Regular assessment of serum vascular endothelial growth factor levels to monitor POEMS syndrome.

BACKGROUND: To investigate the utility of regular serum VEGF (sVEGF) levels assessment in the monitoring of POEMS syndrome. METHODS: We retrospectively reviewed data of 30 patients with POEMS syndrome whose sVEGF was tested regularly every 6 months. sVEGF levels after treatment were measured and correlated with disability (Overall Neuropathy Limitations Scale, ONLS), clinical impairment (measured with the modified Clinical Response Evaluation Scale, mCRES), and relapse-free survival. The ability of sVEGF to predict disease flares during remission and refractory disease was also analysed. RESULTS: Patients with normalised serum VEGF levels (< 1000 pg/ml) at 6 months showed prolonged relapse-free survival (at 3-year 94% for complete VEGF response, 57% partial, 0% none, p < 0.001) and greater later clinical improvement (median ΔmCRES complete VEGF response -5 vs partial -4, p = 0.019, and vs no VEGF response -2, p = 0.006). After remission, the sensitivity of 6-month sVEGF monitoring in predicting clinical relapse was 58% with a specificity of 100%. In patients refractory to treatment, the sensitivity in predicting further clinical worsening was 15%. In addition, in 25% of the patients in remission and 16% of those refractory to therapy, sVEGF levels only increased at the time of relapse. CONCLUSIONS: Regular sVEGF assessment is a valid biomarker in the prediction of disease reactivation in POEMS syndrome and was particularly useful during the phase of remission.

New Onset of Eosinophilic Granulomatosis with Polyangiitis Following mRNA-Based COVID-19 Vaccine.

Anti-SARS-CoV-2 vaccines are safe and effective, also in individuals with allergic and immune-mediated diseases (IMDs). There are reports suggesting that vaccines may be able to trigger de-novo or exacerbate pre-existing IMDs in predisposed individuals. Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, eosinophilia, and eosinophil-rich granulomatous inflammation in various tissues. We describe the case of a 63-year-old man who experienced cardiac, pulmonary, and neurological involvement one day after the administration of the booster dose of anti-SARS-CoV-2 vaccine (mRNA-1273). A diagnosis of EGPA was made and the patient was treated with high-dose steroids and cyclophosphamide, with a good clinical response. Interestingly, our patient had experienced a significant worsening of his pre-existing asthma six months earlier, just after the first two vaccine shots with the ChAdOx1 anti-SARS-CoV-2 vaccine. It is impossible to know whether our patient would have had developed EGPA following natural SARS-CoV-2 infection or at some point in his life regardless of infectious stimuli. Nevertheless, our report may suggest that caution should be paid during the administration of additional vaccine doses in individuals who experienced an increase in IMD severity that persisted over time following previous vaccine shots.

Home monitoring of maintenance intravenous immunoglobulin therapy in patients with chronic inflammatory neuropathy.

To evaluate the utility of different outcome measures to monitor dose adjustment of intravenous immunoglobulin (IVIg) therapy in patients with chronic inflammatory neuropathy (CIN). We assessed the adjustment of IVIg maintenance therapy in 20 patients (10 CIDP and 10 MMN) by regularly monitoring grip strength (GS) using a Martin Vigorimeter, RODS, and quality of life using the SF-36 questionnaire. These measures were regularly performed by the patient at home. We also assessed the extended MRC sumscore (eMRC sumscore) at each outpatient visit for IVIg infusion. We also enrolled 30 healthy controls to measure any possible training effect of GS with time and to analyze random fluctuation of GS. Clinically relevant change was detected by eMRC sumscore in 14 (93%) patients, by RODS in 11 (73%) patients, and by GS in 8 (53%) patients. Early sensitivity was greatest for RODS (73%), followed by GS (53%), and eMRC sumscore (27%). This differed from CIDP, with an early change in RODS in 100% of patients, and MMN with an early change in GS in 75%. None of the outcome measures alone was sufficient to detect clinically significant changes in all patients. Home monitoring of outcome measures objectively assisted clinical decision during individualization of IVIg treatment. We recommend a multimodal approach using different outcome measures to monitor the individual patient with CIN.

Lenalidomide and dexamethasone in patients with POEMS syndrome: results of a prospective, open-label trial.

Given its anti-angiogenic activity, lenalidomide may have a role in the treatment of POEMS (Peripheral neuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder and Skin changes) syndrome. This prospective, open-label, pilot study evaluated the combination of lenalidomide + dexamethasone (RD) in 18 POEMS syndrome patients (13 pre-treated, 5 newly-diagnosed but ineligible for high-dose therapy). Treatment consisted of six cycles of lenalidomide (25 mg/day for 21 days followed by 7 days rest) plus dexamethasone (40 mg/once a week). Patients responding after six cycles continued treatment until progression or unbearable toxicity. The primary endpoint was the proportion of patients with either neurological or clinical improvement. The RD combination was considered as deserving further evaluation if 9 of the first 15 patients responded. Ten responses were observed among the first 15 enrolled patients, meeting the primary endpoint. Fifteen of 18 patients (83%) completed six RD cycles: 13 (72%) patients responded and nine had both clinical and neurological improvement. Among the 15 patients who completed the six RD cycles, four were still on treatment after a 25-month follow-up. At 39 months of follow-up, all patients were alive with a 3-year progression-free survival of 59%. No patient discontinued RD for toxicity. Overall, the RD regimen showed a high incidence of prolonged symptoms improvement and was well tolerated in most POEMS patients.

Chronic motor axonal neuropathy.

The identification of a distinct subgroup of patients within the spectrum of lower motor neuron syndromes (LMNS) is crucial as some are potentially treatable. We describe the clinical and neuropathological characteristics of a patient presenting with a rapidly progressive LMNS associated with high titers of anti-GM1 antibodies, leading to respiratory failure within 10 months. Histopathological study of a biopsy of a obturator nerve motor branch demonstrated a predominantly axonal motor neuropathy, while electron microscopy analysis localized macrophages located within the periaxonal space. Immunohistochemistry demonstrated deposits of complement activation products (C3i) and immunoglobulins (IgM) on nerve fibers. The patient's clinical, immunological and pathological findings are consistent with a diagnosis of a chronic motor axonal neuropathy (CMAN), likely of immune-mediated origin.

Circulating levels of cytokines and their modulation by intravenous immunoglobulin in multifocal motor neuropathy.

We found comparable levels of tumor necrosis factor (TNF)-alpha, interferon-gamma, interleukin (IL)-2, IL-4, IL-10, and IL-12 in the sera of 22 patients with multifocal motor neuropathy (MMN), 12 with amyotrophic lateral sclerosis (ALS), 12 multiple sclerosis, seven chronic inflammatory demyelinating polyneuropathy, five myasthenia gravis, and 13 healthy controls (NS). TNF-alpha levels, however, were higher in 15 (68%) MMN patients than in any NS. In all but one MMN patient tested, TNF-alpha levels repeatedly, albeit slightly, increased after each intravenous immunoglobulin infusion in parallel with clinical improvement and decreased 3-4 weeks after therapy, while in both ALS patients tested, they decreased or remained unchanged. The possible pathogenetic relevance of serum TNF-alpha modification in MMN remains to be clarified.