Advertisement

Giant cell arteritis relapse presenting as idiopathic orbital inflammation

      Giant cell arteritis (GCA) is a systemic vasculitis that can cause permanent vision loss. Even after treatment, relapses have been reported in 40%–64% of patients, depending on how relapses are defined.
      • Alba M.A.
      • García-Martínez A.
      • Prieto-González S.
      • et al.
      Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients.
      • Martinez-Lado L.
      • Calviño-Díaz C.
      • Piñeiro A.
      • et al.
      Relapses and recurrences in giant cell arteritis: a population-based study of patients with biopsy-proven disease from northwestern Spain.
      Here, we present a rare case of a GCA relapse mimicking idiopathic orbital inflammation (IOI) on the side contralateral to the initial episode of the disease. Simultaneous, positive biopsies of the orbit and temporal arteries were obtained, offering histological evidence that the orbital inflammation and GCA flare were linked.
      IOI commonly presents with pain, periorbital edema, injection, diplopia, chemosis, proptosis, and decreased vision.
      • Yuen S.J.A.
      • Rubin P.A.D.
      Idiopathic orbital inflammation: distribution, clinical features, and treatment outcome.
      • Swamy B.N.
      • McCluskey P.
      • Nemet A.
      • et al.
      Idiopathic orbital inflammatory syndrome: clinical features and treatment outcomes.
      As an idiopathic condition, secondary etiologies should be considered before a diagnosis of IOI can be made.
      GCA is a granulomatous vasculitis of medium and large vessels that can have vision and life-threatening consequences if not treated promptly. Although prior cases of orbital inflammation due to GCA have been reported, to our knowledge, this is the first case in the English-language ophthalmic literature of a GCA relapse presenting as orbital inflammation in the contralateral, previously unaffected eye.
      A 74-year-old Caucasian female with a history of biopsy-proven GCA treated with prednisone presented with a 3-week history of painful and progressive vision loss, orbital erythema, epiphora, and periorbital edema in her right eye (OD), as well as pain over her right maxillary sinus.
      She was originally diagnosed with GCA 2.5 years before the current presentation via a left temporal artery biopsy after presenting with left-sided scalp tenderness, jaw claudication, headache, weight loss, and left-sided vision loss from 20/20 to counting fingers at the face. At that time, she had a left-sided relative afferent pupillary defect (RAPD) and an edematous left optic disc (arteritic anterior ischemic optic neuropathy). She had been started on high-dose steroids and was tapered down to 9 mg of oral prednisone, with improvement in vision to 20/30.
      In the current presentation, she complained of associated headaches and facial pain but denied scalp tenderness, jaw claudication, or fever. Her symptoms did not improve with topical antibiotics or steroids, and a short trial of increased systemic steroids (20 mg daily) was also ineffective.
      On physical examination, her corrected visual acuity was 20/70 OD and 20/40 OS, down from 20/25 OU 3 months prior. Ishihara color plates were 4/14 OD and 9/14 OS, down from 14/14 and 12/14, respectively. There was no anisocoria or a relative afferent pupillary defect. Her intra-ocular pressure was normal OU. Slit-lamp examination showed chemosis and injection OD (Fig. 1) and new optic disc edema OD. No iritis or corneal edema was present. Humphrey (24-2 automated) visual field testing showed a new central scotoma OD.
      Fig 1
      Fig. 1Chemosis and injection in the patient's right eye.
      C-reactive protein was elevated at 3.23 mg/dL, but her erythrocyte sedimentation rate was normal at 37 mm/hr. The patient was afebrile, and her hemoglobin, white count, platelets, and thyroid function levels were all normal. Magnetic resonance imaging of the brain and orbits revealed enhancement in the right orbit due to inflammation (Fig. 2) as well as mild mucosal thickening in the maxillary and sphenoid sinuses. Findings of cerebrospinal fluid analysis were within normal limits, with no signs of infectious etiologies.
      Fig 2
      Fig. 2Magnetic resonance imaging of the brain and orbits. (A) Axial T1 precontrast imaging reveals a 1 cm area of hypointensity abutting the posterior right globe and the lateral optic nerve (white arrow). (B) Heterogeneous enhancement on postcontrast T1 imaging (white arrow). (C) Hypointensity of the lesion on T2 imaging (white arrow).
      Biopsies of the right orbit and right temporal artery were taken simultaneously. Chronic inflammation with fibrosis was found in the orbit (Fig. 3A, B). In the right temporal artery, there was multifocal segmental absence of the internal elastic lamina, with transmural CD68+ histiocytic infiltrate (Fig. 3C, D). Medial fibrosis and marked intimal thickening were also observed. Chronic inflammation in the artery consisted predominantly of T-cells. These findings were strongly consistent with active GCA.
      Fig 3
      Fig. 3Orbital and temporal artery biopsy. (A) Histologic section of the orbit showing mature adipose tissue with moderate fibrosis and a mild chronic inflammatory infiltrate with small lymphocytes and scattered histiocytes in the centre. Immunohistochemical staining shows CD68-positive histiocytes in a fibrotic focus. There were predominantly CD-3 and a few CD-20-positive T- and B-lymphocytes, respectively (not shown). No organisms or polarizable foreign material were identified. (B) Orbital biopsy with adipose tissue (star) and stromal (arrow) dense fibrosis with chronic inflammation. No signs of vasculitis seen. Orbital biopsy, higher power on the right panel shows characteristic storiform fibrosis seen in idiopathic orbital inflammation with chronic lymphoplasmacytic inflammatory infiltrate. No eosinophils seen. (C) Histologic section of a temporal artery at low magnification showing a transmural chronic lymphohistiocytic inflammatory infiltrate and extending through the media into the adventitia (double-head arrow). A CD68 immunohistochemical stain prominently highlights a vasculitic process with transmural infiltration of the arterial wall by histiocytes. Several histiocytes are also present at the level of the internal elastic lamina. (D) Higher magnification of the temporal artery shows severe fibrointimal proliferation (double-head arrow), and an accompanying Movat stain shows multifocal segmental absence of the internal elastic lamina, with only a small normal remnant staining in black (arrow).
      The patient was diagnosed as having a GCA relapse mimicking IOI. She received 3 days of 1 g intravenous solumedrol, with dramatic improvement in her symptoms. She was discharged on 80 mg of prednisone. On follow-up 3 weeks later, her visual acuity was 20/50 OD and 20/30 OS without an RAPD. Visual fields and optic disc thickness returned to baseline with stable optic atrophy OU.
      GCA has a lifetime risk of 1% for females and 0.5% for males.
      • Crowson C.S.
      • Matteson E.L.
      • Myasoedova E.
      • et al.
      The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases.
      Although treatment with steroids usually results in a rapid and dramatic improvement of symptoms, between 40% and 64% of patients may relapse.
      • Alba M.A.
      • García-Martínez A.
      • Prieto-González S.
      • et al.
      Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients.
      • Martinez-Lado L.
      • Calviño-Díaz C.
      • Piñeiro A.
      • et al.
      Relapses and recurrences in giant cell arteritis: a population-based study of patients with biopsy-proven disease from northwestern Spain.
      Certain features on initial presentation, such as our patient's scalp tenderness, may indicate a greater risk of relapse in the future.
      • Alba M.A.
      • García-Martínez A.
      • Prieto-González S.
      • et al.
      Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients.
      Our patient had previously been diagnosed with GCA based on a left-sided clinical presentation, a positive temporal artery biopsy, and response to steroid therapy. Although uncommon, the level of visual recovery seen after her initial GCA episode has been previously reported.
      • Foroozan R.
      • Deramo V.A.
      • Buono L.M.
      • et al.
      Recovery of visual function in patients with biopsy-proven giant cell arteritis.
      • Thurtell M.J.
      • Kardon R.H.
      Recovery of vision from no light perception in giant cell arteritis.
      Two and a half years later, she presented with clinical and radiographic findings suggestive of right-sided orbital inflammation. Biopsies of both the right temporal artery and right orbit revealed arterial inflammation diagnostic for GCA with concurrent orbital inflammation. Although it is possible that the orbital inflammation was an unrelated and concurrent idiopathic pathology, the more likely possibility is that it was caused by the patient's underlying GCA.
      Although our patient was on 9 mg prednisone at the onset of her symptoms, one study showed that 22% of patients with their first GCA relapse were taking more than 7.5 mg prednisone.
      • Alba M.A.
      • García-Martínez A.
      • Prieto-González S.
      • et al.
      Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients.
      Recently, adjunctive therapy with tocilizumab has been shown to reduce relapse rates.
      • Stone J.H.
      • Tuckwell K.
      • Dimonaco S.
      • et al.
      Trial of tocilizumab in giant-cell arteritis.
      The most common presentation of GCA relapse is polymyalgia rheumatica. Other common findings include cranial symptoms, such as headache and scalp tenderness, and systemic symptoms such as fever and weight loss.
      • Alba M.A.
      • García-Martínez A.
      • Prieto-González S.
      • et al.
      Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients.
      Orbital inflammation has been reported in a few cases of GCA on initial presentation, but our review of the English literature uncovered only 2 reports during a GCA relapse.
      • Lee A.G.
      • Tang R.A.
      • Feldon S.E.
      • et al.
      Orbital presentations of giant cell arteritis.
      • Puerto B.
      • Noval S.
      • Veiga C.
      • Contreras I.
      • Mateos E.
      Inflamación orbitaria apical en arteritis de la temporal.
      Our case has 2 unique features. First, unlike the 2 prior cases, the eye with orbital inflammation was contralateral to the initial GCA episode. Second, the simultaneous, ipsilateral orbital and temporal artery biopsies provide strong evidence that relapsing GCA may cause inflammation of the orbit, leading to signs and symptoms of IOI. It is also important to highlight that, on relapse, this patient did not have the classic symptoms of GCA. She had no scalp tenderness, jaw claudication, polymyalgia rheumatica, or fever. Rather, IOI was the primary manifestation of the disease.
      Early treatment of GCA is crucial for preventing irreversible vision loss.
      • González-Gay M.A.
      • Blanco R.
      • Rodríguez-Valverde V.
      • et al.
      Permanent visual loss and cerebrovascular accidents in giant cell arteritis: predictors and response to treatment.
      By becoming familiar with the various presentations of the disease's relapses, clinicians can hasten its diagnosis and treatment, reducing morbidity. To our knowledge, this is the first case of a contralateral orbital relapse of GCA to be reported in the English-language ophthalmic literature.

      Footnotes and Disclosure:

      The patient consented to the publishing of this information and signed a form verifying her consent.

      References

        • Alba M.A.
        • García-Martínez A.
        • Prieto-González S.
        • et al.
        Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients.
        Medicine (Baltimore). 2014; 93: 194-201
        • Martinez-Lado L.
        • Calviño-Díaz C.
        • Piñeiro A.
        • et al.
        Relapses and recurrences in giant cell arteritis: a population-based study of patients with biopsy-proven disease from northwestern Spain.
        Medicine. 2011; 90: 186
        • Yuen S.J.A.
        • Rubin P.A.D.
        Idiopathic orbital inflammation: distribution, clinical features, and treatment outcome.
        Arch Ophthalmol. 2003; 121: 491-499
        • Swamy B.N.
        • McCluskey P.
        • Nemet A.
        • et al.
        Idiopathic orbital inflammatory syndrome: clinical features and treatment outcomes.
        Br J Ophthalmol. 2007; 91: 1667-1670
        • Crowson C.S.
        • Matteson E.L.
        • Myasoedova E.
        • et al.
        The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases.
        Arthritis Rheum. 2011; 63: 633-639
        • Foroozan R.
        • Deramo V.A.
        • Buono L.M.
        • et al.
        Recovery of visual function in patients with biopsy-proven giant cell arteritis.
        Ophthalmology. 2003; 110: 539-542
        • Thurtell M.J.
        • Kardon R.H.
        Recovery of vision from no light perception in giant cell arteritis.
        Arch Ophthalmol. 2012; 130: 1080-1082
        • Stone J.H.
        • Tuckwell K.
        • Dimonaco S.
        • et al.
        Trial of tocilizumab in giant-cell arteritis.
        N Engl J Med. 2017; 377: 317-328
        • Lee A.G.
        • Tang R.A.
        • Feldon S.E.
        • et al.
        Orbital presentations of giant cell arteritis.
        Graefes Arch Clin Exp Ophthalmol. 2001; 239: 509-513
        • Puerto B.
        • Noval S.
        • Veiga C.
        • Contreras I.
        • Mateos E.
        Inflamación orbitaria apical en arteritis de la temporal.
        Arch Soc Esp Oftalmol. 2007; 82
        • González-Gay M.A.
        • Blanco R.
        • Rodríguez-Valverde V.
        • et al.
        Permanent visual loss and cerebrovascular accidents in giant cell arteritis: predictors and response to treatment.
        Arthritis Rheum. 1998; 41: 1497-1504