Macrolides et immunité

In order to counteract an ever increasing bacterial resistance, a new trend in antibiotic therapy is to try and obtain compounds with "immunostimulating" properties. Although the macrolides have been known for more than 30 years, their interaction with the host defence system has been poorly investigated. These drugs display an outstanding ability to penetrate and concentrate in phagocytes. Few depressive effects on phagocyte functions have been reported, while some macrolides have been shown to exert an immunostimulating effect in vitro and ex vivo. The data published on this subject are summarized in this review paper. Further studies would be required for a better understanding of structure-immunomodulating activity relationships.     

Allergie à la farine de blé chez l’adulte

The clinical manifestations of allergy to wheat flour are similar to those of allergies to other foods. In adults, food-dependent exercise-induced anaphylaxis, chronic urticaria, and gastrointestinal food allergies (that is, irritable bowel syndrome, eosinophilic colitis, ulcerative colitis) are the most frequently described clinical manifestations of allergy to wheat. Wheat isolates, used as binders and emulsifiers in the food industry, are neo-allergens resulting from chemically induced desamidation of wheat gluten (heating at high temperature in an acidic medium). Wheat isolate allergens can induce severe systemic reactions (e.g., urticaria) and anaphylactic shock. Diagnosis consists of three steps: a suspicion based on the patient's history, identification of the allergen by skin testing and by laboratory tests, and confirmation by oral challenge or by an avoidance regime.     

Allergie aux protéines du lait et aux hydrolysats de protéines de lait : à propos d'une observation au diagnostic retardé

The authors report the case of an infant with a history of eczema due to cow milk and who later had two bouts of urticaria after drinking milk protein hydrolysate. The particular interest in this case is the disconnection between the onset of the eczema (when an allergy workup was not predictive) and the subsequent finding, one year later, of positive IgE-dependant sensitization tests.     

Urticaires : diagnostic,prise en charge et traitement

Urticaria is a common inflammatory skin disease. It is clinically defined as the occurrence of transient papular skin and/or mucosal lesions or subcutaneous lesions called angioedema. Chronic urticaria is defined as a clinical course over more than 6 weeks. Different clinical forms of urticaria can coexist in the same patient. Urticaria results of mast cell activation. The diagnosis of urticaria is based on clinical examination. An allergic etiology for acute urticaria, although rare, is always to find and remove. Chronic urticaria is not allergic. Diagnosis is based on questioning and a careful clinical examination to rule out differential diagnoses. Few diagnostic tests are necessary for diagnosis and management, and are especially useful in case of doubtful diagnosis. The treatment of urticaria is symptomatic and based on anti-H1 second generation antihistamines as first-line therapy. In some chronic urticarial, antihistamines up dosing may be necessary. In the majority of patients, this treatment is sufficient to control chronic urticaria. In case of antihistamines failure, other treatment particularly immunomodulatory treatments can be offered in specialized departments.     

Les urticaires au cours d'un traitement anti-infectieux : le médicament est-il vraiment souvent en cause ?

Hypersensitivity drug reactions, including immediate allergic reactions, are one of many types of adverse drug reactions. While urticaria is one of the most frequent clinical forms of drug allergy, other manifestations may also occur. To determine that the cause of an urticarial reaction is drug-induced is important, although in most cases this diagnosis is not established. Diagnosis is based on immediate skin test reactions and drug provocation testing. These tests are not without danger, which is why a complete clinical history and the patient's responses to the ENDA (European Network for Drug Allergy) questionnaire, as well as careful attention to necessary precautions, are important. The Drug Allergy and Hypersensitivity Database (DAHD) includes 1,267 reports of urticaria possibly due to drugs; β-lactams were the most frequently involved (35.6%). However, a drug allergy work-up demonstrated that only 15.4% of these reactions were actually due to a drug; 44.6% were diagnosed by means of skin tests, the rest by provocation tests. Of the positive tests, 41.2% were positive within the first hour and 16.6% only after 24 hours. Urticaria may be induced by drugs, especially antibiotics, but drugs are not the main cause of urticaria. The diagnosis of drug allergy requires confirmation by relevant tests.     

Utilidad de los macrólidos como antiinflamatorios en las enfermedades respiratorias

The macrolides are antibiotics that, besides their anti-bacterial action, have an anti-inflammatory effect, by decreasing the activity of the immune cells and bacteria cell changes.     

A Case Report of Double‐Filtration Plasmapheresis for the Resolution of Refractory Chronic Urticaria

A 29‐year‐old Chinese female was diagnosed with chronic urticaria. Dexamethasone and gamma globulin initially resolved the illness; however, when dexamethasone was decreased and gamma globulin was withdrawn, urticaria emerged again and could not be controlled by any of the medications used. The diagnosis of refractory chronic urticaria was made and double‐filtration plasmapheresis (DFPP) was performed. The symptoms were relieved during the first DFPP procedure and the disease resolved shortly thereafter. DFPP theoretically removes medium to large molecular substances such as IgG and IgE from circulation, and therefore may prove to be an effective treatment for refractory chronic urticaria.     

Chronic urticaria associated with thyroid carcinoma: report of 4 cases.

Chronic urticaria is a common condition that can be very disabling when severe. A variety of causes has been reported to induce urticaria, including food, infections, drugs and other factors. In more than 50% of cases of chronic urticaria, however, the cause remains unknown and cannot be ascribed to allergic, physical, environmental or other factors. Although an association between chronic idiopathic urticaria and malignancy has been occasionally reported, such an association remains controversial because it is difficult to demonstrate it is not just coincidental. Here we report the cases of four female patients with occult papillary carcinoma of the thyroid who developed chronic urticaria. In all of these cases, removal of the tumor led to prompt resolution of the urticarial lesions, thus suggesting a pathogenetic relationship between the two. This is the first report of papillary thyroid carcinomas associated with chronic urticaria and highlights how chronic urticaria may be an important cutaneous marker for patients with thyroid carcinoma.     

Tako‐tsubo‐like cardiomyopathy after EpiPen administration

Tako‐tsubo‐like cardiomyopathy is characterized by acute chest pain, electrocardiographic changes and increased cardiac enzymes in the absence of obstructive coronary vessel disease. We describe the development of tako‐tsubo‐like cardiomyopathy in an elderly woman after the use of an EpiPen for generalized urticaria and angioedema. As adrenaline may participate in the pathogenesis of this condition, the need for careful patient selection and education in the use of adrenaline self‐injectors remains imperative.     

A case of localized adrenergic urticaria mimicking an allergic reaction to a sweat chloride test

Adrenergic urticaria (AU) is a rare type of physical urticaria triggered by stress. It is frequently confused with IgE‐mediated urticaria or other physical urticarias. This report describes a case of localized adrenergic urticaria triggered by a sweat chloride test in an adolescent male with multiple atopic disorders. A pruritic papular rash at the site of a sweat chloride test prompted an evaluation for allergic and physical urticarias using multiple skin test methods. A positive intradermal skin test to noradrenaline, which reproduced the rash observed during the sweat test, lead to the diagnosis of adrenergic urticaria. This is the first case report describing an immediate adrenergic urticarial reaction to sweat chloride testing in a patient with other atopic disorders. Pediatr Pulmonol. 2009; 44:935–938. © 2009 Wiley‐Liss, Inc.     

Urticaria and urticaria related skin condition/disease in children

Urticaria is a rash, that typically involves skin and mucosa, and is characterized by lesions known as hives or wheals. In some cases there is an involvement of deep dermis and subcutaneous tissue that causes a skin/mucosa manifestation called angioedema. Urticaria and angioedema are very often associated: urticaria-angioedema syndrome. The acute episodic form is the most prevalent in the pediatric population, and it is often a recurrent phenomenon (recurrent urticaria). Acute episodic urticaria it is usually triggered by viruses, allergic reactions to foods and drugs, contact with chemicals and irritants, or physical stimuli. In many instances it is not possible to identify a specific cause (idiopathic urticaria). Chronic urticaria is a condition that can be very disambling when severe. In children is caused by physical factors in 5-10% of cases. Other trigger factors are infections, foods, additives, aeroallergens and drugs. The causative factor for chronic urticaria is identified in about 20% of cases. About one-third of children with chronic urticaria have circulating functional autoantibodies against the high affinity IgE receptor or against IgE. (chronic urticaria with autoantibodies or "autoimmune" urticaria). It is not known why such antibodies are produced, or if the presence of these antibodies alter the course of the disease or influence the response to treatment. Urticaria and angioedema can be symptoms of systemic diseases (collagenopathies, endocrinopathies, tumors, hemolytic diseases, celiachia) or can be congenital (cold induced familiar urticaria, hereditary angioedema). The diagnosis is based on patient personal history and it is very important to spend time documenting this in detail. Different urticaria clinical features must guide the diagnostic work-up and there is no need to use the same blood tests for all cases of urticaria. The urticaria treatment includes identification of the triggering agent and its removal, reduction of aspecific factors that may contribute to the urticaria or can increase the itch, and use of anti-H1 antihistamines (and/or steroids for short periods if antihistamines are not effective). In some instances an anti-H2 antihistamine can be added to the anti-H1 antihistamines, even if the benefits of such practice are not clear. The antileucotriens can be beneficial in a small subgroup of patients with chronic urticaria. In case of chronic urticaria resistant to all the aforementioned treatments, cyclosporine and tacrolimus have been used with good success. When urticaria is associated to anaphylaxis, i.m epinephrine needs to be used, together with antihistamines and steroids (in addition to fluids and bronchodilatators if required).     

Long‐term macrolides for non‐cystic fibrosis bronchiectasis: A systematic review and meta‐analysis

Long‐term macrolides are increasingly being prescribed for stable bronchiectasis. This meta‐analysis assessed the clinical effect of this treatment in bronchiectasis. A systematic review and meta‐analysis were carried out. All randomized, controlled trials (RCT) comparing long‐term macrolides with placebo and/or usual medical care, with outcome measures relating to efficacy and safety were selected. Nine RCT recruiting 530 patients were included. Compared with placebo and/or usual medical care, long‐term macrolides significantly reduced the risk of the exacerbations (number of participants with exacerbations (relative risk = 0.70, 95% confidence interval (CI) 0.60–0.82, P < 0.00001); average exacerbations per participant (weighted mean difference = ?1.01, 95% CI ?1.35 to ?0.67, P < 0.00001)), the St George's Respiratory Questionnaire total scores (weighted mean difference = ?5.39 95% CI ?9.89 to ?0.88, P = 0.02), dyspnoea scale (weighted mean difference = ?0.31 95% CI ?0.42 to ?0.20, P < 0.00001), 24‐h sputum volume (P < 0.00001), and attenuated the decline of forced expiratory volume in 1 s (weighted mean difference 0.02 L, 95% CI 0.00–0.04, P = 0.01). Eradication of pathogens (P = 0.06), overall rate of adverse events (P = 0.61), and emergence of new pathogens (P = 0.61) were not elevated, while gastrointestinal events increased significantly with macrolides (P = 0.0001). Macrolide resistance increased, but a meta‐analysis was not possible due to the diversity of parameters. Long‐term use of macrolides appears to be a treatment option for stable bronchiectasis. The results of this review justify further investigation about adding this intervention to the treatment regimens of bronchiectasis.     

Urticaire médicamenteuse et imputabilité

In France, adverse reactions due to drugs affect 10% of hospitalized patients, which means about one million patients per year. Cutaneous reactions are among the most frequent type of adverse drug reaction, occurring in 2-3% of hospitalized patients. The imputability of drugs that may be responsible calls for a standardized approach leading to a precise score for each drug, and this is a matter that falls in the domain of competence of Pharmacovigilance (PHVG) physicians, not in that of clinicians. Cutaneous reactions can be allergic (implying specific immunity) or pseudoallergic (a non-specific immune reaction). In 95% of the cases of drug-induced urticaria, the mechanism is non-specific and due to a toxic or irritant action of the drug, i.e. a pseudoallergic reaction. There is a true IgE mediated allergy in only about 5% of cases. Drug-induced urticaria has no semiological particularity. CRPVs are responsible for the collection and registration of the reports of adverse effects that are received spontaneously from health professionals. For each report to the PHVG, the causal relation between taking the drug and the onset of the adverse reaction is evaluated according to the official French imputability method. This method includes four chronological criteria and three semiological criteria, and it is accompanied by a bibliographic score. A report of cutaneoallergic effects to the PHVG allows identification of the causative molecule among the many that are potentially responsible, an understanding of the mechanism of action (immunoallergic or pseudoallergic), and results in personalized advice to the patient.     

Cold-induced urticaria

Cold urticaria is characterized by the development of urticaria, usually superficial and/or angioedematous reaction after cold contact. It was found predominantly in young women. The diagnosis is based on the history and ice cube test. Patients with a negative ice cube test may have represented systemic cold urticaria (atypical acquired cold urticaria) induced by general body cooling. The pathogenesis is poorly understood. Cold urticaria can be classified into acquired and familial disorders, with an autosomal dominant inheritance. Idiopathic cold urticaria is most common type but the research of a cryopathy is necessary. Therapy is often difficult. It is essential that the patient be warned of the dangers of swimming in cold water because systemic hypotension can occur. H1 antihistamines can be used for treatment of cold urticaria but the clinical responses are highly variable. The combination with an H2 antagonists is more effective. Doxepin may be useful in the treatment. Leukotriene receptor antagonists may be a novel, promising drug entity. In patients who do not respond to previous treatments, induction of cold tolerance may be tried.     

Urticaire et angio-oedème au froid avec cryofibrinogène chez un enfant

Chronic cold-induced urticaria is rare in children and most often idiopathic. We report a case of chronic cold urticaria with cryofibrinogenaemia in a 3-year-old girl. Since she was 18 months old she had urticaria and angioedema on cold-exposed skin beginning about 20 min after cold stimuli such as aquatic activities and cold drinks. Simultaneously, she had systemic reactions (dizziness, pallor and dyspnoea) that spontaneously resolved after a few minutes. A test for cryofibrinogen was positive. The diagnosis of cold urticaria is usually based on the medical history and confirmed with an ice cube test. Some laboratory tests, such as tests for ANA, cryoglobulin and cryofibrinogen, should be done to rule out secondary cold urticaria. It is imperative that all patients with cold urticaria syndromes be fully informed of the risks associated with cold exposure to prevent potentially severe systemic reactions.     

Prise en charge des urticaires médicamenteuses non allergiques

Drug-induced urticaria occurs frequently and is benign in most cases. It is most often a consequence of intolerance (not a specific allergy), but occasionally it may be the consequence of an authentic IgE-mediated immediate hypersensitivity reaction (IHR). The etiological-pathogenic diagnosis is three-pronged, including history, skin tests and, if necessary, laboratory investigations. In cases of IHR, re-introduction of the medicament is definitely contra-indicated since desensitization is not efficacious. In such cases, one should carry out a battery of skin and/or laboratory tests looking for an allergic cross-reaction caused by molecules of the same class. In cases of intolerance, the medicament can be reintroduced in the large majority of cases, sometimes accompanied by pre-medication with an antihistamine and/or an antileukotriene.     

Génétique du déficit en C1 inhibiteur

C1 esterase inhibitor deficiency is an uncommon disorder characterized by recurrent episodes of angioedema without urticaria, abdominal pain attacks, and life-threatening upper airway obstruction. C1 inhibitor is a serine protease inhibitor that inactivates several different proteases in the complement, contact, coagulation, and fibrinolytic systems. Diagnosis requires careful medical and family history and the measurement of antigenic and functional C1 inhibitor and C4 levels. Inherited C1 inhibitor deficiency is usually transmitted as an autosomal dominant trait and detected during the first or second decades of life. More than 200 mutations have been described (deletion, missense mutations, splice site mutations, stop codon mutations).     

Chronic urticaria caused by cow's milk allergy: immediate or delayed allergy? (apropos of a case)

Chronic urticaria has multiple etiologies, amongst them food allergy, which is not the most frequent. We report a clinical case of chronic urticaria due to cow milk, where paradoxically the responsibility of the food was shown by an epidermo test when the prick test was negative. Development confirmed the responsibility of cow milk. We discuss the mechanisms that relate chronic urticaria to delayed hypersensitivity.     

Partial response to cyclosporine in a patient with Schnitzler's syndrome

Schnitzler's syndrome is an unusual clinical association of chronic urticaria, intermittent fever and monoclonal immunoglobulin M (IgM) gammopathy. The pathogenesis of the urticaria is unclear and treatment is problematic. We describe the case of a 61-year-old woman with a long history of chronic urticaria with severe pruritus, spiking fever and malaise. The IgM-kappa monoclonal component was detected in the patient's serum 4 years after symptom onset. After ineffective treatment with antihistamines and systemic corticosteroids, oral cyclosporine resulted in complete remission of the fever and malaise, which has persisted after an 18-month follow-up. Partial but maintained remission of the urticaria was also observed, allowing corticosteroid doses to be decreased.     

Urticaria and Autoimmunity: Where Are We Now?

There is considerable debate whether chronic urticaria is an autoimmune disease or whether its features suggestive of autoimmunity are epiphenomena. A plethora of circumstantial evidence suggests that chronic urticaria is an autoimmune disease, but criteria to establish autoimmunity require direct proof and indirect evidence, and these are lacking in chronic urticaria. Current approaches to assessing for autoimmunity in vivo via the autologous serum skin test, and in vitro via either basophil histamine release or the basophil activation test are widely utilized, but the results of these tests have limited impact on prediction of the clinical course and efficacy of treatments. Recent guidelines for diagnosing autoimmune urticaria have been proposed, but further investigation is needed.