Co-Presentation of Giant Cell Arteritis and Granulomatosis with Polyangiitis: A Case Report and Review of Literature.

BACKGROUND Systemic vasculitis can present with a multitude of symptoms involving multiple organ systems. Clinicians should avoid anchoring bias and be cognizant that different types of vasculitides can be present in the same patient and that the diagnosis of one should not preclude the subsequent diagnosis of another. CASE REPORT A 67-year-old woman was referred for evaluation of episodes of epistaxis and recurrent severe sinusitis. Her physical examination showed nasal congestion and purpuric rash on the lower extremities. CT of the sinuses showed severe mucosal thickening. ANCA serologies were positive with a c-ANCA titer of 1: 5120 and anti-proteinase-3 (anti-PR3) antibodies of 1061 units. Serum creatinine was elevated at 1.32 mg/dL (GFR of 40.62 ml/min). Urine analysis showed proteinuria and hematuria. The patient declined treatment initially, but while awaiting kidney biopsy she developed episodes of headache and blurry vision. She underwent right temporal artery biopsy 4 days later, which confirmed the diagnosis of GCA. The biopsy showed characteristic histopathology findings and she was started on 60 mg of prednisone daily. The kidney biopsy showed pauci-immune crescentic glomerulonephritis (PICGN) consistent with ANCA-associated vasculitis. We identified all the cases of co-presentation of GCA and GPA in the literature and summarized their clinical features in this report. CONCLUSIONS Astute clinicians should be cognizant of overlapping and atypical presentations of vasculitides to avoid delayed diagnosis and errors in management.

Background

There have been several case reports and case series describing patients diagnosed with giant cell arteritis (GCA) who subsequently developed full-blown granulomatosis with polyangiitis (GPA). This presentation could be characterized as “polyangiitis overlap syndrome” [1]. However, rarely has GCA been reported in patients with an established diagnosis of GPA. We report the case of a 67-year-old woman who initially had a clinical diagnosis of GPA based on severe, recurrent sinusitis, renal biopsy findings, and very high titers of antineutrophil cytoplasmic antibodies (ANCA), who subsequently developed classic clinical features of GCA with diagnosis confirmed by temporal artery biopsy. The symptoms of patients with vasculitides should be continuously reevaluated and existence of a previous diagnosis should not preclude the possibility of another diagnosis (anchoring bias).

Case Report

A 67-year-old woman was referred to the rheumatology clinic for evaluation of episodes of epistaxis and recurrent severe sinusitis for the previous 3 years. Her physical examination showed nasal congestion and purpuric rash on the lower extremities. CT of the sinuses showed severe mucosal thickening in multiple sinuses. ANCA serologies were positive with a c-ANCA titer of 1: 5120 and anti-proteinase-3 (anti-PR3) antibodies of 1061 units. Complete blood count was normal, but serum creatinine was elevated at 1.32 mg/dL (GFR of 40.62 ml/min). Her urine analysis showed proteinuria of 30 mg/dL along with hematuria (>30 red blood cells/high-power field). The patient declined treatment but agreed to schedule a kidney biopsy. While awaiting the biopsy, she developed episodes of headache and blurry vision for which she was referred to the ophthalmology clinic. She was found to have an erythrocyte sedimentation rate (ESR) of 78 mm and a C-reactive protein (CRP) of 8.4 mg/dL. A right temporal artery biopsy showed characteristic histopatho-logic findings of GCA. There were significant foci of histiocytic infiltration of the internal elastic lamina. A Verhoeff-Van Gieson trichrome combination stain demonstrated considerable loss of the internal elastic lamina (IEL), and a CD68 immunostain was positive, demonstrating histiocytic infiltration of the internal elastic lamina. She was started on 60 mg of prednisone daily. The kidney biopsy showed pauci-immune crescentic glomerulonephritis (PICGN), consistent with ANCA-associated vasculitis. She was treated with rituximab and prednisone. The proteinuria and hematuria resolved and her serum creatinine improved.

Discussion

There have been several case reports of patients concomitantly presenting with clinical features of different types of vasculitides. Here, we described a patient who presented with GCA and GPA, identified similar patients in the literature [1-10], and abstracted data on the clinical features of such co-presentations. Some authors use the term polyangiitis overlap syndrome to describe systemic vasculitis that does not fit into a single diagnostic category but has aspects from several categories of vasculitides [11]. In some cases, as in ours, it can involve features of GCA and GPA. A review of the literature revealed that the most common presentation for GCA was headache, while in GPA, epistaxis was the most common. The duration between the presentations of these 2 entities ranged from 1 week to 8 years. A few cases were diagnosed simultaneously. Not all of the reported cases had biopsy confirmation; some diagnoses were made based on clinical features. In this report, we have summarized all the cases of co-presentation of GCA and GPA reported in the literature (Table 1).

Table 1.

Co-presentation of GCA and GPA.

Patient #	Author	Age/sex	Cranial manifestations	Extracranialmanifestations	Time between presentations	ANCA	Histology (via biopsy)	Treatment
GCA preceding GPA
1	Bradley et al. [1]	59/F	Temporal headache	Shoulder pain, pulmonary nodules	6 months	N/A	TA: GCA Lung: giant cells in granulomas	CS, CYC
2	Tone et al. [2]	61/F	Frontal and occipital headache, binocular vertical diplopia, jaw claudication, otitis media, rhinosinusitis, epistaxis	Shoulder and arm pain	None	PR3	TA: GCA. Kidney: PICGN	CS, CYC
3	McCarthy et al. [3]	65/M	Headache, scalp tenderness, visual loss, fronto-temporal dura enhancement	Weight loss	3 months	Negative ANCA	TA: GCA	CS, CYC
4	Palaic et al. [4]	74/M	Right-sided headache, frontal scalp burning, diplopia, loss of vision, recurrent sinus congestion	PMR, pulmonary opacities with cavitation	None	N/A	Sphenoid sinus: vasculitis	CS
5	Small et al. [5]	69/F	Unilateral hearing loss, cough, bitemporal headaches, and tenderness of the scalp	Fever, rash, anemia	1 month	N/A	TA: GCA Kidney: necrotizingvasculitis, with giant cells, focal and segmental GN, with crescents	CS, CYC
6	Vermeulen et al. [6]	62/F	Jaw claudication, nasal discharge, frontal headache	Fatigue, night sweats, weight loss, basal infiltrates	None	N/A	TA: focal intimal fibrosis. Lung biopsy: necrotizing granulomatous vasculitis	CS, CYC
7	Astudillo et al. [7]	51/F	Sinusitis, rhinitis, temporal headaches	Fever, weight loss, arthralgias, hematuria	None	PR3	TA: discretely thickened intima with normal media (clinical diagnosis of GCA & GPA)	CS
8	Nishino et al. [8]	61/F	Jaw claudication	Fever, myalgia, nasal pain, lung nodules	14 months	N/A	TA: GCA Lung.: GPA.	CS, CYC
9	Nishino et al. [8]	65/F	Visual loss, hemoptysis	Malaise, exertional dyspnea, proteinuria, hematuria, lung nodules	6 months	N/A	TA: non-granulomatous arteritis. Lung: necrotizing vasculitis. Kidney: crescentic GN.	CS, CYC
10	Nishino et al. [8]	75/F	Productive cough, otalgia	Myalgia, anemia, proteinuria, hematuria, elevated creatinine	23 months	c-ANCA	TA: arteritis, fibrinoid necrosis	CS, CYC
11	Nishino et al. [8]	61/F	Headache, oral sores, hemoptysis	Dyspnea, alveolar infiltrates, hematuria, proteinuria, purpura, arthralgia	8 years	N/A	TA: non-giant cell arteritis. Lung: diffuse organizing he, bronchiolitis obliterans	CS, CYC
12	Hamidou et al. [9]	63/F	Jaw claudication, rhinitis, sinusitis	Fever, arthritis, myalgia, proteinuria, hematuria	N/A	PR3	TA: GCA	CS, CYC
GPA preceding GCA
13	Zenone et al. [10]	75/F	Temporal and frontal headaches, bilateral conjunctivitis, otitis, hearing loss	Fatigue, fever, muscle weakness, myalgia, dyspnea, chest pain	18 months	N/A	TA: GCA	CS
14	Nishino et al. [8]	71/M	Epistaxis, periorbital headache, diplopia, otitis media	Calcified nodules, hilar lymph nodes, arthralgias, proteinuria, hematuria	9 months	c-ANCA	TA: GCA	CS, CYC
15	Hassane et al.	67/F	Epistaxis, sinusitis, headaches, blurred vision	Purpura, hematuria, proteinuria	1 week	c-ANCA;PR3	TA: GCA. Kidney: PICGN.	CS, RTX

N/A – not available; GCA – giant cell arteritis; GPA – granulomatosis with polyangiitis; PICGN – pauci-immune crescentic glomerulonephritis; PMR – polymyalgia rheumatica; c-ANCA – cytoplasmic pattern of anti-neutrophil cytoplasmic antibody; PR3 – proteinase-3 antibody; TA – temporal artery; GN – glomerulonephritis; CS – corticosteroids; CYC – cyclophosphamide; RTX – rituximab.

Most patients received corticosteroids and/or cyclophosphamide, historically the most widely used medications. Our case is unusual in that GPA preceding GCA is quite rare and this is the third such reported case.

Unlike in the past, it is more important now to differentiate these 2 entities since we have more targeted, effective treatments. Additional diagnosis of GCA in patients with established diagnosis of other systemic vasculitides may also be important since GCA is associated with rapidly-progressive visual loss and cerebrovascular accidents [12,13]. The pathogenesis of GCA has been shown to be mainly cell-mediated [14]. The inflammatory infiltrate is chiefly composed of lymphocytes, macrophages, and multinucleated Langerhans cells [15,16]. The formation of cytokines, particularly interleukin-6, has been shown to be correlated with the severity of systemic symptoms [17]. On the other hand, the pathogenesis of GPA is mainly humoral-mediated through the ANCA-PR3 complex [18]. Hence, pathogenesis-based therapy is often used. For example, tocilizumab, an IL-6 antagonist, has shown efficacy in GCA, while rituximab has been effective in GPA. Although the pathogenesis of GCA and GPA are quite different, there is evidence of a common pathway: B cell activation. Authors have described patients with GCA who were successfully treated with rituximab [19,20].

Conclusions

In summary, systemic vasculitis can present with a multitude of symptoms involving multiple organs. Clinicians should be cognizant that different types of vasculitides can be present in the same patient and that the diagnosis of one should not preclude the subsequent diagnosis of another.