Urgent manifestations of immunoglobulin G4-related disease.

Objective: Immunoglobulin G4-related disease (IgG4-RD) is considered a chronic condition with insidious presentation, but clinical experience suggests that disease onset prompts admission to the emergency department (ED) in a sizeable proportion of patients. We assessed the prevalence of acute manifestations associated with IgG4-RD onset requiring referral to the ED. Method: We revised our database and identified patients admitted to the ED because of symptoms latterly attributed to IgG4-RD onset (Group 1) and those who were referred to our outpatient clinic without previous urgent manifestations (Group 2). Acute manifestations were clustered based on the anatomical region affected by IgG4-RD. Epidemiological, clinical, and serological features of Groups 1 and 2 were compared. Results: The study included 141 patients with IgG4-RD. Of these, 76 (54%) presented to the ED at disease onset. The most common clinical manifestations requiring admission to the ED were jaundice (53%), abdominal pain (41%), and fever (10%). Gastrointestinal involvement was the most frequent cause of referral to the ED (71% of cases), followed by involvement of the retroperitoneum (14.5%) and the nervous system (6.6%). Pancreatobiliary involvement was significantly more frequent in Group 1 than in Group 2. Head and neck, and salivary and lacrimal gland involvement was more frequent in Group 2 than in Group 1. The diagnostic delay was significantly shorter in Group 1 than in Group 2. Conclusion: Clinical manifestations associated with IgG4-RD onset require referral to the ED in most cases. This finding contrasts with the general view of IgG4-RD as a condition with non-acute presentation.

Palate perforation differentiates cocaine-induced midline destructive lesions from granulomatosis with polyangiitis.

Cocaine abuse occasionally causes extensive destruction of the osteocartilaginous structures of the nose, sinuses and palate, which mimics the clinical picture of other diseases associated with necrotising midfacial lesions. The differentiation of cocaine-induced midline destructive lesions (CIMDL) and limited granulomatosis with polyangiitis (GPA) may be difficult, particularly if patients do not readily admit substance abuse. We studied 10 patients with CIMDL and palate perforation referred to our Unit between 2002 and 2015. All cases underwent nasal endoscopy, sinus CT or MRI and ANCA test. In 8 patients, a nasal biopsy was performed. The PubMed database was searched to review all cases of palate perforation described in patients affected by CIMDL or GPA. All 10 cases presented with septal perforation and inferior turbinate destruction. We found hard palate perforation in 7 patients, soft palate perforation in 2 patients, and perforation of both in one patient. ANCA testing was negative in 8 patients and positive in 2, with C-ANCA and P-ANCA specificity, respectively. A review of the English literature identified palate perforation in 5 patients with GPA and in 73 patients with CIMDL. The presence of palate perforation in patients with MDL may represent a clinical marker that strongly favors CIMDL over GPA.

Patients with breakthrough reactions to iodinated contrast media have low incidence of positive skin tests.

BACKGROUND: The term "breakthrough reactions" designates repeated hypersensitivity reactions to iodinated contrast media (ICM) despite premedication with glucocorticoids and antihistamines. We aimed to retrospectively evaluate the rate of positive skin test (STs) in our cohort of patients with previous breakthrough reactions to different ICMs. METHODS: A series of 35 patients, who experienced at least one breakthrough reaction to ICM and who underwent STs within 6 months from the reaction were studied, and results were compared to a control group of patients with a first hypersensitivity reaction occurred without premedication. Skin prick tests (SPT), intradermal tests (IDT) and patch tests (PT) at different dilutions, with a set of three to four ICM were performed. RESULTS: Of the 35 patients with prior breakthrough reactions, 57% had an immediate reaction (IR) and 43% had a non-immediate reaction (NIR). Patients who experienced the first hypersensitivity IR or NIR, later had one or more breakthrough IR or NIR, respectively. Overall, 29% (10/35) of patients with prior breakthrough reactions resulted positive to STs compared to 57% (16/28) of the control group (p < 0.05). No significant difference in allergy history, age, sex, other clinical / demographic features nor chronic use of ACE-inhibitor, beta-blockers or NSAIDs was observed. CONCLUSION: This preliminary finding suggests that patients with prior breakthrough reactions have significantly lower immunologically proven ICM reactions (positive STs) if compared to non-breakthrough patients. According to that, a considerable number of breakthrough reactions seems to be non-allergic hypersensitivity reactions or reactions which could be mostly prevented by a proper, well-timed skin testing. Larger prospective studies are needed to confirm these results, with a more careful analysis of patients' risk factors, a laboratory assessment that includes an in vitro allergy diagnostics, and hopefully a drug provocation test for selected cases.

IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients.

OBJECTIVES: To describe the clinical features, treatment response, and follow-up of a large cohort of Italian patients with immunoglobulin (Ig)G4-related disease (IgG4-RD) referred to a single tertiary care centre. METHOD: Clinical, laboratory, histological, and imaging features were retrospectively reviewed. IgG4-RD was classified as 'definite' or 'possible' according to international consensus guidelines and comprehensive diagnostic criteria for IgG4-RD. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI). RESULTS: Forty-one patients (15 females, 26 males) were included in this study: 26 with 'definite' IgG4-RD and 15 with 'possible' IgG4-RD. The median age at diagnosis was 62 years. The median follow-up was 36 months (IQR 24-51). A history of atopy was present in 30% of patients. The pancreas, retroperitoneum, and major salivary glands were the most frequently involved organs. Serum IgG4 levels were elevated in 68% of cases. Thirty-six patients were initially treated with glucocorticoids (GCs) to induce remission. IgG4-RD RI decreased from a median of 7.8 at baseline to 2.9 after 1 month of therapy. Relapse occurred in 19/41 patients (46%) and required additional immunosuppressive drugs to maintain long-term remission. Multiple flares occurred in a minority of patients. A single case of orbital pseudotumour did not respond to medical therapy and underwent surgical debulking. CONCLUSIONS: IgG4-RD is an elusive inflammatory disease to be considered in the differential diagnosis of isolated or multiple tumefactive lesions. Long-term disease control can be achieved with corticosteroids and immunosuppressive drugs in the majority of cases.

Proposal of a skin tests based approach for the prevention of recurrent hypersensitivity reactions to iodinated contrast media.

The purpose of the present work is to evaluate the efficacy of an approach that combines clinical history, skin tests results, and premedication, in preventing recurrent hypersensitivity reactions to iodinated contrast media (ICM). Skin Prick tests, Intradermal tests, and Patch tests were performed in 36 patients with a previous reaction to ICM. All patients underwent a second contrast enhanced radiological procedure with an alternative ICM selected on the basis of the proposed approach. After alternative ICM re-injection, only one patient presented a mild NIR. The proposed algorithm, validated in clinical settings where repeated radiological exams are needed, offers a safe and practical approach for protecting patients from recurrent hypersensitivity reactions to ICM.

Immunology of IgG4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4(+) plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed.

Circulating Th2 memory cells in IgG4-related disease are restricted to a defined subset of subjects with atopy.

IgG4-related disease (IgG4-RD) is characterized by a lymphoplasmacytic infiltrate composed of IgG4(+) plasma cells, tumefactive lesions, obliterative phlebitis, and mild to moderate eosinophilia. It has been suggested that IgG4-RD is characterized by allergic manifestations and is potentially driven by enhanced T-helper type 2 (Th2) responses. We aimed to investigate the potential contribution of atopy to enhanced Th2 responses in IgG4-RD. Peripheral blood mononuclear cells from 39 patients were isolated and subjected to in vitro mitogenic stimulation with PMA and ionomycin. Following stimulation, gated CD3(+) CD4(+) T cells were analyzed for production of the Th2 cytokines IL-4, IL-5, and IL-13. Among the 39 patients analyzed, only the 18 patients who had a history of atopy showed increases in circulating Th2 memory cells. Our results indicate that Th2 responses that have been reported in IgG4-RD may result from concomitant atopic manifestations in disease subjects.

Epinephrine autoinjector prescription in food-allergic adults: symptom-based only or allergen-based also? An Italian multi-centre study.

BACKGROUND: Epinephrine is the treatment of choice for acute food-allergic reactions but existing guidelines state that it should be prescribed uniquely to patients who already experienced at least one food-induced anaphylactic episode. OBJECTIVE: We investigated whether in Italy epinephrine auto-injector is prescribed uniquely following the existing guidelines only, or is allergen-informed as well (i.e., based on the potential risk associated with sensitization to certain food allergens), and hence preventive. METHODS: 1110 adult patients (mean age 31 years; M/F 391/719) with food allergy seen at 19 allergy outpatient clinics were studied. Patients with a history of probable anaphylaxis were identified. Subjects were classified as having primary (type 1) and/or secondary (type 2) food allergy and were divided into several subgroups based on the offending allergen/food. Epinephrine prescriptions were recorded and analyzed both as a whole and by sensitizing allergen. RESULTS: Epinephrine was prescribed to 138/1100 (13%) patients with a significant difference between subjects with type-1 and type-2 food allergy (132/522 [25%] vs. 6/629 [1%]; p < 0.001). The epinephrine group included most patients with a history of anaphylaxis (55/62 [89%]) or emergency department visits 106/138 (77%). In some specific subsets, namely fish-, tree nuts-, and lipid trasfer protein (LTP)-allergic patients, epinephrine was prescribed to patients without a history of systemic allergic reactions. CONCLUSIONS: Italian allergy specialists prescribe epinephrine auto-injectors both on the basis of clinical history of severe reactions and on a critical analysis of the hazard associated with the relevant protein allergens, which suggests a good knowledge of allergens as well as acquaintance with the guidelines for prescription of emergency medication.

Causes of food-induced anaphylaxis in Italian adults: a multi-centre study.

BACKGROUND: Data about food-induced anaphylaxis in Italy are missing. OBJECTIVE: It was the aim of this study to detect the main foods/food allergens causing anaphylaxis in Italy. METHODS: The frequency of anaphylaxis and the relative importance of many offending foods were assessed in 1,110 adult patients with food allergy diagnosed by common criteria at 19 allergy centres scattered throughout Italy from 1 January to 31 December 2007. RESULTS: Fifty-eight of 1,110 (5%) food-allergic patients experienced at least 1 episode of anaphylaxis. On average, they were older than other food-allergic patients (34 vs. 31 years; p < 0.05). The majority of anaphylactic episodes occurred in patients sensitized to lipid transfer protein (LTP; n = 19), followed by shrimp (n = 10), tree nuts (n = 9), legumes other than peanut (n = 4), and seeds (n = 2); peanut, spinach, celery, buckwheat, wheat, avocado, tomato, fish, meat, and Anisakis caused an anaphylactic reaction in single patients. Among LTP-hypersensitive patients, peach caused 13/19 anaphylactic episodes. Shrimp-allergic patients were significantly older than other patients with food-induced anaphylaxis (p < 0.05), whereas patients allergic to LTP experienced their anaphylactic episodes at a younger age (p < 0.001). The frequency of anaphylaxis among patients sensitized to LTP, shrimp or tree nuts did not differ between northern and central/southern Italy. CONCLUSION: LTP is the most important allergen causing food-induced anaphylaxis in Italy, peach being the most frequently offending food. Peanut-induced anaphylaxis seems very uncommon. Geographic and environmental differences both between Italy and other countries and within Italy seem to play a relevant role in the pattern of sensitization to foods.

EpidemAAITO: features of food allergy in Italian adults attending allergy clinics: a multi-centre study.

BACKGROUND: Studies of the prevalence of different types of food allergy in adults are lacking. OBJECTIVE: To define the prevalence of IgE-mediated food allergies in Italian adults attending allergy clinics and to assess possible differences associated with geographical position and/or dietary habits. METHODS: Seventeen allergy outpatient clinics scattered throughout Italy participated to a multi-centre study in 2007. The number of atopic subjects and of food allergic patients along with clinical features were recorded by pre-defined criteria. Patients with unequivocal history of food allergy confirmed by positive skin prick test were included as cases. RESULTS: Twenty five thousand six hundred and one subjects were screened; 12,739 (50%) were atopic, and 1079 (8,5%) had IgE-mediated food allergy. Sixty four percent of patients were females. Overall, the most frequent food allergy was the pollen-food allergy syndrome (55%), which was associated with oral allergy syndrome in 95% of cases and whose frequency decreased southbound. Forty-five percent of patients had a type 1 food allergy, in most cases (72%) caused by fruits and vegetables, and generally associated with a history of systemic symptoms. Type 1 food allergies represented 96% of food allergies in the South. Lipid transfer protein (LTP) accounted for 60% of sensitizations and caused most primary food allergies in all areas. CONCLUSION: Plant-derived foods cause most food allergies in Italian adults. The pollen-food allergy syndrome is the most frequent type of food allergy followed by allergy to LTP whose frequency increases southbound. The pattern of allergy to certain foods is clearly influenced by specific geographic features such as pollen exposure and dietary habits.

Extension of the BLOCH T(3/2) law to magnetic nanostructures: Bose-Einstein condensation.

We report a newly observed phenomenon, namely, the observation of a visible anomaly in the Bloch T(3/2) law for the temperature dependence of magnetization of nanostructured ferromagnets, for which we give a thermodynamic explanation. Our interpretation extends the Bloch law by introducing the system's chemical potential and assumes a finite Bose-Einstein condensation temperature T(BE) of the magnons. Our extension involves accounting for the possibility of a magnon or magnetic entropy term, leading to a magnon chemical potential (hitherto omitted in the traditional derivation) which varies with temperature. The result is a subtle upturn of the magnetization curves of ferromagnetic nanoparticles in the 10 to 50 K temperature range. Here we show experimental data for nanomaterials and an outline of the extended theory which includes T(BE).

Side effects from polydioxanone.

It is the first case reported of delay hypersensitivity due to polydioxanone (PDS II).

High frequency of anti-endomysial reactivity in candidates to heart transplant.

BACKGROUND: A possible link between coeliac disease and dilated cardiomyopathy has recently been suggested. AIMS: . To assess the frequency of anti-endomysial antibodies, the marker for coeliac disease, in patients with different forms of heart failure, and to establish the clinical features of those endomysial antibody positive. SUBJECTS AND METHODS: . A total of 642 consecutive patients entering the waiting list for heart transplantation from 1995 through 1997 were studied. The prevalence of endomysial IgA antibodies, determined by indirect immunofluorescence, was compared to that observed in three surveys conducted in the Italian general population. RESULTS: Of the 642 patients, 12 (1.9%; 95% confidence interval 0.97-3.2) resulted endomysial antibody positive, versus 34/9,720 healthy controls (0.35%; 95% confidence interval, 0.23-0.47), accounting for a relative risk of 5.3 (95% confidence interval, 2.8-10.3). Anti-endomysial antibodies were found in 6/275 patients with dilated cardiomyopathy and 6/367 with other forms of heart failure (2.2% versus 1.6%; 95% confidence interval 0.8-4.7 and 0.6-3.5), with no statistical difference. The 12 endomysial antibody positive patients were leaner (body mass index, 22.0 +/- 1.9 vs 24.2 +/- 3. 1, p<0. 05) than 36 seronegative patients matched for baseline demographics and aetiology of cardiomyopathy No differences were observed as regards clinical, biochemical and echocardiographic features, mortality in waiting list and 2-year post-transplant survival. CONCLUSIONS: Patients with end-stage heart failure are at increased risk for coeliac disease as compared to the general population.

Sustained response to interferon-alpha2a monotherapy of young blood donors with minimal-to-mild chronic hepatitis C. The Donor Surveillance Study Group.

Subjects with minimal-to-mild chronic hepatitis C may suffer long-term consequences of hepatitis C virus (HCV) infection. Nonetheless, they are not candidates for antiviral treatment, mainly because little data are available concerning the efficacy and safety of therapy. Thirty-two HCV RNA positive individuals aged 18-45 years, who had a histological activity index score < or = 8 and alanine aminotransferase (ALT) levels < or = 1.5 times lower than the normal limit for at least 1 year, were prospectively enrolled among a cohort of 35358 candidate blood donors, and treated with 4.5 mega units (MU) of recombinant interferon-alpha2a (IFN-alpha2a) thrice weekly for 6 months, and for an additional 6 months if a virological response was observed. Twelve months after the completion of treatment, 13 of 31 evaluable patients were HCV RNA negative, accounting for a sustained response rate of 42%. Patients without fibrosis had a lower response rate than those with mild fibrosis (two of 14 vs 11 of 17; P=0.012). In responders, median aminotransferase levels were significantly lower after therapy than before (11.04 +/- 3.98 vs 27.3 +/- 12.32 U l-1, respectively; P < 0. 005). When the analysis was limited to the six responders whose pretreatment aminotransferase levels were consistently normal, this difference was still significant (9.33 +/- 4.12 vs 20.58 +/- 6.73 U l-1; P=0.002). In conclusion, a durable suppression of viraemia can be obtained by IFN monotherapy in a relatively high proportion of young subjects with minimal-to-mild chronic hepatitis C, especially when portal fibrosis is found on liver biopsy. The disappearance of viraemia always leads to a reduction in the degree of hepatocellular necrosis.