Y Küçükardali, Z Çankir, C Top, S Özkan, S Nalbant, O Öncül, H Baloglu, M Danaci
ards, cardiac, cardio-pulmonary support, care unit, critical care, education, emergency medicine, fever, hemodynamics, intensive, intensive care medicine, kikuchi's disease, lympadenitis, medicine, multiorgan failure, neuro, patient care, pediatric, rash, respiratory failure, surgical i, ventilation
Y Küçükardali, Z Çankir, C Top, S Özkan, S Nalbant, O Öncül, H Baloglu, M Danaci. Kikuchi's Disease: Report Of One Case And An Overview. The Internet Journal of Emergency and Intensive Care Medicine. 2002 Volume 6 Number 2.
We describe , to our knowledge, the first Turkish patient with Kikuchi’s
disease which is characterized by histiocytic necrotizing lymphadenitis with
skin, liver, and lymph node involvement. The diagnosis was based on
histopathological findings in open biopsy.
Our patient was a young man, who had bilaterally, tender axillary
lymphadenopathy, fever, arthralgia, cutaneous rash, and fatigue. Laboratory
analyses identified an elevation of C-reactive protein 96 mg/L, lactate
dehydrogenase 2558 U/L, aspartate transaminase 404 U/L, alanine transaminase
up to 196 U/L. The erythrocyte sedimentation rate was 80 mm/h. Hematologic
investigations revealed mild leukopenia, 3.4 x 109 /L, neutropenia, 1.4 x 109
/ L, and hemoglobin 99 g/L. Viral, Toxoplasma, Mcoplasma, Brucella, and
syphilis serology were negative. Also immunological and rheumatological tests
were normal. A biopsy from an axillary lymph node findings confirmed the
diagnosis of Kikuchi’s diseases. After the diagnosis, the patient
received oral corticosteroid therapy, and one month after the onset of
therapy he was totally symptomless and lymph nodes was normal.
The cause of Kikuchi’s disease is unknown. A viral or postviral
hyperimmune reaction has been proposed as its etiology. It is uncommon cause of
fever of unknown origin. Malignant lymphoma and systemic lupus erythematosus
should be considered differential diagnosis. Early recognition of
Kikuchi’s disease will minimize potentially harmful and unnecessary
evaluations and treatments.
The disease was first described in Japan in 1972, but in Turkey, until now, no cases has been reported. Kikuchi disease or histiocytic necrotizing lymphadenitis is a benign, self-limiting condition of unknown cause, which usually affects female patients under the age of 30 years. It presents most often with cervical lymphadenopathy which may be tender and can be accompanied by fever and upper respiratory tract symptoms. Laboratory investigations are usually unremarkable except for mild neutropenia and lymphocytosis in some cases.
Morphologically, it is characterized by a necrotizing lymphadenitis associated with karyorrhexis and by a paucity, or more commonly , an absence of granulocytes. Open biopsy is the only reliable way to establish the diagnosis, but according to some authors fine needle biopsy may also be helpful (1). Malignant lymphoma is the most important differential diagnosis in both clinical and histological terms.
The cause of Kikuchi disease is unknown. Some kind of viral or postviral etiology has been proposed. The association of the disease with several infectious agents has been investigated. These agents include Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, human herpesvirus-6 (2) , human immunodeficiency virus (3), Yersinia enterocolitica (4) and Toxoplasma (5).However, no convincing causal relation berween these infectious and Kikuchi's disease has been shown yet. There have also been reports of a possible link between Kikuchi's disease and systemic lupus erythematosis (6) It has been proposed that Kikuchi's disease is a nonspecific hyperimmune reaction to a variety of infectious, chemical, physical and neoplastic agents (7,8).
We present the clinicopathological findings of first Turkish patients with Kikuchi's disease.
A 21 – year -old man , had been well until two months earlier, when axillary lymphadenopathy developed, soon followed by swelling, pain, and redness in the axilla bilaterally. Two weeks later, also his temperature increased to 39 degrees C almost every day, accompanied by fever, shivering, malaise, arthralgia and loss of appetite. Ten days before admission, the patient was admitted elsewhere. Ceftriaxon was been prescribed , but fever occurred, with worsening swelling and pain. Culture of blood, sputum and urine were negative. Lymph node biopsy showed necrotizing lymphadenitis. Then the patient was transferred to our hospital, for the differential diagnosis of necrotizing lymphadenitis and fever of unexplained origin.
His family and past medical history was unremarkable. On examination, the patient appeared acutely ill. The temperature was 40 degrees C , the pulse was 126, and the respiration were 22 per minute. The blood pressure was 120/70 mmHg. Patch, cutaneous rash were present over the anterior chest wall. Tender lymph nodes were palpated in the axillary regions bilaterally. Ultrasonographic finding showed a conglomerate of hypoechogenic lymph nodes, with enlarged lymph glands. Laboratory analyses identified an elevation in C-reactive protein up to 96 mg/L, lactate dehydrogenase up to 2558 U/L, aspartate transaminase up to 404 U/L, alanine transaminase up to 196 U/L. The erythrocyte sedimentation rate was 80 mm/h. Hematologic investigations revealed mild leukopenia, 3.4 x 109 /L, neutropenia, 1.4 x 109 / L, and hemoglobin was 99 g/L. Viral (rubella, CMV, HSV-1, EBV, HBV) Toxoplasma, Mcoplasma, Brucella, and syphilis serology were negative. Also immunological and rheumatological tests were normal. These tests included antinuclear antibody, DNA antibody, rheumatoid factor and the levels of serum C3 and C4 as well as IgG, IgA and IgM. The urine and sputum cultures and three blood cultures were negative. Urine was positive (++) for protein and had a specific gravity of 1022; the sediment contained 2 to 4 red cells and 5 to 8 white cells per high-power field. No evidence of tuberculosis was found on staining, culture or adenosine deaminase tests. There was hepatomegaly seen in ultrasonography of the abdomen.
A biopsy from an axillary lymph node that had been taken previously re examined by experienced pathology. The lymph nodes showed a proliferative and ,necrotizing process centered in the paracortex and characterized by patchy circumscribed or confluent areas of necrosis associated with karyorrhexis and remarkable by the absence of granulocytes and paucity of plasma cells. These findings were confirmed the diagnosis of Kikuchi's disease. Histopathological examination of the erythematous skin lesions revealed leucocytoclastic vasculitis (LCV). The patient was treated with oral steroid medication (deflazocort 60 mg / day) . One month after the onset of his therapy the fever and lymphadenopathy had disappeared and since then, the patient has been symptomless. Laboratory findings also reverted to normal. Laboratory tests which were performed on the second, third and thirtieth hospital days , were demonstrated on Table. 1.
This patient has many clinical manifestations of systemic lupus erythematosus: generalized lymphadenopathy, erythematos skin lesions , unexplained fever, arthralgia and weight loss. But diagnosis is not confirmed by the absence of autoantibodies, anti-native DNA antibodies which are relatively specific for the diagnosis of systemic lupus erythematosus, and hypocomplementemia. The relation between Kikuchi's disease and SLE is not yet completely understood and remains complex. Moreira also reported a case of Kikuchi disease revealed by malar rash, fever, arthritis and lymphadenopathy, suggesting systemic lupus erythematosus like our patients (10). Dorfman said that, although the differential diagnosis may include several non-neoplastik conditions such as systemic lupus erthematosus, toxoplasmic lymphadenitis, infectious mononucleosis and cat-scratch disease, main diagnostic problem encountered by the referring histopathologist is to distinguish Kikuchi disease from non-Hogkin's lymphoma (9).
Although a proportion of cases was misdiagnosed as Hodgkin's disease we found that the absence of Reed-Sternberg cells and the lack of the characteristic background cell population should have excluded this possibility.
Our patient had cutaneous lesions that were characterized as rash over the anterior chest wall and disappeared within 3 weeks. Histopathological examination of skin revealed LCV. LCV may be the presenting sign sign in many different clinical disorders or it can be idiopathic. All patients must be screened for underlying causes, including drugs, infection, systemic autoimmume disease or neoplasm. Initially, the pathogenesis of LCV is immune complex related, but in its later stages different pathogenetic mechanisms may intensify the reaction and lymphocytes may predominate in the infiltrate. A coetaneous involvement has been observed in 30 % of patients with Kikuchi's disease (11). Cutaneous involvement of the disease may be different pattern like an angiocentric infiltration by mononuclear cells among which plasmacytoid cells and cariorhexis that described by Letawe (12). The skin lesions may be maculopapular, rubellaform, drug eruption, urticaria, or disseminated erythema. But none of the lesions reported is, however, pathognomonic (13).
Some patients may also show hepatosplenomegaly . Liver biopsy revealed reactive changes and hepatic enzymes reverted to normal with in one mount in our patients.
18 Kikuchi diseases were reported in the literature from different country in 2000. The age of the patients ranged from 13 to 40 years. Most of them were predominance of female patients
(F/M: 16/2). The most common presenting symptoms were cervical ( 15 patients), followed by axillary ( 3 patients) and inguinal lymphadenopathy. Two patients has developed lymphoma and three has SLE after 2 years of follow-up.
As a result, symptoms of the disease can be very distressing to the patient, especially the lingering fever and fatigue and early recognition of Kikuchi's disease will minimize potentially harmful and unnecessary evaluations and treatments.