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1.  Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases 
Allergo Journal International  2014;23(8):282-319.
The present guideline (S2k) on allergen-specific immunotherapy (AIT) was established by the German, Austrian and Swiss professional associations for allergy in consensus with the scientific specialist societies and professional associations in the fields of otolaryngology, dermatology and venereology, pediatric and adolescent medicine, pneumology as well as a German patient organization (German Allergy and Asthma Association; Deutscher Allergie- und Asthmabund, DAAB) according to the criteria of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF).
AIT is a therapy with disease-modifying effects. By administering allergen extracts, specific blocking antibodies, toler-ance-inducing cells and mediators are activated. These prevent further exacerbation of the allergen-triggered immune response, block the specific immune response and attenuate the inflammatory response in tissue.
Products for SCIT or SLIT cannot be compared at present due to their heterogeneous composition, nor can allergen concentrations given by different manufacturers be compared meaningfully due to the varying methods used to measure their active ingredients. Non-modified allergens are used for SCIT in the form of aqueous or physically adsorbed (depot) extracts, as well as chemically modified allergens (allergoids) as depot extracts. Allergen extracts for SLIT are used in the form of aqueous solutions or tablets.
The clinical efficacy of AIT is measured using various scores as primary and secondary study endpoints. The EMA stipulates combined symptom and medication scores as primary endpoint. A harmonization of clinical endpoints, e. g., by using the combined symptom and medication scores (CSMS) recommended by the EAACI, is desirable in the future in order to permit the comparison of results from different studies. The current CONSORT recommendations from the ARIA/GA2LEN group specify standards for the evaluation, presentation and publication of study results.
According to the Therapy allergen ordinance (TAV), preparations containing common allergen sources (pollen from grasses, birch, alder, hazel, house dust mites, as well as bee and wasp venom) need a marketing authorization in Germany. During the marketing authorization process, these preparations are examined regarding quality, safety and efficacy. In the opinion of the authors, authorized allergen preparations with documented efficacy and safety, or preparations tradeable under the TAV for which efficacy and safety have already been documented in clinical trials meeting WAO or EMA standards, should be preferentially used. Individual formulations (NPP) enable the prescription of rare allergen sources (e.g., pollen from ash, mugwort or ambrosia, mold Alternaria, animal allergens) for specific immunotherapy. Mixing these allergens with TAV allergens is not permitted.
Allergic rhinitis and its associated co-morbidities (e. g., bronchial asthma) generate substantial direct and indirect costs. Treatment options, in particular AIT, are therefore evaluated using cost-benefit and cost-effectiveness analyses. From a long-term perspective, AIT is considered to be significantly more cost effective in allergic rhinitis and allergic asthma than pharmacotherapy, but is heavily dependent on patient compliance.
Meta-analyses provide unequivocal evidence of the efficacy of SCIT and SLIT for certain allergen sources and age groups. Data from controlled studies differ in terms of scope, quality and dosing regimens and require product-specific evaluation. Therefore, evaluating individual preparations according to clearly defined criteria is recommended. A broad transfer of the efficacy of certain preparations to all preparations administered in the same way is not endorsed. The website of the German Society for Allergology and Clinical Immunology (; DGAKI: Deutsche Gesellschaft für Allergologie und klinische Immunologie) provides tables with specific information on available products for AIT in Germany, Switzerland and Austria. The tables contain the number of clinical studies per product in adults and children, the year of market authorization, underlying scoring systems, number of randomized and analyzed subjects and the method of evaluation (ITT, FAS, PP), separately given for grass pollen, birch pollen and house dust mite allergens, and the status of approval for the conduct of clinical studies with these products.
Strong evidence of the efficacy of SCIT in pollen allergy-induced allergic rhinoconjunctivitis in adulthood is well-documented in numerous trials and, in childhood and adolescence, in a few trials. Efficacy in house dust mite allergy is documented by a number of controlled trials in adults and few controlled trials in children. Only a few controlled trials, independent of age, are available for mold allergy (in particular Alternaria). With regard to animal dander allergies (primarily to cat allergens), only small studies, some with methodological deficiencies are available. Only a moderate and inconsistent therapeutic effect in atopic dermatitis has been observed in the quite heterogeneous studies conducted to date. SCIT has been well investigated for individual preparations in controlled bronchial asthma as defined by the Global Initiative for Asthma (GINA) 2007 and intermittent and mild persistent asthma (GINA 2005) and it is recommended as a treatment option, in addition to allergen avoidance and pharmacotherapy, provided there is a clear causal link between respiratory symptoms and the relevant allergen.
The efficacy of SLIT in grass pollen-induced allergic rhinoconjunctivitis is extensively documented in adults and children, whilst its efficacy in tree pollen allergy has only been shown in adults. New controlled trials (some with high patient numbers) on house dust mite allergy provide evidence of efficacy of SLIT in adults.
Compared with allergic rhinoconjunctivitis, there are only few studies on the efficacy of SLIT in allergic asthma. In this context, newer studies show an efficacy for SLIT on asthma symptoms in the subgroup of grass pollen allergic children, adolescents and adults with asthma and efficacy in primary house dust mite allergy-induced asthma in adolescents aged from 14 years and in adults.
Aspects of secondary prevention, in particular the reduction of new sensitizations and reduced asthma risk, are important rationales for choosing to initiate treatment early in childhood and adolescence. In this context, those products for which the appropriate effects have been demonstrated should be considered.
SCIT or SLIT with pollen or mite allergens can be performed in patients with allergic rhinoconjunctivitis using allergen extracts that have been proven to be effective in at least one double-blind placebo-controlled (DBPC) study. At present, clinical trials are underway for the indication in asthma due to house dust mite allergy, some of the results of which have already been published, whilst others are still awaited (see the DGAKI table “Approved/potentially completed studies” via (according to When establishing the indication for AIT, factors that favour clinical efficacy should be taken into consideration. Differences between SCIT and SLIT are to be considered primarily in terms of contraindications. In individual cases, AIT may be justifiably indicated despite the presence of contraindications.
SCIT injections and the initiation of SLIT are performed by a physician experienced in this type of treatment and who is able to administer emergency treatment in the case of an allergic reaction. Patients must be fully informed about the procedure and risks of possible adverse events, and the details of this process must be documented (see “Treatment information sheet”; available as a handout via Treatment should be performed according to the manufacturer‘s product information leaflet. In cases where AIT is to be performed or continued by a different physician to the one who established the indication, close cooperation is required in order to ensure that treatment is implemented consistently and at low risk. In general, it is recommended that SCIT and SLIT should only be performed using preparations for which adequate proof of efficacy is available from clinical trials.
Treatment adherence among AIT patients is lower than assumed by physicians, irrespective of the form of administration. Clearly, adherence is of vital importance for treatment success. Improving AIT adherence is one of the most important future goals, in order to ensure efficacy of the therapy.
Severe, potentially life-threatening systemic reactions during SCIT are possible, but – providing all safety measures are adhered to – these events are very rare. Most adverse events are mild to moderate and can be treated well.
Dose-dependent adverse local reactions occur frequently in the mouth and throat in SLIT. Systemic reactions have been described in SLIT, but are seen far less often than with SCIT. In terms of anaphylaxis and other severe systemic reactions, SLIT has a better safety profile than SCIT.
The risk and effects of adverse systemic reactions in the setting of AIT can be effectively reduced by training of personnel, adhering to safety standards and prompt use of emergency measures, including early administration of i. m. epinephrine. Details on the acute management of anaphylactic reactions can be found in the current S2 guideline on anaphylaxis issued by the AWMF (S2-AWMF-LL Registry Number 061-025).
AIT is undergoing some innovative developments in many areas (e. g., allergen characterization, new administration routes, adjuvants, faster and safer dose escalation protocols), some of which are already being investigated in clinical trials.
Cite this as Pfaar O, Bachert C, Bufe A, Buhl R, Ebner C, Eng P, Friedrichs F, Fuchs T, Hamelmann E, Hartwig-Bade D, Hering T, Huttegger I, Jung K, Klimek L, Kopp MV, Merk H, Rabe U, Saloga J, Schmid-Grendelmeier P, Schuster A, Schwerk N, Sitter H, Umpfenbach U, Wedi B, Wöhrl S, Worm M, Kleine-Tebbe J. Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases – S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD). Allergo J Int 2014;23:282–319
PMCID: PMC4479478  PMID: 26120539
allergen-specific immunotherapy; AIT; Hyposensitization; guideline; allergen; allergen extract; allergic disease; allergic rhinitis; allergic asthma
2.  Aeroallergen sensitization influences quality of life and comorbidities in patients with nasal polyposis 
Nasal polyposis (NP) is a chronic inflammatory disease of unknown etiology that impairs quality of life (QoL). The role of atopy in NP is not established. The aim of this study was to describe the clinical characteristics and QoL in a broad sample of patients with NP and to evaluate the influence of allergy on this disease.
A multicenter, observational, cross-sectional study was conducted in 67 allergy units in Spain. NP and nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity were diagnosed following EP3OS guidelines. Rhinitis and asthma were classified following Allergic Rhinitis and Its Impact on Asthma and the Global Initiative for Asthma guidelines, respectively. Skin tests with a battery of aeroallergens were performed on all patients. A visual analog scale (VAS) and Short-Form 12 (SF-12) and 31-item Rhinosinusitis Outcome Measure (RSOM 31) questionnaires were completed by all the patients.
Of the 671 patients included, 611 were evaluable. Mean age was 46 years and 50% of patients were men. Also, 50% were atopic. Asthma was present in 66% of patients and NSAID hypersensitivity was present in 26%. The most frequent symptoms were nasal congestion and rhinorrhea. Mean value of VAS was 58.6. Global health and bodily pain were the items most frequently identified in the SF-12 questionnaire and nasal and ocular symptoms in the RSOM-31 questionnaire. There was a good correlation between VAS score and QoL (p < 0.0001). Rhinitis was more severe in nonallergic patients. Asthma was more frequent in atopic patients, whereas ASA triad was more frequent in nonatopic patients. Atopic patients showed higher VAS scores and worse QoL.
Atopic NP patients showed worse QoL, higher incidence of asthma and a less severe form of rhinitis than non-atopic patients.
PMCID: PMC3904043  PMID: 23168143
Aeroallergens; allergy; asthma; atopy; cross-sectional study; nasal polyposis; NSAID hypersensitivity; quality of life; rhinitis; skin tests
3.  376 Epidemiology of Immediate Type Adverse Drug Reactions and Rashes Elicited by Nsaid 
NSAID are frequently used and can often cause adverse drug reactions (ADR) ranging from generally mild to sometimes severe and life-threatening reactions. ADRs are in most cases interpreted as pseudo-allergic, presumably non immunologic, but their dynamics and appearance in a subgroup of patients is suggestive for an IgE-mediated mechanism.
In this study, we retrospectively analysed data of 501 patients from our outpatient clinic population of the past 7 years with ADR to NSAID. Data was evaluated regarding the culprit drug or drugs, type and severity of reactions, age, gender, atopy, number of co-medication, co-morbidity and infections etc. as risk factors. Further, skin test and provocation test results were reviewed for their clinical relevance and reliability.
Acetylsalicylic acid (ASA), paracetamol, diclofenac, mefenamic acid and propyphenazone were found as top five of causative drugs for ADR. The most common symptoms were angioedema, urticaria, pruritus, exanthema and dyspnea. ASA caused dyspnea, angioedema and urticaria in the majority of the cases. Diclofenac was found to be the most common culprit for severe anaphylactic reactions, followed by paracetamol and propyphenazone. Sixty percent of the NSAID reactors suffered from an atopic disease or had an atopic predisposition. There was a significant association between proven hypersensitivity reactions and reaction initiation after drug intake regarding the time interval.
Our data suggest that -atopic predisposition is a risk factor for intolerance reaction to NSAID, -ASS accounts for non-immunologic, intolerance reactions, whereas severe anaphylactic reactions to diclofenac and/or propyphenazone seem to be IgE-mediated, -a shorter time interval between drug intake and appearance of symptoms is supportive for clinical relevance and could be an indicator for IgE-mediated ADR. Acknowledgements: FWF project L467-B05.
PMCID: PMC3512835
4.  Cross-reactivity to Acetaminophen and Celecoxib According to the Type of Nonsteroidal Anti-inflammatory Drug Hypersensitivity 
Identification of tolerable alternative analgesics is crucial for management in nonsteroidal anti-inflammatory drug (NSAID)-sensitive patients. We investigated cross-reactivity of acetaminophen and celecoxib according to the type of aspirin/NSAID hypersensitivity and aimed to determine the risk factors for cross-intolerance.
We retrospectively reviewed the medical records of patients intolerant to aspirin and NSAIDs who had undergone an acetaminophen and/or celecoxib oral provocation test. Aspirin/NSAID hypersensitivity was classified into 4 types according to a recently proposed classification: aspirin-exacerbated respiratory disease (AERD), aspirin-exacerbated chronic urticaria (AECU), aspirin-induced acute urticaria/angioedema (AIAU), and NSAID-induced blended reaction (NIRD).
A total of 180 patients with hypersensitivity to aspirin and NSAIDs were enrolled; 149 acetaminophen provocation test results and 145 celecoxib provocation test results were analyzed. The overall cross-reaction rates to acetaminophen and celecoxib were 24.8% and 10.3%, respectively. There was a significant difference in the cross-reactivity to acetaminophen according to the type of NSAID hypersensitivity. Cross-reactivity to acetaminophen was highest in the AECU group (43.9%), followed by the AERD (33.3%), NIBR (16.7%), and AIAU (12.5%) groups. Underlying chronic urticaria was more prevalent in patients with cross-intolerance to both acetaminophen (P=0.001) and celecoxib (P=0.033). Intolerance to acetaminophen was associated with intolerance to celecoxib (P<0.001).
Acetaminophen and celecoxib may induce adverse reactions in a non-negligible portion of aspirin/NSAID-sensitive patients. Physicians should be aware of the possible cross-reactions of these alternative drugs and consider an oral challenge test to confirm their tolerability.
PMCID: PMC3936045  PMID: 24587953
Acetaminophen; celecoxib; cross reactions; hypersensitivity; intolerance; anti-inflammatory agents; non-steroidal
5.  Therapy of atopic eczema 
Major objective is the evaluation of the medical effectiveness of different therapeutical approaches and the cost effectiveness with relevance for Germany.
This health technology assessment (HTA) evaluates systemically randomized controlled studies (RCT) on the therapy of atopic dermatitis which were published between 1999 and 2004. Further it includes some important clinical studies which have been published after 2004 and other updates the English HTA report by Hoare et al. [1].
Topical corticosteroids and topical calcineurin-inhibitors are the principal substances which are currently used for anti-inflammatory therapy in atopic dermatitis. These substances have shown a significant therapeutic efficacy in controlled studies. In newer controlled studies no difference was observable when corticosteroids were applied once or more than once daily onto the skin. Moreover, there is now one controlled study available which points to the fact that an interval therapy with a stronger topical corticosteroid over a limited time (some weeks) may lower the risk of recurrent flares of atopic dermatitis. Both topical calcineurin-inhibitors pimecrolimus and tacrolimus have shown a significant therapeutical efficacy in a number of placebo-controlled prospective studies. The wealth of data is high for these substances. Both substances have been shown to be efficient in infants, children and adult patients with atopic dermatitis.
The importance of a so-called basic therapy with emollients which have to be adapted to the current status of skin is generally accepted in clinical practice. Controlled studies show the efficacy of ”basic therapy” - although the level of evidence is quite low for this approach. The skin of patients with atopic dermatitis is colonized in the majority with Staphylococcus aureus, a gram-positive bacterium. Therefore, a therapeutical approach for the treatment of atopic dermatitis is the anti-bacterial or anti-septic treatment of the skin. Due to the lack of randomized controlled studies there is still not certain proof that antimicrobial or anti-septic treatment of non-infected eczematous skin is efficient for the treatment of atopic dermatitis. A reduction of Staphylococcus aureus is observable during an anti-inflammatory treatment of the skin with topical corticosteroids and/or the topical calcineurin-inhibitor tacrolimus. Antihistaminic drugs which are orally applied in atopic dermatitis may support the therapy of the itching skin disease. One controlled study showed a rapid reduction of itch during the use of a non-sedating antihistaminic drug. There are, however, no controlled studies which show the efficacy of antihistaminic drugs on the skin condition in atopic dermatitis.
Dietetic restrictions should be applied only after a specific allergological diagnostic clarification. The “gold standard” is still a (blinded) oral provocation test which has to show an influence of a given food on the skin condition. There is sufficient evidence that there is no general dietetic approach which shows efficacy in atopic dermatitis. The treatment of patients with lactobacillae is still controversially discussed. Available studies which showed an efficacy show methodological weaknesses so that this approach can not be generally recommended for clinical practice at the time now. Approaches reducing house dust mite in the surroundings of patients with atopic dermatitis can have an effect on the skin condition so that at least in mite sensitized patients this approach appears to be reasonable. The specific immunotherapy with house dust mite showed clinical efficacy in a controlled study and in some open studies. The education of patients with atopic dermatitis or their parents is a further efficient approach in the management of this chronic skin disease. Interdisciplinary approaches in patients’ education containing also psychological elements appear to be an attractive new approach for the treatment of atopic dermatitis.
Phototherapy is a further possibility of intervention in atopic dermatitis in adolescent or adult patients. The available evidence points to the fact that UVB radiation (both small and broad spectrum), UVA-1 radiation and balneo-phototherapy are efficient therapeutical options for atopic dermatitis. The systemic treatment with the immunosuppressive substance cyclosporine A is efficient in the treatment of severe atopic dermatitis. Cyclosoprine A is approved for the treatment of adult patients with this skin disease. The immunosuppressive substance azathioprine showed a high clinical efficacy in two controlled studies for severe atopic dermatitis in adults. There are still controversial results for the application of antagonists to leucotriens in the treatment of atopic dermatitis: in some open studies a therapeutical efficacy was described which was, however, not reproducible in a newer controlled study. The phosphodiesterase-4-inhibitor cipamphyllin was efficient in the treatment of atopic dermatitis in a controlled study but weaker than a topical class II (i. e. moderate strength) corticosteroide. The HTA assessment further describes so-called complementary therapeutical approaches which have either not properly been studied in controlled clinical trials or which have been shown to be of no value for the treatment of atopic dermatitis.
Altogether six full health-economic evaluations were found which did not cover the whole therapy spectrum of atopic dermatitis. The choice of the most cost effective treatment option of topic corticosteroids depends less on application frequency, but rather on the drug price and more used or unused quantity of the standard packages, so even smallest improvements justify a more frequent application. The results from health economic evaluations of calcineurin-inhibitors are not reliable. The therapy of severe atopic dermatitis in adults with ciclosporin shows comparable cost effectiveness in comparison to UVA/UVB therapy.
The spectrum of therapeutical procedures has increased for atopic dermatitis but is still not sufficient. The spectrum of established substances is much smaller compared to psoriasis, another chronic and common inflammatory skin disease. There is need for the development new substances which can be applied topically and which are aimed to treat atopic dermatitis in early childhood. Another need for new developments can be found for the treatment of severe atopic dermatitis in adults.
The spectrum of therapeutical procedures has increased for atopic dermatitis but is still not sufficient. The spectrum of established substances is much smaller compared to psoriasis, another chronic and common inflammatory skin disease. There is need for the development new substances which can be applied topically and which are aimed to treat atopic dermatitis in early childhood. Another need for new developments can be found for the treatment of severe atopic dermatitis in adults.
Due to lack of health economic evaluations therapy decisions in the treatment of atopic dermatitis must take place on the basis of clinical decision criteria. The prescription of topic corticosteroids should prefer low priced drugs. Reliable statements about the cost effectiveness of the new calcineurin-inhibitors tacrolimus and pimecrolimus.
PMCID: PMC3011357  PMID: 21289970
6.  283 Relationship between Aeroallergen Sensitization and Asthma Severity in Patients with Aspirin-Exacerbated Respiratory Disease 
The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is presumed to involve the aspirin/non steroidal anti-inflammatory drug (NSAID)-induced abnormal metabolism of arachidonic acid, resulting in the production of 5-lipoxygenase metabolites, particularly leukotriene C4. Aspirin intolerance occurs around the same time as asthma onset, and a few of the patients with AERD had suffered from pediatric asthma. Although atopy is not associated with the pathogenesis of AERD, some of the patients with AERD have aeroallergen sensitization. There are few studies in which the association between the pathogenesis of AERD and atopy has been clarified.
Ninety AERD patients, whose aspirin sensitivity was determined by the aspirin challenge test, and 100 aspirin-tolerant asthma (ATA) patients, whose age and sex were adjusted, participated in this study. Atopy was defined as a positive reaction in an intradermal test to one or more of 19 common aeroallergens, or a positive reaction above class one in Immuno CAP RAST. We analyzed the relationships between aeroallergen sensitization and clinical settings of AERD patients.
The atopic and non atopic AERD groups showed median serum total IgE concentrations of 464 and 130 IU/l (P value = 0.004), respectively. The asthma of atopic patients with AERD was milder than that of non atopic patients with AERD. (P value = 0.05) The Lund-Mackay score of atopic patients with AERD was lower than that of non atopic patients with AERD. (P value = 0.02)
Two-thirds of the patients with AERD showed aeroallergen sensitization. The asthma and sinusitis in atopic patients with AERD were significantly milder than those in non atopic patients with AERD. Aeroallergen sensitization might prevent the worsening of asthma in patients with AERD.
PMCID: PMC3512656
7.  Antibody and cytokine responses to house dust mite allergens and Toxoplasma gondii antigens in atopic and non-atopic Brazilian subjects 
Clinical immunology (Orlando, Fla.)  2010;136(1):148-156.
According to hygiene hypothesis, a lower exposure to infection is associated with increased prevalence of allergic diseases. This study aimed to investigate the association between atopy and Toxoplasma gondii (Tg) infection by analyzing the antibody and cytokine responses to house dust mite allergens and T. gondii antigens in Brazilian subjects. A total of 275 individuals were assessed and divided into atopics (n=129) and non-atopics (n=146) based on markers of allergy (positive skin prick test and ELISA-IgE to mite allergens) or Tg-seropositive (n=116) and Tg-seronegative (n=159) groups according to infection markers (positive ELISA-IgG to T. gondii). Tg-seropositive individuals presented lower allergenic sensitization (37%) to mite allergens than Tg-seronegative subjects (54%). A significant association was found between atopy and negative serology to T. gondii (OR: 2.0; 95% CI: 1.23–3.26; P<0.05). Proliferative responses and cytokine production after antigenic stimulation showed predominant synthesis of Th1-cytokines as IFN-γ in Tg-seropositive patients, whether atopics or non-atopics. Conversely, Th2-cytokines as IL-5 prevailed in atopics compared to non-atopics, regardless the seropositivity to T. gondii. Levels of IL-10, IL-13, IL-17, and TGF-β were not able to discriminate the groups. Hence, a negative association between atopy and infection by T. gondii was demonstrated for the first time in Brazilian subjects, focusing on the antibody and cytokine responses and indicating that the immunomodulation induced by the parasite may play a protective role in the development of allergic diseases.
PMCID: PMC3039445  PMID: 20359954
Toxoplasma gondii; Allergic diseases; House dust mites; Hygiene hypothesis; IgE antibodies; Cytokines
8.  Incrimination of Blomia tropicalis as a Potent Allergen in House Dust and Its Role in Allergic Asthma in Kolkata Metropolis, India 
The increasing trend in allergic diseases has become obvious in the present day, especially in developing countries like India, because of many factors such as change in ambient air quality, increased air pollution, metamorphic change in living habits and lifestyle, and climate.1 Mites present in house dust represent a major source of allergens, resulting in different allergic manifestations all over the world, and hypersensitivity to these dust mites may play a pivotal role in pathogenesis of several allergic complaints including bronchial asthma. The present study evaluated the sensitization toward house dust and house dust mites among patients residing in Kolkata metropolis, India, who are suffering from allergic asthma.
The skin prick test was performed on a total of 1079 patients (585 males and 494 females) between the age group 5–50 years and 50 healthy controls using a variety of 16 common aero-allergenic extracts including 4 allergens of interest, viz. Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis and total house dust allergens. Total serum IgE level was measured by using the EIA technique and specific IgE levels against aforesaid allergens were detected with the Pharmacia ImmunoCAP 100 System. The influence of age and sex, if any, on allergen sensitivity was also investigated. All statistical analyses were performed using SPSS 10.0 for Windows and Zar.2
The responses among patients with asthma to house dust and house dust mite allergen tests were as follows: house dust (96.22%), D. pteronyssinus (75.06%), B. tropicalis (72%), and D. farinae (63.72%). The frequency of positive skin response was found to be independent of age and sex. The total serum IgE levels in patients varied between 7.3 and 4040 IU/ml (mean 369 ± 26.51 IU/ml). Specific IgE antibody test proved that 83% patients showed sensitivity toward at least 1 of the allergens tested.
The results indicate that patients are highly sensitive to house dust and 3 other allergenic mites, namely, D. pteronyssinus, D. farinae, and B. tropicalis, as evidenced by the skin prick test, quantification of total serum IgE, and detection of allergen-specific IgE antibodies among patients of Kolkata. Although mites belonging to the genus Dermatophagoides have already been incriminated as a major source of allergen in house dust in India, this is the first time the role of B. tropicalis mites causing allergic asthma has been reported from an Indian population. Thus, the importance of B. tropicalis mite as an aetiopathological agent in causing various allergic manifestations among the Kolkata population should not be undermined and the allergen should be included in routine allergy testing.
PMCID: PMC3488897  PMID: 23268430
allergy; Dermatophagoides spp.; Blomia tropicalis; house dust; skin prick test; IgE
9.  423 Multiple Manifestations of Food Allergy in a Patient with a Change of Eating Habits 
Food-induced allergic reactions are responsible for a variety of symptoms and disorders involving the skin, gastrointestinal and respiratory tracts and can be attributed to IgE-mediated and non–IgE-mediated (cellular) mechanisms.
Food allergy frequency varies according to age, local diet, and many other factors. The diagnosis of food allergy is based on clinical history, skin prick test (SPT), food specific IgE and more recently atopy patch tests (APT). If needed the use of an oral food challenge to confirm allergy or tolerance.
Describes the case of a patient with multiple manifestations of food allergy after eating habit change.
Man 20 years with a history of food allergy to egg in childhood (at date in remission) asthma and rhinitis and urticaria in contact to cats. He presents an atopic dermatitis, recurrent abdominal pain and diarrhea 18 months after change in eating habits (he became vegetarian). He also presents oral syndrome with cow's milk. The patient had 4 episodes of anaphylaxis post prandial grade 3. In 3 of them the patient ate goat cheese and the other cow cheese. Also 2 of the episodes were associated with exercise. Skin prick tests with goat`s cheese: 13 mm, cow´s milk: 8 mm wheat: 3 mm, corn 3 mm, chicken 3.5 mm, egg yolk: 3.5 mm, avocado and rice 3 mm. Atopy patch test: (+ +) goat`s milk (+) peanuts and coffee. Total IgE 686 IU/mL.
Foods with positive results were excluded from the diet and a complete remission of atopic dermatitis, abdominal pain, diarrhea and anaphylaxis was observed. All foods were reintroduced successfully except milk of goats and cows milk. The patient is currently asymptomatic.
The literature describes different kinds of manifestations of food allergy: immediate hypersensitivity (IgE mediated), delayed hypersensitivity (T lymphocytes mediated) and mixed. Highlights in this case an adult patient with a history of atopy who makes changes in eating habits, developping a food allergy to goat´s and cow s milk, with immediate (anaphylaxis, oral syndrome) and delayed manifestations (atopic dermatitis and chronic diarrhea).
PMCID: PMC3512613
10.  Use of Non-Steroidal Anti-Inflammatory Drugs That Elevate Cardiovascular Risk: An Examination of Sales and Essential Medicines Lists in Low-, Middle-, and High-Income Countries 
PLoS Medicine  2013;10(2):e1001388.
Patricia McGettigan and David Henry find that, although some non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac are known to increase cardiovascular risk, diclofenac is included on 74 countries' essential medicine lists and was the most commonly used NSAID in the 15 countries they evaluated.
Certain non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., rofecoxib [Vioxx]) increase the risk of heart attack and stroke and should be avoided in patients at high risk of cardiovascular events. Rates of cardiovascular disease are high and rising in many low- and middle-income countries. We studied the extent to which evidence on cardiovascular risk with NSAIDs has translated into guidance and sales in 15 countries.
Methods and Findings
Data on the relative risk (RR) of cardiovascular events with individual NSAIDs were derived from meta-analyses of randomised trials and controlled observational studies. Listing of individual NSAIDs on Essential Medicines Lists (EMLs) was obtained from the World Health Organization. NSAID sales or prescription data for 15 low-, middle-, and high-income countries were obtained from Intercontinental Medical Statistics Health (IMS Health) or national prescription pricing audit (in the case of England and Canada). Three drugs (rofecoxib, diclofenac, etoricoxib) ranked consistently highest in terms of cardiovascular risk compared with nonuse. Naproxen was associated with a low risk. Diclofenac was listed on 74 national EMLs, naproxen on just 27. Rofecoxib use was not documented in any country. Diclofenac and etoricoxib accounted for one-third of total NSAID usage across the 15 countries (median 33.2%, range 14.7–58.7%). This proportion did not vary between low- and high-income countries. Diclofenac was by far the most commonly used NSAID, with a market share close to that of the next three most popular drugs combined. Naproxen had an average market share of less than 10%.
Listing of NSAIDs on national EMLs should take account of cardiovascular risk, with preference given to low risk drugs. Diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity. Diclofenac should be removed from EMLs.
Please see later in the article for the Editors' Summary
Editors' Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs. Aspirin, the first NSAID, was developed in 1897 but there are now many different NSAIDs. Some can be bought over-the-counter but others are available only with prescription. NSAIDs can help relieve short- and long-term pain, reduce inflammation (redness and swelling), and reduce high fevers. Common conditions that are treated with NSAIDs include headaches, toothache, back ache, and arthritis. NSAIDs work by stopping a class of enzymes called cyclo-oxygenases (COXs) from making prostaglandins, some of which cause pain and inflammation. Like all drugs, NSAIDs have some unwanted side effects. Because certain prostaglandins protect the stomach lining from the stomach acid that helps to digest food, NSAID use can cause indigestion and stomach ulcers (gastrointestinal complications). In addition, NSAIDs increase the risk of heart attacks and stroke to varying degrees and therefore should be avoided by people at high risk of cardiovascular diseases—conditions that affect the heart and/or blood vessels.
Why Was This Study Done?
Different NSAIDs are associated with different levels of cardiovascular risk. Selective COX-2 inhibitors (e.g., rofecoxib, celecoxib, etoricoxib) generally have fewer stomach-related side effects than non-selective COX inhibitors (e.g., naproxen, ibuprofen, diclofenac). However, some NSAIDs (rofecoxib, diclofenac, etoricoxib) are more likely to cause cardiovascular events than others (e.g., naproxen). When doctors prescribe NSAIDs, they need to consider the patient's risk profile. Particularly for patients with higher risk of cardiovascular events, a doctor should either advise against NSAID use or recommend one that has a relatively low cardiovascular risk. Information on the cardiovascular risk associated with different NSAIDs has been available for several years, but have doctors changed their prescribing of NSAIDs based on the information? This question is of particular concern in low- and middle-income countries where cardiovascular disease is increasingly common. In this study, the researchers investigate the extent to which evidence on the cardiovascular risk associated with different NSAIDs has translated into guidance and sales in 15 low-, middle-, and high-income countries.
What Did the Researchers Do and Find?
The researchers derived data on the relative risk of cardiovascular events associated with individual NSAIDs compared to non-use of NSAIDs from published meta-analyses of randomized trials and observational studies. They obtained information on the NSAIDs recommended in 100 countries from national Essential Medicines Lists (EMLs; essential medicines are drugs that satisfy the priority health care needs of a population). Finally, they obtained information on NSAID sales for 13 countries in the South Asian, Southeast Asian, and Asian Pacific regions and NSAID prescription data for Canada and England. Rofecoxib, diclofenac, and etoricoxib consistently increased cardiovascular risk compared with no NSAIDs. All three had a higher relative risk of cardiovascular events than naproxen in pairwise analyses. Naproxen was associated with the lowest cardiovascular risk. No national EMLs recommended rofecoxib, which was withdrawn from world markets 8 years ago because of its cardiovascular risk. Seventy-four national EMLs listed diclofenac, but only 27 EMLs listed naproxen. Diclofenac was the most commonly used NSAID, with an average market share across the 15 countries of nearly 30%. By contrast, naproxen had an average market share of less than 10%. Finally, across both high- and low-/middle-income countries, diclofenac and etoricoxib accounted for one-third of total NSAID usage.
What Do These Findings Mean?
These findings show that NSAIDs with higher risk of cardiovascular events are widely used in low-/middle- as well as high-income countries. Diclofenac is the most popular NSAID, despite its higher relative risk of cardiovascular events, which is similar to that of rofecoxib. Diclofenac is also widely listed on EMLs even though information on its higher cardiovascular risk has been available since 2006. In contrast, naproxen, one of the safest in relative terms of the NSAIDs examined, was among the least popular and was listed on a minority of EMLs. Some aspects of the study's design may affect the accuracy of these findings. For example, the researchers did not look at the risk profiles of the patients actually taking NSAIDs. However, given the volume of use of high-risk NSAIDS, it is likely that these drugs are taken by many individuals at high risk of cardiovascular events. Overall, these findings have important implications for public health and, given the wide availability of safer alternatives, the researchers suggest that diclofenac should be removed from national EMLs and that its marketing authorizations should be revoked globally.
Additional Information
Please access these Web sites via the online version of this summary at 10.1371/journal.pmed.1001388.
This study is further discussed in a PLOS Medicine Perspective by K. Srinath Reddy and Ambuj Roy
The UK National Health Service Choices website provides detailed information on NSAIDS
MedlinePlus provides information about aspirin, ibuprofen, naproxen, and diclofenac; it also provides links to other information about pain relievers (in English and Spanish)
The American Heart Association has information on cardiovascular disease; Can Patients With Cardiovascular Disease Take Nonsteroidal Antiinflammatory Drugs? is a Cardiology Patient Page in the AHA journal Circulation
The British Heart Foundation also provides information about cardiovascular disease and has a factsheet on NSAIDs and cardiovascular disease
The World Health Organization has a fact sheet on essential medicines; the WHO Model List of Essential Medicines (in English and French), and national EMLs are available
PMCID: PMC3570554  PMID: 23424288
11.  Association of Cytokines in Individuals Sensitive and Insensitive to Dust Mites in a Brazilian Population 
PLoS ONE  2014;9(9):e107921.
Allergic reaction to dust mites is a relatively common condition among children, triggering cutaneous and respiratory responses that have a great impact on the health of this population. Anaphylactic hypersensitivity is characterized by an exacerbated response involving the production of regulatory cytokines responsible for stimulating the production of IgE antibodies.
To investigate an association of variants in cytokine genes (IL1A−889, IL1B−511, +3962, IL1R1970, IL1RA11100, IL4RA+1902, IL12−1188, IFNG+874, TGFB1codon 10, codon 25, TNFA−308, −238, IL2−330, +166, IL4−1098, −590, −33, IL6−174, nt565, and IL10−1082, −819, −592) between patients sensitive to dust mites and a control group.
A total of 254 patients were grouped as atopic and non-atopic according to sensitivity as evaluated by the Prick Test and to cytokine genotyping by the polymerase chain reaction-sequence specific primers (PCR-SSP) method using the Cytokine Genotyping Kit.
A comparison between individuals allergic to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Blomia tropicalis and a non-atopic control group showed significant differences between allele and genotype frequencies in the regulatory regions of cytokine genes, with important evidence for IL4−590 in T/C (10.2% vs. 43.1%, odd ratio [OR] = 0.15, p = 5.2 10−8, pc = 0.0000011, and 95% confidence interval [95%CI] = 0.07–0.32) and T/T genotypes (42.9% vs. 13.8%, OR = 4.69, p = 2.5 10−6, pc = 0.000055, and 95%CI = 2.42–9.09). Other associations were observed in the pro-inflammatory cytokines IL1A−889 (T/T, C, and T) and IL2−330 (G/T and T/T) and the anti-inflammatory cytokines IL4RA+1902 (A and G), IL4−590 (T/C, T/T, C, and T), and IL10−592 (A/A, C/A, A, and C).
Our results suggest a possible association between single nucleotide polymorphisms (SNPs) in cytokine genes and hypersensitivity to dust mites.
PMCID: PMC4169580  PMID: 25238536
12.  Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen 
The Journal of Experimental Medicine  1995;181(5):1935-1940.
The cutaneous lymphocyte-associated antigen (CLA) is the major T cell ligand for the vascular adhesion molecule E-selectin, and it has been proposed to be involved in the selective targeting of memory T cells reactive with skin-associated Ag to cutaneous inflammatory sites. To further investigate the relation of CLA and cutaneous T cell responses, we analyzed the CLA phenotype of circulating memory T cells in patients with allergic contact dermatitis and atopic dermatitis (AD) alone vs in patients manifesting bronchopulmonary atopy (asthma with or without AD) and nonallergic individuals. Significant T cell proliferative responses to Ni, a contact allergen, and to the house dust mite (HDM), an allergen to which sensitization is often observed in AD and/or asthma, was noted only in allergic and atopic individuals, respectively. When the minor circulating CLA+CD3+CD45RO+ subset was separated from the major CLA-CD3+CD45RO+ subpopulation in Ni-sensitive subjects, the Ni- dependent memory T cell response was largely confined to the CLA+ subset. A similar restriction of the T cell proliferative response to the CLA+ memory subset was observed for HDM in patients with AD alone. In HDM-sensitive patients with asthma with or without AD, however, the CLA- subset exhibited a strong antigen-dependent proliferation, in contrast to patients with AD alone, whose CLA- subset proliferated very weakly to HDM. In asthma with or without AD, the HDM-dependent proliferation slightly predominated in the CLA- when compared to the CLA+ subset. The functional linkage between CLA expression and disease- associated T cell effector function in AD was also demonstrated by the finding that the circulating CLA+ T cell subset in AD patients, but not nonatopic controls, selectively showed both evidence of prior activation (human histocompatibility antigen-DR expression) and spontaneous production of interleukin 4 but not interferon-gamma. Taken together, these observations demonstrate the correlation of CLA expression on circulating memory T cells and disease-associated memory T cell responses in cutaneous hypersensitivity, and they suggest the existence of mechanisms capable of sorting particular T cell Ag specificities and lymphokine patterns into homing receptor-defined memory subsets.
PMCID: PMC2192003  PMID: 7722470
13.  Traditional Nonsteroidal Anti-Inflammatory Drugs and Postmenopausal Hormone Therapy: A Drug–Drug Interaction? 
PLoS Medicine  2007;4(5):e157.
Suppression of prostacyclin (PGI2) is implicated in the cardiovascular hazard from inhibitors of cyclooxygenase (COX)-2. Furthermore, estrogen confers atheroprotection via COX-2–dependent PGI2 in mice, raising the possibility that COX inhibitors may undermine the cardioprotection, suggested by observational studies, of endogenous or exogenous estrogens.
Methods and Findings
To identify an interaction between hormone therapy (HT) and COX inhibition, we measured a priori the association between concomitant nonsteroidal anti-inflammatory drugs (NSAIDs), excluding aspirin, in peri- and postmenopausal women on HT and the incidence of myocardial infarction (MI) in a population-based epidemiological study. The odds ratio (OR) of MI in 1,673 individuals and 7,005 controls was increased from 0.66 (95% confidence interval [CI] 0.50–0.88) when taking HT in the absence of traditional (t)NSAIDs to 1.50 (95% CI 0.85–2.64) when taking the combination of HT and tNSAIDs, resulting in a significant (p < 0.002) interaction. The OR when taking aspirin at doses of 150 mg/d or more was 1.41 (95% CI 0.47–4.22). However, a similar interaction was not observed with other commonly used drugs, including lower doses of aspirin, which target preferentially COX-1.
Whether estrogens confer cardioprotection remains controversial. Such a benefit was observed only in perimenopausal women in the only large randomized trial designed to address this issue. Should such a benefit exist, these results raise the possibility that COX inhibitors may undermine the cardioprotective effects of HT.
It is controversial whether estrogens confer cardioprotection. This study suggests that even should such a benefit exist, COX inhibitors may undermine cardioprotective effects of hormone therapy.
Editors' Summary
There is currently a great deal of uncertainty regarding the effect of postmenopausal hormone therapy on heart disease in women. Premenopausal women are much less likely to experience heart attacks and strokes than men, a difference that does not exist between postmenopausal women and men. One mechanism that might explain these observations relates to the effect of estrogen, which is thought to have a protective effect on the heart. Hormone replacement therapy (HT) consisting of replacement estrogen, and sometimes progesterone as well, is often taken by women experiencing symptoms of menopause. Evidence from observational studies and the Womens' Health Initiative (WHI) trial has suggested that HT protects against heart disease in perimenopausal women. However, researchers have suggested that any beneficial effect of hormone replacement therapy on the heart might be counteracted by the effects of certain types of painkillers also being taken by women involved in the studies. These painkillers, nonsteroidal anti inflammatory drugs ( NSAIDs), prevent production of a molecule called prostacyclin. Prostacyclin plays a role in preventing blood clotting and is therefore thought to be important in protecting the heart. Estrogen, however, acts to increase production of prostacyclin, and it is therefore theoretically possible that hormone replacement therapy does have a beneficial effect on heart health, but which is counteracted by the negative effects of NSAIDs.
Why Was This Study Done?
In this study, the researchers wanted to find out whether there was any evidence for an interaction between NSAID use, hormone replacement therapy, and heart disease. Such understanding in turn might help to identify more clearly whether hormone replacement therapy protects against heart disease in specific subgroups of postmenopausal women.
What Did the Researchers Do and Find?
This study was carried out using information from the UK's General Practice Research Database, which is the largest computer database of anonymous medical records from primary care anywhere in the world. It contains information entered by UK general practitioners on their patients' drug prescriptions, diagnoses, referrals to hospital, and other data. The researchers here searched for all individuals from the database who were aged between 50 and 84 years on 1 January 1997, and then followed them up through the database for four years, or until the individual died, reached 85 years of age, or was diagnosed with a heart attack or cancer. From this search, the researchers found 1,673 women who had heart attacks or who died from coronary heart disease; these were considered “cases.” Then, these 1,673 women were matched against 20,000 “control” women of similar age. Information was pulled out for each case or control on their use of hormone replacement therapy, NSAIDs (covering 21 different drugs, but most commonly diclofenac, ibuprofen, and naproxen), and various risk factors for heart disease. The researchers then compared use of hormone replacement therapy and NSAIDs between the cases and controls, while making statistical adjustments for other risk factors (such as diabetes and smoking, for example).
  The researchers found that current use of hormone replacement therapy was associated with a lower risk of heart attack than non-use. The odds ratio (chance of a heart attack among HT users compared to the chance among non-users of HT) was 0.78. However, when looking at women who used NSAIDs at the same time as hormone replacement therapy, the researchers found no suggestion of a reduction in risk of heart attack: the odds ratio for the chance of heart attack among this group of women, as compared to nonusers of both NSAIDs and hormone replacement therapy, was 1.50.
What Do These Findings Mean?
These findings suggest that hormone replacement therapy and NSAIDs might interact, with NSAIDs acting against a role for hormone replacement therapy in preventing heart attacks. At face value, these results are in conflict with the findings of one large trial, the WHI trial, which failed to find a benefit of HT in preventing heart attacks. However, a recent analysis of WHI suggests cardioprotective effects of HT in women close to the time of the menopause and this coincides with the younger age of women in the observational studies such as the present one rather than in the WHI overall. Observational research studies, such as the present one, are often difficult to interpret because the groups being compared are not necessarily equivalent. It's possible that women who take hormone replacement therapy, or NSAIDs, are in some way different from women who do not, which will bias the findings. Determination of the clinical implications of these findings would most appropriately be resolved in future trials, designed to address the question of interest.
Additional Information.
Please access these Web sites via the online version of this summary at
Resources from the US National Institutes of Health on menopausal hormone therapy, including links to information about the Women's Health Initiative trials, information about managing menopausal symptoms, and more
Resources from the US National Institutes of Health (MedlinePlus) about heart disease in women
Information from NHS Direct, the UK National Health Service, about hormone replacement therapy
The UK General Practice Research Database is the database utilized in this article
Wikipedia entry on nonsteroidal anti-inflammatory drugs (NSAIDs) (note: Wikipedia is an internet encyclopedia anyone can edit)
PMCID: PMC1872041  PMID: 17518513
14.  Particular characteristics of allergic symptoms in tropical environments: follow up to 24 months in the FRAAT birth cohort study 
Early wheezing and asthma are relevant health problems in the tropics. Mite sensitization is an important risk factor, but the roles of others, inherent in poverty, are unknown. We designed a birth-cohort study in Cartagena (Colombia) to investigate genetic and environmental risk factors for asthma and atopy, considering as particular features perennial exposure to mites, parasite infections and poor living conditions.
Pregnant women representative of the low-income suburbs of the city were randomly screened for eligibility at delivery; 326 mother-infant pairs were included at baseline and biological samples were collected from birth to 24 months for immunological testing, molecular genetics and gene expression analysis. Pre and post-natal information was collected using questionnaires.
94% of families were from the poorest communes of the city, 40% lacked sewage and 11% tap-water. Intestinal parasites were found as early as 3 months; by the second year, 37.9% of children have had parasites and 5.22% detectable eggs of Ascaris lumbricoides in stools (Median 3458 epg, IQR 975-9256). The prevalence of "wheezing ever" was 17.5% at 6 months, 31.1% at 12 months and 38.3% at 24 months; and recurrent wheezing (3 or more episodes) 7.1% at 12 months and 14.2% at 24 months. Maternal rhinitis [aOR 3.03 (95%CI 1.60-5.74), p = 0.001] and male gender [aOR 2.09 (95%CI 1.09 - 4.01), p = 0.026], increased risk for wheezing at 6 months. At 24 months, maternal asthma was the main predisposing factor for wheezing [aOR 3.65 (95%CI 1.23-10.8), p = 0.01]. Clinical symptoms of milk/egg allergy or other food-induced allergies were scarce (1.8%) and no case of atopic eczema was observed.
Wheezing is the most frequent phenotype during the first 24 months of life and is strongly associated with maternal asthma. At 24 months, the natural history of allergic symptoms is different to the "atopic march" described in some industrialized countries. This cohort is representative of socially deprived urban areas of underdeveloped tropical countries. The collection of biological samples, data on exposure and defined phenotypes, will contribute to understand the gene/environment interactions leading to allergy inception and evolution.
PMCID: PMC3331807  PMID: 22439773
Birth cohort study; Wheezing; Allergy; Asthma; Rhinitis; Eczema; Atopic march; The tropics; Parasite; Poverty; Cartagena; Latin America
15.  Clinical and Immunological Changes of Immunotherapy in Patients with Atopic Dermatitis: Randomized Controlled Trial 
ISRN Allergy  2012;2012:183983.
Background. Immunotherapy has proven to be an useful tool in the management of allergic respiratory diseases; however, little has been studied in atopic dermatitis. Objective. To evaluate the clinical and immunological impact of immunotherapy with mites allergen extracts in atopic dermatitis. Methods. Patients with atopic dermatitis were assigned with computer-generated randomization to either of the following groups: (a) controls received only topical treatment with steroids and/or tacrolimus and (b) actively treated patients received topical treatment plus immunotherapy. Levels of serum total IgE, mites-specific IgE and IgG4 were assessed at study start and after one year of immunotherapy. Results. 31 patients in the active group and 29 in the control group completed the study. Symptoms and medication scores were significantly reduced in the active group after six months. Three patients in the control group showed new sensitizations to mites, while 3 patients in the active group showed neosensitization to shrimp with negative oral food challenge. We observed significant increase of mites-specific IgG4 levels in active group. Conclusion. Specific allergen immunotherapy induced a tolerogenic IgG4 response to mite allergens associated with favorable clinical effects in atopic dermatitis patients.
PMCID: PMC3658480  PMID: 23724240
16.  Atopy and House Dust Mite Sensitization as Risk Factors for Asthma in Children 
Yonsei Medical Journal  2005;46(5):629-634.
Asthma is commonly described as an atopic disease in childhood, but some cases of this disorder do not fit this description. The aim of this study was to evaluate the frequency of atopy, asthma, and sensitization to house dust mites in children with allergic symptoms. This study was performed at the Severance Hospital of Yonsei University with patients who visited the allergy clinic for evaluation of nonspecific upper respiratory symptoms, typical symptoms of asthma, or a general health workup. The patients were divided into three age groups: 0-3 years (group 1), 4-7 years (group 2), and 8-12 years (group 3). Of the 1,244 children examined, 844 (67.8%) were atopic and 400 (32.2%) were non-atopic. The frequency of atopy and asthma increased with age. Asthma was diagnosed in the same proportion (64%) of atopic and non-atopic children. As risk factors for asthma symptoms, the positive values of house dust mite (HDM) sensitivity were significantly increased in groups 1, 2, and 3 to 53.5%, 68.9%, and 80.2%, respectively. A significant difference between the percentage of asthmatics sensitized to HDM and that of asthmatics not sensitized to HDM was found only in group 3. In conclusion, asthma is related to atopy with increasing age, and house dust mite sensitization seems to be an important determinant of asthma in older children in Korea.
PMCID: PMC2810567  PMID: 16259059
Asthma; atopy; house dust mite
17.  Non-steroidal anti-inflammatory drug hypersensitivity: association with elevated basal serum tryptase? 
It is hypothesized that because of higher mast cell numbers and mediator release, mastocytosis predisposes patients for systemic immediate-type hypersensitivity reactions to certain drugs including non-steroidal anti-inflammatory drugs (NSAID).
To clarify whether patients with NSAID hypersensitivity show increased basal serum tryptase levels as sign for underlying mast cell disease.
As part of our allergy work-up, basal serum tryptase levels were determined in all patients with a diagnosis of NSAID hypersensitivity and the severity of the reaction was graded. Patients with confirmed IgE-mediated hymenoptera venom allergy served as a comparison group.
Out of 284 patients with NSAID hypersensitivity, 26 were identified with basal serum tryptase > 10.0 ng/mL (9.2%). In contrast, significantly (P = .004) more hymenoptera venom allergic patients had elevated tryptase > 10.0 ng/mL (83 out of 484; 17.1%). Basal tryptase > 20.0 ng/mL was indicative for severe anaphylaxis only in venom allergic subjects (29 patients; 4x grade 2 and 25x grade 3 anaphylaxis), but not in NSAID hypersensitive patients (6 patients; 4x grade 1, 2x grade 2).
In contrast to hymenoptera venom allergy, NSAID hypersensitivity do not seem to be associated with elevated basal serum tryptase levels and levels > 20 ng/mL were not related to increased severity of the clinical reaction. This suggests that mastocytosis patients may be treated with NSAID without special precautions.
PMCID: PMC4002884  PMID: 24782901
Anaphylaxis; Non-steroidal anti-inflammatory drug; Mastocytosis; Drug allergy; Drug reaction; Pseudo-allergy
18.  House Dust Mite Allergy in Korea: The Most Important Inhalant Allergen in Current and Future 
The house-dust mite (HDM), commonly found in human dwellings, is an important source of inhalant and contact allergens. In this report, the importance of HDM allergy in Korea and the characteristics of allergens from dust mite are reviewed with an emphasis on investigations performed in Korea. In Korea, Dermatophagoides farinae is the dominant species of HDM, followed by D. pteronyssinus. Tyrophagus putrescentiae is also found in Korea, but its role in respiratory allergic disease in Korea is controversial. The relatively low densities of mite populations and concentrations of mite major allergens in dust samples from Korean homes, compared to westernized countries, are thought to reflect not only different climatic conditions, but also cultural differences, such as the use of 'ondol' under-floor heating systems in Korean houses. HDM are found in more than 90% of Korean houses, and the level of exposure to HDM is clinically significant. About 40%-60% of Korean patients suffering from respiratory allergies, and more than 40% of patients suffering from atopic dermatitis, are sensitized to HDM. Mite allergens can be summarized according to their inherent auto-adjuvant activities and/or their binding affinities to the adjuvant-like substances: proteolytic enzymes, lipid binding proteins, chitin binding proteins, and allergens not associated with adjuvant-like activity. In general, allergens with a strong adjuvant-like activity or adjuvant-binding activity elicit potent IgE reactivity. In Korea, Der f 2 is the most potent allergen, followed by Der f 1. Immune responses are modulated by the properties of the allergen itself and by the adjuvant-like substances that are concomitantly administered with the antigens. Characterization of allergenic molecules and elucidation of mechanisms by which adjuvant-like molecules modulate allergic reactions, not only in Korea but also worldwide, will provide valuable information on allergic diseases, and are necessary for the development of diagnostic tools and therapeutic strategies.
PMCID: PMC3479224  PMID: 23115727
Allergen; allergy; house dust mite; Korea
Indian Journal of Dermatology  2009;54(3):243-246.
Chronic eczema is commonly encountered in the Indian set up. So also is atopic dermatitis. House dust mites (Dermatophagoides) are implicated in various diseases like atopic dermatitis, asthma, and perennial rhinitis. It has also been proven that patch testing with Dermatophagoides pteronyssinus (DP) is important for detection of contact sensitization in chronic dermatitis.
To study clinical characteristics of DP mix positive patients with regards to chronic dermatitis and atopic dermatitis.
Dermatology outpatients presenting to the department of Skin and STD of Kasturba Medical College (KMC), with clinically diagnosed atopic dermatitis and chronic eczema were chosen for the study. Inclusion and exclusion criteria were well demarked. Eighty six randomly selected patients of dermatitis were subjected to patch testing with standard series and DP mix.
Of the 86, 50 (58%) showed positive reaction to DP mix. Among these positive patients, chronic dermatitis was seen in 42 (84%) with involvement of exposed parts in 37 (74%). Atopic dermatitis was seen in 19 patients (38%) from DP positive group whereas it was observed in 4 patients (17%) from the other group.
Dermatophagoides mix positivity was statistically significant in chronic eczema as well as atopic dermatitis. Patch testing is an important tool to detect delayed type allergy to house dust mite.
PMCID: PMC2810690  PMID: 20161855
Atopic dermatitis; contact sensitization; dermatophagoides; eczema; patch test
20.  Safety of 5-Aminosalicylic Acid Derivatives in Patients with Sensitivity to Acetylsalicylic Acid and Nonsteroidal Anti-inflammatory Drugs 
One of the cornerstones of the management of inflammatory bowel disease is the use of 5-aminosalicylic acid (5-ASA) compounds for treatment of flares and as maintenance therapy during remission. There are concerns about using 5-ASA in patients with a history of hypersensitivity to acetylsalicylic acid (ASA).
To assess the literature with respect to the safety of 5-ASA compounds in patients with documented sensitivity to ASA or nonsteroidal anti-inflammatory drugs (NSAIDs).
Data Sources:
A literature search was conducted in the MEDLINE and Embase databases, using various search terms, including “aminosalicylic acids”, “non-steroidal anti-inflammatory agents,” “hypersensitivity”, and “allergy”. The search was limited to articles (of any study design) published in English. Abstracts, full articles, and reference lists from retrieved articles were assessed to identify further relevant literature.
Study Selection and Data Extraction:
Of 485 citations identified in the initial search, 4 case reports were relevant to the study objective and were analyzed in detail.
Data Synthesis:
Three of the case reports described the successful use of 5-ASA compounds in patients with prior sensitivity to ASA or an NSAID. The fourth report described a reaction to 5-ASA in a patient who had previously tolerated ASA. All of the reports were limited by lack of investigation into the validity of the reported sensitivity to ASA or 5-ASA.
There is a dearth of evidence demonstrating cross-reactivity between ASA or NSAID and 5-ASA. This lack of information may relate to the mechanism of action of 5-ASA. This agent controls inflammation by inhibiting prostaglandin E2 and leukotrienes. In contrast, ASA-induced or NSAID-induced reactions are due to inhibition of the cycloxygenase-1 enzyme and subsequent release of histamine and synthesis of leukotrienes. Further reports describing the safety of 5-ASA use in patients with sensitivity to ASA or NSAIDs are needed before safety in this situation can be definitively determined. In patients with sensitivity to ASA or NSAID who require 5-ASA, a test dose of 5-ASA (to rule out potential cross-reactivity) or further investigation of the ASA or NSAID sensitivity is recommended.
PMCID: PMC3952906  PMID: 24634525
5-ASA; acetylsalicylic acid; nonsteroidal anti-inflammatory drug; hypersensitivity; 5-ASA; acide acétylsalicylique; anti-inflammatoires non stéroïdiens; hypersensibilité
21.  Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults 
The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization.
To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population.
The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs.
Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%.
Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low.
Clinical Implications
Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed.
Capsule summary
Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low.
PMCID: PMC2747487  PMID: 18805578
aeroallergens; rural; farming community; Chinese; food allergens; prevalence; sensitization; skin prick tests
22.  Dust Mites Population in Indoor Houses of Suspected Allergic Patients of South Assam, India 
ISRN Allergy  2011;2011:576849.
Background. In the present study, quality and quantity of indoor dust mites was evaluated at the residence of 150 atopic allergic patients from four different districts of South Assam. Methods. Suspected patients with case history of allergic disease were selected for indoor survey. Dust samples (500 mg) were collected from the selected patient's house and were analyzed using standard methods. Results. About 60% of the selected patients were found suffering from respiratory disorders and rest 40% from skin allergy. The dominant mites recorded from indoor dust samples were Dermatophagoides followed by Blomia, Acarus, and Cheyletus while Caloglyphus was recorded in least number. The distribution of mites on the basis of housing pattern indicates that RCC type of buildings supports maximum dust mite's population followed by Assam type (semi-RCC) buildings, and the lowest count was observed in wooden houses. Environmental factors like temperature, rainfall, and relative humidity are found to determine the indoor mite's population. Severity of allergic attack in some of the typical cases was found to be proportional to the allergen load of mites in the dust samples. Conclusions. The economic status, housing pattern, and local environmental factors determine the diversity and abundance of dust mites in indoor environment.
PMCID: PMC3658589  PMID: 23724231
23.  Seeking allergy when it hides: which are the best fitting tests? 
In the common practice of respiratory allergy, the confirmation by IgE tests of the relationship between the occurrence and duration of symptoms and the exposure to specific inhalant allergens allows an aetiological diagnosis. However, to see patients with suggestive history but negative IgE tests is not rare, and this generally leads to a diagnosis of nonallergic rhinitis or asthma. In many cases, such diagnosis is wrong, because the patient may be revealed as allergic by using additional testing. This is true for local allergic rhinitis, characterized by an exclusive IgE production in the nasal mucosa, that may be correctly diagnosed by performing a nasal IgE measurement or a nasal provocation test with the suspected allergen (s). Another misleading issue is the role of T cell-mediated, delayed hypersensitivity in the pathophysiology of rhinitis and asthma. Recent studies showed that in patients with rhinitis or asthma and negative IgE tests, especially when there is a positive history for current or past atopic dermatitis, the clinical symptoms are actually driven by such mechanism, that may be detected by performing an atopy patch test (APT). The allergen source most frequently responsible for this kind of allergy is the house dust mite, but other allergens may also be involved. Thus, before delivering a diagnosis of nonallergic rhinitis or asthma in patients with negative result to common allergy testing, further tests are needed. To miss the diagnosis of allergy has obvious consequences in terms of management, including allergen avoidance, patient’s education, and specific immunotherapy.
PMCID: PMC3720223  PMID: 23815816
Rhinitis; Asthma; LgE tests; Nonallergic; Local allergic rhinitis; T-cell mediated hypersensitivity; Atopy patch test
24.  485 Therapeutic Effect and Safety of Tropical Mite Allergen Vaccines by Subcutaneous Route in Allergic Asthmatics Patients 
Allergen-specific subcutaneous immunotherapy (SCIT) is presently recognized as a biological response modifier, as it is the only available treatment able to influence the natural course of allergic disease. Extensive clinical evidence supports its efficacy. Safety concerns are related to the risks of anaphylactic reactions during treatment. Standardization of allergen vaccines in terms of allergenic activity allows a more precise control over the administered doses and can be, therefore, very relevant for both efficacy and safety of SCIT. House Dust Mites (HDM), particularly Dermatophagoides pteronyssinus (Dp), Dermatophagoides siboney (Ds) and Blomia tropicalis (Bt) have been described as very relevant allergen sources in Cuba, with a strong association to respiratory allergy symptoms.
To asses the efficacy and safety of standardized allergen vaccines of these 3 mite species (Valergen, Biocen, Cuba) in Cuban asthmatic patients.
Three Double-Blind Placebo-Controlled clinical trials were performed in 40 patients each, showing asthmatic symptoms and positive predominant Skin Prick Test (SPT) to each mite, respectively. Half of patients received the active treatment consisting of subcutaneous injections with increasing doses, up to 6000 BU.
The total 1 year cumulative dose was 63035 BU, in an average of 20.5 injections. The treatment was effective in the reduction of clinical symptoms (up to 32%, 95%CI: 28-36%; P = 0.0006) and medication intake (23%, 95%CI:18-28%), as compared to control treatment. The skin sensitivity to the allergens decreased significantly (P = 0.0001), with regard to the beginning of the treatment. The allergen amount needed to induce a positive SPT increased 297-fold. An improvement of the lung function was observed, expressed in a modest Peak-Expiratory-Flow increase (P < 0.05) and reduction of PEF daily variability. SIT was considered effective in 71% of patients. The frequency of local adverse reactions was 2.4 % of injections.
The results indicates that immunotherapy, using standardized House Dust Mite vaccines, including tropical species, is effective and safe for the control and amelioration of the asthma in our population.
PMCID: PMC3512808
25.  House-dust mite allergy: mapping of Dermatophagoides pteronyssinus allergens for dogs by two-dimensional immunoblotting 
Specific immunotherapy has shown to be very useful for allergy control in dogs, with a common success rate ranging from 65% to 70%. However, this efficacy could probably be improved and the identification of individual allergomes, with the choice of more adequate molecular allergen pools for specific immunotherapy, being the strategy.
To map Dermatophagoides pteronyssinus (Der p) allergens for mite-sensitized atopic dogs, for better understanding how individual allergograms may influence the response to house-dust mite immunotherapy.
Material and methods
To identify the Der p mite allergome for dogs, 20 individuals allergic to dust-mites and sensitized to Der p, were selected. The extract from Der p was submitted to isoelectric focusing (IEF), one-dimensional (1-D) and two-dimensional (2-D) sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Separated proteins were blotted onto polyvinylidene difluoride (PVDF) membranes and immunoblottings were performed with patient sera. Allergen-bound specific IgE was detected.
Eleven allergens were identified from isoelectric focusing (IEF), as well as from 1-D SDS PAGE. From 2-D SDS-PAGE, 24 spots were identified.
Several similarities were found between dog and human allergograms and no absolute correlation between sensitization and allergy was observed either. As in humans, different individual allergograms do not seem to implicate different clinical patterns, but may influence the response to specific immunotherapy. The molecular epidemiology approach in veterinary allergy management, by the characterization of individual patients’ allergoms and by choosing the best molecular allergen pool for each patient could also improve the efficacy of allergy immunotherapy.
PMCID: PMC4436239  PMID: 26015775
allergens; atopy; dog; house-dust mite; immunoblotting

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