acute pulmonary tuberculosis in sle

Acute Pulmonary Tuberculosis in Systemic Lupus Erythematosus

Case-based Discussion & Book ReadingPresented : dr. Khoirul AnwarSupervisor : dr. Ayu P., Sp. PD KR

INTRODUCTION....

Infection, 44%

SLE flare, 24%

Others, 18%

Surgical Cause, 14%

Penyebab Rehospitalisasi

Infection SLE flare Others Surgical Cause

Infection in SLE

• active SLE• nephritis,• Sepsis• and cardiovascular disease

Mortality in SLE

• Prevalence ± 5%• Pulmonary TB > extra pulmonary

Tuberculosis in SLE

THE CASE....

Wanita, 32 tahun penderita SLE dengan keluhan utama saat ini lemas dan sesak

1 2 3 4

Kontrol rutin di poli dengan tx Sandimmun 2x100mg dan MP tape dose

Juli 2016 mondok kembali karena AIHA (hb 6,2) BLPL dengan tx pulang MP 8mg 3-2-0 dan sandimun 2x100mg

Kontrol di poli dengan Tx sandimmun 2x50mg dan novorapid

Okt 2013 tegak SLE (AIHA, efusi pericard, oral ulcer, anti dSDNA (+), LE sel (-) Tx MP dan sandimmun

1 minggu sariawan memberat dan batuk, makan dan minum , ⬇lemas (+)

RPS :Sejak 1 minggu os mengalami lemas, batuk dan sesak yang semakin memberat. Sariawan berupa bercak putih di lidah (+), sulit makan (+), demam (+), batuk dahak (+), darah (-), kejang (-), pingsan (-), nyeri sendi memberrat (+), kaki lemas (+)

Os menyangkal batuk lama, BB, keringat malam, maupun kontak TB⬇

Pemeriksaan FisikKU : sedang, CM, gizi baik

TB 150 cm, BB 40 kg, IMT 21,22kg/m² VS : TD 110/70 mmHg, tidur, manset di lengan kanan, large

adult cuff N 116 x/menit, irama teratur, isi dan tekanan cukup

R 29 x/menit, irama teratur, tipe pernapasan thorakoabdominal T° 38 °C, suhu aksila

Kepala : Insp. : konj. pucat (-), sklera ikterik (-), kulit tipis (+), hirsutisme (+), moon face (+), oral trush (+), oral ulcer (+),

Palp. : tidak ada nyeri tekan, tak teraba massaLeher : Insp. : JVP tak meningkat, buffalo hump (+),

Palp. : lnn ttbThorax :

Pulmo : Insp. :simetris, KG (-), retraksi (-)

Palp. :stem fremitus kanan = kiri

Perk. :sonor (+)

Ausk. :vesikuler (+) RBK (+/+) RBB (-) Wheezing (-)

Cor : Insp.: IC tak tampak

Palp. :IC teraba di SIC V LMCS

Perk. :kardiomegali (-), kesan konfigurasi dbn

Ausk. : S1-2 murni reguler, bising (-)

Pemeriksaan FisikAbdomen : Insp. : rounded

Ausk. : peristaltik (+) NPerk. : timpani di seluruh regioPalp. : NT (+) regio epigastrium, H/L

ttbExtremitas : Insp. : edema − − raynaud

phenomen +/+− −

Palp. : akral hangat, tidak ada nyeri tekan

Ro thorax 07/10/16 :• Round pneumonia segmen

anterior lobus superior dekstra• cardiomegali

PEMERIKSAAN PENUNJANG

Darah Rutin 7/10/16 14/10/16 19/10/16

21/10/16

Hemoglobin 12,2 11,3 8,9 12,8 g/dL

Angka Leukosit 15,06 19,8 9,2 16 /mL

Segmen 97,1 94,4 87,8 89 %

Limfosit 1 5,1 7,3 %

Monosit 1,3 1,8 4,6 %

Eosinofil 0,1 0,1 0,2 %

Basofil 0,1 0,2 0,2 %

Angka Trombosit 362 238 185 186 /mL

Angka Eritrosit 3,9 3,6 2,9 /mL

Hematokrit 38,9 32,9 25,5 %

MCV 99,6 90,6 86 fL

MCH 31,2 30,1 30 Pg

PEMERIKSAAN PENUNJANG

7/10/16 14/10/16 19/10/16 21/10/16

BUN 62 21 15

Creat 2,4 0,9 0.6

AU

Na 133 140 148 148

K 4,4 2,6 2,13 3,5

Cl 98 101 103 107

SGOT 10 16 602

SGPT 17 15 168

TP

Alb 2,5 2,8 3,2

GDS 527

HbsAg (-)

PEMERIKSAAN PENUNJANG

ANA (+)

dSDNA (+)

Coomb test (+)

C3

C4

CD4 7

Anti HIV (-)

Tbil 0,8 5,6

DBil 0,2 4,5

16/10 19/10

CRP

Procalc 2,4 0,9

PEMERIKSAAN PENUNJANG

7/10

pH 6,0

BJ 1,010

Protein (-)

Glukosa +4

Bilirubin (-)

Urobilin (-)

Keton (-)

Nitrit (-)

Eritrosit 5

Silinder (-)

Silinder patologis

(-)

Bakteri 330

LE (-)

Sputum• Cat gram = (-) • BTA 3 kali (-) • K/S tidak tumbuh

Darah • K/S tidak tumbuh

Urine • BTA (-) • K/S tidak tumbuh

EKG 07/10/16 : Sinus Rythm, heart rate 100 kali/menit

SLEDAI 7/10 19/10

Gangguan neuro (-) 8

Gangguan ginjal (-) (-)

Vaskulitis (-) 8

Hemolisis (-) (-)

Trombositopnia (-) (-)

Myositis (-) (-)

Artitis (-) (-)

Mukokutan 2 2

Serositis 2 2

Demam 1 1

Fatigue 1 1

Leukopenia (-) (-)

TOTAL 6 22

Re-assesment1. Sistemik lupus eritematosus dengan manifestasi• Chronic kidney disease stage IV et causa nefritis lupus• Suspek community acquired pnemumoniae dd pneumonitis dd TB paru• Mukokutan (oral ulcer) dengan candidiasis oral• Riwayat efusi paricard moderate tanpa tamponade

2. Hiperglikemia stress pada diabetes mellitus tipe lain3. Hipoalbuminemia4. Hiponatremia normoosmolar

Terapi :• Diet cair / lunak • Sandimun 2x50 mg• MP 16-16-0• Inj. Novomix 6-6-6• Nystatin drop 4x1 cc• Tranfusi albumin 20% 100 cc• Inj. Ampisulbac 1,5 gram/12 jam • Azitromicin 500mg/24 jam• Fluconazole 800mg/24 jam

400mg/24 jam 200mg/24 jam

Plan :• Cukupi kebutuhan cairan 30-

50cc/kgbb/24 jam• Monitor UOP

0,5-1cc/kgbb/jam• Rontgen thoraks serial• Tranfusi albumin s/d ≥3• Oksigenasi NK 3lpm• Cek gene ekspert• BTA urin• USG thoraks hari senin• Ks jamur• Ks darah

Evaluasi klinis paru

• Terjadi efek samping OAT (hepatitis)

• Terjadi Flare ? (NPSLE ?)

• MP 750mg/24jam

• Gambaran pneumonia menetap

• Mulai 4FDC

• Gambaran pneumonia (5 hari batuk, sesak, demam)

• Tx empirik • MP 62,5mg/24 jam• Sandimmun 2x50mg

DISCUSSION....

Points Of Discussion• TB infection risk in SLE:

mechanism and susceptibility factors

• Anti TB and its adverse events in SLE

• Treatment SLE flare (MP) in TB infection

Problems...

Points Of Discussion• TB infection risk in SLE:

mechanism and susceptibility factors

• Anti TB and its adverse events in SLE

• Treatment SLE flare (MP) in TB infection

Problems...

• Prevalence ± 5%• Pulmonary TB > extra pulmonary

Tuberculosis in SLE

TB in SLE

Lingkaran setan hubungan infeksi dengan autoimunitas (SLE)

Immunodeficiency 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

Complement in TB

Role Complement in TBC3-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 sejak 2013• CD4 = 7 ( )⬇• Kadar complement rendah

Points Of Discussion• TB infection risk in SLE:

mechanism and susceptibility factors

• Anti TB and its adverse events in SLE

• Treatment SLE flare (MP) in TB infection

Problems...

Corticosteroid... Immune def.

• Genomic action• Non genomic action

Corticosteroid... Immune def.

• Genomic action• Low dose• Long periode

Corticosteroid, TB risk...

Corticosteroid, TB risk...

Problems... (1)

SLE Complement deficiency Risk for TB

infection

• SLE is Risk factor for TB infection

• Corticosteroid (longterm) is risk factor for TB

Pada Pasien ini• Penderita SLE sejak 2013• CD = 7 ( )⬇• Kadar complement rendah• Penggunaan jangka panjang MP

Corticosteroid treatment

TB in SLE

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

Pada Pasien iniRound pneumonia segmen anterior lobus superior dekstra

TB in SLE

TB in SLE

Perjalanan penyakit TB pada SLE:• Akut • progresif

Pada Pasien ini• Gejala akut• progresif

Points Of Discussion• TB infection risk in SLE:

mechanism and susceptibility factors

1. SLE dan MP jangka panjang resiko TB

2. TB pada SLE dapat bersifat akut dengan gambaran klinis dan radiologis tidak khas

Problems...

Points Of Discussion• TB infection risk in SLE:

mechanism and susceptibility factors

• Anti TB and its adverse events in SLE

• Treatment SLE flare (MP) in TB infection

Problems...

Anti TB Tx is the Key

• Improve clinicaly and radiographic

• Worsening • PCR TB (+)• M. Tb micros (+) • Culture (-) • Start anti TB tx

• 5 days caugh• Dyspnue• Fever • Antibiotic empiric

escalation on antibiotic

Anti TB Tx is the Key

• Drug-induced Hepatitis

• Encephalopaty dd NPSLE

• Clinically Worsening • PCR TB tdk

dikerjakan• M. Tb micros (-) • Culture (-) • Start anti TB tx

• 5 days caugh• Dyspnue• Fever • Antibiotic empiric

escalation on antibiotic

PADA PASIEN INI.....

Anti TB induce hepatitis SLE as a risk??

In Facts• Pasien mengalami OAT-induce

hepatitis• Klinis berat hingga encepalopati• Apakah SLE mempengaruhi

kejadian ini?• Apakah OAT-induce hepatitis

menyebabkan flare ?

Drug induce hepatitis

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

Points Of Discussion• Anti TB and its adverse events

in SLE

1. Early diagnosis and Tx is key point

2. SLE risk for anti TB liver ⬆injury

3. Anti TB liver injury risk ⬆flare SLE

Problems...

Points Of Discussion• TB infection risk in SLE:

mechanism and susceptibility factors

• Anti TB and its adverse events in SLE

• Treatment SLE flare (MP) in TB infection

Problems...

SLE flare

• FLARE ???• Enchepalopathy• NPSLE• Seizure

• Anti TB liver injury

PADA PASIEN INI.....

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

Flare vs infection

REFERENCE :• CRP = ⬆ infection non viral • Procalcitonin =⬆ infection non

viral• Proteinuria (+) = flare• Fever (+) = infection• SLEDAI = ⬆ flare

Pasien :• CRP = NA• Procalcitonin =⬆ infection non

viral• Proteinuria = (-) • Fever = (+) • SLEDAI = 22

• Pasien mengalami (flare ?)

Tx SLE flare in infection

MP pulse dose

MP pulse dose

Tx severe Flare with infection

Pulse MP, hidroxycloroquin, cycophospamide, rituximab

Tx severe Flare with infection

Flare vs infection

REFERENCE :• MP pulse dose infection ⬆• MP pulse dose mortality ± 20%• Trombocytopenia mortality ⬆• IvIg may be the first line tx for

patient immunodeficient

Pasien :• MP pulse dose (+)• Infection (procalcitonin )⬆ ⬆• Trombocytopenia (+)• IvIg ????

• Pemberian pulse MP sudah tepat karena mengalami flare berat• Namun sayangnya pasien mengalami komplikasi dari Pulse MP• Apakah ada pilihan lain? IvIg ?

Points Of Discussion• Treatment SLE flare (MP) in TB

infection

1. Pulse MP meningkatkan resiko infeksi dan mortalitas pada kelompok berisiko

2. Pilihan lain selain pulse MP?

Problems...

CONCLUSION:• SLE dan MP jangka panjang merupakan faktor risiko TB• TB pada SLE bisa bersifat akut dengan gambaran klinis dan

rontgen tidak khas• Anti TB liver injury sering terjadi pada pasien SLE dalam

pengobatan TB • Anti TB liver injury dapat memicu flare• Tatalaksana flare SLE pada infeksi berat menimbulkan

komplikasi dan mortalitas yang tinggi

THANK YOU....