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Letter to the Editor
Cryoglobulinemic purpura and COVID-19 infection
Púrpura crioglobulinémica e infección por COVID-19
Javier Martín Moyano
Servicio de Medicina Interna, Hospital Virgen de la Victoria, Málaga, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The patient is a 54-year-old woman&#44; a former smoker&#44; with a history of hypertension&#44; asthma and osteoarthritis&#46; She presented with a COVID-19 infection in early June 2021 with fever&#44; dry cough and arthralgia&#46; Following resolution of the symptoms at home&#44; she visited the emergency department at the end of June for generalised arthralgia&#44; skin purpura associated with burning pain in the lower limbs and buttocks&#44; pitting oedema up to the thighs&#44; low-grade fever&#44; and hypertension&#46; Additional tests showed microcytic anaemia with transfusion requirements&#44; a nephritic syndrome with C3 complement consumption and elevated RF&#44; with ANCA and other autoimmune tests with negative results&#46; Serology was negative for syphilis&#44; herpesvirus 2&#44; HIV&#44; HBV&#44; HCV&#44; and Epstein-Bar virus &#40;EBV&#41;&#44; with positive IgG for herpesvirus 1 and CMV&#46; A transthoracic echocardiogram showed moderate pericardial effusion and septal hypertrophic cardiomyopathy&#44; with no findings of infiltrative disease on cardiac MRI&#46; A full-<span class="elsevierStyleItalic">body</span> CT ruled out neoplasm and ground glass interstitial infiltrates were detected with possible association to previous viral infection&#46; The patient experienced clinical and laboratory improvement with symptomatic treatment&#44; a tapering corticosteroid regimen and requested discharge due to transfer of home&#46; In August she returned to the hospital with the same symptoms&#44; was admitted and underwent a new study&#46; Nephritic syndrome increased pericardial effusion to moderate-severe and resolution of pulmonary infiltrates on CT scan were observed&#46; Additionally&#44; IGRA and cryoglobulins were requested&#44; which were positive&#59; a skin biopsy reported leukocytoclastic vasculitis and a kidney biopsy detected cryoglobulinaemic membranoproliferative glomerulonephritis&#46; The pericardial fluid study was compatible with exudate&#44; without microbiological isolation&#44; with negative TB PCR and absence of malignant cells&#46; The study was completed with an electromyogram which revealed sensory-motor axonal polyneuropathy and a PET-CT scan which ruled out neoplastic disease or high-grade metabolic lesions&#46; The definitive diagnosis was mixed cryoglobulinaemia with membranoproliferative glomerulonephritis&#44; leukocytoclastic vasculitis and sensory-motor axonal polyneuropathy&#44; with a recent history of COVID-19 infection&#46; Severe pericardial effusion possibly related to previous COVID-19 infection&#46; Latent tuberculosis&#46; Treatment of cryoglobulinaemic syndrome will depend on the severity and&#44; in any case&#44; treatment of the underlying cause should be considered when it exists&#46; Mild cases generally do not require immunosuppressive treatment and as the case becomes more severe&#44; treatment will consist of corticosteroids and rituximab&#44; considering corticosteroid pulses and plasmapheresis in case of a life-threatening situation or organ compromise&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The patient continued treatment with antihypertensives&#44; analgesics&#44; and anticonvulsants for neuropathic pain&#46; As the origin of the pericardial effusion was uncertain&#44; corticosteroids were not started and tuberculostatic agents were prescribed until the results of the mycobacterial fluid culture were negative&#46; The patient showed clinical improvement&#44; returned to normal laboratory parameters&#44; and continued follow-up in outpatient visits with good clinical progression&#44; stabilisation of renal function and adjuvant treatment for lower limb neuropathy&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Numerous cases of autoimmune disease have been described in association with COVID-19 infection&#44; including several types of vasculitis&#44; but no cases of cryoglobulinaemic vasculitis have been described so far&#44; so this is an interesting case to add to the literature&#46; Cryoglobulins are immunoglobulins &#40;Ig&#41; that precipitate at low temperatures&#44; their presence in blood is called cryoglobulinemia and when they produce symptoms&#44; the term cryoglobulinaemic syndrome is used&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This can be suspected in patients with arthralgia&#44; skin purpura or ulcers&#44; glomerulonephritis and peripheral neuropathy&#44; such as our patient&#46; Type I cryoglobulinaemia is composed of monoclonal Ig&#44; it is associated with plasma cell dyscrasias and lymphoproliferative syndromes&#44; while types II and III are grouped under the term mixed cryoglobulinaemia&#44; are composed of polyclonal &#40;III&#41; or monoclonal and polyclonal &#40;II&#41; Ig and are associated with infections&#44; systemic autoimmune diseases and lymphoproliferative syndromes&#46; Regarding infectious processes&#44; chronic HCV infection stands out&#44; although cases with HBV have also been described and occasionally after infection with HIV&#44; CMV&#44; EBV and parvovirus B19&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Viral infections trigger an immune response in the host organism and can sometimes unbalance immune tolerance&#44; giving rise to autoinflammatory and autoimmune disorders&#46; In this sense&#44; the COVID-19 virus has been related to diseases such as Guillain-Barr&#233; syndrome&#44; autoimmune haemolytic anaemia and numerous vasculitides&#44; such as paediatric inflammatory multisystem syndrome &#40;a vasculitis with characteristics similar to Kawasaki disease&#41; or chilblain&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Regarding the latter&#44; cases of cryofibrinogenemia have been described in relation to the COVID-19 pandemic&#44; as demonstrated by the G&#243;mez-Fern&#225;ndez et al&#46; series&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This vasculitis is characterised by the formation of erythematous plaques or purpuric macules located on the feet and toes&#46; Cryofibrinogen precipitates are seen only in plasma&#44; may contain Ig&#44; but are composed primarily of fibrinogen&#44; fibrin&#44; fibronectin&#44; or fibrin degradation products&#46; One difference with cryoglobulins is that cryoglobulins are formed in serum and plasma&#46; In relation to cryoglobulinemia&#44; flares have been described after vaccination against COVID-19<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> in patients previously diagnosed with cryoglobulinemia&#44; but there are no <span class="elsevierStyleItalic">de novo</span> cases described after infection&#46; Our patient presented with a cryoglobulinaemic syndrome after infection&#44; it is unclear whether the COVID 19 infection could be related to the imbalance in immune tolerance and cryoglobulin formation or act as a precipitant of a previously undiagnosed latent condition&#46; What does seem clear is the link between COVID infection and cryoglobulinaemic syndrome&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0015" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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Article information
ISSN: 23870206
Original language: English
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