Treatment of Refractory Neurosarcoidosis with Cladribine
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《新英格兰医药杂志》
To the Editor: Neurosarcoidosis occurs in less than 5 percent of patients with sarcoidosis, yet it can cause significant neurologic impairment.1,2 Although some patients have a rapid response to corticosteroids, many require prolonged treatment or additional immunosuppressants.2,3 We report the use of the antimetabolite cladribine (2-chlorodeoxyadenosine) for the treatment of neurosarcoidosis in a patient with aggressive suprasellar disease.4
A 54-year-old man received a diagnosis of nasal sarcoidosis in 1993, which was successfully treated with prednisone. In 1998, progressive blindness developed, and brain magnetic resonance imaging (MRI) studies revealed a mass-like enhancement in the suprasellar cistern. The findings on examination of a biopsy specimen obtained in 1999 were consistent with the presence of neurosarcoidosis. The patient required 60 to 80 mg of prednisone per day for three years. Type 1 diabetes and obesity developed, followed by panhypopituitarism and hypertension. Attempts to taper the dose of prednisone led to deteriorating vision (right eye, 20/40 with complete temporal-field loss; left eye, 20/400 with a small inferior nasal-field loss). Trials with cyclophosphamide and cyclosporine were unsuccessful. In March 2002, the acuity in the right eye deteriorated (20/100), with a new visual-field loss.
Since cladribine is highly effective for the treatment of central nervous system Langerhans' cell histiocytosis, another disease characterized by histiocytic infiltration, we attempted to treat this patient's refractory neurosarcoidosis similarly.5 Base-line brain MRI scans were obtained; MRI scans of the spine were normal, as were the erythrocyte sedimentation rate and levels of angiotensin-converting enzyme in cerebrospinal fluid and serum. Cladribine was administered intravenously every three weeks (20 mg daily for two days), for a total of five cycles. Brain MRI scans obtained after two cycles showed significant resolution of gadolinium enhancement. By August 2002, treatment with prednisone, insulin, and antihypertensive agents had been discontinued.
Treatment was not resumed until March 2003, when visual loss worsened (right eye, 20/300; left eye, no perception of light). MRI studies revealed persistent suprasellar disease. Vision improved with intravenous methylprednisolone (right eye, 20/100; left eye, finger counting) but then remained unchanged for a month, despite treatment with 80 mg of prednisone per day. Cladribine was then administered every four weeks (20 mg daily for three days), for a total of five cycles. MRI scans obtained after three cycles showed almost complete resolution of gadolinium-enhancement abnormalities and abnormalities on images obtained with fluid-attenuated inversion recovery (FLAIR). There was minimal improvement in acuity (right eye, 20/100 plus two letters in the 20/80 row; left eye, no change) and expansion of visual fields bilaterally. Prednisone was gradually discontinued.
On two occasions, the brain lesions in this patient showed dramatic responsiveness to cladribine. Visual improvement was minimal, possibly because of permanent damage to the chiasm and intraocular optic nerve before the initiation of treatment with cladribine. Our findings suggest that early therapy with cladribine may be justified in patients in whom conventional therapies fail. Such treatment may prevent permanent neurologic impairment from neurosarcoidosis.
Ravi K. Tikoo, M.D.
New York University School of Medicine
New York, NY 10016
tikoo@saturn.med.nyu.edu
Mark J. Kupersmith, M.D.
Beth Israel Medical Center, North Division
New York, NY 10128
Jonathan L. Finlay, M.D., Ch.B.
New York University School of Medicine
New York, NY 10016
References
Zajicek JP, Scolding NJ, Foster O, et al. Central nervous system sarcoidosis -- diagnosis and management. QJM 1999;92:103-117.
Vinas FC, Rengachary S. Diagnosis and management of neurosarcoidosis. J Clin Neurosci 2001;8:505-513.
Gullapalli D, Phillips LH II. Neurologic manifestations of sarcoidosis. Neurol Clin 2002;20:59-83.
Liliemark J. The clinical pharmacokinetics of cladribine. Clin Pharmacokinet 1997;32:120-131.
Giona F, Annino L, Bongarzoni V, et al. Unifocal Langerhans' cell histiocytosis involving the central nervous system successfully treated with 2-chlorodeoxyadenosine. Med Pediatr Oncol 2002;38:223-223. abstract.
A 54-year-old man received a diagnosis of nasal sarcoidosis in 1993, which was successfully treated with prednisone. In 1998, progressive blindness developed, and brain magnetic resonance imaging (MRI) studies revealed a mass-like enhancement in the suprasellar cistern. The findings on examination of a biopsy specimen obtained in 1999 were consistent with the presence of neurosarcoidosis. The patient required 60 to 80 mg of prednisone per day for three years. Type 1 diabetes and obesity developed, followed by panhypopituitarism and hypertension. Attempts to taper the dose of prednisone led to deteriorating vision (right eye, 20/40 with complete temporal-field loss; left eye, 20/400 with a small inferior nasal-field loss). Trials with cyclophosphamide and cyclosporine were unsuccessful. In March 2002, the acuity in the right eye deteriorated (20/100), with a new visual-field loss.
Since cladribine is highly effective for the treatment of central nervous system Langerhans' cell histiocytosis, another disease characterized by histiocytic infiltration, we attempted to treat this patient's refractory neurosarcoidosis similarly.5 Base-line brain MRI scans were obtained; MRI scans of the spine were normal, as were the erythrocyte sedimentation rate and levels of angiotensin-converting enzyme in cerebrospinal fluid and serum. Cladribine was administered intravenously every three weeks (20 mg daily for two days), for a total of five cycles. Brain MRI scans obtained after two cycles showed significant resolution of gadolinium enhancement. By August 2002, treatment with prednisone, insulin, and antihypertensive agents had been discontinued.
Treatment was not resumed until March 2003, when visual loss worsened (right eye, 20/300; left eye, no perception of light). MRI studies revealed persistent suprasellar disease. Vision improved with intravenous methylprednisolone (right eye, 20/100; left eye, finger counting) but then remained unchanged for a month, despite treatment with 80 mg of prednisone per day. Cladribine was then administered every four weeks (20 mg daily for three days), for a total of five cycles. MRI scans obtained after three cycles showed almost complete resolution of gadolinium-enhancement abnormalities and abnormalities on images obtained with fluid-attenuated inversion recovery (FLAIR). There was minimal improvement in acuity (right eye, 20/100 plus two letters in the 20/80 row; left eye, no change) and expansion of visual fields bilaterally. Prednisone was gradually discontinued.
On two occasions, the brain lesions in this patient showed dramatic responsiveness to cladribine. Visual improvement was minimal, possibly because of permanent damage to the chiasm and intraocular optic nerve before the initiation of treatment with cladribine. Our findings suggest that early therapy with cladribine may be justified in patients in whom conventional therapies fail. Such treatment may prevent permanent neurologic impairment from neurosarcoidosis.
Ravi K. Tikoo, M.D.
New York University School of Medicine
New York, NY 10016
tikoo@saturn.med.nyu.edu
Mark J. Kupersmith, M.D.
Beth Israel Medical Center, North Division
New York, NY 10128
Jonathan L. Finlay, M.D., Ch.B.
New York University School of Medicine
New York, NY 10016
References
Zajicek JP, Scolding NJ, Foster O, et al. Central nervous system sarcoidosis -- diagnosis and management. QJM 1999;92:103-117.
Vinas FC, Rengachary S. Diagnosis and management of neurosarcoidosis. J Clin Neurosci 2001;8:505-513.
Gullapalli D, Phillips LH II. Neurologic manifestations of sarcoidosis. Neurol Clin 2002;20:59-83.
Liliemark J. The clinical pharmacokinetics of cladribine. Clin Pharmacokinet 1997;32:120-131.
Giona F, Annino L, Bongarzoni V, et al. Unifocal Langerhans' cell histiocytosis involving the central nervous system successfully treated with 2-chlorodeoxyadenosine. Med Pediatr Oncol 2002;38:223-223. abstract.