Scabies, crusted (Norwegian) scabies and the diagnosis of mite sensitisation

Scabies is observed with relatively high frequency in Allergy and Dermatology clinics in developing countries where poor sanitary conditions are prevalent and increasingly in some areas of the world with increased immigrant populations. Since the immunological response to scabies mites includes the production of IgE class antibodies to Sarcoptes scabiei allergens which cross-react with Dermatophagoides major allergens Der p 1 and Der p 2, positive immediate-type skin tests to house dust mite extracts should be interpreted cautiously. Additionally, scabies should be included routinely in the differential diagnosis of itchy rashes in patients living in those areas

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Biomarkers of treatment efficacy in patients with chronic spontaneous urticaria.

Summary: Background. Currently there are no biomarkers useful to predict the future evolution and the therapeutic response in patients with chronic spontaneous urticaria (CSU). Objective. To review the available information on biomarkers that might be applied for the follow up of the response to guideline recommended therapies for CSU. Methods. A review of the medical literature on CSU potential clinical and laboratory biomarkers in PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, chronic spontaneous urticaria, antihistamines (AHs), omalizumab (OMA), cyclosporine (CyA), and treatment. Results. Clinical manifestations that were associated to poor responses to AHs were atopy, asthma, rhinitis / rhinosinusitis, thyroid disease, hypertension, higher disease activity and duration. Laboratory markers of AH resistance that have been reported include Complement C5a fraction, Autologous Serum Skin Test (ASST), Basophil Activation Test (BAT), D-dimer and LCN2 adipokine. Basophil Histamine Release Assay (BHRA), ASST, and basophil CD203c-upregulating activity in the serum correlated with favorable response to OMA, whereas disease duration and severity, BAT, BHRA, and D-dimer levels were associated with better responses to CyA. Conclusion. Some promising biomarkers useful for patient management in CSU, have been identified in the literature. There is, however, an urgent need of new, easy-to-perform markers that can be made widely available for the optimal care of patients suffering CSU.

Scabies, crusted (Norwegian) scabies and the diagnosis of mite sensitisation.

Scabies is observed with relatively high frequency in Allergy and Dermatology clinics in developing countries where poor sanitary conditions are prevalent and increasingly in some areas of the world with increased immigrant populations. Since the immunological response to scabies mites includes the production of IgE class antibodies to Sarcoptes scabiei allergens which cross-react with Dermatophagoides major allergens Der p 1 and Der p 2, positive immediate-type skin tests to house dust mite extracts should be interpreted cautiously. Additionally, scabies should be included routinely in the differential diagnosis of itchy rashes in patients living in those areas.

Cofactors and comorbidities in patients with aspirin/NSAID hypersensitivity

Hypersensitivity reactions to aspirin and other NSAIDs occur in individuals genetically predisposed and exhibit different clinical manifestations, especially respiratory, cutaneous, and generalised. Five different phenotypes define distinct clinical pictures: aspirin-exacerbated respiratory disease, aspirin/NSAID cutaneous disease, NSAID-induced urticaria, angio-oedema and anaphylaxis, single NSAID reactions, and delayed reactions. They are observed more frequently in middle-aged women, and in atopic individuals. While ASA/NSAID hypersensitivity shares comorbidities with asthma, chronic rhinosinusitis, nasal polyposis, chronic urticaria and angio-oedema, ASA and other NSAIDs can also be cofactors for other clinically relevant conditions, especially food-dependent exercise-induced anaphylaxis, angio-oedema induced by angiotensin-converting enzyme inhibitors, and oral mite anaphylaxis. Awareness on these relationships is required for the correct diagnosis, classification, and treatment of affected patients (AU)

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Justification for IgE as a therapeutic target in chronic spontaneous urticaria.

SUMMARY: Monoclonal anti-IgE antibodies (omalizumab) are able to induce clinically significant benefits in patients with severe chronic spontaneous urticaria (CS). Those results led clinicians and investigators to reconsider a possible pathogenic role not previously supported for IgE and its receptors in this disease, and to investigate additional approaches for understanding its pathogenesis. IgE antibodies to unknown environmental allergens able to trigger chronic urticaria are not generally regarded as the etiologic factor for the disease. Other proposed mechanisms for the production of wheals and angioedema in CSU include IgG autoantibodies and CD4-positive T cells directed to the high-affinity IgE receptor, autoantibodies to IgE itself, IgE autoantibodies directed to thyroid and nuclear autoantigens, highly cytokinergic IgE, and histamine-releasing factors able to bind to IgE and cause mast cell activation. It is expected that a better knowledge on the mechanisms leading to CSU and the clarification of the immunological effects of anti-IgE will provide novel therapies for this frequent condition.

Factors linked to disease severity and time to remission in patients with chronic spontaneous urticaria.

Biomarkers useful for the evaluation and management of patients with chronic spontaneous urticaria (CSU) are not currently available. A review of various clinical and laboratory markers that have been studied to assess their value for determining the severity or predicting the evolution of disease in adult patients with CSU was carried out. A search of the medical literature on PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, CSU, severity, prognosis and treatment was performed. Based on our review of the literature, among the clinical markers studied, higher age at onset, being female, long disease duration and aspirin/NSAID hypersensitivity may be linked to both severe CSU and a long time to spontaneous remission. In addition, a positive autologous serum skin test (ASST) may be associated with severe CSU, and comorbidity of inducible urticaria and concomitant recurrent angio-oedema may be linked to longer CSU duration. Potential biomarkers of CSU severity and/or duration include basophil numbers and susceptibility to activation, inflammatory markers, markers of activation of the extrinsic coagulation pathway, immunoglobulin E and vitamin D. Although the described markers are promising, further studies on representative and well-characterized patient populations are needed to determine the value of these clinical and biological markers for predicting the severity and course of disease in patients with CSU.

Cofactors and comorbidities in patients with aspirin/NSAID hypersensitivity.

Hypersensitivity reactions to aspirin and other NSAIDs occur in individuals genetically predisposed and exhibit different clinical manifestations, especially respiratory, cutaneous, and generalised. Five different phenotypes define distinct clinical pictures: aspirin-exacerbated respiratory disease, aspirin/NSAID cutaneous disease, NSAID-induced urticaria, angio-oedema and anaphylaxis, single NSAID reactions, and delayed reactions. They are observed more frequently in middle-aged women, and in atopic individuals. While ASA/NSAID hypersensitivity shares comorbidities with asthma, chronic rhinosinusitis, nasal polyposis, chronic urticaria and angio-oedema, ASA and other NSAIDs can also be cofactors for other clinically relevant conditions, especially food-dependent exercise-induced anaphylaxis, angio-oedema induced by angiotensin-converting enzyme inhibitors, and oral mite anaphylaxis. Awareness on these relationships is required for the correct diagnosis, classification, and treatment of affected patients.

Demographic and clinical profiles in patients with acute urticaria

BACKGROUND: Urticaria is a common cause for consultation in general and specialised medical practices. There is scarce information on the characteristics of patients suffering acute urticaria in Latin America. OBJECTIVES: To investigate demographic and clinical features of patients with acute urticaria attending two allergy clinics in Caracas, Venezuela. METHODS: A prospective study of all new patients who consulted during a three-year period because of acute urticaria. Information on age, gender, symptom duration, previous medical history, body distribution of wheals and angio-oedema, laboratory investigations, skin prick tests, and pharmacological treatment, was collected. Patients were classified according to their age as children/adolescents and adults. RESULTS: Two hundred and forty eight patients (177 adults and 71 children) were studied. Acute urticaria was more frequent in middle-aged atopic female patients. Lesions more often involved upper and lower limbs and head, and 31% of patients exhibited generalised urticaria. Laboratory investigations, performed only in selected cases, did not contribute to the final diagnosis. Most frequent subtypes of acute urticaria were spontaneous, dermographic, papular, and drug-induced urticaria. Most patients were treated with non-sedating antihistamines, with increased use of cetirizine and levocetirizine in children, while 5.6% of children and 20.3% of adults required the addition of short courses of systemic corticosteroids. CONCLUSIONS: Acute urticaria is a frequent cause of consultation for allergists, affecting more often middle-aged female atopic patients. The use of extensive complementary tests does not seem to be cost-effective for this clinical condition. Spontaneous, dermographic, papular and drug-induced urticaria are the most common subtypes

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Demographic and clinical profiles in patients with acute urticaria.

BACKGROUND: Urticaria is a common cause for consultation in general and specialised medical practices. There is scarce information on the characteristics of patients suffering acute urticaria in Latin America. OBJECTIVES: To investigate demographic and clinical features of patients with acute urticaria attending two allergy clinics in Caracas, Venezuela. METHODS: A prospective study of all new patients who consulted during a three-year period because of acute urticaria. Information on age, gender, symptom duration, previous medical history, body distribution of wheals and angio-oedema, laboratory investigations, skin prick tests, and pharmacological treatment, was collected. Patients were classified according to their age as children/adolescents and adults. RESULTS: Two hundred and forty eight patients (177 adults and 71 children) were studied. Acute urticaria was more frequent in middle-aged atopic female patients. Lesions more often involved upper and lower limbs and head, and 31% of patients exhibited generalised urticaria. Laboratory investigations, performed only in selected cases, did not contribute to the final diagnosis. Most frequent subtypes of acute urticaria were spontaneous, dermographic, papular, and drug-induced urticaria. Most patients were treated with non-sedating antihistamines, with increased use of cetirizine and levocetirizine in children, while 5.6% of children and 20.3% of adults required the addition of short courses of systemic corticosteroids. CONCLUSIONS: Acute urticaria is a frequent cause of consultation for allergists, affecting more often middle-aged female atopic patients. The use of extensive complementary tests does not seem to be cost-effective for this clinical condition. Spontaneous, dermographic, papular and drug-induced urticaria are the most common subtypes.

Aspirin-exacerbated cutaneous disease (AECD) is a distinct subphenotype of chronic spontaneous urticaria.

BACKGROUND: A subset of patients with chronic spontaneous urticaria (CSU) experience disease exacerbations after receiving non-steroidal anti-inflammatory drugs (NSAIDs). This condition has been designated as Aspirin-Exacerbated Cutaneous Disease (AECD). OBJECTIVES: The purpose of this study was twofold: (i) Investigate the demographic and clinical features of patients affected by AECD; (ii) To compare patients with AECD and NSAID-tolerant CSU patients for those characteristics. METHODS: Patients with AECD and a group of unselected CSU patients tolerant to NSAIDs were studied. Demographic and clinical data were obtained by direct questioning and physical examination. Laboratory investigations and allergen skin prick tests were performed only in selected patients, as guided by the medical history. RESULTS: Of 423 CSU patients admitted in the clinics, 52 (12.2%) had AECD. Compared with NSAID-tolerant CSU patients, AECD patients had significantly longer disease duration (57.7 ± 118.4 vs. 24.4 ± 36.6 months, P < 0.05), higher prevalence of angio-oedema (72.7 vs. 30.9%, P < 0.05) and atopy (83.8% vs. 58.4%, P < 0.05) and more frequent involvement of the face and upper respiratory tract (54.5% vs. 29.6%, P < 0.05). CONCLUSIONS: AECD is a distinct phenotype that should be considered for inclusion as a separate subtype of chronic spontaneous urticaria.

Subtypes of chronic urticaria in patients attending allergy clinics in Venezuela.

Chronic urticaria (CU) is one of the most puzzling clinical entities confronted by the medical profession. It is a common motive for consultation, and in a sizable proportion of patients no identifiable cause is evident. Since there are relatively few publications regarding CU in developing countries, we performed a prospective 3-year study on the demographic and clinical features of patients with CU. Four hundred and twenty-three subjects were studied, 52 children and 371 adults, 295 females (69.7%), with a mean age of 38.4 ± 17.8 years. More often, wheals and angioedema (AE) were present on the head, upper and lower limbs and the trunk. AE was present in 162 patients (38.4%). The most frequent subtypes were chronic spontaneous urticaria, aspirin-exacerbated cutaneous disease, dermographic urticaria, and combinations of various subtypes. A better understanding of the characteristics of patients suffering CU is helpful for clinicians dealing with this ailment, and provides guidance for new investigations on its pathogenesis, which will hopefully result in a better management of this vexing condition.

Mite hypersensitivity in patients with rhinitis and rhinosinusitis living in a tropical environment

PURPOSE: Rhinitis and rhinosinusitis are major concerns in public health. Mites are important aetiological agents in the tropics. The present study investigated the in vivo response to mite allergens in patients with rhinitis and rhinosinusitis. METHODS: All patients with presumptive nasal allergy were included. Skin tests were done with inhalants and mite extracts. Patients were classified as allergic or non-allergic according to skin tests and history. RESULTS: Out of 229 patients, 175 (76.4%) showed positive skin tests. Allergic patients showed positivity to mites in 97.1% of cases, 51.4% to dog dander; 40.5% to cat dander; 36.5% to German cockroach; 22.8% to moulds; and 21.1% to grass pollens. Dermatophagoides farinae induced responses in 90.8% of patients, D. pteronyssinus in 90.1%, Blomia tropicalis in 74.8%, Glycyphagus domesticus in 62.2%, Chortoglyphus arcuatus in 58.2%, Acarus siro in 46.2%, Lepidoglyphus destructor in 35.4%, and Tyrophagus putrescentiae in 35.0%. Higher correlations were found between skin test diameters induced by mites from the same family. CONCLUSIONS: Sensitisation to inhalant allergens is present in 76% of allergy clinics' patients with rhinitis or rhinosinusitis. Our results confirm previous observations showing that mites constitute the most important cause of respiratory allergy in tropical settings and suggest that mite allergen cross-reactivity is responsible for the positivity of skin tests to mites not present in the patient's environment since the species Glycyphagus, Chortoglyphus, Acarus, Lepidoglyphus and Tyrophagus have not been found in Caracas house dust

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Mite hypersensitivity in patients with rhinitis and rhinosinusitis living in a tropical environment.

PURPOSE: Rhinitis and rhinosinusitis are major concerns in public health. Mites are important aetiological agents in the tropics. The present study investigated the in vivo response to mite allergens in patients with rhinitis and rhinosinusitis. METHODS: All patients with presumptive nasal allergy were included. Skin tests were done with inhalants and mite extracts. Patients were classified as allergic or non-allergic according to skin tests and history. RESULTS: Out of 229 patients, 175 (76.4%) showed positive skin tests. Allergic patients showed positivity to mites in 97.1% of cases, 51.4% to dog dander; 40.5% to cat dander; 36.5% to German cockroach; 22.8% to moulds; and 21.1% to grass pollens. Dermatophagoides farinae induced responses in 90.8% of patients, D. pteronyssinus in 90.1%, Blomia tropicalis in 74.8%, Glycyphagus domesticus in 62.2%, Chortoglyphus arcuatus in 58.2%, Acarus siro in 46.2%, Lepidoglyphus destructor in 35.4%, and Tyrophagus putrescentiae in 35.0%. Higher correlations were found between skin test diameters induced by mites from the same family. CONCLUSIONS: Sensitisation to inhalant allergens is present in 76% of allergy clinics' patients with rhinitis or rhinosinusitis. Our results confirm previous observations showing that mites constitute the most important cause of respiratory allergy in tropical settings and suggest that mite allergen cross-reactivity is responsible for the positivity of skin tests to mites not present in the patient's environment since the species Glycyphagus, Chortoglyphus, Acarus, Lepidoglyphus and Tyrophagus have not been found in Caracas house dust.

Treatment of recalcitrant chronic urticaria with nonsedating antihistamines: is there evidence for updosing?

Nonsedating antihistamines are the first-choice treatment for all forms of urticaria. In patients with recalcitrant urticaria who do not respond to conventional doses of antihistamines, current guidelines recommend increasing doses by up to 4 times in order to obtain better control of the disease. Although few studies have been conducted, there are convincing data from controlled trials for cetirizine, levocetirizine, and desloratadine that support the use of increased doses of such drugs in unresponsive patients. The use of higher doses of antihistamines has not been associated with increased adverse effects or somnolence. More studies with other second-generation antihistamines are required in order to improve the treatment of patients with severe, recalcitrant urticaria.

Treatment of Recalcitrant Chronic Urticaria With Nonsedating Antihistamines: Is There Evidence for Updosing?

Los antihistamínicos no sedantes constituyen el tratamiento de primera elección para todas las formas de urticaria. En pacientes con urticaria recalcitrante que no responden a dosis convencionales de antihistamínicos los lineamientos actuales recomiendan el incremento de la dosis hasta 4 veces hasta obtener un mejor control de la enfermedad. Aunque el número de investigaciones es reducido, existen datos convincentes de estudios controlados para cetirizina, levocetirizina y desloratadina que sustentan el uso de dosis superiores en pacientes no respondedores. Se ha observado que la utilización de mayores dosis de antihistamínicos no se asocia con un incremento de la frecuencia de efectos adversos o de somnolencia. Se requieren estudios adicionales con otros antihistamínicos de segunda generación para mejorar el tratamiento de los pacientes que presentan urticaria severa recalcitrante (AU)

Nonsedating antihistamines are the first-choice treatment for all forms of urticaria. In patients with recalcitrant urticaria who do not respond to conventional doses of antihistamines, current guidelines recommend increasing doses by up to 4 times in order to obtain better control of the disease. Although few studies have been conducted, there are convincing data from controlled trials for cetirizine, levocetirizine, and desloratadine that support the use of increased doses of such drugs in unresponsive patients. The use of higher doses of antihistamines has not been associated with increased adverse effects or somnolence. More studies with other second-generation antihistamines are required in order to improve the treatment of patients with severe, recalcitrant urticaria (AU)

Increased total and mite-specific immunoglobulin E in patients with aspirin-induced urticaria and angioedema.

BACKGROUND: An increased prevalence of atopy has been observed in patients with intolerance of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVE: To investigate total and mite-specific immunoglobulin (Ig) E in serum from patients with hypersensitivity to NSAIDs and healthy controls. METHODS: Patients who reacted to 2 or more chemically unrelated NSAIDs with urticaria and angioedema, confirmed by a double-blinded provocation test with aspirin, were skin tested with inhalant allergens. Total and specific IgE to Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt) in the serum was quantified by enzyme-linked immunosorbent assay (ELISA) in patients and a control group of healthy blood donors. RESULTS: One-hundred-and-fourteen patients and 74 controls were studied. Skin tests were positive in 95 patients (83.3%). Total mean IgE levels were 107.1 (91.3) IU/mL in controls and 161.0 (150.8) IU/mL in patients (P = .006). Mean (SD) levels of IgE to Dp were 0.210 (0.17) optical density (OD) units in controls and 0.473 (0.65) OD units in patients (P = .001). Levels of specific IgE to Bt were 0.230 (0.20) OD units in controls and 0.522 (0.8) OD units in patients (P =.0001). Positive ELISA results for IgE to Dp were found for 29.6% of controls and 70.4% of patients (P =.0001); the corresponding percentages for Bt were 32.4% of controls and 67.6 % of patients (P = .0001). CONCLUSIONS: Cross-reactive patients with NSAID-induced urticaria and angioedema exhibit an increased prevalence of sensitization to Dp and Bt and increased total serum IgE. Further research is necessary to determine the reasons for this association.

The multiple faces of nonsteroidal antiinflammatory drug hypersensitivity.

Based on the clinical picture and triggering drugs, allergic and pseudoallergic adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) can be classified in four patterns : respiratory, cutaneous, mixed and systemic. This categorization is useful for the purpose of describing patient populations included in studies about NSAID adverse reactions as well as for the routine management of the patient in the clinical setting.

Tolerability to new COX-2 inhibitors in NSAID-sensitive patients with cutaneous reactions.

BACKGROUND: The safety of new anti-inflammatory drugs in patients intolerant to classic cyclooxygenase (COX) inhibitors with urticaria and angioedema has not been determined. OBJECTIVES: To investigate the clinical tolerance to COX-2 inhibitors in patients with cutaneous symptoms attributable to classic nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Patients with urticaria or angioedema triggered by NSAIDs were challenged with COX-2 inhibitors by the single-blinded, placebo-controlled oral method. RESULTS: One hundred ten NSAID-sensitive patients were submitted to 184 oral challenges with COX-2 inhibitors. Eighty-two patients (74.5%) were cross-reactors and 28 patients (25.4%) were single reactors. Reaction rates for COX-2 inhibitors were 21.3% for nimesulide, 17.3% for meloxicam, 33.3% for celecoxib, and 3.0% for rofecoxib. CONCLUSIONS: Some COX-2 inhibitors, such as rofecoxib, are relatively safe in NSAID-sensitive patients with urticaria or angioedema. However, the tolerance profile varies with the drug, which might be related to a differential selectivity of the drug for COX-1 and COX-2. COX-1 inhibition would represent a major mechanism for cutaneous adverse reactions to NSAIDs. Controlled oral provocation with new NSAIDs is useful for the proper management of patients sensitive to classic NSAIDs requiring analgesic and anti-inflammatory treatment.