Kimura’s disease of the lacrimal gland mimicking IgG4-related orbital disease
© Li et al.; licensee BioMed Central Ltd. 2014
Received: 9 October 2014
Accepted: 11 December 2014
Published: 15 December 2014
Kimura’s disease (KD) is a rare and benign chronic inflammatory soft tissue disorder of unknown origin, which predominantly inflicts young male adults in Asia. IgG4-related disease is a new disease concept, established this century and characterized by fibrosis and sclerosis of the involved organs, with infiltration of IgG4-positive plasma cells. These two kinds of diseases share similar characteristics, which may complicate their diagnosis.
A 47-year-old Chinese man presented to our Department of Ophthalmology with a 26-month history of painless swelling and redness left upper eyelid. Surgical excisions of the left lacrimal gland were performed. A histopathology examination showed follicular hyperplasia with reactive germinal centres and eosinophilic infiltration involving the interfollicular areas as well as proliferation of post capillary venules, all signs of Kimura disease. Immunohistochemical analysis of the cells demonstrated positive staining for CK, Vimentin, CD3, CD4, CD20, CD21, CD117, CD5, CD8, CD23, IgG and IgG4 (30 per high-power field) and negative staining for CD10 and CD34. Some ophthalmologists in our department questioned whether the histological and immunohistochemical findings were also compatible with features of IgG4-related diseases. There was no sign of recurrence during the twelve months of regular follow-up.
Kimura’s disease may present with high serum IgG4 levels, which may be an epiphenomenon related to chronic antigen exposure. As clinical doctors, especially ophthalmologists, we should recognize the possibility of the occurrence of increased serum levels of IgG4 in Kimura’s disease to ensure correct diagnosis.
KeywordsKimura’s disease IgG4-related disease Lacrimal gland
Kimura’s disease (KD) is a rare and benign chronic inflammatory soft tissue disorder of unknown origin, which predominantly inflicts head and neck of young male adults in Asia [1, 2]. IgG4-related disease is a new disease concept, established this century and characterized by fibrosis and sclerosis of the involved organs, with infiltration of IgG4-positive plasma cells [3, 4]. Herein, we report a case of KD occurring in the left lacrimal gland with increased serum levels of IgG4, which mimics IgG4-related disease. To our knowledge, few publications in the literature have been reported with KD of lacrimal gland likewise.
A 47-year-old Chinese man presented to our department of ophthalmology with a 26-month history of left upper eyelid painless swelling and redness. The patient was initially treated with a course of intravenous penicillin, which resulted in temporary regression of the lesion. There had been no similar family history of this appearance to date.
The patient was discharged following his surgery and treated with prednisone 25 mg/day for four weeks and then reduce by 5 mg/day every two weeks. His symptoms gradually improved. Serum immunoglobulin E (IgE) levels dropped to 125.9 IU/mL and eosinophil’s decreased to 0.69 × 109/L after 2 months. There was no sign of recurrence in twelve months of regular follow-up.
Kimura disease (KD) is a rare benign chronic inflammatory disease of unknown etiology, which frequently affects young male adults in Asia. It often presents with subcutaneous masses around the head and neck without systemic symptoms. Laboratory tests are characterized by eosinophilia (>5% of white blood cell, or >0.5 × 109/L of blood) and raised IgE levels [1, 2].
Immunoglobulin G4-related disease (IgG4-RD) is a recently defined systemic fibro inflammatory condition characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-bearing plasma cells and fibrosis of the involved organs. It can inflict all the organs, such as pancreas, bile duct, gallbladder, orbit, salivary gland, retro peritoneum, and kidney [3, 4].
Diagnosis of any diseases should be carried out in a comprehensive manner on the basis of physical, imaging, serological and, especially, histopathological findings. However, there are some similar characteristics between KD and IgG4-RD, with eosinophilia or high IgE levels often found in patients with IgG4-RD [5–8]. Herein, we have reported a case study of a 47-year-old man with a 26-month history of left upper eyelid painless swelling and redness. He had a significant eosinophilia and elevated serum IgE and IgG4 levels. Biopsy of his left lacrimal gland suggested the diagnosis of both KD and IgG4-RD. Therefore, we performed a literature review of Kimura’s disease, in which elevated serum levels of IgG4 and/or abundant infiltration of IgG4-bearing plasma cells had also been reported. To our knowledge, there were 5 cases that reported Kimura’s disease with the characteristics of IgG4-RD, which were located in skin, lung, and lymph node [5–8]. No orbital KD has been reported to date.
Although the two kinds of diseases share some similarities, there are still several different features. Expression of IgE in follicular dendritic cells and eosinophilic micro abscesses is routinely seen in Kimura’s disease, but not in IgG4-related disease . High serum IgG4 concentration and marked infiltration of IgG4-positive plasma cells is also seen in IgG4-related disease, but not in KD. Tsubouchi and colleagues observed numerous IgG4-positive plasma cells in a lung biopsy of a patient with Kimura’s disease, and they suggested the coexistence of the two diseases . Even using the low threshold of 10 IgG4 + cells/high powered field, IgG4 staining correlates with marked eosinophilia in the lacrimal gland based on histology and gene expression. Lei Liu and colleagues reported a 23-year-old Chinese man with remarkable eosinophilia and elevated serum IgE levels . Biopsy of his lymph nodes suggested the diagnosis of both Kimura’s disease and IgG4-related disease. They analyzed the relationship between the two diseases and held a view different from Tsubouchi, that the presence of any IgG4-positive plasma cells in the peripheral blood, infiltration of IgG4-positive plasma cells in lymph nodes, and skin lesions are epiphenomena of Kimura’s disease. We agree with the opinion of Lei Liu and his colleagues.
Recently, Wong et al. analyzed gene expression and the prevalence of IgG4-immunostaining among subjects with orbital inflammatory diseases and made a conclusion that IgG4 + plasma cells are common in orbital tissue from patients with sarcoidosis, granulomatosis with polyangiitis (GPA), or nonspecific orbital inflammatory disease (NSOI) . Aithough KD patients was not collected in his study, the investigation was a indirect support to our opinion.
In summary, we report a rare case of Kimura’s disease occurring in the left lacrimal gland with increased serum levels of IgG4 mimicking IgG4-related disease. Although rare, as clinical doctors, especially ophthalmologists, we should recognize the possibility of occurrence of KD with increased serum levels of IgG4 and pay attention to the disease in our clinical work. Only in this manner can we diagnose it correctly when we meet this situation and then choose the best treatment strategy in order to decrease the rate of recurrence.
Kimura’s disease may present with high serum IgG4 levels, which is just an epiphenomenon related to chronic antigen exposure. As clinical doctors, especially ophthalmologists, we should recognize the possibility of the occurrence of increased serum levels of IgG4 in Kimura’s disease and diagnose the disease correctly.
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Financial support: National Natural Science Foundation of China (81371052).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Chen H, Thompson LD, Aguilera NS, Abbondanzo SL: Kimura disease: a clinicopathologic study of 21 cases. Am J Surg Pathol. 2004, 28: 505-513. 10.1097/00000478-200404000-00010.View ArticlePubMedGoogle Scholar
- Wang DY, Mao JH, Zhang Y, Gu WZ, Zhao SA, Chen YF, Liu AM: Kimura disease: a case report and review of the Chinese literature. Nephron Clin Pract. 2009, 111: c55-c61. 10.1159/000178980.View ArticlePubMedGoogle Scholar
- Stone JH, Zen Y, Deshpande V: IgG4-related disease. N Engl J Med. 2012, 366: 539-551. 10.1056/NEJMra1104650.View ArticlePubMedGoogle Scholar
- Mahajan VS, Mattoo H, Deshpande V, Pillai SS, Stone JH: IgG4-related disease. Annu Rev Pathol. 2014, 9: 315-347. 10.1146/annurev-pathol-012513-104708.View ArticlePubMedGoogle Scholar
- Hattori T, Miyanaga T, Tago O, Udagawa M, Kamiyama Y, Nagai Y, Ishikawa O: Isolated cutaneous manifestation of IgG4-related disease. J Clin Pathol. 2012, 65: 815-818. 10.1136/jclinpath-2012-200749.View ArticlePubMedGoogle Scholar
- Tsubouchi K, Imanaga T, Yamamoto M, Hirata K, Nakano T: A case of IgG4-positive multi-organ lymphoproliferative syndrome associated with Kimura disease. Nihon Kokyuki Gakkai Zasshi. 2010, 48: 524-528.PubMedGoogle Scholar
- Liu L, Chen Y, Fang Z, Kong J, Wu X, Zhang Z: Kimura's disease or IgG4-related disease? A case-based review. Clin Rheumatol. 2013Google Scholar
- McKelvie PA, Lyons B, Barnett G, Allen PW: Kimura’s disease in two Caucasians, one with multiple recurrences associated with prominent IgG4 production. Pathology. 2012, 44: 275-278. 10.1097/PAT.0b013e3283513f95.View ArticlePubMedGoogle Scholar
- Wong AJ, Planck SR, Choi D, Harrington CA, Troxell ML, Houghton DC, Stauffer P, Wilson DJ, Grossniklaus HE, Dailey RA, Ng JD, Steele EA, Harris GJ, Czyz C, Foster JA, White VA, Dolman PJ, Kazim M, Patel PJ, Edward DP, al Katan H, al Hussain H, Selva D, Yeatts RP, Korn BS, Kikkawa DO, Rosenbaum JT: IgG4 immunostaining and its implications in orbital inflammatory disease. PLoS One. 2014, 9: e109847-10.1371/journal.pone.0109847.View ArticlePubMedPubMed CentralGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2415/14/158/prepub
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