Adverse reactions to allopurinol are frequently observed and potentially severe, which occur in up to 10% of treated patients, ranging from urticaria and angioedema, fixed drug eruption, maculopapular exanthema to Stevens Johnson syndrome (SJS), toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms.1 Allopurinol hypersensitivity has been associated with the presence of the allele HLA-B 5801, which appears to increase the risk of developing severe adverse reactions.

BACKGROUND:Migrants from developing to Western countries tend to become more sensitised to host than to origin country allergens, although substantial changes in migration patterns have occurred in recent decades. METHODS:We investigated adult immigrants with respiratory allergy, first tested for allergic sensitisation between 1985 and 2012 in a highly industrialised area in Italy. A comparison was made of the sensitisation pattern between immigrants and a random sample of native-born subjects affected by a respiratory allergy, and among immigrants according to macro-region of origin and time period. RESULTS:Between 1985 and 2012, 480 immigrants with respiratory allergy had a first positive allergy test. Immigrants were sensitised mainly to grass (67.1%), house dust mites (HDM) (38.5%) and birch (27.5%), with a pattern of sensitisation very similar to that observed in Italians (native-born). An increase in the proportion of subjects with asthma and of subjects with polysensitisation was observed from the first (1985-2002) to the middle (2003-2007) and the most recent period (2008-2012). In recent years, the proportion of subjects with polysensitisation in immigrants is higher than in Italians (native-born) (53.3% vs. 40.1%). Among immigrants, the risk of sensitisation to grass was higher in those from Sub-Saharan Africa (odds ratio, OR=2.76) and Latin America (OR=2.49), whereas risk of sensitisation to HDM was higher among immigrants from South Asia (OR=2.71), compared to immigrants from Eastern Europe. CONCLUSIONS:Immigrants develop multiple sensitisations more frequently than native-born people, and are especially sensitised to local allergens; the country of origin seems to play a role.

Background: Anisakis simplex (As), a parasite in fish, is able to sensitize humans via the alimentary tract. The prevalence of hypersensitivity and allergy to As outside the Iberian peninsula has not been investigated so far. We investigated Anisakis hypersensitivity in different areas of Italy.Methods: Consecutive subjects seen at 34 Italian allergy centers from October to December 2010 were investigated both by specific interview and by skin prick test (SPT) with As extract.Results: A total of 10 570 subjects were screened, of which 474 (4.5%) scored positive on Anisakis SPT and 66 of these (14% of those sensitized; 0.6% of the studied population) had a history of As allergy. Marinated anchovies were the most frequent cause of allergic reactions. Thirty-four (52%) patients were mono-sensitized to Anisakis. Sensitization rate showed marked geographic differences (range: 0.4-12.7%), being highest along the Adriatic and Tyrrhenian coasts, where homemade marinated anchovies are an age-old tradition. In inland centers in northern Italy, the prevalence was directly related to the number of inhabitants. The analysis of the impact of immigration on the prevalence of Anisakis hypersensitivity showed that about 60% of sensitized subjects in Milano and Torino came from southern Italy or from non-European countries.Conclusions: Anisakis hypersensitivity and allergy are mainly a matter of dietary habits. Areas where marinated anchovies are popular can be considered as 'endemic' for this type of food allergy, whereas immigration and, possibly, new or imported trendy food styles, such as eating raw fish carpaccios or sushi, are a major causative factor in big cities of inland zones.

Method 25 outpatients (15 females, 10 males; mean age 39 years, range 15-68) who experienced previous anaphylactic reactions, following the exposure to a likely food allergen, were evaluated. The diagnosis of anaphylaxis was performed according to the 2005 criteria. Detailed history and physical examination of patients, skin prick test (SPT) with food commercial extracts and with aeroallergens and panallergens LTP and profilin (Alk), prick-toprick with fresh foods, and serum specific IgE detection (CAP, Phadia) were performed in order to confirm the causative role of the suspected food. Oral food-challenges with positive tested foods were not performed, because of previous severe anaphylaxis. Only in one patient a single-blind placebo-controlled food-challenge (with tomato, positive to SPT but negative to history) was performed, resulting negative.

Methods A 58-year-old man was admitted to the emergency care unit because of urticaria and hypotension, warmth, flushing and thoracic pain. Ten minutes earlier he had ingested amoxycillin/clavulanic acid (1 g) and paracetamol/chlorphenamine (300/2 mg) (Zerinol) for a sore throat. On admission, he was conscious, his blood pressure (BP) was 80/60 mmHg, pulse rate 80 bpm and oxygen saturation 77%. His history revealed essential systemic hypertension treated with candesartan/hydrochlorothiazide (16/12.5 mg once daily) (Blopresid),

An increasing number of children, usually with gastrointestinal symptoms, is diagnosed with eosinophilic esophagitis (EE), and a particular subset of these patients complains of airway manifestations. We present the case of a 2-year-old child with chronic dry cough in whom EE was found after a first diagnosis of gastroesophageal reflux disease (GERD) due to pathological 24-hour esophageal pH monitoring. Traditional allergologic tests were negative, while patch tests were diagnostic for cow's milk allergy. We discuss the intriguing relationship between GERD and EE and the use of patch test for the allergologic screening of patients.

Tosoni, Cinzia; Cinquini, Massimo; Gretter, Valeria; Minetti, Stefano; Rizzini, Fabio L. Author Information

Angioedema is a hereditary or acquired disease characterized by localized non-pitting swelling of the subcutaneous tissue which can affect either skin or mucous membranes. Acquired angioedema can often be related to a heterogeneous group of etiological factors including physical stimuli, although up to 38% of cases remain idiopathic. We describe 5 patients who developed an angioedema following sun exposures. All patients reported an intensely stinging angioedema strictly limited to face and extremities, when exposed to solar light. Urticarial wheals were never observed or reported by patients, and oral antihistamines proved to be of no help in preventing or improving the condition of lesions. Laboratory and phototesting data allowed ruling out all other acquired or inherited diseases characterized by photosensitivity. We propose that solar angioedema should be considered a novel clinical entity.

Background. Urticarial vasculitis (UV) is an uncommon type of chronic urticaria (CU), which exhibits leucocytoclastic vasculitis. Painful and long-lasting (> 24 h) weals associated with purpura or bruising are considered indicative of UV. It is often responsive to oral corticosteroids and poorly to oral antihistamines. Hypocomplementaemia and systemic involvement are also commonly reported.Aims. To diagnose patients with UV histologically and then compare their clinical features and response to various treatment regimens.Methods. Biopsies were taken from 312 subjects with CU unresponsive to oral antihistamines; of these, 47 were histologically diagnosed as having UV. Biopsies were taken irrespective of the clinical features of weal eruption. Other diseases known to be associated with small-vessel vasculitis had previously been excluded.Results. Individual weals lasted < 24 h in 57.4% of patients, and pain or tenderness was reported only by 8.6%. Extracutaneous features were present in 81%, hypocomplementaemia in 11% and abnormalities of other laboratory parameters (i.e. raised erythrocyte sedimentation rate, microscopic haematuria) in 76.6%. Hydroxyzine was effective in only one patient. Both oral corticosteroids and cinnarizine were effective in a high percentage of the patients.Conclusion. This diagnostic approach allowed us to identify a large group (47 patients) with UV. Most did not present the clinical (prolonged duration of weals and bruising) and laboratory features that have previously been described as characteristic of UV. Cinnarizine was found to be a valuable treatment option.

The prevalence of atopy and asthma, and their association with familial and environmental factors were investigated among 13- to 14-yr-old children living in Brescia, an industrialized town in North Italy. All the 1450 children attending primary school in the town were invited to participate, and 967 of them (66.7%, 493 males) provided a valid questionnaire filled in by their parents at home. We used a modified version of the questionnaire adopted in the Italian Study of Respiratory Disorders in Childhood and Environment, which is an extended version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Six hundred and twenty-eight subjects underwent skin prick test (SPT), and 308 of them (49%) were positive for at least one of the 12 allergen extracts commonly employed. Ninety-nine children (10.2%) had a physician's diagnosis of asthma - 12.4% of the males and 8.0% of the females (p = 0.03). The prevalence of wheezing in the past 12 months was 6.2%. Atopy was found in 76.8% of the subjects with, and in 45.6% of those without physician's diagnosis of asthma (p < 0.001). Analysis by multiple logistic regression showed an inverse association between physician-diagnosed asthma and female sex (odds ratio, OR = 0.5); presence of relatives in the bedroom in initial years of life (OR = 0.6); attending day care (OR = 0.4) and infant school (OR = 0.4); a positive association with parental history of wheezing (OR = 2.5) and asthma (OR = 3.8); and the child's history of asthmatic bronchitis (OR = 31.9) and atopic eczema (OR = 3.8) in the first 2 yr of life. The strength of the associations did not change when restricting the analysis to atopic asthma. In conclusion, atopy and clinical asthma among 13- to 14-yr-old adolescents are significantly associated with some familial and environmental factors, providing further support for the hygiene hypothesis. Prevalence of atopy, but not of asthma, is high in this industrialized area. The strong association found between atopy and clinical asthma suggests that atopy may play a role in causing asthma in genetically predisposed children only.

Enfuvirtide is a milestone in antiretroviral salvage therapy. When combined with a backbone regimen optimized through results of HIV drug resistance testing, it allows virological control to be regained even after many failures. Rare cases of hypersensitivity reactions (HSR) to enfuvirtide have been described, which may limit the possibility to benefit from this drug. Less than 1% patients in the TORO trials experienced HSR to enfuvirtide [1]. Two male patients have so far been reported in the literature, both developing a mild skin reaction, whose recurrence was successfully prevented by short desensitization procedures [2,3]. It is currently unknown what is the actual pathogenesis of the event and whether a short desensitization procedure could be applied successfully to more severe HSR. Case report A 34-year-old white woman who failed all three classes of antiretroviral drugs (nucleoside and non-nucleoside reverse transcriptase inhibitors and protease inhibitors) was prescribed tenofovir/emtricitabine with darunavir and enfuvirtide on the basis of resistance testing results when her CD4 T-cell count was 306 cells/μl (14.6%) and HIV plasma viral load was 63 000 copies/ml. Her nadir CD4 T-cell count was 126 cells/μl (9%). After 5 weeks from starting the new combination, she developed a maculopapular generalized rash and described symptoms possibly related to laryngopharyngeal oedema, with breathing difficulties. Enfuvirtide was stopped and prednisone was started at a dose of 25 mg a day. One week later, the patient recovered from HSR. For the sake of the diagnosis and trying to elucidate the possible pathogenesis of this phenomenon, a skin test evaluation was performed. In particular, we tested the hypothesis of an IgE-mediated mechanism responsible for the skin eruption. This hypothesis was formuled because IgE-mediated reactions are held to be responsible for clinical symptoms on the second administration of allergen or during the first administration after at least 10 days of continuous treatment, as was the case with our patient. A skin prick test was performed either with enfuvirtide alone or with enfuvirtide previously incubated with albumin, thanks to its ability to link to plasma proteins, particularly albumin. Albumin preincubation served to increase the molecular weight of enfuvirtide, should it work as an aptenic drug. We performed a skin prick test with enfuvirtide or enfuvirtide plus albumin at the following dilutions 1: 100, 1: 10, and with the undiluted drug. In the first instance, the skin prick test turned out to be negative but after 2 h a pruritic diffuse wheal eruption appeared. Therefore, we decided to start a desensitization protocol. This was initiated one week later according to protocols described in the literature [2], starting with 0.00625 mg of enfuvirtide, with subsequent dose increases at 1 h intervals so as to reach the undiluted dose after 11 h. Two hours after the highest dose, itching red lesions appeared at the sites of the current and all the previous injections in the abdomen and legs, notwithstanding the administration of hydroxyzine cloridrate (25 mg three times a day) during the entire procedure (see Fig. 1). A punch biopsy was performed at one of the abdominal lesions and stained with haematoxylin-eosin. Mixed lymphocytic infiltrate with granulocytic and eosinophil cell infiltrations were demonstrated, resembling the histological characteristics of an acute urticaria-like pattern.Fig. 1: Pruriginous and erythematous indurations developed at the previous enfuvirtide injection site after the short desensitization schedule (injection site reactions are indicated by the arrows).During the subsequent week, the patient recovered from the nodular exanthema. At that time, a new protocol was applied with a more gradual increase in dosages of enfuvirtide (see Table 1). Hydroxyzine cloridrate was continued. Through this protocol, the patient was successfully desensitized and was continued on the previously described combination. Ten weeks later, the patient's HIV-1 load was less than 50 copies/ml and the CD4 T-lymphocyte count was 368 cells/μl (22.9%).Table 1: Prolonged enfuvirtide desensitization protocol (dose increase was performed at intervals of 2 h).Enfuvirtide is an antiretroviral drug, electively used in rescue regimens. Hypersensitivity reactions occur rarely, but result in a treatment-limiting effect [1–4]. Our patient experienced a diffuse cutaneous reaction. The pathogenic mechanisms are unclear. A negative skin prick test did not corroborate the hypothesis of an immediate IgE-mediated immune reaction. Nevertheless, after a latency of 2 h from the skin testing, the patient developed a diffuse pruritic skin eruption, suggesting a close link between the administration of enfuvirtide and clinical symptoms. Because of the known rapid development of resistance to this drug [5,6], we started a literature-derived short course desensitization protocol that turned out to be ineffective. Interestingly, skin reactions developed at all previous injection points. The local reactivation at the previous injection sites of subcutaneous administration may have been caused by cytokine and histamine releasing from infiltrating cells reactivated by an endocrine and paracrine mechanism [7]. In conclusion, this case demonstrates that short desensitization procedures for HRS to enfuvirtide may be ineffective and a more prolonged and cautious desensitization protocol may be needed. Our protocol demonstrated a favourable tolerance and outcome. Therefore we propose an alternative protocol to short course desensitization procedures after more severe skin reactions occur.

BACKGROUND:Churg-Strauss syndrome (CSS) is a rare disorder characterized by asthma, eosinophilia, and systemic vasculitis. Renal involvement is not regarded as a prominent feature, and its prevalence and severity vary widely in published reports that usually refer to small series of selected patients.METHODS:We examined the prevalence, clinicopathologic features, and prognosis of renal disease in 116 patients with CSS.RESULTS:There were 48 men and 68 women with a mean age of 51.9 years (range, 18 to 86 years). Signs of renal abnormalities were present in 31 patients (26.7%). Rapidly progressive renal insufficiency was documented in 16 patients (13.8%); urinary abnormalities, 14 patients (12.1%); and chronic renal impairment, 1 patient. There were 3 additional cases of obstructive uropathy. Sixteen patients underwent renal biopsy, which showed necrotizing crescentic glomerulonephritis in 11 patients. Other diagnoses were eosinophilic interstitial nephritis, mesangial glomerulonephritis, and focal sclerosis. Antineutrophil cytoplasmic antibody (ANCA) was positive in 21 of 28 patients (75.0%) with nephropathy versus 19 of 74 patients without (25.7%; P < 0.001). In particular, all patients with necrotizing crescentic glomerulonephritis were ANCA positive. After a median follow-up of 4.5 years, 10 patients died (5 patients with nephropathy) and 7 patients developed mild chronic renal insufficiency. Five-year mortality rates were 11.7% (95% confidence interval, 3.9 to 33.3) in patients with nephropathy and 2.7% (95% confidence interval, 0.7 to 10.7) in those without (P = 0.10).CONCLUSION:Renal abnormalities are present in about one quarter of patients with CSS. The prevailing picture is ANCA-associated necrotizing crescentic glomerulonephritis; however, other forms of nephropathy also may occur. Outcome and long-term follow-up usually are good.

We describe a diagnostic and therapeutic protocol for the management of chronic urticaria. It is derived from an extensive review of current literature, with a cost-effective evaluation of laboratory investigations and therapeutic approaches. Our protocol may not represent a cornerstone for chronic urticaria: much has in fact to be clarified on pathogenetic mechanisms and aetiological factors. Nevertheless, its application should be able, in our opinion, to identify what is useful or not in the everyday management of chronic urticaria patients.