A Case of Systemic Lupus Erythematosus Presenting As Aseptic Meningitis

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J Neurocrit Care 2008;1:62-64 ISSN 2005-0348

A Case of Systemic Lupus Erythematosus Presenting as Aseptic Meningitis

Mi-hwa Kim, MD, Dong-Gun Kim, MD, Young-Ho Koo, MD, Seung-Hun Oh, MD, Hyun Sook Kim, MD, Won-Chan Kim, MD and Ok Joon Kim, MD, PhD Department of Neurology, College of Medicine, Pochon CHA University, Seongnam, Korea

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems. Although various neuropsychiatric manifestations occur in SLE, development of aseptic meningitis as an initial manifestation is rare. Case Report: A 26- year-old woman with fever, headache and vomiting was diagnosed with aseptic meningitis in cerebrospinal fluid study. Neuroimaging studies were not remarkable, and hematologic study showed mild leucopenia and thromocytopenia. After 12 days of conservative management, high fever, leucopenia, thrombocytopenia, malar rash and cervical lymph nodes enlargement developed. She had subsequent pleural and pericardial effusions. The rheumatoid factor and anti-nuclear antibody (ANA) were positive and SLE was diagnosed based on clinical manifestations and laboratory studies. After treatments with intravenous immunoglobulin, corticosteroid, antibiotics and hydrochloroquine sulfate, her symptoms gradually improved. Conclusion: We report a rare case with aseptic meningitis as an initial manifestation of SLE. J Neurocrit Care 2008;1:62-64

KEY WORDS: Systemic lupus erythematosus·Aseptic meningitis.

Introduction onance imaging (MRI) and magnetic resonance angiography (MRA) were normal. The laboratory studies showed mild Systemic lupus erythematosus (SLE) is an autoimmune, leucopenia [3,160/mm3 (neutrophils: 76.3%)], thrombocy- inflammatory disorder affecting multiple organ systems. Al- topenia (99,000/μL) and elevated erythrocyte sedimentation though it is known as many as 14% to 80% of patients with rate (74 mm/hr). On cerebrospinal fluid (CSF) study, the

SLE develop various neuropsychiatric manifestations includ- opening pressure was 200 mmH2O, and mild CSF-pleocy- ing cerebrovascular disorders, seizure or psychosis,1-5 aseptic tosis [WBC 22/mm3 (lymphocyte 94%)] with normal protein meningitis as an initial manifestation of SLE is rare. and glucose level were found. Blood and CSF tests for viral, Here we present a case with aseptic meningitis as an in- tuberculous, fungal and bacterial agents were all negative. tial manifestation of SLE. Through conservative management, her clinical symptoms partially improved. Case On the 12th hospital day, she complained painful palpable left neck mass. Computed tomography (CT) (Fig. 1A) and A 26-year-old woman without significant past medical ultrasonography (Fig. 1B) of neck showed multiple enlarge- history was admitted with fever, headache and vomiting for ment of bilateral cervical lymph nodes up to 18.2×15.8 mm 20 days. She had taken analgesics for a few days but there of size with subcutaneous fat infiltrations. Malar rash was was no improvement. Physical examinations were unrema- shown on her face, high fever developed again, leucopenia kable except mild fever (37.5℃). Neurological examination [2,390/mm3 (neutrophils: 73.6%)] and thrombocytopenia showed no focal deficit. The findings of brain magnetic re- (75,000/μL) were aggravated. After three days, severe dy- spnea developed, and chest X-ray showed mild cardiome- Address for correspondence: Ok Joon Kim, MD, PhD galy and bilateral diffuse peribronchial opacities with massive Department of Neurology, College of Medicine, Pochon CHA Uni- pleural effusion on right lower lung field (Fig. 2A). Echo- versity, 351 Yatapdong, Bundang-gu, Seongnam 463-712, Korea Tel: +82-31-780-5480, Fax: +82-31-780-5198 cardiogram showed pericardial effusion (Fig. 2B). The rhe- E-mail: [email protected], [email protected] umatoid factor and anti-nuclear antibody (ANA) were po-

Aseptic Meningitis and Systemic Lupus Erythematosus ■ MH Kim, et al.

FIGURE 1. Computed tomography of neck revealed bilateral diffuse cervical lymph nodes enlargement with diffuse subcutaneous fat infil- tration (A). Neck sonography showed lymph node enlargement with A B increased vascularities (B).

FIGURE 2. Chest AP showed bilateral diffuse peribronchial opacities with massive pleural effusion on right lung field (A). Echocardiogram revealed normal sized cardiac cham- bers dimension with minimal peri- A B cardial effusion (B). sitive but anti-dsDNA Ab, anti-SM Ab and anti-Ribonu- Neurological manifestations of SLE include cerebrovascular cleoprotein Ab were all negative, and anti-cardiolipin Ab disease, headache (migraine tension headache), cognitive IgM and IgG were within normal limits. disorders (delirium, dementia), movement disorders (chorea), Based on her clinical symptoms including malar rash, se- depression, psychosis, seizure and aseptic meningitis.7 The rositis, multi-organ involvement and hematologic manifesta- frequency of central nervous system (CNS) involvement in tion including positive ANA titer, diagnosis of SLE was then SLE is various, ranging from 14 to 80% in previous li- made. Immediate intravenous immunoglobulin (IVIg) 0.4 terature.1-5 Aseptic meningitis as an initial manifestation in g/kg and methyl prednisolone 62.5 mg were infused for 5 SLE is extremely rare, and there were only 10 cases in days. Subsequent 31.25 mg of methylprednisolone were tre- previous literature using PubMED from 1966 to 2000, to our ated for another 5 days and hydrochloroquine sulfate 400 mg knowledge.8 In one report showing 28% of patients with was added. Intravenous ciprofloxacin 800 mg and teicoplanin SLE-associated neuropsychiatric events, only 3 cases (1.2%) 200 mg were started at 15th hospital day for the treatment of had aseptic meningitis, indicating that aseptic meningitis in pneumonia. Fever subsided at 19th hospital day and pneu- SLE is very rare phenomenon.2 Another report showed that monia and pleural effusion improved gradually. Chest x-ray aseptic meningitis was diagnosed in only four (1.6%) out of at 28th hospital day showed clear lung field bilaterally. She 257 patients with CNS lupus.9 discharged with maintaining treatment of oral prednisolone The exact pathomechanism of SLE-associated aseptic me- 7.5 mg per day without any symptoms 32 days after admission. ningitis still remains unclear. One possible explanation is that CNS manifestation in SLE is associated with vasculitis in Discussion some cases.9 Another is that most of aseptic meningitis in patients with SLE are associated with drugs for the treatment of The initial clinical features and CSF findings in this case SLE, such as nonsteroidal anti-inflammatory drugs (NSAIDs), were typical of aseptic meningitis. Later symptoms could antimicrobials (especially sulfa drugs), IVIg and OKT3 mo- satisfy diagnostic criteria of SLE according to the ARA.6 noclonal antibodies.10 The pathogenic mechanism of drug-

J Neurocrit Care ■ 2008;1:62-64 induced aseptic meningitis is not fully understood and it is ropsychiatric events in systemic lupus erythematosus: attribution and clinical significance. J Rheumatol 2004;31:2156-62. generally believed to be an immunologic hypersensitivity 4. Brey RL, Holliday SL, Saklad AR, Navarrete MG, Hermosillo-Ro- 8 reaction. In our case, the possibility of triggering chemical mo D, Stallworth CL, et al. Neuropsychiatric syndromes in lupus: pre- meningitis by the use of analgesics in preclinical period of valence using standardized definitions. Neurology 2002;58:1214-20. SLE could not be excluded. 5. Ainiala H, Loukkola J, Peltola J, Hietaharju A. The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Neu- Another interesting finding in our case is that our patient rology 2001;57:496-500. developed lymphadenopathy on her left neck. Through the 6. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et clinical course of her illness, we initially assume that she had al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-7. Kikuchi’s disease (KD), but she was diagnosed as SLE later. 7. The American College of Rheumatology nomenclature and case de- Although lymphadenopathy in this case is thought to be a finitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; kind of lupus lymphadenitis (LL), co-occurrence of KD co- 42:599-608. 8. Dong J, Suwanvecho S, Chen L, Keung YK. Initial presentation of uld not be excluded because KD can be associated with SLE systemic lupus erythematosus masquerading as bacterial meningitis. 11-14 or aseptic meningitis in some cases in literature. In this J Am Board Fam Pract 2001;14:470-3. situation, lymph-node biopsy may enable to distinguish KD 9. Jennekens FG, Kater L. The central nervous system in systemic lupus : from LL. Histologically, the presence of hematoxyphilic bo- erythematosus. Part 1. Clinical syndromes a literature investigation. Rheumatology (Oxford) 2002;41:605-18. dies, abundant plasma cells and true vasculitis outside the 10. Moris G, Garcia-Monco JC. The challenge of drug-induced aseptic areas of necrosis also favors a diagnosis of LL,15 whereas the meningitis. Arch Intern Med 1999;159:1185-94. absence or paucity of neutrophils confirms the diagnosis KD.12 11. Hu S, Kuo TT, Hong HS. Lupus lymphadenitis simulating Kikuchi’s lymphadenitis in patients with systemic lupus erythematosus: a clini- Unfortunately, we could not perform biopsy due to rapid ex- copathological analysis of six cases and review of the literature. Pathol acerbation of her systemic symptoms. Int 2003;53:221-6. In conclusion, this is a rare case because aseptic meningitis 12. Martinez-Vazquez C, Hughes G, Bordon J, Alonso-Alonso J, Ani- barro-Garcia A, Redondo-Martinez E, et al. Histiocytic necrotizing was presented as a first sign of SLE. lymphadenitis, Kikuchi-Fujimoto’s disease, associated with systemic lupus erythemotosus. QJM 1997;90:531-3. REFERENCES 13. Murthy SC, Dandin SM, Dandin AS, Patwardan MY. Kikuchi’s disease associated with systemic lupus erythematosus. Indian J Dermatol 1. Mikdashi J, Handwerger B. Predictors of neuropsychiatric damage in Venereol Leprol 2005;71:338-41. systemic lupus erythematosus: data from the Maryland lupus cohort. 14. Sato Y, Kuno H, Oizumi K. Histiocytic necrotizing lymphadenitis Rheumatology (Oxford) 2004;43:1555-60. (Kikuchi’s disease) with aseptic meningitis. J Neurol Sci 1999;163: 2. Hanly JG, Urowitz MB, Sanchez-Guerrero J, Bae SC, Gordon C, 187-91. Wallace DJ, et al. Neuropsychiatric events at the time of diagnosis of 15. Basu D, Mutha SM. Histiocytic necrotizing lymphadenitis (Kikuchi systemic lupus erythematosus: an international inception cohort study. Fujimoto Disease)--a report of four cases. Indian J Pathol Microbiol Arthritis Rheum 2007;56:265-73. 2002;45:89-91. 3. Hanly JG, McCurdy G, Fougere L, Douglas JA, Thompson K. Neu-