clearance. Single mAbs in contrast may lead to higher GM-CSF bioavailability. Anti type I IFN-specific autoantibodies derived from autoimmune polyglandular syndrome type I patients are of extreme high affinity and negatively correlate with the incidence of type I diabetes and may be thus considered to be protective. Hypomorphic severe combined immune deficiency may be associated with complex anticytokine patterns and the emergence of anti type I IFN autoantibodies correlates with severe viral infection histories.Anticytokine autoantibodies may cause susceptibility to infections. In autoimmune/autoinflammatory conditions, anticytokine autoantibodies may be protective or promote disease.

Primary Immunodeficiency Diseases (PID) comprise inborn defects of the immune system which are and therefore difficult to study For this reason, the European Society for ImmunoDeficiencies (ESID) has set up an internet-based international patient and research database which integrates research data with more detailed clinical information. These disorders are not only found in children, but also in adults resulting in a wide range of clinical manifestations. Primary immunodeficiency adults are much less known and may remain undiagnosed.

Objective: The study was conducted to determine activation of coagulation in patients undergoing open and endovascular infrarenal abdominal aortic aneurysm repair (EVAR).Methods: In a prospective, comparative study, 30 consecutive patients undergoing open repair (n = 15) or EVAR (n = 15) were investigated. Blood samples to determine fibrinopeptide A, fibrin monomer, thrombin-antithrombin complex, and D-dimer were taken up to 5 days postoperatively. Routine hematologic and hematochemical parameters as well as clinical data were collected.Results: Both groups showed comparable demographic variables. Operating time was longer in open repair (249 +/- 77 minutes vs 186 +/- 69 minutes, P < .05). Perioperatively elevated markers of coagulation were measured in both groups. Fibrinopeptide A levels did not differ significantly between the groups (P = .55). The levels of fibrin monomer and thrombin-antithrombin complex were significantly higher in patients undergoing EVAR (P < .0001), reflecting increased thrombin activity and thrombin formation compared with open surgery. The D-dimer level did not differ significantly between the groups. These results were also valid after correction for hemodilution.Conclusion: These data suggest increased procoagulant activity in EVAR compared with open surgery. A procoagulant state may favor possible morbidity derived from micro- and macrovascular thrombosis, such as in myocardial infarction, multiple organ dysfunction, venous thrombosis and thromboembolism, or disseminated intravascular coagulation.

Background Several studies have shown a high prevalence of immunoglobulin deficiencies in patients with chronic rhinosinusitis (CRS). Objective We sought to perform a systematic review and meta-analysis to estimate this prevalence more precisely and to identify patients who need substitution treatment. Methods All case series published after 1990 describing patients with CRS, which was defined as symptomatic rhinosinusitis for more than 12 weeks and documented immunoglobulin deficiencies (including deficiencies of IgG with subclasses, IgA, and IgM; specific antibody deficiencies; and potential common variable immunodeficiency), were retrieved. A meta-analysis of the proportion of any combination of common variable immunodeficiency, IgG deficiency, IgA deficiency, and IgM deficiency in patients with CRS was performed by using logit transformation of the prevalence. Recurrent CRS was defined as rhinosinusitis not controlled by appropriate conservative management for 4 months, and difficult-to-treat CRS was defined as noncontrollable rhinosinusitis despite successful sinus surgery and appropriate conservative management for at least 1 year. Results The meta-analysis revealed a prevalence of pooled IgG, IgA, and IgM deficiencies in 13% of patients with recurrent CRS and 23% of patients with difficult-to-treat CRS. The prevalence of IgG subclass deficiency (5% to 50%) and specific antibody deficiency (8% to 34%) was increased in patients with CRS, as was the prevalence of respiratory allergies in patients with recurrent CRS (31% to 72%). Conclusion Immunoglobulin deficiency is a frequent condition in patients with CRS. An even higher prevalence of atopy was observed in patients with recurrent CRS. Therefore immunoglobulin titers and accurate allergy diagnostic workups are strongly recommended in these patients to provide specific treatments for symptom alleviation. However, there is a need for larger prospective studies addressing the effect of specific therapeutic interventions for CRS.

In August 2009, a 28-year-old Spanish woman was referred in reduced general condition after at least four medical consultations with a 2 week history of remittent fever, night sweats, exanthema and intermittent arthralgias. Noticeable in the clinical examination was only an urticarial rash on the trunk and extremities and body temperature of 39.6°C. Laboratory tests: WBC with a slight left shift (32%), mild thrombocytopenia (128 G/l), CRP 78 mg/l (N: < 5), elevated transaminases [ASAT 67 U/l (N: 10-37), ALAT 45 U/l (N: 30-65)]. On the fifth day maximum values for ASAT 322 U/l and ALAT 378 U/l were reached. During hospitalisation recurrent fever up to 39.0°C has been documented associated with arthralgias and myalgias. An infection with blood cultures and serology tests was excluded. Rheumatology analysis, urine analysis, chest X-ray, and abdominal ultrasound were inconspicuous. A serum ferritin level of 5493 μg/l (N: 23-110) was detected with peak four days later (8530 μg/l). AOSD was suspected and prednisolone (1 mg/kg body weight) started. The patients recovered rapidly. Transaminases (ASAT 47 U/l, ALAT 149 U/l), CRP (34 mg/l), and ferritin level (1969 μg/l) regressed within 3 days. 3 months later, prednisolone was discontinued; she presented fever (40°C), myalgias, macular rash on the trunk, sore throat and oligoarthritis. Laboratory tests including WBC were without pathologic findings except for transaminases (ASAT 83 U/l, ALAT 53 U/l), CRP (370 mg/l) and ferritin (7434 μg/l). An infectious process was excluded. After resumption of prednisolone 10 mg daily, quick relief of symptoms occurred. Given the short time of relapse, immunosuppressive therapy with cyclosporin was initiated (4 mg/kg body weight). Since that time the patient remained symptom free for over 8 months.

The case history of a 75-year-old woman, who was hospitalized with the diagnosis of an acute erosive colitis, is presented. The patient was treated with hysterectomy for an endometrial cancer in 2000 and had suffered from multiple sclerosis for 15 years. A persistent non-productive cough with fever requested a pneumological consultation. Multiple small alveolar opacities and cavitating lesions were found at chest imaging, but no precise diagnosis was possible. Only 3 weeks after hospitalization, we noticed that a urine analysis had been forgotten. This additional test clearly demonstrated a nephritic sediment and further analysis confirmed the diagnosis of a ANCA-positive microscopic polyangiitis, which promptly responded to immunosuppressive therapy. The necessity of a routine urine analysis in the majority of internal medicine patients and the possible link between small vessel vasculitis and multiple sclerosis are discussed.