Incidental cardiac uptake of 99mTc-diphosphonates is predictive of poor outcome: data from 9616 bone scintigraphies.

BACKGROUND: Bone scintigraphy (BS) is highly diagnostic for amyloid transthyretin (ATTR) cardiomyopathy. Prevalence and prognostic value of BS cardiac uptake is not well established. Our aim was to assess the prevalence of subclinical cardiac ATTR amyloidosis in patients undergoing [99mTc]MDP/DPD scintigraphy and to define their phenotype and prognosis. METHODS AND RESULTS: BS scans performed for any clinical indications from 2009 to 2020 were reviewed. Patients were stratified according to Perugini visual score of cardiac uptake. Follow-up data were collected. Among 9616 BS scans, 0.7% (n = 67) showed cardiac uptake. In 47 (70%) patients, Perugini score was 1 and in 20 (30%) patients uptake was ≥ 2, suggesting cardiac ATTR amyloidosis. Forty subjects (61%) died during the follow-up (mean 47 ± 30 months). Compared with patients with Perugini score 1, those Perugini score ≥ 2 showed increased death rate (P = .018). Two (2/67) subjects were investigated for TTR gene mutations resulting negative. CONCLUSIONS: In patients undergoing BS for different clinical indications, cardiac uptake suggesting cardiac ATTR amyloidosis is a rare, but still neglected finding, thus preventing possible diagnosis of ATTR cardiomyopathy. Importantly, cardiac uptake negatively affects the survival. Physicians should be aware of this rare, but crucial finding for timely diagnosis and treatment.

Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus.

Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington's disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients' characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.

Bendamustine-rituximab (BR) combined therapy for treatment of immuno-mediated neuropathies associated with hematologic malignancy.

In chronic polyneuropathies associated with hematologic malignancy (HM) the optimal treatment management is primarily focused on the HM, but the parallel response of the neuropathy is still unclear. Rituximab is a recognized therapeutic choice in anti-MAG antibody polyneuropathy, that might be useful also in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with HM. The efficacy of immunochemotherapy, which is the standard approach to malignant lymphoproliferative diseases, has been poorly investigated in polyneuropathies. We describe a six-months combined bendamustine-rituximab (BR) treatment in nine patients affected by CIDP or paraproteinemic IgM neuropathies with antibodies to peripheral nerve antigens in course of malignant HM. All patients had a long-lasting response with an average relapse free-survival (RFS) time of 31.5 months. Clinical improvement was evident at 6 months from the beginning of therapy, even earlier in 6/9 patients (<2 months). Two patients dramatically improved the disabling attitudinal and intentional tremor and pathogenic autoantibodies significantly declined in 4/5 patients. Neurological relapses occurred in three patients after a mean of 38 months of sustained stability, even if HM remitted. In such cases rituximab was administered but was associated with a shorter RFS time (1 year) compared to the previous BR scheme (3 years). In our case series, the combined BR regimen was a valid option in immune-mediated neuropathies associated with HM. Moreover, in some patients BR scheme allowed an earlier response and a long-lasting improvement than rituximab alone.

Risk factors for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): antecedent events, lifestyle and dietary habits. Data from the Italian CIDP Database.

BACKGROUND AND PURPOSE: The role of lifestyle and dietary habits and antecedent events has not been clearly identified in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Information was collected about modifiable environmental factors and antecedent infections and vaccinations in patients with CIDP included in an Italian CIDP Database. Only patients who reported not having changed their diet or the lifestyle habits investigated in the study after the appearance of CIDP were included. The partners of patients with CIDP were chosen as controls. Gender-matched analysis was performed with randomly selected controls with a 1:1 ratio of patients and controls. RESULTS: Dietary and lifestyle data of 323 patients and 266 controls were available. A total of 195 cases and 195 sex-matched controls were used in the analysis. Patients eating rice at least three times per week or eating fish at least once per week appeared to be at decreased risk of acquiring CIDP. Data on antecedent events were collected in 411 patients. Antecedent events within 1-42 days before CIDP onset were reported by 15.5% of the patients, including infections in 12% and vaccinations in 1.5%. Patients with CIDP and antecedent infections more often had an acute onset of CIDP and cranial nerve involvement than those without these antecedent events. CONCLUSIONS: The results of this preliminary study seem to indicate that some dietary habits may influence the risk of CIDP and that antecedent infections may have an impact on the onset and clinical presentation of the disease.

Obinutuzumab, a new anti-CD20 antibody, and chlorambucil are active and effective in anti-myelin-associated glycoprotein antibody polyneuropathy.

BACKGROUND AND PURPOSE: Rituximab, a chimeric anti-CD20 monoclonal antibody, has been used in polyneuropathy associated with anti-myelin-associated glycoprotein (anti-MAG) antibody polyneuropathy with controversial results. Herein, two patients with anti-MAG antibody neuropathy and concurrent chronic lymphocytic leukemia (CLL) are reported, who dramatically responded to obinutuzumab, a novel glycoengineered humanized anti-CD20 monoclonal antibody. METHODS: Patient 1 was an 82-year-old man with severe demyelinating sensory-motor neuropathy. He was wheelchair-bound, with loss of sensation up to the knees. He had a CLL, immunoglobulin M (IgM) lambda monoclonal gammopathy, with anti-MAG antibodies >70 000 Bühlmann titer units (BTU). Patient 2 was an 84-year-old woman with demyelinating neuropathy, paresthesias and gait instability. She had CLL and IgM kappa paraprotein with anti-MAG antibodies >70 000 BTU. Both patients were treated with obinutuzumab intravenously at 100 mg on day +1, 900 mg +2, then at 1000 mg on days 8 and 15 of cycle 1 and day 1 of cycles 2-6; chlorambucil was given orally at 0.5 mg/kg on days 1 and 15 of cycles 1-6. RESULTS: Patient 1 at cycle 6 was able to stand, gait was possible with monolateral support, hypoesthesia and strength improved. M-protein and IgM level decreased. In patient 2, already after three cycles, the monoclonal component disappeared and there was dramatic improvement of symptoms and gait normalization. At the end of therapy anti-MAG antibody titer decreased to 5462 BTU. Neurophysiology also improved. CONCLUSIONS: In our patients, obinutuzumab was effective as a first-line treatment of anti-MAG antibody polyneuropathy. CLL might have had a role in the response to therapy, but the associations might be considered in future trials.

Brain anatomical substrates of mirror movements in Kallmann syndrome.

Among male patients affected by Kallmann syndrome, a genetically determined disease due to defective neural migration leading to hypogonadropic hypogonadism and hypo/anosmia, about 40% present the peculiar phenomenon of mirror movements, i.e. involuntary movements mirroring contralateral voluntary hand movements. Several pathogenic hypotheses have been proposed, but the ultimate neurological mechanisms are still elusive. The aim of the present study was to investigate brain anatomical substrates of mirror movements in Kallmann syndrome by means of a panel of quantitative MRI analyses. Forty-nine male Kallmann syndrome patients underwent brain MRI. The study protocol included 3D-T1-weighted gradient echo, fluid attenuated inversion recovery and diffusion tensor imaging. Voxel-based morphometry, sulcation, curvature and cortical thickness analyses and tract based spatial statistics were performed using SPM8, Freesurfer and FSL. All patients underwent a complete physical and neurological examination including the evaluation of mirror movements (according to the Woods and Teuber criteria). Kallmann syndrome patients presenting with mirror movements (16/49, 32%) displayed the following brain changes: 1) increased gray matter density in the depth of the left precentral sulcus behind the middle frontal gyrus; 2) decreased cortical thickness in the precentral gyrus bilaterally, in the depth of right precentral sulcus and in the posterior portion of the right superior frontal gyrus; and 3) decreased fractional anisotropy in the left hemisphere involving the temporal lobe and peritrigonal white matter. No differences were shown by cortical curvature and sulcation analyses. The composite array of brain changes observed in Kallmann syndrome patients with mirror movements likely represents the anatomical-structural underpinnings leading to the peculiar derangement of the complex circuitry committed to unilateral hand voluntary movements.

Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin.

BACKGROUND: The different perception and assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) between healthcare providers and patients has not yet been fully addressed, although these two approaches might eventually lead to inconsistent, possibly conflicting interpretation, especially regarding sensory impairment. PATIENTS AND METHODS: A cohort of 281 subjects with stable CIPN was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC v. 2.0) sensory scale, the clinical Total Neuropathy Score (TNSc©), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (mISS) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). RESULTS: Patients' probability estimates showed that the EORTC QLQ-CIPN20 sensory score was overall more highly related to the NCI-CTC sensory score. However, the vibration perception item of the TNSc had a higher probability to be scored 0 for EORTC QLQ-CIPN20 scores lower than 35, as vibration score 2 for EORTC QLQ-CIPN20 scores between 35 and 50 and as grade 3 or 4 for EORTC QLQ-CIPN20 scores higher than 50. The linear models showed a significant trend between each mISS item and increasing EORTC QLQ-CIPN20 sensory scores. CONCLUSION: None of the clinical items had a perfect relationship with patients' perception, and most of the discrepancies stood in the intermediate levels of CIPN severity. Our data indicate that to achieve a comprehensive knowledge of CIPN including a reliable assessment of both the severity and the quality of CIPN-related sensory impairment, clinical and PRO measures should be always combined.

High ultrasound variability in chronic immune-mediated neuropathies. Review of the literature and personal observations.

Chronic immune-mediated neuropathies show high clinical variability. Diagnosis is based on clinical and neurophysiological studies, but recently ultrasound (US) of peripheral nerves has been shown to provide useful morphological information. US has already been shown to crucially influence diagnosis and clinical care in entrapment neuropathies, in traumatic nerve lesions and in tumors. The role of US in the evaluation of polyneuropathies is still not clearly defined, but increasing attention has recently been focused on the immune-mediated neuropathies and specific US measures (namely the intra- and inter-nerve cross-sectional area variability) have been developed. The aim of the current paper is to make a review of the available nerve US studies and provide data from personal observations in the most common chronic immune-mediated neuropathies.

Rasch-built Overall Disability Scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS).

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary R-ODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN.

[Scrotal ultrasound: anatomy and pathological findings]. / Ecografia del testicolo: anatomia e quadri patologici.

Ultrasonography (US) is the imaging modality of choice for the evaluation of scrotal disease. It provides high anatomical detail and in most cases, it is essential to enable a correct diagnosis and to obtain the right management of the patient. Color Doppler ultrasonography is a non invasive technique that aids important information about testicular perfusion, necessary in reaching a specific diagnosis in many pathologic conditions; moreover contrast-enhanced ultrasonography (CEUS), recently introduced in the clinical practice, may be considered an additional tool in the classification and differentiation of testicular pathology. The purpose of this review, is to provide the state of the art on the role of ultrasonography in the evaluation of different scrotal pathologies including vaginal process' disorders, acute scrotum, varicocele, hydrocele, chronic inflammatory diseases and testicular tumours.

Ultrasound as a useful tool in the diagnosis and management of traumatic nerve lesions.

OBJECTIVE: The possibility of depicting through ultrasound (US) the nerve and its surroundings should be very useful in traumatic nerve lesion (TNL) management. Our study aimed at evaluating the contribution of US as complementary tool in a neurophysiological laboratory for the diagnosis and management of TNL. METHODS: A total of 112 nerves from 98 consecutive patients with clinical suspicion of TNL were considered. Two independent and blinded clinicians, different from the examiners performing electrodiagnosis and US, classified clinical, neurophysiological and US findings and classified the contribution of US as follows: 'contributive' and 'non-contributive' if US confirmed the clinical and neurophysiological diagnosis or if US findings were unremarkable. RESULTS: US was 'contributive' (strongly modified the diagnostic and therapeutic path) in 58% of cases (n: 65) providing information on therapeutic approach (immediate or delayed surgery), diagnosis and follow-up. US specifically contributed to the (1) assessment of nerve continuity/discontinuity, hence neurotmesis/axonotmesis; (2) identification of aetiology; and (3) demonstration of multiple sites of damage. US was contributive mainly in cases with neurophysiological evidence of complete axonal damage. CONCLUSIONS: US should be used, when available, in all patients in whom TNL is suspected as it provides a more comprehensive diagnosis than neurophysiologic studies alone. Anatomical information is often crucial for choosing the most appropriate therapeutic strategies (and for surgical planning). SIGNIFICANCE: US can improve the outcome of TNL.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS: After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION: Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

Advanced age and liability to oxaliplatin-induced peripheral neuropathy: post hoc analysis of a prospective study.

BACKGROUND AND PURPOSE: The aim of this post hoc analysis of data extracted from a prospective, multicenter study is to test in a large homogenous population of chemotherapy-naïve patients with colorectal cancer (CRC) treated with oxaliplatin (OXA)-based chemotherapy whether advanced age increases the risk of developing OXA-induced peripheral neuropathy (OXAIPN). METHODS: One-hundred and forty-five patients with CRC, without other significant co-morbidities predisposing to peripheral neuropathy, were divided according to their age into two groups: patients aged between 50 and 68 years (group I, n = 75); and patients aged ≥ 69 years (group II, n = 70). Patients were prospectively monitored at baseline and followed-up during chemotherapy using the motor and neurosensory National Cancer Institute Common Toxicity criteria, the clinical version of the Total Neuropathy Score and neurophysiology. The incidence and severity of both the acute and cumulative OXAIPN was thoroughly determined and then compared between age groups. RESULTS: No statistically significant difference was observed in the incidence of both the acute (n = 64/75 vs. 56/70; P = 0.510) and cumulative OXAIPN (n = 51/75 vs. 49/70; P = 0.858) between age groups. The severity of OXAIPN was also similar between age groups. In line with the clinical data, the neurophysiological results between age groups were also comparable. CONCLUSION: The results of this study indicate that advanced age does not seem to represent a significant risk factor of OXAIPN in patients with CRC without any other significant co-morbidities.

Ultrasound assessment of oxaliplatin-induced neuropathy and correlations with neurophysiologic findings.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy is a major adverse effect of oxaliplatin (OXL) treatment. Whereas neurophysiologic study is commonly used to assess the occurrence and severity of polyneuropathies, ultrasound (US) analysis of the peripheral nerves, an emerging technique in the study of peripheral nerve diseases, has never been used in chemotherapy-induced peripheral neuropathy. PATIENTS AND METHODS: Fifteen patients (four women; 11 men; mean age, 60.1 ± 10.6 years; median, 62; range, 37-75) with colorectal cancer treated with OXL-based treatment have been clinically and neurophysiologically evaluated before and after OXL therapy. At the end of chemotherapy, all patients underwent also nerve US study at four limbs, and the findings correlated with clinical and neurophysiologic measures. RESULTS: Clinical and neurophysiological evaluation showed that 13 of 15 (86.7%) patients developed sensory axonal neuropathy, 10 of whom severe (two or more sensory nerve action potential amplitude absent and the other amplitudes decreased of ≥50%). Nerve US did not reveal decreased cross-sectional area (CSA), a reported finding in axonal neuropathies. Instead increased CSA at entrapment sites (median nerve at wrist and ulnar nerve at elbow) was found in 09/15 (60%) of patients. DISCUSSION: Sensory axonal neuropathy is a very common complication of OXL therapy, affecting almost 90% of patients. US findings of enlargement of median and ulnar nerves, mostly at entrapment sites, in patients with no history or symptoms of neuropathies at recruitment, and no neurophysiologic evidence of entrapment, may be expression of increased, OXL-induced, nerve susceptibility to mechanical damage. An ongoing prospective study will help clarify these findings.

Peripheral neurotoxicity of oxaliplatin in combination with 5-fluorouracil (FOLFOX) or capecitabine (XELOX): a prospective evaluation of 150 colorectal cancer patients.

BACKGROUND: To report our prospective experience on the incidence and pattern of oxaliplatin (OXA)-induced peripheral neuropathy (OXA-IPN) in patients with colorectal cancer (CRC) treated with either FOLFOX-4 or XELoda + OXaliplatin (XELOX). PATIENTS AND METHODS: One hundred and fifty patients scheduled to be treated with either FOLFOX or XELOX for CRC were prospectively monitored at baseline and followed-up during chemotherapy. The incidence and severity of symptoms secondary to OXA-IPN were recorded using three different types of assessment, i.e. the motor and neurosensory National Cancer Institute common toxicity criteria, version 3.0 (NCI-CTCv3), the clinical version of the total neuropathy score (TNSc) and electrophysiological scores. RESULTS: Patients treated with either FOLFOX-4 or XELOX manifested similar incidence rates and severities of acute OXA-IPN. However, FOLFOX-4 was associated with increased incidence of chronic neurotoxicity, compared with XELOX-treated patients (n = 64/77 versus 44/73; P = 0.002), at a very similar OXA median cumulative dose during both regimens. Both the NCI-CTCv3 and TNSc demonstrated that the severity of cumulative OXA-IPN in FOLFOX-4-treated patients is higher than in those treated with XELOX. CONCLUSION: The incidence of acute neurotoxicity during FOLFOX-4 therapy is similar to XELOX. However, it seems that FOLFOX-4 is more neurotoxic than XELOX in terms of cumulative OXA-IPN, despite comparable OXA cumulative dose.

Spectrum of paraneoplastic disease associated with lymphoma.

OBJECTIVE: To define the frequency and clinical and immunologic characteristics of patients affected by paraneoplastic neurologic syndromes (PNS) and lymphoma. METHODS: Patients fulfilling the criteria for PNS associated with lymphoma collected from the European Commission-funded PNS Euronetwork group database were analyzed. RESULTS: Fifty-three patients with Hodgkin lymphoma (HL) (24 patients, mean age 51, range 16-84) or non-Hodgkin lymphoma (NHL) (29 patients, mean age 64, range 31-82) and PNS were analyzed. The most commonly associated PNS was paraneoplastic cerebellar degeneration, present in 21 cases, with a higher prevalence in HL (16/24 cases). Peripheral nervous system (mainly demyelinating polyradiculopathies) and motor neuron involvement were more common in NHL. Onconeural antibodies were more frequent in patients with paraneoplastic cerebellar degeneration, most commonly against the Tr antigen. Fifty percent of the patients with PNS and HL responded to chemotherapy, whereas neurologic improvement was less frequent (24%) in patients with PNS and NHL. In both groups, the survival rate was good. Overall, 10 out of 53 patients eventually died, with only 2 patients (1 with HL, 1 with NHL) dying from PNS. CONCLUSIONS: PNS in patients with lymphoma are relatively rare. Paraneoplastic cerebellar degeneration, mainly associated with anti-Tr antibodies, is more prevalent in HL and NHL, followed in our study by motor neuron disease in patients with NHL. Involvement of the peripheral nervous system is heterogeneous, with a prevalence of polyradiculoneuritis in patients with NHL.

Multiple paraneoplastic diseases occurring in the same patient after thymomectomy.

Thymoma-associated paraneoplastic diseases include myasthenia gravis (MG), neuromyotonia (NMT), Morvan's syndrome, and several non-neurological paraneoplastic manifestations, including glomerulonephritis. Paraneoplastic syndromes often precede the occurrence of thymoma, but cases occurring after thymomectomy, which sometimes herald the recurrence of thymoma, have also been described. We report on a patient who developed MG after thymomectomy for a malignant thymoma. After MG remission, NMT and Morvan's syndrome occurred, which heralded a mediastinic recurrence, as demonstrated only by autopsy findings.

Lupus: improving long-term prognosis.

Over recent decades short- and medium-term survival has greatly improved in patients affected with systemic lupus erythematosus, but long-term prognosis still remains poor mainly due to complications of the disease and/or its treatment. To improve long-term prognosis in systemic lupus erythematosus, we should try to adopt, early in the disease course, strategies that can contribute to reducing long-term complications, including screening for and prophylaxis against infections, control of risk factors for atherosclerosis, and cancer surveillance. However, in patients with systemic lupus erythematosus all these preventive strategies are often not sufficient. Indeed, two important systemic lupus erythematosus-related factors play a relevant role in all these complications: severe disease manifestations, such as glomerulonephritis and central nervous system involvement, and corticosteroid and cyclophosphamide use. Therefore, to prevent long-term complications, we should try to control disease activity and severity using the lowest effective dosage of these drugs. Moreover, strategies directed at preventing clinical manifestations in asymptomatic antinuclear antibody-positive individuals or in antiphospholipid antibody-positive systemic lupus erythematosus patients, as well as at preventing severe manifestations in patients with mild systemic lupus erythematosus at the time of the diagnosis should be considered.