ANGIOID STREAKS IN A PATIENT WITH HEMOCHROMATOSIS AND SECONDARY PORPHYRIA CUTANEA TARDA Jose S. Pulido, MD, MS, MPH,* Mark J. Donaldson, MBBS(HONS),* Anna S. Kitzmann, MD,* Leonid Skorin Jr, DO,† Helmut Buettner, MD,* Karen Chen, MD‡
Purpose: To present the clinical findings in a patient with hemochromatosis, secondary porphyria cutanea tarda and angioid-like streaks. Methods: Retrospective clinical report. Results: This patient presented with angioid like streaks and choroidal neovascularization. Hemochromatosis is a common genetic disease in the general population and presents at variable ages. The iron deposition may predispose to angioid streaks. In addition, secondary porphyria cutanea tarda (PCT) is associated with hemochromatosis and care should be taken during intraocular surgery since PCT may predispose to phototoxcity. Conclusion: In patients with angioid-like streaks, there should be consideration of hemochromatosis as a possible cause. RETINAL CASES & BRIEF REPORTS 1:254 –256, 2007
From the *Department of Ophthalmology, Mayo Clinic, Rochester; and from the †Albert Lea Eye Clinic-Mayo Health System and ‡Albert Lea Medical Clinic, Albert Lea, Minnesota.
case of angioid streaks associated with hemochromatosis.3 We now report a second case, suggesting that it may be more common than previously noted.
Angioid streaks may be idiopathic or secondary to systemic diseases including pseudoxanthoma elasticum, Paget’s disease, Ehlers Danlos syndrome, sickle cell disease, and thalassemia major.1 The pathogenesis of angioid streak formation in the latter two conditions is probably due to the secondary hemosiderosis. The first report of retinal findings in hemochromatosis noted only pigmentary changes, most prominent in the peripapillary region.2 We have recently published a
Case Report A 73-year-old woman was referred for evaluation of an epiretinal membrane. She had a history of a peripapillary choroidal neovascular membrane on the nasal aspect of her right optic disk associated with angioid streaks first noted in 2002 (Fig. 1, A and B). On examination, her visual acuity was 20/200 in the right eye and 20/30 in the left eye. Ophthalmoscopic evaluation was remarkable for an intraocular lens in her right eye and two plus nuclear sclerotic cataract in the left eye. Fundus examination of the right eye revealed a subretinal hemorrhage at the inferonasal aspect of the disk and a peripapillary choroidal neovascular membrane associated with angioid streaks extending from the disk superiorly (Fig. 2, A and B). In addition, there was a dense epiretinal membrane. Angioid streaks were also present in the left eye. Detailed discussion revealed that she was being followed by a dermatologist for porphyria cutanea tarda secondary to her hemochromatosis, which was being treated with weekly phlebotomy.
Supported in part by an unrestricted grant to the Department of Ophthalmology, Mayo Clinic, from Research to Prevent Blindness Inc., New York, and by the Mayo Foundation. Presented at the Macula 2006 Conference; New York, New York; 2006. Reprint requests: Jose S. Pulido, MD, MS, MPH, Department of Ophthalmology, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905; e-mail: [email protected]
254
255
ANGIOID STREAKS
Fig. 1. A, Fundus photograph of the right eye from 2002 showing a peripapillary choroidal neovascular membrane and angioid streaks. B, Fundus photograph of the left eye from 2002 depicting angioid streaks.
She had a ferritin level of 1,709 ng/mL (normal 13–150 ng/mL). Her serum iron levels were 246 g/dL (normal 35–150 g/dL) and her iron saturation was 94% (normal 20%–55%). Her 24-hour urinary uroporphyrin level was 2,544 g/24 hours (normal 3–25) and her heptacarboxylporphyrin 1,170 g/24 hours (normal 0 –7). She was homozygous for the C282Y mutation in the hemochromatosis gene.
Discussion The patient was homozygous for the C282Y gene variant, which is the most common variant that is causative for hemochromatosis.4 Patients with porphyria cutanea tarda have a higher incidence of mutations in the hereditary hemochromatosis gene.5 This patient also had angioid streaks and represents the second reported case of angioid streaks associated with hemochromatosis.3 Considering that the hemochromatosis gene is very prevalent in the population and that hemochromatosis is a very common and overlooked disease, it may be that at least some cases of angioid streaks that in the past were considered to be idiopathic may be related to hemochromatosis. The pathophysiology of angioid streaks in some disorders
is thought to be due to mineralization of Bruch’s membrane, either due to calcification or deposition of iron. While this provides a biologically plausible mechanism for the development of angioid streaks in hemochromatosis, a cause and effect relationship has not been conclusively proven. The patient had been referred for consideration of epiretinal membrane peeling. Considering the photosensitivity of these patients due to the circulating porphyrins and because porphyrins are known photosensitizing agents to the retina,6 it is important to achieve the lowest possible levels of porphyrins possible before surgery. Porphyrin levels may be lowered with chloroquine but in patients who have hemochromatosis, phlebotomy is the treatment of choice. In summary, hemochromatosis is a common disease that is present in 1 in 200 people.4,5 It appears to be another cause of angioid streaks. In addition, patients with hemochromatosis may have secondary porphyria cutanea tarda and before ocular surgery, it is important to make sure that porphyrin levels are adjusted as well as possible to prevent retinal phototoxicity.
Fig. 2. A, Fundus photograph showing the right eye in 2006. Note the peripapillary choroidal neovascular membrane and angioid streaks as well as the subretinal blood. There is also an epiretinal membrane. B, Late venous phase fluorescein (left) and indocyanine green (right) angiogram of the right eye. Note the peripapillary choroidal neovascular membrane, the angioid streaks, prominent pigment mottling, and hypofluorescence from the subretinal hemorrhage. Note also the straightening of the vessels from the epiretinal membrane.
RETINAL CASES & BRIEF REPORTSℜ
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References 1. 2. 3. 4.
Singerman LJ. Angioid streaks in thalassanemia major. Br J Ophthalmol 1983;67:558. Maddox K. The retina in hemochromatosis. Br J Ophthalmol 1933;17:393–394. Win PH, Pulido JS, Mahr MA. Choroidal neovascular membrane secondary to primary hemochromatosis. Retina 2006; (in press). Beutler E. Hemochromatosis: genetics and pathophysiology. Ann Rev Med 2006;57:331–47.
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6.
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2007
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Mehrany K, Drage LA, Brandhagen DJ, Pittelkow MR. Association of porphyria cutanea tarda with hereditary hemochromatosis. J Am Acad Dermatol 2004;51:205–211. TAP Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report. Treatment of age-related macular degeneration with photodynamic therapy [erratum appears in 2000;118:488]. Arch Ophthalmol 1999;117:1329– 1345.
Purpose: To present the clinical findings in a patient with hemochromatosis, secondary porphyria cutanea tarda and angioid-like streaks. Methods: Retrospective clinical report. Results: This patient presented with angioid like streaks and choroidal neovascularization. Hemochromatosis is a common genetic disease in the general population and presents at variable ages. The iron deposition may predispose to angioid streaks. In addition, secondary porphyria cutanea tarda (PCT) is associated with hemochromatosis and care should be taken during intraocular surgery since PCT may predispose to phototoxcity. Conclusion: In patients with angioid-like streaks, there should be consideration of hemochromatosis as a possible cause. RETINAL CASES & BRIEF REPORTS 1:254 –256, 2007
From the *Department of Ophthalmology, Mayo Clinic, Rochester; and from the †Albert Lea Eye Clinic-Mayo Health System and ‡Albert Lea Medical Clinic, Albert Lea, Minnesota.
case of angioid streaks associated with hemochromatosis.3 We now report a second case, suggesting that it may be more common than previously noted.
Angioid streaks may be idiopathic or secondary to systemic diseases including pseudoxanthoma elasticum, Paget’s disease, Ehlers Danlos syndrome, sickle cell disease, and thalassemia major.1 The pathogenesis of angioid streak formation in the latter two conditions is probably due to the secondary hemosiderosis. The first report of retinal findings in hemochromatosis noted only pigmentary changes, most prominent in the peripapillary region.2 We have recently published a
Case Report A 73-year-old woman was referred for evaluation of an epiretinal membrane. She had a history of a peripapillary choroidal neovascular membrane on the nasal aspect of her right optic disk associated with angioid streaks first noted in 2002 (Fig. 1, A and B). On examination, her visual acuity was 20/200 in the right eye and 20/30 in the left eye. Ophthalmoscopic evaluation was remarkable for an intraocular lens in her right eye and two plus nuclear sclerotic cataract in the left eye. Fundus examination of the right eye revealed a subretinal hemorrhage at the inferonasal aspect of the disk and a peripapillary choroidal neovascular membrane associated with angioid streaks extending from the disk superiorly (Fig. 2, A and B). In addition, there was a dense epiretinal membrane. Angioid streaks were also present in the left eye. Detailed discussion revealed that she was being followed by a dermatologist for porphyria cutanea tarda secondary to her hemochromatosis, which was being treated with weekly phlebotomy.
Supported in part by an unrestricted grant to the Department of Ophthalmology, Mayo Clinic, from Research to Prevent Blindness Inc., New York, and by the Mayo Foundation. Presented at the Macula 2006 Conference; New York, New York; 2006. Reprint requests: Jose S. Pulido, MD, MS, MPH, Department of Ophthalmology, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905; e-mail: [email protected]
254
255
ANGIOID STREAKS
Fig. 1. A, Fundus photograph of the right eye from 2002 showing a peripapillary choroidal neovascular membrane and angioid streaks. B, Fundus photograph of the left eye from 2002 depicting angioid streaks.
She had a ferritin level of 1,709 ng/mL (normal 13–150 ng/mL). Her serum iron levels were 246 g/dL (normal 35–150 g/dL) and her iron saturation was 94% (normal 20%–55%). Her 24-hour urinary uroporphyrin level was 2,544 g/24 hours (normal 3–25) and her heptacarboxylporphyrin 1,170 g/24 hours (normal 0 –7). She was homozygous for the C282Y mutation in the hemochromatosis gene.
Discussion The patient was homozygous for the C282Y gene variant, which is the most common variant that is causative for hemochromatosis.4 Patients with porphyria cutanea tarda have a higher incidence of mutations in the hereditary hemochromatosis gene.5 This patient also had angioid streaks and represents the second reported case of angioid streaks associated with hemochromatosis.3 Considering that the hemochromatosis gene is very prevalent in the population and that hemochromatosis is a very common and overlooked disease, it may be that at least some cases of angioid streaks that in the past were considered to be idiopathic may be related to hemochromatosis. The pathophysiology of angioid streaks in some disorders
is thought to be due to mineralization of Bruch’s membrane, either due to calcification or deposition of iron. While this provides a biologically plausible mechanism for the development of angioid streaks in hemochromatosis, a cause and effect relationship has not been conclusively proven. The patient had been referred for consideration of epiretinal membrane peeling. Considering the photosensitivity of these patients due to the circulating porphyrins and because porphyrins are known photosensitizing agents to the retina,6 it is important to achieve the lowest possible levels of porphyrins possible before surgery. Porphyrin levels may be lowered with chloroquine but in patients who have hemochromatosis, phlebotomy is the treatment of choice. In summary, hemochromatosis is a common disease that is present in 1 in 200 people.4,5 It appears to be another cause of angioid streaks. In addition, patients with hemochromatosis may have secondary porphyria cutanea tarda and before ocular surgery, it is important to make sure that porphyrin levels are adjusted as well as possible to prevent retinal phototoxicity.
Fig. 2. A, Fundus photograph showing the right eye in 2006. Note the peripapillary choroidal neovascular membrane and angioid streaks as well as the subretinal blood. There is also an epiretinal membrane. B, Late venous phase fluorescein (left) and indocyanine green (right) angiogram of the right eye. Note the peripapillary choroidal neovascular membrane, the angioid streaks, prominent pigment mottling, and hypofluorescence from the subretinal hemorrhage. Note also the straightening of the vessels from the epiretinal membrane.
RETINAL CASES & BRIEF REPORTSℜ
256
References 1. 2. 3. 4.
Singerman LJ. Angioid streaks in thalassanemia major. Br J Ophthalmol 1983;67:558. Maddox K. The retina in hemochromatosis. Br J Ophthalmol 1933;17:393–394. Win PH, Pulido JS, Mahr MA. Choroidal neovascular membrane secondary to primary hemochromatosis. Retina 2006; (in press). Beutler E. Hemochromatosis: genetics and pathophysiology. Ann Rev Med 2006;57:331–47.
5.
6.
●
2007
●
VOLUME 1
●
NUMBER 4
Mehrany K, Drage LA, Brandhagen DJ, Pittelkow MR. Association of porphyria cutanea tarda with hereditary hemochromatosis. J Am Acad Dermatol 2004;51:205–211. TAP Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report. Treatment of age-related macular degeneration with photodynamic therapy [erratum appears in 2000;118:488]. Arch Ophthalmol 1999;117:1329– 1345.
![[Porphyria cutanea tarda with sclerodermatous changes and hemochromatosis].](/assets/img/hold.png)
