SLE and CNS Toxoplasmosis Ruhaila Abdul Rahim Hospital Melaka

�  Malar rash �  Oral ulcers �  Arthritis �  Fever �  Thrombocytopenia o  ANA 1:10,240 o  Anti Ro 196 U/mL o  dsDNA negative o  Low C3,C4 o  DX: SLE o  Rx: Prednisolone 50mg

OD, HCQ 200mgOD, esomeprazole 40mgOD

24y/Malay/ Male First presentation at private hospital February 2013

�  Fever �  Rash �  Headache �  Lethargy �  Dypsnea �  CXR normal �  HB 9.5g/dL, WC 4.0

Platlet 197,ESR34 �  Rx: IV

Methylprednisolone 250mg OD x3/7

30/4/2013 Private Hospital - prednisolone 20mg OD

29/05/2013

� Fitting x1 at Kota Baharu on 26/05/2013

� Fever 1/52 � Behavioral

changes � Headache � Lethargy � AOR Discharge

from ED KB 1st Hospital Melaka Rheumato clinic Visit

�  L UMN CN VII palsy �  Hands tremors �  Power 5/5 all limbs �  Hyperpigmented skin

lesions �  RS,CVS,PA NAD �  No arthritis �  T 38.9C �  Imp: Active SLE with

Cerebral Lupus Plan Admit ward CT brain urgent IV Methylprednisolone 1g OD x3/7 IV Cyclophosphomide once infection excluded

Investigations � HB 8.3g/L, WC 2.7,

Platlet 131, lymphocytes 0.6

� CRP 0.2 mg/L � ESR 15 mm/h � ALT 70 U/L � HBsAg,anti-HepC

virus, HIV Non Reactive

� UFEME Normal � FBP and HB

analysis: beta thalassaemia trait

� Septic workout � LP- refused � CT brain � MRI appointment

Treatment �  IV Ceftriaxone 2g OD �  IV methylprednisolone 1g OD 3/7, later

change to oral prednisolone 30mg bd � T. hydroxychloroquine 200mg OD � C phenytoin 300mg ON � Calcium lactate 600mg OD � Alpha-calcitriol 0.25mcg OD

Progress � Fitted GTC in ward D4 of admission �  Insisted for AOR discharge-social reason

and readmit after 2/7 for IV Cyclophosphomide

�  Blood C&S: Serratia Marcescens, S to cefuroxime

�  FBC normalized �  No seizure �  No fever �  Continue antibiotics �  Cyclophosphomide

deferred to other week

02/06/2013 Readmission for Cyclo

�  IV cyclophosphomide 1.2g ( NIH protocol)

�  1st cycle �  Prednisolone 30mg BD

2/52 then �  Prednisolone 25mg BD

till TCA �  Fitted once at home

post cyclo 10/06/2013

Day Care

MRI Brain 1/7/2014

Small infarcts bilateral periventricular white matter region. Focal lesion on the left thalamus with wall enhancement and perilesional edema suggestive of toxoplasmosis

Toxoplasmosis??

Toxoplasmosis??

Toxoplasmosis??

Further investigations �  Toxoplasma serology

�  Ig G positive �  Ig M negative

�  LP �  C&S NG �  Protein 1.71 g/l �  No cells seen �  India ink negative �  TB PCR not detected �  Toxoplasma rejected

�  Anticardiolipin, anti-b2 glycoprotein-1, Lupus anticoagulant antibodies -ve

Treatment

Induction 3w �  Fansidar 2 tabs od �  Clindamycin 600mg od �  Folinic acid 10mg od

Maintenance 6m �  Fansidar 2 tabs 3x/w �  Dapsone 100mg od �  To continue

maintainace as long as patient is on significant immunosuppressants

Progress

2/52 6/52

2/52

6/52

� Back to premorbid personality

� No headache/fit � FBC normal � RX � Azathioprine

50mg OD � Prednisolone

tapering down to 10mg OD

Clinic follow up 24 July 2013

CRAZY CAT LADY SYNDROME TOXOPLASMOSIS

Toxoplasmosis

Toxoplasmosis � parasitic disease caused by the

protozoan Toxoplasma gondii � T gondii infects a large proportion of the

world's population (perhaps one third) but uncommonly causes clinically significant disease

� Acute toxoplasmosis is asymptomatic in 80-90% of healthy hosts

Acute toxoplasmosis in hosts who do not have AIDS but are immunodeficient �  CNS toxoplasmosis occurs in 50% of patients �  Ocular toxoplasmosis �  Signs and symptoms similar to those observed

in immunocompetent hosts- flulike symptoms and lymphadenopathy

�  Myocarditis �  Toxoplasmic pneumonitis - Typical symptoms

of a pulmonary infection, mirroring in particular P (carinii) jiroveci, including nonproductive cough, dyspnea, chest discomfort, and fever

CNS TOXOPLASMOSIS 3 major pathologic pattern � Diffuse encephalopathy with or without

seizure � Single or large progressive mass lesion � Meningoencephalitis

Remington J , Desmonts G . Toxoplasmosis . In: Remington JS ,  Klein JO editor. Infectious Diseases of the Fetus and Newborn Infant . 3rd ed.. Philadelphia, Pa: WB Saunders Co; 1990;p. 89–95

Procedures for diagnosis � Lumbar puncture � Brain biopsy � Lymph node biopsy � Amniocentesis - Perform amniocentesis at

20-24 weeks' gestation if congenital disease is suggested

� Bronchoalveolar lavage

Immunology �   Anti-Toxoplasma immunoglobulin G (IgG)

titers present a 4-fold increase that peak 6-8 weeks following infection and then decline over the next 2 years, although they remain detectable for life.

� Anti-Toxoplasma IgM appears in the first week of the infection and then declines in the next few months

Murat H,Toxoplasmosis, http://emedicine.medscape.com/article/229969-workup#a0756

Association of antibodies to T.Gondii with SLE � The toxoplasma serological status of 50

patients with SLE was compared with that of 50 healthy controls; high titres of toxoplasma antibody were significantly more common in the patients with SLE. These titres did not correlate with any of the routinely measured indices in SLE nor with the patients' prior treatment

MH wilcox, R J Powel, et., Toxoplasmosis and SLE ,Ann Rheum Dis. Apr 1990; 49(4): 254–257.

Imaging � MRI has superior sensitivity to CT scanning,

and often demonstrate a single or multiple lesion(s) or more extensive disease not apparent on CT scans.

� One study showed that MRI detected abnormalities in 40% of patients whose abnormalities were not detected on CT.

Levy RM, Mills CM, Posin JP, Moore SG, Rosenblum ML, Bredesen DE. The efficacy and clinical impact of brain imaging in neurologically symptomatic AIDS patients: a prospective CT/MRI study. J Acquir Immune Defic Syndr. 1990;3(5):461-71. [Medline].

Imaging � Joseph et al reported that 35% of

computed tomography (CT) brain scans were abnormal and 65% of magnetic resonance (MR) scans, but CT scanning remains valuable in identifying hemorrhages and larger infarcts in patients with systemic lupus erythematosus

Joseph FG, Lammie GA, Scolding NJ. CNS lupus: a study of 41 patients. Neurology. Aug 14 2007;69(7):644-54. [Medline

Cerebral toxoplasmosis in SLE Case reports

�  There have been many reports of toxoplasmosis in SLE patients, mimicking SLE manifestations , and they emphasized the diagnostic problems and recommended serologic analysis for toxoplasmosis before initiation of and during treatment with corticosteroids (2-5)

�  Zamir et al diagnosed toxoplasmosis infection from a post mortem findings of a patient mimicking lupus cerebritis. CT brain was normal

�  Feinglass et al detected CSF abnormalities consistent with Toxoplasmosis infection in 32% of 37 patients with NPSLE

1.Feinglass EJ , Amett FC , Dorsch CA , Zizic TM , Stevens MB . Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease . Medicine (Baltimore) .1976;55:323–339 2.Wechsler B , Le Thi Huong Du , Vignes B , Piette JC , Chomette G , Godeau P . Toxoplasmosis and lupus: a review of die literature apropos of 4 cases [in French] . Ann Med Interne (Paris) . 1986;137:324–330 3. Deleze M , Mintz G , del Carmen Mejia M . Toxoplasma gondii encephalitis in systemic lupus erythematosus: a neglected cause of treatable nervous system infection Rheumatol .1985;12:994–996 4.L pagavalan,FK Kan, Cerebral toxoplasmosis in systemic lupus erythematosus following intravenous methylprednisolone http://www.emjm.org/2011/v66n1/Systemic_lupus_erythematosus.pdf 5.Zamir D,Amar M,Grolsman G,Welner P.Toxoplasma Infection systemic lupus erythematosus mimicking lupus cerebritis.Mayo Clinic Proceedings 1999;74:575-78

Case reports � Seta et al reported a case of

toxoplasmosis in SLE patient who was in low disease activity, with high CD4 ratio

� ? Relationship with HIV patients on HAART with Immune Reconstruction Inflammatory Syndrome(IRIS)

1.N. Seta,T. Shimizu, M. Nawata, R. Wada, K. Mori, I. Sekigawa, N. Iida, M. Maeda, and H. HashimotoA possible novel mechanism of opportunistic infection in systemic lupus erythematosus, based on a case of toxoplasmic encephalopathy Rheumatology (2002) 41 (9): 1072-1073 doi:10.1093/rheumatology/41.9.1072

? Possible mechanism � Normalization of immunity in patients who

have inactive SLE and are receiving relatively low doses of steroids and/or immunosuppressants may contribute to the manifestation of opportunistic infections, as the immune system of SLE patients may originally show hyper‐responsiveness to non‐self as well as self‐antigens

Mizukawa Y, Shiohara T. Virus‐induced immune dysregulation as a triggering factor for the development of drug rashes and autoimmune diseases: with emphasis on EB virus, human herpesvirus 6 and hepatitis C virus. J Dermatol Sci2000;22:169–80

Role of prophylaxis? � Opportunistic infections – rare, ?

underreported � Lack of literature � No guidelines exist � ? Implementing guidelines from

preventing OI in HIV or bone marrow transplanted patients

Perspectives on prevention of OI in SLE patients � Yearly influenza shot � Pneumococcal vaccination � Regular pap smears � TB skin test prior to immunosuppressive � HBAg, HCV, HIV serology baseline � Strongyloides screening in endemic areas

Barber, C.; Gold, W.L. & Fortin, P.R. (2011). Infections in the lupus patient: perspectives on prevention. Current Op Rheumatol, Vol.23, No.4 (July), pp.358-365.

Back to case…..

SLE with CNS toxoplasmosis mimicking NPSLE

SLE �  Pancytopenia �  ANA �  Hypocomplementamia �  Mucocutaneous

CNS Toxoplasmosis �  Imaging �  Immunology �  Responded to

toxoplasmosis treatment

Conclusion � Cerebral lupus is a diagnostic challenge � Essential TRO CNS infections prior to

administration of immunosuppressant � Toxoplasmosis presentations are

nonspecific and may be considered if NPSLE symptoms does not abate with standard immunosuppressive therapy

Conclusions � Further study is warranted before routinely

recommending prophylaxis for all SLE patients on steroid therapy.

�  In patients receiving combination steroid and cytotoxic therapies such as cyclophosphomide, prophylaxis with trimethoprim-sulfamethoxazole should be considered