Myasthenia Gravis and Thymectomy

Myasthenia gravis (MG) is a rare autoimmune neuromuscular disorder. Though MG was diagnosed four centuries ago, its rational management started in 1930s. In the present era, MG is managed by multimodality care including pharmacological agents, plasmapheresis, intravenous immunoglobulins, and surgical thymectomy. Thymectomy has evolved from open trans-sternal to video-assisted thoracoscopic and robotic thymectomy. In this article, the concise history of MG, its clinical features, diagnosis, and management are described.

Toxic Epidermal Necrolysis/Stevens-Johnson Syndrome at A University Hospital in Saudi: Causative Factors and Outcomes

Introduction:Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are rare, life-threatening conditions caused mainly by drugs. Their management relies on the withdrawal of the culprit medication and supportive measures. Different pharmacotherapies have varied effects. However, data related to TEN and SJS in Saudi is limited. This study aimed to identify the causative agents, associated factors, and outcomes of TEN/SJS cases admitted to a teaching hospital (King Abdulaziz University) in Jeddah during the last 10 years.Methods: We retrospectively analyzed the data of TEN/SJS patients admitted to the hospital over the last 10 years.Results: We identified 12 patients with TEN/SJS. Of these, nine survived the condition and were discharged. The culprit medication was identified in eight of them, including antibiotics in six cases and Tegretol and allopurinol in one case each. Most of the patients received systemic steroids and intravenous immunoglobulins.Conclusion: TEN/SJS is mainly caused by medications of which antibiotics are the most implicated. Consistent with other studies, the mortality rate associated with TEN/SJS in Saudi is 25%. Limitations: restricted to a single center and small sample size.

Case Report: High Doses of Intravenous Immunoglobulins as a Successful Treatment for Late Onset Immune Agranulocytosis After Rituximab Plus Bendamustine

Late onset neutropenia (LON) related to rituximab or rituximab plus chemotherapy is defined as an unexplained absolute neutrophil count of ≤1.5 × 109/L starting at least four weeks after the last rituximab administration. LON is infrequent and its pathophysiology remains unknown. There are no guidelines or consensus strategies for the optimal management of patients developing LON. The majority of the patients recover promptly with no specific treatment and only some cases need to be managed with granulocytic colony stimulating factor (G-CSF), usually with a rapid response. Here, we describe a 69-year-old patient with Waldenström’s macroglobulinemia who presented a septic event in the context of severe LON after rituximab plus bendamustine. The diagnosed of agranulocytosis was established by bone marrow examination. Interestingly, anti-neutrophil antibodies bound to the patient’s granulocytes were found suggesting an autoimmune mechanism. The patient did not respond to G-CSF but achieved a rapid response after high doses of intravenous immunoglobulins with full white blood cell recovery.

Аcute transverse myelitis and Guillain – Barre overlap syndrome in a patient with СOVID-19

We report a case of transverse myelitis and Guillain–Barre syndrome (GBS) overlap in the 42-year-old patient with moderate course of Coronavirus disease 2019 (СOVID-19). Nasopharyngeal SARS-CoV 2 RT-PCR was positive. Severe neck pain developed in this patient on the 5-th day of СOVID-19. A few hours later weakness in the feet arised and then spread to the thighs and arms. Quadriparesis, arefl exia in all limbs, sensory loss below the level of T4 and bladder/bowel dysfunction were present. Pyramidal signs were negative. There was no increase of COVID-19 severity at the time of neurological signs development. Magnetic resonance imaging of the spinal cord showed the focal lesion in the C2-T1 segments, which was consistent with the features of longitudinally extensive transverse myelitis. Along with the myelitis, acute motor axonal polyneuropathy was diagnosed. This diagnosis of GBS was supported by ascending weakness with arefl exia, albumin-cytological dissociation in cerebrospinal fl uid and the data of neuroelectrophysiological examination. We proposed that both myelitis and GBS had disimmune nature associated with COVID-19. The other possible causes of damage to the spinal cord and peripheral nervous system were excluded.Immunotherapy with high dose of intravenous immunoglobulins was administered. Steroids also were used taking into account the myelitis. At the follow up in 4 months the motor functions were found to be improved nonsignifi cantly, the patient was still severe disabled.

In vitro Characterization of Anti-SARS-CoV-2 Intravenous Immunoglobulins (IVIg) Produced From Plasma of Donors Immunized With the BNT162b2 Vaccine and Its Comparison With a Similar Formulation Produced From Plasma of COVID-19 Convalescent Donors

Despite vaccines are the main strategy to control the ongoing global COVID-19 pandemic, their effectiveness could not be enough for individuals with immunosuppression. In these cases, as well as in patients with moderate/severe COVID-19, passive immunization with anti-SARS-CoV-2 immunoglobulins could be a therapeutic alternative. We used caprylic acid precipitation to prepare a pilot-scale batch of anti-SARS-CoV-2 intravenous immunoglobulins (IVIg) from plasma of donors immunized with the BNT162b2 (Pfizer-BioNTech) anti-COVID-19 vaccine (VP-IVIg) and compared their in vitro efficacy and safety with those of a similar formulation produced from plasma of COVID-19 convalescent donors (CP-IVIg). Both formulations showed immunological, physicochemical, biochemical, and microbiological characteristics that meet the specifications of IVIg formulations. Moreover, the concentration of anti-RBD and ACE2-RBD neutralizing antibodies was higher in VP-IVIg than in CP-IVIg. In concordance, plaque reduction neutralization tests showed inhibitory concentrations of 0.03–0.09 g/L in VP-IVIg and of 0.06–0.13 in CP-IVIg. Thus, VP-IVIg has in vitro efficacy and safety profiles that justify their evaluation as therapeutic alternative for clinical cases of COVID-19. Precipitation with caprylic acid could be a simple, feasible, and affordable alternative to produce formulations of anti-SARS-CoV-2 IVIg to be used therapeutically or prophylactically to confront the COVID-19 pandemic in middle and low-income countries.

Resistant Chorea Successfully Treated with Intravenous Immunoglobulin: A Case Report

Sydenham’s chorea (SC) is common cause of acquired chorea in childhood. SC occurs mainly in children with untreated streptococcal infections. An effective list of therapeutic options has been used to treat this disorder: antiepileptic drugs (valproic acid, carbamazepine etc.), haloperidol, chlorpromazine, amphetamines, steroids, plasma exchange and intravenous immunoglobulins (IVIG). We report a 12-year-old girl with carditis and severely generalized chorea and successfully treated with IVIG. This case report shows that IVIG is an effective treatment for the chorea cases resistant to anticonvulsants, dopamine antagonists and steroids, although larger studies are needed to confirm this conclusion.

Catastrophic anti-phospholipid syndrome with Libman-Sacks endocarditis following eltrombopag therapy for immune thrombocytopenic purpura: A case report

Background Immune thrombocytopenic purpura (ITP) is an autoimmune disease, with accelerated destruction of platelets, estimated to affect 1.6–3.9 in 100,000 adults every year in the European Union. Glucocorticoids and intravenous immunoglobulins are common drug therapies. In refractory cases, drugs that enhance thrombopoiesis may be used. Eltrombopag is a thrombopoietin receptor agonist, known to increase platelet count in patients with refractory ITP. Thrombotic adverse events have been described in association with Eltrombopag administration. Case report A young female patient of Ethiopian ancestry with systemic lupus erythematosus, triple Antiphospholipid (APLA) positive serology and refractory ITP who received Eltrombopag and 2 weeks later developed catastrophic APLA syndrome with severe Libman-Sacks endocarditis of the mitral and aortic valves, multiple intracerebral infracts and arterial thrombosis of the left upper limb. Conclusion Eltrombopag is a salvage drug, used in refractory ITP. Thrombotic adverse events, some of which may be life-threatening, are a possible complication, especially in high-risk patients.

Polyvalent immunoglobulin preparations inhibit pneumolysin-induced platelet destruction

Platelets play an important role in the development and progression of respiratory distress. Functional platelets are known to seal inflammatory endothelial gaps and loss of platelet function has been shown to result in loss of integrity of pulmonary vessels. This leads to fluid accumulation in the pulmonary interstitium, eventually resulting in respiratory distress. Streptococcus pneumoniae is one of the major pathogens causing community-acquired pneumonia. Previously, we have shown that its major toxin pneumolysin forms pores in platelet membranes and renders them non-functional. In vitro, this process was inhibited by polyvalent intravenous immunoglobulins (IVIG). In this study, we compared the efficacy of a standard intravenous immunoglobulin preparation (IVIG, 98% IgG; Privigen, CSL Behring, USA) and an IgM/IgA-enriched immunoglobulin preparation (21% IgA, 23% IgM, 56% IgG; trimodulin, Biotest AG, Germany) to inhibit pneumolysin-induced platelet destruction. Platelet destruction and functionality were assessed by flow cytometry, intracellular calcium release, aggregometry, platelet viability, transwell, and flow chamber assays. Overall, both immunoglobulin preparations efficiently inhibited pneumolysin-induced platelet destruction. The capacity to antagonize pneumolysin mainly depended on the final IgG content. As both polyvalent immunoglobulin preparations efficiently prevent pneumolysin-induced platelet destruction and maintain platelet function in vitro, they represent promising candidates for clinical studies on supportive treatment of pneumococcal pneumonia to reduce progression of respiratory distress.

Atypical Kawasaki disease in an early infant, a diagnostic challenge: Case report

A 4.5-month-old girl presented to us with continuous fever for 10 days and loose stools for 2 days. She received short courses of multiple oral antibiotics during this period however, was not relieved. Initial investigations were suggestive of urinary tract infection for which broad spectrum antibiotics were started. However, fever persisted even after 72 h of antibiotics. Blood counts showed persistently high total leukocyte count and increasing platelet count, along with high C-reactive protein. Consequently, a diagnosis of Kawasaki disease (KD) was suspected, which was supported by echocardiographic findings. After she received intravenous immunoglobulins, her fever subsided and lab parameters showed significant improvement. This case highlights an unusual presentation of KD in an uncommonly young age group without much clinical pointers except for persistent fever.

A Retrospective Comparative Analysis of Factors Affecting the Decision and Outcome of Initial Intravenous Immunoglobulin Alone or Intravenous Immunoglobulin Plus Methylprednisolone Use in Children With the Multisystem Inflammatory Syndrome

Background: Use of intravenous immunoglobulins (IVIG) with or without methylprednisolone is the most preferred therapeutic strategy for the multisystem inflammatory syndrome in children (MIS-C). This study aimed to compare the use of IVIG plus methylprednisolone vs IVIG alone in children with MIS-C. Methods: This retrospective cohort study was conducted during the period between April 1, 2020, and November 1, 2021. All children with MIS-C were included in the study. The patients were divided in two groups according to whether they were administered IVIG alone or IVIG plus methylprednisolone as an initial treatment for MIS-C. While the patients in group I were administered IVIG with a dosage of 2 gr/kg, the patients in group II were administered IVIG (dosage of 2 gr/kg) plus methylprednisolone (2 mg/kg/day). The re-occurrence of fever, duration of hospital stay, admission to pediatric intensive care unit were compared between these two groups. Results: A cohort of 91 patients under 18 years old and diagnosed as MIS-C was included in the study. Of these patients, 42 (46.2%) were in IVIG alone group. (group I) and 49 (53.8%) were in IVIG plus methylprednisolone (group II). The ratio of severe MIS-C was 36.7% for patients in the group II and significantly higher compared to the rate of severe MIS-C patients in the group I (9.5%) (p=0.01). The rate of hypotension was significantly higher in the group II (30.6 %) compared to the group I (9.5%) (p=0.014). Moreover, the mean serum levels of C-reactive protein were significantly higher for the patients in group II. The re-occurrence of fever was 26.5% in the group II and 33.3% in the group, however this difference was not statistically significant (p>0.05). Conclusions: The decision of the treatment choice of patients with MIS-C should be individually evaluated. In the clinically severe MIS-C patients who were with hypotension, and/or admitted to PICU should be treated with IVIG plus methylprednisolone. However, randomized double-blind studies are required for the treatment modalities of children with MIS-C.