CASE PRESENTATION A 17-year-old previously healthy girl of South Asian descent presented to the emergency department with a 1-month history of bilateral, enlarging, tender cervical lymphadenopathy and 1 week of intermittent fevers and night sweats. There was no history of urinary symptoms, weight loss, sick contacts or travel. The remainder of the review of systems was unremarkable. Family history was non-contributory. Examination revealed a well-looking girl with normal vital signs. She was found to have a right-sided cervical lymph node 2 cm in diameter, many left-sided cervical lymph nodes 1 cm to 1.5 cm in diameter and a right-sided axillary lymph node 0.5 cm in diameter. No inguinal lymph nodes were palpable. The remainder of the examination was unremarkable. Complete blood count revealed a leukocyte count of 2.3 × 109/L, with neutrophils of 0.48 × 109/L and lymphocytes of 1.47 × 109/L, platelet count of 223 × 109/L, hemoglobin level of 128 g/L and a normal smear. Lactate dehydrogenase and erythrocyte sedimentation rate were elevated at 1178 U/L and 29 mm/hour, respectively. Electrolytes, kidney function tests and liver transaminases were within normal limits. A lymph node biopsy was recommended and confirmed the diagnosis. DISCUSSION Over the next 4 weeks, the patient developed migratory arthralgias involving her wrists, ankles and knees. Her cervical lymphadenopathy was tender and persistent, yet waxing and waning in severity. Associated symptoms included fatigue and anorexia, as well as the development of anosmia and hair loss. While her long-standing eczema flared during this period, there were no other skin rashes noted. An infectious workup, including Epstein–Barr virus, cytomegalovirus, parvovirus, histoplasma and toxoplasma serologies, was negative. Rheumatologic investigations included negative antinuclear antibodies and anti-double-stranded DNA, normal complement (C3 and C4) and normal urinalysis. A head and neck magnetic resonance imaging for investigation of the anosmia revealed no intracranial abnormalities, but did show multiple enlarged cervical lymph nodes involving levels II to VI bilaterally. Chest radiographs and abdominal ultrasounds, assessing for further lymphadenopathy and organomegaly, were unremarkable. On follow-up blood work, the initial neutropenia resolved and lactate dehydrogenase and erythrocyte sedimentation rate normalized, though she did develop a mild iron deficiency anemia. A biopsy showed early-phase histiocytic necrotizing lymphadenitis, otherwise known as Kikuchi disease (KD). The patient was started on non-steroidal anti-inflammatory medication and referred to a rheumatologist and hematologist for continued care. Over time, her arthralgias and lymphadenopathy resolved, although the anosmia and mild fatigue remain. Histiocytic necrotizing lymphadenitis, also known as KD, is a rare condition most commonly presenting in Asian populations. It is found predominantly in patients less than 30 years of age, with a higher ratio of females to males affected, though there is some evidence to show that in younger children, the opposite is true (1). The pathophysiology of KD remains unclear, but there is evidence of association with autoimmune diseases, specifically systemic lupus erythematosus (SLE), and certain infectious agents including Epstein–Barr virus, Yersinia, toxoplasma, human herpesvirus 6 and 8, human T-lymphotropic virus type 1 and parvovirus B19. A definitive diagnosis requires tissue pathology, which delineates between three subtypes of KD: necrotizing, proliferative and xanthomatous types. The necrotizing type is the most common, comprising about half of all known cases (2). The primary clinical manifestation of KD is cervical lymphadenopathy, and rarely generalized lymphadenopathy. It may also be associated with fever, night sweats, malaise, anorexia, weight loss, hepatomegaly and leukopenia. Less frequently, cutaneous rashes, myalgias, arthralgias, bone marrow disease and interstitial lung disease can also be seen (1). Of particular note, our patient developed anosmia, which has never (to our knowledge) been reported in KD. Aseptic meningitis has been reported as the most common neurological association, with cases reported of sensory neuropathy in the lower limbs, and right ulnar and bilateral deep peritoneal axonal neuropathy. The pathophysiology of neurologic complications in KD remains unclear (2). KD should be considered part of the differential diagnosis of lymphadenopathy (Table 1), which includes infectious, autoimmune and malignant etiologies. It becomes necessary to rule out conditions such as leukemia and lymphoma, tuberculosis and SLE, given the prompt treatment required for these conditions, prior to consideration of a rare, self-limited diagnosis like KD. Tissue diagnosis is required in the case of suspicious lymphadenopathy to ascertain the definitive diagnosis. Table 1. Differential diagnosis of lymphadenopathy Diagnosis Examples Infectious EBV, CMV, HIV, Mycobacterium tuberculosis, atypical mycobacterium, histoplasmosis, tularemia, cat scratch disease Autoimmune SLE, sarcoid Malignant Leukemia, lymphoma (Hodgkin, non-Hodgkin), neuroblastoma, rhabdomyosarcoma, histiocytosis Miscellaneous* Kikuchi disease, storage diseases, vaccinations Diagnosis Examples Infectious EBV, CMV, HIV, Mycobacterium tuberculosis, atypical mycobacterium, histoplasmosis, tularemia, cat scratch disease Autoimmune SLE, sarcoid Malignant Leukemia, lymphoma (Hodgkin, non-Hodgkin), neuroblastoma, rhabdomyosarcoma, histiocytosis Miscellaneous* Kikuchi disease, storage diseases, vaccinations CMV Cytomegalovirus; EBV Epstein–Barr virus; SLE Systemic lupus erythematosus. *Rare diagnoses View Large Treatment is symptomatic and supportive, since spontaneous recovery usually occurs after 1 to 4 months. Analgesics, antipyretics and non-steroidal anti-inflammatory medications are used to manage fevers and arthralgias. Occasionally, corticosteroids have been used, as they have been found to shorten the course of the fever, though not the overall course of illness (2). There is a small (3% to 4%) risk of future recurrence of KD, and an association with the development of systemic autoimmune diseases in patients with KD has been described. It is recommended that patients who have a definitive diagnosis of KD be monitored over time for the appearance of SLE or other autoimmune diseases (2). CLINICAL PEARLS Infection is the leading cause for lymphadenopathy; however, rheumatologic, malignant and other less common conditions need to be considered in the differential diagnosis of persistent or atypical findings. Excisional lymph node biopsy is required for pathologic diagnosis when other investigations prove non-contributory. Kikuchi disease is an uncommon, self-limited illness, but does require continued monitoring for recurrence and the potential development of autoimmune diseases, especially systemic lupus erythematosus. References 1. Kim TY, Ha KS, Kim Y, Lee J, Lee K, Lee J. Characteristics of Kikuchi-Fujimoto disease in children compared with adults. Eur j Pediatr 2014; 173( 1): 111– 6. Google Scholar CrossRef Search ADS PubMed 2. Lazzareschi I, Barone G, Ruggiero Aet al. Paediatric Kikuchi-Fujimoto disease: A benign cause of fever and lymphadenopathy. Pediatr Blood Cancer 2008; 50( 1): 119– 23. Google Scholar CrossRef Search ADS PubMed © The Author(s) 2017. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: email@example.com
Paediatrics & Child Health – Oxford University Press
Published: Feb 1, 2018
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