| OCR Text |
Show ORIGINAL CONTRIBUTION Optic Neuropathy Associated With Periostitis in Relapsing Polychondritis Parima Hirunwiwatkul, MD and Jonathan D. Trobe, MD Abstract: Optic neuropathy is an uncommon manifestation of relapsing polychondritis ( RPC), a rare systemic disease affecting cartilaginous and proteoglycan- rich structures. The optic neuropathy has been attributed to ischemia, intrinsic inflammation of the optic nerve, or spread of inflammation to the nerve from adjacent intraconal orbital tissues. We report a case of recurrent corticosteroid- responsive optic neuropathy in which MRI did not show ocular, optic nerve, or intraconal orbital abnormalities but did show periosteal thickening and enhancement in the apical orbit and adjacent intracranial space consistent with periostitis. The periostitis, which is a manifestation of a systemic vasculitis or an autoimmune reaction to progenitors of cartilage, probably caused the optic neuropathy by compression or inflammation. It is important to recognize this mechanism of optic neuropathy as its imaging features may be a subtle yet critical clue to an underlying systemic condition that can be life- threatening if not properly managed. (/ Neuro- Ophthalmol 2007; 27: 16- 21) Relapsing polychondritis ( RPC) is a rare multisystem disease affecting cartilaginous tissue and proteoglycan-rich structures such as the eye, heart, blood vessels, and inner ear ( 1). Several reports support autoimmunity to collagen types II, IX, and XI and other cartilaginous protein ( 2,3). In RPC, the major causes of death are pulmonary infection and respiratory collapse, renal failure, and cardiac valvular complications ( 1,4). Common ophthalmic manifestations include conjunctivitis, episcleritis, uveitis, and scleritis. Inflammatory orbitopathy and optic neuropathy have been reported rarely ( 5). The mechanism of optic neuropathy is believed to be ischemia, intrinsic Kellogg Eye Center, Department of Ophthalmology and Visual Sciences ( PH, JDT), and Department of Neurology ( JDT), University of Michigan, Ann Arbor, Michigan. Address correspondence to Jonathan D. Trobe, MD, Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48109; E- mail: jdtrobe@ umich. edu inflammation of the optic nerve, or spread of inflammation from adjacent intraconal orbital tissues. We report a case of RPC with optic neuropathy apparently caused by an extraconal process, namely inflammation of the periorbita (" periostitis"), a mechanism not previously recognized. CASE REPORT A 78- year- old woman had new onset of acute painless visual loss in the left eye. She denied fever, jaw claudication, weight loss, muscle pain, joint pain, or lethargy. However, she had had six bouts of redness, pain, and tenderness of either ear and of the dorsum of her feet over the past 4 years. Her primary care physician attributed the ear and foot lesions to granuloma annulare, a benign papular skin eruption that does not, however, involve the ear. Each episode would resolve within days after treatment with 10- 20 mg prednisone daily. There was also a history of chronic hypertension for which she had been treated with a combination of hydrochlorothiazide and bisoprolol. Examination elsewhere disclosed a best- corrected visual acuity of 20/ 25 in the right eye and 20/ 70 in the left eye. An afferent pupillary defect was present in the left eye with a swollen left optic disc. Humphrey visual fields showed nerve fiber bundle defects in both eyes with mean deviations of - 5.6 db and - 5.8 db. The rest of the ophthalmic examination was reported as normal. An erythrocyte sedimentation rate ( ESR) was 60 mm/ h. A temporal artery biopsy was negative. She received a diagnosis of optic neuritis in the left eye of uncertain cause and was treated with 60 mg prednisone daily over 2 weeks. Visual acuity dramatically improved within 3 days of starting treatment and was recorded at 20/ 25 in both eyes 1 month later with resolution of optic disc edema in the left eye. Three months later, she complained of left periocular pain and diminished vision in the left eye. Visual acuity was reported as 20/ 30 in the right eye and 20/ 100 in the left eye. The left optic disc was reported to be slightly swollen again. She was diagnosed with recurrent optic neuritis and retreated with 60 mg oral prednisone daily. Within days she noted visual improvement. Visual acuity was recorded 16 J Neuro- Ophthalmol, Vol. 27, No. 1, 2007 Optic Neuropathy in Relapsing Polychondritis J Neuro- Ophthalmol, Vol. 27, No. 1, 2007 FIG. 1. A, B. Midorbital T1 coronal MRI. Comparison of precontrast ( A) and postcontrast ( B) studies shows no enhancement of the optic nerves. C, D. Orbital apex T1 coronal MRI. Comparison of the precontrast ( C) and postcontrast ( D) studies shows enhancement of the thickened periosteum of the orbital apices and adjacent intracranial meninges, which is greater on the left ( arrows). The left optic nerve may be compressed by the thickened periosteum. as 20/ 30 in both eyes 3 days after treatment was started. Two weeks after treatment was started, ESR was 26 mm/ h. Our examination 1 week later revealed a best-corrected visual acuity of 20/ 20 in both eyes. Visual fields showed mean deviations of - 0.67 db and - 1.72 db with scattered high threshold points but no obvious nerve fiber bundle defects. Pupils were normal in size and reactivity and displayed no afferent defect. The right optic disc was normal, but the left optic disc still showed mild swelling. There were no other neurologic deficits and no evidence of inflammation of her ears or feet. Brain and orbit MRI showed enhancement and thickening of the periosteum within the orbital apices and the adjacent intracranial meninges, especially on the left side ( Fig. 1). There was no thickening or enhancement of either optic nerve or other intracranial abnormalities. Standard laboratory studies for an inflammatory disorder, including angiotensin- converting enzyme ( ACE), antinuclear antibodies ( ANA), dilute Russell viper venom, and coarse granular antineutrophil cytoplasmic antibodies ( c- ANCA), were negative. The only positive test was perinuclear antineutrophil cytoplasmic antibodies ( p- ANCA). FIG. 2. A. The right ear is red and swollen during a relapse of polychondritis. B. The left ear is normal. 17 J Neuro- Ophthalmol, Vol. 27, No. 1, 2007 Hirunwiwatkul and Trobe TABLE 1. Previous reports of optic neuropathy in relapsing polychondritis Number Author of 1. Ischemic mechanism Herman and Dennis, 1973 ( 3) Killian et al, 1978 ( 6) Isaak et al, 1986 ( 7) cases 1 1 2 Author's diagnosis Ischemic optic neuritis Nonarteritic ischemic optic neuropathy Nonarteritic ischemic optic neuropathy 2. Inflammatory/ infiltrative mechanism Kaye et al, 1964 ( 8) Anderson, 1967 ( 9) McKay et al, 1974 ( 10) Isaak et al, 1986 ( 7) Pazirandeh et al, 1988 ( 11) Tanaka et al, 1990 ( 12) Tucker et al, 1993 ( 13) Lichauco et al, 2001 ( 14) 1 1 1 6 1 1 1 1 3. Indeterminate mechanism Eckardt, 1981 ( 15) 1 Optic neuritis Bilateral optic neuritis Optic neuritis Optic neuritis Optic neuritis Optic neuritis Chronic orbital inflammation with lymphoid hyperplasia Mucosa- associated lymphoid tissue ( MALT) ± type B cell lymphoma Bilateral optic atrophy Other ophthalmic findings in affected eye NA History of recurrent episcleritis, scleritis NA Episcleritis, keratoconjunctivitis, iritis Episcleritis Posterior scleritis, proptosis, infiltration of superior rectus NA Uveitis Total ophthalmoplegia " Salmon patch" conjunctival and orbital mass Inflammatory orbital mass Paresis of the extraocular muscles Other systemic diseases None None None None None Thyrotoxicosis None Ankylosing spondylitis Myelodysplastic syndrome None None Inflammatory sinus disease Comment about mechanism of optic neuropathy Likely to be purely ischemic as no response to corticosteroids Unquestionably ischemic Uncertain because no details provided Uncertain because no details provided about clinical course Uncertain because no details provided about clinical course Uncertain because no details provided about clinical course Uncertain because no details provided Uncertain because no details provided about clinical course Uncertain because no response to multiple immune- modulating agents Likely to be inflammatory/ infiltrative because of dramatic response to corticosteroid treatment Uncertain because no details provided about clinical course Uncertain although resembles Wegener granulomatosis Continued on next page 18 © 2007 Lippincott Williams & Wilkins Optic Neuropathy in Relapsing Polychondritis J Neuro- Ophthalmol, Vol. 27, No. 1, 2007 TABLE 1. ( Continued) Author Isaak et al, 1986 ( 7) Hoang- Xuan et al, 1990 ( 16) Tamm et al, 1993 ( 17) Massry et al, 1995 ( 18) Number of cases 4 1 1 1 Author's diagnosis Papilledema Papilledema Papilledema Bilateral optic disc edema Other ophthalmic findings in affected eye NA Necrotizing scleritis, peripheral ulcerative keratitis, iritis, retinopathy Episcleritis, posterior scleritis Conjunctivitis, episcleritis Other systemic diseases None None None Cerebral vasculitis Comment about mechanism of optic neuropathy Not supported by clinical information such as intracranial pressure measurement Not supported by clinical information such as intracranial pressure measurement May be inflammatory as patient responded to corticosteroid treatment May be inflammatory as patient responded to corticosteroid treatment and had cerebral vasculitis NA, Not available. CT scans of the abdomen and pelvis were negative. An echocardiogram showed minimal mitral, tricuspid, and pulmonic regurgitation accompanied by pulmonary hypertension. Chest x- ray was normal, but CT scanning of the chest showed multiple lung nodules. Bronchoscopic biopsy revealed fragments of bronchial wall with thick sclerotic vessels consistent with pulmonary hypertension. Visual function remained unchanged without treatment during a follow- up period of 8 months. Repeat MRI performed 1 month and 5 months after our first consultation showed no change. However, she developed recurrent inflammation ( Fig. 2) affecting either the right or left ear but sparing the earlobe that always resolved within days after treatment with 10- 20 mg prednisone daily for 1 week. A presumptive diagnosis of RPC was made. DISCUSSION Our patient with RPC displayed recurrent unilateral optic neuropathy that appeared to be responsive to oral corticosteroid treatment. There were no clinical or imaging signs of inflammation of the eyes or intraconal orbital tissues. MRI showed thickening and enhancement of the apical periorbita and adjacent intracranial meninges, probably reflecting inflammation. We presume that the recurrent optic neuropathy was caused by compression of the apical optic nerve or inflammation of its dural covering. Neither intracranial dural nor periosteal inflammation has been described in RPC. There have been 25 reported cases of optic neuropathy in RPC, 12 of which are derived from one review of ophthalmic manifestations of RPC and 13 from other single or double case reports ( 3,6- 18). The optic neuropathy has been labeled as " optic neuritis" ( ON), " anterior ischemic optic neuropathy" ( AION), or " papilledema." Although most reports do not provide enough detail to ascertain the precise mechanism, it has been presumed to be inflammatory ( ON) if the vision improved with antiinflammatory treatment and ischemic if it did not ( Table 1). Based on our review of reported case material for which there is enough detail, we would designate 4 cases as ischemic, 13 as inflammatory, and 8 of indeterminate mechanism. Imaging was available in only 2 cases. In one of these, CT scanning showed attenuation of orbital fat signal and intraconal biopsy- proven lymphoid hyperplasia ( 13); in the other, biopsy- proven mucosa- associated lymphoid tissue ( MALT) ( 14) appeared to deform and perhaps infiltrate the optic nerve. To our knowledge, the periosteal inflammation (" periostitis") seen in our patient has not been reported 19 J Neuro- Ophthalmol, Vol. 27, No. 1, 2007 Hirunwiwatkul and Trobe in RPC, but it has been reported in other connective tissue or vasculitic disorders such as polyarteritis nodosa ( 19,20), sarcoidosis ( 21), and lupus erythematosus ( 22,23). In these disorders, vaso- occlusion is believed to cause hypoxia with release of bone- derived growth factors that induce inflammation of the periosteum ( 20). Why might the periosteum be a target in RPC? Vaso-occlusion may result from immune complex attachment, as occurs in scleral vessels in RPC ( 16). Another possible mechanism is an autoimmune reaction to damaged periosteum, which has been reported to contain collagen type II, a progenitor of cartilage ( 24,25). The chondroge-nicity of the periosteum arises because the cambium layer of the periosteum contains chondrocyte precursor cells that form cartilage during limb development and growth in utero and does so once again in injured periosteum during fracture healing ( 26- 28). A third possible mechanism for periostitis in RPC is a limited form of pachymeningitis. Focal pachymeningitis has not been described in RPC, but there have been reports of what seems to be leptomeningeal involvement as part of " aseptic meningitis" ( 29- 32), " migratory leptomeningeal inflammation" ( 33), and " meningoencephalitis" ( 34,35). These manifestations may be part of an autoimmune reaction to collagen type II, a minor component of the dura and notochord remnants ( 36). Moreover, pachymeningitis is reported in conditions similar to RPC, including rheumatoid arthritis ( 37- 39), Wegener granulomatosis ( WG) ( 40,41), and p- ANCA- positive microscopic polyangiitis ( 42- 46). Indeed, WG ( 47,48), ankylosing spondylitis ( 49), lupus ( 50), and Behcet disease ( 51) have been reported to manifest auricular chondritis. Given that we did not obtain tissue, did our patient actually have RPC or one of these other autoimmune disorders? We believe our diagnosis of RPC is justified on the basis of the modified McAdam criteria, which specify the presence of chondritis at two or more separate anatomic locations with response to corticosteroids or dapsone ( 52- 54). She also had mitral valve regurgitation, which has been reported in RPC ( 55,56). Finally, there was no serologic support for WG or alternative diseases. In conclusion, our patient showed a previously undocumented mechanism of optic neuropathy. Recognizing this mechanism is important for two reasons: 1) orbitocranial imaging features may be subtle, and 2) the diagnosis of RPC is critical because its effects on other cartilaginous and proteoglycan tissues may be life-threatening if not properly managed. REFERENCES 1. Gergely P Jr, Poor G. Relapsing polychondritis. Best Pract Res Clin Rheumatol 2004; 18: 723- 38. 2. Foidart JM, Abe S, Martin GR, et al. Antibodies to type II collagen in relapsing polychondritis. N EnglJ Med 1978; 299: 1203- 7. 3. Herman JH, Dennis MV Immunopathologic studies in relapsing polychondritis. J Clin Invest 1973; 52: 549- 58. 4. Letko E, Zafirakis P, Baltatzis S, et al. Relapsing polychondritis: a clinical review. Semin Arthritis Rheum 2002; 31: 384- 95. 5. Herman JH. Clinical manifestation of relapsing polychondritis. In: Rose BD, ed. UpToDate. Waltham, MA: UpToDate; 2005. Available at: http:// www. utdol. com/. 6. Killian PJ, Susac J, Lawless OJ. Optic neuropathy in relapsing polychondritis. JAMA 1978; 239: 49- 50. 7. Isaak BL, Liesegang TJ, Michet CJ Jr. Ocular and systemic findings in relapsing polychondritis. Ophthalmology 1986; 93: 681- 9. 8. Kaye RL, Sones DA. Relapsing polychondritis: clinical and pathologic features in fourteen cases. Ann Intern Med 1964; 60: 653- 64. 9. Anderson B Sr. Ocular lesions in relapsing polychondritis and other rheumatoid syndromes: the Edward Jackson memorial lecture. Am J Ophthalmol 1967; 64: 35- 50. 10. McKay DA, Watson PG, Lyne AJ. Relapsing polychondritis and eye disease. Br J Ophthalmol 1974; 58: 600- 5. 11. Pazirandeh M, Ziran BH, Khandelwal BK, et al. Relapsing polychondritis and spondyloarthropathies. J Rheumatol 1988; 15: 630- 2. 12. Tanaka K, Nakamura E, Naitoh K, et al. Relapsing polychondritis in a patient with myelodysplastic syndrome [ in Japanese]. Rinsho KetsueU 1990; 31: 1851- 5. 13. Tucker SM, Linberg j y Doshi HM. Relapsing polychondritis, another cause for a " salmon patch." Ann Ophthalmol 1993; 25: 389- 91. 14. Lichauco JJ, Lauer S, Shigemitsu HH, et al. Orbital mucosa-associated lymphoid tissue ( MALT)- type lymphoma in a patient with relapsing polychondritis. Arthritis Rheum 2001; 44: 1713- 5. 15. Eckardt C. Rare form of ocular involvement in relapsing polychondritis. Klin Monatsbl Augenheilkd 1981; 178: 368- 72. 16. Hoang- Xuan T, Foster CS, Rice BA. Scleritis in relapsing polychondritis: response to therapy. Ophthalmology 1990; 97: 892- 8. 17. Tamm S, Wild J, Schonherr U. Recurrent episcleritis with hyperemia of the external ear as an early symptom of chronic polychondritis. Klin Monatsbl Augenheilkd 1993; 203: 230- 1. 18. Massry GG, Chung SM, Selhorst JB. Optic neuropathy, headache, and diplopia with MRI suggestive of cerebral arteritis in relapsing polychondritis. JNeuroophthalmol 1995; 15: 171- 5. 19. Aries PM, Reuter M, Lamprecht P, et al. Periostitis as the initial manifestation of systemic vasculitis. Ann Rheum Dis 2005; 64: 329- 30. 20. Astudillo LM, Rigal F, Couret B, et al. Localized polyarteritis nodosa with periostitis. J Rheumatol 2001; 28: 2758- 9. 21. Korkmaz C, Efe B, Tel N, et al. Sarcoidosis with palpable nodular myositis, periostitis and large- vessel vasculitis stimulating Takayasu's arteritis. Rheumatology ( Oxford) 1999; 38: 287- 8. 22. Glickstein M, Neustadter L, Dalinka M, et al. Periosteal reaction in systemic lupus erythematosus. Skeletal Radiol 1986; 15: 610- 2. 23. Ball J, Grayzel AL Arteritis and localised periosteal new bone formation. J Bone Joint Surg Br 1964; 46: 244- 50. 24. Sandberg MM, Hirvonen HE, Elima KJ, et al. Co- expression of collagens II and XI and alternative splicing of exon 2 of collagen II in several developing human tissues. Biochem J 1993; 294: 595- 602. 25. Izumi T, Scully SP, Heydemann A, et al. Transforming growth factor ( 3 1 stimulates type II collagen expression in cultured periosteum-derived cells. J Bone Miner Res. 1992; 7: 115- 21. 26. Ito Y, Fitzsimmons JS, Sanyal A, et al. Localization of chondrocyte precursors in periosteum. Osteoarthritis Cartilage 2001; 9: 215- 23. 27. O'Driscoll SW, Fitzsimmons JS. The role of periosteum in cartilage repair. Clin Orthop Relat Res 2001; 391( Suppl): S190- 207. 28. Emans PJ, Surtel DA, Frings EJ, et al. In vivo generation of cartilage from periosteum. Tissue Eng 2005; 11: 369- 77. 29. Berg AM, Kasznica J, Hopkins P, et al. Relapsing polychondritis and aseptic meningitis. J Rheumatol 1996; 23: 567- 9. 30. Ragnaud JM, Tahbaz A, Morlat P, et al. Recurrent aseptic purulent meningitis in a patient with relapsing polychondritis. Clin Infect Dis 1996; 22: 374- 5. 20 © 2007 Lippincott Williams & Wilkins Optic Neuropathy in Relapsing Polychondritis J Neuro- Ophthalmol, Vol. 27, No. 1, 2007 31. Nagashima T, Tanaka H, Ito M, et al. A case of aseptic meningitis caused by relapsing polychondritis [ in Japanese]. Rinsho Shinkeigaku 2006; 46: 40^ k 32. Hsu KC, Wu YR, Lyu RK, et al. Aseptic meningitis and ischemic stroke in relapsing polychondritis. Clin Rheumatol 2006; 25: 265- 7. 33. Kothare SV, Chu CC, VanLandingham K, et al. Migratory leptomeningeal inflammation with relapsing polychondritis. Neurology 1998; 51: 614- 7. 34. Hanslik T, Wechsler B, Piette JC, et al. Central nervous system involvement in relapsing polychondritis. Clin Exp Rheumatol 1994; 12: 539^ 1. 35. Taborcias D, Rubiales A, Altadill A, et al. Recurrent polychondritis and meningoencephalitis [ in Spanish]. Med Clin ( Bare) 1996; 107: 597- 8. 36. Brod S, Booss J. Idiopathic CSF pleocytosis in relapsing polychondritis. Neurology 1988; 38: 322- 3. 37. Bathon JM, Moreland LW, DiBartolomeo AG. Inflammatory central nervous system involvement in rheumatoid arthritis. Semin Arthritis Rheum 1989; 18: 258- 66. 38. Agildere AM, Tutar NU, Yucel E, et al. Pachymeningitis and optic neuritis in rheumatoid arthritis: MRI findings. Br J Radiol 1999; 72: 404- 7. 39. Tan HJ, Raymond AA, Phadke PP, et al. Rheumatoid pachymeningitis. Singapore Med J 2004; 45: 337- 9. 40. Seror R, Mahr A, Ramanoelina J, et al. Central nervous system involvement in Wegener granulomatosis. Medicine ( Baltimore) 2006; 85: 54- 65. 41. Fam AG, Lavine E, Lee L, et al. Cranial pachymeningitis: an unusual manifestation of Wegener's granulomatosis. J Rheumatol 2003; 30: 2070^. 42. Sugiyama Y, Shimizu M, Hoshi A, et al. An old man presenting with fluctuating bilateral multiple cranial nerve palsies and positive test for perinuclear antineutrophil cytoplasmic antibody [ in Japanese]. No To Shinkei 1999; 51: 825- 32. 43. Nagashima T, Maguchi S, Terayama Y, et al. P- ANCA- positive Wegener's granulomatosis presenting with hypertrophic pachymeningitis and multiple cranial neuropathies: case report and review of literature. Neuropathology 2000; 20: 23- 30. 44. Kono H, Inokuma S, Nakayama H, et al. Pachymeningitis in microscopic polyangiitis ( MPA): a case report and a review of central nervous system involvement in MPA. Clin Exp Rheumatol 2000; 18: 397^ 00. 45. Jacobi D, Maillot F, Hommet C, et al. P- ANCA cranial pachymeningitis: a case report. Clin Rheumatol 2005; 24: 174- 7. 46. Newman NJ, Slamovits TL, Friedland S, et al. Neuro- ophthalmic manifestations of meningocerebral inflammation from the limited form of Wegener's granulomatosis. Am J Ophthalmol 1995; 120: 613- 21. 47. Diaz- Jouanen ED, Alarcon- Segovia D. Chondritis of the ear in Wegener's granulomatosis. Arthritis Rheum 1977; 20: 1286- 8. 48. Daou S, Mohseni- Zadeh M, Lesens O, et al. Auricular chondritis and Wegener's granulomatosis: a rare association but doubtless not fortuitous [ in French]. Rev Med Interne 2004; 25: 165- 6. 49. Lee- Chiong TL Jr. Pulmonary manifestations of ankylosing spondylitis and relapsing polychondritis. Clin Chest Med 1998; 19: 747- 57. 50. Kitridou RC, Wittmann AL, Quismorio FP Jr. Chondritis in systemic lupus erythematosus: clinical and immunopathologic studies. Clin Exp Rheumatol 1987; 5: 349- 53. 51. Kim MK, Park KS, Min JK, et al. A case of polychondritis in a patient with Behcet's disease. Korean J Intern Med 2005; 20: 339^ 2. 52. McAdam LP, O'Hanlan MA, Bluestone R, et al. Relapsing polychondritis: prospective study of 23 patients and a review of the literature. Medicine ( Baltimore) 1976; 55: 193- 215. 53. Damiani JM, Levine HL. Relapsing polychondritis- report of ten cases. laryngoscope 1979; 89: 929^ 6. 54. Trentham DE, Le CH. Relapsing polychondritis. Ann Intern Med 1998; 129: 114- 22. 55. Otasevic P, Pavlovski K, Popovic AD. Isolated mitral regurgitation complicating relapsing polychondritis. Int J Cardiol 1997; 60: 213- 5. 56. Del Rosso A, Petix NR, Pratesi M, et al. Cardiovascular involvement in relapsing polychondritis. Semin Arthritis Rheum 1997; 26: 840^ k 21 |
