Janaina M Melo

Omalizumab in Chronic Spontaneous Urticaria: A Brazilian Real-Life Experience

Background: Current guidelines on chronic spontaneous urticaria (CSU) suggest a treatment based on a 3-step approach that aims at total symptom control, starting with H1-antihistamines. However, a significant number of patients present an antihistamine-resistant urticaria that must be treated with an alternative third-line therapy such as omalizumab. Methods: Patients with a history of CSU who did not respond to treatment with high doses of modern antihistamines were treated with 150 or 300 mg of omalizumab every 4 weeks. The response to treatment was recorded as complete (CR), partial (PR) or no response. A dose adjustment was proposed according to response. Results: We treated 47 CSU patients with omalizumab (40 females), of whom 39.5% had evidence of autoimmunity. The average number of treatments was 11.4 (range 2-87). All patients had been refractory to high-dose modern antihistamines. A CR was seen in 84.6% of patients who started with 300 mg and in 60% of those who started with 150 mg. Only 1 patient had no response to both the 150- and 300-mg doses. In 6 of the PR patients with 150 mg, a higher dose of 300 mg was proposed and 4 had a CR. Four patients discontinued the treatment. No severe adverse events were reported in the patients who finished the study. Discussion: Although good results were seen in both groups, CR rates were higher in those under a high-dose initial treatment. Our data strongly suggest that the therapy should be individualized.

Lung function in hyper IgE syndrome.

Pneumatoceles and bronchiectasis are secondary complications of respiratory infections in patients with hyper IgE syndrome (HIgES).

Renal Abscess in Hyper-IgE Syndrome

Kidney disease due to Aspergillus fumigatus is a rare finding in hyper-IgE syndrome. We report a patient with autosomal dominant hyper-IgE syndrome, recurrent pneumonia, and acute necrosuppurative pyelonephritis caused by Aspergillus fumigatus with a fatal outcome. We emphasize the severity and the difficulties in the management of renal complications that could be limiting the survival of these patients.

Anafilaxia a cloridrato de benzidamina: relato de caso

RESUMO 1. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Departamentos de Clínica Médica e Pediatria, Ribeirão Preto, SP, Brasil. 316 Reações de hipersensibilidade a medicamentos (RHM) podem induzir manifestações clínicas heterogêneas, desde leves até graves. São classificadas em imunológicas ou alérgicas quando mediadas por anticorpos ou linfócitos T, e não imunológicas quando decorrentes de efeitos farmacológicos da droga, incluindo inibição da enzima cicloxigenase (Cox). Os dois grupos mais frequentemente implicados nas RHM são os anti-inflamatórios não esteroidais (AINEs), e os antibióticos betalactâmicos. O manejo adequado das reações aos AINEs depende da identificação do mecanismo fisiopatológico envolvido, que permitirá classificar em reator seletivo (indivíduo que reage a um único fármaco e a outros com estrutura química similar), ou reator múltiplo ou intolerante cruzado (aquele que reage a múltiplos fármacos de estrutura química não relacionada). O cloridrato de benzidamina (CBZ) é um AINE de uso frequente e relativamente seguro, sem descrições de reações graves associadas ao seu uso. Atua inibindo as enzimas Prostaglandina Endoperoxidase H Sintase 1 e/ou 2, e a Fosfolipase A2. Em pacientes com história de reações aos AINEs, o teste de provocação é a ferramenta diagnóstica padrão ouro para confirmar ou excluir a reatividade cruzada a outros AINEs e definir um fármaco alternativo seguro. Descreveremos um caso raro de anafilaxia ao CBZ durante teste de provocação oral. Descritores: Benzidamina, anti-inflamatórios não esteroidais, hipersensibilidade a drogas, anafilaxia. Hypersensitivity drug reactions (HDRs) may induce mild to severe heterogeneous clinical manifestations. They are classified as immunological or allergic when mediated by antibodies or T lymphocytes, and non-immunological when resulting from pharmacological effects of the drug, including inhibition of the cyclooxygenase (Cox) enzyme. The two groups of drugs most frequently implicated in HDRs are non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibiotics. Appropriate management of NSAID reactions depends on identification of the pathophysiological mechanism involved, which will allow to classify the patient as selective reactor (patient reacting to a single drug and others with similar chemical structure) or multiple or cross-intolerant reactor (patient reacting to multiple drugs with unrelated chemical structure). Benzydamine hydrochloride (BZH) is a frequently used, relatively safe NSAID for which descriptions of severe reactions are not available. BZH acts inhibiting the enzymes prostaglandin endoperoxide H synthase (PGHS) 1 and/ or 2 and phospholipase A2. In patients with a history of NSAID reactions, the challenge test is the gold standard diagnostic tool to confirm or exclude cross-reactivity to other NSAIDs, and to define a safe alternative drug. In this paper, we describe a rare case of anaphylaxis to BZH during an oral drug provocation test.

Hypertrophic lichen planus-like atopic dermatitis: a case report

Results The lesions started at age 18 during the patient s first pregnancy and had a predominant flexural distribution pattern. At the physical exam, the patient presented with erythema and infiltrative lesions in forearm and periorbital regions, and scaly erythematous papules, especially in inferior extremities. Some of these lesions presented an ulcerous center and had linear form. The patient had high specific serum IgE levels for house dust mites (Dermatophagoides farinae and D. pteronyssinus), grass and dog; sea food, fish, soy, wheat and latex. Serum total IgE was 11,100kU/L, and serology for hepatitis B and C was negative. The patient was treated with antihistamines, topical emollients and oral corticosteroids with low improvement. Because of this atypical presentation, other differential diagnoses were considered, including hypertrophic lichen planus. Skin biopsy was performed, showing hyperkeratosis, sub-acute spongiotic dermatitis and moderate acanthosis, compatible with atopic dermatitis and an evolution to lichen simplex chronicus. Conclusions Hypertrophic lichen planus is one of the differential diagnosis of atopic dermatitis and it commonly involves the flexor surfaces of the extremities bilaterally. Adultonset AD can present with non-typical morphology and localization, therefore it is important to distinguish these two entities, since lichen planus can be associated with other diseases, such as viral hepatitis.

Hydroa vacciniforme as a differential diagnosis of atopic dermatitis.

Results Patient’s symptoms started at age 4, presenting with vesiculopapular eruptions and pruritus on photoexposed areas, evolving into crusts. She had been treated with anti-histamines and topical steroids for several years, with no improvement. Sometimes the patient referred other associated symptoms, including dizziness, dyspnea, chest pain and strong pain in the thighs. Additional treatments included oral corticosteroids, moisturizers, sunscreen filter factor 30 and cyclosporine. On physical exam, the patient presented erythematous papules, infiltrated, associated with lichenification, crusts and chafing on the surface of the exposed areas in the upper limbs, anterior chest, lumbar region and lower limbs, and erythematous plaques in the nasal and malar region. Differential diagnosis included Atopic Dermatitis, Besnier’s Prurigo, Idiopathic Prurigo, Subacute Erythematosus Lupus, Protoporphyria and Contact Dermatitis. At our hospital she underwent skin biopsy, and the results showed characteristic features of Hydroa vacciniforme. The patient now is being treated with chloroquine 250mg/day, Pimecrolimus cream twice daily on the face, mometasone once a week, hydroxyzine 25mg twice daily, and sunblock factor 30. She reports great improvement of symptoms.

Efficacy and safety of the use of omalizumab in a patient with difficult-to-control severe asthma and antiphospholipid antibody syndrome

Results Female, 36-year-old patient, with uncontrolled asthma, dependent on oral corticosteroid. Patient had a history of cough, wheezing and dyspnea since childhood with worsening in the past few years, with dyspnea on minimal activities and use of rescue albuterol 3-10 times a day. She had a history of intensive care unit admission and intubation for asthma on two occasions. Associated conditions were: APS (thrombosis of the leg, miscarriage, stillbirth and positive lupus anti-coagulant, use of aspirin, depression, GERD, and allergic rhinitis. She was on Formoterol/Budesonide 12/400mcg plus inhaled Beclomethasone 800mcg twice daily; Montelukast 10mg a day; Prednisone 5mg daily; Fluoxetine 40mg daily; nasal Budesonide 50mcg twice a day; Omeprazole 20mg once a day. Her initial spirometry showed an FEV1 of 47% predicted, with response to bronchodilator (21% and 300mL reversibility). This pattern remained throughout her follow up in our Clinic. Her total IgE was 120kU/L, and she presented positive skin prick tests to Dermatophagoides pteronyssinus, D. farinae and Trichophyton and negative to Aspergillus. Chest tomography and bronchoscopy were unremarkable. Despite correct use of medications, the patient had frequent exacerbations and need for increasing doses of oral prednisone up to 80mg daily, with weight gain of 18kg in 3 years. Omalizumab was started, and within two weeks the patient showed marked improvement of symptoms, making it possible to withdraw prednisone. There was reduction in use of rescue albuterol, improvement in quality of life and weight loss. After 9 months, treatment with omalizumab was discontinued due to supply problems, with worsening of asthma and return of oral corticosteroids. Provision of omalizumab was restored after 6 months, and the patient again had improvement of symptoms and discontinuation of oral corticosteroids. Currently, she uses rescue bronchodilator 2 times a week, lost 20kg and practices physical activity.

Diagnostic profile among patients with chronicurticaria/angioedema attending a reference clinic in Brazil: the role of auto-immunity.

Methods Two hundred and fifty four patients aged 13-80 years (202 females,79.5%), with chronic urticaria/angioedema who receive care at the Allergy Clinic of the Clinical Hospital of Ribeirao Preto Medical School in Brazil, were evaluated prospectively. Patients were inquired about triggering of symptoms by medications and/or physical agents and presence of anaphylaxis. In addition, they were investigated by skin testing and tests for eosinophilia, IgE, and hepatitis B and C. Autoimmune basis was characterized by presence of positive autologous test, anti-thyroid or antinuclear antibodies (ANA). When indicated, a skin biopsy was performed. Use of medications for urticaria was analyzed.

Oral challenge test with nsaids: evaluation of patients attending a specialty clinic in Ribeirão Preto, Brazil

Methods Prospective study including 116 patients with positive history of hypersensitivity to NSAIDs, evaluated at the Allergy Clinic of the Clinical Hospital of Ribeirao Preto Medical School, between October 2010 and July 2014. Patients were evaluated using the European Network for Drug Allergy questionnaire, and underwent single blind, placebo controlled OCT, in a hospital-controlled environment. Patients were required to be clinically stable, and to withdraw antihistamines or corticosteroids seven days prior to the OCT. Patients were given 10%, 20%, 30% and 40% of the therapeutic NSAID dosage, selecting an NSAID different from the one implicated in the allergic reaction. Fifteen minutes after each dosage, patients were evaluated with Peak Flow and blood pressure measurements, heart and respiratory rates and general examination.

A systematic intervention for assistance of patients with asthma in Brazil: partnership between university and public health system

Methods A group of 16 allergists/immunologists developed a capacitating program in 11 Public Health Units in the city of Ribeirao Preto, Brazil. The program comprised lectures on asthma and hands-on training on spirometry and use of inhalation devices; production of didactic material; and development of a protocol on management of asthma. Spacers and spirometry were provided. Each researcher visited one Health Unit 2-4 times a month, to accompany the non-specialist on patients’ visits to the clinic, perform case discussions, and deliver short lectures to the health professionals. Records of asthma medications provided to patients upon physicians’ prescription in the North Region were compared to those from three other Regions with no intervention.