Outcome of Localized Granulomatosis with Polyangiitis: A Case Study

A Reum Choe; In Je Kim; Jisoo Lee; Sun Hee Sung

doi:10.4078/jrd.2016.23.3.174

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Choe, Kim, Lee, and Sung: Outcome of Localized Granulomatosis with Polyangiitis: A Case Study

Original Article

J Rheum Dis 2016;23(3):174-178.

Published online: 31 October 2016

DOI: https://doi.org/10.4078/jrd.2016.23.3.174

Outcome of Localized Granulomatosis with Polyangiitis: A Case Study

A Reum Choe¹, In Je Kim¹, Jisoo Lee¹, Sun Hee Sung²

¹Division of Rheumatology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea

²Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea

Corresponding to: Jisoo Lee, Division of Rheumatology, Department of Internal Medicine, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea. E-mail: leejisoo@ewha.ac.kr

Received 17 March 20168 April 2016 Accepted 11 April 2016

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

A substantial portion of granulomatosis with polyangiitis (GPA) patients present with localized disease limited to the upper respiratory tract, however; disease spectrum and prognosis of these patients are unclear. The aim of this study is to describe the clinical characteristics and outcome of patients with localized GPA.

Methods

This was a retrospective descriptive case series of patients with a biopsy proven localized GPA presenting to a single tertiary rheumatology service between January 1995 and September 2015.

Results

A total of 5 patients, median age 56 years (range 48 to 59 years) at diagnosis and 80% female, were identified. The median follow-up period was 42 months (range 15 to 62 months). Diagnosis was delayed with median time to diagnosis of 12 months (range 3 to 36 months), and patients underwent 1-3 ear, nose, and throat surgeries during the period of diagnostic delay. Sinusitis was the most frequent symptom in all patients, followed by otomastoiditis with cranial nerve palsies (n=2) and orbital mass (n=1). Antineutrophil cytoplasmic antibody (ANCA) was positive initially in 2/5 patients (40%). Two patients with otomastoiditis and cranial nerve palsies progressed to systemic disease with ANCA positive conversion. These two cases along with a case with orbital mass were refractory to standard treatment of cyclophosphamide with glucocorticoids requiring rituximab treatment.

Conclusion

Patients with localized GPA may progress to systemic disease over the disease course, and may have aggressive disease refractory to standard treatment. Close monitoring for systemic symptoms and repeated ANCA testing is required in patients with localized GPA.

Keywords: Granulomatosis with polyangiitis, Localized, Outcome

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Figure 1.

Case 1 in 2012. Computed tomography of paranasal sinus image showed mass extends to the intraorbital portin of the left oribt (arrow). Soft tiss densities along the both maxillary and frontoethmoidal sinuses.

Figure 2.

Case 1 in 2013. Naso-pharyngeal biopsy revealing granulomatous inflammation with palisading necrosis (A), and vasculitis (B) (H&E, ×200).

Figure 3.

Case 3 in 2014. Gadolinium enhanced T1-weighted sagittal magnetic resonance image showed diffuse enlargement of pituitary gland (11.5 mm in height) with thickened enhanced pituitary stalk (arrow).

Table 1.

Initial clinical and histologic characteristics of patients with localized GPA

Variable	Case
Variable	1	2	3	4	5
Sex	Female	Male	Female	Female	Female
Age at diagnosis (yr)	48	56	58	59	56
Time to diagnosis (mo)	9	36	15	3	12
Initial symptoms	Sinusitis, otitis, mastoiditis, and bilateral facial nerve palsy	Sinusitis, and orbital mass	Sinusitis, otitis, mastoiditis, and multiple lower cranial nerve palsies	Sinusitis	Sinusitis
Number (type) of surgery performed	1 (Bilateral mastoidectomy)	3 (FESS, uncinectomy, ethmoidectomy)	1 (FESS)	0	1 (Infundibulectomy)
Histologic features	Granuloma, necrosis, vasculitis^*	Granuloma, necrosis, vasculitis	Granuloma, necrosis, vasculitis	Granuloma	Granuloma, microabscess
Local bone destruction	Nasal bone, septum, and sphenoid bone	Intraorbital portion of the left orbit wall	Bilateral orbit	No	No
ANCA positivity	Negative	PR-3	Negative	MPO	Negative

ANCA: antineutrophil cytoplasmic antibody, FESS: functional endoscopic sinus surgery, GPA: granulomatosis with polyangiitis, MPO: myeloperoxidase, PR-3: proteinase-3.

^* Initially negative but GPA proven by biopsy after developing early systemic/ generalized disease.

Table 2.

Outcome and treatment of patients with localized granulomatosis with polyangiitis

Variable	Case
Variable	1	2	3	4	5
Median follow up duration (mo)	32	42	48	62	15
Development of systemic disease	Yes	No	Yes	No	No
Time to diagnosis^* (mo)	Diagnosis made at onset of systemic disease	NA	36	NA	NA
Symptoms^†	Fever, weight loss, lymphadenopathy, and acute nasal swelling	NA	involvement (diabetes insipidus) Pituitary gland	NA	NA
ANCA positivity^‡	Yes (MPO)	NA	Yes (PR-3)	NA	NA
Refractory disease	Yes	Yes	Yes	No	No
Treatment	CS, CY, MTX, RTX	CS, CY, RTX	CS, CY, RTX	CS, CY, MTX	CS, MTX
Current status of follow up	Out-patient	Out-patient	Out-patient	Out-patient	Out-patient

ANCA: antineutrophil cytoplasmic antibody, CS: corticosteroid, CY: cyclophosphamide, MPO: myeloperoxidase, MTX: methotrexate, NA: not applicable, PR-3: proteinase-3, RTX: rituximab.

^* Time from diagnosis to systemic disease.

^† At development of systemic disease.

^‡ Conversion to ANCA positivity at development of systemic disease.

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