Unexpected outcome ( positive or negative) including adverse drug reactions
CASE REPORT
Giant cell arteritis: a closer look at its ophthalmological manifestations Nuno G Pinto Ferreira,1 Luiz Menezes Falcão,2,3 Antonio T Alves,4 Fatima Campos1 1
Department of Ophthalmology, Hospital de Santa Maria, Lisbon, Portugal 2 Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal 3 Department of Internal Medicine, Hospital de Santa Maria, Lisbon, Portugal 4 Department of Pathology, Hospital de Santa Maria, Lisbon, Portugal Correspondence to Professor Luiz Menezes Falcão, [email protected] Accepted 10 September 2015
SUMMARY Giant cell arteritis with ocular involvement is an ocular emergency. Arteritic anterior ischaemic optic neuropathy (AAION) is the most common ophthalmological manifestation associated with this disease. Visual loss is usually permanent with rare cases showing visual recovery. Visual improvement, if it occurs, is generally limited, and the visual field defects are persistent and severe. The main goal of AAION treatment is the preservation of vision in the fellow eye. In patients with neurophthalmological manifestations, high-dose corticosteroids should be initiated immediately and aggressively, and maintained thereafter. We present a case of AAION and severe vision loss where significant visual recovery was seen after treatment.
BACKGROUND This case is remarkable in that, unlike most cases, our patient showed significant visual recovery of the affected eye. This case also sustains the well-known emergent necessity of starting corticosteroids in giant cell arteritis with ocular involvement, in order to preserve and recover a degree of visual function. This visual recovery will probably be reflected in those with sudden visual loss, treated in the emergency room after a short presentation of symptoms.
CASE PRESENTATION
To cite: Pinto Ferreira NG, Menezes Falcão L, Alves AT, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2015210995
An 83-year-old woman presented to the eye casualty department with a 3 h history of sudden visual loss in her left eye. She also reported fatigue and severe headaches for 6 months and jaw claudication of 10 days duration. Both the headache and the tactile hyperaesthesia were predominantly over the frontoparietal area of the left hemicranium. The patient denied any fever, nausea or vomiting. Her medical history included hypertension, asthma and dyslipidaemia. There was no medical history of polymyalgia rheumatica. Her ophthalmological history was notable for high myopia, cataract surgery in both eyes (OU) and bilateral ocular hypertension. She was taking antihypertensive drugs and topical brimonidine. Her best-corrected visual acuity in both eyes was 20/20 at her previous ophthalmological examination. The patient was afebrile and had a tender temporal artery. Cardiovascular examination was unremarkable, with a regular heart rhythm at a rate of 70 bpm and a moderately high systolic blood pressure of 158/74 mm Hg. The blood pressure was measured on both upper limbs, with no asymmetric values.
Examination revealed visual acuity (VA), on the Snellen scale, of 20/20 in the right eye (OD) and no light perception in the left eye (OS). No direct pupillary response to light was present in the left eye. The intraocular pressures were asymmetric: 16 mm Hg OD and 5 mm Hg OS. Slit-lamp examination was unremarkable in OU. Funduscopy revealed bilateral chorioretinal atrophic lesions associated with high myopia and, in the left eye, a pale optic disc oedema and narrowed vascular arcades with sludging and segmentation of the blood column (figure 1).
INVESTIGATIONS Laboratory investigations Investigations revealed raised inflammatory markers, in particular thrombocytosis, an elevated erythrocyte sedimentation rate (ESR: 120 mm/h) and increased C reactive protein (CRP: 15 mg/dL).
Colour Doppler ultrasound of both temporal arteries Colour Doppler ultrasound was unremarkable, with absence of the typical inflammatory halos characteristic of giant cell arteritis.
Brain CT CT of the brain was unremarkable, with no evidence of new-onset ischaemic lesions.
Left temporal artery biopsy Biopsy results showed fragmentation of the inner elastic layer and multinucleated giant cells
Figure 1 Retinography of the right and left eye (the images were obtained at presentation): OU, high myopia chorioretinal degeneration; OS, pale oedematous optic disc at the nasal and superior quadrants, with narrowing of the retinal vessels.
Pinto Ferreira NG, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-210995
1
Unexpected outcome ( positive or negative) including adverse drug reactions
Figure 2 Left temporal artery biopsy: (A) arterial changes due to the inflammatory reaction; (B) granuloma with giant cell infiltration and (C) destruction of the internal elastic lamina. (figure 2). These histological findings are consistent with the diagnosis of giant cell arteritis.
Automated static perimetry: visual field tests
Visual field of the right and left eye 2 weeks after beginning corticosteroid treatment (figure 3) with subsequent follow-up examinations.
DIFFERENTIAL DIAGNOSIS The clinical findings at presentation were consistent with arteritic anterior ischaemic optic neuropathy (AAION). A diagnosis of giant cell arteritis was made based on the clinical history and histological findings from the temporal artery biopsy performed on day 4 of treatment.
TREATMENT The patient was started on methylprednisolone 1 g/day intravenous on admission and was continued on this treatment for 3 days, after which she was changed to oral prednisone 1 mg/kg/ day. Soon after starting treatment, prompt resolution of systemic symptoms (headaches, malaise and jaw claudication) occurred associated with progressive decrease of the inflammatory markers (ESR 8 mm/h, CRP 0.8 mg/dL). The patient was discharged under oral prednisolone (dose guided by ESR and CRP), vitamin D, calcium, omeprazol and low-dose aspirin.
OUTCOME AND FOLLOW-UP Remarkably, the patient’s left eye visual acuity improved significantly, from no light perception on admission to 20/25 at the follow-up appointment 2 weeks after discharge. A left relative afferent pupillary defect was present. There was also partial
resolution of the left eye optic disc oedema, with full filled retinal vessels (figure 4). However, due to a rise in the ESR and CRP values, the dose of prednisolone was increased to 60 mg/ day. A follow-up appointment 3 months later revealed stable visual acuity (OD 20/20 and OS 20/25), normal intraocular pressures (OD 16 mm Hg and OS 16 mm Hg) and an unchanged fundal appearance. The patient displayed a Cushingoid habitus. Despite the remarkable improvement in the visual acuity of the left eye, the visual field defect of the left eye remained unchanged on repeated visual fields studies. At this point, the patient was started on alendronate. The patient developed a hyperosmolar hyperglycaemic state 4 months after beginning treatment, after which she was started on metformin and the dose of prednisolone reduced. Clinical improvement of her glycaemic control and progressive resolution of her Cushingoid habitus with no need of adjuvant immunosuppressive therapies were achieved, maintaining a low ESR and CRP.
DISCUSSION Giant cell arteritis with ocular involvement is an ocular emergency. AAION has been reported as being the most common ophthalmological manifestation associated with giant cell arteritis.1 It usually presents with a sudden vision loss of the affected eye, a relative pupillary afferent defect and a pale optic disc oedema.2 Visual loss is usually permanent, with rare cases showing visual recovery.1 3 The visual improvement, if it occurs, is generally limited, and the visual field defects are persistent and severe.4 An associated history of fatigue and headache is characteristic of giant cell arteritis. Likewise, the inflammatory markers (ESR and CRP) are usually raised in this condition. A definite diagnosis is made via temporal artery biopsy.5 Although essential to the diagnosis, the temporal arterial biopsy can be negative due to the segmental nature of this vasculitis.6 Temporal artery colour Doppler ultrasound with a positive finding makes the diagnosis of giant cell arteritis very likely, but a negative result does not exclude this condition.7 The main goal of AAION treatment is the preservation of vision in the fellow eye. In patients with neurophthalmological manifestations, high-dose corticosteroids should be initiated immediately and aggressively, and maintained thereafter with slow dose reduction guided by the ESR and CRP. If untreated, fellow eye involvement occurs in 54–95% of cases in a relatively short period of time.2 To date, there is no evidence that immunosuppressive drugs are better than corticosteroids in the treatment of giant cell arteritis. Some recommend methotrexate as an adjuvant to reduce the cumulative corticosteroid exposure, although adverse effects reduction was not seen with this combined treatment.8 9
Figure 3 Automated static perimetry 2 weeks after beginning treatment showing a deep visual field defect of the left eye with only central vision preserved (5°–10°).
2
Pinto Ferreira NG, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-210995
Unexpected outcome ( positive or negative) including adverse drug reactions
Figure 4 Retinography of the right and left eye 2 weeks after treatment. This case is remarkable in that, unlike most cases, our patient showed a significant visual recovery of her left eye (from no light perception to 20/25). This clinical case sustains the well-known emergent necessity of beginning corticosteroids in giant cell arteritis with ocular involvement, in order to preserve and recover a degree of visual
function. This visual recovery will probably be reflected in those with sudden visual loss, treated in the emergency room after a short presentation of symptoms. Nevertheless, the persistent severe visual field defect seen highlights the irreversibility of the visual dysfunction associated with AAION.4 Finally, this case also demonstrates the clinical challenge in the management of these patients, in particular the intrinsic duality of corticosteroids treatment. Although guided by the ESR and CRP, treatment should weigh the potential adverse reactions associated with it. Acknowledgements The authors would like to acknowledge Luis Paixão, Raquel Paixão, Cecilia Alves, Rita Couceiro, Helena Proença and Mun Faria. Competing interests None declared. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
Learning points ▸ Giant cell arteritis with ocular involvement is an ocular emergency. ▸ High-dose corticosteroids should be initiated immediately and aggressively, and maintained thereafter with slow dose reduction guided by the erythrocyte sedimentation rate and reactive protein. ▸ The definite diagnosis is made via temporal artery biopsy. Although essential to the diagnosis, the temporal arterial biopsy can be negative due to the segmental nature of this vasculitis. ▸ Although rare, visual recovery will probably be reflected in those with sudden visual loss, treated in the emergency room after a short presentation of symptoms.
2
3 4 5
6 7 8 9
Danesh-Meyer HV, Savino PJ. Giant cell (temporal) arteritis. Curr Opin Ophthalmol 2007;18:443–9. Arnold AC. Ischemic optic neuropathy. In: Miller NR, Newman NJ, Biousse Kerrison JB, eds. Walsh and Hoyt's Clinical Neuro-Ophthalmology. 6th ed, Vol 1. Baltimore, MD: Lippincott-Williams & Wilkins, 2005:349–84. Hayreh SS, Zimmerman B. Management of giant cell arteritis. Our 27-year clinical study: new light on old controversies. Ophthalmologica 2003;217:239–59. Danesh-Meyer HV, Savino PJ, Gamble GG. Poor prognosis of visual outcome after visual loss from giant cell arteritis. Ophthalmology 2005;112:1098–103. Gonzales-Gay MA, Lopez-Diaz MJ, Barros S, et al. Giant cell arteritis: laboratory tests at the time of diagnosis in a series of 240 patients. Medicine 2005;84: 277–90. Poller DN, van Wik Q, Jeffrey MJ. The importance of skip lesions in temporal arteritis. J Clin Pathol 2000;53:137–9. Ball EL, Walsh SR, Tang TY, et al. Role of ultrasonography in the diagnosis of temporal arteritis. Br J Surg 2010;97:1765–71. Fraser JA, Weyand CM, Newman NJ, et al. The treatment of giant cell arteritis. Rev Neurol Dis 2008;5:140–52. Mahr AD, Jover JA, Spiera RF, et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum 2007;56: 2789–97.
Copyright 2015 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
Pinto Ferreira NG, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-210995
3
CASE REPORT
Giant cell arteritis: a closer look at its ophthalmological manifestations Nuno G Pinto Ferreira,1 Luiz Menezes Falcão,2,3 Antonio T Alves,4 Fatima Campos1 1
Department of Ophthalmology, Hospital de Santa Maria, Lisbon, Portugal 2 Faculdade de Medicina de Lisboa, Universidade de Lisboa, Lisbon, Portugal 3 Department of Internal Medicine, Hospital de Santa Maria, Lisbon, Portugal 4 Department of Pathology, Hospital de Santa Maria, Lisbon, Portugal Correspondence to Professor Luiz Menezes Falcão, [email protected] Accepted 10 September 2015
SUMMARY Giant cell arteritis with ocular involvement is an ocular emergency. Arteritic anterior ischaemic optic neuropathy (AAION) is the most common ophthalmological manifestation associated with this disease. Visual loss is usually permanent with rare cases showing visual recovery. Visual improvement, if it occurs, is generally limited, and the visual field defects are persistent and severe. The main goal of AAION treatment is the preservation of vision in the fellow eye. In patients with neurophthalmological manifestations, high-dose corticosteroids should be initiated immediately and aggressively, and maintained thereafter. We present a case of AAION and severe vision loss where significant visual recovery was seen after treatment.
BACKGROUND This case is remarkable in that, unlike most cases, our patient showed significant visual recovery of the affected eye. This case also sustains the well-known emergent necessity of starting corticosteroids in giant cell arteritis with ocular involvement, in order to preserve and recover a degree of visual function. This visual recovery will probably be reflected in those with sudden visual loss, treated in the emergency room after a short presentation of symptoms.
CASE PRESENTATION
To cite: Pinto Ferreira NG, Menezes Falcão L, Alves AT, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2015210995
An 83-year-old woman presented to the eye casualty department with a 3 h history of sudden visual loss in her left eye. She also reported fatigue and severe headaches for 6 months and jaw claudication of 10 days duration. Both the headache and the tactile hyperaesthesia were predominantly over the frontoparietal area of the left hemicranium. The patient denied any fever, nausea or vomiting. Her medical history included hypertension, asthma and dyslipidaemia. There was no medical history of polymyalgia rheumatica. Her ophthalmological history was notable for high myopia, cataract surgery in both eyes (OU) and bilateral ocular hypertension. She was taking antihypertensive drugs and topical brimonidine. Her best-corrected visual acuity in both eyes was 20/20 at her previous ophthalmological examination. The patient was afebrile and had a tender temporal artery. Cardiovascular examination was unremarkable, with a regular heart rhythm at a rate of 70 bpm and a moderately high systolic blood pressure of 158/74 mm Hg. The blood pressure was measured on both upper limbs, with no asymmetric values.
Examination revealed visual acuity (VA), on the Snellen scale, of 20/20 in the right eye (OD) and no light perception in the left eye (OS). No direct pupillary response to light was present in the left eye. The intraocular pressures were asymmetric: 16 mm Hg OD and 5 mm Hg OS. Slit-lamp examination was unremarkable in OU. Funduscopy revealed bilateral chorioretinal atrophic lesions associated with high myopia and, in the left eye, a pale optic disc oedema and narrowed vascular arcades with sludging and segmentation of the blood column (figure 1).
INVESTIGATIONS Laboratory investigations Investigations revealed raised inflammatory markers, in particular thrombocytosis, an elevated erythrocyte sedimentation rate (ESR: 120 mm/h) and increased C reactive protein (CRP: 15 mg/dL).
Colour Doppler ultrasound of both temporal arteries Colour Doppler ultrasound was unremarkable, with absence of the typical inflammatory halos characteristic of giant cell arteritis.
Brain CT CT of the brain was unremarkable, with no evidence of new-onset ischaemic lesions.
Left temporal artery biopsy Biopsy results showed fragmentation of the inner elastic layer and multinucleated giant cells
Figure 1 Retinography of the right and left eye (the images were obtained at presentation): OU, high myopia chorioretinal degeneration; OS, pale oedematous optic disc at the nasal and superior quadrants, with narrowing of the retinal vessels.
Pinto Ferreira NG, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-210995
1
Unexpected outcome ( positive or negative) including adverse drug reactions
Figure 2 Left temporal artery biopsy: (A) arterial changes due to the inflammatory reaction; (B) granuloma with giant cell infiltration and (C) destruction of the internal elastic lamina. (figure 2). These histological findings are consistent with the diagnosis of giant cell arteritis.
Automated static perimetry: visual field tests
Visual field of the right and left eye 2 weeks after beginning corticosteroid treatment (figure 3) with subsequent follow-up examinations.
DIFFERENTIAL DIAGNOSIS The clinical findings at presentation were consistent with arteritic anterior ischaemic optic neuropathy (AAION). A diagnosis of giant cell arteritis was made based on the clinical history and histological findings from the temporal artery biopsy performed on day 4 of treatment.
TREATMENT The patient was started on methylprednisolone 1 g/day intravenous on admission and was continued on this treatment for 3 days, after which she was changed to oral prednisone 1 mg/kg/ day. Soon after starting treatment, prompt resolution of systemic symptoms (headaches, malaise and jaw claudication) occurred associated with progressive decrease of the inflammatory markers (ESR 8 mm/h, CRP 0.8 mg/dL). The patient was discharged under oral prednisolone (dose guided by ESR and CRP), vitamin D, calcium, omeprazol and low-dose aspirin.
OUTCOME AND FOLLOW-UP Remarkably, the patient’s left eye visual acuity improved significantly, from no light perception on admission to 20/25 at the follow-up appointment 2 weeks after discharge. A left relative afferent pupillary defect was present. There was also partial
resolution of the left eye optic disc oedema, with full filled retinal vessels (figure 4). However, due to a rise in the ESR and CRP values, the dose of prednisolone was increased to 60 mg/ day. A follow-up appointment 3 months later revealed stable visual acuity (OD 20/20 and OS 20/25), normal intraocular pressures (OD 16 mm Hg and OS 16 mm Hg) and an unchanged fundal appearance. The patient displayed a Cushingoid habitus. Despite the remarkable improvement in the visual acuity of the left eye, the visual field defect of the left eye remained unchanged on repeated visual fields studies. At this point, the patient was started on alendronate. The patient developed a hyperosmolar hyperglycaemic state 4 months after beginning treatment, after which she was started on metformin and the dose of prednisolone reduced. Clinical improvement of her glycaemic control and progressive resolution of her Cushingoid habitus with no need of adjuvant immunosuppressive therapies were achieved, maintaining a low ESR and CRP.
DISCUSSION Giant cell arteritis with ocular involvement is an ocular emergency. AAION has been reported as being the most common ophthalmological manifestation associated with giant cell arteritis.1 It usually presents with a sudden vision loss of the affected eye, a relative pupillary afferent defect and a pale optic disc oedema.2 Visual loss is usually permanent, with rare cases showing visual recovery.1 3 The visual improvement, if it occurs, is generally limited, and the visual field defects are persistent and severe.4 An associated history of fatigue and headache is characteristic of giant cell arteritis. Likewise, the inflammatory markers (ESR and CRP) are usually raised in this condition. A definite diagnosis is made via temporal artery biopsy.5 Although essential to the diagnosis, the temporal arterial biopsy can be negative due to the segmental nature of this vasculitis.6 Temporal artery colour Doppler ultrasound with a positive finding makes the diagnosis of giant cell arteritis very likely, but a negative result does not exclude this condition.7 The main goal of AAION treatment is the preservation of vision in the fellow eye. In patients with neurophthalmological manifestations, high-dose corticosteroids should be initiated immediately and aggressively, and maintained thereafter with slow dose reduction guided by the ESR and CRP. If untreated, fellow eye involvement occurs in 54–95% of cases in a relatively short period of time.2 To date, there is no evidence that immunosuppressive drugs are better than corticosteroids in the treatment of giant cell arteritis. Some recommend methotrexate as an adjuvant to reduce the cumulative corticosteroid exposure, although adverse effects reduction was not seen with this combined treatment.8 9
Figure 3 Automated static perimetry 2 weeks after beginning treatment showing a deep visual field defect of the left eye with only central vision preserved (5°–10°).
2
Pinto Ferreira NG, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-210995
Unexpected outcome ( positive or negative) including adverse drug reactions
Figure 4 Retinography of the right and left eye 2 weeks after treatment. This case is remarkable in that, unlike most cases, our patient showed a significant visual recovery of her left eye (from no light perception to 20/25). This clinical case sustains the well-known emergent necessity of beginning corticosteroids in giant cell arteritis with ocular involvement, in order to preserve and recover a degree of visual
function. This visual recovery will probably be reflected in those with sudden visual loss, treated in the emergency room after a short presentation of symptoms. Nevertheless, the persistent severe visual field defect seen highlights the irreversibility of the visual dysfunction associated with AAION.4 Finally, this case also demonstrates the clinical challenge in the management of these patients, in particular the intrinsic duality of corticosteroids treatment. Although guided by the ESR and CRP, treatment should weigh the potential adverse reactions associated with it. Acknowledgements The authors would like to acknowledge Luis Paixão, Raquel Paixão, Cecilia Alves, Rita Couceiro, Helena Proença and Mun Faria. Competing interests None declared. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
Learning points ▸ Giant cell arteritis with ocular involvement is an ocular emergency. ▸ High-dose corticosteroids should be initiated immediately and aggressively, and maintained thereafter with slow dose reduction guided by the erythrocyte sedimentation rate and reactive protein. ▸ The definite diagnosis is made via temporal artery biopsy. Although essential to the diagnosis, the temporal arterial biopsy can be negative due to the segmental nature of this vasculitis. ▸ Although rare, visual recovery will probably be reflected in those with sudden visual loss, treated in the emergency room after a short presentation of symptoms.
2
3 4 5
6 7 8 9
Danesh-Meyer HV, Savino PJ. Giant cell (temporal) arteritis. Curr Opin Ophthalmol 2007;18:443–9. Arnold AC. Ischemic optic neuropathy. In: Miller NR, Newman NJ, Biousse Kerrison JB, eds. Walsh and Hoyt's Clinical Neuro-Ophthalmology. 6th ed, Vol 1. Baltimore, MD: Lippincott-Williams & Wilkins, 2005:349–84. Hayreh SS, Zimmerman B. Management of giant cell arteritis. Our 27-year clinical study: new light on old controversies. Ophthalmologica 2003;217:239–59. Danesh-Meyer HV, Savino PJ, Gamble GG. Poor prognosis of visual outcome after visual loss from giant cell arteritis. Ophthalmology 2005;112:1098–103. Gonzales-Gay MA, Lopez-Diaz MJ, Barros S, et al. Giant cell arteritis: laboratory tests at the time of diagnosis in a series of 240 patients. Medicine 2005;84: 277–90. Poller DN, van Wik Q, Jeffrey MJ. The importance of skip lesions in temporal arteritis. J Clin Pathol 2000;53:137–9. Ball EL, Walsh SR, Tang TY, et al. Role of ultrasonography in the diagnosis of temporal arteritis. Br J Surg 2010;97:1765–71. Fraser JA, Weyand CM, Newman NJ, et al. The treatment of giant cell arteritis. Rev Neurol Dis 2008;5:140–52. Mahr AD, Jover JA, Spiera RF, et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum 2007;56: 2789–97.
Copyright 2015 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
Pinto Ferreira NG, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-210995
3
