Sequential Blood Purification for Pediatric Fatal Toxic Epidermal Necrolysis: A Case Series

<b><i>Background:</i></b> Extracorporeal therapy that included therapeutic plasma exchange (TPE) or continuous hemofiltration (CHF) for toxic epidermal necrolysis (TEN) syndrome was used in small number of patients. We aimed to describe the sequential mode of combined application of CHF and TPE in 3 TEN patients with multiple organ dysfunction (MODS) in pediatric intensive care unit. <b><i>Methods:</i></b> Three patients with fatal TEN received sequential CHF and TPE due to unsatisfactorily conventional treatments. CHF was initiated and performed on a daily basis with 35–50 mL/kg.h replacement fluid at the rate of 3–5 mL/kg.min blood flow. CHF was temporarily interrupted for TPE, which was performed with exchange 1–1.5-fold of one body calculated plasma volume in each section. <b><i>Results:</i></b> All 3 fatal TEN (with &#x3e;30% involvement of body surface and MODS) following unsuccessful treatment with corticosteroids and intravenous immunoglobulin. Antibiotics were suspected in the TEN-triggered drugs. The range number of TPE sessions was 3–5 and the duration of CHF was from 120 h to 202 h. After initiation of TPE and CHF, blistering with extensive epidermal necrosis halted and the skin re-epithelialized within 2 weeks. Serum C-reactive protein, procalcitonin, tumor necrosis factor-α , and interlukin-6 decreased and percentage of natural killer cells increased in surviving children. Two patients survived to discharge and one case died due to nosocomial infection with multidrug-resistant <i>Acinetobacter baumannii.</i> <b><i>Conclusion:</i></b> After sequential TPE and CHF, skin lesions and inflammatory response improved in TEN. Our result indicates extracorporeal therapy could be used as an alternative modality for fatal pediatric TEN.

Epidemiological, clinical and morphological aspects of kidney damage in COVID-19

The mini-review presents modern data on the epidemiology, clinical and morphological aspects of kidney damage in COVID-19. Potential mechanisms of kidney involvement in the clinical picture of the disease may include cytokine damage, cross-organ damage, and systemic effects that determine the treatment strategy. These mechanisms are closely interrelated and are especially important for individuals undergoing extracorporeal therapy and kidney transplants. Autopsy data provide evidence of SARS-CoV-2 virus invasion into kidney tissue with damage to tubular epithelial cells and podocytes, and erythrocyte aggregation in persons with severe COVID-19. By including people with chronic kidney disease in planned COVID-19 research protocols, an evidence base for effective and safe treatments can be generated.

COVID-19 and kidneys

COVID-19 poses a real threat to patients with comorbid conditions such as diabetes mellitus (DM), hypertension, cardiovascular, renal or hepatic disorders. Kidney damage is very likely in people with diabetes who have undergone a new infection, and the risk of developing acute renal injury is associated with mortality. Potential mechanisms of kidney involvement in theclinical picture of the disease may include cytokine damage, cross-organ damage, and systemic effects that determine the treatment strategy. These mechanisms are closely interrelated and are important for individuals on extracorporeal therapy and kidney transplants. Autopsy data provide evidence of SARS-CoV-2 virus invasion into kidney tissue with damage to tubular epithelium cells and podocytes, and red blood cell aggregation in severely COVID-19 patients. By including individuals with chronic kidney disease in planned COVID-19 research protocols, an evidence base for effective and safe treatments can be generated.

A New Solid-Phase Immunosorbent for Selective Binding of Desmoglein 3 Autoantibodies in Patients with Pemphigus Vulgaris

Autoantibodies, immunoglobulins G (IgG) againstthe desmosomal proteins desmogleins 1 and 3, play a significant role in the pathogenesis of pemphigus vulgaris. The basic therapy for pemfigus includes systemic corticosteroids, but their use should be as briefas possible because of the severe side effects. In cases of corticosteroid-resistant pemfigus, adjuvant therapy, in particularextracorporeal methods, is used. The most effective and safest extracorporeal therapy is immunosorbtion. Immunosorbtion is based on the removal of pemphigus antibodies from the blood using an affinity sorbent during a therapeutic apheresis procedure. Existing immunosorbents are nonselective and increase the risk of infection. We designed an immunosorbent based on an agarose matrix, Affi-Gel 15, and human recombinant desmoglein 3, as aligand, for a selective removal of autoantibodies from pemphigus patients sera. It was shown on a pemphigus experimental modelin vivo(neonatal Balb/c mouse model) andin vitrothat the immunosorbent can effectively remove desmoglein 3-associated autoantibodies. The experimental results demonstrate that the solid-phase matrix immunosorbent Affi-Gel 15Dsg3 is a promising product for the development of pemphigus therapy.