Case Report: A New Gain-of-Function Mutation of STAT1 Identified in a Patient With Chronic Mucocutaneous Candidiasis and Rosacea-Like Demodicosis: An Emerging Association.

Purpose: Heterozygous missense STAT1 mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of STAT1 with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis. Methods: Genetic analysis via targeted next-generation sequencing (NGS; NGS panel DIPAI v.1) exploring the 98 genes most frequently involved in primary immunodeficiencies, including STAT1, was performed to identify an underlying genetic defect. Results: NGS identified a novel variant of STAT1, c.884C>A (exon 10), p.T295Y, not previously described. This variant was found to be gain of function using an in vitro luciferase reporter assay. Rosacea-like demodicosis was confirmed by substantial Demodex proliferation observed via the microscopic examination of a cutaneous sample. A review of literature retrieved 20 other cases of STAT1 GOF mutations associated with early-onset rosacea-like demodicosis, most with ocular involvement. Conclusion: We describe a new STAT1 GOF mutation associated with a phenotype of CMC and rosacea-like demodicosis. Rosacea-like demodicosis appears as a novel and important clinical phenotype among patients with STAT1 GOF mutation.

Emerging RNA-Dependent RNA Polymerase Mutation in a Remdesivir-Treated B-cell Immunodeficient Patient With Protracted Coronavirus Disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma.

Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19.

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.

Value of PCR, Serology, and Blood Smears for Human Granulocytic Anaplasmosis Diagnosis, France.

We prospectively examined the effectiveness of diagnostic tests for anaplasmosis using patients with suspected diagnoses in France. PCR (sensitivity 0.74, specificity 1) was the best-suited test. Serology had a lower specificity but higher sensitivity when testing acute and convalescent samples. PCR and serology should be used in combination for anaplasmosis diagnosis.

Progressive Multifocal Leukoencephalopathy after Treatment with Nivolumab.

Progressive multifocal leukoencephalopathy (PML) is increasingly being reported in patients undergoing immunotherapy. We report a case of progressive multifocal leukoencephalopathy after treatment with nivolumab, a PD-1 blocker that is used to restore impaired T-cell responses in patients with cancer and infections. Data for 4 other cases were obtained from pharmacovigilance databases.

Endovascular Treatment of Infected Brachial Pseudoaneurysm in an Intravenous Drug Abuser: A Case Report.

We report the case of a 36-year-old male, admitted in the emergency room with a nonruptured brachial pseudoaneurysm after buprenorphine injection, with no signs of distal acute ischemia. After endovascular treatment with a nitinol covered stent associated with adapted antibiotherapy and 35 days of hospitalizations, the patient was discharged with good short results but stent need to be removed at 6 months for thrombosis and partial exposure through the wound.

Immunoglobulin deficiency in patients with Streptococcus pneumoniae or Haemophilus influenzae invasive infections.

OBJECTIVES: Immunoglobulin (Ig) deficiency is a well-known risk factor for Streptococcus pneumoniae or Haemophilus influenzae infections and noteworthy invasive diseases. However, the proportion of these deficiencies in cases of invasive disease is unknown. The objective of this study was to evaluate the rate of Ig deficiency in cases of invasive disease. METHODS: A prospective study was conducted from January 2008 to October 2010 in two French hospitals. Measurement of Ig levels was carried out in patients hospitalized for invasive diseases. RESULTS: A total of 119 patients were enrolled in the study, with nine cases of H. influenzae and 110 cases of S. pneumoniae invasive disease. There were 18 cases of meningitis, 79 of invasive pneumonia, and 22 other invasive diseases. Forty-five patients (37.8%) had an Ig abnormality, 37 of whom had an Ig deficiency (20 IgG <6g/l, four isolated IgA <0.7g/l, and 13 isolated IgM <0.5g/l), while eight had an elevated monoclonal paraprotein. Nineteen of these 45 patients had a clearly defined Ig abnormality, with five primary deficiencies (three common variable immunodeficiencies and two complete IgA deficiencies) and 14 secondary deficiencies, mainly lymphoproliferative disorders. All these deficiencies were either not known or not substituted. CONCLUSIONS: Humoral deficiency is frequent in patients with S. pneumoniae or H. influenzae invasive disease and Ig dosage should be proposed systematically after such infections.