- Email: [email protected]
Necrotizing lymphadenitis: Not always tuberculosis, its Kikuchi-Fujimoto's disease
indian journal of tuberculosis xxx (xxxx) xxx
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.journals.elsevier.com/ indian-journal-of-tuberculosis/
Case report
Necrotizing lymphadenitis: Not always tuberculosis, its Kikuchi-Fujimoto's disease Sharad Joshi a, Ankit Bhatia a,*, Nitesh Tayal a, Rajesh Gupta a, Rajesh Tandon b a b
Pulmonology, Max Super Speciality Hospital, Vaishali, Ghaziabad, UttarPradesh, 201011, India Pathology, Max Super Speciality Hospital, Vaishali, Ghaziabad, UttarPradesh, 201011, India
article info
abstract
Article history:
Kikuchi-Fujimoto's disease is an uncommon self limiting, benign cause of generalised
Received 21 August 2019
lymphadenopathy with fever. It can present as a triad of fever, night sweats and lymph-
Accepted 11 October 2019
adenopathy which resembles more common causes like tuberculosis and lymphoma.
Available online xxx
Being an endemic country a patient may be treated on the lines of tuberculosis often. We
Keywords:
responding to antitubercular treatment. Pathologists and Clinicians must be aware of this
Necrotizing lymphadenitis
condition to prevent unnecessary treatment.
present case of a young female who was diagnosed as Kikuchi-Fujimoto's disease after not
Tuberculosis
© 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.
Lymphadenopathy
1.
Introduction
Kikuchi-Fujimoto's disease (KFD) also described as histiocytotic necrotising lymphadenitis is a rare, benign self limiting condition characterized by fever, cervical or generalised Lymphadenopathy and Necrotizing lymphadenitis.1 It was first reported by pathologists Kikuchi and Fujimoto in Japan in the year 1972. Although considered exclusive in asian women it has been found prevalent in many other ethnic groups as well.2,3 It is a poorly recognized entity of unknown etiology, although many infectious and environmental factors have been reckoned.1 The clinical picture resembles tuberculosis or lymphoma and occasionally patients are on antitubercular treatment before an eventual diagnosis of KFD is made.
The triad of fever, lymphadenopathy and night sweats can always point towards Tuberculosis in a high prevalent population like India. We report the case of a 33 year old lady who was on antitubercular drugs for cervical lymphadenopathy which eventually turned out to be Kikuchi's disease on histopathology of Lymph node excision biopsy. We aim to raise awareness about the disease and its importance in the differential diagnosis of lymphadenopathy so as to prevent unnecessary treatment.
2.
Case
A 33-year-old woman with no previous comorbidities presented to the chest clinic with a 1 month history of low grade fever, lethargy, bodyache and an enlarging painful swelling over the
* Corresponding author. E-mail address: [email protected] (A. Bhatia). https://doi.org/10.1016/j.ijtb.2019.10.006 0019-5707/© 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved. Please cite this article as: Joshi S et al., Necrotizing lymphadenitis: Not always tuberculosis, its Kikuchi-Fujimoto's disease, Indian Journal of Tuberculosis, https://doi.org/10.1016/j.ijtb.2019.10.006
2
indian journal of tuberculosis xxx (xxxx) xxx
left side of her neck. She was initially investigated by a general practitioner, Fine Needle aspirate of the swelling were done which was suggestive of epitheloid cells and Langherhan's giant cells. The Acid fast bacilli stain was however negative. Patient was started on 4 drug antitubercular treatment, rifampicin, isoniazid, pyrazinamide, ethambutol after which her symptoms worsened. She developed high grade fever with accompanying headache after which she was admitted to the hospital. Clinical examination revealed left sided level II enlarged, firm swelling measuring 2.5 2 cm. A CT thorax and neck region was done which showed multiple enlarged bilateral cervical nodes (L>R) involving the bilateral level II, level III and few small in left supraclavicular region and Fibrocalcific lesions are seen in apical segment of right upper lobe (Fig. 1). The microbiological culture of the FNA done was negative, as well repeat FNA of lymph node was negative for genexpertmtb test, hence a repeat workup was planned. The antitubercular treatment was kept on hold. The Leucocyte counts, differential count and C reactive protein (CRP) were all within normal limits. The paired Blood cultures were negative, malaria, Dengue, typhoid serologies were also negative. An excision biopsy of the cervical lymph node was done; which showed effacement of lymph node architecture by a paracortical necrotizing lesion showing collection of numerous histiocytes and karyorrhectic debris (Fig. 2). No epitheloid granuloma seen as well as AFB stain and fungal stains were negative. Histomorphology is suggestive of Histiocytic Necrotizing Lymphadenitis (Kikuchis disease). Her Serum Antinuclear antigen, Rheumatoid factor and ds-DNA were negative. Once her TB drugs were stopped the fever spikes improved as well other symptoms were better.
Fig. 1 e CT thorax and neck region was done which showed multiple enlarged bilateral cervical nodes.
Fig. 2 e Biopsy specimen showing effacement of lymph node architecture by a paracortical necrotizing lesion showing collection of numerous histiocytes and karyorrhectic debris.
3.
Discussion
It is a rare, self-limiting cause of cervical or generalized lymphadenopathy, affecting young female aged 20e40 years predominantly described in South-Eastern Asia.1 The predominant clinical presentation is of fever with either generalized or cervical lymphadenopathy. These and other symptoms-generalized bodyache, night sweats, weight loss, nausea, vomiting and hepatosplenomegaly closely resembles tuberculosis or lymphoma.4,5 The Cervical group of nodes are usually affected however other groups involving axillary, mesenteric or inguinal nodes can also be involved rarely.6 Our patient had a typical presentation of Tubercular lymphadenopathy. She had fever, night sweats and weight loss. In a high prevalence country, there would have been little doubt about Tuberculosis being the cause of her lymphadenopathy. KFD has been often misdiagnosed as Tuberculosis, Lymphomas and have occasionally received inappropriate and aggressive treatments based on the wrong diagnosis.7 The etiology is not well described in literature. An autoimmune origin with an infectious trigger of viruses like Cytomegalovirus, human herpes virus (HHV), varicella zoster virus, para-influenza virus and EpsteineBarr virus or Toxoplasmosis have been suspected. A strong autoimmune link with systemic lupus erythematosus (SLE) has been implicated in some patients.8 Blood abnormalities may include raised inflammatory markers, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leucopenia, anemia and slightly raised liver enzyme. However no laboratory study is confirmatory.9 The diagnosis is confirmed on excisional lymph node biopsy. The histological picture is of follicular hyperplasia, necrotising foci with a high degree of karyorrhexis and the
Please cite this article as: Joshi S et al., Necrotizing lymphadenitis: Not always tuberculosis, its Kikuchi-Fujimoto's disease, Indian Journal of Tuberculosis, https://doi.org/10.1016/j.ijtb.2019.10.006
indian journal of tuberculosis xxx (xxxx) xxx
absence of neutrophils and eosinophils paracortical histiocytic and lymphocytic infiltrates.10 The disease if self-limiting, treatment is of supportive care however corticosteroids, antibiotics, Hydroxychloroquine and have been used to aid recovery in some case with persistent symptoms. The symptoms usually resolve in 4e6 months.11 A positive antinuclear antibody test (ANA) has been found to be associated with higher chances of relapse.12 The clinical spectrum of Kikuchi-Fujimoto can mimic many common conditions and pose difficulties to experienced pathologists and physicians.13 Our case emphasizes on the importance of considering other differentials of lymphadenopathy if the initial diagnosis is not certain so as to prevent inadvertent therapeutic misadventures.
Declaration of Competing Interest The authors have none to declare.
references
1. Joean O, Thiele T, Raap M, Schmidt RE, Stoll M. Take a second look: it's Kikuchi's disease! A case report and review of literature. Clin Pract. 2018;8(4):1095. 2. Kucukardali Y, Solmazgul E, Kunter E, et al. Kikuchi-Fujimoto Disease: analysis of 244 cases. Clin Rheumatol. 2007;26:50e54. 3. Poulose V, Chiam P, Poh WT. Kikuchi's disease: a Singapore case series. Singap Med J. 2005;46:229e232.
3
4. Bosch X, Guilabert A, Miquel R, Campo E. Enigmatic KikuchiFujimoto disease: a comprehensive review. Am J Clin Pathol. 2004;122:141e152. 5. Mathew LM, Kapila R, Schwartz RA. Kikuchi-Fujimoto disease: a diagnostic dilemma. Int J Dermatol. 2016;55:1069e1075. 6. Nayak HK, Mohanty PK, Mallick S, et al. Diagnostic dilemma: kikuchi's disease or tuberculosis? BMJ Case Rep. 2013;2013. https://doi.org/10.1136/bcr-2012-008026, 2013:pii: bcr2012008026. 7. McKenna C, Whitfield T, Patel N, Bonington A. TB or not to be? Kikuchi- Fujimoto disease: a rare but important differential for TB. BMJ Case Rep. 2017;2017. 8. Quintas-Cardama A, Fraga M, Cozzi SN, et al. Fatal KikuchiFujimoto disease: the lupus connection. Ann Hematol. 2003;82:186e188. https://doi.org/10.1007/s00277-003-0611-7. 9. Dumas G, Prendki V, Haroche J, et al. Kikuchi-Fujimoto disease: retrospective study of 91 cases and review of the literature. Medicine. 2014;93:372e382. 10. Barbat B, Jhaj R, Khurram D. Fatality in Kikuchi-Fujimoto disease: a rare phenomenon. World J Clini Cases. 2017;5:35e39. 11. Rezai K, Kuchipudi S, Chundi V, et al. Kikuchi-Fujimoto disease: hydroxychloroquine as a treatment. Clin Infect Dis. 2004;39:e124ee126. https://doi.org/10.1086/426144. 12. Vivekanandarajah A, Krishnarasa B, Hurford M, et al. Kikuchi's disease: a rare cause of fever and lymphadenopathy. Clin Med Insights Pathol. 2012;5:7e10. https://doi.org/10.4137/CPath.S8685. 13. Min KK, Min BW, Lee KJ, Choi JH. Kikuchi-Fujimoto disease misdiagnosed as relapse of the infection after treatment of periprosthetic hip joint infection. Hip & Pelvis. 2016;28:254e258.
Please cite this article as: Joshi S et al., Necrotizing lymphadenitis: Not always tuberculosis, its Kikuchi-Fujimoto's disease, Indian Journal of Tuberculosis, https://doi.org/10.1016/j.ijtb.2019.10.006
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.journals.elsevier.com/ indian-journal-of-tuberculosis/
Case report
Necrotizing lymphadenitis: Not always tuberculosis, its Kikuchi-Fujimoto's disease Sharad Joshi a, Ankit Bhatia a,*, Nitesh Tayal a, Rajesh Gupta a, Rajesh Tandon b a b
Pulmonology, Max Super Speciality Hospital, Vaishali, Ghaziabad, UttarPradesh, 201011, India Pathology, Max Super Speciality Hospital, Vaishali, Ghaziabad, UttarPradesh, 201011, India
article info
abstract
Article history:
Kikuchi-Fujimoto's disease is an uncommon self limiting, benign cause of generalised
Received 21 August 2019
lymphadenopathy with fever. It can present as a triad of fever, night sweats and lymph-
Accepted 11 October 2019
adenopathy which resembles more common causes like tuberculosis and lymphoma.
Available online xxx
Being an endemic country a patient may be treated on the lines of tuberculosis often. We
Keywords:
responding to antitubercular treatment. Pathologists and Clinicians must be aware of this
Necrotizing lymphadenitis
condition to prevent unnecessary treatment.
present case of a young female who was diagnosed as Kikuchi-Fujimoto's disease after not
Tuberculosis
© 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.
Lymphadenopathy
1.
Introduction
Kikuchi-Fujimoto's disease (KFD) also described as histiocytotic necrotising lymphadenitis is a rare, benign self limiting condition characterized by fever, cervical or generalised Lymphadenopathy and Necrotizing lymphadenitis.1 It was first reported by pathologists Kikuchi and Fujimoto in Japan in the year 1972. Although considered exclusive in asian women it has been found prevalent in many other ethnic groups as well.2,3 It is a poorly recognized entity of unknown etiology, although many infectious and environmental factors have been reckoned.1 The clinical picture resembles tuberculosis or lymphoma and occasionally patients are on antitubercular treatment before an eventual diagnosis of KFD is made.
The triad of fever, lymphadenopathy and night sweats can always point towards Tuberculosis in a high prevalent population like India. We report the case of a 33 year old lady who was on antitubercular drugs for cervical lymphadenopathy which eventually turned out to be Kikuchi's disease on histopathology of Lymph node excision biopsy. We aim to raise awareness about the disease and its importance in the differential diagnosis of lymphadenopathy so as to prevent unnecessary treatment.
2.
Case
A 33-year-old woman with no previous comorbidities presented to the chest clinic with a 1 month history of low grade fever, lethargy, bodyache and an enlarging painful swelling over the
* Corresponding author. E-mail address: [email protected] (A. Bhatia). https://doi.org/10.1016/j.ijtb.2019.10.006 0019-5707/© 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved. Please cite this article as: Joshi S et al., Necrotizing lymphadenitis: Not always tuberculosis, its Kikuchi-Fujimoto's disease, Indian Journal of Tuberculosis, https://doi.org/10.1016/j.ijtb.2019.10.006
2
indian journal of tuberculosis xxx (xxxx) xxx
left side of her neck. She was initially investigated by a general practitioner, Fine Needle aspirate of the swelling were done which was suggestive of epitheloid cells and Langherhan's giant cells. The Acid fast bacilli stain was however negative. Patient was started on 4 drug antitubercular treatment, rifampicin, isoniazid, pyrazinamide, ethambutol after which her symptoms worsened. She developed high grade fever with accompanying headache after which she was admitted to the hospital. Clinical examination revealed left sided level II enlarged, firm swelling measuring 2.5 2 cm. A CT thorax and neck region was done which showed multiple enlarged bilateral cervical nodes (L>R) involving the bilateral level II, level III and few small in left supraclavicular region and Fibrocalcific lesions are seen in apical segment of right upper lobe (Fig. 1). The microbiological culture of the FNA done was negative, as well repeat FNA of lymph node was negative for genexpertmtb test, hence a repeat workup was planned. The antitubercular treatment was kept on hold. The Leucocyte counts, differential count and C reactive protein (CRP) were all within normal limits. The paired Blood cultures were negative, malaria, Dengue, typhoid serologies were also negative. An excision biopsy of the cervical lymph node was done; which showed effacement of lymph node architecture by a paracortical necrotizing lesion showing collection of numerous histiocytes and karyorrhectic debris (Fig. 2). No epitheloid granuloma seen as well as AFB stain and fungal stains were negative. Histomorphology is suggestive of Histiocytic Necrotizing Lymphadenitis (Kikuchis disease). Her Serum Antinuclear antigen, Rheumatoid factor and ds-DNA were negative. Once her TB drugs were stopped the fever spikes improved as well other symptoms were better.
Fig. 1 e CT thorax and neck region was done which showed multiple enlarged bilateral cervical nodes.
Fig. 2 e Biopsy specimen showing effacement of lymph node architecture by a paracortical necrotizing lesion showing collection of numerous histiocytes and karyorrhectic debris.
3.
Discussion
It is a rare, self-limiting cause of cervical or generalized lymphadenopathy, affecting young female aged 20e40 years predominantly described in South-Eastern Asia.1 The predominant clinical presentation is of fever with either generalized or cervical lymphadenopathy. These and other symptoms-generalized bodyache, night sweats, weight loss, nausea, vomiting and hepatosplenomegaly closely resembles tuberculosis or lymphoma.4,5 The Cervical group of nodes are usually affected however other groups involving axillary, mesenteric or inguinal nodes can also be involved rarely.6 Our patient had a typical presentation of Tubercular lymphadenopathy. She had fever, night sweats and weight loss. In a high prevalence country, there would have been little doubt about Tuberculosis being the cause of her lymphadenopathy. KFD has been often misdiagnosed as Tuberculosis, Lymphomas and have occasionally received inappropriate and aggressive treatments based on the wrong diagnosis.7 The etiology is not well described in literature. An autoimmune origin with an infectious trigger of viruses like Cytomegalovirus, human herpes virus (HHV), varicella zoster virus, para-influenza virus and EpsteineBarr virus or Toxoplasmosis have been suspected. A strong autoimmune link with systemic lupus erythematosus (SLE) has been implicated in some patients.8 Blood abnormalities may include raised inflammatory markers, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leucopenia, anemia and slightly raised liver enzyme. However no laboratory study is confirmatory.9 The diagnosis is confirmed on excisional lymph node biopsy. The histological picture is of follicular hyperplasia, necrotising foci with a high degree of karyorrhexis and the
Please cite this article as: Joshi S et al., Necrotizing lymphadenitis: Not always tuberculosis, its Kikuchi-Fujimoto's disease, Indian Journal of Tuberculosis, https://doi.org/10.1016/j.ijtb.2019.10.006
indian journal of tuberculosis xxx (xxxx) xxx
absence of neutrophils and eosinophils paracortical histiocytic and lymphocytic infiltrates.10 The disease if self-limiting, treatment is of supportive care however corticosteroids, antibiotics, Hydroxychloroquine and have been used to aid recovery in some case with persistent symptoms. The symptoms usually resolve in 4e6 months.11 A positive antinuclear antibody test (ANA) has been found to be associated with higher chances of relapse.12 The clinical spectrum of Kikuchi-Fujimoto can mimic many common conditions and pose difficulties to experienced pathologists and physicians.13 Our case emphasizes on the importance of considering other differentials of lymphadenopathy if the initial diagnosis is not certain so as to prevent inadvertent therapeutic misadventures.
Declaration of Competing Interest The authors have none to declare.
references
1. Joean O, Thiele T, Raap M, Schmidt RE, Stoll M. Take a second look: it's Kikuchi's disease! A case report and review of literature. Clin Pract. 2018;8(4):1095. 2. Kucukardali Y, Solmazgul E, Kunter E, et al. Kikuchi-Fujimoto Disease: analysis of 244 cases. Clin Rheumatol. 2007;26:50e54. 3. Poulose V, Chiam P, Poh WT. Kikuchi's disease: a Singapore case series. Singap Med J. 2005;46:229e232.
3
4. Bosch X, Guilabert A, Miquel R, Campo E. Enigmatic KikuchiFujimoto disease: a comprehensive review. Am J Clin Pathol. 2004;122:141e152. 5. Mathew LM, Kapila R, Schwartz RA. Kikuchi-Fujimoto disease: a diagnostic dilemma. Int J Dermatol. 2016;55:1069e1075. 6. Nayak HK, Mohanty PK, Mallick S, et al. Diagnostic dilemma: kikuchi's disease or tuberculosis? BMJ Case Rep. 2013;2013. https://doi.org/10.1136/bcr-2012-008026, 2013:pii: bcr2012008026. 7. McKenna C, Whitfield T, Patel N, Bonington A. TB or not to be? Kikuchi- Fujimoto disease: a rare but important differential for TB. BMJ Case Rep. 2017;2017. 8. Quintas-Cardama A, Fraga M, Cozzi SN, et al. Fatal KikuchiFujimoto disease: the lupus connection. Ann Hematol. 2003;82:186e188. https://doi.org/10.1007/s00277-003-0611-7. 9. Dumas G, Prendki V, Haroche J, et al. Kikuchi-Fujimoto disease: retrospective study of 91 cases and review of the literature. Medicine. 2014;93:372e382. 10. Barbat B, Jhaj R, Khurram D. Fatality in Kikuchi-Fujimoto disease: a rare phenomenon. World J Clini Cases. 2017;5:35e39. 11. Rezai K, Kuchipudi S, Chundi V, et al. Kikuchi-Fujimoto disease: hydroxychloroquine as a treatment. Clin Infect Dis. 2004;39:e124ee126. https://doi.org/10.1086/426144. 12. Vivekanandarajah A, Krishnarasa B, Hurford M, et al. Kikuchi's disease: a rare cause of fever and lymphadenopathy. Clin Med Insights Pathol. 2012;5:7e10. https://doi.org/10.4137/CPath.S8685. 13. Min KK, Min BW, Lee KJ, Choi JH. Kikuchi-Fujimoto disease misdiagnosed as relapse of the infection after treatment of periprosthetic hip joint infection. Hip & Pelvis. 2016;28:254e258.
Please cite this article as: Joshi S et al., Necrotizing lymphadenitis: Not always tuberculosis, its Kikuchi-Fujimoto's disease, Indian Journal of Tuberculosis, https://doi.org/10.1016/j.ijtb.2019.10.006