Clinical association between Kikuchi׳s disease and systemic lupus erythematosus: A systematic literature review

https://doi.org/10.1016/j.semarthrit.2017.01.011Get rights and content

Abstract

Objective

To perform a systematic review of all cases of the association between Kikuchi’s disease (KD) and systemic lupus erythematosus (SLE), and to ascertain the clinical and laboratory characteristics of this association (KD-SLE).

Methods

We conducted a systematic search of the scientific literature until 31 January 2016. For study purposes, only patients aged >14 years, with histologically proven KD, definite SLE and adequate clinical data were included. To compare KD-SLE against isolated KD and SLE, we selected 2 large series of patients with KD and 4 series of SLE patients.

Results

The search found 158 adults with proven KD-SLE. Of these, 113 with sufficient clinical information were included; 86 were women (female:male ratio = 5.0); mean age at diagnosis was 34 years (range: 14–56 years); and an ethnic distribution of 50.5% Asian, 34% Caucasian, and 15% other. KD-SLE patients differed significantly from patients with isolated KD, presenting with a higher frequency of high fever (90%), severe KD (88%), and extranodal manifestations. When compared to patients with SLE, those with KD-SLE presented with a higher frequency of fever and systemic symptoms and a lower frequency of lupus nephritis (22%). SLE had been diagnosed before KD in 18% of cases, simultaneously in 51%, and after KD in 31%. No significant differences were found in terms of time of diagnosis.

Conclusions

While KD-SLE patients share many clinical and laboratory manifestations with SLE, they differ in a lower frequency of lupus nephritis. The relative time of diagnosis of each disease did not affect the clinical expression of KD-SLE.

Introduction

It is estimated that about 12–59% of patients with systemic lupus erythematosus (SLE) develop lymphadenopathies at some point during the course of the disease [1], [2]. In most cases, no biopsy is performed and thus the histological diagnosis remains unknown. The only work published to date in which a biopsy of the lymph–nodes associated with SLE was performed, reported that 20% of cases displayed histological and ultrastructural findings indistinguishable from Kikuchi׳s disease (KD) [3].

Kikuchi׳s disease and SLE share many characteristics, not only histological but also clinical, since both diseases affect young women with greater frequency, and many of the symptoms and laboratory disorders of KD patients are diagnostic criteria for SLE. Anti-nuclear antibodies (ANAs) are positive at the time of diagnosis in 30% of patients with KD [4], [5], [6], [7], and several cohorts of KD patients with prolonged follow-up have shown that many of such patients develop SLE over time [4], [8]. In addition, the treatments shown to be efficient in KD are the same as those used in SLE, that is, corticosteroids, hydroxychloroquine, intravenous immunoglobulins and, in the most severe cases, rituximab [9], [10], [11], [12]. Hence, most authors agree that the association between both disorders runs so deep that it cannot be explained purely by chance [13], [14].

Since the similarity between both diseases is so intriguing, most authors tend to accept that the 2 may coexist, and indeed isolated cases of this association continue to be reported. However, the meaning of this association is still confusing, and the question of whether histiocytic necrotizing lymphadenitis in SLE should properly be regarded as SLE with lupus lymphadenitis [5], [6], [15], [16] or as isolated KD mimicking SLE [17], [18], [19], remains unresolved [20], [21], [22], [23], [24], [25].

Literature reviews of the association between KD and SLE (KD-SLE) conducted to date have been incomplete, and have included some patients who failed to meet SLE or KD criteria [12], [16], [26], [27], [28].

Accordingly, the aim of this study was to conduct a systematic review of every reported KD-SLE case to describe the characteristics of the association, by analyzing the clinical, laboratory, and prognostic differences compared with KD or SLE in isolation.

Section snippets

Bibliographic search criteria

We conducted a systematic search of the scientific literature, without restrictions as to language or type of article until January 31st 2016. In agreement with the current recommendations [29] 4 different databases [MedLine (PubMed), Embase (from 1980), Web of Science and Google Scholar] were used for literature searching. The search was completed by reviewing the references cited in each article. The terms used were “Histiocytic Necrotizing Lymphadenitis,” “Kikuchi” and “Kikuchi׳s disease”

Results of the literature search

A total of 688 studies were identified by the search. After reviewing the title and abstract of all the papers, 554 were ruled out for not meeting the inclusion criteria or for having duplicated information (Fig.). Of the remaining 124, the full text of 111 papers was retrieved. In the case of the other 13 papers (10.5%), a request for the full text was mailed to the corresponding authors without success and, since the abstracts did not provide enough information, these papers had to be ruled

Discussion

This is the first systematic literature review to study the association between KD and SLE. All available data of the 113 patients with KD-SLE were gathered in order to improve the knowledge about the clinical characteristics of this association.

KD-SLE patients differed significantly from KD patients, in that 88% of them met criteria for clinical severity, 87% presented with prolonged high fever and a high frequency of extranodal manifestations, particularly dermopathy, joint disease,

Key points

  • Clinical and laboratory data of patients having Kikuchi׳s disease associated to systemic lupus erythematosus (KD-SLE), are more similar to those of patients having classic SLE than to those of patients having isolated KD.

  • In patients with KD-SLE, male gender and fever are more frequent than in patients with classic SLE, but the prevalence of lupus nephritis is lower than that of patients with classic SLE.

  • Histiocytic necrotizing lymphadenitis in patients with SLE should not be excluded from the

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