Maria Teresa Mascia

Recommendations for the management of mixed cryoglobulinemia syndrome in hepatitis C virus-infected patients.

OBJECTIVE The objective of this review was to define a core set of recommendations for the treatment of HCV-associated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. METHODS Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. RESULTS An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigen-content diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. CONCLUSION Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.

Treatment of cryoglobulinemic neuropathy with alpha-interferon

To the Editor: We read with interest the article by Khella et al on the treatment of cryoglobulinemic neuropathy with alpha-interferon (alpha-IFN). [1] Our group has been studying the relationship between HCV and essential mixed cryoglobulinemia (EMC) since 1990. We are a collaborating center of the Italian Group for the Study of Cryoglobulinemias (GISC), and have recently published the results obtained from a large sample (654 patients with EMC). [2] In this context, we have also studied the occurrence …

Immunodeficiency and autoimmune phenomena in female hyper-IgM syndrome.

Abstract:  We report an unusual case that highlights the clinical problems associated with autoimmune phenomena. A female (born 1972) was referred to our hospital with systemic lupus erythematosus (SLE) diagnosis. During the follow‐up (7 years), we observed the appearance and the disappearance of a lot of autoantibodies detected. The history of recurrent bacterial sinopulmonary infections since puberty and enlargement of lymphonodes, elevated IgM, very low IgA and normal IgG levels, and the variable autoantibody profile oriented toward a “defective Ig class switch recombination” disorder: the hyper‐IgM syndrome. Immunodeficiency and autoimmune phenomena may occur concomitantly in the same individual and sometimes the differential diagnosis is difficult.

Effectiveness of standing frame on constipation in children with cerebral palsy: a single-subject study.

Children with cerebral palsy (CP) and quadriplegia or severe diplegia suffer from highly reduced mobility and consequent constipation. Clinicians recommend standing frames to exercise the support reaction in this population, sharing the opinion that the upright position may facilitate intestinal transit, although no evidence supports this assumption. We conducted this study to determine the effects of the standing frame on spontaneous evacuation in children with CP. Moreover, we studied its effects on the frequency of induction of evacuation, the characteristics of the stool and the pain suffered by the child due to constipation and/or evacuation. We implemented a single-subject research design in one chronically constipated child with CP and quadriplegia, Gross Motor Function Classification System Level V. To monitor the effects of the standing frame, we measured the outcome of interest throughout the study using a daily diary and the Bristol Stool Scale. This study was approved by the local Ethics Committee. This study has several limitation; primarily, the use of a single-subject research design only makes possible the visual analysis of data obtained from a unique patient. So, by themselves, data obtained do not allow us any generalization for the target population. Future research should verify our results collecting more data and also investigating the effect of the standing-frame on respiratory functions. Although the standing frame did not affect the frequency of evacuations or the characteristics of the stool, its employment reduced the inductions of evacuation and the related pain suffered by the child. However, this study has several limitations, such as the lack of generalization due to the fact that we studied a unique patient and the overall brevity of the study due to external circumstances. Therefore, we suggest future research to verify our results, also investigating the effect of the standing frame on respiratory functions. Relevance to clinical practice. The standing frame may positively influence the management of constipation of these children, possibly improving their quality of life.

Beyond Cat Scratch Disease: A Case Report of Bartonella Infection Mimicking Vasculitic Disorder

Cat scratch disease (CSD) is a bacterial disease caused by Bartonella henselae and it is mainly characterized by self-limiting lymphadenopathy in the draining site of a cat scratch or bite. We report a patient with history of fever, swelling lymph nodes, vasculitic-like skin lesions, and positivity of Bartonella serology initially considered as expression of a disimmune disease.

Nonalcoholic steatohepatitis heralding olmesartan-induced sprue-like enteropathy

ttp://dx.doi.org/10.1016/j.dld.2016.07.004 590-8658/© 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All to what occurs in celiac sprue, liver injury could be a common finding also in olmesartan-induced enteropathy. Here we report on the first case of olmesartan-induced sprue-like enteropathy associated with nonalcoholic steatohepatitis (NASH) unrelated to the metabolic syndrome (MetS). A 72 year-old Caucasian man presented with new-onset anorexia and fatigue. Laboratory profile featured hypertransami-

Hepatocellular carcinoma in a patient treated with efalizumab for psoriasis.

We read with great interest the paper by Tanaka and Urata reporting on the high incidence of hepatitis B virus (HBV) reactivation and related liver damage in patients treated with long-term anti-tumor necrosis factor (TNF)-a therapy. Accelerated development of cirrhosis and increased risk of hepatocellular carcinoma (HCC) are ominous complications of long-standing naturally occurring high-titer HBV viral load. Although it is logical to speculate that high HBV load resulting from pharmacological immunomodulation might be conducive to the identical spectrum of liver disease, to the best of our knowledge, no reports of HCC developing in patients receiving biologic therapies are available. One such case recently came to our observation. A 60-year-old white man with a 17-year history of hepatitis B surface antigen positivity with normal liver tests received efalizumab from November 2007 until July 2008 for the treatment of unresponsive severe psoriasis. In September 2008, he developed mild fever associated with anorexia and weight loss. Laboratory profile showed a moderate increase in transaminase levels (aspartate aminotransferase/alanine aminotransferase 216/206 U/L), HBV reactivation with high viral load (244.153.832 UI/mL) and significantly raised a-fetoprotein (1453.9 ng/mL). Abdominal ultrasonography (US) highlighted an enlarged liver with multiple nodular lesions, the largest having a diameter of 7.5 cm, with contrast-enhanced computed tomography suggestive of HCC. US-directed liver biopsy on the major lesion confirmed a moderately differentiated HCC and showed concurrent chronic hepatitis in the perilesional tissue with immunohistochemical signs of viral replication, moderate inflammatory activity, marked fibrosis and nodular pattern (pre-cirrhotic stage). The patient started antiviral therapy with entecavir with marked viral load reduction, and sorafenib, stopped after 3 months for rapid progression of the disease, with development of portal vein thrombosis and esophageal varices. He died in May 2009 from hepatic encephalopathy. Efalizumab, approved for the treatment of chronic moderate to severe plaque psoriasis, is a monoclonal antibody which binds the CD11a subunit and inhibits T-lymphocyte activation and adhesion to other cells, including endothelial cells and keratinocytes. Although the risk of HBV reactivation after anti-CD11a monoclonal antibody-mediated immunosuppression is not well defined, suppression of T-lymphocyte function may promote viral reactivation, as in the case of John Cunningham virus. Interestingly, the development of blood and solid tumors including cervical cancer in human papilloma virus carriers has been reported in patients treated with efalizumab through impaired T-cell activity. In conclusion, our case, added to the report by Tanaka and Urata, clearly demonstrates that immunomodulation obtained through biologic agents (not only antiTNF) recapitulates an accelerated version of the natural history of HBV infection including the development/ progression of HCC.

Post-infectious sensory neuropathy with anti-GT1a and GQ1b antibodies associated with cold urticaria

A 64 years-old woman presented subacute onset distal paraesthesia concurrently with cold-induced urticaria, a rare form of physical urticaria. Both the disturbances developed a fortnight after an upper respiratory tract infection. EMG confirmed an exclusively sensory polyneuropathy, with prolongation of distal latencies and reduction of amplitudes. Anti-GQ1b and anti-GT1a antigangliosides antibodies were found in serum. The clinical workout included CSF analysis, cryoglobulin and paraprotein search, neurotropic infective agents, neoplastic markers and extensive autoimmune disease antibodies analysis, all of which resulted negative. Intravenous immunoglobulins were administered, leading to progressive resolution of the sensory disturbance, while a combination of steroid and anti-histaminics treatment was used for the urticaria. The positivity for anti-ganglioside search with an EMG pattern characterized by a mixture of demyelinating and axonal features may suggest a nodo-paranodopathy at early stages. This is the first case of an association between an acute sensory neuropathy and cold urticaria, two immune mediated conditions apparently due to very different hypersensitivity pathways. A proposed mechanism for the co-occurence of these two conditions is presented, whereas this case expands the clinical spectrum of autoimmune diseases associated with anti-GQ1b and anti-GT1a antibodies.

THU0705 Experimental use of 3d printing technology for the construction of devices as integration of occupational therapy intervention with rheumatoid arthritis patients (RA)

Background RA is a chronic inflammatory disease that can interfere with the ability to perform activities of daily living. The adoption of aid devices allows to maintain and/or improve employment performance, reducing the pain preventing further joint damage. However, it is known that the abandonment rate of such devices is quite high, resulting in failure of the rehabilitation project, and waste of resources. The reasons people give for abandoning support technology are that they have not been involved in the process of provision, and that the devices do not have the intended effect (1). Objectives technology may allow customization of 3D printing devices agreed together with patients, utilizing materials which are cheap, fast and easily adjustable. Methods The study was organized into the following phases: recruitment of RA patients for the “joint protection laboratories”; sessions of the “joint protection laboratories”; recruitment of patients for the identification of needs for customized aid devices; co-design of customized aid devices; printing of customized aid devices; delivery of customized aid devices; detection using customized aid devices. We have collected a list of needs to be able to develop such customized aid devices at the end of a course to educate on joint protection covering: ergonomic gestures, management of fatigue and pain, environmental adaptations and aid devices. 18 patients (17 women and 1 man), age between 30 and 75 years old, were organized into small groups for the “joint protection laboratories”. 9 patients expressed their specific needs regarding the aid devices and therefore subsequent meetings were organized that have allowed us to produce and deliver customized objects. Autodesk® Fusion360 for object modeling; Ultimaker Care for slicing; 3D printing DeltaWASP 20 40. For the collection of the design features we used the PA board (product analysis) of the USERfit tool. For the psycho-social impact assessment of the assistance, the PIADS (Psychosocial Impact of Assistive Devices Scale – scale -3+3) was used, and for the evaluation of the patients satisfaction with respect to the aid device, QUEST (Quebec User Evaluation of Satisfaction with Technical Aids, scale 1–5) was used. Results 6 aid devices were customized: hand grip holder for chalk, toothbrush, ignition key, tablespoon, iron, as well as a handle to open the moka coffee machine. The psychosocial assessment of 6 delivered aid devices, collected through PIADS, showed an overall positive outcome (mean competence +1.488; adaptability: +1.690; self-esteem: +1.375). The assessment of patient satisfaction through QUEST, was good overall (scale 1–5: satisfaction aid: 4.75; service satisfaction: 4.68). Conclusions This work also demonstrated, over a range of small numbers, that the path of co-design and production of customized aid devices via rapid manufacturing with 3D printing technology is feasible and fulfilling. References Tuntland H, Kjeken I, Nordheim L, Falzon L, Jamtvedt G, Hagen K. The Cochrane review of assistive technology for rheumatoid arthritis Eur J Phys Rehabil Med. 2010 Jun;46(2):261–8. Disclosure of Interest None declared

SAT0633-HPR Articular Involvement of the Scleroderma Hand: An Assessment Protocol for Planning Occupational Therapy Strategies

Background Systemic sclerosis (SSc) is a rare inflammatory connective tissue disease acquired, chronic, progressive of unknown etiology characterized by irregular autoimmune response, changes in the small circle due to vascular disease, fibrosis of the skin and internal organs. Hand impairment is a major cause of morbidity and disability in about 90% of SSc patients Although physiotherapy and rehabilitation programs to prevent and reduce the disability resulting from osteo-articular and skin involvement are recommended, only a few studies have been published on this feature. Objectives Our study aims an analysis of scleroderma hand through the application of instrumental tests and rating scales to suggest a specific evaluation protocol in order to highlight the main anomalies for planning occupational therapy strategies and to have specific outcome measure. Methods The study was conducted on 45 patients with SSc. In the protocol were included total active motion-TAM (Strickland), strength of the grip (Jamar dynamometer and pinchmeter) and the evaluation of 16 different types of prehension of objects encountered during activities of daily life. Results The Strickland measurement showed a symmetrical involvement of the hands for almost all patients (93%); furthermore observed that only 30% of patients have an excellent level in TAM (percentage of scoring higher 85%). A statistically significant reduced total active movement of the dominant hand was documented in diffuse SSc. Furthermore, the fingers more limited and therefore with lower TAM are the 2nd and 5th finger in both hands. At the second finger there is a statistically significant weaker strength of dominant hand related to disease duration in patients with dSSc (P value equals 0.0021). The grip strength (Jamar Dynamometer and Jamar pinchmeter) is extremely reduced in 75% of patients and focuses mainly on the dominant hand. If <15 kg (below normal range), the difference between the strength of dominant and non dominant hand is considered to be very statistically significant and the dominant is weaker (P value <0.017); in subjects without involvement of the hands with strength normal, dominant hand is stronger but there are not statistical difference (p=0.55) The evaluation of 16 different types of prehension tested by a set of objects of different shapes has documented the impairment mainly of palmar grip (44%), tip to tip (37%) and vice (30%), followed by thenar grip, spherical grip and three jaw in a few cases. Conclusions The documentation for greater involvement of the dominant hand with a reduction of the ROM in particular of 2 and 5 finger associated to decreased grip strength focus on confirm the importance of the hand use in daily life as the cause of greater disease damage. It is essential to plan quickly in patients with early systemic sclerosis an educational program to make the best use of work strategies equally distributed between dominant and non dominant hand and replacement activities for digit handheld, end-to- terminal and vice grip. Disclosure of Interest None declared