Azathioprine as a therapeutic alternative for refractory chronic urticaria.

BACKGROUND: Chronic urticaria (CU) affects up to 1% of the general population. Its impact on quality of life is immense, and patients might require multiple drugs to control symptoms. The main therapeutic challenge in the treatment of CU is to maintain symptomatic control while minimizing the use of glucocorticosteroids and their plethora of side effects. METHODS: Two patients with severe, refractory CU after treatment failure with various drugs, including high-dose cyclosporine, were administered azathioprine. RESULTS: In both patients, the treatment with azathioprine resulted in a significant clinical improvement, enabling steroid withdrawal. CONCLUSION: Azathioprine should be considered as a therapeutic option for chronic, steroid-dependent urticaria, refractory to other treatments.

Omalizumab therapy for chronic spontaneous urticaria: the Israeli experience.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common, debilitating disease that is frequently resistant to standard therapy. Omalizumab, anti-immunoglobulin-E humanized monclonal antibody, was recently shown to be effective in treating resistant CSU. OBJECTIVES: To investigated the treatment of CSU with omalizumab in Israel. METHODS: We conducted a multicenter retrospective analysis of patients with refractory CSU treated with omalizuamb in Israel during 2012-2013. Complete improvement was defined as resolution of symptoms with no need for other medications, or satisfactory when patients' condition improved but required regular or intermittent doses of antihistamines. RESULTS: Forty-three patients received omalizumab off-label for refractory CSU. Their mean age was 45 +/- 12 years and CSU duration was 4.3 +/- 4 years. In this cohort, 98% were unsuccessfully treated with high dose H(1)-antihistamines, 88% with systemic glucocorticoids and 30% with cyclosporine and/ or other immune-modulators. Fourteen patients received only one injection of omalizumab, while the other 29 received on average of 4.3 +/- 3.2 injections; 30 patients received 150 mg/ month and 13 received 300 mg/month. Following omalizumab therapy, disease remitted within weeks in 86% of patients, of whom half achieved complete remission. The latter was associated with usage of high dose omalizumab, 300 mg/month vs. 150 mg/month (P = 0.02) and repeated therapy (i.e., multiple injections vs. a single injection) (P = 0.0005). CONCLUSIONS: Omalizumab is an effective and safe treatment for refractory CSU with rapid onset of action for inducing and maintaining remission. Treating CSU patients mandates an individual approach, because while low dose omalizumab will suffice for some patients others might need higher doses and prolonged therapy.

Azathioprine-induced fever in autoimmune hepatitis.

Underdiagnosis of drug-induced fever leads to extensive investigation and prolongation of hospitalization, and may lead to multiple unnecessary invasive procedures and a wrong diagnosis. Azathioprine is a widely used immunosuppressive drug. We report a case of a 53-year-old female patient diagnosed with autoimmune hepatitis treated with azathioprine, who presented to the emergency room with a 6-wk history of fever and chills without other associated symptoms. Since the patient's fever was of unknown origin, she was hospitalized. All treatment was stopped and an extensive workup to explore the source of fever and chills was performed. Results of chest X-ray, viral, urine, and blood cultures, autoimmune serology, transthoracic and transesophageal echocardiography, and abdominal ultrasound revealed no source of infection. A rechallenge test of azathioprine was performed and the fever and chills returned within a few hours. Azathioprine was established as the definite cause following rechallenge. Fever as an adverse drug reaction is often unrecognized. Azathioprine has been reported to cause drug-induced fever in patients with inflammatory bowel disease, rheumatoid arthritis, and sarcoidosis. To the best of our knowledge there have been no previous reports documenting azathioprine-induced fever in patients with autoimmune hepatitis. The occurrence of fever following the readministration of azathioprine suggests the diagnosis of drug-induced fever, particularly after the exclusion of other causes. A careful rechallenge is recommended to confirm the diagnosis.

Late-onset sarcoidosis after liver transplantation for primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) and systemic sarcoidosis are granulomatous diseases of unknown etiology whose hepatic manifestations may infrequently be imitative of one another. Described herein is the first reported case in the medical literature of systemic sarcoidosis developing after liver transplantation for PBC. The presented patient, who suffered from typical clinical, laboratory, and pathologic manifestations of PBC, developed decompensated liver cirrhosis within a course of 8 years, necessitating orthotopic liver transplantation. A year and a half after transplantation, the patient developed diffuse, biopsy-proven, dermatologic and pulmonary manifestations of systemic sarcoidosis, which promptly responded to corticosteroid treatment. In retrospect, the patient's longstanding liver disease was probably caused by an unrecognizable, isolated hepatic form of sarcoidosis or an overlap between PBC and sarcoidosis. This patient illustrates the complexity that may be rarely encountered in differentiating between PBC and hepatic sarcoidosis. Discussed are the clinical, laboratory, and pathologic overlaps between hepatic sarcoidosis and PBC, and clues that may aid in the diagnosis and differentiation between the 2 disorders. Hepatologists and liver transplantation specialists should be aware of the rare possibility of hepatic sarcoidosis imitating PBC, and exacerbating systemically after liver transplantation.

Saliva secretion in patients with allergic rhinitis.

BACKGROUND: Allergic rhinitis is manifested by watery discharge; however its clinical effect on the watery volume in the oral cavity is unknown. In addition, the low incidence of dry mouth due to treatment with the new generation antihistamines is based on subjective patients' reports only. This study aimed to examine the effect of loratadine and fexofenadine on the salivary gland function in patients diagnosed with allergic rhinitis compared to untreated allergic patients and healthy individuals. METHODS: A comparative observational study assessed parameters related to the patients' perception of dry mouth as well as clinically observed parameters in fexofenadine-treated patients (group A) and in loratadine-treated patients (group B). Allergic patients without pharmacological treatment (group C) and healthy individuals (group D) served as a double control in order to evaluate the effect of allergy itself on dry mouth. A total of 36 patients were enrolled. RESULTS: Patients in groups A and C reported the highest intensity of xerostomia. Sialometry values were significantly lower in these 2 groups compared to the healthy controls (p = 0.02 and 0.03, respectively). Average sialometry was over 0.2 ml/min in all groups and subjective dry mouth sensation ranged in the lower quarter of the visual analogue scale. CONCLUSIONS: In this pilot study, patients diagnosed with allergy presented a significant difference in salivary flow rate compared to healthy controls. Unlike the effect of loratadine, fexofenadine-treated patients showed significantly lower salivary flow rates compared to healthy individuals. In all cases the intensity of dry mouth was low.

Liver abscess in inflammatory bowel disease: report of two cases and review of the literature.

Hepatic abscesses are a rare complication of inflammatory bowel disease (IBD). Despite the fact that certain hepatobiliary complications of IBD, including cholelithiasis, primary sclerosing cholangitis (PSC) and cholangiocarcinoma predispose patients with IBD to ascending cholangitis, previously published data does not demonstrate that biliary infection is an important mechanism underlying liver abscess development in these patients. We describe two patients with inflammatory bowel disease, both with PSC, who developed multiple liver abscesses, and review the literature on liver abscesses in association with inflammatory bowel disease.

Knowledge and expectations of patients receiving aeroallergen immunotherapy.

BACKGROUND: Patients receiving aeroallergen immunotherapy frequently have poor knowledge and unfounded expectations of various important aspects of their treatment. OBJECTIVE: To evaluate patients' knowledge about the content, benefit, and risk related to the aeroallergen immunotherapy that they were receiving. METHODS: A self-administered questionnaire was distributed to all patients older than 16 years who had undergone aeroallergen immunotherapy for allergic rhinitis at 3 university-affiliated allergy clinics. RESULTS: A total of 132 patients (77 males and 57 females; mean +/- SD age, 30 +/- 13 years) participated in the study. The mean +/- SD duration of treatment was 30 +/- 60 months. Complete recovery of their allergies was expected by 39% of the patients. One fifth of the study group did not know when improvement should be expected, and 18% anticipated improvement to occur within days or weeks from the initiation of treatment. Only 32% were aware that immunotherapy might have some potential risk or adverse effects, and 24.2% failed to identify at least one of the allergens they were receiving. Patients who were interviewed during their first 6 months of aeroallergen immunotherapy had more knowledge about it than those who had been undergoing long-term treatment. CONCLUSIONS: There is a grave lack of knowledge and numerous misconceptions among substantial numbers of patients receiving aeroallergen immunotherapy. More educational effort is needed to increase patients' knowledge about immunotherapy before and during aeroallergen immunotherapy to improve their compliance and the success and safety of this therapeutic modality.

Evaluation of adverse reactions to local anesthetics: experience with 236 patients.

BACKGROUND: Adverse reactions to local anesthetics (LAs) are frequently reported. Although most of these reactions are not immune mediated, many patients are referred to allergy clinics and undergo extensive evaluation. OBJECTIVE: To determine the prevalence of true LA allergy among the patients referred for suspected hypersensitivity and to evaluate the usefulness of the currently used evaluation protocol. METHODS: A total of 236 patients referred to our allergy clinic for investigation of LA hypersensitivity were included in this study. The evaluation protocol was composed of skin prick and intradermal tests, followed by subcutaneous challenge with unrelated LA preparations that contained preservatives. RESULTS: Skin prick and intradermal test results were negative for all subjects. No objective adverse reactions were observed during the challenge in all but 1 patient, who developed local erythema at the site of injection and later underwent an uneventful challenge with a different LA. CONCLUSIONS: Allergic reactions were not reproduced during testing and challenge with LA preparations that contained preservatives or preservatives with adrenaline in our large group of patients with suspected LA allergy. Since both prick and intradermal skin test results were negative in all the patients and did not provide us with useful information, we propose to modify the standard protocol by omitting intradermal tests and shortening the challenge. We also suggest that the whole procedure be performed with LAs that contain preservatives, which are usually the preferred preparations widely used in daily practice.

Metastatic carcinoma presenting with concomitant eosinophilia and thromboembolism.

A case of a 58-year-old female patient who presented with significant blood eosinophilia and thromboembolic events is described. The patient was eventually diagnosed as suffering from a disseminated malignancy of gastrointestinal origin. Immunohistochemical studies of the tumor are presented. These studies show that tumor cells produce interleukin-3 and -5 and granulocyte macrophage-colony stimulating factor. These cytokines are known to support differentiation, proliferation, and survival of eosinophils. Their secretion is the probable explanation for the appearance of high blood eosinophilia in this patient. To the best of our knowledge, combined blood eosinophilia and thromboembolism as presenting manifestations of a solid tumor have never been reported.

[Anti-IgE--a new treatment for allergic diseases].

Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases. Cross-linking of IgE molecules on mast cell and basophil surface membrane by allergens, triggers the release of multiple mediators, leading to the development of IgE-mediated immediate and late hypersensitivity reactions. In view of the pivotal role of IgE, it became an attractive target for intervention in the treatment of allergic diseases. Murine monoclonal non-anaphylactogenic antibodies directed to the receptor-binding domain of IgE, were found to reduce IgE levels and production. Anti-IgE antibodies have been recently evaluated in several clinical trials involving hundreds of asthmatic patients both adults and children, including patients with allergic rhinitis. Clinical efficacy and good tolerability were demonstrated. This novel therapeutic approach also appears to be promising for potential treatment of patients suffering concomitantly from several allergic disorders.