Kikuchi-Fujimoto Disease Following COVID-19 Vaccination: Experience at a Population-Based Referral Center

Objectives: Multiple case reports describe Kikuchi-Fujimoto disease (KFD) following COVID-19 vaccination, but the true nature of this phenomenon is unknown. The purpose of this study was to further assess the relationship between KFD and COVID-19 vaccination at the population level.Methods: Confirmed KFD cases from January 2018 to April 2022 were identified from provincial pathology archives and analyzed in the context of vaccination statistics from public health resources.Results: Our statistical models provide evidence of a temporal association between KFD and both antecedent COVID-19 vaccine administration as well as age-stratified vaccination rates. Eight new cases of plausible COVID-19 vaccine-associated KFD are presented, collectively exhibiting clinical and pathologic features that overlap substantially with those of idiopathic KFD.Conclusions: Our findings indicate that KFD is observed in association with COVID-19 vaccination and suggest that mechanistic studies are warranted.

Kikuchi-Fujimoto Disease: A Case of SARS-CoV-2 Infection Triggering the Rare Disease.

Kikuchi-Fujimoto disease (KFD), or histiocytic necrotizing lymphadenitis, is a rare, benign, and self-limited disease caused by subacute necrotizing regional lymphadenopathy. The etiology is unknown, although virus and autoimmune mechanisms have been proposed. Patients develop enlarged lymph nodes, fever, and, less frequently, extranodal signs. No specific laboratory test contributes to the diagnosis, and lymph node biopsy is the gold standard to define the diagnosis. The treatment is generally with supportive therapy and usually is spontaneously resolved within six months.  In this article, the authors present the case of a 41-year-old female with mild SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection 10 weeks before she was admitted to the emergency department (ED) due to cervical lymphadenopathies and fever lasting over three weeks. Physical examination revealed multiple lymphadenopathies on the submandibular and jugular regions, cutaneous rash, and hepatosplenomegaly. Blood tests showed elevated acute phase proteins, thrombocytopenia, and increased transaminases and lactate dehydrogenase (LDH). Computed tomography (CT) of the neck showed multiple adenopathies at levels I, II, III, and IV according to the Classification for Lymph Nodes from the American Head and Neck Society and American Academy of Otolaryngology on the right side. Excision biopsy was performed and histopathological examination confirmed KFD. A comprehensive analysis performed was unrevealing of an infectious or autoimmune cause and was assumed to be most likely triggered by SARS-CoV-2 infection given the timeframe correlation. KFD diagnosis is challenging and there are few reported cases of association with SARS-CoV-2 in the literature. Although further investigation is still needed to better understand the relation between them, it is important that physicians take SARS-CoV-2 infection and vaccination into consideration in KFD's differential diagnosis.

Kikuchi's Disease Diagnosed by an Excisional Biopsy in a Patient With COVID-19.

COVID-19 is an ongoing pandemic caused by the novel coronavirus SARS-CoV-2. The clinical features of COVID-19 are myriad. Though it is a multisystem illness, it predominantly involves the respiratory system. There have been case reports on rare manifestations of COVID-19, of which COVID-19-related Kikuchi's disease is one of them. To our knowledge, this is the third reported case in the world. We report a lady in her late 60s with COVID-19 infection and secondary bacterial pneumonia, which necessitated ICU admission, having ongoing fever spikes with high inflammatory markers and leukopenia. She was also found to have tender cervical lymphadenopathy on the third week of illness, whose biopsy revealed histiocytic necrotizing lymphadenitis in keeping with Kikuchi's disease. The patient had an uneventful recovery in two weeks without any intervention. The pathophysiology of COVID-19-related Kikuchi's disease is unclear. However, COVID-19 is a viral illness that involves changes in interleukins. The latter is postulated in Kikuchi's disease.

SARS-CoV-2-fertozés okozta Kikuchi-Fujimoto-betegség sikeres gyógyítása.

The Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis) is an autolimited process, which can be caused by viral agents like Epstein-Barr virus, human herpes virus, HIV, B19 parvovirus, paromyxoviruses, SARS-CoV-2, Toxoplasma and Yersinia. The correct diagnosis is based on histological findings. A 45-year-old female patient presented in our ambulatory room with a unilateral neck mass, fever, dysphonia and dysphagia. The patient was double-tested positive for SARS-CoV-2 approximately 1 month before the symptoms started. Before examination, the nasopharyngeal rapid test for SARS-CoV-2 resulted negative. After hospitalization, intravenous antibiotic (Augmentin, 3 × 1.2 g; Klion, 2 × 100 mg) and steroid (Solu-Medrol, 2 × 125 mg) therapy were administered. The neck and chest CT described a right-sided retropharyngeal abscess with bilateral neck lympadenopathy. Urgent tracheotomy, neck dissection and lymph node biopsy were made. The intraoperative findings excluded the presence of the abscess. The histological findings confirmed the necrotizing histiocytic lymphadenitis. Despite of the fact that the Kikuchi-Fujimoto disease is autolimited, we can see that, in this particular case, the lymphadenopathy after the SARS-CoV-2 infection caused a life-threatening situation. The formed extratissular liquid imitated the image of a retropharyngeal abscess. In the searched worldwide literature, similar intervention for this type of process was not described. Tracheotomy, neck dissection and removing the lymph nodes as ,,trigger zones" caused the full recovery of the patient. In the future, we consider important proving and clarifying the correlation between SARS-CoV-2 and Kikuchi-Fujimoto disease. Orv Hetil. 2022; 163(27): 1061-1065.

Multisystem Inflammatory Syndrome in Adults Accompanied with Kikuchi-Fujimoto Disease.

We herein report a case of multisystem inflammatory syndrome in adults (MIS-A) complicated with Kikuchi-Fujimoto disease (KFD). A previously healthy 41-year-old man presented with painful swelling of the cervical lymph nodes, fever, diarrhea, conjunctivitis, edema, and hypotension one month after the onset of asymptomatic coronavirus disease 2019. Laboratory investigations revealed an elevation of CRP, and echocardiography indicated diastolic dysfunction. We diagnosed the patient to have MIS-A. Histopathology of the lymph nodes showed necrotizing lymphadenitis. After the initiation of hydrocortisone and diuretics, his symptoms resolved immediately. This case suggested that post-viral immune dysregulation in MIS-A could play a role in the etiology of KFD.

Pathological Findings in COVID-19 and Non-COVID-19 Vaccine-Associated Lymphadenopathy: A Systematic Review.

COVID-19 vaccine-associated lymphadenopathy (C19-VAL) is increasingly encountered with the widespread use of the vaccine in controlling the outbreak. We aim to characterize the pathological findings of COVID-19 and non-COVID-19 vaccine-associated lymphadenopathy (NC19-VAL). A search for studies that reported pathological findings in vaccine-associated lymphadenopathy on PubMed and Google Scholar was performed on 11 December 2021. C19-VAL studies were pooled for analysis. These studies were split into clinical lymphadenopathy (CL) and subclinical lymphadenopathy detected on imaging (SLDI) for subgroup analysis. A total of 25 studies were related to COVID-19 vaccines, and 21 studies were included in the pooled analysis. The pooled analysis included 37 patients with a mean age of 47.8 ± 19.1 years old, and 62.2% were females. The mean duration from last vaccination to development of CL/SLDI was 14.5 ± 11.0 days. Most were diagnosed as reactive or negative for malignancy (28/37, 75.5%), followed by Kikuchi-Fujimoto disease (KFD) (3/37, 8.1%), florid lymphoid hyperplasia (2/37, 5.4%), and granulomatous inflammation (2/37, 5.4%). Metastases were reported in two patients with a history of malignancy (2/37, 5.4%). Cases with florid lymphoid hyperplasia and KFD were younger than those with reactive changes. A total of 14 studies were related to non-COVID-19 vaccines. Caseating granulomatous inflammation was reported in BCG vaccine-associated lymphadenopathy, while other vaccines were associated with reactive lymphoid hyperplasia, florid post-vaccinal reactions, and KFD. Although most C19-VAL cases were reported as reactive or negative for malignancy, other diagnoses included florid lymphoid hyperplasia, KFD, and granulomatous inflammation. Metastases were reported in lymphadenopathy of patients with a history of malignancy, who had been incidentally vaccinated. In conclusion, C19-VAL can yield different histopathological diagnoses when sampled, most of which require clinical and radiological correlation for optimal patient management.

Baffling Case of a Patient With History of Lupus in a COVID-19 Pandemic.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a myriad of clinical presentations and periodic flares. We present a case of a young lady with a history of SLE who presented with constitutional symptoms 1 week after starting Isoniazid and Rifampin for treatment of latent TB. Her presentation shared similarities with several diseases including TB lymphadenitis, SLE flare, Kikuchi-Fujimoto Disease (KFD) and hemophagocytic lymphohistiocytosis (HLH) posing a diagnostic dilemma. Additionally, she presented not long after the onset of the global COVID-19 pandemic, further expanding the differential diagnosis. She was ultimately diagnosed with a severe SLE flare caused by rifampin induced suppression of the CYP3A4 system, thereby reducing the therapeutic efficacy of steroids. This case highlights the deadly potential of drug-drug interactions, especially in patients with autoimmune conditions.

Kikuchi-Fujimoto Disease Following COVID-19 Infection in a 7-Year-Old Girl: A Case Report and Literature Review.

The coronavirus disease 2019 (COVID-19) symptoms in children are relatively mild and often do not require treatment. Nonetheless, complications caused by the immune response to COVID-19 in children are possible and diverse. We present the case of a 7-year-old girl with persistent fever and lymphadenopathy arising from SARS-CoV-2 infection, diagnosed with Kikuchi-Fujimoto Disease (KFD) on lymph node biopsy. KFD is a rare benign disease, clinically characterized by fever and tender cervical lymphadenopathy affecting posterior cervical lymph nodes. We also reviewed six previously reported cases of COVID-19-associated KFD that occurred in school-aged children and compared them with the present case. The clinical course of COVID-19-associated KFD was similar to that of previous reports of KFD with a favorable prognosis. This is the first report of a school-aged child developing KFD following SARS-CoV-2 infection. KFD should be considered when approaching patients with hyperinflammatory states who present with prolonged fever and cervical lymphadenopathy after COVID-19.

Kikuchi-Fujimoto's Disease or Histiocytic Necrotizing Lymphadenitis Following mRNA COVID-19 Vaccination: A Rare Case.

Kikuchi-Fujimoto disease (KFD), also known as necrotizing histiocytic lymphadenopathy, is a rare and benign lymph node disorder that mainly occurs in young women. It is clinically characterized by fever with tender and painful cervical lymphadenopathy mostly; however, all areas of lymph nodes can be involved. This disorder is often mistaken for malignant lymphoma or infection. The precise pathophysiology of KFD remains unknown, but it is theorized that it may be post-viral or associated with an autoimmune disease. The diagnosis is based on the histological analysis of the excised involved lymph node. The treatment is mainly supportive with favorable outcomes within a few weeks or months. In this case, we present a 24-year-old woman without a past medical history, who consulted for painful bilateral cervical lymphadenopathy associated with fever that has been evolving for one month following the coronavirus disease 2019 (COVID-19) vaccination. The initial diagnostic workup was performed and the diagnosis of KFD was confirmed based on the histopathological findings of the excised lymphadenopathy. Therapeutic management was based on oral corticosteroid treatment with clinical and radiological improvement after a few days without recurrence during follow-up. This article aims to report a rare case of KFD in a patient after receiving the messenger ribonucleic acid (mRNA)-based COVID-19 vaccine. Therefore, this case highlights the possible association between COVID-19 vaccination and KFD and this should be considered in the differential diagnosis.

Kikuchi-Fujimoto disease can present as delayed lymphadenopathy after COVID-19 vaccination.

Following COVID-19 vaccination, ipsilateral axillary and cervical lymphadenopathy may occur, called vaccine-related hypermetabolic lymphadenopathy, which is considered reactive lymphadenopathy. We report here a case of Kikuchi-Fujimoto disease, which occurred three months after vaccination with COVID-19 vaccine. The patient had cervical and axillary lymph node enlargement and a short-term fever that resolved spontaneously after the first and second vaccines. On the 90th day after the first vaccination, the patient developed a high fever and pathologically diagnosed necrotizing lymphadenitis in the axilla, which was diagnosed as Kikuchi-Fujimoto disease. Gallium scintigraphy showed localized swelling and strong uptake in the ipsilateral axilla. It implies the possibility of Kikuchi-Fujimoto Disease in axillary drainage lymph nodes in association with COVID-19 vaccine. Although only a few cases have been reported so far, this case is novel because of its later onset and diagnosis based on pathological and gallium scintigraphy imaging findings.

Self-limiting COVID-19-associated Kikuchi-Fujimoto disease with heart involvement: case-based review.

BACKGROUND: The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of different autoantibodies by SARS-CoV-2 infection. Kikuchi-Fuimoto disease (KFD) as a form of histiocytic necrotizing lymphadenitis of unknown origin. OBJECTIVE: Here we present a rare case of KFD with heart involvement after COVID-19 infection. To our best knowledge only a few cases of COVID-19-associated KFD were published so far. Based on presented case, we summarize the clinical course of KFD and its association with autoimmune diseases, as well we discuss the potential causes of perimyocarditis in this case. METHODS: We reviewed the literature regarding cases of "Kikuchi-Fujimoto disease (KFD)" and "COVID-19" and then "KFD" and "heart" or "myocarditis" by searching medical journal databases written in English in PubMed and Google Scholar. RESULTS: Only two cases of KFD after COVID infection have been described so far. CONCLUSION: SARS-CoV-2 infection can also be a new, potential causative agent of developing KFD.

Kikuchi-Fujimoto Disease Following COVID-19.

Kikuchi-Fujimoto Disease (KFD) is a rare self-limiting condition of unknown etiology. It is characterized by fever, and lymphadenopathy most commonly involving posterior cervical lymph nodes. Although it is of uncertain etiology, it is associated with viral infections and autoimmune diseases. Distinction from lymphadenopathy-associated alternate disorders is crucial to avoid unneeded diagnostic procedures and treatment. KFD is diagnosed based on histopathologic examination of the excised lymph node. The management is supportive with favorable outcomes within a few weeks or months. In this case, we describe a 13-year-old boy who complained of painful cervical lymphadenopathy and fever for more than three weeks following COVID-19. Diagnostic workup has been established and KFD diagnosis made based on the histopathologic features of the involved lymph node. The patient showed complete recovery with no recurrence during follow-up. So, this case highlights the possible association between COVID-19 and KFD during this pandemic and keeping it in the differential diagnosis.

Kikuchi-Fujimoto Disease Post COVID-19 Vaccination: Case Report and Review of Literature.

With the rapid development of various coronavirus disease 2019 (COVID-19) vaccines in a bid to counter and contain the COVID-19 pandemic, unusual and uncommon side effects of COVID-19 vaccination have been increasingly reported in the literature. Ipsilateral lymphadenopathy is a fairly common side effect of vaccination of any kind, with its etiology most commonly related to reactive lymphadenopathy. However, Kikuchi-Fujimoto Disease (KFD) or necrotizing histiocytic lymphadenitis is rarely observed post-vaccination, with only one other case of KFD post COVID-19 vaccination reported to date. We report two more cases of KFD post COVID-19 vaccination in the Asian population, highlighting the clinical course and salient clinical, radiological and histologic findings. In addition, we provide a literature review of the existing cases of lymphadenopathy post COVID-19 vaccination with cytologic and/or histologic correlation.

COVID-19 in a case with Kikuchi-Fujimoto disease.

The accurate diagnosis of Kikuchi-Fujimoto disease can protect children from unnecessary diagnostic procedures and treatments. Also, the co-occurrence of rare diseases with other diseases can improve or worsen the symptoms of the patients.