Case Reports :The Use of Intravenous

Methylprednisolone in the Treatment of Systemic Lupus Erythematosus

(SLE) with Infection and TB

dr. Khoirul Anwar

Pendahuluan

• Cornerstone Tx• Severe SLE IVMP (pulse dose) • Double-edged sword • Risk vs benefit• Komplikasi IVMP detection, risk factor, prevention and

treatment

KASUS

Kasus

•Wanita 27 tahun• Bengkak badan• SLE• Susp nefritis lupus CKD stage V• Susp NPSLE• AIHA• Serositis (efusi pericard, efusi pleura)• Hematologi (trombositopenia, limfopenia)

Kasus

• Pleuropneumonia ec TB• ISK ec ESBL• Riwayat TB paru

Kasus

• TD 140/90 N 100 RR 26 T 37,3•Malar rash (-) • Edem anasarka• Paru : redup di aspek inferior paru dextra, roncho (-) • Jantung : cardiomegali (+), muffled sound (-), bising (-) • Abdomen : ascites (+)

Kasus

Hb 8,8 AL 15,4 S 92,7 L 4,3 AT 94Procal 4,9

Bun 77,7 creat 6,4 Na 133 K 4,2 Cl 93

UR : protein +4 Nit - LE +3 bakt 30.020 Leu 45.444

SGOT 15 SGPT 80 alb 1,6

ANA IF (+) titer 1:100Pola homogendsDNA 1173 (N=<100)C3 48 (N=90-180)C4 26,2 (N=10-90)Coomb (+)

K/S urin

Klebseilla pneumonie

ESBL (+)

Rontgen torax• Edema pulmo• Cardiomegali

USG torax• Hemitorax sinistra didapatkan hasil pleuropneumonia (penebalan dan irreguleritas pleura viseralis sinistra,

B line (+), didapatkan efusi pleura minimal• Hemithorax dextra didapatkan efusi pleura minimal• Curiga efusi pericard

USG ginjal• Ren dextra : ukuran 10,09 x 5,2 cm, echostruktur meningkat, batas kortek medula mengabur, SPC tidak melebar, tak tampak massa/batu• Ren sinistra : ukuran 8,04 x4,42 cm, echostruktur meningkat, batas kortek medula mengabur, SPC tidak melebar, tak tampak massa/batu• Kesan : inflamasi renal bilateral terutama sinistra

Problem• Severe SLE• Infection • CKD V• TB paru

Apakah penggunakan IVMP aman pada kondisi infeksi ? Komplikasi IVMP dan faktor yang mempengaruhi munculnya komplikasi IVMP

Apakah yang harus diketahui dengan TB pada SLE ?

PEMBAHASAN

Hubungan infeksi dengan SLE

Infection, 44%

SLE flare, 24%

Others, 18%

Surgical Cause, 14%

Penyebab Rehospitalisasi

Infection SLE flare Others Surgical Cause

Lata S Bichile, Vaibhav C Chewoolkar Lupus Flare: How to Diagnose and Treat, Medicine update 2011

Faktor-faktor yang menyebabkan SLE flare

Lingkaran setan hubungan infeksi dengan autoimunitas (SLE)

Inadequately of

immune response

Using

immunosupressant

agent

Molecular mimicry theory

Molecular mimicry theory

• SLE dan terapi SLE• penurunan innate dan

adaptive immune• infeksi ⬆

Flare vs infection

Procal ⬆ in SLE infection

Flare vs infection

• CRP increased in 92% of the group with infection

• 89% of the group with lupus flare• CRP tended to be higher in the group with

non-viral • but this did not reach significance (p=0.98).

Flare vs infection

• serum PCT increased significantly in patients with SLE with non-viral infection compared with patients with lupus flare

Flare vs infection

Flare vs infection• Proteinuria • Fever • SLEDAI

Apa resiko/komplikasi penggunaan IVMP pada

SLE

Genomic and non genomic action of glucorticoids

Genomic action of glucorticoidsTransactivation

the synthesis of anti-inflammatory proteins (such as, for example, annexin (lipocortin)

1, IκB, interleukin (IL)-10)

Transrepressionsuch as nuclear factor-κB, activator

protein-1 and nuclear factor for activated T cells, as a consequence

reducing the expression of proinflammatory proteins such as IL-1,

IL-6 or tumor necrosis factor (TNF) alpha

Genomic and non genomic action of glucorticoids

optimization of the genomic action• by low-dose administration• modified-release prednisone

optimization of the nongenomic action• high doses• any time of the day

genomic

Glucocorticoids effects

Genomic effect

NonGenomic effect

Glucocorticoids effects on SLE flare

Corticosteroid... antiinflamation

SLE Flare• > High dose• Antiinflamasi• Infeksi ⬆ tapi

tidak seberat penggunaan low dose (genomic effect)

THEORY

EVIDENCE

Apakah penggunaan corticosteroid aman pada SLE flare dengan infeksi ?

MP pulse dose

MP pulse dose

RiskPreventabl

eTherapy

Detection

Tx Flare

Apakah penggunaan corticosteroid aman pada SLE flare dengan infeksi ?

HASIL

Tx Flare

Apakah penggunaan corticosteroid aman pada SLE flare dengan infeksi ?

Infection

Apakah penggunaan corticosteroid aman pada SLE flare dengan infeksi ?

• Infeksi harus diatasi (molecular mimicry)

• Tx optimal sesuai KS• Faktor resiko prediktor harus

dioptimalkan terapinya• Albumin• Limfositopenia• Trombositopenia • Fungsi ginjal

Terapi • Inj. Methylprednisolone 125 mg/ 12 jam• Cellcept 2x1000mg• Kloroquin 1x150mg• Inj. Meropenem 500mg/12jam• Inj. Moxifloxacin 400mg/12jam• Transfusi albumin• HD sesuai jadwal

Evaluasi

Hb 8,8 10,7 8,2AL 15,4 19 9,7S 92,7 93,3 93,5L 4,3 3,6 3,7AT 94 137 138Procal 4,9 N/AAlb 1,6 2,2 2,6

UR : Prot +4 +4Nit - -LE +3 +3bakt 30.020 1274Leu 45.444 8841

Klinis :

Demam (-)

Sesak (+) ⬇

Bengkak (+) ⬇

Nyeri perut (-)

Kejang (-)

Penkes (-)

Nyeri kepala (-)

Kesimpulan• Infeksi membaik dengan pengobatan antibiotik• Aktivitas SLE membaik setelah pemberian IVMP

TB pada SLE

• Prevalence ± 5%• Pulmonary TB > extra

pulmonary

Tuberculosis in SLE

Immunodeficiency in SLE

Immune respone in TB

Melibatkan sel T (CD4 CD8), sitokin, sel B, complemen

Complement in TB

C3-dependent entry pathwayinto resident alveolar macrophages

Problems... (1)

SLE Complement

deficiency

Risk for TB

infection

SLE is Risk factor for TB infection

Pada Pasien ini• Penderita SLE • Kadar complement rendah

TB in SLE

Rontgen thorax :• Milier• Konsolidasi diffuse• TB klasik (konsolidasi

apex)

Pada Pasien iniGambaran parenkim paru normalTB ditegakan dari gambaran USG

TB in SLE

TB in SLE

Perjalanan penyakit TB pada SLE:• Akut • progresif

Pirazinamide in liver

SLE pathophysiology

SLE in drug induced hepatitis

Tissue inflamation and necrosis (liver injury)

SLE in drug induced hepatitis EVIDENCE...??

• Incidence 12,9% overall

• SLE increase risk for Anti TB liver injury

SLE in drug induced hepatitis EVIDENCE...??

• 237 pts SLE 3 pts TB

• 3 pts TB Anti TB liver injury

• SLE ⬆ risk anti TB liver injury

Terapi • INH 1x300mg• Rifampisin 1x450mg• Pirazinamide 1250mg 3x/minggu• Etambutol 750mg 3x/minggu

Evaluasi

SGOT 15 23 15 SGPT 80 9 4Tbil NA 0,55 0,21Dbil NA 0,16 0,12

Kesimpulan • Pasien mendapat OAT • Monitoring tidak didapatkan efeksamping DILI

TAKE HOME MESSAGE • Risk and benefit• Judgment klinis (referensi, evidence, experience)•Monitoring• Edukasi

THANK YOU....