CD3G gene defects in familial autoimmune thyroiditis.

The patients with CD3γ deficiency can present with different clinical findings despite having the same homozygous mutation. We report three new CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+ immunodeficiency and their variable clinical and cellular phenotypes despite the same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation. The median age at diagnosis was 11 years (14 months-20 years). We found all five patients to display autoimmunity: autoimmune thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as well as high IgE (n = 2) and atopic eczema (n = 2). While CD3(+) TCRαß+T cell percentages were low in all patients, only one had lymphopenia and 3 had CD3(+) T cell lymphopenia. Strikingly, we report frequent and multiple autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%), and frequent autoimmunity in family members not available for testing (n = 5, in 80%). The results suggest that CD3G should be studied as a candidate gene for autoimmunity and that CD3gamma deficiency should be considered among other primary immunodeficiencies with predominantly autoimmune manifestations.

Awareness of allergy patients about herbal remedies: a cross-sectional study of residents of Ankara, Turkey.

OBJECTIVE: The use of herbs in patients with allergic diseases is a special problem and still controversial. The objective of this questionnaire-based study was to determine the rate of herbal use in allergy clinic outpatients as well as to explore patient knowledge. METHODS: Patients with respiratory and/or skin disease, either atopic or non-atopic were assigned to a prospective questionnaire study conducted in allergy clinic outpatients. RESULTS: Three hundred and ninety-five patients enrolled in the study. The mean age was 33.50+/-12.14 years. Participants generally had a high educational level (40.5% college and 39% university graduated). The rate of herbal use was 14.2%. All characteristics were similar within herbal user and non-user patients, except gender and age. The number of female patients who use herbal products was greater than for males (p=0.043). Herbal use was common in patients in their late thirties (p=0.024). Three main rationales for herbal use were revealed: (i) acting upon advice of someone (41.1%); (ii) the belief that "herbals are always more beneficial than chemicals" (37.5%); and (iii) the trust that "herbals are always safe" (21.4%). Most of the participants have "no idea" (41.5%) or are "not sure" (33.7%) about potential harmful effects of herbs to allergic people. CONCLUSION: People will continue to use herbals for one reason or another. Allergists and clinical immunologists need to become more knowledgeable about herbal therapies so that they can inform patients about either the benefits or possible harmful effects of herbs.

Recurrent urticaria lesions in a heparin-allergic patient: most likely another form of "recall urticaria".

In this report we describe a female patient with a history of heparin allergy and recurrent urticaria lesions at definite locations where the heparin injections were administered previously.

Not all food additive related reactions originate from commercial foods: chronic urticaria due to home-made canned tomato.

Additives and preservatives in commercial foods have been implicated in the etiology of chronic urticaria, but such foods have not been widely accepted. In some countries, as in ours, people prefer to use home-made foodstuffs to avoid potentially hazardous commercial additives. However, not all home-made foodstuffs are safe, especially regarding allergies. In this report, we describe a patient with chronic urticaria due to home-made canned tomato prepared using "tomato drug" as a "safe (!)" additive.

Combination therapy versus monotherapy for the treatment of patients with rheumatoid arthritis.

OBJECTIVE: The response to single disease modifying antirheumatic drug (DMARD) is often suboptimal in patients with rheumatoid arthritis (RA). Thus, despite the limited data on the therapeutic efficacy of combination therapies, many patients are currently treated with a combination of DMARDs. METHODS: We studied prospectively the efficacy of combination therapy with DMARDs. The study was designed as a randomized trial and a single DMARD or two or three DMARD combinations were administered to 180 consecutive, age- and sex-matched patients with active RA, each of whom was followed up for a period of 2 years under treatment. Patients were divided into 3 groups which did not differ with regard to demographic, clinical and laboratory parameters. Patients in group I were treated with a single DMARD [methotrexate (MTX) 7.5-15 mg/week or sulfasalazine (SSZ) 1-2 g/day or hydroxychloroquine (HCQ) 200 mg/day], group II with MTX + SSZ or MTX + HCQ, and group III with a combination of all three drugs. Patients were re-evaluated at regular intervals by means of clinical and biochemical tests designed to detect specific rheumatic activity. Radiological assessments were also performed and scored according to Larsen by the same radiologist who was blinded to the treatment groups. RESULTS: At the end of the trial there were significant improvements in the clinical and laboratory parameters in all 3 groups. However, improvements were greater and much more significant in the patients who were given combination therapies. The combination of MTX + SSZ + HCQ was more effective than both monotherapy and the two-drug combinations. CONCLUSION: In conclusion, we suggest that patients with RA should be treated with combinations of DMARDs.

Skin test positivity to aeroallergens in the patients with chronic urticaria without allergic respiratory disease.

The etiology of chronic urticaria and angioedema remains uncertain in most of the patients. There are several agents and factors including medications, foods and food additives, infections, contactants, inhalants, physical factors and autoimmunity that implicated in provoking urticaria symptoms. In addition, the possible role of house dust mites has been considered in a few reports. We investigated skin test positivity to house dust mites and other inhalants in 259 patients with chronic idiopathic urticaria and angioedema but without allergic rhinitis and/or asthma. Results were compared with both 300 healthy controls and 300 atopic patients. Immediate cutaneous reactivity to one or more allergens was detected in 71 patients in the study group (27.4%). The most common allergens were house dust mites (24.7%). Skin prick test sensitivity to other inhalant allergens including pollens, molds and cockroach were 7.7%, 0.4% and 0.8%, respectively. In the healthy control group 7% of patients were found as atopic with respect to skin prick test results. The most common allergens in healthy controls were pollens (6%), and house dust mites (4.7%). In atopic control group, pollens and mites are also the most common allergens detected in skin prick test (62% and 50.3%, respectively). The difference between study and healthy control group was statistically significant with respect to presence of atopy and mite sensitivity (p < 0.001). Similar differences were not established in other inhalant allergens. Significant mite sensitivity in the study group is not a coincidence. Because, ratio of skin test positivity to house dust mites in the study group was higher than the healthy controls, but was not as high as atopic patients. Furthermore, the rate of skin reactivity to other aeroallergens was not different from healthy controls. Urticaria as a sole clinical manifestation in mite sensitive patients was unusual.

The allergen spectrum in Turkey and the relationships between allergens and age, sex, birth month, birthplace, blood groups and family history of atopy.

This study was performed retrospectively on 2,342 patients who were treated in the allergy department from 1985 to 1996. All patients had been skin prick tested with 40 common aeroallergens in Turkey. Allergen immunotherapy was given to 1,455 of them. Mean age of the patients was 25.9 (range 5 to 69). Fifty-five percent were males and 45.1% females. Forty percent had bronchial asthma and 60.2% had allergic rhinitis. Fifty-five percent of them had a family history of atopy. Sensitization to pollens was 59.7%, to house dust 20.5%, to molds 2%, to pollens and molds 2.9%, to pollens and house dust 11.5%, to molds and house dust 1.4%, and to pollens, molds and house dust 2%. The grass pollen sensitivity was threefold more common than that for trees, and fourfold more common than that for weed pollens. The diagnosis of bronchial asthma in the 5 to 9 age group was higher than in the other age groups (p < 0.005). The mold sensitization increased in parallel with age and it was the highest in 60 to 69 age group (p < 0.0001). There was no relationship between the allergens and sex, history of family atopy or blood group (p > 0.05) (except for house dust allergen). However, there was a relationship between month of birth (p < 0.005, p < 0.05, respectively) and birthplace (p < 0.001) with pollen and house dust allergen. House dust and molds were more common causes of bronchial asthma than pollens (p < 0.001, p < 0.01, respectively). In conclusion, the most common allergen was pollen in Turkey. In addition, atopic diseases are multifactorial, including such factors as genes and environment. Month and place of birth may influence early exposure and subsequent risk for allergy.

Systemic reactions due to allergen immunotherapy.

The purpose of this study was to evaluate the incidence, type and potential risk factors of systemic reactions due to conventional allergen immunotherapy with aqueous extracts. The study was carried out retrospectively and included 1,506 patients to whom allergy injections had been given during the last 12 years. Symptoms in each reaction were classified with respect to time of onset, involvement of respiratory tract or skin, and presence of hypotension. The results showed 125 systemic reactions in 109 patients (1 per 1,831 injections), of which 52.8% were of the skin, 12% were respiratory symptoms, 30.4% respiratory symptoms and skin, 0.8% hypertension only, and 4% hypotension with respiratory symptoms and skin reactions. Most of the systemic reactions (84.8%) occurred within the 30 min after injection. Forty-one per cent of the systemic reactions were observed in the build-up period (1/52 patients, 1/1, 158 injections) and 58.4% in the maintenance injection period (1/73 patients, 1/2,311 injections). Seventy-six systemic reactions were related to pollen season (60.8%), 11 were related to injection from a new vial (8.8%) and eight to both pollen season and a new vial (6.4%). Thirty-five per cent of the patients who experienced systemic reactions had bronchial asthma, but there was no correlation between frequency of the two. There was also no correlation between systemic reactions and age or sex. It was concluded that immunotherapy has a low rate of systemic reactions and that maintenance immunotherapy appears to be associated with fewer such reactions than the build-up period. The 30 min waiting period is adequate for conventional immunotherapy. However, a longer waiting period may be necessary for high-risk subjects.

Impact of Helicobacter pylori and Giardia lamblia infections on chronic urticaria.

The etiology of chronic urticaria is largely unknown. The role of Helicobacter pylori infection, which is the most important cause of gastritis and peptic ulcer, is not clear in the pathophysiology of chronic urticaria. In this study, we aimed to define the impact of H. pylori on chronic urticaria. Thirty-eight patients who had chronic urticaria of unknown origin and dyspepsia were included in the study. In all patients, standard laboratory tests for detection of urticaria etiology were performed. Mean urticaria symptom scores of patients were carried out. All patients underwent upper gastrointestinal endoscopy. The presence of H. pylori was investigated using urease testing and histopathology. Duodenal fluid aspirated during upper endoscopy was examined for the presence of Giardia lamblia. H. pylori infection was detected in 29 patients. After successful eradication of H. pylori infection, the mean symptom score of patients did not change significantly (2.6 +/- 0.6 vs., 2.4 +/- 0.8). Only one patient had a total disappearance of urticaria symptoms. Out of 38 patients, only one had G. lamblia infection. The results of our study suggest that there is no association between H. pylori infection and chronic urticaria.

Erythropoietic protoporphyria with antinuclear antibody positivity: avoiding misdiagnosis of systemic lupus erythematosus.

A young eunuchoid man was referred to our hospital with suspected erythropoietic protoporphyria. Serum antinuclear antibody (ANA) was found to be positive immediately after the porphyria attack and disappeared 30 days later. Many authors have mentioned the coexistence of systemic lupus erythematosus (SLE) and porphyria. As these two disorders have similar clinical features, the clinician must be alert and use strict diagnostic criteria in determining the presence of SLE with porphyria. In the past, elevation of ANA was reported in the cases of acute intermittent porphyria. However, there have been no reports in the cases of erythropoietic protoporphyria. In addition, the patient was found to have hypogonadotropic hypogonadism consistent with Kallmann's syndrome. To our knowledge, this report is the first case showing the coexistence of Kallmann's syndrome and erythropoietic protoporphyria. As yet, the clinical importance of this association remains unknown.

Levothyroxine versus ketotifen in the treatment of patients with chronic urticaria and thyroid autoimmunity.

BACKGROUND: Thyroid hormone replacement therapy has previously been discussed as a feasible therapeutic approach in patients with chronic urticaria and/or angio-oedema (CUA) and thyroid autoimmunity (TA). OBJECTIVE: The efficacy of levothyroxine was investigated in patients with CUA and TA by comparing it with ketotifen treatment. METHODS: A total of 60 patients with CUA and TA were included in the study. Patients were divided into two groups, which were matched with respect to sex, age and symptom score. Each group consisted of 30 patients. Patients in one group were treated with ketotifen and the other with levothyroxine. After completion of the treatment periods, the pre- and post-treatment symptom scores, onset time of drug effects, duration of symptom-free period, recurrence ratios, recurrence times and side effects were evaluated for each drug. The two drugs were compared with each other according to these parameters. RESULTS: Ketotifen treatment provided significant relief of symptoms. However, these beneficial effects were observed only in ongoing treatment. Symptoms reappeared in all patients during the drug-free follow-up period. On the other hand, 18 of 30 patients were completely improved and three patients partially improved with levothyroxine treatment. Symptoms did not recur in the completely improved patients. CONCLUSION: Levothyroxine is an important and inexpensive treatment alternative in patients with CUA and TA.

Evaluation of vascular injury with proinflammatory cytokines, thrombomodulin and fibronectin in patients with primary fibromyalgia.

OBJECTIVE: Cold intolerance, cold induced peripheral vasospasm, Raynaud's phenomenon, livedo reticularis and immunoglobulin deposition in the skin are often encountered clinical and laboratory findings in patients with primary fibromyalgia (FM). These findings are suggestive of vascular injury. METHODS: Eighty patients (4 male, 76 female) with fulfilling primary FM criteria (FM (+) patient group), 60 patients (3 male, 57 female) with chronic musculoskeletal complaints but without FM (FM (-) patient control group) and 40 healthy volunteers (1 male, 39 female) without musculoskeletal complaints (healthy control group) were enrolled in this cross-sectional study. The study was carried out in two steps. In the first step, the clinical findings, routine laboratory tests, autoantibodies and radiological findings were investigated. The second step were consisted of the laboratory investigations of thrombomodulin and fibronectin as the mediators indicating vascular injury and proinflammatory cytokines in FM patients with Raynaud's phenomenon and/or livedo reticularis and in control groups. RESULTS: There were no differences between study and control groups with regard to laboratory, radiological and immunological (ANA, AntidsDNA, ENA, anticardiolipin IgG and IgM) results. No statistically significant differences were found in the levels of proinflammatory cytokines between FM (+) patient group and control groups (p > 0.05). Thrombomodulin was also shown statistically insignificant difference between FM (+) patient group and control groups (p > 0.05). However, fibronectin, another mediator of vascular injury, was higher in FM (+) patient group and the differences between FM (+) patients and each control groups were statistically significant (p < 0.0001). CONCLUSION: Our results were suggestive of the presence of a non-immunological vascular injury in FM patients with Raynaud's phenomenon and/or livedo reticularis.

Primary non-Hodgkin's lymphoma of the liver (case report).

Primary non-Hodgkin's lymphoma of the liver is very uncommon, and fewer than 100 cases have been reported in the literature. Most reports describe either solitary or multiple mass lesions in the liver. A diffuse lesion without nodule formation is a relatively rare form of the disease. The histologic feature of the disease is a predominantly large cell lymphoma of B-cell lineage. We report a case of primary B-cell non-Hodgkin's lymphoma which had diffusely infiltrated the liver without nodule formation.

Renin angiotensin aldosterone system and drug allergies complicated with hypotension.

It has been discussed in several studies that non-immunologic factors, such as renin angiotensin aldosterone system (RAAS) may play a role in the pathophysiology of anaphylaxis. This study aimed to determine whether RAAS plays a part in the fall in blood pressure during drug reactions or not. Twenty patients who experienced hypotension during drug reaction and 15 healthy volunteers were enrolled in this study. None of the patients in the study or control groups were under treatment with any drug that was capable of influencing to RAAS. Serum levels of angiotensin-I (A-I), angiotensin-II (A-II), angiotensin converting enzyme (ACE) and aldosterone were measured in both study and control groups. The Mann-Whitney U test was used to compare the results of the groups. There were no statistically significant differences between the groups with respect to A-I, A-II, ACE and aldosterone levels. It was concluded that a fall in blood pressure during drug reaction must be the result of mast cell mediator effects on the vascular wall rather than RAAS impairment.

A case of textile dermatitis due to disperse blue on the surgical wound.

Disperse blue (DB) 106 and DB 124 are the most frequent fabric dye allergens inducing textile dermatitis, but contact allergy to them may easily undiagnosed because the clinical picture usually needs high index of suspicion. We present the case of a 35-year-old woman who was referred for a recurred lesion over the incision scar of right total hip replacement surgery, which did not respond to treatment with povidone-iodine, mupirocin, and rifampicin. Patch testing, conducted with a European standard series and therapeutics that were used in the treatment of the lesion, revealed a positive reaction to dispersion mix blue 106/124. The patient was questioned in detail and reported that she has been wearing dark-colored synthetic panties for long years. The correlation was done between the positive antigen in the patch test and the clinical findings. The patient was treated with a corticosteroid cream for 2 weeks. She did not wear any dark-colored synthetic panties afterward and no flare-up was seen in the follow-up period. In this report, we emphasize the importance of detailed questioning of patients and that contact dermatitis should be considered potential cause of dermatitis at skin sites where the barrier function is compromised.

Is allergenic similarity predictable in respiratory allergies?

BACKGROUND: First degree relatives of patients with allergic diseases are at increased risk of having the disorder. However, it is not clear whether two such related patients with allergic diseases are sensitive to the same antigens or not. OBJECTIVE: The aim of this study to determine whether or not first degree relatives with respiratory allergies are more likely to be skin test positive to the same allergen extracts as unrelated patients. PATIENTS AND METHODS: Skin test results for 35 common aeroallergens were compared in 264 pairs of genetically related subjects and 264 pairs of age and sex matched, but unrelated, subjects. We calculate the percentages of the concordant and discordant results in each group. Results are compared by using chi2 test. RESULTS: For all related and unrelated groups combined, there were significant differences with mites (der. pteronyssinus, der. farinae) and some moulds (aspergillus mix and rhizopus nigricans) (p<0.05); When the groups were subdivided into parent-child pairs and same or different sibling pairs, and the same comparisons were made, a significant difference was only found in both sibling pairs (p<0.05), not in parent-child pairs (p>0.05). Since there was no both positivity with aspergillus mix and rhizopus nigricans in the two groups, these two allergens were excluded from the study. CONCLUSION: It is concluded that we could not say that if one or both of parents are atopic to any allergens, their child will be atopic to the same allergens. Besides, when a respiratory allergy occurs in siblings, only the one who has house dust mite allergy sensitivity can possess the similar antigen sensitivity.

The role of ace gene polymorphism in the development of angioedema secondary to angiotensin converting enzyme inhibitors and angiotensin II receptor blockers.

BACKGROUND: Angiotensin Converting Enzyme inhibitors (ACEi) may cause angioedema, with an incidence of 0.1 % to 1 %, which may be life-threatening. ACEi induce angioedema by increasing the levels of bradykinin. Angiotensin II receptor blockers (ATRB), have a pharmacological profile similar to ACEi. The polymorphism of the ACE gene is based on the presence or absence of a 287-bp element on intron 16 on chromosome 17. The plasma level of ACE is related to gene polymorphism. ACE level in genotype DD is double that in genotype II. OBJECTIVE: The aim of this study was to investigate whether the relationship between ACE gene polymorphism and ACEi induced angioedema is present or not. METHODS: ACE gene polymorphism was investigated in patients with angioedema due to the use of ACEi or ATRB (n:32, group 1), in patients receiving ACEi or ATRB without angioedema (n:46, group 2), and healthy controls (n:96, group 3). RESULTS: ID polymorphism was the most frequent genotype in all groups, without any significant difference among the groups (p:0.868). ACE gene polymorphism was not related with the drugs used (ACEi or ATRB), localisation of angioedema, and female sex, in group 1. CONCLUSION: Our results showed that ACE gene polymorphism has no effect on ACEi or ATRB induced angioedema.

Not all ACE inhibitor related angioedema is always evident: a case which is misdiagnosed as panic attack and speech disorder.

Angiotensin-converting enzyme (ACE) inhibitors are the most common medications responsible for angioedema. Angioedema is a potentially life threatening conditions especially in geriatric age patients that they have take a several medications include ACE inhibitors and non steroidal anti inflammatory drugs. We present a case an ACE inhibitor induced angioedema that confused many clinical events.

A successful pregnancy and uncomplicated labor with C1INH concentrate prophylaxis in a patient with hereditary angioedema.

Patients with hereditary angioedema (HAE) need a special concern during pregnancy. Although, the disease has a relatively benign course during pregnancy, maternal mortality has been reported. We present a HAE patient with recurrent attacks during pregnancy, but uncomplicated labor under C1INH concentrate prophylaxis.