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.

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.

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.

Auditory and somatosensory evoked potentials in coma following spontaneous cerebral hemorrhage: early prognosis and outcome.

The aim of this study was to check the prognostic power of auditory brain-stem responses (ABRs) and somatosensory evoked potentials (SEPs) in coma following spontaneous cerebral hemorrhage. Seventy patients comatose following subarachnoidal or hypertensive hemorrhage were submitted to ABR and SEP recordings during the acute phase of clinical course. Twenty-one patients survived (30%), two remained vegetative (2.9%) and 47 died (68.1%). The Glasgow Coma Score (GCS) was significantly related to the outcome (P < 0.001), but showed a low sensitivity, since about 50% of patients with GCS = 5-8 died or remained vegetative. ABRs and SEPs showed a much closer correlation with outcome (P < 0.001): their combined use allowed there to be a sensitivity of 96%, a specificity of 90% and a predictive power of 96%; the relative risk of poor outcome in patients with at least one abnormal modality was equal to 223 times the one for patients with normal evoked potentials. Moreover, in surviving patients a significant relationship appeared to exist between abnormalities of SEPs during the acute phase and the severity of disability. Our results confirm the prognostic effectiveness of short latency evoked potentials in cerebral hemorrhage: they are far superior to clinical data, being able to yield a marked decrease of falsely optimistic predictions.

The Post-Stroke Depression Rating Scale: a test specifically devised to investigate affective disorders of stroke patients.

Owing to the lack of instruments specifically constructed to study emotional and affective disorders of stroke patients, the nature of post-stroke depression (PSD) remains controversial. With this in mind, the authors constructed a new scale, the Post-Stroke Depression Scale (PSDS) which takes into account a series of symptoms and problems commonly observed in depressed stroke patients. The PSDS and the Hamilton Depression Rating Scale (HDS) were administered to a group of 124 patients, who had been classified, on the basis of DSM III-R diagnostic criteria, in the following categories: No depression (n = 32); Minor PSD (n = 47); Major PSD (n = 45). Scores obtained by these stroke patients on the PSDS and on the HDS were compared to those obtained on the same scales by 17 psychiatric patients also classified as major depression on the basis of DSM III-R diagnostic criteria. An analysis of the symptomatological profiles clearly showed that: (1) a continuum exists between the so-called "major" and "minor" forms of PSD; (2) in both groups of depressed stroke patients the depressive symptomatology seems due to the psychological reaction to the devastating consequences of stroke, since the motivated aspects of depression prevailed in depressed stroke patients, whereas the (biologically determined) unmotivated aspects prevailed in patients with a functional form of major depression; and (3) in stroke patients a DSM III-based diagnosis of major PSD could be in part inflated by symptoms (such as apathy and vegetative disorders) that are typical of major depression in a patient free from brain damage, but that could be due to the brain lesion per se in a stroke patient.

Some preliminary findings concerning a new scale for the assessment of depression and related symptoms in stroke patients.

The authors describe a new scale, the Post-Stroke Depression Rating Scale (PSDRS), specifically constructed to investigate the emotional, affective and vegetative disorders of stroke patients. They also report some preliminary data concerning the validity and reliability of the new scale and of its sections and the first results obtained administering the PSDRS to 68 stroke patients and 10 subjects affected by a "functional" form of major depression. The comparison between the results obtained on the PSDRS by patients classified (on the basis of DSM III diagnostic criteria) as having major depression of either vascular or functional origin seems to show an incomplete overlap between these two forms of depression. In patients classified as having major post-stroke depression, part of the symptomatology seems to be due either to the direct effect of the brain lesion or to the psychological reaction of the patient to the disabilities and handicaps provoked by the lesion.