A Rare Presentation of IgG4-Related Sinusitis With Chronic Nasal Obstruction and Headache: A Case Report and Literature Review

Dong Won Jung; Ji Yun Choi

doi:10.18787/jr.2024.00025

J Rhinol > Volume 31(3); 2024

Jung and Choi: A Rare Presentation of IgG4-Related Sinusitis With Chronic Nasal Obstruction and Headache: A Case Report and Literature Review

Case Report

Journal of Rhinology 2024;31(3):179-183.

Published online: November 30, 2024

DOI: https://doi.org/10.18787/jr.2024.00025

A Rare Presentation of IgG4-Related Sinusitis With Chronic Nasal Obstruction and Headache: A Case Report and Literature Review

Dong Won Jung, MD^*

, Ji Yun Choi, MD, PhD

Department of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, Gwangju, Republic of Korea

Address for correspondence: Ji Yun Choi, MD, PhD, Department of Otolaryngology- Head and Neck Surgery, Chosun University College of Medicine, 365 Pilmun-daero, Dong-gu, Gwangju 61453, Republic of Korea
Tel: +82-62-220-3200, Fax: +82-62-225-2702, E-mail: happyent@naver.com

*Current affiliation: Departments of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Dong-A University, Busan, Republic of Korea

Received July 5, 2024 Revised July 24, 2024 Accepted August 9, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

IgG4-related disease (IgG4-RD) is a systemic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells and a tendency to form mass-like lesions in various organs. IgG4-related sinusitis, although a relatively rare manifestation of IgG4-RD, significantly impacts the paranasal sinuses. A 52-year-old man presented with persistent rhinorrhea, nasal obstruction, and headaches. He was diagnosed with IgG4-RD involving the bilateral nasal cavity, paranasal sinuses, submandibular glands, lacrimal glands, and parotid glands. We recently managed a case of IgG4-related sinusitis, which was successfully diagnosed and treated. This condition represents a distinct subset of chronic rhinosinusitis, with unique pathophysiological and clinical features. Accurate diagnosis and effective management of IgG4-related sinusitis require a high index of suspicion and a multidisciplinary approach.

KEY WORDS: IgG4-related disease; Sinusitis; Headache

INTRODUCTION

IgG4-related disease (IgG4-RD) is a systemic inflammatory condition characterized by the infiltration of tissues with IgG4-positive plasma cells and a propensity to form mass-like lesions in various organs. Among its many manifestations, IgG4-related sinusitis is a relatively rare yet significant condition that affects the paranasal sinuses [1,2].

IgG4-related sinusitis is part of the broader spectrum of IgG4-RD, which encompasses conditions such as autoimmune pancreatitis, sclerosing cholangitis, and retroperitoneal fibrosis [1].

This condition typically presents with chronic sinus symptoms, including nasal obstruction, rhinorrhea, facial pain, and occasionally anosmia [3].

Unlike typical chronic rhinosinusitis, IgG4-related sinusitis frequently exhibits a unique histopathological pattern. This pattern is characterized by a dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis, accompanied by an elevated number of IgG4-positive plasma cells [4].

The etiology of IgG4-related sinusitis remains unclear, but it is believed to involve an aberrant immune response. This condition often requires differentiation from other types of chronic rhinosinusitis, as well as from malignancies and other systemic inflammatory diseases, making accurate diagnosis crucial. Diagnostic criteria typically include clinical presentation, elevated serum IgG4 levels, radiological findings, and histopathological confirmation through biopsy [5,6].

The management of IgG4-related sinusitis typically involves corticosteroids as the first-line treatment, which can lead to significant improvement in symptoms and reduction in tissue infiltration [3]. However, relapses are common, and long-term immunosuppressive therapy may be necessary for some patients [7].

Early recognition and appropriate management of this condition are essential to prevent complications and improve the quality of life for affected individuals [8].

CASE REPORT

A 52-year-old man presented with persistent rhinorrhea, nasal obstruction, and headaches. These symptoms persisted for one year, and although periodic medication provided temporary relief, it did not prevent their recurrence. His medical history included pulmonary sarcoidosis, for which he had received steroid treatment. Upon examination, the patient exhibited chronic fatigue, bilateral submandibular gland swelling, and bilateral exophthalmos. Nasal endoscopy revealed polyps and purulent discharge in both nasal cavities, as well as mucosal swelling (Fig. 1).

Head and neck computed tomography (CT) revealed generalized enlargement of the bilateral parotid and submandibular glands, enlargement of the bilateral lacrimal glands, and enlarged lymph nodes at levels 1–2 on both sides of the neck (Fig. 2). CT of the paranasal sinuses showed signs of sinusitis in the frontal, ethmoid, maxillary, and sphenoid sinuses, along with polypoid lesions in the nasal cavity. The chest X-ray appeared normal. Blood tests indicated an elevated erythrocyte sedimentation rate of 42 mm/h, while the complete blood cell count, electrolyte panel, serology tests, urinalysis, complement C3, C4, fluorescent antinuclear antibody, anti-DNA antibody, anti-Sjögren syndrome-A & B antibodies, and coagulation tests were all within normal limits. Anosmia was noted during olfactory testing.

The patient expressed a desire for surgical intervention to address his sinusitis, leading to the performance of bilateral endoscopic sinus surgery. Immunohistochemical analysis revealed dense lymphoplasmacytic and eosinophilic infiltration, with an IgG4/IgG positive plasma cell ratio exceeding 40%, indicative of IgG4-RD (Fig. 3). A subsequent ultrasound-guided biopsy of the submandibular glands showed similar dense lymphoplasmacytic infiltration and stromal fibrosis, with 50–78 IgG4-positive plasma cells per high-power field.

The patient was ultimately diagnosed with IgG4-RD, which affected the bilateral nasal cavity, paranasal sinuses, submandibular glands, lacrimal glands, and parotid glands. He was subsequently referred to the rheumatology department for further evaluation. Tests revealed an IgG level of 1,956 mg/dL, which is above the normal range of 700–1,600 mg/dL, and an IgG4 subclass level of 1,340 mg/dL, within the reference range of 30-2,010 mg/L. Treatment commenced with oral corticosteroids (prednisolone 30 mg/day) and methotrexate. The patient experienced symptom improvement, and the medications were gradually tapered off until treatment was discontinued. Postoperatively, the wounds in the nasal cavity and sinuses healed well, showing no signs of recurrence.

DISCUSSION

IgG4-related sinusitis, a manifestation of the systemic IgG4-RD, is a rare yet increasingly recognized condition that presents diagnostic and therapeutic challenges. It is crucial to understand its pathophysiology, clinical presentation, and management to provide effective patient care [1,5]. Involvement of the nasal cavity and paranasal sinuses is rare worldwide, with only seven cases reported in South Korea to date (Table 1) [9-13].

Pathophysiology and clinical presentation

IgG4-related sinusitis is characterized by chronic inflammation and tissue infiltration by IgG4-positive plasma cells. The exact etiology of this immune-mediated condition remains unclear; however, it is believed to involve a dysregulated immune response. Unlike typical chronic rhinosinusitis, IgG4-related sinusitis is distinguished by a unique histopathological triad: dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. Clinically, patients may experience nasal obstruction, rhinorrhea, facial pain, and sometimes anosmia. Although these symptoms resemble those of chronic rhinosinusitis, the underlying pathology is markedly different [14].

Diagnostic challenges

Diagnosing IgG4-related sinusitis can be challenging due to its nonspecific clinical symptoms and the necessity to differentiate it from other forms of chronic rhinosinusitis, malignancies, and systemic inflammatory diseases. Key diagnostic criteria include elevated serum IgG4 levels, characteristic radiological findings, and histopathological confirmation via biopsy. Imaging studies frequently show diffuse thickening of the sinus mucosa and occasionally mass-like lesions. A definitive diagnosis is confirmed through biopsy, which reveals the hallmark features of IgG4-RD and a significant presence of IgG4-positive plasma cells [1,15].

Management strategies

The cornerstone of treatment for IgG4-related sinusitis is corticosteroid therapy, which typically leads to a marked improvement in symptoms and a reduction in inflammatory tissue infiltration. The standard initial dose of prednisone or an equivalent corticosteroid is often effective; however, the dosage must be carefully tapered to prevent relapse. Despite initial responsiveness to steroids, relapses are common, necessitating long-term management strategies. In cases of recurrent or refractory disease, immunosuppressive agents such as azathioprine, mycophenolate mofetil, or rituximab may be considered [4-6].

Long-term outcomes and follow-up

The long-term prognosis for patients with IgG4-related sinusitis varies. Although many respond favorably to corticosteroids, the disease’s chronic and relapsing nature can significantly affect their quality of life. Regular follow-up is crucial to monitor disease recurrence and manage any long-term treatment effects. A multidisciplinary approach involving otolaryngologists, rheumatologists, and immunologists is essential for comprehensive management and improved patient outcomes [1,8,14].

Future directions

Further research is needed to elucidate the pathogenesis of IgG4-related sinusitis and to develop targeted therapies. Exploring the genetic and environmental factors that contribute to this condition could lead to more effective treatments and potential preventive strategies. Additionally, studies focusing on long-term outcomes and optimal management protocols are crucial for enhancing patient care and quality of life [2].

Conclusion

IgG4-related sinusitis is a distinct subset of chronic rhinosinusitis, characterized by unique pathophysiological and clinical features. Accurate diagnosis and effective management of this condition necessitate a high index of suspicion and a multidisciplinary approach. Although corticosteroids are the primary treatment, ongoing research and clinical vigilance are essential to optimize patient outcomes for this challenging condition.

Notes

Ethics Statement

This study was reviewed by the Institutional Review Board of Chosun University Hospital, which determined it qualified for exempt review (CHOSUN IRB 2024-07-016.). The requirement for informed consent was waived.

Availability of Data and Material

The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors have no potential conflicts of interest to disclose.

Author Contributions

Conceptualization: Ji Yun Choi. Formal analysis: Ji Yun Choi. Methodology: Ji Yun Choi. Resources: Ji Yun Choi. Supervision: Ji Yun Choi. Visualization: Dong Won Jung, Ji Yun Choi. Writing—original draft: Dong Won Jung, Ji Yun Choi. Writing—review & editing: Dong Won Jung, Ji Yun Choi.

Funding Statement

None

Acknowledgments

None

Fig. 1.

Preoperative endoscopic findings show generalized mucosal swelling with thick mucoid rhinorrhea. A: Right. B: Left.

Fig. 2.

Preoperative computed tomography findings demonstrate right frontal, ethmoid, and sphenoid sinusitis, as well as left ethmoid sinusitis. There is mucosal thickening of the bilateral maxillary sinuses. A: Coronal. B: Axial.

Fig. 3.

Histopathologic findings of IgG4-related sinusitis. A and B: Infiltration by inflammatory cells, consisting of lymphocytes and plasma cells (hematoxylin and eosin stain). C and D: Prominently increased IgG4 plasma cells with inflammation (IgG4 special stain).

Table 1.

Overview of the reviewed cases of IgG4-related disease with sinusitis

Case	Age (yr)	Sex	Underlying diseases	Presenting symptoms	Involvement sites		Diagnostic findings		Treatment	Progress
Case	Age (yr)	Sex	Underlying diseases	Presenting symptoms	Intranasal	Extranasal	Serum IgG4 (reference range; 30–2,010 mg/L)	Pathology	Treatment	Progress
Lee et al. [9]	54	F	None	NO, Rt	IT, Rt	Pituitary gland	550 mg/L	IgG4(+) plasma cells (>106/HPF)	- Diagnostic endoscopic IT mass excision, Rt	- Recurred 10 months after surgery, prednisolone 60 mg/day for 3 weeks and then tapering for 10 months
Lee et al. [9]	54	F	None	R, Rt	IT, Rt	Pituitary gland	550 mg/L	IgG4(+) plasma cells (>106/HPF)	- Endoscopic TSA for pituitary lesion	- No symptoms or recurrence for 4 years thereafter
Lee et al. [9]	26	F	None	NO, both	Septum	None	Unknown	IgG4(+) plasma cells (>30/HPF)	- Methylprednisolone 32 mg/day for 4 weeks and taper	- No symptoms or recurrence for 2 months after treatment and follow-up loss
				R, both	Cribriform plate			IgG4(+) plasma cells (>30/HPF)
				PND				Inflammatory myofibroblastic tumor
				Sneezing				Inflammatory myofibroblastic tumor
Lee et al. [9]	20	M	None	NO, both	MS, both	None	530 mg/L	Infiltration of lymphoplasma cells and fibrosis	- Diagnostic ESS, both	- No symptoms or recurrence for 2 months after treatment and follow-up loss
					ES, both			Infiltration of lymphoplasma cells and fibrosis	- Postoperative methylprednisolone 16 mg/day for 6 weeks
					FS, Lt			IgG4(+) plasma cells	- Postoperative methylprednisolone 16 mg/day for 6 weeks
Chung and Lee [10]	43	F	None	Facial pain, Lt	MS, Lt	None	3,000 mg/L	Infiltration of lymphoplasma cells and fibrosclerosis	- Diagnostic ESS, Lt	- No symptoms or recurrence for 6 months after treatment
				NO, Lt	ES, Lt			Infiltration of lymphoplasma cells and fibrosclerosis	- Postoperative prednisolone 0.6 mg/kg for 4 weeks and 10 mg/day for 2 months in sequence
				Headache	FS, Lt			IgG4(+) plasma cells (>60/HPF)
				Headache	LP, Lt			IgG4(+) plasma cells (>60/HPF)
Ko et al. [11]	40	F	Unknown	Saddle nose	MS, Lt	None	37.5 mg/L	Infiltration of lymphoplasma cells and fibrosclerosis	- Prednisolone 60 mg/day for 5 weeks	- Still no improvement, stopping MTX and changing to AZA 100 mg/day, showing response
				Epistaxis	LNW, Lt			Infiltration of lymphoplasma cells and fibrosclerosis	- Steroid-only therapy showed no improvement and was changed to combined therapy with MTX 7.5 mg/ day for 4 weeks
				Crust	Septum			IgG4(+) plasma cells (>35/HPF)		- No symptoms or recurrence for 2 months after low-dose steroid and AZA combination therapy
				Crust	UP, both			IgG4/IgG ratio 40%
Mun et al. [12]	69	F	HTN	Epistaxis	MS, both	None	1,028 mg/L	Infiltration of lymphoplasma cells	- Diagnostic ESS, both	- Symptoms and endoscopic findings improved for 6 months after treatment
			CKD	Mucopurulent	ES, both			IgG4(+) plasma cells (>90/HPF)	- Postoperative prednisolone 40 mg/day for 1 week, 20 mg/day for 2 weeks, and 10 mg/day for 6 months in sequence	- Intermittent use of steroids as needed
			Pulmonary Tb	R, both	Septum			IgG4/IgG ratio 70%		- Acute cerebral infarction in the left pons 3 months after ESS
			Corneal ulcer	R, both	IT, both			IgG4/IgG ratio 70%		- Died from complications of cerebral infarction 1 year after onset
Han et al. [13]	70	M	HTN	NO, both	MS, Rt	Lung, both	4,960 mg/L	Infiltration of lymphoplasma cells and storiform fibrosis	- Prednisolone 40 mg/day for 4 weeks, tapering for 6 months	- No symptoms or recurrence for 6 months after treatment
			CRS	PND	ES, Rt			Infiltration of lymphoplasma cells and storiform fibrosis	- Curative ESS, both	- Prednisolone 5 mg/day maintenance therapy for residual lung lesions
				Dry nose	SS, Rt			IgG4(+) plasma cells (>100/HPF)
				Crust				IgG4(+) plasma cells (>100/HPF)
				Hyposmia				IgG4/IgG ratio 30%
Our case	52	M	None	Rhinorrhea, Nasal obstruction, headache, Anosmia	MS, both	Lacrimal gland, Parotid gland, Submandibular gland	1,956 mg/L	Infiltration of lymphoplasma cells and stromal fibrosis	- Prednisolone 0 mg/day for 2 weeks, tapering for 6 months	- No symptoms or recurrence for 6 months after treatment
					ES, both			IgG4(+) plasma cells (50–78/HPF)	- Curative ESS, both
					FS, both			IgG4(+) plasma cells (50–78/HPF)
					SS, both			IgG4/IgG ratio >40%

HTN, hypertension; CKD, chronic kidney disease; Tb, tuberculosis; CRS, chronic rhinosinusitis; NO, nasal obstruction; R, rhinorrhea; PND, postnasal drip; Rt, right; Lt, left; IT, inferior turbinate; MS, maxillary sinus; ES, ethmoid sinus; FS, frontal sinus; LP, lamina papyracea; LNW, lateral nasal wall; UP, uncinate process; SS, sphenoid sinus; TSA, transsphenoidal approach; ESS, endoscopic sinus surgery; MTX, methotrexate; AZA, azathioprine

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