Diffuse Lymphadenopathy Syndrome as a Flare-Up Manifestation in Lupus and Mixed Connective Tissue Disease Following Mild COVID-19

Abstract

Case series Patients: Male, 28-year-old • Female, 25-year-old • Female, 68-year-old Final Diagnosis: Lupus Symptoms: COVID-19 pneumonia with deteriration of clinical symptoms • lymphadenopathy Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Rare coexistence of disease or pathology Background: Manifestations of Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, are highly variable among healthy populations. In connective tissue disease patients, the spectrum of clinical manifestations is even broader. In mild COVID-19 patients, diffuse lymphadenopathy (DL) has not been described as a late manifestation, and only severe COVID-19 has been associated with lupus flare-ups. Herein, we report 3 cases of connective tissue disease patients that presented with DL after diagnosis and complete resolution of mild COVID-19 disease. Case Reports: Case 1. A 28-year-old man with inactive lupus, mixed connective tissue disease (MCTD), and a history of lung and cutaneous involvement. He presented with fever, polyarthralgia, and multiple lymphadenopathies 3 weeks after COVID-19 disease resolution. After evaluation, immunosuppressive treatment was initiated, with rapid response. Case 2. A 25-year-old woman with inactive lupus with a history of articular, hematologic, and cutaneous involvement. Four weeks after resolution of COVID-19 disease, she presented with malaise and cervical lymph-adenopathies. After laboratory testing and imaging, she was treated for lupus flare-up, with rapid response. Case 3. A 68-year-old woman with inactive lupus with a history of articular and cutaneous involvement. Four weeks after COVID-19 resolution, she presented with malaise and cervical and axillary lymphadenopathies. After extensive evaluation, immunosuppressive treatment resulted in a rapid response. Conclusions: After 3 to 4 weeks of mild, outpatient-treated COVID-19 and complete resolution of symptoms, 3 patients with connective tissue disease presented diffuse lymphadenopathy associated with inflammatory and constitutional symptoms. Infectious and neoplastic causes were thoroughly ruled out. All patients responded to reintroduction of or an increase in immunosuppressive therapy. We recommend considering the diffuse lymphadenopathy as a possible post-acute COVID-19 syndrome (PACS) manifestation in these patients, mainly when they are in the inactive phase.

A novel case of lupus nephritis and mixed connective tissue disorder in a COVID-19 patient

“…Fever, rash, arthralgia, malaise, acute renal damage, and cytopenias are also symptoms of both disorders. Only four instances were documented to have a flare of lupus during the COVID-19 infection, according to our research [ 21 , 22 , 27 , 46 ].…”

“…Out of the total papers, eleven articles were from Asia [ 19 , 22 , 25 , 30 , 32 , 33 , 36 , 39 , 41 , 43 , 44 ], eight from Europe [ 15 , 17 , 18 , 20 , 24 , 27 , 38 , 45 ], eleven from North America [ 14 , 16 , 26 , 28 , 29 , 34 , 35 , 37 , 40 , 42 , 46 ], two from South America [ 21 , 31 ] and one from Africa [ 23 ].…”

“…Fourteen of the cases had underlying LN. At the same time, there was only one patient who had underlying MCTD [ 21 ]. Moreover, most of the cases had musculoskeletal involvement [ 15 , 19 , 23 , 24 , 27 , 28 , 31 , 34 , 39 ].…”

“…The relation of acute exacerbations of rheumatic and connective tissue diseases with viral infections like HIV, poliomyelitis, and influenza [ 47 , 48 ]. Because of the current COVID-19 pandemic, attention has been drawn to the possible flare-ups seen in patients with SLE and MCTD associated with mild COVID-19 infection, including diffuse lymphadenopathy [ 21 ] and full-blown SLE vasculitis [ 38 ]. A study by Jose L Pablos et al statistically demonstrated how severe COVID-19 infection was a risk factor in diagnosing connective tissue disease, omitting inflammatory arthritis [ 49 ].…”

Clinical evolution of antisynthetase syndrome after SARS-CoV2 infection: a 6-month follow-up analysis

“…Although the effect of COVID-19 on patients with rheumatic disorders has been extensively assessed [ 1 – 3 ], the influence of SARS-CoV2 infection on the clinical course of these diseases is not fully elucidated. Diffuse lymphadenopathy and cerebritis have been reported as short-term flare-up manifestations of systemic lupus erythematosus (SLE) after COVID-19 [ 4 , 5 ]. To the best of our knowledge, however, no data on longer periods are available, neither for SLE nor for other connective tissue diseases.…”