ABSTRACT
Introduction: Increase in cases with chilblain-like acral lesions has been observed during the pandemic period. Epidemiological data suggest that children have different immunological responses to SARS-CoV-2 virus, which can cause mild respiratory illness but more frequently involve other organ systems. Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae has been described both in adults and pediatrics (1). Objectives: To analyze clinical features, laboratory and instrumental findings of a group of patients with chilblain-like lesions during SARS-CoV-2 pandemic period. Methods: Retrospective analysis of 4 patients with chilblain-like lesions. Results: We present 4 patients with chilblain-like acral lesions (2 female and 2 male). The median age was 15.5 years (13 to 16 years old). Two patients had lesions only in toes whilst others had both hand and feet perniosis. All patients had no laboratorical signs of inflammation (CRP, ESR, WBC, neutrophil, and lymphocyte count were in normal range) and markers for rheumatic and connective tissue diseases (cryoglobulins, antinuclear antibodies, anti-double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor) were negative. Levels of serum complement C3 (mean value 0.775 g/l) and complement C4 (mean value 0.1425 g/l) was reduced in all cases. Two patients had positive Chlamydia pneumonia antibodies (IgM titers of >12 were defined as positive), others were not tested. The first patient had lesions in toes and for the second patient, both hands and feet were damaged. All patients underwent ultrasound of affected sites. One of 4 patients was diagnosed with reactive arthritis in metatarsophalangeal joints in ultrasound and MRI. There was no epidemiological anamnesis or clinical manifestation or any evidence of SARS-CoV-2 infection (SARS-CoV-2 antibodies were negative) for all patients. Also, there was no anamnesis of any respiratory tract symptoms or diagnosed infection in the last 4 months in all patients. Patients with C. pneumoniae IgM antibodies positive were given a course of clarithromycin. Despite the prescribed course of antibiotics, the skin lesions remained. One patient with arthritis was treated with NSAIDs. Others resolved by themselves without requiring any treatment. Conclusion: Chilblain-like lesions in the skin can be one of the signs of previous SARS-CoV-2 infection despite negative virus antibodies (2). Possible hypothesis is a high production of type I interferon (IFN) associates with early viral control and suppression of antibody production. A strong IFN response can cause skin manifestations (3). Coinfection with other atypical bacteria can intensify immune complexes formation and skin injury (4). This phenomenon can be observed with low levels of C3 and C4 in blood samples.
ABSTRACT
Introduction: Multisystem inflammatory syndrome in children (MISC) associated with COVID-19 presents with fever, severe illness, laboratory signs of inflammation, two or more organ systems impairment, and evidence of SARS-CoV-2 infection. Some symptoms of MIS-C mimic Kawasaki disease, toxic shock syndrome, or secondary hemophagocytic lymphohistiocytosis (HLH) (1). Objectives: To present MIS-C clinical and laboratorical features according to the type and follow-up six weeks later after hospital discharge. Methods: A monocentric retrospective study was done, including hospitalized children who met the criteria for the MIS-C. We analyzed clinical features, laboratory and instrumental examinations, treatment, and duration of hospitalization in the intensive care unit (ICU). Data were analysed using SPSS 20. P value <0.05 was considered significant. Results: 15 patients were included in the study, 73.3 % of whom were male. The mean age was 6.8 ± 4.22 years (1 to 17 years old). Five patients of 15 were identified as Kawasaki-like disease, 3 as toxic shock syndrome, and 1 as secondary HLH. The longest duration of fever (6.33 ± 3.21 days) and hospitalization in ICU (5.67 ± 3.21 days) was in cases with toxic shock syndrome, shortest - MIS-C patients (3.16 ± 1.94 and 0.33 ± 0.51 days) (p= 0.514, p=0.726, respectively). The following organ systems were damaged: hematologic (n=15, 100 %), coagulation (n=15, 100 %), gastrointestinal (n= 14, 93.3 %), lymphatic (n=10, 66.67 %), mucocutaneus (n=8, 53.3 %), cardiac (n=7, 46.67 %), respiratory (n=2, 13.3 %), renal (n=1, 6.6 %). Inflammatory laboratory biomarkers (high CRP, WBC, Neu, ESR) were presented in all MIS-C types except HLH where only ESR was elevated (p=0.062). Highest (CRP, WBC, Neu) mean values were in the toxic shock syndrome (CRP 212 ± 92.9 mg/l, WBC 30.4 ± 22.4 x 109/l, Neu 25.7± 31.8 x 109/l) (p=0.271, p=0.930, p=0.863, respectively). The mean value of PLT was low in HLH (67 x 109/l ) and toxic shock syndrome (88.6 ± 12.6 x 109/l) (p=0.260). Low Hgb was presented in all types except typical MISC (p=0.260). All patients had normal LDH. The highest mean levels of troponin I and D-dimer were found in the toxic shock syndrome (1.36 ± 1.19 mcg/l and 5.5 ± 1.57 mg/l) and Kawasaki-like disease (0.2 ± 0.39 mcg/l and 3.56 ± 1.32 mg/l) (p= 0.801, p=0.125, respectively). All the types were treated with antibiotics (till negative bacteria culture tests), glucocorticoids, and anticoagulants. Treatment with intravenous immunoglobulin was administered with Kawasaki-like disease (80 %) and toxic shock syndrome (33.33 %). Vasoactive support was received by 2 from 3 patients with toxic shock syndrome. 13 patients of 15 came to followup after 6 weeks, no residual symptoms were found. All the patients, who had any cardiac system involvement, had no changes in echocardiography and cardiac markers during the follow-up. Conclusion: Manifestation of MIS-C is nonspecific and there is a wide variety of symptoms, but we observed that all of the patients had a fever, laboratory signs of inflammation, coagulation disorders, almost all of them had gastrointestinal symptoms, moreover mucocutaneous system and lymphadenopathy involvement also was a common sign. All patients, that came to follow-up, had no lasting effects of MIS-C.