eMedicine Specialties > Dermatology > Reactive & Inflammatory Dermatoses

Cutaneous Kikuchi Disease

Author: Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, New York Medical College-Metropolitan Hospital; Private Practice
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Updated: Feb 12, 2008

Introduction

Background

Kikuchi disease (KD) was reported for the first time in 1972 in Japan by Kikuchi and by Fujimoto and his colleagues. KD is an idiopathic, self-limited necrotizing lymphadenitis. KD commonly presents with cervical lymphadenopathy accompanied by fever, myalgia, neutropenia, and rash in one third of cases. Involvement of extranodal sites is unusual but is described, especially in Asia where KD is more common than in North America or Europe. It is most common in young women.

KD can clinically and histologically mimic Hodgkin disease or high-grade lymphoma. It can also resemble the lymphadenitis of systemic lupus erythematosus (SLE).

For additional information on related topics, see the following:

• Hodgkin Disease (hematology focus)
• Hodgkin Disease (pediatric focus)
• Lymphoma, High-Grade Malignant Immunoblastic
• Lymphadenitis
• Systemic Lupus Erythematosus
• Medscape's Lupus Resource Center

Pathophysiology

Investigators have postulated that apoptosis plays an important part in the pathogenesis of KD. They believe that cytotoxic T lymphocytes are apoptotic effectors as well as target cells and that histiocytes could possibly enhance apoptosis in KD. The trigger of this process may have either a viral pathogenesis or an autoimmune pathogenesis.

Plasmacytoid monocytes have been suggested to play a role in the pathogenesis of KD via a cell-mediated cytotoxic immune response.

KD has been reported in 2 nontwin sisters with HLA-identical phenotypes, who presented 10 years apart.

Zhang et al¹ described an association between parvovirus B19 and Kikuchi-Fujimoto disease. Specifically, from one case of KD, they reported that the in situ hybridization and immunohistochemistry double-staining assay results revealed that parvovirus B19 – infected cells were mainly lymphocytes and a small number of histiocytes.

Frequency

United States

KD is rare.

International

KD is more prevalent among Asians and is a relatively common disorder among Koreans.

In Taiwan, Chuang et al² studied 64 patients younger than 18 years with pathologic proof of KD. In this group of 35 males and 29 females, the age range was 2-18 years, with a median age of 16.63 years for the males.

The female patients had cervical lymphadenopathy, and 1 had generalized lymphadenopathy. In 50% of patients, the lymph nodes were painful, tender, or both. In 82.5% of patients, the lymphadenopathy was unilateral. In 32.8% of patients, the lymphadenopathy was associated with fever.

Rash, hepatomegaly, or weight loss occurred in less than one third of the patients. Leukopenia was present, and 3% had leukocytosis. Mild liver dysfunction was present in approximately 25% of patients. Most patients had normal virologic or immunologic study results. Patients with prolonged fever were more likely to have leukopenia (P <.05). All 64 patients had remissions of KD, but 1 developed SLE 5 years later and another had a vasculitis syndrome 2 years later.

Rau and Kini³ reported 20 patients with KD from an Indian referral center, one of whom had skin involvement.

Mortality/Morbidity

• KD is benign; thus, besides the pain associated with the condition, it has minimal mortality and morbidity.
• If KD occurs in patients who have undergone transplantation, it can be fatal.
• KD can evolve into lupus, in which case morbidity and mortality are substantially increased.

Race

This disease affects Asians more than other races, but it has been reported worldwide.

Sex

Females are more commonly affected than males, with a female-to-male ratio of 4:1.

Age

KD affects a wide age range from 10 months to 75 years, with a mean patient age in the third decade.

Clinical

History

KS commonly presents with cervical lymphadenopathy accompanied by fever, myalgia, and neutropenia. A rash occurs in one third of patients. The range of symptoms and abnormalities is wide; Lima et al⁴ described a case of a 27-year-old woman presenting with fever, urinary tract infections, skin rash, polyarthritis, generalized lymphadenopathy, pancytopenia, hepatic cytolysis and cholestasis, abnormal coagulation test results, and elevated serum lactate dehydrogenase levels.

KD can be associated with cervical pain in as many as one half of patients. Most cases resolve within 2 months, but recurrences have been reported. The time from onset of symptoms to diagnosis ranges from 1-24 months.

• Harris et al⁵ reported a case of a dengue viral infection causing an abnormal immune response leading initially to KD and later to SLE.
• KD has been associated with a case of Still disease.
• KD has also been linked to parvovirus B19 and antiphospholipid syndrome.
• Fever is present in 33-50% of patients.
• Constitutional symptoms may include diarrhea, chills, sweats, nausea, vomiting, chest pain, abdominal pain, and rash.
• Childhood hemophagocytic syndrome associated with KD in children has been reported.
• Brachial plexus neuritis and mononeuritis multiplex have been reported in association with KD.
• Mycobacterium szulgai lymphadenitis mimicking KD has been reported in Thailand.
• Bilateral panuveitis has been reported as a possible association with KD.
• KD with aseptic meningitis has been reported.
• One case report has associated KD with brucellosis.
• In 2003, Viseux et al⁶ reported KD associated with cutaneous manifestations evoking Wells syndrome.
• Corynebacterium pseudotuberculosis necrotizing lymphadenitis is an infectious cause of necrotizing lymphadenitis that should not be confused with KD.⁷
• Carlson et al⁸  noted a cefprozil-induced rash in a patient with infectious mononucleosis and a minocycline-associated drug hypersensitivity syndrome for which histology studies demonstrated an acute vacuolar interface superficial and deep perivascular and interstitial lymphocytic dermatitis. CD8⁺ lymphocytes predominated in conjunction with non-neutrophilic nuclear (karyorrhectic) debris and numerous small CD68⁺ and CD123⁺ monocytes — findings similar to those of KD. Both patients had serologic but not cutaneous polymerase chain reaction evidence of active and chronic-active Epstein-Barr virus (EBV) infection.

Physical

KD can affect the lymph nodes, the liver, the spleen, and the skin. Physical findings involve these organ systems.

• Skin changes occur in about one third of patients (16-40%) and are often of a nonspecific nature.
  • Most cutaneous lesions present as erythematous macules, papules, plaques, nodules, or ulcers on the upper part of the body, such as the trunk, the upper extremities, and the face.
  • Kim et al⁹ reported a case of Kikuchi-Fujimoto disease with a papulopustular eruption over the torso, arms, and legs.
  • Imai et al¹⁰ described a patient with lip edema. This patient had facial, neck, and arm desquamation and erosions and transient indurated erythematous papules. Kaur et al¹¹ described a patient with KD with erythema multiforme–like lesions and a facial rash.
  • In some cases, KD is associated with cutaneous lupus erythematosus.
  • Rao et al¹²  presented a case of a 32-year-old woman with fever and swelling in the axillae for 8 weeks, facial erythema, fluid-filled lesions on the trunk, oral ulcers, crusting of the lips, and a 3-day history of injection and watering of the eyes who ultimately was diagnosed with KD and SLE.
  • A case of KD manifested with eyelid edema.¹³
  • Letawe et al¹⁴ noted arciform papulonodular lesions on the face in a patient with KD.
  • Erosion and ulcerated gingivae have been reported.
• KD with leukocytoclastic vasculitis has been reported in a 10-year-old girl.
• KD usually demonstrates adenopathy at a single site, predominantly in the cervical region, but it may also affect other and multiple lymph node regions, including axillary, supraclavicular, mediastinal, inguinal, intraparotid, iliac, celiac, and peripancreatic groups. Pain and tenderness of the lymph nodes may be present. Reports note generalized lymphadenopathy.
• Splenomegaly and hepatomegaly are rare.
• Kim and Oh¹⁵ noted KD in association with a transient eruption in a 7-year-old boy.

Causes

The etiology of KD is not yet well known. Viral triggering on KD has been suggested as its cause. In particular, EBV and parvovirus B19 have been linked to cases of KD.

• Huh et al¹⁶ used polymerase chain reaction tests for herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, or EBV on the lymph nodes of 12 patients with KD and could not isolate viral material.
• Aqel et al¹⁷ performed immunofluorescence studies on tissue from involved and uninvolved cheek and forehead samples. They found immunoglobulins and complement deposited at the dermoepidermal junction and in dermal blood vessel walls. These researchers believed these findings supported an autoimmune basis for KD.

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