Case Report: Autoimmune Hemolysis Anemia After Dihydroartemisinin and Piperaquine for Uncomplicated Plasmodium falciparum Malaria

Malaria is still an endemic disease in Africa, with many imported cases in Europe. The standard treatment is intravenous artesunate for severe malaria and oral artemisinin-based combination therapy (ACT) for uncomplicated malaria. Delayed hemolytic anemia (DHA) after intravenous artesunate has been extensively described, and guidelines recommend biological monitoring until 1 month after the end of the treatment. A link with an autoimmune process is still unsure. Nevertheless, cases with positive direct antiglobulin test (DAT) have been reported. Conversely, DHA is not recognized as an adverse effect of oral ACT. Previously, only few cases of DHA occurring after oral ACT without intravenous artesunate administration have been reported. We report the case of a 42-year-old man returning from Togo. He was treated with dihydroartemisinin/piperaquine combination for uncomplicated Plasmodium falciparum malaria, with low parasitemia. Nine days after the end of the treatment, the patient developed hemolytic anemia with positive DAT. Eventually, the patient recovered after corticotherapy. After excluding common causes of autoimmune hemolytic anemia, we considered that dihydroartemisinin/piperaquine treatment was involved in this side effect.

Normobaric interval hypoxytherapy in the correction of neuroimmunoendocrine disorders in children and adolescents with autoimmune thyroiditis

130 children and adolescents aged 6 to 16 years with a diagnosis of autoimmune thy-roiditis (AIT) at the stage of hypothyroidism underwent a course of hypoxytherapy. The high ef-ficiency of the normobaric interval hypoxic training method in the treatment of hypothyroidism on the background of AIT is shown. An increase in the function and number of CD8+ cells after a course of hypoxytherapy prevents the progression of the autoimmune process and promotes the restoration of thyroid function, which in turn leads to positive dynamics in the neurological status of patients: improved indicators of mental performance and fine coordination of move-ments. Key words: autoimmune thyroiditis, hypothyroidism, hypoxytherapy, interval hypoxic training, neuroimmunoendocrine disorders.

Graves’ disease associated with cholestatic jaundice and persistent diarrhoea

Liver involvement in Graves’ disease can be seen as a part of autoimmune process or rarely, due to the direct effects of thyrotoxicosis on liver. Hyperthyroidism can also have gastrointestinal manifestations like frequent bowel movements, diarrhoea, even malabsorption with steatorrhoea. We report a 36-year-old man with hyperthyroidism, presenting with cholestatic jaundice and persistent small bowel diarrhoea. He was diagnosed to have Graves’ disease and after ruling out more common causes, the cause of cholestatic jaundice was supposed to be Graves’ disease. Considering this possibility, the patient was started on treatment with carbimazole. As patient’s thyroid function tests started improving, he showed significant clinical and biochemical improvement from liver point of view as well.

Precision Medicine in Graves’ Disease and Ophthalmopathy

Graves’ disease (GD) is a condition caused by an autoimmune process involving the thyroid gland, whose main outcome is hyperthyroidism. TSAb start the autoimmune process stimulating the overproduction of thyroid hormones. In addition, TSAb can stimulate TSH-R expressed in fibroblasts and orbital pre-adipocytes leading to the manifestation of Graves’ ophtalmopathy (GO). Also, autoantibodies directed against IGF-1R have an important role in immune-pathogenesis of GO. Fundamental is the role played by cytokines (IFN-γ, TNF-α, Il-6), and Th1 chemokines in the immune-pathogenesis of both disorders, particularly in the active phase. Novel discoveries in the field led to the investigation of promising therapies, such as immune-therapies towards specific antigens (for example against TSH-R), aiming in restoring the immune tolerance versus the immune dominant epitopes associated with autoimmunity in GD. Moreover, Etanercept (that blocks the TNF-mediated inflammatory responses), TCZ (that acts against the IL-6 receptor), and RTX (that acts against CD20) have proven to be useful and safe therapeutic options in refractory GO treatment. Furthermore, teprotumumab (a human monoclonal anti-IGF-1R blocking antibody), have been revealed effective in the treatment of patients with moderate-severe GO and it is now approved for GO therapy in United States. Molecules able to act as antagonists of CXCR3, or to block CXCL10, are also under study. More extensive researches are needed to deepen out these drugs as well as to identify new targeted and effective therapies, that will permit a more precise identification of GD, or GO, patients able to respond to specific targeted therapies.

Long-term β-cells autoimmune destruction markers persistence and residual C-peptide secretion in type 1 diabetes mellitus

Backgraund: It believed that autoimmune process maintained only during the first 5 years of diabetes mellitus type 1 (T1D). Recently scientists discovered the high levels of islet autoantibodies (Ab) in long-standing T1D and some of these patients had residual insulin secretion, determined by the level of C-peptide. According to various sources, the prevalence of such observations ranges from 12 to 48%.Aims: The aim of our study was to assess the duration of autoimmune β-cells destruction markers persistence and residual fasting C-peptide secretion in the long-standing T1D, as well as to determine the possible causes and patterns of these processes.Materials and methods: In the study included 237 patients (91 men, 146 women) with T1D. Patients divided in 4 groups, according to disease duration: а — up to 1 year, n=69 (29%); b — 1–5 years, 52 (22%); c — 5–10 years, 57 (24%); d — more than 10 years, 59 (25%). Ab to glutamic acid decarboxylase (GADA), tyrosine phosphatase-like IA-2 (IA2) and zinc T8 (ZnT8A) were detected by Enzyme Immunoassay. Also detected C-peptide levels and retrospectively HbA1с.Results: Antibodies to antigens of β-cell components were detected in 26 (37%) patients in group A, in 17 patients (33%) in group B, in 15 (29%) in group C and in 14 (23%) — G.In the control group (n = 19), an increased level of antibodies was not revealed. Fasting C-peptide levels were as follows: in group «A» — 0.86 ng / ml [0.53; 1.4], «B» — 0.65 ng / ml [0.27; 0.98], « B «- 0.19 ng / ml [0.17; 0.33],» D «- 0.01 ng / ml [0.01; 0.01]. However, in 13 (22%) patients in group D, fasting C-peptide levels were more than 0.09 ng / ml.Conclusion: The data obtained indicate a long-term persistence of markers of the autoimmune process in patients with T1DM. In groups with a long (more than 5 years) course of T1DM, levels of fasting C-peptide more than 30 pmol/L (0.09 ng / ml or 0.03 nmol / L) were noted in 39 (33.6%) cases.

Vertigo in Systemic Lupus Erythematosus: A Case Report

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiorgan involvement based on an autoimmune process. SLE, although rare, is associated with comorbid vertigo. Vertigo in SLE is caused by a disturbance in the balance system in the inner ear. Few journals discuss SLE related to vertigo. We will report a case SLE with complaints of recurrent vertigo. Case: A-37-year-old woman came with complaints of recurrent vertigo since 1 day ago with a duration of about 15 minutes associated with nausea, vomiting and nystagmus. Patient did not complain tinnitus or hearing disorders. The patient has been diagnosed as SLE since two years ago. The physical examination showed normal and Neuro-otological examination revealed nystagmus horizontal unidirectional, negative skew deviation test, positive Head Impulse Test (HIT). Conclusion: Patients with a diagnosis of SLE can find comorbid peripheral vestibular disorders such as vertigo where there is an antibody mechanism that can damage the inner ear. Treatment of audiovestibular symptoms is usually strongly associated with systemic conditions and in patients with vertigo used betahistine to treatment. Keywords: SLE, Inner Ear, Vertigo.

Features of nervous system damage in antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune process that increases the risk of arterial and venous thrombosis. The mechanism of damage to the central nervous system (CNS) can be not only due to thrombosis, but also antiphospholipid antibodies (APA) circulating in the peripheral blood. The latter can damage the cerebral vascular endothelium, alter the resistance of the blood-brain barrier and penetrate into the central nervous system, exerting a damaging effect on astroglia and neurons, as evidenced by the release of neurospecific proteins into the peripheral bloodstream. The role of APS in developing cerebral ischemia, migraine, epilepsy, chorea, transverse myelitis, multiple sclerosis, cognitive impairment and mental disorders, as well as the peripheral nervous system is described. It should also be noted about a role of APS for emerging neurological disorders in COVID-19, enabled apart from thrombogenesis due to APA via 2 potential mechanisms - molecular mimicry and neoepitope formation. Further study of the APS pathogenesis and interdisciplinary interaction are necessary to develop effective methods for patient management.

Correlations between Electrophysiological Parameters, Lymphocyte Distribution and Cytokine Levels in Patients with Chronic Demyelinating Inflammatory Polyneuropathy

The goal of this study was to analyse, in relation to electrophysiological results, the distribution of lymphocyte subpopulations and the level of cytokines in patients with the typical form of chronic demyelinating inflammatory polyneuropathy (CIDP) before immunoglobulin treatment. The study group consisted of 60 patients (52 men, eight women), with a mean age 64.8 ± 11.2, who fulfilled the diagnostic criteria for the typical variant of CIDP, with (23 patients) and without (37 patients) diabetes mellitus. We analysed the results of the neurophysiological tests, and correlated them with the leukocyte subpopulations, and cytokine levels. In CIDP patients, IL-6, IL-2, IL-4 and TNF-α levels were significantly increased compared to the control group. Fifty patients had decreased levels of T CD8+ lymphocytes, and 51 patients had increased levels of CD4+ lymphocytes. An increased CD4+/CD8+ ratio was also found. Negative correlations were observed mainly between compound muscle action potential (CMAP) amplitudes and cytokine levels. The study enabled the conclusion that electrophysiological parameters in CIDP patients are closely related to the autoimmune process, but without any clear differences between patients with and without diabetes mellitus. Correlations found in the study indicated that axonal degeneration might be independent of the demyelinating process and might be caused by direct inflammatory infiltration.

Reactivation of Vogt-Koyanagi-Harada disease under control for more than 6 years, following anti-SARS-CoV-2 vaccination

Background/purpose Vogt-Koyanagi-Harada (VKH) disease is a primary stromal choroiditis with bilateral granulomatous panuveitis. If initial-onset VKH is treated early and relentlessly the disease can be controlled and even “cured” in a substantial number of cases. We are reporting on a patient treated early and in a sustained fashion who was inflammation free for seven years but who presented a reactivation 6 weeks after the second dose of anti-SARS-CoV-2 vaccination. Case report A 43-year-old woman presented with severe initial-onset VKH disease which was brought under control using steroidal and non-steroidal Immunosuppression (mycophenolic acid and cyclosporine) with additional infliximab infusions because of the persistence of subclinical choroiditis identified on ICGA. Under infliximab alone disease had been inflammation free with no subclinical disease and absence of sunset glow fundus for 6 years. However, following anti-SARS-CoV-2 vaccination, severe resurgence of the disease occurred with exudative retinal detachments. Disease was rapidly brought again under control with oral prednisone (1 mg/kg) therapy and a new loading scheme of infliximab therapy. Conclusion VKH disease results from an autoimmune process directed against melanocyte associated antigens which can be controlled when early and sustained immunosuppressive treatment is introduced. It seems that anti-SARS-CoV-2 vaccination can be at the origin of reactivation of long-time controlled disease.

Autoimmune Hemolysis Anemia After Dihydroartemisinin and Piperaquine for Uncomplicated Plasmodium Falciparum Malaria

BackgroundMalaria is still an endemic disease in Africa with many imported cases in Europe. The standard treatment is intravenous artesunate for severe malaria and oral artemisinin-based combination therapy (ACT) for uncomplicated malaria. Delayed hemolytic anemia (DHA) after intravenous artesunate has been extensively described and guidelines recommend a biological monitoring until one month after the end of the treatment. The link with an autoimmune process is unsure. Nevertheless, cases with positive direct antiglobulin test (DAT) have been reported. Conversely, DHA is not recognized as an adverse effect of oral ACT. Previously, only two cases of DHA occurring after oral ACT without intravenous artesunate administration have been reported. Case presentationWe report the case of a 42 year old man returning from Togo. He was treated with dihydroartemisinin / piperaquine combination for an uncomplicated Plasmodium falciparum malaria. Nine days after the end of the treatment he developed hemolytic anemia with positive DAT. Eventually, the patient recovered after corticotherapy. ConclusionThis is the first case report of autoimmune hemolytic anemia after treatment with dihydroartemisinin and piperaquine.