Abstract Background The association of Kikuchi Fujimoto disease (KFD) with cryptogenic organizing pneumonia (COP) is extremely rare. We report a case of simultaneous diagnosis of KFD and COP. Case Presentation A 33-year-old male presented with a 1-month cough illness and fever lasting for 5 days. The chest radiograph revealed double lower lobe infiltrate, which was unresponsive to antibiotics. A cervical lymph node was first found in the development of this disease. Bronchoscopy, bronchoalveolar lavage and lung biopsy established the diagnosis of COP, while a lymph node biopsy was consistent with KFD. The patient improved on steroids. Conclusions KFD and COP are possible part of a disease continuum, rather than separate entities.</p

AU Wells

CE Wilkinson

F Cousin

Feng Hua

GR Epler

HC Hollingsworth

JF Cordier

JL Myers

Lei Zhu

LP Menasce

M Tanaka

N Pallet

RH Lohr

TI George

TT Kuo

V Poletti

Y Sumiyoshi

English

PubMed

Abstract Background The association of Kikuchi Fujimoto disease (KFD) with cryptogenic organizing pneumonia (COP) is extremely rare. We report a case of simultaneous diagnosis of KFD and COP. Case Presentation A 33-year-old male presented with a 1-month cough illness and fever lasting for 5 days. The chest radiograph revealed double lower lobe infiltrate, which was unresponsive to antibiotics. A cervical lymph node was first found in the development of this disease. Bronchoscopy, bronchoalveolar lavage and lung biopsy established the diagnosis of COP, while a lymph node biopsy was consistent with KFD. The patient improved on steroids. Conclusions KFD and COP are possible part of a disease continuum, rather than separate entities.</p

Hua Feng

Zhu Lei

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Kikuchi Fujimoto disease associated with cryptogenic organizing pneumonia: case report and literature review

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CASE REPORT Open AccessKikuchi Fujimoto disease associated withcryptogenic organizing pneumonia: case reportand literature reviewFeng Hua1,2, Lei Zhu1*AbstractBackground: The association of Kikuchi Fujimoto disease (KFD) with cryptogenic organizing pneumonia (COP) isextremely rare. We report a case of simultaneous diagnosis of KFD and COP.Case Presentation: A 33-year-old male presented with a 1-month cough illness and fever lasting for 5 days. Thechest radiograph revealed double lower lobe infiltrate, which was unresponsive to antibiotics. A cervical lymphnode was first found in the development of this disease. Bronchoscopy, bronchoalveolar lavage and lung biopsyestablished the diagnosis of COP, while a lymph node biopsy was consistent with KFD. The patient improved onsteroids.Conclusions: KFD and COP are possible part of a disease continuum, rather than separate entities.BackgroundCryptogenic organizing pneumonia (COP) is an intersti-tial lung disease characterized by intra-alveolar buds ofconnective tissue [1]. It can be idiopathic or associatedwith a known underlying disease.In this case report, we present a 33-year-old man withCOP, followed by concomitant Kikuchi Fujimoto disease(KFD). KFD was first described in 1972 by Kikuchi andFujimoto and others. It is a clinicopathological entitythat commonly presents with cervical lymphadenopathyand fever in the absence of an active infectious disease.KFD is a rare histiocytic necrotizing lymphadenitis,which has a benign self-limiting clinical course. Its ori-gin is unknown, but an abnormal autoimmune reactionhas been suggested and infection is often considered asan inducing feature [2].To the best of our knowledge, this is the first casereport of COP and KFD.Case PresentationA 33-year-old man presented with a 1-month coughingillness and fever that lasted for 5 days. Before admission,the patient experienced expectoration of yellow sputumand antibiotic therapy for 2 weeks. There was no historyof fever, rash or respiratory distress, and there was nofamily history of autoimmune or connective tissue disor-ders. Respiratory examinations revealed fine crackles inboth lungs. Examination of other systems wasunremarkable.The laboratory investigation showed hemoglobin140 g/L, leukocytes 3.9 × 109/L with a normal differen-tial count, platelets 142 × 109/L, C-reactive protein1.2 mg/L, and an erythrocyte sedimentation rate (ESR)of 14 mm/h. Heterophil agglutination trial was nega-tive. Serum biochemistry findings including liver andrenal function were within normal limits. The resultsof cellular immunity assay showed a decrease in theCD4/CD8 ratio (0.63). Test results were negative fortoxoplasma, cytomegalovirus (CMV), rubella, Epstein-Barr virus (EBV), human herpes virus type 1 andhuman immunoddficiency virus (HIV). Also rheumato-logical and immunological tests were normal. Thesetests included antinuclear antibody, rheumatoid factor,antistreptolysin O, antineutrophil cytoplasmic antibodyand the levels of serum C3 and C4 as well as IgG, IgA,IgE and IgM.Bacteriological analysis of blood, sputum and urine didnot reveal any pathogenic agents. Pulmonary functionpresented restrictive ventilatory functional disturbance.* Correspondence: fan615@yahoo.com1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University,180 Feng Lin Road, Shanghai, 200032, PR ChinaHua and Zhu BMC Infectious Diseases 2010, 10:64http://www.biomedcentral.com/1471-2334/10/64© 2010 Hua and Zhu; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.In addition, chest computed tomography (CT) demon-strated diffuse infiltrating lesions in both lungs, predo-minantly in the lower lobes (Fig. 1A).With an initial diagnosis of bilateral pneumonia, moxi-floxacin and cefepime were initiated. Eleven days afteradmission, a solitary lymph node was first found in theright anterior cervical chain. The lymph node was tenderand measured 3 cm in diameter. At this point, thepatients had leucopenia (4.3 × 109/L) and lymphopenia(0.8 × 109/L). The ESR was slightly accelerated to40 mm/h. The serum C-reactive protein level was nor-mal. The serum galactomannan enzyme immunoassayand 1, 3 b-glucan assays for diagnosis of invasive fungalinfection were negative. Findings were negative for anintradermal tuberculin test, as well as for sputum andurine tests for the Mycobacterium tuberculosis. The sero-logical test for coxsackie B virus suggested infection inthe recent past.A cervical lymph node biopsy showed normal lymphnode architecture in some areas, but a few irregularnecrotic areas with intense karyorrhexis. Around thenecrotic areas, macrophages, plasma cells, histiocytesand lymphocytes were noted. No neutrophils weredetected (Fig. 2A). No tuberculoid granuloma, caseat-ing necrosis, or evidence of malignancy was found.Immunohistochemistry studies showed that the lym-phoid cells adjacent to the necrotic foci were positivefor CD3, LCA and CD45RO, but negative for CD20.CD79-positive cells were seen farther away from thenecrotic foci. Histiocytic cells at the periphery of thenecrotic foci were strongly positive for CD68. This his-tological pattern was suggestive of KFD [3].Bronchoalveolar lavage fluid showed no increase ineosinophil or lymphocyte counts, but a decrease in theCD4/CD8 ratio (0.52). Lung biopsy by video-assistedthoracoscopy was performed 12 days post-admissionand revealed granulation tissue in the alveolar spaces,with associated marked alveolar wall thickening andfrequent metaplasia of bronchiolar and alveolar cells(Fig. 2B). The staining of reticular fiber, PAS and hex-amethylenetetramine silver were negative. These find-ings of BAL and lung biopsy were compatible withCOP [4,5].After the diagnosis of KFD associated with COP,45 mg/day prednisone was administered, with a gradualimprovement in symptoms. A second HRCT was done,which showed marked resolution of the alveolar exu-dates (Fig. 1B), and cervical lymphadenopathy hadresolved 8 days post-treatment. At 12 weeks follow-up,the patient remained well, with no other symptoms orlymph node enlargement.ConclusionsCOP is a rare disease. The characteristic clinical featuresof COP are flu-like illness, followed by progressive dys-pnea, patchy infiltrates on chest radiography and CT, arestrictive spirometric pattern with diffusion impair-ment. And, the histopathological pattern of COP isintraluminal organization, predominantly within thealveolar ducts and alveoli [6].KFD was first described in 1972 by the Japanesepathologists Kikuchi and Fujimoto as a benign, self-lim-ited syndrome of necrotizing lymphadenitis with a char-acteristic histopathological appearance that mimicsFigure 1 Chest CT finding of COP. A: HRCT was performed before glucocorticoids were administered, and showed patchy areas of ground-glass attenuation and consolidation in the lower lobes that contained air bronchograms. B: A follow-up HRCT was performed 8 days afterglucocorticoid administration. It showed improvement in both the lungs with few residual lesions.Hua and Zhu BMC Infectious Diseases 2010, 10:64http://www.biomedcentral.com/1471-2334/10/64Page 2 of 4malignant lymphoma. It typically presents as localizedlymphadenopathy, predominantly in the cervical region,accompanied by fever and leukopenia in up to 50% ofcases [7].Reports in the literature of an association betweenrespiratory manifestation and KFD are not frequent. In1990, Tanaka et al. [8] reported one patient with KFDwho presented with respiratory symptoms, and T-lym-phocyte alveolitis was diagnosed. Additionally, antinuc-lear antibodies were positive, and antibodies againsthuman T-lymphotrophic virus type 1 (HTLV-I) werefalse positive. These findings suggested an immunologi-cal abnormality. Cervical lymph node swelling and infil-trative shadow on chest X-ray film improved withsteroid therapy.Several suggestions on the etiology of COP or KFDhave been raised. Certain microorganisms (EBV, HTLV-I, herpes human 6 virus, Toxoplasma, parvovirus B19,CMV, Brucella, Yersinia enterocolitica and parainfluenzavirus) have been suggested as the causative agents of thedisease, and initiate a hyper-immune response of the Tcells and histiocytes to the infectious agents. Positiveserological test for Coxsackie B virus in this case mightbe same mechanism. However, none of these possibili-ties have been definitively proven [9,10]. In addition,many cases of KFD in patients with lupus have beenreported. KFD has also been reported in other autoim-mune diseases, including Still disease [11], rheumatoidarthritis [12], polymyositis [13], and mixed connectivetissue disease [14].Similarly, COP has been described in various autoim-mune diseases [15], primarily in rheumatoid arthritis[16] but also in systemic lupus erythematosus andpolymyositis [12]. It is clear that an immunologicalabnormality is the common pathogenesis of COP andKFD. Although the precise mechanism may be differ-ent, response of corticosteroids on this case indicatedthat the pathogenesis of both diseases may beimmune-mediated. Therefore, the concomitant appear-ance of COP and KFD probably reflects two diseasesthat are part of a continuum, rather than separateentities.In summary, we presented a case of COP that wasdiagnosed concurrently with KFD. The potential etiologyof concomitant COP and KFD in our case could havebeen a nonspecific reaction to lung injury, unclearimmunologically mediated response, occult virus infec-tion, or immunosuppression. Further studies on a seriesof COP patients are necessary to elucidate thismechanism.ConsentWritten informed consent was obtained from the patientfor publication of this case report and any accompany-ing images. A copy of the written consent is availablefor review by the Editor-in-Chief of this journal.Author details1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University,180 Feng Lin Road, Shanghai, 200032, PR China. 2Department of PulmonaryMedicine, Huzhou central Hospital, 198 Hongqi Road, Huzhou city, Zhejiangprovince, 313000, PR China.Authors’ contributionsFH has acquisition of data and interpretation of data; LZ has been involvedin drafting the manuscript. Both authors read and approved the finalmanuscript.Competing interestsThe author denies that he has any intention to obtain any financial interests.Received: 25 September 2009 Accepted: 11 March 2010Published: 11 March 2010Figure 2 Histopathological findings. A: Lymph node histology of the patient showed aggregation of histiocytes and plasmacytoid monocyteswith focal necrosis, scattered pyknotic nuclei and karyorrhexis (HE, ×20). Insert shows more details (HE, ×40). B: Lung biopsy illustratingintraluminal fibrous tissue plugs with adjacent thickened interstitium, intraalveolar macrophages, and lymphoplasmacytic inflammation (HE, ×20).Insert shows more details (HE, ×40).Hua and Zhu BMC Infectious Diseases 2010, 10:64http://www.biomedcentral.com/1471-2334/10/64Page 3 of 4References1. Lohr RH, Boland BJ, Douglas WW, Dockrell DH, Colby TV, Swensen SJ,Wollan PC, Silverstein MD: Organizing pneumonia - Features andprognosis of cryptogenic, secondary, and focal variants. Arch Intern Med1997, 157(12):1323-1329.2. Menasce LP, Banerjee SS, Edmondson D, Harris M: Histiocytic necrotizinglymphadenitis (Kikuchi-Fujimoto disease): Continuing diagnosticdifficulties. Histopathology 1998, 33(3):248-254.3. Sumiyoshi Y, Kikuchi M, Takeshita M, Ohshima K, Masuda Y, Parwaresch MR:Immunohistologic studies of kikuchis disease. Hum Pathol 1993,24(10):1114-1119.4. American Thoracic Society/European Respiratory Society InternationalMultidisciplinary Consensus Classification of the Idiopathic InterstitialPneumonias. This Joint Statement of the American Thoracic Society(ATS), and the European Respiratory Society (ERS) was adopted by theATS Board of Directors, June 2001 and by The ERS ExecutiveCommittee, June 2001. Am J Resp Crit Care 2002, 165(2):277-304.5. Poletti V, Cazzato S, Minicuci N, Zompatori M, Burzi M, Schiattone ML: Thediagnostic value of bronchoalveolar lavage and transbronchial lungbiopsy in cryptogenic organizing pneumonia. Eur Respir J 1996,9(12):2513-2516.6. Wells AU: Cryptogenic organizing pneumonia. Sem Resp Crit Care M 2001,22(4):449-459.7. Kuo TT: Kikuchis disease (histiocytic necrotizing lymphadenitis) - aclinicopathological study of 79 cases with an analysis of histologicsubtypes, immunohistology, and dna-ploidy. Am J Surg Pathol 1995,19(7):798-809.8. Tanaka M, Yano T, Ichikawa Y, Kaji M: [A case of subacute necrotizinglymphadenitis with localized interstitial pneumonia]. Nihon Kyobu ShikkanGakkai Zasshi 1990, 28(9):1234-1238.9. George TI, Jones CD, Zehnder JL, Warnke RA, Dorfman RF: Lack of humanherpesvirus 8 and Epstein-Barr virus in Kikuchi’s histiocytic necrotizinglymphadenitis. Hum Pathol 2003, 34(2):130-135.10. Hollingsworth HC, Peiper SC, Weiss LM, Raffeld M, Jaffe ES: Aninvestigation of the viral pathogenesis of kikuchi-fujimoto disease - lackof evidence for epstein-barr-virus or human herpesvirus type-6 as thecausative agents. Arch Pathol Lab Med 1994, 118(2):134-140.11. Cousin F, Grezard P, Roth B, Balme B, Gregoire-Bardel M, Perrot H: Kikuchidisease associated with Still disease. Int J Dermatol 1999, 38(6):464-467.12. Cordier JF: Organizing pneumonia: Cryptogenic and disease associated.Sem Resp Crit Care M 2003, 24(5):595-606.13. Wilkinson CE, Nichol F: Kikuchi-Fujimoto disease associated withpolymyositis. Rheumatology 2000, 39(11):1302-1304.14. Pallet N, Aaron L, Larousserie F, Therby A, Dupont B, Viard JP: Kikuchi-Fujimoto disease associated with mixed connective tissue disease. ScandJ Rheumatol 2004, 33(6):434-436.15. Epler GR: Bronchiolitis Obliterans Organizing Pneumonia. Arch Intern Med2001, 161(2):158-164.16. Myers JL, Colby TV: Pathological manifestations of bronchiolitis,constrictive bronchiolitis, cryptogenic organizing pneumonia, anddiffuse panbronchiolitis. Clin Chest Med 1993, 14(4):611-622.Pre-publication historyThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/10/64/prepubdoi:10.1186/1471-2334-10-64Cite this article as: Hua and Zhu: Kikuchi Fujimoto disease associatedwith cryptogenic organizing pneumonia: case report and literaturereview. BMC Infectious Diseases 2010 10:64.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitHua and Zhu BMC Infectious Diseases 2010, 10:64http://www.biomedcentral.com/1471-2334/10/64Page 4 of 4

CASE REPORT Open Access
Kikuchi Fujimoto disease associated with
cryptogenic organizing pneumonia: case report
and literature review
Feng Hua1,2, Lei Zhu1*
Abstract
Background: The association of Kikuchi Fujimoto disease (KFD) with cryptogenic organizing pneumonia (COP) is
extremely rare. We report a case of simultaneous diagnosis of KFD and COP.
Case Presentation: A 33-year-old male presented with a 1-month cough illness and fever lasting for 5 days. The
chest radiograph revealed double lower lobe infiltrate, which was unresponsive to antibiotics. A cervical lymph
node was first found in the development of this disease. Bronchoscopy, bronchoalveolar lavage and lung biopsy
established the diagnosis of COP, while a lymph node biopsy was consistent with KFD. The patient improved on
steroids.
Conclusions: KFD and COP are possible part of a disease continuum, rather than separate entities.
Background
Cryptogenic organizing pneumonia (COP) is an intersti-
tial lung disease characterized by intra-alveolar buds of
connective tissue [1]. It can be idiopathic or associated
with a known underlying disease.
In this case report, we present a 33-year-old man with
COP, followed by concomitant Kikuchi Fujimoto disease
(KFD). KFD was first described in 1972 by Kikuchi and
Fujimoto and others. It is a clinicopathological entity
that commonly presents with cervical lymphadenopathy
and fever in the absence of an active infectious disease.
KFD is a rare histiocytic necrotizing lymphadenitis,
which has a benign self-limiting clinical course. Its ori-
gin is unknown, but an abnormal autoimmune reaction
has been suggested and infection is often considered as
an inducing feature [2].
To the best of our knowledge, this is the first case
report of COP and KFD.
Case Presentation
A 33-year-old man presented with a 1-month coughing
illness and fever that lasted for 5 days. Before admission,
the patient experienced expectoration of yellow sputum
and antibiotic therapy for 2 weeks. There was no history
of fever, rash or respiratory distress, and there was no
family history of autoimmune or connective tissue disor-
ders. Respiratory examinations revealed fine crackles in
both lungs. Examination of other systems was
unremarkable.
The laboratory investigation showed hemoglobin
140 g/L, leukocytes 3.9 × 109/L with a normal differen-
tial count, platelets 142 × 109/L, C-reactive protein
1.2 mg/L, and an erythrocyte sedimentation rate (ESR)
of 14 mm/h. Heterophil agglutination trial was nega-
tive. Serum biochemistry findings including liver and
renal function were within normal limits. The results
of cellular immunity assay showed a decrease in the
CD4/CD8 ratio (0.63). Test results were negative for
toxoplasma, cytomegalovirus (CMV), rubella, Epstein-
Barr virus (EBV), human herpes virus type 1 and
human immunoddficiency virus (HIV). Also rheumato-
logical and immunological tests were normal. These
tests included antinuclear antibody, rheumatoid factor,
antistreptolysin O, antineutrophil cytoplasmic antibody
and the levels of serum C3 and C4 as well as IgG, IgA,
IgE and IgM.
Bacteriological analysis of blood, sputum and urine did
not reveal any pathogenic agents. Pulmonary function
presented restrictive ventilatory functional disturbance.
* Correspondence: fan615@yahoo.com
1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University,
180 Feng Lin Road, Shanghai, 200032, PR China
Hua and Zhu BMC Infectious Diseases 2010, 10:64
http://www.biomedcentral.com/1471-2334/10/64
© 2010 Hua and Zhu; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
In addition, chest computed tomography (CT) demon-
strated diffuse infiltrating lesions in both lungs, predo-
minantly in the lower lobes (Fig. 1A).
With an initial diagnosis of bilateral pneumonia, moxi-
floxacin and cefepime were initiated. Eleven days after
admission, a solitary lymph node was first found in the
right anterior cervical chain. The lymph node was tender
and measured 3 cm in diameter. At this point, the
patients had leucopenia (4.3 × 109/L) and lymphopenia
(0.8 × 109/L). The ESR was slightly accelerated to
40 mm/h. The serum C-reactive protein level was nor-
mal. The serum galactomannan enzyme immunoassay
and 1, 3 b-glucan assays for diagnosis of invasive fungal
infection were negative. Findings were negative for an
intradermal tuberculin test, as well as for sputum and
urine tests for the Mycobacterium tuberculosis. The sero-
logical test for coxsackie B virus suggested infection in
the recent past.
A cervical lymph node biopsy showed normal lymph
node architecture in some areas, but a few irregular
necrotic areas with intense karyorrhexis. Around the
necrotic areas, macrophages, plasma cells, histiocytes
and lymphocytes were noted. No neutrophils were
detected (Fig. 2A). No tuberculoid granuloma, caseat-
ing necrosis, or evidence of malignancy was found.
Immunohistochemistry studies showed that the lym-
phoid cells adjacent to the necrotic foci were positive
for CD3, LCA and CD45RO, but negative for CD20.
CD79-positive cells were seen farther away from the
necrotic foci. Histiocytic cells at the periphery of the
necrotic foci were strongly positive for CD68. This his-
tological pattern was suggestive of KFD [3].
Bronchoalveolar lavage fluid showed no increase in
eosinophil or lymphocyte counts, but a decrease in the
CD4/CD8 ratio (0.52). Lung biopsy by video-assisted
thoracoscopy was performed 12 days post-admission
and revealed granulation tissue in the alveolar spaces,
with associated marked alveolar wall thickening and
frequent metaplasia of bronchiolar and alveolar cells
(Fig. 2B). The staining of reticular fiber, PAS and hex-
amethylenetetramine silver were negative. These find-
ings of BAL and lung biopsy were compatible with
COP [4,5].
After the diagnosis of KFD associated with COP,
45 mg/day prednisone was administered, with a gradual
improvement in symptoms. A second HRCT was done,
which showed marked resolution of the alveolar exu-
dates (Fig. 1B), and cervical lymphadenopathy had
resolved 8 days post-treatment. At 12 weeks follow-up,
the patient remained well, with no other symptoms or
lymph node enlargement.
Conclusions
COP is a rare disease. The characteristic clinical features
of COP are flu-like illness, followed by progressive dys-
pnea, patchy infiltrates on chest radiography and CT, a
restrictive spirometric pattern with diffusion impair-
ment. And, the histopathological pattern of COP is
intraluminal organization, predominantly within the
alveolar ducts and alveoli [6].
KFD was first described in 1972 by the Japanese
pathologists Kikuchi and Fujimoto as a benign, self-lim-
ited syndrome of necrotizing lymphadenitis with a char-
acteristic histopathological appearance that mimics
Figure 1 Chest CT finding of COP. A: HRCT was performed before glucocorticoids were administered, and showed patchy areas of ground-
glass attenuation and consolidation in the lower lobes that contained air bronchograms. B: A follow-up HRCT was performed 8 days after
glucocorticoid administration. It showed improvement in both the lungs with few residual lesions.
Hua and Zhu BMC Infectious Diseases 2010, 10:64
http://www.biomedcentral.com/1471-2334/10/64
Page 2 of 4
malignant lymphoma. It typically presents as localized
lymphadenopathy, predominantly in the cervical region,
accompanied by fever and leukopenia in up to 50% of
cases [7].
Reports in the literature of an association between
respiratory manifestation and KFD are not frequent. In
1990, Tanaka et al. [8] reported one patient with KFD
who presented with respiratory symptoms, and T-lym-
phocyte alveolitis was diagnosed. Additionally, antinuc-
lear antibodies were positive, and antibodies against
human T-lymphotrophic virus type 1 (HTLV-I) were
false positive. These findings suggested an immunologi-
cal abnormality. Cervical lymph node swelling and infil-
trative shadow on chest X-ray film improved with
steroid therapy.
Several suggestions on the etiology of COP or KFD
have been raised. Certain microorganisms (EBV, HTLV-
I, herpes human 6 virus, Toxoplasma, parvovirus B19,
CMV, Brucella, Yersinia enterocolitica and parainfluenza
virus) have been suggested as the causative agents of the
disease, and initiate a hyper-immune response of the T
cells and histiocytes to the infectious agents. Positive
serological test for Coxsackie B virus in this case might
be same mechanism. However, none of these possibili-
ties have been definitively proven [9,10]. In addition,
many cases of KFD in patients with lupus have been
reported. KFD has also been reported in other autoim-
mune diseases, including Still disease [11], rheumatoid
arthritis [12], polymyositis [13], and mixed connective
tissue disease [14].
Similarly, COP has been described in various autoim-
mune diseases [15], primarily in rheumatoid arthritis
[16] but also in systemic lupus erythematosus and
polymyositis [12]. It is clear that an immunological
abnormality is the common pathogenesis of COP and
KFD. Although the precise mechanism may be differ-
ent, response of corticosteroids on this case indicated
that the pathogenesis of both diseases may be
immune-mediated. Therefore, the concomitant appear-
ance of COP and KFD probably reflects two diseases
that are part of a continuum, rather than separate
entities.
In summary, we presented a case of COP that was
diagnosed concurrently with KFD. The potential etiology
of concomitant COP and KFD in our case could have
been a nonspecific reaction to lung injury, unclear
immunologically mediated response, occult virus infec-
tion, or immunosuppression. Further studies on a series
of COP patients are necessary to elucidate this
mechanism.
Consent
Written informed consent was obtained from the patient
for publication of this case report and any accompany-
ing images. A copy of the written consent is available
for review by the Editor-in-Chief of this journal.
Author details
1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University,
180 Feng Lin Road, Shanghai, 200032, PR China. 2Department of Pulmonary
Medicine, Huzhou central Hospital, 198 Hongqi Road, Huzhou city, Zhejiang
province, 313000, PR China.
Authors’ contributions
FH has acquisition of data and interpretation of data; LZ has been involved
in drafting the manuscript. Both authors read and approved the final
manuscript.
Competing interests
The author denies that he has any intention to obtain any financial interests.
Received: 25 September 2009 Accepted: 11 March 2010
Published: 11 March 2010
Figure 2 Histopathological findings. A: Lymph node histology of the patient showed aggregation of histiocytes and plasmacytoid monocytes
with focal necrosis, scattered pyknotic nuclei and karyorrhexis (HE, ×20). Insert shows more details (HE, ×40). B: Lung biopsy illustrating
intraluminal fibrous tissue plugs with adjacent thickened interstitium, intraalveolar macrophages, and lymphoplasmacytic inflammation (HE, ×20).
Insert shows more details (HE, ×40).
Hua and Zhu BMC Infectious Diseases 2010, 10:64
http://www.biomedcentral.com/1471-2334/10/64
Page 3 of 4
References
1. Lohr RH, Boland BJ, Douglas WW, Dockrell DH, Colby TV, Swensen SJ,
Wollan PC, Silverstein MD: Organizing pneumonia - Features and
prognosis of cryptogenic, secondary, and focal variants. Arch Intern Med
1997, 157(12):1323-1329.
2. Menasce LP, Banerjee SS, Edmondson D, Harris M: Histiocytic necrotizing
lymphadenitis (Kikuchi-Fujimoto disease): Continuing diagnostic
difficulties. Histopathology 1998, 33(3):248-254.
3. Sumiyoshi Y, Kikuchi M, Takeshita M, Ohshima K, Masuda Y, Parwaresch MR:
Immunohistologic studies of kikuchis disease. Hum Pathol 1993,
24(10):1114-1119.
4. American Thoracic Society/European Respiratory Society International
Multidisciplinary Consensus Classification of the Idiopathic Interstitial
Pneumonias. This Joint Statement of the American Thoracic Society
(ATS), and the European Respiratory Society (ERS) was adopted by the
ATS Board of Directors, June 2001 and by The ERS Executive
Committee, June 2001. Am J Resp Crit Care 2002, 165(2):277-304.
5. Poletti V, Cazzato S, Minicuci N, Zompatori M, Burzi M, Schiattone ML: The
diagnostic value of bronchoalveolar lavage and transbronchial lung
biopsy in cryptogenic organizing pneumonia. Eur Respir J 1996,
9(12):2513-2516.
6. Wells AU: Cryptogenic organizing pneumonia. Sem Resp Crit Care M 2001,
22(4):449-459.
7. Kuo TT: Kikuchis disease (histiocytic necrotizing lymphadenitis) - a
clinicopathological study of 79 cases with an analysis of histologic
subtypes, immunohistology, and dna-ploidy. Am J Surg Pathol 1995,
19(7):798-809.
8. Tanaka M, Yano T, Ichikawa Y, Kaji M: [A case of subacute necrotizing
lymphadenitis with localized interstitial pneumonia]. Nihon Kyobu Shikkan
Gakkai Zasshi 1990, 28(9):1234-1238.
9. George TI, Jones CD, Zehnder JL, Warnke RA, Dorfman RF: Lack of human
herpesvirus 8 and Epstein-Barr virus in Kikuchi’s histiocytic necrotizing
lymphadenitis. Hum Pathol 2003, 34(2):130-135.
10. Hollingsworth HC, Peiper SC, Weiss LM, Raffeld M, Jaffe ES: An
investigation of the viral pathogenesis of kikuchi-fujimoto disease - lack
of evidence for epstein-barr-virus or human herpesvirus type-6 as the
causative agents. Arch Pathol Lab Med 1994, 118(2):134-140.
11. Cousin F, Grezard P, Roth B, Balme B, Gregoire-Bardel M, Perrot H: Kikuchi
disease associated with Still disease. Int J Dermatol 1999, 38(6):464-467.
12. Cordier JF: Organizing pneumonia: Cryptogenic and disease associated.
Sem Resp Crit Care M 2003, 24(5):595-606.
13. Wilkinson CE, Nichol F: Kikuchi-Fujimoto disease associated with
polymyositis. Rheumatology 2000, 39(11):1302-1304.
14. Pallet N, Aaron L, Larousserie F, Therby A, Dupont B, Viard JP: Kikuchi-
Fujimoto disease associated with mixed connective tissue disease. Scand
J Rheumatol 2004, 33(6):434-436.
15. Epler GR: Bronchiolitis Obliterans Organizing Pneumonia. Arch Intern Med
2001, 161(2):158-164.
16. Myers JL, Colby TV: Pathological manifestations of bronchiolitis,
constrictive bronchiolitis, cryptogenic organizing pneumonia, and
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Cite this article as: Hua and Zhu: Kikuchi Fujimoto disease associated
with cryptogenic organizing pneumonia: case report and literature
review. BMC Infectious Diseases 2010 10:64.
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Hua and Zhu BMC Infectious Diseases 2010, 10:64
http://www.biomedcentral.com/1471-2334/10/64
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Kikuchi Fujimoto disease associated with cryptogenic organizing pneumonia: case report and literature review

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