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Hemophagocytic lymphohistiocytosis (HLH) is a group of rare diseases characterized by over-activation of the immune system. They form two groups: primary and secondary HLH. Primary HLH are linked to mutations impairing lymphocyte cytotoxicity. Secondary HLH are triggered by infections, autoimmune diseases or neoplasia, the remaining cases being labeled idiopathic. HLH manifest as febrile states, cytopenias and hepatosplenomegaly. In the absence of treatment, they quickly lead to multiple organ failure. The diagnosis is currently based on the presence of several clinical and biological markers. Treatment consists of suppression of the triggering factor, organ support and immunosuppression. Primary forms, affecting a pediatric population, have been the subject of intense research, and are nowadays treated with established therapeutic protocols. Several recent retrospective studies have improved our knowledge of secondary HLH, which affects mostly adults and whose incidence seems to be increasing. Thus, new diagnostic criteria are currently being studied for secondary HLH, and several treatment protocols have just been published or are being evaluated. [ABSTRACT FROM AUTHOR]

Olmesartan-induced enteropathy was first described twelve years ago. Clinically it is characterized by diarrhea, weight loss and malabsorption. Histological analysis may show duodenal villous atrophy and/or epithelial lymphocytosis (duodenal/colic). Celiac-specific antibodies are negative and gluten avoidance does not improve the symptomatology. This adverse event can occur months or years after the introduction of the causative drug, making it a real diagnostic challenge. The treatment is the avoidance of olmesartan, which will lead to both clinical and histological improvement., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Mixed connective tissue disease (MCTD) is a rare autoimmune condition. Since its first description 50 years ago, its mere existence has been debated, given that it shares features of other autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myopathy, rheumatoid arthritis and Sjogren's syndrome. Also, while antibodies to U1-RNP are essential for the diagnosis of MCTD, these antibodies may be expressed in other circumstances, such as in case of SLE. Nevertheless, the patient fulfilling criteria for MCTD needs specific management. In this review, we describe the clinical features and the potential complications of this complex disease, often wrongly disregarded as benign. We will also emphasize the recommended follow-up exams and address treatment, which is currently lacking formal recommendations., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

The diagnosis of cardiac sarcoidosis, particularly in its isolated cardiac form, represents a major challenge due to non-specific symptoms and the limited sensitivity and specificity of basic cardiac investigations. MRI and metabolic PET-CT are important elements in the diagnostic process. Corticosteroids remain the cornerstone for the treatment of the inflammatory phase, in association with biological agents and steroid-sparing therapies. The goal is to limit the progression of fibrosis, which is a source of malignant arrhythmias and heart failure. The indication for implantation of a cardiac defibrillator must be carefully evaluated to reduce the risk of sudden death. Multidisciplinary collaboration is essential for optimal care., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Cellular therapy using genetically modified T lymphocytes expressing synthetic receptors, known as CAR (Chimeric Antigen Receptor), has revolutionized the treatment of certain hematologic malignancies. This success has led to exploring the same approach in the treatment of severe autoimmune diseases refractory to conventional therapies. Initial results in systemic lupus erythematosus have shown complete remissions that appear to persist over time. Consequently, there is a growing number of ongoing clinical trials. In this review, we discuss the rationale behind the use of CAR-T therapies, the targeted autoimmune diseases, and the associated risks., Competing Interests: Le Pr Y. D. Müller est inventeur d’une licence sur les CAR-T (US 2023/0340068 A1) et responsable de site d’une étude CAR-T (NCT05798117). Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting various organs and characterized by profound immune disturbances. Monoclonal antibodies such as anifrolumab, targeting type I interferon, and belimumab, targeting a cytokine that activates B-cells and plasmocytes, have shown efficacy in SLE. Voclosporine, a novel calcineurin inhibitor, improves renal outcomes when combined with standard immunosuppression in lupus nephritis. Other approaches like obinutuzumab and CAR-T cells offer hope for refractory patients. These advances diversify SLE management, though their long-term efficacy remains to be established. It is crucial to emphasize basic measures in patients with SLE, including smoking cessation, sun protection, and early use of hydroxychloroquine., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Within the group of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (GPA) is the most frequent. The incidence is around 10 to 20 cases/million/year. Clinical manifestations are varied, with ENT, lungs and kidneys most frequently involved. ANCA are pathogenic by triggering neutrophil activation, which leads to vascular damage. Detection of ANCA is most helpful in establishing the diagnosis, but serology may be negative in GPA limited to the airways. Diagnostic work-up and therapy require a multidisciplinary approach. Treatment includes an induction and maintenance phase, combining corticosteroids and immunosuppressive drugs. It aims at limiting the risk of relapses, which is important in GPA, and at reducing corticosteroids toxicity., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Anti-glomerular basement membrane disease is a rare disease. In its classical presentation it associates rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage, linked to the presence of antibodies targeting type IV collagen in the glomerular and alveolar basal membrane. Anti-GBM disease warrants prompt medical management to limit permanent kidney damage and mortality. Treatment includes plasma exchanges to quickly remove pathogenic antibodies and immunosuppressants to stop their production. This article reviews the pathogenesis and current treatments., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Janus kinase inhibitors (JAKi), such as tofacitinib, baricitinib, upadacitinib or ruxolitinib, are small molecules active on specific intracellular targets and used orally for the treatment of autoimmune or myeloproliferative diseases. Their remarkable therapeutic efficacy is offset by a significant risk of toxicities, essentially dose-dependent and a variable pharmacokinetic profile. The JAKi represent a new therapeutic armamentarium for treating autoimmune, myeloproliferative and inflammatory diseases (incl. COVID-19), but require thorough treatment individualization and close monitoring. Therapeutic Drug Monitoring (TDM) of JAKi could allow a personalized prescription and improve the efficacy-toxicity profile., Competing Interests: Le Pr Yves Chalandon déclare les conflits d’intérêts suivant en relation avec cet article : membre de l’Advisory Board et Travel Support de Novartis et Incyte. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Intravenous iron infusions rarely result in severe hypersensitivity reactions. The primary suspected hypersensitivity mechanism is an abnormal complement activation by non-IgE antibodies to the carbohydrate moieties stabilizing iron formulations. A major risk factor for hypersensitivity reactions is related to the infusion speed. Fishbane-like reactions usually resolve after pausing the infusion, which can be resumed under medical surveillance and at a lower infusion rate. Yet, anaphylactic reactions require emergency first aid and subsequent strict avoidance of intravenous iron. Desensitization protocols can be implemented in selected cases and under strict medical surveillance to reduce the risks of severe reactions upon re-exposure., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Anisakis simplex is a parasitic worm. It infects marine mammals that feed on fish and cephalopods, its intermediary hosts. Human disease is caused by accidental ingestion of Anisakis larvae. Upon consumption of contaminated fish, cuttlefish or squid, human may develop two distinct clinical pictures: Anisakiasis is provoked by living larvae penetrating the digestive mucosa. Allergy is caused by IgE-mediate hypersensitivity to living or dead larvae in a previously sensitized individual. Anisakiasis may manifests with violent epi gastric pain, acute abdomen or eosinophilic gastroenteritis. The larvae may be visualized by endoscopy or histology. The main Anisakis allergens are not denaturated by heat or cold and resist to digestion. Allergy diagnosis relies on careful history and detection of specific IgE., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Glucocorticosteroids (GC) remain the mainstay of treatment in most systemic inflammatory diseases. GC have a broad anti-inflammatory action of rapid onset. The downsides of prolonged GC therapy are well established and include infections, osteoporosis and metabolic adverse effects, among others. In systemic sclerosis, GC are associated with an increased risk of scleroderma renal crisis and must be avoided. Adjunction of second-line immunosuppressive drugs may improve disease control and limit GC usage. We summarize here the findings of two studies published in 2021, one reporting the benefits of combining GC with mycophenolate mofetil in immune thrombocytopenia, the other suggesting that blockage of interleukin-6 may decrease disease progression in systemic sclerosis with lung involvement., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Asthma is a chronic disease and asthma control can be affected by many factors. In case of difficult asthma, intensifying drug therapy is not the key. This type of asthma needs an overall management in order to diagnose and treat each factor known to be associated with poor asthma control. The aim of this article is to describe the structured and systematic approach for these patients., Competing Interests: Le Pr Christophe von Garnier reçoit des honoraires pour activité de consultant ou orateur pour des présentations de : AstraZeneca, Boehringer Ingelheim, GSK, Mundipharma, Novartis, Pfizer, OM Pharma, PneumRx et Pulmonx, Sanofi et Schwabe Pharma AG. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Cannabis-fruit and vegetable syndrome is of recent discovery and linked to lipid transfer protein (LTP) sensitization. It is thought that the primary sensitization originates from the cannabis LTP (Can s 3). Sensitized patients can cross-react to others LTP homologs such as peach LTP (Pru p 3). Diagnosis may be challenging, as consumption of cannabis is often omitted by the patient and needs to be specifically addressed during the interview. Thus, meticulous history taking is mandatory. Laboratory workup includes LTP-specific IgE and skin testing. Management relies on allergen eviction., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Many vaccine strategies have been developed to control the COVID-19 pandemic. This article presents the mechanisms of action and the efficacy of different vaccines including mRNA- and adenovirus-based vaccines. We will discuss the different vaccine targets, immune responses and allergic reactions which have been reported during the vaccination campaigns. Finally, the latest recommendations for the prevention and management of severe allergic reactions will be summarized., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Sjögren's syndrome (SS) is an auto-immune condition involving salivary and lacrymal glands leading to dry mouth and dry eyes symptoms. Some patients also present with systemic manifestations. Diagnosis of SS is made after clinical, serological, and histological assessment according to the American College of Rheumatology and European League Against Rheumatism (EULAR) classification criteria. Recent clinical trials showed a significant decrease of systemic activity of SS in patients treated with iscalimab (anti-CD40) and ianalumab (anti-BAFF-R). These results need to be confirmed in larger studies. However, two phase 3 randomized trials did not show efficacy treating SS with abatacept. We also describe in this article the first EULAR recommendations on SS management., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, by reshaping the prognosis of many cancers and are progressively becoming the standard of care. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), of which cardiovascular irAEs are particularly feared. ICI-induced myocarditis is often a diagnostic challenge because of the vast heterogeneity of clinical presentations, and it is associated with a high mortality rate of around 50%. The present article summarizes the cardiac manifestations, the diagnostic strategy and the therapeutic management of patients with ICI-induced myocarditis used in the treatment of cancer., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Patient suffering from autoimmune diseases (AID) typically have an increased risk of infection, which is attributed to the disease itself, but also to immunosuppressive drugs (IS) and comorbidities. During the current COVID-19 outbreak, the way to manage these diseases remains elusive. Limited data is currently available on AID and IS in the context of this new coronavirus infection. To date, there is no evidence to support an increase in complications of COVID-19 in these patients. In addition, certain drugs that are commonly used to treat AID could be part of the therapeutic arsenal used in COVID-19. The purpose of this article is to review the unique aspects of patients with AID during the COVID-19 outbreak., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Hereditary angioedema type 1 and 2 are due to a deficiency in C1--esterase inhibitor. This molecule inhibits the generation of bradykinin, a potent inflammatory mediator that increases vascular permeability. Upon accumulation of bradykinin, patients affected develop painful subcutaneous or submucosal edemas that last for several days. In case the upper airways are affected, there is risk of suffocation. This type of angioedema does not respond to antihistamines, cortico-steroids or epinephrine. Management of angioedema attacks consists in injecting C1-esterase inhibitor concentrate or icatibant, a bradykinin receptor B2 antagonist. Preventive measures aim at reducing the frequency and the severity of angioedema attacks. Inhibition of -plasma kallikrein by lanadelumab, a monoclonal antibody adminis-tered subcutaneously, is effective and well tolerated., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

The antiphospholipid syndrome (APS) is a complex autoimmune -disease characterized by the expression of antiphospholipid -antibodies (APL) and a variety of clinical presentation. The latest classification defines APS by the occurrence of vascular thrombosis and/or typical obstetrical morbidity together with persistently -detectable APL at least 12 weeks apart. The latest recommendation proposes a risk profile based on the type and titer of APL detected, in order to guide the intensity of prophylactic measures. Based on current knowledge, novel oral anticoagulants should not be used in APS, particularly in patients with a high-risk APL profile or arterial thrombosis. Beyond the mere aspect of anticoagulant treatment, immunomodulatory approaches to the APS such as hydroxychloroquine are under investigation., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Allergic reactions to fish are potentially life-threatening. We detail here various reactions to fish, notably anaphylaxis and food protein induced enterocolitis syndrome, as well as confounders such as reactions to the parasite Anisakis and scombroid poisoning. Most IgE-mediated reactions are directed to β-parvalbumin. This thermo-resistant protein is highly conserved between species of osseous fish, and accounts for allergic cross-reactivity. Cartilaginous fish such as rays express α-parvalbumin, and may constitute an alternative food source in subjects allergic to the beta-form. Diagnosis relies on a meticulous history, skin-prick testing preferably with fresh fish; search for specific IgE and food challenge. Once the diagnosis is established, prevention consists in avoiding all fish products susceptible to induce a reaction., Competing Interests: les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Asthma is a chronic disease that is still frequently poorly controlled, despite recent advances in understanding its pathophysiology. Poor compliance and ineffective inhalation technique remain the main causes of treatment failure. The comorbidities associated with asthma, such as obesity and chronic rhinosinusitis, are other elements to consider in the management of patients. Biological treatments targeting inflammation mediators show encouraging results in recurrent asthma exacerbations despite optimal management. However, their benefit remains limited to certain patients, thus requiring the study of predictive biomarkers to better delineate their indication., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Hemophagocytic Lymphohistiocytosis Abstract. Hemophagocytic lymphohistiocytosis (HLH) is a group of rare diseases characterized by over-activation of the immune system. They form two groups: primary and secondary HLH. Primary HLH are linked to mutations impairing lymphocyte cytotoxicity. Secondary HLH are triggered by infections, autoimmune diseases or neoplasia, the remaining cases being labeled idiopathic. HLH manifest as febrile states, cytopenias and hepatosplenomegaly. In the absence of treatment, they quickly lead to multiple organ failure. The diagnosis is currently based on the presence of several clinical and biological markers. Treatment consists of suppression of the triggering factor, organ support and immunosuppression. Primary forms, affecting a pediatric population, have been the subject of intense research, and are nowadays treated with established therapeutic protocols. Several recent retrospective studies have improved our knowledge of secondary HLH, which affects mostly adults and whose incidence seems to be increasing. Thus, new diagnostic criteria are currently being studied for secondary HLH, and several treatment protocols have just been published or are being evaluated.

Allergic diseases are currently amongst the most frequent diseases of our time. Of all the allergies in the Western countries, allergic rhinoconjunctivitis is the most common. Its diagnosis is based mainly on the history and the correlation between symptoms and contact with the allergen. A step-by-step approach helps optimize diagnostic resources and minimize costs., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Hypersensitivity to human seminal plasma is rare, but probably under-diagnosed. It should be suspected in women with unexplained anaphylaxis, vulvo-vaginitis, pelvic pain and dyspareunia. The diagnosis relies on the clinical presentation, the exclusion of other causes, a positive skin test result to seminal plasma and the detection of IgE directed to allergenic proteins (such as prostate specific antigen). Use of condoms is the best preventive measure. Premedication with antihistamines or anti-inflammatory agents is often unreliable. Some patients may benefit from intra-vaginal or subcutaneous desensitization procedures to seminal plasma, which then require to measures to uphold tolerance. In case of pregnancy wish, artificial insemination or in-vitro fertilization with spermatozoids is an alternative to desensitization., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

These past years, double-blinded placebo controlled food challenges in subjects with irritable bowel syndrome (IBS) reporting sensitivity to gluten have identified a group of individuals without celiac disease (CD) in whom symptoms were clearly aggravated by wheat. Not only did the exposure to wheat trigger intestinal symptoms, but also frequently fatigue and a sensation of foggy mind. Recent studies in mice and sensitive subjects suggest an immune activation by various wheat proteins, with a rapid increase of intestinal mucosal permeability and recruitment of intraepithelial lymphocytes. Moreover, markers of epithelial damage and immune activation are increased in the peripheral blood of wheat-sensitive subjects upon challenge, and decrease under gluten-free diet. Larger studies are needed to better characterize this entity and to distinguish it from food-aggravated IBS and a « forme fruste » of CD., Competing Interests: L’auteur n’a déclaré aucun conflit d’intérêts en relation avec cet article.

The term « eosinophilic gastrointestinal disorders » describes a group of diseases that comprises eosinophilic esophagitis, gastritis, enteritis, and colitis. Eosinophilic esophagitis is the most prevalent form while eosinophilic gastritis, enteritis, and colitis are rare. Food antigens have increasingly been found to trigger the inflammatory response. This review will highlight the epidemiology, clinical manifestations, diagnostic modalities and therapeutic options of eosinophilic gastritis, enteritis, and colitis., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Itchy skin rashes are a frequent reason to seek medical advice. The symptoms may be caused by hypersensitivity reactions to arthropod bites, waterborne parasites or setae from moth caterpillars and are sometimes mistaken for spontaneous urticaria or eczema. Some of these pests are resurging in Switzerland and elsewhere and increasingly responsible for emergency consultation. In this article we review itchy skin rashes caused by bed bugs, scabies, lice, cercariae, Pyemotes spp, caterpillars and harvest mites, which may be confounded with urticaria and allergic contact dermatitis. We detail here clinical manifestations, topographical distribution of skin lesions, epidemiology, treatment and preventive measures.

Sjögren's syndrome (SS) is an autoimmune disease leading to mucosal dryness. It may also involve joints, nerves, kidneys and lungs. Patients with SS are also at increased risk for lymphoma. Diagnosis of SS relies on clinical, biological, histological and radiological criteria, after exclusion of other causes. Initial work-up may be performed in general practice, by serology (antinuclear and anti-SSA/SSB antibodies, rheumatoid factor) and by measuring lacrimal and salivary flow. Antibodies may be within normal range in up to one third of patients and when present are not specific for SS. Histological proof of lymphocytic sialadenitis is precious but invasive. Major salivary glands sonography may help select candidates for labial biopsy. This article elaborates the steps to be taken in case of suspected SS, in order to facilitate early diagnosis.

Acquired inflammatory myopathies and systemic sclerosis are chronic autoimmune conditions. These diseases arise from sustained activation of the innate and adaptive immune system, resulting in damage to blood vessels, muscles, connective tissues and internal organs. Auto-antibodies are found in a majority of cases, which makes the immune serology an important diagnostic tool. The immuno dot assays detect a variety of disease-specific-or-associated antibodies. A positive result should be correlated with the indirect immunofluorescence pattern of the antinuclear antibody screen. Some antibodies are associated with specific organ involvement, other may indicated an underlying neoplastic condition. The scope of this article is to review the diagnostic and prognostic value of antibodies in inflammatory myopathies and systemic sclerosis.

Although most delayed drug hypersensitivity reactions are mild and show rapid improvement after drug discontinuation, there are severe systemic and/or cutaneous drug reactions which may be life-threatening. These entities are discussed here, namely DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). Early detection of warning signs and symptoms may help to take appropriate measures precociously.

Although not specific, an increased in peripheral blood eosinophils may contribute substantially to the diagnosis of numerous infectious, allergic and inflammatory diseases. The scope of this article is to detail pathologies associated with peripheral eosinophilia by order of frequency and to guide further investigations.

Immediate hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAID) can be classified into allergic (immune-mediated) reactions to a single NSAID molecule or a group of chemically similar structure, and pseudo-allergic (or intolerance) linked to pharmacological Cox-1 inhibition. Distinction between these two entities is clinically difficult but important to quantify risks associated with the prescription of another NSAID. Oral challenge test can help the diagnosis. In case of an allergic reaction, a structurally chemically different NSAID will be offered. In case of a pseudo-allergic reaction, cross-sensitivity between non-selective NSAID is common; in these patients selective inhibitors of Cox-2 may be considered. If necessary, tolerance to acetylsalicylic acid can be induced, but has to be maintained by continous administration of the drug.

Relapsing polychondritis is a rare systemic disease. Clinical manifestations are variable and the condition is frequently associated with other diseases. Chondritis typically involves ears, nose, costal cartilages and upper airways. Other classical features include scleritis and episcleritis, mucocutaneous lesions, arthralgia and constitutional symptoms. Repeated inflammation of cartilaginous structures may lead to deformities of the ears, the nose and the airways. Tracheobronchomalacia and aortitis of the ascending portion resulting in aortic regurgitation or aneurysm are feared complications. Treatment is mainly based on systemic corticosteroids alone or in association with immunosuppressants. Several biological immunosuppressive agents are reported effective in refractory disease.

Systemic lupus erythematosus (SLE) is a rare disease mainly affecting women of childbearing age. It is characterized by a very large spectrum of clinical manifestations accompanied by prototypic abnormalities of the immune system. While recent advances in therapeutic approaches have taken place, SLE still has a profound impact on the quality of life and life expectancy of affected persons. The Swiss cohort for longitudinally studying SLE named SSCS responds to the necessity of better understanding the history of the disease, the mechanisms involved in its pathogenesis, to identify and apply new therapeutic and prevention strategies, as well as to analyze the impact that SLE has at the social and personal levels in Switzerland. SSCS is a tool to be used by all researchers interested to provide answers to the many open questions in SLE.