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 Table of Contents  
CASE REPORT
Year : 2013  |  Volume : 3  |  Issue : 3  |  Page : 116-119

IgG4-related dacryoadenitis


1 Department of Ophthalmology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan
2 Division of Immunology and Rheumatology, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan

Date of Web Publication22-Aug-2013

Correspondence Address:
Pei-Yuan Su
Department of Ophthalmology, Far-Eastern Memorial Hospital, 21, Section 2, Nan-Ya South Road, Ban-Chiao District, New Taipei City
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.1016/j.tjo.2013.05.003

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  Abstract 


A 44-year-old female presented with bilateral eyelid swelling and painless, palpable mass over the lacrimal gland area for more than 1 year. A bilateral enlarged lacrimal gland with mild contrast enhancement was noted on computed tomography. Biopsy of the lacrimal gland showed lympho- plasmacytic infiltrate with focal hyaline and sclerotic change, and immunohistochemical staining revealed numerous IgG4-positive plasma cells, which was characteristic of IgG4 dacryoadentitis. Serum IgG and IgG4 levels were within normal range. The patient was treated with surgical excision instead of systemic steroid owing to poor tolerance. No tumor recurrence or systemic involvement was noted during the follow-up period. Our case highlights the importance of IgG4 dacryoadenitis in differentiating bilateral lacrimal gland inflammatory conditions. A normal serum IgG4 level does not rule out the diagnosis and surgical excision may be an alternative for those who are considered ineligible for corti- costeroid treatment.

Keywords: dacryoadenitis, IgG4-related disease, lacrimal gland tumor, orbital inflammation


How to cite this article:
Su PY, Wu CS, Chang SW. IgG4-related dacryoadenitis. Taiwan J Ophthalmol 2013;3:116-9

How to cite this URL:
Su PY, Wu CS, Chang SW. IgG4-related dacryoadenitis. Taiwan J Ophthalmol [serial online] 2013 [cited 2022 Aug 16];3:116-9. Available from: https://www.e-tjo.org/text.asp?2013/3/3/116/203876




  1. Introduction Top


IgG4-related diseases (IgG4 RDs) are recently described sys- temic syndromes characterized by elevated serum IgG4 and IgG4- positive lymphoplasmacytic infiltrative lesions in the body. The first reported case was an autoimmune pancreatitis.[1] Orbital tissues can also be affected, and was first reported by Yamamoto et al[2] in a case of Mikulicz’s disease, which is characterized by symmetrical enlargement and hyposecretion of lacrimal and salivary glands. Later on, IgG4 RDs involving different ocular adnexal tissues had been reported.[3],[4],[5],[6] Orbital IgG4 RDs should be differentiated from idiopathic orbital inflammation (IOI) and ocular adnexal lymphoma to ensure appropriate treatment. We present a case of isolated bilateral IgG4-related dacryoadenitis, which was confirmed by pathologic observation and treated with surgical excision. The clinical presentation, pathologic findings of differential diagnosis, and management of orbital IgG4 RDs are reviewed.


  2. Case report Top


A 44-year-old woman presented with progressive bilateral eyelid swelling with mild erythematous change for 2 years. Moreover, no pain or symptoms of dry eye was noted. Her medical history was unremarkable except for a history of allergic rhinitis.

Clinical examination revealed a bilateral swollen eyelid with palpable mass lesions in the lacrimal fossa, which were firm, nontender, and not movable [Figure 1]. The visual acuity, intraocular pressure, and eye movement were not affected. Hertel exophthal- mometer measurements were 13 mm in both eyes. No ptosis or abnormal eyelid shape was noted. Slit-lamp biomicroscopy and fundoscopy examination were normal. Orbital computed tomography showed circumscribed mass lesion within the bilateral lacrimal fossa with mild contrast enhancement, and normal adjacent bony structure [Figure 2]. No adjacent sinus or deep orbital invasion was noted. No systemic infection or inflammation signs were noted according to the blood test. Thyroid function test result was within normal limits. Serum IgG level was 1600 mg/dL (normal range: 700.0̵1600.0 mg/dL) and IgG 4 level was 103 mg/dL (normal range: 3.0–201.0 mg/dL). According to the clinical and image studies, orbital pseudotumor or sclerosing dacryoadenitis cannot be ruled out; therefore, oral prednisolone (30 mg/day) was prescribed. However, lid swelling did not show much improvement after 2 months. Excisional biopsy of the right lacrimal gland was done, and the specimen measured 2.5 cm × 1.3 cm × 0.5 cm in size with a relatively smooth surface [Figure 3]A. The pathology examination showed the following: florid mixed lymphoid, plasma cells and scattered eosinophilic infiltrate, focal hyaline, and sclerotic change [Figure 3]B and [Figure 3]C; immunohistochemically, the number of IgG4-positive plasma cells was >10 under high power field (40×), and the ratio of the IgG4/IgG plasma cells was more than 50% [Figure 3]D. The clinical and pathologic findings were consistent with IgG4-related dacryoadenitis.
Figure 1: Clinical appearance showed bilateral upper eyelid swelling with mild skin erythematous change. Physical examination revealed firm, nontender palpable mass lesion over bilateral lacrimal gland fossa.

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Figure 2: Computed tomography of orbit–(A) coronal view, (B) axial view–revealing bilateral lacrimal gland enlargement (arrow) without adjacent bony destruction. The tumors were mildly enhanced by contrast. No sinus or deep orbital invasion was noted.

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Figure 3: (A) Lacrimal gland excised measured 2.5 cm × 1.3 cm × 0.5 cm in size with a relatively smooth surface. (B) Hematoxylineeosin stain of low power field (40×) showed abundant inflammatory infiltrations in lacrimal ducts with focal hyaline and sclerosing changes (arrow). (C) Hematoxylineeosin stain of high power field (100×) showed that most infiltrates comprise plasma cells. (D) Immunohistochemistry study (400×) showed that a high proportion of plasma cells are positive for IgG4.

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The postoperation course was smooth and showed substantial improvement without any sign of dryness or ocular surface complications [Figure 4]A. Excision of the left lacrimal gland was arranged 7 months after the first surgery because of persistent swelling of the left eyelid and poor tolerance of systemic steroids. The pathologic findings were still consistent with IgG4-related dacryoadenitis despite the normal serum IgG4 level. The patient had been followed for more than 1 year and remained symptom-free without other systemic involvement [Figure 4]B.
Figure 4: (A) Seven months after excision of the right lacrimal gland, normal appearance of the right eye and persistent left upper eyelid swelling with palpable mass over lacrimal fossa (arrow) were observed. (B) Two months after excision of the left lacrimal gland, normal appearance of both eyes was noted.

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  3. Discussion Top


IgG4 RDs are a relatively newly described disease entity used to demonstrate fibroinflammatory diseases occurring at various sites of the body. It is characterized by elevated serum IgG4 (>135 mg/ dL) and histological observation of IgG4-positive plasma cell infiltration (ratio of IgG4/IgG-positive cells >40% and >10 IgG4-positive plasma cells/HPF) and fibrosis of the affected organ.[7] The first reported case of IgG4 RD is sclerosing pancreatitis.[1] Other frequently reported cases include retroperitoneal fibrosis, Riedel thyroiditis, panniculitis, sclerosing cholangitis, and sialadenitis.[7]

Orbital and ocular adnexal tissue can also be affected, and it was first reported by Yamamoto et al[2] in 2005 for observation of bilateral symmetric enlargement of lacrimal and salivary glands, which was referred to as Mikulicz’s disease. The median age of patients with orbital IgG4 RD is 59 years, and both sexes are equally affected, except for bilateral lacrimal gland lesions, which is female- predominant. [2],[4],[5],[6] The most reported common site of orbital IgG4 RDs is the lacrimal gland (69%), and it is usually bilaterally involved (48%). Other sites reported include the extraocular muscle, the infraorbital nerve, the optic nerve sheath, the lacrimal sac, the cavernous sinus, or intracranial invasion.[3],[4],[5],[6],[8]

Orbital IgG4 RDs usually present as chronic lid swelling or proptosis, with minimal inflammation or restriction of ocular motility. Visual disturbance is rare, unless there is orbital apex lesion. Most orbital IgG4 RDs present as the only site involved, although some have other systemic lesions, such as those found in submandibular glands, lymph nodes, pancreas, bile duct,[4],[5],[6] or thyroid and pituitary glands.[9],[10] Clinically, it should be differentiated from IOI, which is characterized by acute onset of orbital inflammation. Orbital IgG4 RDs have a more indolent course. However, tissue biopsy is essential for making specific diagnosis. In many cases with presumed IOI, like our case initially, patients do not undergo biopsy, or IgG4 staining is not routinely performed even if biopsy is done. As a result, an accurate diagnosis of orbital IgG4 RD cannot be made.

Histopathologic findings of ocular IgG4 RD include marked lymphoplasmacytic infiltration, lymphoid follicles, admixed with dense fibrosis, and abundant infiltration of IgG4-positive plasma cells.[6] IgG4-related dacryoadenitis has been considered a subtype of Sjogren syndrome because of their pathological resemblance. However, it differs from Sjogren syndrome in that patients with IgG4-related dacryoadenitis lack anti-SS antibodies, and are characterized with elevated serum IgG4 levels, numerous IgG4-positive plasma cells, and maintained lacrimal gland function.[11] Another important disease that should be differentiated is ocular adnexal marginal B-cell lymphoma, because some cases may show IgG4- positive plasma cells and elevated serum IgG4 levels.[12] Evidence of light chain restriction by in situ hybridization and immuno- globulin heavy chain gene rearrangement by Southern blotting seen in lymphoma cases can differentiate between these diseases. However, there are reports of ocular adnexal marginal B-cell lym- phomas arising from IgG4-related dacryoadenitis.[13] In our case, Sjogren syndrome had been ruled out by blood test, and lymphoma had not been noted by histopathologic examination. However, long-term surveillance for malignant transformation may be indicated.

The laboratory data of patients with orbital adnexal IgG4 RD usually showed elevated serum IgG4. However, there are some cases that only meet either serum or pathologic criteria for IgG4 RD. For example, Cheuk et al[14] reported six cases of IgG4-related dacryoadenitis, and two out of four patients tested showed normal serum IgG4 levels. Sato et al[6] reported 21 cases of ocular adnexal IgG4-RD, and three out of 13 patients tested had normal serum IgG4 levels. Plaza et al[5] reported 11 orbital IgG4-RD, and three out of five patients tested had normal serum IgG4 levels. Previous reports had suggested less possibility of systemic involvement and better prognosis in these cases. Our case met only the pathologic criteria of IgG4 RD, and we speculate that previous systemic steroid treatment may confound the serum IgG4 level.

Treatment options for patients with IgG4 RD include systemic steroids, radiotherapy, or immunosuppressants.[4],[5],[6] Corticosteroids are very effective, but recurrence had been observed after treatment was discontinued.[15] For those patients considered ineligible for steroid or immunosuppressant therapy, surgical excision may be an alternative.[3] As for our patient, steroid therapy was tried initially with minimal response and poor patient tolerance; therefore, surgical excision of bilateral lacrimal glands was performed with a satisfying outcome.

In conclusion, the case of IgG4-related dacryoadenitis presented here falls under a new disease entity with unique laboratory and pathologic findings. It should be considered as a differential diagnosis of bilateral lacrimal gland inflammatory conditions. A normal serum IgG4 level does not rule out the diagnosis. Our case illustrates the importance of surgical biopsy and IgG4 staining in indeterminate cases. Accurate diagnosis is essential because of the disease’s association with systemic involvement and lymphoma.



 
  References Top

1.
Hamano H, Kawa A, Horiushi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. NEngJMed 2001;344:732–8.  Back to cited text no. 1
    
2.
Yamamoto M, Takahashi H, Sugai S, Imai K. Clinical and pathological characteristics of Mikulicz’s disease. Autoimmun Rev 2005;4:195–200.  Back to cited text no. 2
    
3.
Takahira M, Kawano M, Zen Y, Minato H, Yamada K, Sugiyama K. IgG4-related chronic sclerosing dacryoadenitis. Arch Ophthalmol 2007;125:1575–8.  Back to cited text no. 3
    
4.
Kubota T, Moritani S, Katayama M, Terasaki H. Ocular adnexal IgG4-related lymphoplasmacytic infiltrative disorder. Arch Ophthalmol 2010;128:577–84.  Back to cited text no. 4
    
5.
Plaza JA, Garrity JA, Dogan A, Ananthamurthy A, Witzig TE, Salomao DR. Orbital inflammation with IgG4-positive plasma cells: manifestation of IgG4 systemic disease. Arch Ophthalmol 2011;129:421–8.  Back to cited text no. 5
    
6.
Sato Y, Ohshima K, Ichimura K, Sato M, Yamadori I, Tanaka T, et al. Ocular adnexal IgG4-related disease has uniform clinicopathology. Pathol Int 2008;58:465–70.  Back to cited text no. 6
    
7.
Sato Y, Notohara K, Kojima M, Takata K, Masaki Y, Yoshino T. IgG4-related disease: historical overview and pathology of hematological disorders. Pathol Int 2010;60:247–58.  Back to cited text no. 7
    
8.
Batra R, Mudhar HS, Sandramouli S. A unique case of IgG4 sclerosing dacryo- cystitis. Ophthal Plast Reconstr Surg 2012;28:e70–2.  Back to cited text no. 8
    
9.
Jakobiec FA, Stacy RC, Hatton MP. Clinical characterization and immunopath- ologic features of sclerosing dacryoadenitis and Riedel thyroiditis. Arch Oph- thalmol 2010;128:1626–8.  Back to cited text no. 9
    
10.
Patel SM, Szostek JH. IgG4-related systemic disease in a native American man. Intern Med 2011;50:931–4.  Back to cited text no. 10
    
11.
Yamamoto M, Harada S, Ohara M, Suzuki C, Naishiro Y, Yamamoto H, et al. Clinical and pathological differences between Mikulicz’s disease and Sjogren’s syndrome. Rheumatology (Oxford) 2005;44:227–34.  Back to cited text no. 11
    
12.
Kubota T, Moritani S, Yoshino T, Nagai H, Terasaki H. Ocular adnexal marginal zone B cell lymphoma infiltrated by IgG4-positive plasma cells. J Clin Pathol 2010;63:1059–65.  Back to cited text no. 12
    
13.
Cheuk W, Yuen HK, Chan AC, Shih LY, Kuo TT, Ma MW, et al. Ocular adnexal lymphoma associated with IgG4+ chronic sclerosing dacryoadenitis: a previously undescribed complication of IgG4-related sclerosing disease. Am J Surg Pathol 2008;32:1159–67.  Back to cited text no. 13
    
14.
Cheuk W, Yuen HK, Chan JK. Chronic sclerosing dacryoadenitis: part of the spectrum of IgG4-related sclerosing disease? Am J Surg Pathol 2007;31: 643–5.  Back to cited text no. 14
    
15.
Yamamoto M, Takahashi H, Ohara M, Suzuki C, Naishiro Y, Yamamoto H, et al. A new conceptualization for Mikulicz’s disease as an IgG4-related plasmacytic disease. Mod Rheumatol 2006;16:335–40.  Back to cited text no. 15
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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Abstract
1. Introduction
2. Case report
3. Discussion
References
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