LETTER TO THE EDITOR
Central Nervous System Involvement in Relapsing Polychondritis To the Editor: elapsing polychondritis (RPC) is a rare autoimmune disease in which the cartilaginous tissues are the primary target for inflammation and destruction. Of the patients with RPC, only 3% are reported to develop neurologic involvement. Neurologic manifestations in RPC include hemiplegia, cranial nerve involvement, seizures, myelitis, peripheral neuropathy, rhomb encephalitis, or limbic encephalitis.1,2 The occurrence of meningitis in patients with RPC is rare; having only been reported in 11 patients previously.3 In our literature search, we have identified only 2 case reports of patients with RPC who developed granulomatous brain lesions.4,5 We hereby present a case of RPC who developed severe symptomatic pachymeningitis and, in whom a single brain granuloma was identified on brain biopsy.
R
CASE A 56-year-old Hispanic man with RPC previously manifested by auricular (“cauliflower ears”), sternal, and articular manifestations presented to the emergency department with rapidly declining mental status and headache. On physical examination, he was lethargic, disoriented, and emotionally labile. Both ears were dusky red and tender, and there was sternal tenderness on palpation. No focal neurologic deficits were noted. Blood work revealed negative antinuclear antibody, antineutrophil cytoplasmic antibody, HIV, and Lyme titers. Inflammatory markers were elevated with erythrocyte sedimentation rate of 60 mm/h and CRP 1.8 mg/L. Angiotensin-converting enzyme level was within reference range. Magnetic resonance imaging of the brain revealed multiple enhancing foci involving both cerebral hemispheres. Cerebrospinal fluid analysis showed elevated protein of 162 mg/dL and white blood cell count of 204 per high-power field with 82% lymphocytes. PPD test was positive. Tuberculous meningitis was initially suspected, and hence he was started on an antituberculous regimen including isoniazid, rifampin, and ethambutol with dexamethasone. There was slow improvement in his cognitive function, and the patient
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FIGURE 1. Magnetic resonance imaging of the brain: interval development of hyperintense signal within the subarachnoid space in bilateral cerebral hemispheres with enhancement in bilateral basal ganglia.
was discharged home. However, he was readmitted with similar symptoms 2 weeks later. Subsequent brain magnetic resonance imaging showed progressive T2-enhancing foci (Fig. 1). Acid-fast bacillus cultures from blood and cerebrospinal fluid remained negative. Brain biopsy revealed extensive arachnoiditis, white matter gliosis, and a single well-formed granuloma adjacent to the cortex (Fig. 2). Immunohistochemical stains for herpesvirus (types I and II) were negative. Special stains for mycobacteria and fungi (acid-fast bacillus and Grocott’s methenamine silver stains) did not demonstrate any microorganisms.
The patient was started on pulse doses of corticosteroids and intravenous cyclophosphamide. His mental status gradually improved including his ability to communicate with his family and to perform his activities of daily living. Ear, nose, and joint symptoms also alleviated. He did well for 1 year after discharge according to the immediate family but was admitted for pneumonia and unfortunately died of hypoxic respiratory failure. Diagnosis of meningoencephalitis secondary to RPC is primarily made clinically; however, laboratory and imaging studies are useful in excluding other etiologies such as
FIGURE 2. Brain biopsy: extensive neutrophilic arachnoiditis with dense gliosis and a single well-formed granuloma. Color on-line figure available at http://www.jclinrheum.com. JCR: Journal of Clinical Rheumatology • Volume 20, Number 7, October 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
JCR: Journal of Clinical Rheumatology • Volume 20, Number 7, October 2014
infections, malignancy, paraneoplastic syndromes, and other autoimmune diseases. Because our patient had a relapse while he was on antituberculous treatment, but improved on corticosteroids and cyclophosphamide, we believe that his brain and meningeal involvement was most likely secondary to RPC. Neurosarcoidosis was not completely excluded, but was felt to be unlikely given the absence of hilar adenopathy and normal angiotensin-converting enzyme levels. The prognosis of patients with RPC complicated by meningoencephalitis is poor. The treatment of neurologic involvement in RPC is largely empiric because of insufficient published evidence. There are references in the literature on the use of pulse methylprednisolone therapy as well as the use of cyclophosphamide in refractory cases of RPC.6 Our case illustrates the rapidly progressive nature of meningoencephalitis in RPC and empha-
© 2014 Lippincott Williams & Wilkins
sizes the importance of early diagnosis. Although our patient died of complications from pneumonia, he did have 1 year of disease control with cyclophosphamide. We believe that careful assessment of risks versus benefits should be performed for such cases and that cyclophosphamide could be a potential treatment option for refractory cases. Kalpita Hatti, MD Vincent Giuliano, MD University of Virginia Charlottesville, VA [email protected]
The authors declare no conflict of interest. REFERENCES 1. Edrees A. Relapsing polychondritis: a description of a case and review article; Rheumatol Int. 2011;31:707–713.
Letter to the Editor 2. Garcia-Egido A, Gutierrez C, de la Fuente C, et al. Relapsing polychondritis-associated meningitis and encephalitis: response to infliximab. Rheumatology. 2011;50:1721–1723. 3. Hsu KC, Wu YR, Lyu RK, et al. Aseptic meningitis and ischemic stroke in relapsing polychondritis; Clin Rheumatol. 2006; 25:265–267. 4. Itoh M, Miura H, Shimamura H, et al. Relapsing polychondritis with an intracranial granuloma: a case report. Rinsho Shinkeigaku. 2004; 44:350–354. 5. Sato K, Kubota T, Kitai R, et al. Meningeal plasma cell granuloma with relapsing polychondritis. Case report. J Neurosurg. 2006;104:143–146. 6. Lahmer T, Treiber M, von Werder A, et al. Relapsing polychondritis: an autoimmune disease with many faces; Autoimmun Rev. 2010;9:540–546.
www.jclinrheum.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
397
Central Nervous System Involvement in Relapsing Polychondritis To the Editor: elapsing polychondritis (RPC) is a rare autoimmune disease in which the cartilaginous tissues are the primary target for inflammation and destruction. Of the patients with RPC, only 3% are reported to develop neurologic involvement. Neurologic manifestations in RPC include hemiplegia, cranial nerve involvement, seizures, myelitis, peripheral neuropathy, rhomb encephalitis, or limbic encephalitis.1,2 The occurrence of meningitis in patients with RPC is rare; having only been reported in 11 patients previously.3 In our literature search, we have identified only 2 case reports of patients with RPC who developed granulomatous brain lesions.4,5 We hereby present a case of RPC who developed severe symptomatic pachymeningitis and, in whom a single brain granuloma was identified on brain biopsy.
R
CASE A 56-year-old Hispanic man with RPC previously manifested by auricular (“cauliflower ears”), sternal, and articular manifestations presented to the emergency department with rapidly declining mental status and headache. On physical examination, he was lethargic, disoriented, and emotionally labile. Both ears were dusky red and tender, and there was sternal tenderness on palpation. No focal neurologic deficits were noted. Blood work revealed negative antinuclear antibody, antineutrophil cytoplasmic antibody, HIV, and Lyme titers. Inflammatory markers were elevated with erythrocyte sedimentation rate of 60 mm/h and CRP 1.8 mg/L. Angiotensin-converting enzyme level was within reference range. Magnetic resonance imaging of the brain revealed multiple enhancing foci involving both cerebral hemispheres. Cerebrospinal fluid analysis showed elevated protein of 162 mg/dL and white blood cell count of 204 per high-power field with 82% lymphocytes. PPD test was positive. Tuberculous meningitis was initially suspected, and hence he was started on an antituberculous regimen including isoniazid, rifampin, and ethambutol with dexamethasone. There was slow improvement in his cognitive function, and the patient
396
www.jclinrheum.com
FIGURE 1. Magnetic resonance imaging of the brain: interval development of hyperintense signal within the subarachnoid space in bilateral cerebral hemispheres with enhancement in bilateral basal ganglia.
was discharged home. However, he was readmitted with similar symptoms 2 weeks later. Subsequent brain magnetic resonance imaging showed progressive T2-enhancing foci (Fig. 1). Acid-fast bacillus cultures from blood and cerebrospinal fluid remained negative. Brain biopsy revealed extensive arachnoiditis, white matter gliosis, and a single well-formed granuloma adjacent to the cortex (Fig. 2). Immunohistochemical stains for herpesvirus (types I and II) were negative. Special stains for mycobacteria and fungi (acid-fast bacillus and Grocott’s methenamine silver stains) did not demonstrate any microorganisms.
The patient was started on pulse doses of corticosteroids and intravenous cyclophosphamide. His mental status gradually improved including his ability to communicate with his family and to perform his activities of daily living. Ear, nose, and joint symptoms also alleviated. He did well for 1 year after discharge according to the immediate family but was admitted for pneumonia and unfortunately died of hypoxic respiratory failure. Diagnosis of meningoencephalitis secondary to RPC is primarily made clinically; however, laboratory and imaging studies are useful in excluding other etiologies such as
FIGURE 2. Brain biopsy: extensive neutrophilic arachnoiditis with dense gliosis and a single well-formed granuloma. Color on-line figure available at http://www.jclinrheum.com. JCR: Journal of Clinical Rheumatology • Volume 20, Number 7, October 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
JCR: Journal of Clinical Rheumatology • Volume 20, Number 7, October 2014
infections, malignancy, paraneoplastic syndromes, and other autoimmune diseases. Because our patient had a relapse while he was on antituberculous treatment, but improved on corticosteroids and cyclophosphamide, we believe that his brain and meningeal involvement was most likely secondary to RPC. Neurosarcoidosis was not completely excluded, but was felt to be unlikely given the absence of hilar adenopathy and normal angiotensin-converting enzyme levels. The prognosis of patients with RPC complicated by meningoencephalitis is poor. The treatment of neurologic involvement in RPC is largely empiric because of insufficient published evidence. There are references in the literature on the use of pulse methylprednisolone therapy as well as the use of cyclophosphamide in refractory cases of RPC.6 Our case illustrates the rapidly progressive nature of meningoencephalitis in RPC and empha-
© 2014 Lippincott Williams & Wilkins
sizes the importance of early diagnosis. Although our patient died of complications from pneumonia, he did have 1 year of disease control with cyclophosphamide. We believe that careful assessment of risks versus benefits should be performed for such cases and that cyclophosphamide could be a potential treatment option for refractory cases. Kalpita Hatti, MD Vincent Giuliano, MD University of Virginia Charlottesville, VA [email protected]
The authors declare no conflict of interest. REFERENCES 1. Edrees A. Relapsing polychondritis: a description of a case and review article; Rheumatol Int. 2011;31:707–713.
Letter to the Editor 2. Garcia-Egido A, Gutierrez C, de la Fuente C, et al. Relapsing polychondritis-associated meningitis and encephalitis: response to infliximab. Rheumatology. 2011;50:1721–1723. 3. Hsu KC, Wu YR, Lyu RK, et al. Aseptic meningitis and ischemic stroke in relapsing polychondritis; Clin Rheumatol. 2006; 25:265–267. 4. Itoh M, Miura H, Shimamura H, et al. Relapsing polychondritis with an intracranial granuloma: a case report. Rinsho Shinkeigaku. 2004; 44:350–354. 5. Sato K, Kubota T, Kitai R, et al. Meningeal plasma cell granuloma with relapsing polychondritis. Case report. J Neurosurg. 2006;104:143–146. 6. Lahmer T, Treiber M, von Werder A, et al. Relapsing polychondritis: an autoimmune disease with many faces; Autoimmun Rev. 2010;9:540–546.
www.jclinrheum.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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