[Omalizumab for the treatment of chronic urticaria: Real-life findings]. / Traitement de l'urticaire chronique par omalizumab : données en vie réelle.

OBJECTIVE: Assessment of the efficacy and safety of omalizumab in chronic urticaria refractory to conventional treatment (H1-antihistamines at high dosage and montelukast) in real-life practice. PATIENTS AND METHODS: A retrospective, descriptive, single-centre study was performed of the data for all patients presenting refractory chronic spontaneous urticaria or inducible urticaria and receiving omalizumab (300mg every four weeks) from November 2012 to June 2016. RESULTS: In all, 23 patients were included. Omalizumab led to complete or significant remission in 19 patients (83%) with chronic urticaria, with remission in 9 patients (47%) occurring within 72hours of the first injection. One patient had a partial response and 3 (13%) showed no response. Only 2 patients (9%) in complete remission stopped their treatment at 1 and 3 years. 52% of patients presented non-serious adverse events, which in one case resulted in treatment withdrawal. CONCLUSION: Omalizumab exhibited good real-life efficacy in a small series of chronic urticaria patients in France.

Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

BACKGROUND: The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. OBJECTIVE: This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. METHODS: Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. RESULTS: Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. CONCLUSIONS & CLINICAL RELEVANCE: For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%).

[Bullous rash around a peritoneal dialysis catheter exit site]. / Éruption bulleuse péri-ombilicale autour d'un cathéter de dialyse péritonéale.

BACKGROUND: Cutaneous eruption around a peritoneal dialysis (PD) catheter exit site is a rare complication. Herein we report a case of bullous eruption; we discuss the diagnostic approach and the related therapeutic implications. PATIENTS AND METHODS: A 63-year-old man presented a bullous periumbilical eruption two months after initiation of PD. Cultures of laboratory samples ruled out an infectious origin and systemic corticosteroids initiated at 0.5mg/kg for suspected eosinophilic peritonitis produced significant improvement of the cutaneous eruption. Recurrence of the bullous eruption was observed upon dose-reduction of the corticosteroid. Skin histology showed a clinical picture of eczema and direct immunofluorescence was negative. Patch testing was carried out using the European Standard Battery comprising antiseptic, cosmetic and plastic series; a semi-open test was performed with the dressing used for PD, and ROAT was carried out on the povidone iodine (Betadine™) 10% used for topical care during PD. The patch testing and ROAT were positive (++), confirming contact dermatitis due to Betadine™. The eruption totally disappeared on substitution of Betadine™ by chlorhexidine for topical antisepsis of the PD catheter, thus enabling PD to be continued rather than instituting hemodialysis. DISCUSSION: Allergic contact dermatitis around a PD catheter is a rare and little-known complication. In the present case, ROAT testing showed sensitization to Betadine™ and enabled an alternative antisepsis solution to be found, allowing PD to be continued.

[A study of 19 cases of allergy to heparins with positive skin testing]. / Étude de 19 cas d'allergie aux héparines prouvée par des tests cutanés.

BACKGROUND: Allergic hypersensitivity to unfractioned or low-molecular-weight heparins is uncommon but is known, and in particular the most common form is localized dermatitis, although such cases have seldom turned into maculopapular exanthema. Since cross-reactions with other heparins are frequent, identification of therapeutic alternatives is essential. PATIENTS AND METHODS: This retrospective study included patients referred to the Department of Dermatology and Allergology at Tenon Hospital between 2000 and 2012 with suspicion of allergy to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and sensitized to at least one heparin (i.e. positive skin tests to at least one heparin). The heparins and hirudins used were tested in the forearm by means of intradermal skin tests. All patients were contacted in 2012 to establish whether they had used some form of heparin since the cutaneous allergy tests. RESULTS: Nineteen patients had at least one positive skin test for heparin; 1 patient had presented anaphylactic shock, while 18 others had presented localized eczema (12) or generalized dermatitis (6). The heparin most often responsible for these adverse reactions was enoxaparin (13/19). An LMWH was responsible in most cases (18 vs. 1 with UFH). Of these 18 patients, 16 also presented positive skin tests for UFH, 9 for synthetic heparinoid and 1 for hirudin. 11/19 patients were tested for fondaparinux (a synthetic pentasaccharid) and all had negative skin tests. 5/7 patients with negative skin tests had taken fondaparinux without any visible reaction, whereas 2 who also tested negative experienced localized eruption at the injection site. DISCUSSION: Our results underline the greater frequency of delayed hypersensitivity reactions compared with immediate reactions to heparins. Skin tests can help to identify substitution molecules. Fondaparinux might be an alternative but certain diagnosis relies on rechallenge.

Cutaneous adverse drug reaction to oral acetazolamide and skin tests.

BACKGROUND: Few cases of cutaneous adverse drug reactions (CADR) to oral acetazolamide, a non-antimicrobial sulfonamide, have been previously reported, and the interest of acetazolamide skin tests has never been studied. OBJECTIVES: We report a series of ten patients with oral acetazolamide CADR and skin tests. PATIENTS AND METHODS: The files of ten patients with CADR secondary to oral acetazolamide prescribed for cataract surgery in most cases referred between 2001 and 2011 in four French dermatology and allergy departments were retrospectively reviewed. Skin tests with acetazolamide were performed in nine patients and twelve controls. Other sulfonamides were tested in five of ten patients. RESULTS: Seven patients developed maculopapular exanthema and four had acute generalized exanthematous pustulosis. Patch tests were positive for 8/9 patients, prick tests for 2/4 and intradermal tests for 3/3. Patch and prick or intradermal test results were concordant in 2/3 positive subjects. Patch tests for other sulfonamides were negative, as were patch tests in controls. CONCLUSIONS: We report the largest series of CADR to oral acetazolamide (maculopapular exanthema or acute generalized exanthematous pustulosis). A drug eruption after cataract surgery should be investigated for accountability of acetazolamide. In view of this retrospective study, skin tests and particularly intradermal tests appear to be an important contribution to demonstrate accountability.

Five cases of contact dermatitis to a trendy pet.

Skin contact with animal hair may induce contact urticaria (syndrome) or protein contact dermatitis. We report here 5 cases of dermatitis due to contact with ferrets kept as pets. The nature of the skin lesions, i.e. eczematous dermatitis, as well as the history of our 5 cases point to protein contact dermatitis. Further studies are requested to confirm this hypothesis and to identify the mechanisms and allergens. Physicians must be aware of the possibility of contact dermatitis with ferrets, especially when the patient has no previous history of atopic dermatitis and presents dermatitis of the neck, arm and around mouth.

[Contact urticaria induced by hydrolyzed wheat proteins in cosmetics]. / Urticaire de contact aux hydrolysats de protéines de blé contenus dans des cosmétiques.

BACKGROUND: Hydrolyzed wheat protein, produced by hydrolysis of gluten, is used in certain cosmetics and foods as emulsifiers and stabilizers. It can induce contact urticaria to cosmetics and/or anaphylaxis to food via an immunologic mechanism. PATIENTS AND METHODS: A 28-year-old female beautician presented recurrent contact urticaria, initially on the hands and then more diffused, immediately after applying cosmetics of the same brand containing hydrolyzed wheat protein. Skin tests were positive with the cosmetics and with the hydrolyzed wheat protein contained therein. A 34-year-old woman presented four episodes of generalized urticaria after eating industrially prepared foods. She had also experienced contact urticaria with cosmetics. Skin tests with hydrolyzed wheat protein were positive. For both patients, withdrawal of cosmetics and foods containing hydrolyzed wheat protein led to the regression of symptoms. They were both tolerant to traditional wheat products, such as bread and pastries. DISCUSSION: Although contact urticaria to hydrolyzed wheat protein is rarely described, it must be understood since treatment by eradication of this product is simple and because contact urticaria may precede food allergy. Patients are tolerant to products containing unmodified wheat protein.

[Indications for rapid readout skin tests]. / Tests cutanés à lecture immédiate : indications.

Rapid readout skin tests are indicated in the investigation of antigens involved immediate reactions, whether or not IgE-mediated. They are thus indicated in the exploration of some immediate reactions in allergology-dermatology reactions such as immunological contact urticaria (latex allergy for example) and protein contact dermatitis.

The Src tyrosine kinase Hck is required for Tel-Abl- but not for Tel-Jak2-induced cell transformation.

Tel-Abl and Tel-Jak2 are fusion proteins associated with human haematologic neoplasms. They possess constitutive tyrosine kinase activity and activate common downstream signalling pathways like Stat-5, PI3-K/Akt, Ras/MapK and NF-kappaB. In this study, we showed the specific requirement of Src family members for the Tel-Abl-mediated cell growth, activation of Stat5, PI3-K/Akt and Ras/MapK while dispensable for Tel-Jak2. Hck was found strongly phosphorylated in Tel-Abl-expressing Ba/F3 cells and sensitive to imatinib mesylate treatment, providing evidence that Hck is a target of Tel-Abl tyrosine kinase activity. Overexpression of a kinase dead form of Hck inhibits the proliferation of Ba/F3 cells expressing Tel-Abl as the phosphorylation of Akt and Erk1/2. These results argue for an important role of Hck in Tel-Abl oncogenic signalling.

PDGFRB mutants found in patients with familial infantile myofibromatosis or overgrowth syndrome are oncogenic and sensitive to imatinib.

Recently, germline and somatic heterozygous mutations in the platelet-derived growth factor receptor ß (PDGFRB) have been associated with familial infantile myofibromatosis (IM), which is characterized by soft tissue tumors, and overgrowth syndrome, a disease that predisposes to cancer. These mutations have not been functionally characterized. In the present study, the activity of three PDGFRB mutants associated with familial IM (R561C, P660T and N666K) and one PDGFRB mutant found in patients with overgrowth syndrome (P584R) was tested in various models. The P660T mutant showed no difference with the wild-type receptor, suggesting that it might represent a polymorphic variant unrelated to the disease. By contrast, the three other mutants were constitutively active and able to transform NIH3T3 and Ba/F3 cells to different extents. In particular, the germline mutant identified in overgrowth syndrome, P584R, was a stronger oncogene than the germline R561C mutant associated with myofibromatosis. The distinct phenotypes associated with these two mutations could be related to this difference of potency. Importantly, all activated mutants were sensitive to tyrosine kinase inhibitors such as imatinib, nilotinib and ponatinib. In conclusion, the PDGFRB mutations previously identified in familial IM and overgrowth syndrome activate the receptor in the absence of ligand, supporting the hypothesis that these mutations cause the diseases. Moreover, imatinib seems to be a promising treatment for patients carrying these mutations. To our knowledge, these are the first confirmed gain-of-function point mutations of PDGFRB in human cancer.

Persistent STAT5 activation in myeloid neoplasms recruits p53 into gene regulation.

STAT (Signal Transducer and Activator of Transcription) transcription factors are constitutively activated in most hematopoietic cancers. We previously identified a target gene, LPP/miR-28 (LIM domain containing preferred translocation partner in lipoma), induced by constitutive activation of STAT5, but not by transient cytokine-activated STAT5. miR-28 exerts negative effects on thrombopoietin receptor signaling and platelet formation. Here, we demonstrate that, in transformed hematopoietic cells, STAT5 and p53 must be synergistically bound to chromatin for induction of LPP/miR-28 transcription. Genome-wide association studies show that both STAT5 and p53 are co-localized on the chromatin at 463 genomic positions in proximal promoters. Chromatin binding of p53 is dependent on persistent STAT5 activation at these proximal promoters. The transcriptional activity of selected promoters bound by STAT5 and p53 was significantly changed upon STAT5 or p53 inhibition. Abnormal expression of several STAT5-p53 target genes (LEP, ATP5J, GTF2A2, VEGFC, NPY1R and NPY5R) is frequently detected in platelets of myeloproliferative neoplasm (MPN) patients, but not in platelets from healthy controls. In conclusion, persistently active STAT5 can recruit normal p53, like in the case of MPN cells, but also p53 mutants, such as p53 M133K in human erythroleukemia cells, leading to pathologic gene expression that differs from canonical STAT5 or p53 transcriptional programs.

[Allergic risk of aprotinin]. / Le risque allergique de l'aprotinine.

OBJECTIVE: To analyse the risk of anaphylactic reaction with the administration of aprotinin, either by i.v. route or as a biological sealant application and to propose updated guidelines in accordance with current data of the literature. DATA SOURCES: Search in the Medline data base of articles in French, English and German, published since 1960, using following key words: aprotinin, allergy, anaphylaxis. STUDY SELECTION: All categories of articles on this topic have been selected. DATA EXTRACTION: Articles have been analysed for history, incidence and mechanisms of anaphylactic reactions, symptomatology, factors of risk, diagnosis and precautions of use. DATA SYNTHESIS: Aprotinin is widely used for decreasing preoperative bleeding, especially in cardiac and orthopaedic surgery. This heterologue protein can cause anaphylactic reactions in 0.5 to 5.8% of patients, depending of the inclusion criteria. They are mediated by IgG and IgE antibodies. Aprotinin has also a direct, non specific, histaminoliberation effect. The clinical presentation includes various degrees of severity, up to cardiac arrest. Documented factors of risk are a previous parotinin administration, 15 days to 6 months before, and intolerance to beef meat, white of egg, cheese and milk. The immediate biological diagnosis is obtained on assessing the degranulation of basophiles (histamine) and mastocytes (tryptase), as well as the concentration of anti-aprotinin antibodies (RAST IgE), with a test of inhibition. The secondary assessment, six weeks later, includes prick-tests and intradermoreactions if the former are negative. The mean precaution consists to search factors of risk at preanaesthetic assessment. The predictive value of systematic prick-tests has not yet been validated. Anti H1 and anti H2 premedication is inefficient. A test dose can trigger a severe reaction. CONCLUSION: Considering a significant anaphylactic risk, aprotinin administration becomes only licit after a careful evaluation of the benefit-risk ratio.

[Peroperative anaphylactic shock caused by latex]. / Choc anaphylactique peropératoire au latex.

A case is reported of severe anaphylactic shock occurring in a 32 yr old woman after foetal extraction during caesarean section. The agent responsible was the latex from the surgical gloves used. This was proved by the different allergological tests carried out: positive prick-tests to the latex, positive human basophil degranulation test and the finding of specific anti-latex IgE. All the tests carried out using the anaesthetic drugs were negative.

[Photoplethysmography and laser Doppler velocimetry in the study of cutaneous vasomotility at high altitudes]. / Utilisation de la photopléthysmographie et de la vélocimétrie laser Doppler dans l'exploration de la vasomotricité cutanée en haute altitude.

During the second French scientific medical expedition to the Himalaya (ARPE, Annapurna IV, 1985), modifications of cutaneous circulation in hypoxia were studied. Two techniques were used for the first time to evaluate cutaneous vasoactivity under such conditions: laser Doppler velocimetry and photoplethysmography. Measurements were performed on the pulp of the third and fourth fingers of the right hand in 6 subjects native of sea-level countries: first at sea level, then in hypoxia after 15 days at 4,800 m before and after ingestion of a vasodilator drug (nicardipine 20 mg). Cutaneous circulation was explored under three thermal conditions: baseline (ambient temperature); after vasodilation obtained by immersion of the hand in hot water (40 degrees C), and after immersion of the hand in cold water (12 degrees C). In prolonged hypoxia a reduction in vasoconstriction at 12 degrees C was observed with both techniques. No significant change was observed at 40 degrees C. After dosing with nicardipine, the results differed according to the exploratory technique: a slight increase of the laser Doppler signal (NS) and a decrease of the photoplethysmographic signal were recorded. Acclimatization to cold and to hypoxia may concur to determine this response of cutaneous circulation. The action of vasodilating agents on cutaneous microcirculation in prolonged hypoxia is not clear and deserves further investigation. These drugs must be used with caution in the prevention and treatment of frostbite.

[Anaphylactic reactions to aprotinin: intradermal diagnostic tests] . / Réaction anaphylactique à l'aprotinine: intérêt diagnostique des tests intradermiques.

A 66-year-old patient, undergoing heart surgery, developed an anaphylactic reaction following the first administration of a test-dose of aprotinin. Skin tests were performed six months later. Prick-tests with 10(-2) and 10(-1) aprotinin dilutions were negative but intradermal reaction with a 10(-3) dilution was clearly positive. The level of aprotinin specific IgE was high, both in the serum obtained before surgery and in the one sampled on the day of the testing. As no reaction was observed during the tests, skin-testing and specific IgE appear to be an interesting alternative to a potentially dangerous test-dose, but they both need further evaluation.

[Anisakis simplex and immediate hypersensitivity reactions]. / Anisakis simplex et réactions d'hypersensibilité immédiate.

BACKGROUND: Anisakis simplex is one of the nematode worms that parasitize sea mammals. When its larvae are accidentally ingested by humans, they can infect the host, resulting in anisakiasis manifested by digestive symptoms, or they may cause an allergic reaction, which in some cases may be severe. CASE REPORTS: We report three cases of acute urticaria associated with abdominal pain, and hypotension in two of them, starting two to six hours after ingestion of raw fish. The diagnosis of an allergic reaction caused by Anisakis simplex was based on the clinical histories and positive tests for anisakis-specific IgE. DISCUSSION: In patients with acute urticaria associated with abdominal symptoms, a history of ingestion of raw fish in the preceeding hours is evocative of gastro-allergic anisakiasis. In association with symptomatic treatment, gastrointestinal endoscopy allows the larvae to be visualized and removed, which may relieve the symptoms and provide a diagnosis before the results of skin testing and serological assay are known.

[Value of correlated immunofluorescence and immunoperoxidase study of monoclonal markers in 2 adult cases of histiocytosis X]. / Intérêt de l'étude corrélée par immunofluorescence et immunoperoxydase des marqueurs monoclonaux dans deux observations d'histiocytose X de l'adulte.

Two cases of adult histiocytosis X have been studied using monoclonal antibodies on skin sections by two techniques: indirect immunofluorescence and immunoperoxidase. This study confirm: --that histiocytosis X express two specific antigens Ia and T6, --the relations between Langerhans cell and histiocytosis X. Especially, it suggests that histiocytosis X cell would be a dedifferentiated cell with receptors OKT4 and OKT10.

[Chronic urticaria, thyroiditis and autologous serum test]. / Urticaire chronique, thyroïdite auto-immune et test au sérum autologue.

INTRODUCTION: The autoimmune nature of certain forms of chronic urticaria remains debatable. Aim of the study. To find a correlation in terms of autoimmune pattern between chronic urticaria and thyroiditis using the autologous serum test and the search for anti-thyroid antibodies. PATIENTS AND METHODS: Study in a single center of 59 patients having consulted for urticaria that had progressed for more than six weeks and without precise etiology. An autologous serum test was conducted and anti-thyroid autoantibodies were searched for in the serum stored after the test. RESULTS: Out of 59 patients, 51 had an interpretable autologous serum test and 57 underwent research for anti-thyroid antibodies. Twelve patients out 57 (21 p.cent) exhibited one or more types of positive (n=10) or borderline (n=2) anti-thyroid antibodies, and eight out of 12 (66.6 p.cent) had a known thyroid disease before the onset of urticaria. The systematic blood test permitted the discovery of 4 cases of unknown anti-thyroid antibodies. The symptoms regressed in two of these patients without any specific treatment, one patient was treated with L thyroxin for hyperthyroidism without any improvement in the symptoms and one other patient had normal thyroid function. Among these 12 patients, 11 underwent autologous serum tests, but only 3 of them exhibited clearly positive results and one was doubtful. CONCLUSIONS: Within the limits of this study, we found a 21 p.cent rate of patients with chronic urticaria exhibiting one or more anti-thyroid antibodies. The positivity of the autologous serum test does not appear to be related with autoimmune thyroid disorders.

[Immediate hypersensitivity to latex: a new problem. Future perspectives]. / L'allergie immédiate au latex: un problème nouveau. Perspectives d'avenir.

From a series of 30 cases of immediate allergy to the latex of Hevea Brasiliensis, the authors recall the principal clinical aspects of these allergies, specially contact urticaria (during the use of surgical or cleaning gloves) and systemic anaphylactic accidents, essentially the anaphylactic shock during surgical procedures. They mention the diagnostic procedures; skin tests and measurement of specific IgE (RAST). They show the interest of biological research, yielding to the identification of the allergens of the latex in order to obtain non allergenic latex. Such a result would be of interest to limit the number of the accidents in a period where the use of rubber protective material is much larger/gloves and condoms).