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PubMed1996

Involvement of cell-mediated killing in apoptosis in histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease).

Histiocytic necrotizing lymphadenitis, also called Kikuchi-Fujimoto (KF) disease, is a benign disorder characterized histologically by paracortical necrotic foci surrounded by histiocytic aggregates. We analysed affected lymph node tissues from 34 patients with the disease in an attempt to elucidate its histogenesis. The 'necrotizing' cells showed typical apoptotic changes, including cell shrinkage and condensed and fragmented nuclei. Apoptotic bodies with a peculiar ultrastructure were demonstrated, and DNA fragmentation was detected in these cells by in situ end labelling. Immunostaining for the apoptosis-regulating proteins bcl-2, bax, c-myc and p53 failed to show their involvement in KF disease. However, perforin, a killer cell-specific cytolytic protein essential for provoking apoptosis in target cells, was found to be expressed abundantly by the infiltrating cells, which were thought to be cytotoxic T-lymphocytes. Perforin-expressing cells were present in the apoptotic foci of 28 of the 34 patients (82.4%). Virtually no cells containing perforin granules were present in non-pathological regions, lymph node tissues from control subjects with reactive or tuberculous lymphadenitis or those from patients with KF disease with negligible apoptosis. Therefore, the 'necrosis' associated with KF disease appears to be attributable to trans apoptotic death of the killer cell target in the affected nodes. We propose that KF disease should be called apoptotic lymphadenitis.

Adolescent↗
PubMed2001

Noncervicofacial atypical mycobacterial lymphadenitis in childhood.

BACKGROUND/PURPOSE: Atypical mycobacterial (AM) lymphadenitis is common in children but rarely occurs outside the cervicofacial region. The authors report their experience in the diagnosis and management of noncervicofacial AM lymphadenitis. METHODS: A retrospective review was conducted of cases diagnosed at our institution between January 1976 and December 1999, based on positive culture of atypical mycobacteria or consistent histology with supportive skin testing. RESULTS: Thirty-seven patients were identified over the 23-year review period. The median age was 4.3 years (range, 8 months to 13 years and 5 months), with 19 boys and 17 girls. The median duration of symptoms was 4 weeks, and the most commonly affected sites were the inguinal region (n = 17), axilla (n = 8), and lower limb (n = 6). Preceding local trauma was described in 10 patients and a viral illness in 4. Laboratory culture for atypical mycobacteria was positive in 22, and skin testing suggestive in 21 and equivocal in 2. Treatment was by excision in 28 and drainage with or without curettage in 9. At a median follow-up of 19.7 months, disease had recurred in 4 patients, none of whom had been treated initially by excision. CONCLUSIONS: Atypical mycobacterial infection is an uncommon cause of noncervicofacial lymphadenitis in children. It typically presents with a 4-week history of painless regional lymphadenopathy that may follow penetrating trauma. If untreated, the overlying skin becomes involved with a violaceous discoloration, and ulceration may occur. Definitive treatment involves complete surgical excision, preferably before suppuration extending beyond the involved lymph nodes.

Age Distribution↗
PubMed1999

[Postoperative antibiotic therapy of cervical lymphadenitis caused by nontuberculous, atypical mycobacteria].

BACKGROUND: Cervical lymphadenitis caused by atypical mycobacteria is increasingly observed in immunocompetent children between 1 and 5 years of age. Surgical excision of all affected lymph nodes represents the treatment of choice. However, due to the infiltrative nature of the disease, surgery is occasionally unable to provide a complete cure and is associated with a high risk of recurrence. Such cases might derive benefit from an additional antibiotic therapy. METHODS: The study includes 4 children with demonstrated or clinically suspected nontuberculous mycobacterial lymphadenitis, in whom partial surgery had been performed. Postoperatively, two patients were treated with clarithromycin, rifabutin, and protionamide, the others with clarithromycin alone. Antibiotics were administered orally for 6-12 weeks and were continued four weeks after local signs of inflammation were no longer detectable. RESULTS: In all cases, symptoms of lymphadenitis resolved within 1-2 months and did not recur. One patient was affected by WHO grade I leukopenia after 6 weeks, which soon disappeared after administration of rifabutin and protionamid had been discontinued. CONCLUSIONS: Postoperative antibiotic therapy seems to be an effective approach to treat residual disease following incomplete surgery. It remains to be clarified, however, if such a therapy should comprise combinations of agents or if administration of clarithromycin alone might be sufficient.

Anti-Bacterial Agents↗
PubMed2002

Interferon-gamma, interleukin-18, monokine induced by interferon-gamma and interferon-gamma-inducible protein-10 in histiocytic necrotizing lymphadenitis.

Apoptosis of histiocytes is a characteristic feature of necrotizing lymphadenitis (HNL). Recent studies have indicated that Fas and perforin-based pathways are involved in the apoptotic process of HNL. Elevated levels of serum interferon (IFN)-gamma are reported in HNL. The CXC chemokine interferon-gamma-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) cause tissue necrosis, and interleukin (IL)-18 induces the expression of IFN-gamma and Fas ligand (FasL) by T and natural killer (NK) cells. This study was designed to determine the expression of IFN-gamma, IL-18, MIG and IP-10 in HNL. Ten cases of HNL were analyzed by using immunohistochemical staining and/or reverse transcriptase-polymerase chain reaction (RT-PCR). As a control, we included four cases of non-specific lymphadenitis. MIG and IP-10 proteins, which enhance the release of granzyme, showed a similar distribution pattern in viable tissues surrounding dead tissue, mostly within histiocytes, and lymphocytes in HNL. IL-18 was located within histiocytes, especially phagocytic histiocytes, but not within lymphocytes. In addition, IFN-gamma-positive lymphocytes were frequently detected in the surrounding dead tissue, and the lymphocytes in the same area were frequently positive for CXCR3, a specific receptor of MIG and IP-10. In non-specific lymphadenitis, MIG, IP-10 and IL-18 positive cells were detected, but their numbers were relatively small compared with HNL, while IFN-gamma positive cells were rarely encountered. Our findings suggest that the cytokine and chemokine pathways of IFN-gamma, IL-18, MIG and IP-10 play an important role in the pathogenesis of apoptosis associated with HNL.

Adolescent↗
PubMed2001

Lymphadenitis caused by Scedosporium apiospermum in an immunocompetent patient.

A case of lymphadenitis caused by Scedosporium apiospermum in a 25-year-old immunocompetent woman had been misdiagnosed as tuberculous lymphadenitis. Clinical response to itraconazole therapy was obtained in 6 months; to our knowledge, this is the first report of lymphadenitis caused by S. apiospermum in humans.

Adult↗
PubMed2005

Cervicofacial lymphadenitis in children caused by Mycobacterium haemophilum.

BACKGROUND: Nontuberculous mycobacterial (NTM) lymphadenitis in children is most often caused by Mycobacterium avium. In a prospective, multicenter trial of the optimal treatment, 23.7% of the NTM cervicofacial lymphadenitis cases in children were caused by Mycobacterium haemophilum. In this article, we describe the epidemiological and clinical features of M. haemophilum cervicofacial lymphadenitis. METHODS: The diagnosis of Mycobacterium avium or M. haemophilum infection was established by culture or polymerase chain reaction. Demographic characteristics and data regarding clinical presentation and possible environmental exposure were compared for patients infected with M. avium and those infected with M. haemophilum. RESULTS: Ninety-four (69.9%) of 135 infections were caused by M. avium, 32 (23.7%) by M. haemophilum, and 9 (6.4%) by other NTM species. The median age of the M. haemophilum-infected children was 72 months, compared with 41 months for the M. avium-infected children (P < .001), with an equal distribution for both sexes. Involvement of multiple lymph nodes was frequently observed among the M. haemophilum-infected patients (56% of patients). Extranodal localizations were only observed in M. haemophilum-infected patients. Children with M. haemophilum infection were more likely to have a non-Dutch background (P = .001), and in most cases, they had a history of contact with swimming water (P = .03), whereas M. avium-infected patients were more likely to have a history of playing in sandpits (P = .01). In a multivariate analysis, only older age and a non-Dutch background were predisposing risk factors for M. haemophilum infection, compared with M. avium infection. CONCLUSION: Higher age, non-Dutch background, and involvement of multiple cervicofacial lymph nodes with extranodal localizations distinguished M. haemophilum infection from M. avium infection.

Aging↗
PubMed1991

Herpes simplex lymphadenitis.

Localized herpetic lymphadenitis is an extremely uncommon complication of herpes simplex virus (HSV) infection. The authors report two cases of localized herpetic lymphadenitis, both showing well-circumscribed areas of necrosis containing cells with diagnostic intranuclear inclusions. Electron microscopic studies in both cases revealed characteristic viral particles, and in situ hybridization studies using a herpes simplex genomic probe demonstrated HSV DNA in both specimens. Immunohistochemical studies demonstrated that the cells containing the inclusions were stromal, not lymphoid, cells. Combining the current two cases with the six well-documented cases previously reported in the literature, seven of the eight cases of HSV lymphadenitis have developed in inguinal lymph nodes, with four occurring in patients with previously or subsequently diagnosed hematopoietic malignancies, including both patients in the current series.

Adult↗
PubMed2000

Kikuchi-Fujimoto necrotizing lymphadenitis associated with cutaneous lupus erythematosus: a case report.

Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease is a rare entity, and even more rarely, it is associated with other diseases. In a few cases, the condition is associated with cutaneous lupus erythematosus (CLE). Histiocytic necrotizing lymphadenitis predominantly affects young women, who present with solitary or multiple cervical lymphadenopathy accompanied by symptoms such as fever, weight loss, sweating, or, in exceptional cases, hepatosplenomegaly. Laboratory examinations show normal or nonspecific results. The disease is of unknown origin, although a viral origin has been suggested, with the suspected agents including Epstein-Barr virus, herpesvirus type 6, and cytomegalovirus (CMV). Although the first and most of the more recent cases have been reported in Oriental patients, the disease has a wide geographic distribution. The clinical evolution is favorable, with spontaneous remission in less than 4 months in almost all cases. We present a case of a 37-year-old woman from Peru who presented with cervical adenopathies on two occasions. Biopsy of a lymph node revealed a histopathologic picture compatible with Kikuchi-Fujimoto histiocytic necrotizing lymphadenitis. The adenopathy disappeared in a few months. A year later, she presented with a maculopapular rash in the nasal and malar regions. The results of the skin biopsy and immunofluorescence examination were compatible with chronic CLE. The results of the serology testing for CMV were positive. Treatment with chloroquine was initiated, with almost complete recovery by 5 months. No manifestations of systemic lupus erythematosus have occurred since. The epidemiologic, clinical, and anatomopathologic aspects as well as the differential diagnosis of this entity are reviewed.

Adult↗
PubMed1998

Preoperative diagnosis of Mycobacterium avium lymphadenitis in two immunocompetent children by polymerase chain reaction of gastric aspirates.

BACKGROUND: Analysis of gastric aspirates is a routine procedure for detection of Mycobacterium tuberculosis in pediatric pulmonary tuberculosis. However, identification of nontuberculous mycobacteria in gastric aspirates of immunocompetent children is not thought to be clinically significant. METHODS: A PCR method was devised for the detection of M. avium in clinical specimens. The method is based on the amplification of a M. avium-specific DNA fragment present in the 3'-end of the repetitive element IS1245. Surgically removed lymphatic tissue was analyzed prospectively by microscopy, culture and PCR in 13 children admitted to our hospital with suspected mycobacterial lymphadenitis. In 4 of these children 1 to 4 gastric aspirates were obtained before surgical treatment and submitted to the same analysis. RESULTS: We report the detection of M. avium in the gastric aspirates of two children with cervical lymphadenitis before surgical intervention by a novel PCR method. The subsequently surgically removed lymph nodes were also positive by PCR and culture. In one child cultures of both sources grew M. avium. The isolates could be identified as the same strain by DNA fingerprinting. The PCR assay was almost twice as sensitive as culture in detecting M. avium. CONCLUSIONS: Our findings suggest the possibility for noninvasive diagnosis of cervical lymphadenitis caused by nontuberculous mycobacteria before surgery. In addition detection of M. avium in gastric aspirates without evidence of fistula formation provides new insights into the pathogenesis of mycobacterial infection and disease in immunocompetent children.

DNA Fingerprinting↗
PubMed1999

Mycobacterial lymphadenitis associated with the initiation of combination antiretroviral therapy.

OBJECTIVE: To characterize the impact of combination antiretroviral therapy on the clinical and laboratory features of mycobacterial lymphadenitis, we conducted a retrospective chart review of HIV-related mycobacterial lymphadenitis at St. Paul's hospital between 1989 and 1997. Among 52 evaluable patients, 12 presented within 12 weeks of initiating combination antiretroviral therapy (group 1, n = 12); the others developed lesions while receiving no antiretrovirals, monotherapy, or a stable combination regimen of >12 weeks duration (group 2, n = 40). RESULTS: Group 1 patients had higher absolute CD4 lymphocyte counts (median, 150 versus 20 cells/mm3, respectively; p = .001) and hemoglobin levels (median, 113 versus 88 g/L, respectively; p = .002) at the time of mycobacterial diagnosis. Clinical comparison showed that group 1 patients were more likely to develop a draining sinus (50% versus 0%; p < .001), but less often to have weight loss (17% versus 74%; p < .0001) or disease which was disseminated (25% versus 70%; p = .04) or caused by Mycobacterium tuberculosis (0% versus 33%; p = .04). CONCLUSIONS: Mycobacterial lymphadenitis developing within 12 weeks of initiating combination antiretroviral therapy is often localized Mycobacterium avium complex disease, associated with a relatively high CD4 count. The clinical course is often complicated by the development of a draining sinus. The close temporal association suggests that such treatment may unmask subclinical infection by enhancing the immune response to mycobacterial antigens.

AIDS-Related Opportunistic Infections↗
PubMed2003

Kikuchi-Fujimoto lymphadenitis.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, was initially described as a distinct histologic pattern of lymphadenitis generally associated with a benign self-limited clinical course. While most common in Southeast Asia, where KFD was initially described in 1972 in young women, this lesion has since been reported in patients of virtually any age, gender, or ethnic background from a variety of geographic locations, including the United States. In addition, cases showing extranodal involvement have been described. The spectrum of clinical and histologic features associated with this disorder suggest that KFD more likely represents a common pattern of response to a variety of etiologic factors rather than a single clinicopathologic entity. In this review, the characteristic clinical, laboratory, histologic, and immunophenotypic features of this disorder are described, with emphasis on differential diagnosis with other types of necrotizing lymphadenitis and with malignant lymphoma. Unusual clinical presentations and features of disease when present at extranodal sites are also reviewed.

Adolescent↗
PubMed1995

Calcium oxalate crystal deposition in epithelioid histiocytes of granulomatous lymphadenitis: analysis by light and electronmicroscopy.

In this study of 55 cases of granulomatous lymphadenitis of various aetiologies, both haematoxylin and eosin stained and unstained sections were examined by light and polarizing light microscopy for crystals within epithelioid histiocytes. This investigation was prompted by a case of granulomatous lymphadenitis in which the identification of ovoid birefringent structures within epithelioid histiocytes led to an initial false suggestion of foreign body reaction. Identical single, small, ovoid or biconvex, intensely birefringent crystals, invisible by ordinary light microscopy, were found within the cytoplasm of mononuclear epithelioid histiocytes in 37 cases. There was only minor crystal loss with routine H & E staining. The sections were also examined by scanning electronmicroscopy in secondary and backscattered electron imaging modes and 27 cases were found to contain biconvex crystals which were shown on X-ray energy dispersive spectroscopic microanalysis to be consistent with calcium oxalate. There was a good quantitative correlation between light and scanning electron microscopy. Tissue from the index case was also examined by transmission electronmicroscopy, and electron dense crystals were identified. We confirm the previous findings of ovoid oxalate crystals in a variety of granulomatous conditions including Mycobacterial infection, sarcoidosis and Crohn's disease. Ovoid crystals of calcium oxalate, a common finding in granulomatous lymphadenitis, appear to be endogenously derived, and should be more widely recognized in order to avoid misdiagnosis of foreign body reaction.

Calcium Oxalate↗
PubMed1994

A case of non-tuberculous mycobacterial lymphadenitis diagnosed with new skin tests and PCR.

Non-tuberculous mycobacterial (NTM) cervical lymphadenitis has been rarely reported in Japan. We report on a case of a 15 month old child with NTM cervical lymphadenitis who was diagnosed with new skin tests containing NTM antigens and a polymerase chain reaction (PCR) method. These two diagnostic methods were highly useful in the present case, therefore we anticipate they will become available to other Japanese physicians to expedite the diagnosis of NTM lymphadenitis.

Humans↗
PubMed1986

Histiocytic necrotizing lymphadenitis (Kikuchi's disease).

We report a typical case of histiocytic necrotizing lymphadenitis. To our knowledge, this is the first reported case in Australasia. Histiocytic necrotizing lymphadenitis (Kikuchi's disease) is a distinct disorder originally reported in Japan. It commonly affects young females and involves mainly cervical lymph nodes. The condition is benign. The etiology of histiocytic necrotizing lymphadenitis and its distinction from other causes of benign and malignant lymphadenopathies are discussed. The clinical importance of this disorder is that, histopathologically, it could be misdiagnosed as malignant lymphoma and therefore patients may receive incorrect treatment.

Adult↗
PubMed1991

Acute mesenteric lymphadenitis due to Yersinia pseudotuberculosis lacking a virulence plasmid.

A serotype 4a strain of Yersinia pseudotuberculosis lacking the virulence plasmid pYV (pYV- strain) was isolated from the mesenteric lymph nodes but not from the stool or the appendix of a 10-year-old girl with a diagnosis of acute mesenteric lymphadenitis. Microscopically, reticulocytic abscess and lymphadenitis were persent in the enlarged mesenteric lymph nodes. Antibody against the isolate was detected in the serum. The isolate was negative for the presence of plasmid pYV and plasmid pYV-mediated properties, including autoagglutination and calcium dependency, but was positive for chromosome-mediated properties, including invasion into HeLa cells and tissues of mice and the Serény test. Mice were orally infected with this pYV- strain, and rapid elimination from the intestine occurred 14 days later. Hence, the potential to inhibit the phagocytosis encoded by plasmid pYV was lacking. As the pYV- strain was recovered from the mesenteric lymph nodes and the spleen, the invasiveness was encoded by chromosomal genes. The count of the pYV- strain in the mesenteric lymph nodes increased to 10(4.6) cells per g within 4 days. These findings suggest that pYV- Y. pseudotuberculosis was the causative agent of acute mesenteric lymphadenitis in the absence of gastroenteritis.

Animals↗
PubMed2001

Novel mycobacterium related to Mycobacterium triplex as a cause of cervical lymphadenitis.

The Mycobacterium avium complex (MAC) is an important cause of cervical lymphadenitis in children, and its incidence appears to be increasing in the United States and elsewhere. In areas where Mycobacterium tuberculosis is not prevalent, M. avium causes the vast majority of cases of mycobacterial lymphadenitis, although several other nontuberculous mycobacterial species have been reported as etiologic agents. This report describes the case of a child with cervical lymphadenitis caused by a nontuberculous mycobacterium that could not be identified using standard methods, including biochemical reactions and genetic probes. Direct 16S ribosomal DNA sequencing showed greater than 99% homology with Mycobacterium triplex, but sequence analysis of the 283-bp 16S-23S internal transcribed spacer (ITS) sequence showed only 95% identity, suggesting that it is a novel species or subspecies within a complex of organisms that includes M. triplex. Mycolic acid high-performance liquid chromatography analysis also identified this isolate as distinct from M. triplex, and differences in susceptibility to streptomycin and rifampin between this strain and M. triplex were also observed. These data support the value of further testing of clinical isolates that test negative with the MAC nucleic acid probes and suggest that standard methods used for the identification of mycobacteria may underestimate the complexity of the genus Mycobacterium. ITS sequence analysis may be useful in this setting because it is easy to perform and is able to distinguish closely related species and subspecies. This level of discrimination may have significant clinical ramifications, as closely related organisms may have different antibiotic susceptibility patterns.

Base Sequence↗
PubMed1984

Herpes simplex lymphadenitis: a case report and review of the published work.

Viral lymphadenitis may lead to a histological appearance that can simulate malignancy. The histological features of herpes simplex lymphadenitis have not previously been described in detail. We report a case of proved herpes simplex lymphadenitis in a 30 year old man which was characterised by a pronounced proliferation of immunoblasts. The microscopical findings are described and the published work is reviewed.

Adult↗
PubMed1985

Clinical experience with short-course chemotherapy in patients with tubercular pleural effusion and lymphadenitis.

Twenty-one patients with pleural effusion and 27 patients with lymphadenitis, both tubercular in origin, were administered isoniazid, rifampicin and ethambutol in a daily single dose for 9 months. 100% response was seen in patients with pleural effusion. In the case of tuberculous lymphadenitis the therapeutic response was unsatisfactory, and complete resolution of lymph nodes was achieved in 16 out of 27 patients only (59%). Drug treatment had to be extended for another 3 months which gave 89% response. In view of our present findings, short-course chemotherapy appears not to be the ideal mode of treatment for tuberculous lymphadenitis. There were no side effects from drug therapy in either group of patients.

Adolescent↗