Eosinophil-associated diseases: the allergist's and clinical immunologist's perspective.

Summary: Eosinophil-associated diseases (EADs) refer to heterogeneous conditions in which eosinophils are believed to play critical pathological roles. They encompass common respiratory conditions, such as asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), less common primary eosinophilic disorders of gastrointestinal tract, and rare conditions including eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). A literature search was carried out in January 2024 in the MEDLINE and Scopus databases using the PubMed search engine (PubMed, National Library of Medicine, Bethesda, MD). We focused on blood eosinophilia and hypereosinophilia. A diagnostic workup is proposed. From allergist's point of view, we focused the review on 4 groups of eosinophilic disorders of specific interest. Our increased understanding of type 2 inflammation and biology has recently led to development of highly effective precision targeted therapies that are now approved for a growing number of eosinophilic disorders. Novel targeted biologics have a major impact on treatment strategies and have resulted in major advances in our understanding of the pathogenesis of these disorders. In the context of EADs, according to the heterogeneity of eosinophilic disorders a multidisciplinary approach should be adopted. Allergists and Clinical Immunologists play an important role as they have a clear understanding of the eosinophilic inflammation and the role of cytokines and are trained to recognize and characterize type 2 (T2) inflammation and its associated pathologies.

Peripheral nervous system involvement in systemic lupus erythematosus: a retrospective study on prevalence, associated factors and outcome.

BACKGROUND: Despite its potentially significant impact on disease outcome, peripheral nervous system involvement in systemic lupus erythematosus has received little attention. OBJECTIVE: The objective of this study was to assess the prevalence and clinical features of peripheral nervous system involvement in a large cohort of systemic lupus erythematosus patients. METHODS: The records of systemic lupus erythematosus patients examined at two tertiary referral centres over a period of 14 years (from 2000 to 2014) were analyzed. Peripheral nervous system events were ascertained according to the 1999 American College of Rheumatology case definitions and by using an attribution algorithm for neuropsychiatric events. Prevalence of peripheral nervous system in systemic lupus erythematosus and demographic, clinical and laboratory features were assessed. Patients with peripheral nervous system events were compared with a control group of systemic lupus erythematosus patients without peripheral nervous system involvement. RESULTS: In a retrospective cohort of 1224 patients, the overall prevalence of peripheral nervous system involvement was 6.9% (85 patients, 95% confidence interval 0.06-0.08), with 68% of peripheral nervous system events attributable to systemic lupus erythematosus. Polyneuropathy was the most common manifestation observed (38 events, 39.2%), followed by cranial neuropathy in 30 cases (30.9%) and 12 cases of single (12.4%) or multiple (eight events, 8.2%) mononeuritis. The average age of systemic lupus erythematosus onset was significantly higher in patients with peripheral nervous system events than in controls (mean ± standard deviation: 45.9 ± 14.8 vs. 37.1 ± 14.0) and they were more likely to have higher SLEDAI-2K and SLICC/ACR Damage Index scores, as well as hypertension and livedo reticularis. A subgroup analysis of events deemed to be systemic lupus erythematosus-related provided similar results. CONCLUSION: Peripheral nervous system manifestations are a potential complication of systemic lupus erythematosus. Careful neurological assessment should therefore be included in the diagnostic workup of patients with systemic lupus erythematosus, especially in those with later onset and greater damage and disease activity.

Musculoskeletal manifestations as determinants of quality of life impairment in patients with systemic lupus erythematosus.

Objective The objective of this study was to identify determinants of health-related quality of life (HRQoL) impairment in patients with systemic lupus erythematosus (SLE). Methods Overall, 101 SLE patients were recruited; 37 healthy subjects and 35 rheumatoid arthritis (RA) patients served as controls. HRQoL was evaluated using three patient reported outcomes (PROs): the Short Form-36 version 2 (SF-36v2) health survey, the fatigue scale version 4 (FACITv4) and the Heath Assessment Questionnaire (HAQ). A large set of demographic and clinical variables, including SLE arthritis subtypes, was evaluated searching for factors independently associated with worse QoL. Multivariate models were applied to identify factors independently associated with outcomes. Bonferroni's corrected p values < 0.05 were considered significant. Results SLE patients showed worse results than healthy controls ( p < 0.01) in all SF-36v2 domains and, with reference to the mental QoL, also than RA patients ( p < 0.01). Jaccoud's deformities, active arthritis, and fibromyalgia were the only factors independently associated with worse results in both physical and mental components summary of the SF-36v2 ( p < 0.01) and FACITv4 fatigue scale ( p < 0.01). Fragility fractures, deformities, and active arthritis negatively affected disability perception measured by the HAQ ( p < 0.01). No statistically significant differences in perceived HRQoL were highlighted between patients with deforming and erosive arthritis. However, they had significantly worse results than patients with non-deforming non-erosive arthritis across all investigated PROs ( p < 0.01). Conclusion In order to limit musculoskeletal manifestations as a source of impaired QoL in SLE patients, therapeutic strategies targeted to successfully manage active arthritis and fibromyalgia and to prevent deforming damage are needed.

Early Lupus Project: one-year follow-up of an Italian cohort of patients with systemic lupus erythematosus of recent onset.

Objective To describe the clinical and serological features of a prospectively followed cohort of early diagnosed systemic lupus erythematosus (SLE) patients during a one-year follow-up period. Methods SLE patients with disease duration less than 12 months were consecutively enrolled in a multicentre, prospective study. At study entry and then every 6 months, a large panel of data was recorded. Results Of 260 patients enrolled, 185 had at least 12 months of follow-up; of these, 84.3% were female, 92.4% were Caucasians. Mean diagnostic delay was about 20 months; higher values of European Consensus Lupus Activity Measurement (ECLAM) and of organs/systems involved were both associated with shorter diagnostic delay. Clinical and serological parameters improved after study entry. However, patients' quality of life deteriorated and cardiovascular risk factors significantly increased. About one-third of patients with active disease at study entry went into remission (ECLAM = 0). Negative predictors for remission were: oral ulcers, arthritis, low C4, anti-SSB (Ro) antibodies and therapy with mycophenolate. There was a widespread use of glucocorticoids both at baseline and during follow-up. Conclusion Clinical symptoms and serological parameters improve during the first period after diagnosis. However, patients' quality of life deteriorates. The widespread use of glucocorticoids is probably the reason for the early significant increase of some cardiovascular risk factors.

Demyelinating syndrome in SLE: review of different disease subtypes and report of a case series.

Demyelinating syndrome (DS) is a rare manifestation of systemic lupus erythematosus (SLE) (1%) with high clinical heterogeneity and potentially severe prognosis. It can represent a diagnostic and therapeutic challenge for clinicians. A recent study described 5 different patterns of demyelinating disease presentation, characterised by specific clinical, laboratory and brain and spine magnetic resonance imaging abnormalities: 1) neuromyelitis optica; 2) neuromyelitis optica spectrum disorders; 3) DS prevalently involving the brain; 4) DS prevalently involving the brainstem; 5) clinically isolated syndrome. In this review we briefly discuss typical characteristics of each DS presentation in SLE and we describe 5 illustrative clinical cases, one for each subset of DS, considering both diagnostic and therapeutic options.

Population-based analysis of hospitalizations in a West-European region revealed major changes in hospital utilization for patients with systemic lupus erythematosus over the period 2001-2012.

OBJECTIVE: The objective of this paper is to evaluate hospital admissions in systemic lupus erythematosus (SLE) patients through a retrospective population-based study analyzing hospitalization data during 2001-2012 in Sardinia, an Italian region with universal health system coverage. METHODS: Data on the hospital discharge records with the ICD-9-CM code for SLE (710.0) were obtained from the Department of Health and Hygiene and analyzed, mostly focusing on primary and non-primary diagnosis and Diagnosis-Related Group (DRG) code. In order to establish the significance of the annual trend for number and type of primary and non-primary discharge diagnosis, the two-tailed Cochran-Armitage test for trend was applied. In order to estimate SLE prevalence, data from administrative database and medical records were assembled. RESULTS: This study included 6222 hospitalizations in 1675 patients (87% women). Hospitalizations with SLE as primary diagnosis were 3782 (58.0%) and significantly decreased during the study period. The annual number of renal, hematologic and neuropsychiatric disorders as non-primary diagnosis associated with SLE remained constant; however, their percentage increased (p < 0.0001) because of a declining number of admissions for SLE without associated diagnosis and without complications. Hospitalizations with SLE as non-primary diagnosis showed a significant upward trend in number and percentage of cerebrovascular accident (p = 0.0004), acute coronary syndrome (p = 0.0004) and chronic renal failure (p = 0.0003) as underlying primary diagnosis, while complications of pregnancy, labor and childbirth (p = 0.3375), malignancies (p = 0.6608) and adverse drug reactions (p = 0.2456) did not show statistically significant changes. Infections showed an increasing trend between 2001 and 2012 but did not reach statistical significance (p = 0.0304). After correction for hospitalization (93.8%) and survival (91.1%) rates calculated over the study period, the 2012 SLE prevalence in Sardinia was estimated to be 99.3 per 100,000 inhabitants. CONCLUSIONS: While overall hospitalizations for SLE patients declined, those for cerebrovascular accident, acute coronary syndrome and chronic renal failure as underlying primary diagnosis increased during the study period.

Early Lupus Project - A multicentre Italian study on systemic lupus erythematosus of recent onset.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with a high degree of variability at onset that is problematic for a correct and prompt diagnosis. We undertook this project with the purpose of collecting an inception cohort of Italian patients with recent-onset SLE, in order to obtain information on the main clinical and serological characteristics at the beginning of the disease. In this first report we describe the characteristics of this cohort at study entry. METHODS: All patients with a diagnosis of SLE (1997 ACR criteria) and a disease duration less than 12 months were consecutively enrolled between 1 January 2012 and 31 December 2013 in a multicentre prospective study. Information on clinical and serological characteristics at study entry and then every six months was collected into a specific electronic database. Statistical analysis was performed by means of the Openstat program. RESULTS: Among 122 patients enrolled (103 F) 94.3% were Caucasians. Mean age (SD) of patients at study entry was 37.3 (14.3) years, mean age at disease onset was 34.8 (14.3) years, mean age at diagnosis was 36.9 (14.3) years, and mean disease duration was 2.9 (3.9) months. The frequency of the manifestations included in the 1997 ACR criteria was as follows: ANA 97.5%, immunologic disorders (anti-dsDNA, anti-Sm, antiphospholipid antibodies) 85.2%, arthritis 61.8%, haematologic disorders 55.7%, malar rash 31.1%, photosensitivity 29.5%, serositis 27%, renal disorders 27%, oral/nasal ulcers 11.5%, neurologic disorders 8.2%, and discoid rash 5.7%. The cumulative frequency of mucocutaneous symptoms was 77.8%. At enrolment, autoantibody frequency was: ANA 100%, anti-dsDNA 83.6%, anti-SSA 28%, anticardiolipin 24.5%, anti-nRNP 20.4%, anti-beta2GPI 17.2%, lupus anticoagulant 16.3%, anti-Sm 16%, and anti-SSB 13.1%. CONCLUSIONS: In this paper we describe the main clinical and serological characteristics of an Italian inception cohort of patients with recent-onset SLE. At disease onset, mucocutaneous manifestations, arthritis and haematologic manifestations were the most frequent symptoms; ANA, anti-dsDNA and complement reduction were the most frequent laboratory findings. Our data confirm that the diagnosis of SLE is a challenging one, and that SLE is a severe disease even at onset, since the majority of patients require at least a hospitalization before the diagnosis.

ABOUT PATIENTS, "INVENTORS", JOURNALISTS, SCIENTISTS AND IRBs (TO SAY NOTHING OF THE INSTITUTIONS): CCSVI AND MS.

In this article, the Author analyzes her own experience as a member of the IRB that approved a trial to determine the efficacy of a disobstruction procedure of extracranial veins by means of angioplasty in patients with multiple sclerosis (MS). The so-called "liberation therapy" was proposed by an Italian vascular surgeon, who theorized a condition called "chronic cerebrospinal venous insufficiency" (CCSVI) as playing a role in the pathogenesis of MS. This approval, given after an animated discussion amongst IRB members, lacked any solid scientific evidence of a causal relationship between CCSVI and MS, and was accepted despite the concerns about potential risks associated with the proposed therapy. Undoubtedly, considerable pressure was exerted on IRB by MS sufferers, who rushed off to get the surgery from the many clinics who offered liberation therapy.The remaining sense of bitter has raised a reflection on how to prevent similar future cases.

Rituximab treatment for 'rhupus syndrome': clinical and power-Doppler ultrasonographic monitoring of response. A longitudinal pilot study.

OBJECTIVE: To evaluate the safety and efficacy of rituximab in patients suffering from rhupus unresponsive to therapy with non-biological disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Six patients fulfilling criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and with a DAS28 score >5.1 were enrolled to receive two fortnightly 1000 mg rituximab doses at baseline and after 28 weeks. All patients underwent clinical, laboratory, and power- Doppler (PD) ultrasonographic (US) assessment at baseline and after 14, 28 and 56 weeks. RESULTS: A sustained improvement in DAS28, SLEDAI, HAQ, laboratory markers and ultrasound indices together with a significant reduction in the daily dose of prednisone were observed throughout follow-up. CONCLUSION: Rituximab may be a safe and effective therapeutic option in refractory rhupus patients.

Status of the circle of Willis and intolerance to carotid cross-clamping during carotid endarterectomy.

PURPOSE: During carotid endarterectomy (CEA), an intolerance to the cross-clamping (CC) can occur. The purpose of this study was to evaluate whether preoperative magnetic resonance angiography (MRA) can predict CC intolerance. MATERIAL AND METHODS: Seventy-one patients (57 males, 14 females, mean age 71.8 years, age range 46-86 years) underwent 71 CEA procedures under local anaesthesia. Before CEA, patients underwent an MRA of the Circle of Willis (CoW) and were then classified into three groups: group A consisted of patients with a complete CoW, group B included patients with one agenesia/obstruction in the CoW and group C comprised patients with two or more agenesiae/obstructions in the CoW. The association between the number of anatomical variants in the CoW, corrected for the status of the contralateral carotid artery, and the onset of CC intolerance was evaluated. RESULTS: The prevalence of intolerance to CC was 15.5% (11/71). The Fisher test and logistic regression analysis showed a statistically significant association between the intolerance to CC and two or more agenesiae/obstructions in the CoW (p value < 0.00001 and p < 0.001, respectively). No neurological complications were observed. CONCLUSION: The results of our study showed that two or more agenesiae/obstructions of the CoW identified by MRA were associated with a high risk of intolerance to CC during CEA.

Susceptibility to ankylosing spondylitis but not disease outcome is influenced by the level of HLA-B27 expression, which shows moderate variability over time.

OBJECTIVE: Previous reports have highlighted the relevance of HLA-B27 expression in the pathogenesis of ankylosing spondylitis (AS). The aim of the current study was to estimate the level of HLA-B27 expression on the cell surface of ex vivo monocytes and lymphocytes by a quantitative method and to correlate this with AS disease susceptibility, disease clinical indexes, and the occurrence of acute anterior uveitis (AAU). METHOD: We recruited 32 B27-positive patients with AS and 32 B27-positive healthy normal controls (NCs) for evaluation at different time points. The expression of HLA-B27 molecules was quantified by flow cytometry on ex vivo peripheral blood mononuclear cells (PBMCs). Patients were also evaluated by scores on the Bath AS disease activity (BASDAI), functional (BASFI), and metrology (BASMI) indexes. RESULTS: The expression of HLA-B27 molecules was significantly higher in patients with AS than in B27-matched controls in the case of both monocytes [219K (IQR 174K-308K) vs. 137K (IQR 96K-170K), p < 0.0001] and lymphocytes [82K (IQR 58K-118K) vs. 54K (IQR 44K-61K), p < 0.0001]; AS only vs. AS with AAU: p = 0.744 in monocytes and p = 0.701 in lymphocytes. Comparisons with metrology and functional indexes were also not significant (BASMI: r = 0.05, p = 0.77; BASFI: r = -0.09, p = 0.67). The overexpression of HLA-B27 molecules was stable after 1 week of follow-up. At 3 years follow-up, the variability was moderate and did not correlate with variations in disease activity (BASDAI: r = -0.01, p = 0.92 ns). CONCLUSIONS: The level of HLA-B27 expression in PBMCs correlates with the susceptibility to AS but not with the disease outcome, nor with the occurrence of extra-articular manifestations such as AAU.

Genetics of Behçet's disease in Sardinia: two distinct extended HLA haplotypes harbour the B*51 allele in the normal population and in patients.

OBJECTIVES: To define the contribution of HLA genes and extended HLA haplotypes to the susceptibility to Behçet's disease (BD) in Sardinia. METHODS: Forty-five unrelated Sardinian patients with BD, diagnosed according to the ISG criteria, 45 HLA-B*51 positive and 185 unselected healthy controls were enrolled in the study. DNA samples were typed for HLA class I and class II alleles and genotyped for microsatellites (MICA-TM) and single-nucleotide polymorphisms (rs1264457 HLA-E; rs2281820 motilin; rs1799724 at -857, rs361525 at -238 TNF-alpha) spanning the HLA region. RESULTS: HLA-B*5101 was confirmed as conferring susceptibility to BD (pc=0.0042; OR=4.4; 95% CI=2.0 to 9.6). It is noteworthy that in Sardinia this allele was found more frequently within a haplotype (HLA-A2; -Cw2; -B*5101; -DRB1*11; -DQA1*05; - DQB1*03) that reached its highest frequency in patients with BD. Linkage disequilibrium analysis showed the existence of an additional B*51 haplotype (HLA-A2; -Cw2; -B*5101; -DRB1*04; -DQA1*03; -DQB1*03) not associated with susceptibility to the disease. CONCLUSIONS: In Sardinia, the BD-associated HLA-B*5101 allele is inherited as part of two distinctive haplotypes differently distributed in patients and controls. These findings can be interpreted as suggestive of the presence of additional genes within the MHC region conferring susceptibility to BD. The hypothesis that an environmental pressure could have contributed to the preservation of the BD-associated HLA haplotype in Sardinia is also discussed.

Thrombotic sinusoiditis and local diffuse intrasinusoidal coagulation in the liver of subjects affected by COVID-19: the evidence from histology and scanning electron microscopy.

OBJECTIVE: Liver injury has been reported in patients with COVID-19. This condition is characterized by severe outcome and could be related with the ability of SARS-CoV-2 to activate cytotoxic T cells. The purpose of this study is to show the histological and scanning electron microscopy features of liver involvement in COVID-19 to characterize the liver changes caused by the activation of multiple molecular pathways following this infection. PATIENTS AND METHODS: Liver biopsies from 4 patients (3 post-mortems and 1 in vivo) with COVID-19 were analyzed with histology and by scanning electron microscopy. RESULTS: The liver changes showed significant heterogeneity. The first case showed ground glass hepatocytes and scattered fibrin aggregates in the sinusoidal lumen. The second evidenced intra-sinusoidal thrombi. The third was characterized by sinusoidal dilatation, atrophy of hepatocytes, Disse's spaces dilatation and intra-sinusoidal aggregates of fibrin and red blood cells. The fourth case exhibited diffuse fibrin aggregates in the dilated Disse spaces and microthrombi in the sinusoidal lumen. CONCLUSIONS: In COVID-19-related liver injury, a large spectrum of pathological changes was observed. The most peculiar features were very mild inflammation, intra-sinusoidal changes, including sinusoidal dilatation, thrombotic sinusoiditis and diffuse intra-sinusoidal fibrin deposition. These findings suggested that a thrombotic sinusoiditis followed by a local diffuse intra-vascular (intra-sinusoidal) coagulation could be the typical features of the SARS-CoV-2-related liver injury.

Defective cerebral gamma-aminobutyric acid-A receptor density in patients with systemic lupus erythematosus and central nervous system involvement. An observational study.

Gamma-aminobutyric acid-A (GABA-A) receptors play a crucial role in regulating neuronal excitability and cognitive functions. Single-photon emission computerized tomography (SPECT) analysis of GABA-A receptors binding by (123)I-labelled Iomazenil ((123)I-IMZ) has been applied in some neuropsychiatric disorders to investigate conditions where GABA-A receptor density can be detected in several pathophysiological conditions. In this study we investigate cerebral GABA-A receptor density in a small series of patients with systemic lupus erythematosus (SLE) and cognitive impairment characterized by recurrent, episodic memory loss. Nine female patients with SLE and cognitive alterations underwent to a clinical neuropsychiatric evaluation including digital video-EEG, brain MRI, (99m)Tc-ECD brain SPECT and (123)I-IMZ brain SPECT. All patients tested showed diffuse or focal GABA-A receptor density reduction. This is, to our knowledge, the first report on GABA-A receptor density abnormalities associated with cognitive defects in SLE patients. We hypothesize that in our series a decrease in GABA-A receptor density might be related to the neurological manifestations. Further studies are needed to clarify this aspect and the possible mechanisms. GABA-A receptor density impairment might be due to the SLE-related cerebral vasculopathy, or to neuronal-reacting auto-antibodies or drugs which could interfere with GABA-A receptors expression/binding. This study may support the concept that cognitive impairment in systemic lupus erythematosus could be the outcome of fine-tuned neurotransmission alterations.

Liver involvement in systemic lupus erythematosus: incidence, clinical course and outcome of lupus hepatitis.

OBJECTIVES: The aims of this study were to assess the spectrum of liver disease occurring in systemic lupus erythematosus (SLE), primarily the incidence, clinical course and outcome of lupus hepatitis (LH). METHODS: The records of 283 SLE out-patients referred to our Unit between 1994 and 2008 were reviewed to identify clinical or laboratory evidence of liver involvement. Liver enzyme values were considered abnormal when a sustained increase in serum transaminase levels above the normal value was observed for a period of at least three months or when the increase was confirmed in two consecutive assessments. Study inclusion criteria were a follow-up of at least 12 months and three liver function tests per year over the course of disease. RESULTS: A total of 242 patients with a mean follow-up of 72.2+/-59.1 months were identified. Liver enzyme abnormalities were observed in 45 (18.6%) patients. Of these, only 14 cases (5.8%) could be attributed to LH. Clinical course and response to therapy enabled the identification of three different patterns: remitting, unremitting and relapsing forms. Acute hepatitis and liver failure were not observed. Low serum alanine transaminase levels at diagnosis and high doses of prednisone were associated to resolution of LH. Clinical course or response to therapy did not appear to be affected by liver histology or serological findings. CONCLUSIONS: LH is generally sub-clinical with a fluctuating course and responds well to moderate to high doses of prednisone without progression to end-stage liver disease.

HLA-B*2709 and lack of susceptibility to sacroiliitis: further support from the clinic.

Interferons (IFN) are well known triggers of immunomediated diseases in genetically predisposed subjects. We describe the unique case of a HLA-B*2709 positive subject who underwent IFN-alpha treatment for essential thrombocythemia and developed arthritis of the proximal interphalangeal joints of the hands but not sacroiliitis. The possible mechanisms of IFN-induced arthritis are discussed.

Amiodarone-induced thyrotoxicosis. A review.

Amiodarone (AM), a potent class III anti-arrhythmic drug, is an iodine-rich compound with a structural resemblance to thyroid hormones triiodothyronine (T3) and thyroxine (T4). At the commonly employed doses, AM causes iodine overload up to 50-100 times the optimal daily intake, which may be responsible of a spectrum of effects on thyroid function often counterbalancing its heart benefits. Although most patients on chronic AM treatment remain euthyroid, a consistent proportion may develop thyrotoxicosis (AM-induced thyrotoxicosis, AIT) or hypothyroidism. AIT is more prevalent in iodine-deficient areas and is currently subdivided in two different clinico-pathological forms (AIT I and AIT II). AIT I develops in subjects with underlying thyroid disease, and is caused by an exacerbation by iodine load of thyroid autonomous function; AIT II occurs in patients with no underlying thyroid disease and is probably consequent to a drug-induced destructive thyroiditis. Mixed or indeterminate forms of AIT encompassing several features of both AIT I and AIT II may be also observed. The differential diagnosis between AIT I and AIT II (which is important for the choice of the appropriate therapy) is currently made on radioiodine uptake (RAIU), which may be high, normal or low but detectable in AIT I, while is consistently very low or undetectable in AIT II and on colour-flow Doppler sonography (CFDS) showing normal or increased vascularity in AIT I and absent vascularity in AIT II. Quite recently, studies carried out in our Units at the University of Cagliari (Italy) showed that sestaMIBI thyroid scintigraphy may represent the best single test to differentiate AIT I (showing increased MIBI retention) from AIT II (displaying no significant uptake). Treatment of AIT is dependent from its etiology. AIT usually responds to combined thionamides and potassium perchlorate (KClO4) therapy, AIT II generally responds to glucocorticoids, while indeterminate forms may require both therapeutic approaches. In patients with AIT I definitive treatment of hyperthyroidism by administration of (131)I, initially not feasible for the low RAIU and/or the risk of thyrotoxicosis exacerbation, is advised after normalization of iodine overload. To control severe AIT additional treatment with lithium carbonate, the use of short course of iopanoic acid and plasmapheresis have been also proposed. In cases resistant to medical treatment and/or in patients with severe cardiac diseases who cannot interrupt AM or require quick AM reintroduction, total thyroidectomy (possibly carried out by minimally invasive video-assisted technique) may be proposed after rapid correction of thyrotoxicosis with combination of thionamides, KClO4, corticosteroids and a short course of iopanoic acid.

[IFN-alpha-induced psoriatic arthritis and HCV-related liver cirrhosis. Therapeutic options and patient's opinion]. / Paziente con cirrosi epatica HCV correlata e sviluppo di artrite psoriasica indotta da IFN-alpha. Opzioni terapeutiche e volontà del paziente.

Hepatitis C virus (HCV) infection in the setting of Psoriatic Arthritis is an additional variable to be considered in the therapeutic approach to the disease because of the complications of an immunosuppressive treatment in the course of a chronic infection and the possible hepatotoxicity of many drugs conventionally used to treat psoriatic arthritis. The case reported explores the therapeutic options in a patient with IFN-alpha-induced psoriatic arthritis, characterised by severe arthritis and psoriasis but also the concomitant presence of HCV chronic hepatitis, in light of the patient's concerns.

Genetics of psoriasis and psoriatic arthritis.

Psoriasis and psoriatic arthritis are linked diseases characterised by (distinct ?) immune-mediated pathogenetic mechanisms and by a genetic background interacting with environmental factors. Some candidate susceptibility genes have been studied extensively; they include HLA genes, genes within the HLA region and genes outside the HLA region; among them corneodesmosin and other genes of PSORS1 region, MICA and TNF-a polymorphisms. The main findings in the literature are discussed.