Ali Kutlu

Healing effects of omalizumab in a patient with cholinergic urticaria associated severe dyspeptic complaints.

To the Editor: Cholinergic urticaria (CU) is a type of physical urticaria characterized by a number of short-lasting, highly pruritic weals. The underlying pathological mechanism of CU is not fully understood.[1] Omalizumab is a humanized, monoclonal IgG anti-IgE antibody that binds specifically to circulating IgE molecules, thus interrupting the allergic cascade.[2] The efficacy of anti-IgE treatment has been shown in many disorders with complex and unclear etiology, comprising physical urticarias, chronic idiopathic urticaria, angioedema and eosinophil-associated gastrointestinal disorders.[3] A 38-year-old Caucasian male with severe CU was presented to GATA Haydarpasa Training Hospital in September 2014. Severe dyspeptic complaints including epigastric pain and upper abdominal fullness were accompanied the urticarial lesions for 6 months. He mentioned that approximately 20–30 min after many kind of foods and mild exercise severe pruritic hives took place, especially on the trunk and upper extremities [Figure 1]. He also indicated that the dyspeptic complaints were not improved by use of H2 receptor antagonists or proton pump inhibitors (PPIs). His physical examination was unremarkable. Laboratory tests including whole and routine blood count, liver and thyroid function tests, anti-nuclear antibody, rheumatoid factor and total tryptase levels were normal. Total IgE levels were 46 U/ml. He was prescribed various sedating and nonsedating antihistamines, leukotriene receptor antagonist and anticholinergics. Corticosteroids had a positive effect on urticarial lesions but were ceased due to severe dyspeptic complaints. He underwent an upper gastrointestinal endoscopy and was diagnosed as “eritematous pangastritis.” Histopathological examination revealed minimal to moderate chronic superficial inflammation without activation. Helicobacter pylori infection and “eosinophilic gastritis” were not detected. He was then prescribed different PPIs (lansoprazole and esomeprazole), but, unfortunately, his gastric complaints were not improved. Although using high dose antihistamines and leukotriene antagonists, his CU associated symptoms were not healed. Afterwards, he was prescribed omalizumab 150 mg solution for injection monthly. One month later he was re-evaluated. The life quality of the patient was prominently improved shortly after the first dose, as demonstrated with the dermatologic life quality index,[4] and gastric complaints almost completely disappeared. He is still given omalizumab treatment regularly. He has had minimal skin complaints, only with heavy exercise, during the period when using omalizumab, but no more gastric complaints. Figure 1 Cholinergic urticarial lesions of this 38-year-old male patient. To date, the therapeutic efficacy of omalizumab on CU associated resistant dyspeptic complaints has not been reported. The effectiveness of anti-IgE treatment is not only restricted to inhibition of allergen IgE interactions. It has rather complicated consequences. Stimulation of FceRI in human umbilical cord mast cells causes a substantial change in expression of many genes, including 18 cytokines, 13 chemokines, and several adhesion molecules involved in potential interactions with T cells, B cells, or dendritic cells.[5] It is well-known that the gastrointestinal system plays a central role in immune system homeostasis and its relationship with the immune system is rather complicated. With current information, it is not easy to comment on how this newly emerged multi-potent immune therapeutic agent had these effects on dyspeptic complaints. In conclusion, the therapeutic spectrum of anti-IgE treatment comprises allergic disorders related to many clinical problems, including CU associated dyspeptic complaints.

An unusual garlic burn occurring on an unexpected area

A 24-year-old otherwise healthy woman presented with an itchy, burning, erythematous lesion located over her neck. She had applied crushed raw garlic over her neck for about 5 h following a sore throat. On dermatological examination an erythematous demarcated area with eruption, patchy squamous and vesicular lesions were present over the submandibular region (figure 1). On the basis of history …

Arterial Stiffness Without Other Inflammatory Markers May Not Accurately Provide Information to Clinicians About the Severity of Psoriasis

We read the article ‘‘Aortic Arterial Stiffness is a Moderate Predictor of Cardiovascular Disease in Patient with Psoriasis Vulgaris’’ by Balta et al with interest. This well-presented study investigated the relationship between arterial stiffness and high-sensitivity CRP (hsCRP) in patients with psoriasis. The authors concluded that arterial stiffness correlated positively with age, sex, body mass index, diastolic blood pressure, and hsCRP level. These findings provide further evidence of a link between premature atherosclerosis and psoriasis. Arterial stiffness represents vascular damage and is a measure of the degree of atherosclerosis. Arterial stiffness has received increased attention because of its role as an independent predictor of cardiovascular disease and relationship to the metabolic syndrome. Increased arterial stiffness is a common indicator of atherosclerotic involvement of the vascular structure, indicating cardiovascular diseases, stroke and renal diseases, as well as total mortality. It can also be affected by atherosclerotic risk factors such as smoking, alcohol consumption, hypercholesterolemia, hypothyroidism, plasma homocysteine, and serum gamma-glutamyltransferase (GGT). Furthermore, in recent studies, plasma homocysteine concentrations were found to be significantly higher in patients with psoriasis. In this point of view, in the present study, the authors did not mention about some of the factors affecting arterial stiffness, including alcohol consumption, hypothyroidism, plasma homocysteine, and serum GGT levels. If the authors had described these factors, they would have obtained different results. More severe psoriasis was significantly associated with higher prevalence of concomitant disease, greater involvement (nails, scalp, palm soles), and poorer quality of life. Severe psoriasis is also associated with increased risk of cardiovascular mortality and morbidity due, in part, to shared immune–inflammatory mechanisms. In our opinion, it would have been better if the authors of the present study had included information about disease severity (mild, moderate, or severe), mean Psoriasis Area and Severity Index, and presence of psoriatic arthritis. In conclusion, arterial stiffness was shown as a noninvasive method to assess endothelial dysfunction in clinical practice, which is affected by many factors. Arterial stiffness itself without other inflammatory markers may not provide information to the clinicians about the endothelial inflammation on psoriasis. So we believe that it should be evaluated together with other serum biochemical markers.

Could aluminum be a new hidden allergen in type 1 hypersensitivity reactions when used as a drug additive

Medications usually contain numerous additives and preservatives. Some of these agents have been reported as causative factors in adverse drug reactions, including asthma attacks, urticaria and/or angioedema, and even severe systemic anaphylaxis. Moreover, allergens such as additives and preservatives may be hidden as they are not easily identified during etiological investigations.

Efficacy of Omalizumab in a Patient with Angioedema Clinically Resembling a Hereditary Angioedema.

Dear Editor: A 20-year-old man was referred to our allergy and immunology department with complaints of recurring angioedema attacks, lasting 48~96 h, on his lips, eyes, and face, as well as swelling of the extremities and testicles during the last 1 year. Regular use of antihistamine and steroid drugs was generally ineffective against the frequency and severity of the angioedema attacks. He experienced recurrent abdominal pain attacks during the evaluation period. He was hospitalized in another center with a prediagnosis of familial Mediterranean fever; however, that diagnosis was excluded later. Urticarial lesions were not observed during the angioedema attacks. He did not have a history of drug or food allergy, and no specific family history for angioedema was reported. A detailed evaluation for arthritis and rheumatologic disorder was done but no specific findings were found. Furthermore, rheumatologic markers were negative (IRB No. 1491-21-16/1539). Routine laboratory tests for the management of chronic urticaria-angioedema and for anti-nuclear antibody, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, C3, and C4 were within the reference limits. The total immunoglobulin E (IgE) value was 213 IU/ml, and the C4 levels during the attacks were normal. However, C1 esterase inhibitor was measured to be 28.3 mg/dl (reference, 32~39 mg/dl), and hereditary angioedema (HAE) was clinically considered. Danazol treatment up to 400~600 mg/day was started; however, no significant benefit was observed. As the 1,000 U C1 esterase inhibitor administered during the attacks (Cetor, 500 U; Sanquin, Amsterdam, The Netherlands) was ineffective, the diagnosis of HAE was excluded. Because the urticarial complaints started in addition to the angioedema complaints, our patient received 300 mg omalizumab (Xolair 150 mg; Novartis Pharmaceuticals, Basel, Switzerland) subcutaneously every 4 weeks according to conventional asthma treatment protocols. He was treated with omalizumab for 6 months. His angioedema attacks ceased completely within 2 weeks after the start of this treatment. Except for the very short period for the formal procedures required for the procurement of the drug, he had no other complaints during the 6 months follow-up. In randomized, placebo-controlled trials, omalizumab was shown to have excellent efficacy in chronic spontaneous urticaria1. A growing number of case reports and series suggest that anti-IgE treatment may also be beneficial for patients with physical urticarias and chronic angioedema. Recently, omalizumab treatment for inducing and maintaining long-term remission in patients with severe chronic urticaria has been demonstrated2. Unfortunately, for such disorders with complex and unclear etiology, no randomized placebo-controlled trial has been performed yet3. The mechanism of omalizumab activity in angioedema is currently not well defined. However, several mechanism may be considered. Even if the pathogenesis of angioedema in the present case may not be directly mediated by IgE, omalizumab may be effective through an unidentified and indirect anti-inflammatory manner. Sayama et al.4 reported that the stimulation of high-affinity IgE receptor (FceRI) in human umbilical cord mast cells causes substantial change in the expression of many genes, including Interleukin-11 (IL-11), and at least 30 other cytokines and chemokines and several adhesion molecules involved in potential interactions with T cells, B cells, or dendritic cells. Another work, in which the anti-inflammatory activity of omalizumab was mediated, has provided evidence showing the efficacy of this drug in idiopathic angioedema through eosinophil apoptosis induction and downregulation of the inflammatory cytokines IL-2 and IL-135. In conclusion, it seems that therapeutic efficacy spectrum of anti-IgE treatment comprises many allergic disorders with unknown etiology, including angioedema.

Erythrocyte zinc level in patients with atopic dermatitis and its relation to SCORAD index

Introduction Atopic dermatitis (AD) is a chronic, pruritic inflammatory disease, characterized by a relapsing-remitting course. The pathogenesis of atopic dermatitis is not completely understood, although the disorder appears to result from the complex interaction between immune abnormalities, genetic and environmental factors. Trace elements are essential for normal functioning of the immune system. Aim To determine zinc levels in serum and erythrocytes of patients with AD using an atomic absorption spectrometric technique and to investigate the relationship between those levels and disease activity. Material and methods Sixty-seven patients and 49 controls were enrolled into the study. The disease severity of AD patients was determined according to the Scoring Atopic Dermatitis (SCORAD) index. We measured zinc levels in serum and erythrocytes by the atomic absorption spectrophotometric technique. Results Erythrocyte zinc levels were significantly lower in AD patients than in the control group (p < 0.001), whereas serum zinc levels did not differ between the groups (p = 0.148). In the AD patient group there was a negative correlation between the SCORAD score and erythrocyte zinc levels (r = –0.791; p < 0.001). Conclusions The negative relationship between disease severity and erythrocyte zinc levels might suggest an immunopathological link between AD progression and intracellular zinc metabolism.

Besinlerle Yapılan Atopi Yama Testinin SCORAD İle İlişkisi

Amaç: Besinlerle atopik dermatit (AD) kliniği arasındaki ilişki tartışmalıdır.Besinlerle yapılan “fresh prick testleri”nin (FPT) özgünlüğünün düşük olması, AD’de çoğunlukla lezyonların geç ortaya çıkması ve buna bağlı anamnezdeki tutarsızlıklar, provokasyon testinin zaman alıcı ve riskli olması, hastalığın fizyopatolojisinde T lenfositlerin oynamış olduğu rol, atopi yama testini (APT: “Atopy Patch Test”) ön plana çıkartmaktadır. Bu çalışmada besinlerle yapılan APT ve FPT’nin hastalığın ağırlığını yansıtan SCORAD indeksi ile olan ilişkisi araştırılmıştır. Gereç ve Yöntem: Çalışmaya Mayıs 2006-Mayıs 2007 tarihleri arasında polikliniğimizde AD tanısı alan, yaşları 2–15 yaş arasında 21’i erkek, 24’ü kız 45 hasta dahil edildi. Tüm hastalara yumurta, süt ve buğday unu ile FPT ve APT uygulandı. Hastalığın şiddeti SCORAD indeksi kullanılarak değerlendirildi. Çalışmanın istatistiksel analizinde SPSS sürüm 11.0. istatistik paket programı kullanıldı. P<0,05 ise istatistiksel olarak anlamlı kabul edildi. Bulgular: Besinlerle yapılan FPT hastaların %32,5’inde pozitif, %67,5’inde negatif olarak bulundu. En yüksek besin FPT pozitifliği %20 ile buğday ununa karşı gözlendi. Besinlere karşı 21 (%56,8) hastada pozitif APT reaksiyonu vardı. Besinlerle en yüksek APT pozitifliği yumurtaya karşı (%54,1) gözlendi. SCORAD indeksi ile besin allerjenlerine karşı FPT pozitifliği arasında anlamlı ilişki gözlenmedi. Aynı şekilde besinlerle yapılan APT ile SCORAD indeksi arasında ilişki saptanmadı. Sonuç: Çalışmamızda besinlerle allerji testleri pozitifliklerinin AD’nin klinik şiddetini yansıtan parametrelerle ilişkisi gözlenmedi. Özellikle besin APT sonuçlarına göre eliminasyon diyeti kararı vermenin uygun olmadığını düşünmekteyiz. (Türk derm 2013; 47: 99-102) Anah tar Ke li me ler: Atopik dermatit, atopi yama test, skin prick test, SCORAD

Cold-induced urticaria with systemic reactions after hymenoptera sting lasting for 10 years

A 20-year-old man was referred to our allergy and immunology department with the complaints of intense pruritus, generalised erythema and oedema on the trunk, face and extremities after exposure to cold. He had experienced the same symptoms on cold rainy days. The patient reported that all his cold-related complaints had begun 10 years ago shortly after a common wasp sting on his head, which was limited to mild local reaction. Two years after the wasp sting, he experienced a mild anaphylactic reaction (chest tightness, nausea, dizziness, abdominal pain) while standing in a cold river for fishing. Although the patient was able to prevent himself from cold exposure in his civil life, he was unable to avoid cold during his military service and he experienced systemic reaction with chest tightness, nausea, dizziness, abdominal pain while waiting outside for muster on a cold day. The patient was evaluated by cold contact stimulation test (CST) with an ice cube in a plastic bag (3, 5 and 8 min). The test was positive only at 8 min. Other physical urticaria forms were not observed. Laboratory evaluation included complete blood count, erythrocyte sedimentation rate, C-reactive protein, anti-nuclear antibody, rheumatoid factor, antistreptolysin-O, cold agglutinins, cryoglobulins, complement C4, syphilis, hepatitis B and C and HIV serologies, thyroid hormones, thyroid stimulating hormone, and anti-thyroid peroxidase. All laboratory tests were within normal limits. Bee venom-specific IgE were found class II positive for Apis Mellifera (1.32 kUA/L), and Vespula Spp (1.08 kUA/L). He was instructed to avoid cold exposure and medical therapy with a second generation antihistamine, desloratadine, was prescribed. After 1 week of antihistamine treatment, his tolerance to cold increased considerably and CST at 8 min was found negative. Acquired cold urticaria (ACU) induced symptoms are generally restricted to cold-exposed skin areas, however more severe clinical manifestations can be observed in case of extensive cold exposure. Those symptoms may range from generalised urticarial symptoms to systemic reactions affecting respiratory, gastrointestinal or cardiovascular system.1 ACU is idiopathic in most cases. Insect bite,2 jellyfish sting,3 bee and wasp sting4 and venom immunotherapy5 are reported as trigger factors for ACU. Although the sensitisation to hymenoptera venom is common, ACU following hymenoptera sting is rarely reported.4 Although the prevalence of atopic disorders in patients with ACU was reported similar to the general population1 high rates of atopy in these patients have also been reported.6 The pathogenesis of ACU is still unknown. Histamine is released after cold challenge in ACU patients.7 Increased levels of IgE and functional anti IgE antibodies (IgG and IgM) have been demonstrated in patients with ACU.8 These may act as a functional autoantibodies and histamine-releasing factors described in some patients with chronic idiopathic urticaria.9 ACU generally tends to have a chronic course and the mean duration of symptoms ranges between 4.8 and 9.3 years.1 However, Kalegeromitros et al. have reported four cases of Hymenoptera sting induced ACU. The severity of the symptoms decreased in time and all cases had complete remission in less than one year.4 However, our case had systemic reaction even after 10 years from Hymenoptera sting. It seems that ACU after Hymenoptera sting may last for several years. These patients must be informed that their disease may not disappear in the short term.

Wheat Dependent Exercise Induced Ana flaxy ; Discussion Of Diagnostic Difficulties in Wheat Allergy due to a Case

Wheat is the most consumed and the most common allergic nutirent among grains in the world. It is included in many daily consumed products and difficult to remove from diet. Since it is consumed with many foods, different nutrients are accused in anamnesis and it is not regarded as allergic food by many patients and their relatives. Allergic skin tests applied with commercial preparats of wheat may not always yield result. Here, we discuss a 26 years male patient showing wheat allergy and anaflaksi induced by exercise. In this case, there is no reactions when a small amount of wheat consumed, however if a large large amount of wheat consumed, urticarial lesions occur. Moreover if exercise is done after wheat intake, it causes anaphylaxis. Although giving positive reaction to many foods that are not compatible with anamnesis in skin tests, there was no reaction to wheat. Therefore, It was diagnosed with provocation test.

Does the atopic phenotype prevent development of active tuberculosis infection

This study investigated the relationship between the atopic phenotype and the development of active tuberculosis. A total of 82 human immunodeficiency virus-negative males with active pulmonary tuberculosis and 88 healthy controls were enrolled into this prospective study. Serum immunoglobulin E (IgE) levels were measured and skin prick tests performed before initiation of treatment. Skin prick tests were positive in 34.1% of the tuberculosis patients and 39.8% of the controls. Allergic respiratory symptoms were significantly less frequent in skin prick test positive tuberculosis patients (21.4%) compared with skin prick test positive controls (62.9%). Median IgE levels in atopic tuberculosis patients were significantly higher than in atopic controls. The low rate of atopic respiratory complaints seen in the tuberculosis patients, despite having similar allergic skin prick test sensitivities to the controls, could be attributed to a weak T-helper (Th) 2 immune reaction and its effects on Th1–Th2 interaction.