Cycles Of Intravenous Immunoglobulin Research Articles

Neurolymphomatosis mimicking a Guillain–Barré syndrome triggered by COVID‐19 vaccination

Guillain–Barré syndrome (GBS) is an acute disorder of the peripheral nervous system, causing flaccid paralysis, areflexia, and variable sensory involvement. Proximal as well distal muscles of the limbs can be involved, and in most severe and advanced cases progresses to respiratory failure and death. GBS is considered an autoimmune disease, and at the basis of the attack at the peripheral nervous system different mechanisms have been recognized, in particular viral infections or other immune stimulations. Cranial nerve involvement in patients with diffuse large B‐cell lymphoma (DLBCL) and primary central nervous system lymphoma are rare conditions that could present with similar clinical features. Here we present a case of a 36‐year‐old man hospitalized for acute polyradiculoneuritis of the cranial nerves and lumbar roots that arose a 14 days after severe acute respiratory syndrome COVID‐19 2 (Sars‐CoV‐2) vaccination. Most of the main criteria for the diagnosis of GBS were met, including clinical and electrophysiological criteria. Albuminocytologic dissociation and high protein level in cerebrospinal fluid were also found. Therefore, the patient was treated with a cycle of intravenous immunoglobulin (IVIG) with notable improvement of symptoms and gradual recovery of motility. A five months later, following SARS‐CoV‐2 infection, the patient presented with worsening of neurological symptoms and was readmitted to the hospital. He underwent instrumental tests again and was treated with repeated cycles of IVIG and then with a cycle of plasmapheresis without any improvement. In the following 10 days he developed very serious conditions; he was transferred to intensive care unit and deceased after 6 days. The cause of the neurological syndrome was determined only after autoptic analysis, which revealed the presence of primary peripheral nervous system (PNS) DLBCL. The reported case highlights that GBS‐like presentation always requires a careful differential diagnosis, and physicians should also consider the possibility of an occult cancer.

Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy after Ad26.COV2.S COVID-19 Vaccination (P13-8.006)

<h3>Objective:</h3> NA <h3>Background:</h3> Acute onset demyelinating neuropathy has been reported after coronavirus disease 2019 (COVID-19) vaccination. Only a limited number of cases continued progression and became chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), mostly after ChAdOx1 nCoV-19 vaccination. Here, we report the first case of acute-onset CIDP after Ad26.COV2.S (Johnson &amp; Johnson) vaccination. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 67-year-old man presented with one-week history of progressive left facial droop, unsteady gait, slurred speech, double vision, and patchy numbness; he reported Ad26.COV2.S vaccination three weeks before presentation. On initial examination, he had left facial palsy, partial left abducens nerve palsy, generalized areflexia, severe lower extremities ataxia, and diminished vibratory sensation in toes. Cerebrospinal fluid analysis showed albuminocytologic dissociation. He received intravenous immunoglobulin (IVIG) for five days for presumptive diagnosis of Guillain-Barré syndrome (GBS). Electrodiagnostic studies demonstrated impersistent F-waves, decreased recruitment in lower extremities, and bilaterally absent blink reflexes. He developed right facial weakness on day three and asymmetric appendicular muscle weakness on day five of treatment. Seven weeks after symptom onset, his lower extremities weakness worsened, and received a second cycle of IVIG. The lower extremity weakness did not improve but remained stable until seventeen weeks after symptom onset when he returned with progressive upper extremities weakness and dyspnea. Electrodiagnostic studies demonstrated demyelinating features consistent with CIDP. Neuromuscular ultrasound demonstrated multifocal median nerve enlargements at non-entrapment sites. At this point, given the clinical course, electrodiagnostic and ultrasonographical findings, CIDP diagnosis was established. <h3>Conclusions:</h3> This patient’s acute-onset CIDP and other reported GBS cases after adenoviral vector COVID-19 vaccinations shared similar and atypical presenting symptoms, which were not seen in GBS after mRNA COVID-19 vaccinations. While a causal relationship cannot be established to his COVID-19 vaccination, this case adds to the evolving literature of COVID-19 vaccination-associated neurological events. <b>Disclosure:</b> Dr. Bendi has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Danielson has nothing to disclose.

Intravenous immunoglobulin bridging to rituximab in NMDAR encephalitis patients non-responders to first-line treatments

BackgroundThe immunotherapy strategy for autoimmune encephalitis is based on several types and schedules of both first- and second-line drugs. Failing to respond to the latter prompts the use of non-conventional rescue therapies, with higher risks of severe adverse effects. We report on a protocol that entails the use of intravenous immunoglobulin cycles to bridge the 4-month period that the second-line drug rituximab needs to exert its full therapeutic effects.MethodsThree patients with NMDAR encephalitis who were non-responders to first-line treatments entered the study. The protocol consisted of six monthly cycles of intravenous immunoglobulins (IVIG, 0.4 mg/kg/die for 5 days), starting 1 month after the last rituximab infusion (1000 mg at days 0 and 15). Brain MRI and [18F]-FDG-PET were performed at onset and at six and 18 months after onset.ResultsIn the three patients, substantial improvements of disability or complete recovery were achieved, without modifications over the 30-to-50-month follow-up. No adverse events nor laboratory test abnormalities were recorded. Imaging findings paralleled the favorable disease courses. Brain [18F]-FDG-PET was more sensitive than MRI in detecting abnormalities.DiscussionOur observations suggest that the herein-described protocol might be used in patients with NMDAR encephalitis at risk for poor prognosis in the mid-term when they need to shift to rituximab. [18F]-FDG-PET confirmed to be a sensitive tool to detect the minimal brain lesions that can underlie isolated cognitive and psychiatric symptoms.

Outcomes in Guillain-Barré Syndrome following a second therapeutic cycle – A single-centre retrospective observational study

IntroductionThe treatment of Guillain-Barré Syndrome (GBS) with intravenous immunoglobulin (IVIg) or plasma exchange (PE) reduces time to clinical recovery. Although sometimes used in clinical practice, the benefit of a second treatment cycle is of unproven benefit. AimsOur aim was to compare GBS prognosis in patients treated with one or two cycles of IVIg or PE. MethodsWe selected patients with electrophysiological studies compatible with acute inflammatory demyelinating polyneuropathy or acute motor-sensory axonal neuropathy, from January 2018 to December 2020 in our hospital. Our primary outcome was any improvement in the Guillain-Barré Syndrome Disability Score (GBS-DS) at a mean of twelve weeks. We compared patients treated with one or two treatment cycles with a binary regression. ResultsWe included twenty-six patients, 65.4% with the classical presentation and 30.8% were treated with two cycles. Patients treated with two cycles presented a higher basal GBS-DS (median 4; IQR 1–5) compared with the group of patients treated with one cycle (median 3; IQR 1–5), p = 0.01. The remaining basal characteristics were similar between groups. The two-cycle treatment regimen did not associate with an improvement in GBS-DS (OR 0.28, 95% CI 0.03–2.35, p = 0.24). Likewise there was no benefit in the need for intensive care unit (OR 2.0, 95% CI 0.37–10.92, p = 0.42) or mechanical invasive ventilation (OR 10.2, 95% CI 0.86–120.96, p = 0.66). DiscussionOur analysis reinforces the recent literature data regarding the absence of benefit of two treatment cycles in patients with GBS.

Dengue infection triggered immune mediated necrotizing myopathy in children: a case report and literature review

BackgroundImmune-mediated necrotizing myopathy (IMNM) is a subgroup of idiopathic inflammatory myopathies manifesting with progressive weakness, elevated serum creatine kinase (CK) levels, and necrotizing myopathic features on muscle biopsy. There is a paucity of data on the clinical presentation of IMNM in children. We report a paediatric patient who developed anti-3-hydroxy-3-methylglutaryl-CoA reductase (anti-HMGCR)-positive necrotizing myopathy after recent dengue infection.Case presentationA previously healthy 9-year-old boy presented with acute proximal muscle weakness after recovery from dengue infection. Five days after the fever subsided, he could not stand from a squatting position. He denied having skin rash, arthritis, or other systemic features. He had marked elevation of CK level of 30,833 mg/dL and was put on steroid therapy. The patient initially responded to oral prednisolone, however the weakness persisted and muscle enzymes increased as steroids were decreased. He was then referred to our hospital for further assessment. Subsequent investigation revealed anti-HMGCR positivity along with specific histopathological findings consistent with IMNM. The patient was treated with six cycles of intravenous immunoglobulin (IVIG) monthly, then followed by a gradual taper of prednisolone and oral methotrexate weekly with complete recovery in motor power.ConclusionsOur report presents a child with clinical manifestations of IMNM which can be categorized as acute onset of muscle weakness following dengue infection. Two key points supporting a diagnosis in this case are clinical response after immunosuppressive therapy and absence of rashes found in juvenile dermatomyositis.

Long‐term remission of severe livedoid vasculopathy treated with a short course of intravenous immunoglobulin

We present a case of acute flare of severe livedoid vasculitis (LV) which had been refractory to a combination of immunosuppressive and anti-thrombotic agents, but remitted for 7 years after only two cycles of intravenous immunoglobulin (IVIV). This suggests that IVIG may exert unique immunological and/or anti-thrombotic actions different from other agents, and that only short-term or on-demand use of IVIG for acute flare of LV may dampen down disease activity and induce a prolonged remission of LV.

Corticosteroids Plus Intravenous Immunoglobulin Compared with Corticosteroids for the Treatment of Immune Thrombocytopenia in Pregnancy: An Observational Multicenter Study in China

Immune thrombocytopenia (ITP) affects 1-10 in 10,000 pregnancies (American College of Obstetricians and Gynecologists, et al. Int J Gynaecol Obstet. 1999). In contrast to ITP in nonpregnant individuals, treatment of ITP in pregnancy is limited and no consensus has been reached regarding treatment. Although corticosteroids and intravenous immunoglobulin (IVIg) are acceptable treatments for ITP in pregnancy, the evidence from large-scale clinical trials is still insufficient. Here we retrospectively analyzed the data from 5 collaborative centers in China to compare the effectiveness of corticosteroids plus IVIg with that of corticosteroids alone for the treatment of immune thrombocytopenia in pregnancy.Between January 2001 and July 2017, 521 women (572 pregnancies) were enrolled in this retrospective study. The diagnosis of ITP was confirmed in women previously diagnosed with ITP. Patients whose platelet counts remained above 70×109/L during pregnancy and normalized in the postpartum period were deemed to have gestational thrombocytopenia and were excluded (Sun D, et al. Blood 2016). The median initial prednisone dose was 15 mg/d (interquartile range [IQR] 10-30 mg/d) in both the combined therapy group and the monotherapy group. IVIg was given concomitantly at a daily dose of 20g during the first 3-5 days in the combined therapy group. Another 3 cycles of IVIg were given every 2-4 weeks if maternal platelet response was observed (platelets ≥30×109/L). Withdrawal of IVIg could be performed when platelets rose above 300×109/L in <14 days. A total of 2 cycles of IVIg could be given for no platelet response (platelets <30×109/L).The intervention was not introduced in 340 pregnancies (340/572, 59%). Among the remaining 232 women with pregnancies, 105 (45%) were given prednisone plus IVIg as the initial treatment and 127 were given only prednisone. The maternal characteristics, including age, maternal pretreatment platelet count, bleeding score and more, did not differ between the two groups. No differences between the two groups were observed with regard to the maternal response to the initial treatment (including complete response [CR] and partial response [PR], prednisone plus IVIg 48% vs. prednisone 36%, p=0.08), nor were differences observed with regard to the proportion of maternal complications, including bleeding episodes in the antenatal period, platelet count at delivery, pre-delivery platelet transfusion, mode of delivery (vaginal delivery or cesarean section), abortion and premature delivery. For patients with an initial response, there was a significant difference between the time to response (TTR) of the corticosteroids plus IVIg group (median and range, 3 and 1-14 days) and the TTR of the corticosteroid group (7 and 2-18 days) (p <0.01). Notably, 62 of 81 pregnancies with no response to prednisone were given IVIg, and the response to the treatment was 34% (21/62). Moreover, of 324 women (357 pregnancies) with a history of ITP, the majority of pregnancies (255/357, 71%) did not require treatment. A review of 197 women (215 pregnancies) with newly diagnosed ITP during pregnancy revealed that most ITP (161/215, 74.8%) was first recognized in the first trimester. With regard to the neonatal characteristics, 599 neonates (572 pregnancies) were live births and none were intrauterine death. Among 389 neonates (389/599, 65%) whose cord blood platelet counts were measured, platelet counts<100×109/L were observed in 118/389 (30%) neonates, and specifically in 18/155 neonates (12%) whose mothers were not treated. No fatal or severe neonatal hemorrhage was observed. The proportion of neonates with an Apgar score <7 at 5 minutes and neonatal platelet counts at birth did not differ between the groups. Neonatal cord platelet count compared with maternal platelet count at delivery indicated a lack of linear relation. Adverse events, including hyperglycemia requiring treatment, infection, and others, were reported in 19/105 (18%) of the prednisone plus IVIg group and in 31/127 (24%) of the prednisone group (p=0.28).In conclusion, no better maternal platelet count response but a shorter TTR were shown in the prednisone plus IVIg group compared with the prednisone group in this observational study of ITP patients in pregnancy. Prospective studies are needed to better identify the effectiveness and safety of these regimens and to explore new therapeutic options. DisclosuresNo relevant conflicts of interest to declare.

Intravenous Immunoglobulin Therapy in Livedoid Vasculopathy: Retrospective Observation of Clinical Outcome and Patient's Activity Level.

BackgroundLivedoid vasculopathy (LV) is a rare disease characterized by livedo racemosa, atrophie blanche, ulcerations, and severe pain. Low molecular weight heparins and rivaroxaban can be used in LV-patients. In addition, intravenous immunoglobulins (IVIG) have been described as treatment-option.ObjectivesObjective was to investigate the therapeutic effect of IVIG on ulcer, pain and restrictions in daily life.MethodsThirty-two LV-patients who received IVIG at the Department of Dermatology Tübingen between 01/2014 and 06/2019 were identified. Twenty-five of these patients were available for further follow up and were included in the study. Patients were interviewed using a questionnaire focusing on the course of the disease, symptoms, and subjective response to IVIG-treatment.ResultsTwenty-five patients were included in the study (mean follow up: 28.9 months). Patients received an average of 6.8 cycles (range 1-45) of IVIG during the observed period.Significant improvements were seen regarding skin findings, pain, and limitation of daily activities. Complete remission of symptoms was observed in 68% of patients. Good tolerability of IVIG was shown in 92%.ConclusionsA good therapy response regarding ulceration, pain, and daily life restrictions with good tolerability was demonstrated for IVIG (2 g/kg bodyweight over 5 days).

Neutropenia resulting from high-dose intravenous immunoglobulin in dermatological patients.

Current guidelines recommend high-dose intravenous immunoglobulin (IVIG) as a rescue therapy to treat severe cutaneous autoimmune disorders. Data on IVIG-induced hematological adverse events are limited in dermatological patients. We assessed the incidence and clinical implications of IVIG-induced neutropenia. Patients who received one or several cycles of IVIG between 2014 and 2019 were retrospectively evaluated. IVIG was given according to standardized infusion protocols. Daily differential blood counts were performed. Information on clinical baseline data, dermatological diagnosis, immunosuppressive pre-treatment, and IVIG-related adverse events was retrieved from patient files. Seventeen patients received 106 IVIG treatment cycles. Neutrophil counts below 1,500/μL were documented during 36 (34.0%) cycles, and neutrophils fell below 1,000/μL in 14 (13.2%) cases. The average drop of neutrophils from day one (pre-dose) to days 2 and 3 of IVIG therapy was statistically significant (p=0.006, and p=0.002, respectively) despite correction for hemodilution, and so was a slight decrease of thrombocytes (p=0.029, and p=0.011, respectively). Four patients developed seven episodes of bacterial infections during or immediately after IVIG therapy. IVIG-induced neutropenia is frequent in dermatological patients. A risk of secondary bacterial infections cannot be excluded.

NEUROPATIA AXONAL MOTORA AGUDA COM PIORA AO TRATAMENTO COM IMUNOGLOBULINA: RELATO DE CASO

Neuropatias são condições que acometem o sistema nervoso periférico, podendo estar relacionadas a doenças sistêmicas. A síndrome de Guillain-Barré é o principal exemplo quando se fala em polirradiculoneuropatia aguda, geralmente seu quadro é associado a uma infecção prévia de Campylobacter jejuni sendo a neuropatia axonal motora aguda uma de suas variantes motoras puras e tem sua incidência variante de acordo com o espaço geográfico estudado entre 30 a 65% dos quadros totais de Guillain-Barré. As manifestações dessa variação são paralisia das extremidades de caráter simétrico e ascendente, arreflexia, com acometimento da musculatura respiratória, ocular e facial. Descrevemos um caso no qual o paciente apresentou, após uma infecção de vias aéreas superiores, parestesia de mãos e pés associada a fraqueza de caráter progressiva e ascendente, diplopia e disfagia, evoluindo para insuficiência respiratória aguda, após exames comprobatórios foi iniciado protocolo de tratamento com Hiperimunoglobulina Humana Endovenosa para o tratamento de Síndrome de Guillain-Barré. O paciente evoluiu com tetraplegia flácida e necessidade de ventilação mecânica após isso, no exame de eletroneuromiografia evidenciou-se Neuropatia Axonal Motora Aguda. Por fim novo ciclo de imunoglobulina humana intravenosa obtendo resultado. O paciente recebeu alta hospitalar com sequelas motoras, mantendo acompanhamento domiciliar multiprofissional após 63 dias de internamento em unidade de terapia intensiva.

A paraneoplastic limbic encephalitis from an anorectal small cell neuroendocrine carcinoma: a case report

BackgroundParaneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome observed in cancer patients. PLE is difficult to diagnose and presents a variable response to treatment, depending on the characteristics of the tumor and neuronal autoantibodies.Case presentationA 64-year-old, Caucasian, non-smoker man presented with a rapidly developing cognitive impairment, personality change, spatial disorientation, and short-term memory loss associated with anorexia and cervical and inguinal lymph nodes. The 18F-FDG PET scan documented intensely hypermetabolic lymph nodes, which histologically corresponded to a metastasis from a small cell neuroendocrine carcinoma. The brain MRI revealed a high T2-weighted FLAIR signal of the hippocamps, consisted with a PLE. The presence of anti-neuronal Hu antibodies confirmed the diagnosis. The patient underwent plasmapheresis, associated to a systemic chemotherapy resulting in a partial and temporary improvement of the neurological symptoms. Four cycles of intravenous immunoglobulins were also necessary. After six cures of chemotherapy, the lymph node metastases regressed. However, a new anorectal lesion was detected and was histologically confirmed as a primary small cell neuroendocrine carcinoma, which was treated with concomitant chemoradiotherapy. At the end of this treatment, the patient showed a rapid tumor progression leading to his death.ConclusionsThis case highlights the rare entity, PLE, which is difficult to diagnose and manage. In addition, this is the first published case of PLE associated with an anorectal small cell neuroendocrine carcinoma, which appeared after completion of systemic chemotherapy.

Treatment with intravenous immunoglobulins in systemic lupus erythematosus: a single-center experience with 63 patients.

Intravenous immunoglobulin (IVIG) is prepared using purified human plasma. IVIG therapy has immunomodulatory effects on autoimmune diseases, including severe systemic lupus erythematosus (SLE). However, reports of its effects on large cohorts are scarce. This single-center retrospective study included SLE patients treated with at least one IVIG cycle for SLE complications. Demographic data, indications, cycle numbers, and clinical improvement with IVIG were evaluated. SLE Disease Activity Index 2000 (SLEDAI-2K) scores were calculated at admission and after IVIG treatment in order to measure clinical improvement. Sixty-three SLE patients treated with IVIG (median age: 29 years; interquartile range 21-36 years; 84.13% female) were included, who received 2 g/kg IVIG for two to five days. Main indications were immune thrombocytopenia, hypogammaglobulinemia, infection during a SLE flare, bicytopenia, and immune hemolytic anemia. Seven patients received more than one IVIG cycle without severe adverse effects. Significant differences were found in SLEDAI-2K scores when the indications were immune thrombocytopenia and hypogammaglobulinemia, with a trend for hemolytic anemia. Patients with concomitant infection, myopathy, and gastrointestinal involvement showed a considerable reduction in their last SLEDAI-2K scores. Fourteen patients died during hospitalization, mainly due to septic shock and active SLE. IVIG showed adequate tolerance and effectiveness in selected severe SLE manifestations, mainly hematological involvement. It was useful for concomitant infection.

Bilateral phrenic neuropathy responsive to intravenous immunoglobulin treatment

The aetiology of phrenic neuropathy is often unknown, but immune mechanisms may play a role. In a typical case of bilateral phrenic neuropathy with paradoxical breathing (video), an inflammatory pathogenesis was suggested by prolonged distal latency of phrenic nerve compound muscle action potentials in nerve conduction studies and a clear-cut albumin-cytologic dissociation. This encouraged us to treat the patient with a standard dose of intravenous immunoglobulin. After obtaining a strong improvement at spirometry, we repeated the second cycle of intravenous immunoglobulin and observed normalization of symptoms within few weeks and no relapse after 3 years. This case suggests that lumbar puncture should be performed in the acute phase of phrenic neuropathies to detect potential responders to immunomodulatory treatment.

An upfront immunomodulatory therapy protocol for pediatric opsoclonus-myoclonus syndrome.

Treatment of opsoclonus-myoclonus syndrome (OMS) has historically involved corticosteroids and intravenous immunoglobulin (IVIG) for a duration of 6-12 months or longer. This study evaluated whether a brief upfront immunomodulatory therapy protocol with rituximab reduces the duration of OMS therapy without adversely affecting OMS outcomes. Retrospective chart review was performed for consecutive children diagnosed with OMS from 2006 to 2019 at The Hospital for Sick Children (Toronto, Canada). Children treated within 3 months of diagnosis with a treatment protocol involving pulse methylprednisolone (3-5 days, followed by an oral steroid taper), IVIG and/or plasma exchange, and rituximab (protocol group, n=7) were compared to a historical group treated primarily with prednisone and IVIG (n=8). The duration of corticosteroid treatment was shorter in the protocol (median 4.5 [range 3-12] months) compared to that in the historical group (median 21.5 [range 6-70] months, P=.005), and subjects in the protocol group received fewer cycles of IVIG (median 1 [range 0-7] cycle vs 7 [range 1-70] cycles, P=.01). The proportion of children with OMS relapse was similar between the protocol and historic groups (2/6 vs 5/8, P=.59). OMS symptom rating scales at 12-month follow-up were similar in the protocol group (median 2.5, range 0-3) compared to that in the historical group (median 1, range 0-7; P=.66). An upfront immunomodulatory therapy protocol with rituximab permits reduction in the duration of corticosteroid and IVIG therapy without a detrimental effect on OMS outcomes. Future studies with longer follow-up will have to determine whether neurocognitive and psychosocial outcomes are improved by this approach.

Retrospective analysis of a single-center clinical experience toward development of curative treatment of 123 pemphigus patients with a long-term follow-up: efficacy and safety of the multidrug protocol combining intravenous immunoglobulin with the cytotoxic immunosuppressor and mitochondrion-protecting drugs.

Pemphigus vulgaris (PV) is a life-long IgG autoantibody-mediated blistering disease affecting the mucosal surfaces lined by the stratified epithelium (oral, nasal, genital) and sometimes also the skin. While corticosteroid treatment is life saving, the high dose and prolonged courses required for disease control are associated with significant adverse effects, including death. Although introduction of rituximab (RTX) provided for a favorable outcome, the high relapse rate, that is, up to 80%, precludes successful use of RTX as a monotherapy. Intravenous immunoglobulin (IVIg) is being increasingly utilized as off-label therapy for a variety of autoimmune and inflammatory diseases, including PV and pemphigus foliaceus (PF). The goal of pemphigus research is to develop an effective treatment modality that would allow patients to achieve and maintain a stable clinical remission without the need for additional treatments, or cure. This article summarizes clinical outcome of 123 pemphigus patients treated with a combination of IVIg, an immunosuppressive cytotoxic drug (ICD) and mitochondrion-protecting drugs in the Blistering Disease Clinic at the University of California, Irvine from 2007 to 2017. The mean time to disease control was 0.2 months and time to complete remission - 1.7 months. Duration of complete remission on drugs until relapse or end of treatment was 19.3 months. The mean duration of complete remission off drugs until relapse was 15.8 months. That until end of follow up was 48.4 months, with a minimum of 14 and a maximum of 91 months. The overall complete remission rate off all drugs was 100%, with 12% overall relapse rate. Most relapses, 8.1 vs. 3.3%, occurred during the time of treatment, compared to posttreatment. No patients had more than a single relapse. The duration of the posttreatment follow-up ranged from 9 to 97 months with a mean of 64.8 months, or 5.4 years. The total number of IVIg cycles ranged from 26 in patients without a relapse to 37 in patients with a relapse. The clinical outcome in patients that received IVIg with RTX or another ICD were found to be very similar. Thus, the multidrug IVIg regimen allowed to achieve three principal treatment objectives: (i) rapid control of pemphigus symptoms; (ii) stable disease remission; and (iii) overall safety of treatment. While the individualized therapeutic approaches to eradicate the autoreactive B cell clones causing disease in each particular PV or PF patient are being developed, all pemphigus patients can benefit from the treatment protocol described in this study.

Intravenous immunoglobulin is an effective treatment for refractory cutaneous dermatomyositis.

Cutaneous dermatomyositis (DM) is often refractory to multiple systemic medications, suggesting a need for effective alternative treatments. To investigate the effects of intravenous immunoglobulin (IVIG) on patients with refractory cutaneous DM. This was a retrospective review of 42 patients treated with IVIG for refractory cutaneous DM at our institution with clinical data available at DM diagnosis. IVIG was initiated for refractory cutaneous DM alone (n = 15) or refractory cutaneous and muscle/lung disease (n = 27) in patients with various DM subtypes. Overall, 83% of patients had cutaneous DM improvement, including 87% treated for refractory skin disease alone and 81% treated for refractory skin/muscle/lung disease. Cutaneous DM improvement occurred regardless of DM subtype, and was observed after a mean of 1.82 ± 1.38 IVIG cycles. No statistically significant clinical predictors of IVIG response or lack of response were detected. IVIG use resulted in decreased systemic glucocorticoid exposure with or without a decrease in steroid-sparing immunosuppressive medications in 80% of patients. This study is limited by its retrospective nature and lack of objective cutaneous DM activity assessment. Use of IVIG resulted in improvement of refractory cutaneous DM in the vast majority of patients relatively soon after initiation and regardless of DM subtype or clinical manifestations. Additionally, IVIG allowed decrease or discontinuation of immunosuppressive medications in 80% of patients. These findings suggest that IVIG can be a clinically efficacious and cost-effective treatment for refractory cutaneous DM and warrants prospective study.

Long-term neurophysiological and clinical response in patients with chronic inflammatory demyelinating polyradiculoneuropathy treated with subcutaneous immunoglobulin

ObjectiveTo assess the long-term effects of subcutaneous immunoglobulin (SCIg) on neurophysiological and clinical parameters in patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods16 drug-naïve CIDP patients, fulfilling the clinical and neurophysiological criteria for typical CIDP, were treated with one cycle of intravenous immunoglobulin (IVIg) (0.4 g/kg/day for 5 consecutive days) and then shifted to the subcutaneous treatment (SCIg) (0.4 g/kg/week) after 4 weeks. Patients were evaluated (i) at the diagnosis (t0), (ii) after 4 weeks since the last IVIg infusion (t1), and (iii) after long-term treatment with SCIg (t2 = 12 months; t3 = 24 months) by (1) neurophysiological parameters of nerve conduction studies and (2) clinical assessment scales for evaluation of (a) strength, by medical research council (MRC) sum score, (b) sensory functions, by inflammatory neuropathy care and treatment (INCAT) sensory sum score and (c) disability, by overall disability sum score (ODSS). ResultsLong-term SCIg treatment induced a significant improvement of neurophysiological parameters, in particular primary demyelinating features of nerve conduction, and clinical variables. Correlation analysis showed (1) a direct positive correlation between the MRC sum score and the amplitude of the distal compound muscle action potential (dCMAP) amplitude, (2) an inverse correlation between dCMAP amplitude and ODSS score, and (3) an inverse correlation between sensory nerve action potential (SNAP) amplitude and the INCAT sensory sum score. ConclusionsOur findings revealed a significant long-term effect of the SCIg treatment on the neurophysiological parameters, associated with improvement of global strength, sensory deficits and overall disability in patients with CIDP. SignificanceEarly start of the SCIg treatment after IVIg infusions induced a significant and long-term improvement of clinical and neurophysiological parameters in CIDP patients.

Results of intravenous immunoglobulin use and treatment in the South Province of Turkey

Objective In this study, we aimed to evaluate the use of intravenous immunoglobulin (IVIG) in our clinic and investigate the effect of its treatment on diseases in patients with pemphigus. Materials and methods Age, sex, disease, skin biopsy result, duration of illness, treatments received, IVIG adverse effects, and clinical course were recorded by screening medical records of patients with different diagnoses receiving IVIG. The findings were evaluated retrospectively. Findings The total number of cases treated with IVIG was 21. A total of 14 cases were diagnosed as having pemphigus, and three cases were diagnosed as having pyoderma gangrenosum, one (4.8%) case as Sweet syndrome, one (4.8%) case as lichen planus, one (4.8%) case as resistant urticaria, and one (4.8%) case as hyperimmunoglobulin E syndrome. The mean time to start IVIG treatment from diagnosis in patients with pemphigus was 2.62±2.3 years (minimum–maximum: 1–10 years). The mean number of cure IVIG treatment cycles given to patients was 11.38±7.63 (minimum–maximum: 1–30). In patients with pemphigus, a partial remission was achieved with an average cure IVIG treatment cycle of 2.71±3.3 (minimum–maximum: 0–10 cures). In three (21.4%) of the pemphigus cases that received IVIG, the treatment was terminated owing to remission. In pemphigus cases where the treatment was terminated owing to remission, the mean number of IVIG cycles was 12.7±5.9 (minimum–maximum: 6–17). Conclusion IVIG treatment has become a reliable treatment option in our clinic, which is preferred owing to successful treatment results and clinical experience in many different diseases, especially pemphigus.

A rare case of fulminant GBS mimicking brain death with clinical recovery

A 28-year-old male patient admitted with an acute onset areflexic quadriparesis requiring mechanical ventilation within 24 h of admission. The clinical findings of absent motor response and loss of brainstem reflexes mimicked a “brain death” pattern. MRI brain and spine were normal. Nerve conduction studies were suggestive of early acute inflammatory demyelinating polyneuropathy and cerebrospinal fluid (CSF) showed albumino-cytological dissociation. Electroencephalographic (EEG) showed 5–6 Hz generalized slowing. He was treated with 2 cycles of intravenous immunoglobulins (0.4 gm/kg) for 5 days starting on day 1 and 19. Extensive work up was done to rule out other causes of acute flaccid areflexic quadriparesis with multiple cranial nerve involvement. Five sessions of plasma exchange (50 mL/kg) were carried out between day 45 to 55. He showed gradual recovery after being in “locked in” state for almost 55 days. At 9 months post on-set the patient has regained bulbar function and has MRC grade 3/5 power in all four limbs. Other published cases with a similar admission pattern were reviewed. The prognosis is usually very poor as most of the patients died or remained severely disabled.

Utility of somatosensory evoked potentials in the assessment of response to IVIG in a long-lasting case of chronic immune sensory polyradiculopathy

BackgroundChronic immune sensory polyradiculopathy (CISP) identifies a progressive acquired peripheral dysimmune neuropathy recognized as a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant. We describe a young woman with a thirteen-year history of CISP with a belated variable response to intravenous immunoglobulin (IVIG) and an almost erratic anticipation of symptoms between IVIG cycles. The association of IVIG and corticosteroids, immunosuppressants, plasmapheresis, did not lead to clinical improvement and was characterized by significant side effects. We evaluated a combined clinical and somatosensory evoked potentials (SSEPs) approach aimed to identify possible predictive parameters concerning the effect and duration of each IVIG administration. Neurologic disability was evaluated using INCAT - Overall Disability Sum Score (INCAT-ODSS).Case presentationA 30-year-old woman presented on 2004 for the subacute onset of asymmetric paresthesias in the lower limbs over the previous six months. The symptoms had been relapsing-remitting during the first four months, followed by a slow progression, resulting in limbs ataxia and a progressive gait disturbance requiring Canadian crutches. Motor and sensory nerve conduction studies and electromyographic evaluation were into normal limits. Median SSEPs were normal, while tibial SSEPs were characterised by the bilateral absence of both lumbar and cortical responses. Cerebrospinal fluid detected an increased protein concentration, while spinal MRI showed a pronounced thickening of the sacral nerve roots, together with a tube-shaped enlargement. These findings led to the diagnosis of CISP and the patient was treated with IVIG reaching a stable remission over the following 9 years. In early 2014, the patient began to show a variable response to treatment with erratic anticipation of sensory disturbances, and a more pronounced walking disability: corticosteroids, plasmapheresis, mycophenolate mofetil and cyclophosphamide were uneffective and burdened by relevant side effects. To better assess the response to IVIG in terms of time-effect, consistency and duration, we have combined a scheduled clinical and SSEPs evaluation during and after each IVIG cycle.ConclusionsThe correlation between the neurophysiological data and the INCAT-ODSS scores has allowed the modulation of IVIG cycles with a significant reduction of the clinical fluctuations and disability. SSEPs may therefore represent an useful and recommended additional aid for the treatment schedule of this rare clinical form.