Practice Essentials
Kikuchi disease (KD), also termed Kikuchi-Fujimoto disease or benign histiocytic necrotizing lymphadenitis, is a rare disorder most common in Asian females that presents with systemic symptoms and cervical lymphadenopathy. Patients with KD can have cutaneous manifestations, known as cutaneous KD. A wide variety of morphologies exist, and biopsy is required for diagnosis. KD is a self-limited condition; however, patients with KD, and especially cutaneous KD, have an increased risk of cutaneous and/or systemic lupus erythematosus and thus should have appropriate long-term follow up and monitoring.
Background
Benign histiocytic necrotizing lymphadenitis or Kikuchi disease (KD) is a rare disease of unknown etiology first reported in 1972 in Japan by Kikuchi and later that year by Fujimoto and his colleagues. [1, 2] KD is most common in Asians and typically affects females younger than 40 years. It presents with persistent low-grade fever and enlargement of the cervical lymph nodes. [3, 4, 5, 6] The presence of lymphadenopathy with systemic symptoms often raises concern for lymphoma, prompting lymph node biopsy. Lymph node histopathology of KD is diagnostic, revealing characteristic necrosis, histiocytic infiltration, and karyorrhectic debris without neutrophils. [7] In up to one third of cases, KD may have skin findings. [3] This subset of disease is known as cutaneous KD. Numerous reports have cited an association between KD and systemic and cutaneous lupus erythematosus, with a diagnosis of lupus erythematosus either preceding or following the diagnosis of KD. [8, 9, 10, 11, 12] Fortunately, KD is usually self-limited, resolving on its own in 1-4 months. Systemic steroids and/or NSAIDs can be given to hasten resolution if symptoms are severe. [9, 13] Patients are expected to make a full recovery, although they should be monitored for the development of lupus erythematosus.
Pathophysiology
The pathogenesis of Kikuchi disease (KD) is unknown. Investigators have postulated that apoptosis plays an important part in the pathogenesis of KD, as apoptosis leading to necrosis is a prominent finding in both lymph nodes and skin affected by KD. Activated cytotoxic T cells, plasmacytoid monocytes, and CD68-positive histiocytes are commonly found on biopsy, suggesting that these cell types play a role in initiating and/or maintaining the inflammation that ultimately leads to apoptosis and necrosis. An autoimmune or viral trigger may be the inciting event that initiates the inflammatory cascade, although no antigen or viral trigger has been consistently identified. [14]
Etiology
The etiology of Kikuchi disease (KD) is not yet known, but most authorities favor either an infectious or an autoimmune etiology. The association of KD with lupus erythematosus especially has prompted consideration of an autoimmune etiology for KD, but as yet, no pathogenic antigen has been identified. Reports have also described viral triggers for KD, including Epstein-Barr virus, parvovirus B19, and human herpesvirus 8, but no definitive causative pathogen has been identified and other studies failed to isolate viral material from lymph nodes of patients with KD. [7, 15, 16] It is possible that the etiology is related to an environmental trigger in a genetically susceptible individual that leads to the initiation of an autoimmune-mediated inflammatory process. Studies have demonstrated immunoglobulins and complement deposition at the dermoepidermal junction and in dermal blood vessel walls, which may support an autoimmune basis for KD. [17] Furthermore, studies have demonstrated an increased risk of disease in patients with certain HLA haplotypes, specifically HLA-DPA1 and HLA-DPB1. These alleles are more common in Asian patients, which helps explain the predominance of disease in Asia and supports the idea that there is a genetic susceptibility to this disease. [9]
Epidemiology
Frequency
Kikuchi disease (KD) is more prevalent among Asians and is a relatively common disorder among Koreans. [18] It has been reported worldwide, but it is rare in European countries and the United States. [9] Cutaneous KD may arise in 16.6-40% of patients with KD, [19] with one study of 91 patients reporting cutaneous involvement in a third of cases. [3]
Race
This disease affects Asians more than other races, but it has been reported worldwide. [9]
Sex
Females are more commonly affected than males, with a female-to-male ratio of 4:1. [3, 20]
Age
KD can affect a wide range of ages from childhood to adulthood, with a mean patient age in the third decade. It is most common in patients younger than 40 years. [9, 21]
Prognosis
Kikuchi disease (KD) is a self-limited condition. Therefore, the prognosis overall is excellent. Most studies site recurrence rates of around 3-4%, [9, 14] although one study had a higher recurrence rate of 20%. [3]
Besides the pain associated with the condition, it has minimal mortality and morbidity. However, KD can evolve into lupus erythematosus, in which case morbidity and mortality are substantially increased. Patients who have cutaneous KD may have an increased risk of developing systemic lupus erythematosus and thus should be closely monitored. [3] One study by Dumas et al examined 91 patients with KD. [3] Of these patients, 12% had a known diagnosis of systemic lupus erythematosus at time of their KD diagnosis and another 13% of patients were diagnosed with systemic lupus erythematosus at the same time as KD or within the year following their KD diagnosis. This study found that cutaneous disease, arthralgias, weight loss, and a positive antinuclear antibody titer greater than 1/320 were significantly associated with an increased risk of developing systemic lupus erythematosus after a diagnosis of KD.
Patient Education
Patients should know that Kikuchi disease (KD) is a benign and self-limited condition. However, they should also be aware of the association of KD with systemic and/or cutaneous lupus erythematosus and that the risk may be increased if they have cutaneous KD. [3]
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Very high magnification micrograph of histiocytic necrotizing lymphadenitis, also known as Kikuchi disease. Hematoxylin and eosin stain. Courtesy of Nephron (own work), via Wikimedia Commons.
