Kikuchi Disease-Like Inflammatory Pattern in Cutaneous Inflammatory Infiltrates Without Lymph Node Involvement

Abstract

Kikuchi–Fujimoto disease (KFD) is a rare and benign disorder that usually occurs in young adults with enlarged lymph nodes containing infiltrate of cytotoxic T cells and nuclear debris. It can be a manifestation of systemic lupus erythematosus (SLE) although the strength of this association has varied among studies. Although specific KFD cutaneous lesions are well described, pure cutaneous lesions have never been reported. We studied a series of patients prospectively entered into a database between 2007 and 2014 with skin biopsies showing diffuse or localized inflammatory infiltrates reminiscent of cutaneous KFD, without lymph-node-related KFD. We called these skin lesions “Kikuchi disease-like inflammatory pattern” (KLIP). Twenty-nine patients, whose median age was 49 years at the time of skin biopsy, were selected and retrospectively analyzed using standardized clinical and histology charts. In skin biopsies, KLIP was localized to restricted areas within the inflammatory infiltrate (17%) or diffuse (83%), and was the only histological finding (45%) or accompanied interface dermatitis with or without dermal mucinosis (55%). Clinical dermatological findings varied widely. A definite diagnosis could be established for 24 patients: 75% had connective tissue diseases or vasculitis, mainly cutaneous lupus erythematosus (CLE) (n = 16, 67%), including 5 SLE with satisfying American College of Rheumatology criteria; 3 of the remaining patients had malignant hemopathies. CLE patients were mostly young females with acute (n = 5), subacute (n = 4), or chronic CLE (n = 6) or lupus tumidus (n = 1). Two were classified as having anti-tumor necrosis factor-alpha–induced lupus. Because two-thirds of these patients were finally diagnosed with CLE, we think that KLIP may represent a new histopathological clue for the diagnosis of lupus based on skin biopsy, requiring clinical-immunological comparison to make the correct diagnosis. KLIP should not be considered a variant of classical KFD, but rather as an elementary pattern of cutaneous inflammation, that might be the expression of the same cytotoxic process within skin infiltrates as that involved in KFD. This lesion might reflect a particular T-cell-mediated autoimmune process directed against mononuclear cells within cutaneous lupus infiltrates.

Cutaneous Kikuchi disease-like inflammatory pattern without lymph node involvement is associated with systemic disease and severe features in lupus erythematous: A case-control study

“…These findings are in accordance with the study of Thai et al. 5 showing that the clinical features of KLIP are very heterogeneous.…”

“…In the study of Thai et al, among 16 lupus patients, 8 (50%) had extracutaneous symptoms. 5 In our series, 9/13 had (69%) SLE and interestingly, 6 (46%) had severe haematological, lung, cardiac or renal involvement. In order to assess whether KLIP was associated with SLE and severe systemic features with selected 3/1 age- and sex-matched control lupus patients without KLIP identified from our informatic pathological database blindly from clinical data.…”

“…As Thai et al. suggested KLIP could be a clue for the diagnosis of lupus, 5 we suggest that it may be a clue for progression from CLE to SLE although our limited sample size prevents definite conclusions.…”

“…4 Severe SLE was defined by the presence of at least one severe systemic feature among lupus nephritis, serositis or haematological lupus (immune thrombocytopenia purpura or autoimmune hemolytic anemia). KLIP was defined as a dermal infiltrate or foci within dermal infiltrates, composed of mononuclear cells (CD163þ macrophages including some MPOþ cells, CD123þ plasmacytoid dendritic cells and CD8þ lymphocytes including some cytotoxic granzyme Bþ cells) and nuclear debris without neutrophils 5 (Figure 1). For each case, KLIP was determined as extensive or localized.…”

“…described “Kikuchi disease-like inflammatory pattern” (KLIP) in cutaneous lesions showing histological features similar to KFD without lymph node involvement. 5 In their cohort 67% of patients had either isolated cutaneous lupus (CLE) or SLE. In order to better characterize this entity, we aimed to describe clinical, immunological, pathological features, and the response to treatment of lupus patients with KLIP observed in the skin biopsies.…”