Posted: March 24th, 2023

Kikuchi disease

Kikuchi disease or histiocytic necrotizing lymphadenitis is one of the rare medical condition in pediatric and adult care, which affects cervical lymph nodes (Dorfman and Berry 329). Pathologists, Dr. Kikuchi and Dr. Fujimoto, originally described the disease in 1972 (Kikuchi 379; Fujimoto and Kozima 920). The condition is considered self-limiting in many cases, but evidence shows that it can be severe and fatal in rare cases. It affects young adults mostly women, with an estimated ratio of men to women of 1:4 (Dumas et al.372), except reports from Far East Asia, which shows the ratio at almost 1:1. (Jung et al.1). The prevalence rate in Saudi Arabia is unknown because of inadequate national statistics. Recent studies in Saudi Hospital revealed an estimated rate of KFD diagnosis of 9 out of 1805 of examined lymph nodes (rate of 0.0049) in one hospital and 15 cases in 2500 examined lymph node (0.006) in another (Al-Maghrabi and Kanaan 319; Alghamdi et al. 24).

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The cause of KFD remains unclear. However, some viruses and autoimmune processes are implicated in the disease process. Viruses, such as EBV are found in almost 50% of the cases (Al-Maghrabi 1111). Genetically susceptible individuals show T-cells and histocytes immune response to an infectious agent or an antigen. The condition is associated with various autoimmune diseases, most commonly SLE. Almost 12% of adult with KFD had suffered SLE before the KFD diagnosis (Dumas et al. 374). On the other hand, KFD may precede an SLE diagnosis, and hence, the need for autoantibodies screening and extended follow up. Other autoimmune diseases associated with KFD are Juvenile idiopathic arthritis, Stills disease, Wegener granulomatosis, Sjogren disease, Graves disease, and Hashimoto disease.

Classically, KFD presents itself with localized swelling lymph node, with or without an acute sign of inflammation. The swelling varies in size, but it is commonly described as huge lymphadenopathy in the pediatric population (Zou et al. 959). Although the condition can affect any lymph nodes, cervical lymph nodes are commonly affected followed by axillary lymph nodes (Dorfman and Berry 329; Wong and Khan 1). Constitutional symptoms vary from case to case with fever being the commonly reported constitutional symptom (Dumas et al. 374). Other Constitutional symptoms which less frequency and rigor include chills, malaise, night sweet, weight loss, and arthralgia.

In some case, extra-nodal symptoms and other rare presentations have been identified, such as arthralgia and hepatosplenomegaly, and cutaneous involvement (Williams et al. 416; Dumas et al. 374). Laboratory findings are nonspecific but common, such as those that show leukopenia, raised ESR and CRP, LDH, ferritin, and abnormal liver enzymes (Perry and Choi 1342). Beside, HLH has been described with some cases. (Sykes et al. 792). The initial presentation (especially febrile cervical lymphadenitis) is usually worrisome and challenging for clinicians because of the need to rule out serious differential diagnosis. Lymphoma and tuberculosis are the common forms of differential diagnoses (Srikantharajah et al. 4; Lo et al. 520; Lahma et al. 3; Wong and Khan 2). Other types of diagnosis common in KFD include bacterial lymphadenitis, cat scratch disease, atypical mycobacterial lymphadenopathy, mononucleosis, and SLE.

Early excisional biopsy can confirm the KFD diagnosis and rule out other serious diagnoses. Major false negatives and easy fragmentation results with FNA might confuse the clinician and create uncertainty. Regardless of the outcome, some authors still recommend FNA (Bosch et al. 144). The immunohistochemical analysis plays an important role in ruling out an unusual malignant cell in lymphomas. The  KFD can mimic the SLE lymphadenopathy in terms of morphology because both have non-neutrophilic necrotic lymphadenitis. However, SLE cases reveal hematoxylin bodies and a spare of CD8-positive T lymphocytes (Al-Maghrabi 1113). Such findings necessitate clinical correlation to diagnose patients with SLE formally. Although there are major advances in technology and imaging, Kikuchi disease diagnosis is still based on the histopathological diagnosis. The role of imaging in KFD is limited to facilitating the choice of the lymph node to excise. PET/CT is a commonly used imaging technique in oncology. Clinicians can use PET/CT with DTPI FDG when a case is suspected to be malignant like in some cases of KFD. The test is used to distinguish between malignant from benign conditions. However, clinicians are hesitant to use PET/CT alone in diagnosing KFD or other benign conditions because PET/CT has false positives, which can cause misdiagnoses of malignant cases as benign conditions (Aoyama et al. 69).

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Medical experts believe that KFD is a self-limiting disease. However, it is known for prolonged symptoms that may last a few months. The symptoms may be severe and affect the quality of life. KFD has been reported to recur (Bi et al. 1167; Jaleel et al.134; Yoo et al. 1195; Honda et al. 3375) and may cause death in some cases. The treatment takes various forms, such as simple observation, nonsteroidal anti-inflammatory medications (NSAID), short course steroid, hydroxychloroquine, or Intravenous Immunoglobulin infusion (Lin et al. e18; Dumas et al. 374).

Empirical data will enhance the understanding of the disease characteristics and treatment options in our center. We will conduct this study to further delineate the clinical features and management, course and outcomes for a cohort of Saudi individuals with Kikuchi-Fujimoto disease, and review histopathological features of Kikuchi disease.

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