Kikuchi disease

* Context.-Kikuchi-Fujimoto disease is a benign disorder, predominantly affecting young women with a predilection for cervical lymphadenopathy. Although the disease has been recognized worldwide, to our knowledge no cases have been reported previously from Nepal.

Objectives.-To determine the prevalence of Kikuchi-Fujimoto disease in Nepal and to analyze clinicopathologic features.

Methods.-We reviewed 6 cases of Kikuchi-Fujimoto disease recorded at 3 different hospitals in Nepal during a period from June 1998 to June 2002. Clinical data and histopathology are presented.

Results.-This study included 5 females and 1 boy, aged 13 to 32 years. These patients presented with prolonged fever and lymphadenopathy. The 5 female patients had cervical lymphadenopathy, and the boy had axillary lymphadenopathy. Complete blood counts revealed raised erythrocyte sedimentation rates in all patients and anemia in 2 patients. The size of excised lymph nodes (in greatest dimension) ranged from 1.5 to 5 cm. Typical histologic features were seen, namely, architectural effacement due to presence of pale nodular lymphohistiocytic foci with karyorrhectic debris, coagulation necrosis, eosinophilic debris, and absence of granulocytic infiltration. In a follow-up of the cases, disease recurrence was not found.

Conclusion.-Our study emphasizes that Kikuchi-Fujimoto disease should be considered as one of the differential diagnoses in patients with prolonged fever and cervical lymphadenopathy and that it should be differentiated from tuberculous lymphadenitis in regions where tuberculosis is prevalent.

Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis) was first described in Japan in 1972(1,2) and is now recognized worldwide3-5 with a higher prevalence in the east Asian population. It is a benign disorder, predominantly affecting young women6 with a predilection for cervical lymphadenopathy. The etiology of this disease is unknown, although several microorganisms, such as Epstein-Barr virus,7,8 human herpesviruses,8,9 toxoplasma,10 and Yersinia enterocolitica," have been suspected. This disease manifests clinically with cervical lymphadenopathy, fever,3,5 weight loss, loss of appetite, nausea, vomiting, diarrhea, chest pain, splenomegaly,3,5 and hepatomegaly.3,5 Leukopenia5,12 and atypical lymphocytosis12 also may occur.

The diagnosis is based on characteristic histopathologic findings. The lymph node consists of multiple round to irregular, pale nodular foci with karyorrhectic debris, pre-dominantly in the paracortical region13; prominent mottling by histiocytes or transformed lymphoid cells in the nonpathologic areas14; and variable amounts of nuclear debris,14 plasmacytoid monocytes,14 and zones of coagulative necrosis. The pale nodules are composed of phagocytic and nonphagocytic histiocytes, small lymphocytes, and immunoblasts intermixed with eosinophilic granular debris and basophilic karyorrhectic debris." Absence of neutrophilic infiltration is the rule.4

Although it is recognized worldwide, no cases have been reported from Nepal to date. To the best of our knowledge, this is the first study regarding Kikuchi-Fujimoto disease in Nepal.

MATERIALS AND METHODS

Six cases of Kikuchi-Fujimoto disease were recorded from 3 different hospitals in Nepal from June 1998 to June 2002. Three cases were selected from the records of Patan Hospital, United Mission to Nepal, Lalitpur; 2 cases were from Tribhuvan University Teaching Hospital, Kathmandu, Nepal; and 1 case was from Advanced Diagnostic Centre and Polyclinic, Kathmandu, Nepal. Clinical findings, treatment, and follow-up data were reviewed from the medical records at these hospitals.

RESULTS

The clinicopathologic features of these 6 cases are summarized in the Table. Five patients described in this study were female and 1 was a boy. The mean age at diagnosis was 21.67 years, with a range of 13 to 32 years. Most patients presented with fever of more than 1 month's duration and cervical lymphadenopathy. One patient developed axillary lymphadenopathy without any other symptoms. Cervical lymphadenopathy was unilateral in 3 cases and bilateral in 2 cases. Most patients received courses of antibiotics prior to biopsy. In 5 cases, a clinical diagnosis of tuberculosis was made, as it is one of the most common causes of lymphadenitis in our region. Most patients were treated with steroids and improved. The patient in case 6 had only lymphadenopathy and did not receive any treatment. Complete blood counts revealed raised erythrocyte sedimentation rates (18-56 mm/h in the first hour) in all patients and anemia in 2 patients (cases 4 and 5). The size of excised lymph nodes in greatest dimension ranged from 1.5 to 5 cm (Figure 1).

On histologic examination, all lymph nodes showed architectural effacement due to presence of pale nodular foci (Figure 2) with karyorrhectic debris, predominantly in the paracortical region. These pale nodules were composed of phagocytic and nonphagocytic histiocytes, plasmacytoid monocytes, immunoblasts, and lymphocytes (Figure 3). Focal coagulative necrosis, karyorrhectic debris, and eosinophilic debris (Figure 4) between cellular components were found in all cases. Neutrophils were not found.

Follow-up on 2 patients (cases 4 and 5) revealed no evidence of disease; the other patients were lost to follow-up.

COMMENT

Kikuchi-Fujimoto disease is now a well-known, benign, self-limiting disease. This disease usually affects young women.6 The youngest patient described to date was 8 years, 8 months old.15 The reported female-male ratio varies from 1:1 to 4:1.3,12,13 In this study, the youngest patient was 13 years old and the female-male ratio was 5:1. This disease usually involves cervical lymph nodes16; however, involvement of axillary,16,17 mesenteric,18 mediastinal,3 inguinal, intraparotid, iliac, celiac, and peripancreatic3 lymph nodes has been reported as well.

Generalized lymphadenopathy sometimes occurs.12 In our study, 5 patients had cervical lymphadenopathy, 1 patient had axillary lymphadenopathy, and none had generalized lymphadenopathy. The clinical manifestations include lymphadenopathy, fever,3,5 cutaneous erythema,19 diarrhea, vomiting, chest pain, arthralgia, and hepatosplenomegaly.3,5 All patients in this study had lymphadenopathy and 5 had fever. Hepatosplenomegaly and cutaneous rashes were not found. Patients with Kikuchi-Fujimoto disease may develop anemia, leukopenia,5,12 atypical lymphocytosis,12 and raised erythrocyte sedimentation rate. We found anemia in 2 patients and raised erythrocyte sedimentation rate in all our patients. Leukopenia and atypical lymphocytosis were not noted in our patients.

The histopathologic features are architectural effacement of lymph node; presence of pale nodular foci composed of histiocytes, immunoblasts, monocytes, and lymphocytes; presence of eosinophilic debris and karyorrhectic debris; and absence of neutrophils. Our cases were typical, and we found most of these features.

This disease should be differentiated from tuberculous lymphadenitis, malignant lymphoma,14,20 and systemic lupus erythematosus.3,21 In our study, all cases were diagnosed as Kikuchi-Fujimoto disease only after histopathologic examination of excised lymph nodes. Five cases were clinically diagnosed as tuberculous lymphadenitis, and 1 was diagnosed as reactive lymphadenitis. The distinction from tuberculous lymphadenitis is very important (especially in our region, where tuberculosis is quite common), since these diseases have differing treatments and prognoses. The epithelioid cell granulomas, multinucleated giant cells of Langhans type, caseous necrosis, and absence of karyorrhectic debris clearly favor the diagnosis of tuberculosis. Systemic lupus erythematosus is the most difficult differential diagnosis. The presence of numerous plasma cells and hematoxyphilic bodies and neutrophilic infiltration favor a diagnosis of systemic lupus erythematosus,3 while the complete absence of polymorphs is a good clue in diagnosing Kikuchi-Fujimoto disease.22 Approximately 30% of Kikuchi-Fujimoto disease cases are mistaken for malignant lymphoma.3 Presence of immunoblasts and atypical histiocytes and loss of architecture of lymph node may mimic lymphoma. The distinctive features14 favoring Kikuchi-Fujimoto disease include prominent mottling by benign histiocytes or transformed lymphoid cells, presence of pale nodular foci with karyorrhectic debris, and absence of inflammatory and granulomatous reaction.

Kikuchi-Fujimoto disease is self-limiting, as spontaneous improvement and disappearance of symptoms frequently happen within 1 to 6 months of initial onset. However, recurrence of lymphadenopathy12,13,23 and fatal cases24,25 have been reported. In this study, 2 cases with follow-up information did not develop recurrence, but the others were lost to follow-up.

This study emphasizes the fact that Kikuchi-Fujimoto disease should be considered as one of the differential diagnoses in patients with prolonged fever and cervical lymphadenopathy who do not respond to antibiotic treatment.

References

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19. Yasukawa K, Matsumura T, Sato-Matsumura KC, et al. Kikuchi's disease and the skin: case report and review of the literature. Br J Dermatol. 2001;144:885-889.

20. Yoshimo T, Mannami T, Ichimura K, et al. Two cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) following diffuse large B-cell lymphoma. Hum Pathol. 2000;31:1328-1331.

21. El-Ramahi KM, Karrar A, Ali MA. Kikuchi disease and its association with systemic lupus erythematosus. Lupus. 1994;3:409-411.

22. Ali MH, Horton LWL. Necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's disease). J Clin Pathol. 1985;38:1252-1257.

23. Blewitt RW, Kumar SN, Abraham JS. Recurrence of Kikuchi's lymphadenitis after 12 years. J Clin Pathol. 2000;53:157-158.

24. O'Neill D, O'Grady J, Variend S. Child fatality associated with pathological features of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease). Pediatr Pathol Lab Med. 1998;18:79-88.

25. Shih-Hua L, Wang-Sheng K, Herng-Sheng L, Wei-Shou H. Kikuchi's disease associated with lupus-like syndrome: a fatal case. J Rheumatol. 1992;19:1995-1996.

Ram Chandra Adhikari, MD; Gita Sayami, PhD; Min Chul Lee, PhD; Ranga Bahadur Basnet, MD; Pradeep Krishna Shrestha, MD; Hari Govinda Shrestha, MD

Accepted for publication April 16, 2003.

From the Departments of Pathology (Drs Adhikari, Sayami, Lee, and H. G. Shrestha) and Medicine (Dr P. K. Shrestha), Tribhuvan University Teaching Hospital, Kathmandu, Nepal; and Advanced Diagnostic Centre and Polyclinic, Kathmandu, Nepal (Dr Basnet).

Reprints: Ram Chandra Adhikari, MD, GPO Box 2496, Kathmandu, Nepal (e-mail: rcadhikari@hotmail.com).

Copyright College of American Pathologists Oct 2003
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