Granulocytes and mast cells in AllergoOncology-Bridging allergy to cancer: An EAACI position paper.

Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer. We highlight key mechanisms which may inform cancer treatment and propose pertinent areas for future research. We suggest areas where understanding the communication between granulocytes, mast cells, and the tumor microenvironment, will be crucial for identifying immune mechanisms that may be harnessed to counteract tumor development. For example, a comprehensive understanding of allergic and immune factors driving distinct neutrophil states and those mechanisms that link mast cells with immunotherapy resistance, might enable targeted manipulation of specific subpopulations, leading to precision immunotherapy in cancer. We recommend specific areas of investigation in AllergoOncology and knowledge exchange across disease contexts to uncover pertinent reciprocal functions in allergy and cancer and allow therapeutic manipulation of these powerful cell populations. These will help address the unmet needs in stratifying and managing patients with allergic diseases and cancer.

AllergoOncology: Biomarkers and refined classification for research in the allergy and glioma nexus-A joint EAACI-EANO position paper.

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE-mediated diseases and glioma. Allergic disease stems from a Th2-biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour-immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro-Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult-type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune-glioma interactions to ultimately improve patient prognosis and survival.

Omalizumab ensures compatibility to bee venom immunotherapy (VIT) after VIT-induced anaphylaxis in a patient with systemic mastocytosis.

BACKGROUND: Systemic reactions and anaphylaxis due to Hymenoptera venoms occur in up to 7.5% of the European population. Fatal sting reactions are very rare. Serum tryptase levels should be measured in all patients with a history of severe reactions in order to detect mastocytosis and to determine the risk of severe reactions to venom immunotherapy (VIT). The risk to experience severe or even fatal anaphylaxis due to insect stings is quite high in patients with mastocytosis. Therefore, lifelong VIT is recommended in these highly threatened patients. Multicenter studies involving a large population report that up to 20% of patients undergoing VIT have intolerance and systemic reactions to immunotherapy. Some of these side effects occur repeatedly and cannot be managed by standard treatment. A pre-treatment with the anti-IgE antibody omalizumab was useful in many cases. However, omalizumab is not approved for the indication anaphylaxis. Therefore, there is still no defined protocol for omalizumab pre-treatment, and the optimal duration, dosage as well as long-time benefits are still unclear. CASE REPORT: We present a 60-year-old female patient with mastocytosis who developed a severe anaphylactic reaction during initiation of bee VIT. Serum tryptase was elevated, and a KIT mutation D816V was subsequently confirmed. Component-resolved diagnostic tests revealed specific IgE antibodies to recombinant Api m 1 only. The patient was treated with 150 mg omalizumab, administered subcutaneously 5 weeks, 3 weeks, and 1 week prior to re-start of immunotherapy and for 2 months in parallel to VIT. Updosing was done by a 7-day rush schedule. During this period, no anaphylactic reaction developed, and the bee VIT was well tolerated with up to 200 µg bee venom. The patient is currently in the 3rd year of treatment and tolerates the treatment very well. CONCLUSION: Omalizumab may be used as a premedication in patients with mastocytosis who do not tolerate VIT. Although there is no consensus on the treatment protocol, treatment for 2 - 6 months is considered adequate. The long-term benefits of such treatment require further research.

Biologics for atopic diseases: Indication, side effect management, and new developments.

With the advent of biologicals, more and more therapeutics are available that specifically address specific switch points in the pathomechanism of immunologically dominated diseases. Thus, the focus of diagnostics and therapy (precision medicine) is more on the individual disease characteristics of the individual patient. Regarding the different phenotypes of atopic diseases, severe asthma was the first entity for which biologicals were approved, followed by urticaria, and finally atopic dermatitis and chronic rhinosinusitis with nasal polyps. Experience in the treatment of severe bronchial asthma has shown that the intensity of the response to biological therapy depends on the quality of clinical and immunological phenotyping of the patients. This also applies to different diseases of the atopic form, as patients can suffer from several atopic diseases at the same time, each with different characteristics. Biologics are already emerging that may represent a suitable therapy for allergic bronchial asthma, which often occurs together with severe neurodermatitis, and chronic rhinosinusitis with nasal polyps. In practice, however, the question of possible combinations of biologicals for the therapy of complex clinical pictures of individual patients is increasingly arising. In doing so, the side effect profile must be taken into account, including hypersensitivity reactions, whose diagnostic and logistical management must aim at a safe and efficient therapy of the underlying disease. Increased attention must also be paid to biological therapy in pregnancy and planned (predictable) vaccinations as well as existing infections, such as SARS-CoV-2 infection. Before starting a biological therapy, the immune status should be checked with regard to chronic viral and bacterial infections and, if necessary, the vaccination status should be refreshed or missing vaccinations should be made up for before starting therapy. Currently, reliable data on the effect of biologicals on the immunological situation of SARS-CoV-2 infection and COVID-19 are not available. Therefore, research and development of suitable diagnostic methods for detection of immunologically caused side effects as well as detection of potential therapy responders and non-responders is of great importance.

IgE Epitope Profiling for Allergy Diagnosis and Therapy - Parallel Analysis of a Multitude of Potential Linear Epitopes Using a High Throughput Screening Platform.

Immunoglobulin E (IgE) is pivotal for manifestation and persistence of most immediate-type allergies and some asthma phenotypes. Consequently, IgE represents a crucial target for both, diagnostic purposes as well as therapeutic approaches. In fact, allergen-specific immunotherapy - aiming to re-route an IgE-based inflammatory response into an innocuous immune reaction against the allergen - is the only curative approach for IgE-mediated allergic diseases known so far. However, this requires the cognate allergen to be known. Unfortunately, even in well-characterized allergics or asthmatics, often just a small fraction of total IgE can be assigned to specific target allergens. To overcome this knowledge gap, we have devised an analytical platform for unbiased IgE target epitope detection. The system relies on chemically produced random peptide libraries immobilized on polystyrene beads ("one-bead-one-compound (OBOC) libraries") capable to present millions of different peptide motifs simultaneously to immunoglobulins from biological samples. Beads binding IgE are highlighted with a fluorophore-labeled anti-IgE antibody allowing fluorescence-based detection and isolation of positives, which then can be characterized by peptide sequencing. Setting-up this platform required an elaborate optimization process including proper choice of background suppressants, secondary antibody and fluorophore label as well as incubation conditions. For optimal performance our procedure involves a sophisticated pre-adsorption step to eliminate beads that react nonspecifically with anti-IgE secondary antibodies. This step turned out to be important for minimizing detection of "false positive" motifs that otherwise would erroneously be classified as IgE epitopes. In validation studies we were able to retrieve artificial test-peptide beads spiked into our library by using IgE directed against those test-peptides at physiological concentrations (≤20 IU/ml of specific IgE), and disease-relevant bead-bound epitopes of the major peanut allergen Ara h 2 by screening with sera from peanut allergics. Thus, we established a platform with which one can find and validate new immunoglobulin targets using patient material which displays a largely unknown immunoglobulin repertoire.

Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA)A, Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI)B, Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI)D, Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI)E, Österreichische Gesellschaft für Pneumologie (ÖGP)F in co-operation with the German, Austrian, and Swiss ARIA groupsG, and the European Academy of Allergy and Clinical Immunology (EAACI)H.

BACKGROUND: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2. MATERIALS AND METHODS: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic. RESULTS: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future. CONCLUSION: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.

Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events.

Purpose: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction.Methods: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs.Results: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV).Conclusion: There is an urgent need for a simpler symptom- or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future.Cite this as Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events. Allergo J Int 2020; 29:97-125https://doi.org/10.1007/s40629-020-00126-6.

Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events.

PURPOSE: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction. METHODS: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs. RESULTS: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV). CONCLUSION: There is an urgent need for a simpler symptom- or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future.

Glycan and Peptide IgE Epitopes of the TNF-alpha Blockers Infliximab and Adalimumab - Precision Diagnostics by Cross-Reactivity Immune Profiling of Patient Sera.

Biological drugs like therapeutic antibodies are widely used for the treatment of various diseases like inflammatory disorders and cancer. A drawback of these novel treatments is the substantial proportion of patients experiencing adverse reactions such as loss-of-drug effect or hypersensitivity reactions. These reactions are associated with pre-existing and/or developing anti-drug antibodies. Especially IgE development is a risk factor for life-threatening systemic anaphylaxis. METHODS: In order to characterize the individual drug-specific serum IgE, an IgE cross-reactivity immune profiling (ICRIP) assay was developed. Individual IgG epitopes of anti-drug antibodies against adalimumab were identified by epitope mapping via peptide microarray. RESULTS: ICRIP analyses of sera from patients treated with the therapeutic antibodies adalimumab (ADL) and infliximab (IFX) reveal individual, distinct IgE binding patterns. IgG epitopes were identified mostly located in the variable region of ADL. CONCLUSIONS: Using ICRIP and peptide microarrays for pharmacovigilance of the TNF-α blockers IFX and ADL, risk factors and biomarkers before and during therapy shall be identified. These diagnostic systems provide the basis for a safe and efficacious therapy decision for each patient in cases of adverse drug reactions mediated by different types of anti-drug antibodies.

Peanut oleosins associated with severe peanut allergy-importance of lipophilic allergens for comprehensive allergy diagnostics.

BACKGROUND: Peanut allergy is one of the most common and most severe food allergies in Western countries and its accurate diagnosis to prevent potential life-threatening allergic reactions is crucial. However, aqueous extracts used for routine diagnostic measurements are devoid of lipophilic allergens such as oleosins. We have recently succeeded in the isolation and purification of these unique proteins, and the present study evaluates their allergenic potential and clinical relevance. OBJECTIVE: We sought to assess allergenicity and sensitization prevalence of oleosins obtained from both raw and in-shell roasted peanuts. In addition, we tested the utilization of natural and recombinant oleosins for allergy diagnostic purposes. METHODS: Oleosin sensitization, prevalence, and impact of thermal processing were analyzed by immunoblot with sera from 52 peanut-allergic individuals displaying different clinical phenotypes. The application of natural and recombinant oleosins for allergy diagnostics was investigated by basophil activation test (BAT). IgE-binding epitopes were identified by oligopeptide microarray. RESULTS: Sensitization to oleosins was observed exclusively in peanut-allergic subjects suffering from severe systemic reactions. IgE-binding capacity of oleosins derived from in-shell roasted peanuts was increased as shown by immunoblot analysis and BAT. Both natural and recombinant molecules can be used to identify oleosin-sensitized patients by BAT. A linear epitope of Ara h 15 was determined that displays high similarity to other seed-derived oleosins. CONCLUSIONS: Oleosins are clinically relevant peanut allergens and most likely associated with severe allergic symptoms. In-shell roasting increases their allergenicity, which is consistent with the observation that most allergic reactions are in connection with roasted peanuts.

Development of a novel strategy to isolate lipophilic allergens (oleosins) from peanuts.

BACKGROUND: Peanut allergy is one of the most severe class I food allergies with increasing prevalence. Especially lipophilic allergens, such as oleosins, were found to be associated with severe symptoms, but are usually underrepresented in diagnostic extracts. Therefore, this study focused on isolation, molecular characterization and assessment of the allergenicity of peanut oleosins. METHODS AND RESULTS: A comprehensive method adapted for the isolation of peanut oil bodies of high purity was developed comprising a stepwise removal of seed storage proteins from oil bodies. Further separation of the oil body constituents, including the allergens Ara h 10, Ara h 11, the presumed allergen oleosin 3 and additional oleosin variants was achieved by a single run on a preparative electrophoresis cell. Protein identification realized by N-terminal sequencing, peptide mass fingerprinting and homology search revealed the presence of oleosins, steroleosins and a caleosin. Immunoblot analysis with sera of peanut-allergic individuals illustrated the IgE-binding capacity of peanut-derived oleosins. CONCLUSION: Our method is a novel way to isolate all known immunologically distinct peanut oleosins simultaneously. Moreover, we were able to provide evidence for the allergenicity of oleosins and thus identified peanut oleosins as probable candidates for component-resolved allergy diagnosis.

Pathologic skeletal muscle perfusion in patients with myositis: detection with quantitative contrast-enhanced US--initial results.

PURPOSE: To prospectively determine whether contrast material-enhanced ultrasonography (US) can depict inflammation-induced changes in muscle perfusion for patients suspected of having dermatomyositis or polymyositis and to compare these findings with those of magnetic resonance (MR) imaging and muscle biopsy. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Perfusion in skeletal muscles was quantified with contrast-enhanced intermittent power Doppler US by applying a modified model that analyzed the replenishment kinetics of microbubbles. In 22 patients (16 women, six men; mean age, 52 years +/- 17) who were suspected of having myositis and in 10 healthy volunteers (two women, eight men; mean age, 28 years +/- 4), contrast-enhanced US of the clinically affected right biceps muscle was performed to measure blood flow, blood volume, and blood flow velocity. Additionally, the right upper arm was examined with a 1.5-T unit by using three different MR imaging techniques. Findings were compared with the results of clinical examinations and muscle biopsy. Data for perfusion-related parameters obtained at contrast-enhanced US were analyzed by using a nonparametric Mann-Whitney U test. RESULTS: Eight patients had histologically confirmed myositis and showed significantly higher blood flow velocity (P = .01), blood flow (P = .001), and blood volume (P = .002) at contrast-enhanced US than did patients who did not have myositis. Blood flow velocity (P = .001) and blood flow (P = .002) were significantly higher in patients with myositis than in volunteers. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis, while contrast material enhancement on fat-suppressed T1-weighted MR images was found in only four of seven patients with myositis. CONCLUSION: Initial results show that contrast-enhanced US is a feasible method for noninvasively demonstrating increased perfusion in the involved muscle groups in patients with myositis.

Contrast-enhanced ultrasound in dermatomyositis- and polymyositis.

OBJECTIVE: To evaluate prospectively contrast-enhanced ultrasound (CEUS) in patients suspected of having dermatomyositis or polymyositis. METHODS: In 35 patients (23 women, 12 men; mean age, 51 years+/-16 years) who were suspected of having dermatomyositis or polymyositis, perfusion in clinically affected skeletal muscles was quantified with contrast-enhanced intermittent power Doppler ultrasound. By applying a modified model that analyzed the replenishment kinetics of microbubbles, the perfusion-related parameters blood flow, local blood volume and blood flow velocity were measured. Findings were compared with muscle biopsy appearances and with the results of MRI that was performed with a 1.5-Tesla unit. Receiver operating characteristic analysis was performed and optimum thresholds for diagnosis of myositis were determined. RESULTS: Eleven patients had histologically confirmed dermatomyositis or polymyositis and showed significantly higher blood flow velocity (P=.01 for dermato- and P<.001 for polymyositis), blood flow (P<.001 for dermato- and polymyositis), and blood volume (P=.007 for dermato- and P<.001 for polymyositis) on contrast-enhanced ultrasound than those who did not have myositis. An increase in signal intensity on T2-weighted MR images was found in all patients with myositis. MRI had a sensitivity, specificity, positive (PPV), and negative predicting values (NPV) of 100%, 88%, 77%, and 100% for diagnosis of myositis, respectively. CEUS blood flow was the best ultrasound measure for diagnosis of dermato- or polymyositis with sensitivity, specificity, PPV, and NPV of 73%, 91%, 80%, and 88%, respectively. CONCLUSIONS: Increased skeletal muscle perfusion measured by CEUS could serve as an additional measurer for the diagnosis of an inflammatory myopathy.

[Contact dermatitis to permanent make up: manifestation of a pre-existing nickel allergy]. / Manifestation einer Nickelallergie als Kontaktdermatitis auf Permanent-Make-up.

During recent years demands for permanent make up and especially permanent lip liner is increasing not only in the USA but also in Germany. Adverse reactions to these products are almost unknown and not documented in literature. Declaration of contents and side effects are not required for tattoo colors, in contrast to the rules for medical treatments. Our patient developed inflammation and vesiculation within the area of tattooing three days after injection of a permanent lip liner. Treatment with steroids induced complete resolution of the lip liner-associated dermatitis. However, not only the effect of the lip liner was lost but also the natural color of her lip was partly destroyed by inflammation. Diagnostic allergy testing revealed strong delayed hypersensitivity to nickel and a mild patch test reaction to the permanent lip liner. Examination of the permanent make-up by mass spectrometry detected nickel in a concentration of 1.8 ppm. No allergic reaction could be seen when the purified red dye itself was tested. This patient with pre-existing nickel allergy developed an allergic contact dermatitis from the injection of a permanent lip liner contaminated with nickel.

Methicillin-resistant Staphylococcus aureus colonization in inflammatory versus non-inflammatory skin diseases: who should be screened?

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was prospectively investigated in a dermatology outpatient setting. Swabs were taken from anterior nares, perineum and lesional skin in 229 patients with erosive inflammatory skin diseases (n=88), venous leg ulcers (n=58) or basal cell carcinoma (n=83) and processed by standard methods. The isolated MRSA strains were characterized by pulsed-field gel electrophoresis after digestion with the restriction enzyme SmaI. MRSA carriage was detected in 10/88 patients with inflammatory skin diseases, 5/58 with venous leg ulcers and 0/83 with basal cell carcinoma. Most of the MRSA isolates could be identified as either the Rhine-Hessen epidemic strain or local epidemic strains. None of the isolated strains was resistant to vancomycin, gentamicin or mupirocin. MRSA is uncommon in outpatients in our dermatology clinic; however, the presence of chronic ulcers and erosions was significantly associated with MRSA positivity. Therefore, patients with chronic ulcers and erosions should be screened for MRSA colonization to implement infection control measures.

Lymphangioma circumscriptum of the vulva following surgical and radiological therapy of cervical cancer.

BACKGROUND: Lymphangioma circumscriptum of the vulva rarely develops after postoperative pelvic irradiation. GOAL: The goal was to describe two cases of lymphangioma circumscriptum and their treatment and present a brief review of the literature. STUDY: Two female patients, aged 75 years and 46 years, presented with persistent edema, papules, and vesicles of the labia majora, which had developed 15 and 9 years after hysterectomy, lymph node dissection, and subsequent irradiation of cervical cancer. The external diagnosis was genital warts. RESULTS: In both cases histology revealed lymphangioma circumscriptum of the vulva. Whereas the older woman's condition responded well to laser treatment, keloids developed in the second patient at the site of carbon dioxide laser vaporization. CONCLUSION: CO2 laser treatment recently has been recommended for vulvar lymphangioma circumscriptum and is effective in vaporizing the communicating vessels to deeper cisterns. To our knowledge this is the first description of keloid development after laser therapy for vulvar lymphangioma circumscriptum, and such an effect should be considered before CO2 laser surgery is applied for this particular entity.