PENYAKIT AUTOIMUN:

Mengenali Gejala dan

Pendekatan Diagnosis yang Efektif
dr. Faisal Parlindungan, M.Ked(PD), Sp.PD, K-R
Divisi Reumatologi Departemen Ilmu Penyakit Dalam RSCM-FKUI
KSM Penyakit Dalam Rumah Sakit Universitas Indonesia

Jakarta, 30 Juli 2023

 Introduc5on

• The overall prevalence of autoimmunity is approximately 3–5% in the general

population
• Contemporary theories suggest that the development of an autoimmune disease
requires a genetic predisposition and environmental factors.
• Despite extensive research, there are no genetic tools that can be used clinically to
predict the risk of autoimmune disease. Indeed, the concordance of autoimmune
disease in identical twins is 12–67%, highlighting not only a role for environmental
factors, but also the potential importance of stochastic or epigenetic phenomena.
 Autoimmune diseases could be divided into two classes:

An organ-specific disease
is one in which an immune
response is directed In non-organ-specific

toward antigens in a disorders, autoimmune

single organ. acDvity is widely

spread throughout the
body = SYSTEMIC
(Bellanti JA (Ed). Immunology IV: Clinical Applications in Health
and Disease. I Care Press, Bethesda, MD, 2012]
Association of Autoimmune Disease and MHC

• The MHC class I molecules play a pivotal role

in triggering cellular immune responses, binding and
presenting intracellularly derived peptide antigens.
Studies of MHC class I expression revealed a complex
regulatory mechanism that integrates tissue-specific
and hormonal modulation.
• Failure to appropriately regulate class I levels
is predicted to result in autoimmunity.
Environmental Factors In Autoimmunity

Multiple environmental factors have been

implicated in the development of
autoimmunity.
Diagnostic Platform for
Autoimmune Diseases.
 History and physical
examina9on vary
according to the
autoimmmune disease
• Organ specific autoimmune
disease à specific symptoms
• Systemic autoimmune disease
à non specific symptoms,
might affect different
organs/system organs
 LABORATORY TEST
IN RHEUMATOLOGY

Laboratory tests in rheumatology can be divided into three

main categories:
1. Nonspecific measures of inflammation
2. Markers of end-organ involvement
3. Autoantibodies suggestive of an individual disease or group
of diseases

Brigham and Women's Experts' Approach to Rheumatology (2010)

 Nonspecific Measures of Inflamma5on
Markers commonly use in Markers commonly use for
Clinical Practice experimental

CRP ESR IL-6 TNF-Alpha

• These laboratory tests can be used to detect inflammation when it is not clinically
obvious, and in some cases follow disease activity over time.
• However, they are not diagnostic of a particular disease nor are they specific to
rheumatologic diseases, because infections, malignancies, and other disorders can
also increase their levels.
Brigham and Women's Experts' Approach to Rheumatology (2010)
 • The C-reactive protein (CRP) takes its
C-Reactive Protein name from the fact that it reacts with the
C-polysaccharide on bacteria.

• It rises and falls faster with changes in

inflammatory activity than the ESR. The
maximum ESR value is limited by the
length of the Westergren tube (usually
120 mm), but the CRP has no upper limit.

• Cigarette smoking, obesity, diabetes, and

pregnancy may also elevate the CRP,
although the latter has more of an impact
on the ESR.
Brigham and Women's Experts' Approach to Rheumatology (2010) 12
Erythrocyte Sedimentation Rate
The ESR can be elevated in any
autoimmune disease, but in rheumatology
very high values of 100 or more are most
commonly thought of in association with
polymyalgia rheumatica (PMR) and giant
cell arteritis (GCA). Although it is often
measured as part of a rheumatology
workup, the ESR may be elevated in any
inflammatory condition.
Brigham and Women's Experts' Approach to Rheumatology (2010) 13
 The most common causes of an ESR of 100 or more:

33% 17% 17%

Infection Malignancy Renal Disease
Only 14%

Autoimmune Disorders

ü The relevance of an elevated ESR must

It is not specific for autoimmune be interpreted in the setting of other
disease clinical evidence.
ü Other conditions that may increase the
sedimentation rate include some anemia
and pregnancy.
 Markers of end-organ involvement

Renal Function Liver Function

Blood Counts
Test Test

• It refers to changes in laboratory tests such as liver function tests, blood

counts, and renal function tests that may signal disease involvement of
particular organ systems.
 General Laboratory studies in Rheumatologic Disorders

• In addition to specific autoantibodies and nonspecific markers of inflammation, some autoimmune

diseases cause changes in laboratory values that suggest organ involvement.
Brigham and Women's Experts' Approach to Rheumatology (2010) 16
 Autoan'bodies sugges've of an individual disease or group of diseases

• It can be helpful in confirming the diagnosis of

Anti autoimmune diseases. However, these tests must be
CCP
interpreted carefully, because they can be found in
the general population and their significance depends

ANA RF on the prior probability of disease.

• Therefore, they should not be used as a general
screen in persons who do not have symptoms or
signs suggestive of a particular rheumatologic
disorder.

Brigham and Women's Experts' Approach to Rheumatology (2010)

 ANTINUCLEAR ANTIBODIES (ANA)

• Autoimmune an+bodies that bind nuclear

components:
o Double-stranded DNA
o Small nuclear ribonucleoproteins
(eg, SS-A/Ro, SS-B/La, RNP, Smith
an+gen)
o Enzymes (eg, topoisomerase/Scl70)
o Histone proteins
o Centromeric proteins
• >150 epitopes iden+fied to-date
18
 RHEUMATOID FACTOR (RF) AND
ANTI-CYCLIC CITRULLINATED PEPTIDE (ACCP)

• Patients with rheumatoid arthritis à the prevalence of RF can be upwards of 60-80%

• Of note, it can be positive in 4% of the normal population at large and in 25% of the older
population. Therefore, it is unsuitable as a screening tool, because 90% of RF-positive individuals
will not have rheumatoid arthritis and as many as 80% may convert back to seronegative status
over a period of a few years.

• In addition to rheumatoid arthritis, RF can also be positive in SLE, Sjögren’s syndrome, mixed
cryoglobulinemia, chronic liver disease (most commonly hepatitis C), Lyme disease, SBE, and
tuberculosis

Brigham and Women's Experts' Approach to Rheumatology (2010)

19
• The anti-cyclic citrullinated peptide (aCCP) is an ELISA assay that detects antibodies to cyclic
citrullinated peptides. It was developed in 2000 following the discovery of anti-citrullinated protein
antibodies in rheumatoid arthritis patients. It is more specific than RF for rheumatoid arthritis (95%
vs. 85%), with similar sensitivity (67% vs. 69%)

• When choosing laboratory tests for a patient with symptoms consistent with rheumatoid arthritis, it may
be useful to check both the RF and the aCCP, because 34% of rheumatoid arthritis patients with a
negative RF have a positive aCCP.

Brigham and Women's Experts' Approach to Rheumatology (2010)

20
 Ilustrasi Kasus 1
• Ny FA, 30 tahun
• Keluhan utama: Nyeri persendian memberat sejak 1 bulan ini.
• Nyeri persendian dirasakan mulai sejak 1 tahun ini.
• Nyeri dirasakan terutama di pagi saat bangun tidur
• Nyeri sendi dirasakan di jari tangan, pergelangan tangan, siku. Pasien
minum obat berupa parasetamol dan tidak respons dengan baik.
• Rambut rontok dijumpai sejak 1 tahun ini

21
Pasien mengatakan hamil 3 kali:
• Hamil 1,usia 20 tahun, keguguran usia 2 bulan, tidak
diketahui penyebabnya
• Hamil 2 , usia 22 tahun, lahir pada usia 37 minggu, bayi sehat
• Hamil 3, usia 26 tahun, keguguran, usia 4 minggu, tidak
diketahui penyebabnya
Pemeriksaan Fisik
Pertanyaan 1
Apa yang dijumpai pada pemeriksaan fisik?
A. Alopecia
B. Artritis, alopecia
C. Dactylitis, alopecia
D. Non scarring alopecia
E. Artritis, dermatitis seboroik
Pemeriksaan Fisik
Gait : normal
Arms : tenderness PIP 1 manus bilateral, wrist bilateral
Leg : normal
Spine: normal
Pemeriksaan Fisik
• mata: pucat negatif tidak ikterik
• Kepala: non scarring alopesia (+)
• leher: JVP 5-2 cm H2O tiroid KGB dbn
• thorax: vesikular positif tidak ada ronkhi dan tidak ada
wheezing, BJ I-II regular murmur dan gallop negative
• abdomen: supel nyeri tekan tidak ada, asites negatif tidak
ada
• ekstremitas: edema negatif CRT <2 detik
Penunjang
ANA IF = 1:320
Pertanyaan 2
Pemeriksaan penunjang apa yang akan Anda mintakan selanjutnya?
A. ANA profile
B. C3,C4
C. Antibodi antifosfolipid
D. Anti ds DNA
E. Anti Sm
 SLE Classifica,on Criteria
1971 1982 1997 2012 2019 Now

ACR 1971

ACR 1982

ACR 1997

SLICC 2012

ACR/EULAR
2019
Kriteria Klasifikasi ACR/EULAR 2019

v Sensitivitas 96,12%
v Spesifisitas 93,38%
v Kriteria klasifikasi ini dapat digunakan jika titer ANA-IF positif ≥1:80 (atau
positif dengan metode pemeriksaan lain yang ekuivalen) dan tidak ada
kemungkinan penyebab selain LES
v Dimasukkan dalam klasifikasi LES jika memiliki skor total ≥10 dengan minimal
satu kriteria klinis

Rekomendasi Perhimpunan Reumatologi Indonesia . Diagnosis dan Pengelolaan Lupus Eritematosus Sistemik.2019
 kekakuan sendi minimal 30 menit
Domain neurologi
Delirium 2
Psikosis 3
Kriteria Klasifikasi ACR/EULAR 2019 Kejang
Domain serositis
5

Efusi pleura atau perikardium 5

Perikarditis akut 6
Tabel 3.3. Kriteria Klasifikasi ACR/EULAR 201821 Domain hematologik
Domain Klinis Poin Leukopenia 3
Trombositopenia 4
Domain konstitusional
Hemolisis autoimun 4
Demam 2
Domain ginjal
Domain kulit
Proteinuria >0,5 g/24 jam 4
Nonscarring alopesia 2
Lupus nefritis kelas II atau V 8
Ulkus oral 2 Lupus nefritis kelas III atau V 10
Lupus kutaneus subakut atau diskoid 4 Domain imunologi Poin
Lupus kutaneus akut 6 Domain antibodi antifosfolipid
Domain Artritis IgG antikardiolipin >40 GPL atau IgG anti-β2GP1 >40 unit atau antikoagulan lupus 2
Sinovitis pada minimal 2 sendi atau nyeri sendi pada minimal 2 sendi, dan Domain protein komplemen
6
kekakuan sendi minimal 30 menit C3 rendah atau C4 rendah 3
Domain neurologi C3 rendah dan C4 rebdah 4
Delirium 2 Domain antibodi yang sangat spesifik
Psikosis 3 Antibodi anti-dsDNA 6
Kejang 5 Antibodi anti-Smith 6
Domain serositis
Efusi pleura atau perikardium 5
Perikarditis akut 6
Kriteria klasifikasi dapat digunakan untuk memandu diagnosis LES. Pada beberapa kasu
Domain hematologik
Leukopenia mungkin
3 menemukan kasus bukan LES yang memenuhi kriteria klasifikasi. Sebaliknya, mungk
Trombositopenia ditemukan
4 kasus LES yang tidak memenuhi kriteria sehingga diperlukan pengkajian secara men
Hemolisis autoimun terhadap
4 keseluruhan aspek klinis pasien oleh dokter spesialis atau subspesialis yang berpenga
Domain ginjal dalam mendiagnosis dan menangani kasus LES.
Proteinuria >0,5 g/24 jam 4
Lupus nefritis kelas II atau V 8
Lupus nefritis kelas III atau V 10
Domain imunologi B. Diagnosis
Poin Banding LES
Domain antibodi antifosfolipid Beberapa penyakit atau kondisi di bawah ini seringkali membingungkan diagnosis
IgG antikardiolipin >40 GPL atau IgG anti-β2GP1 >40 unit atau antikoagulan lupus 2
Domain protein komplemen
gambaran klinis yang mirip atau beberapa tes laboratorium yang serupa yaitu undiffere
C3 rendah atau C4 rendah connective
3 tissue disease, sindrom Sjögren primer, sindrom antibodi antifosfolipid primer, fibrom
 Kepadatan rambut
Regio skalp berkurang, empty
follicles
 SLICC 2012
The Systemic Lupus Collabora5ng Clinics

• Sensitivitas: 97%
• Spesifitas: 84%
• Termasuk klasifikasi LES jika memenuhi
4 dari 17 kriteria (minimal memiliki 1
kriteria klinis dan 1 imunologi), ATAU
pasien dengan nefritis yang sesuai
dengan LES dan terbukti dari biopsi
disertai dengan pemeriksaan ANA atau
anti-dsDNA positif
Diagnosis dan Pengelolaan Lupus Eritematosus Sistemik. Perhimpunan Reumatologi
Indonesia. 2019
Apa itu ANA
• Autoimmune antibodies that bind nuclear components:
o Double-stranded DNA
o Small nuclear ribonucleoproteins (eg, SS-A/Ro, SS-B/La,
RNP, Smith antigen)
o Enzymes (eg, topoisomerase/Scl70)
o Histone proteins
o Centromeric proteins
• >150 epitopes identified to-date
 Arthritis Care & Research
Vol. 65, No. 3, March 2013, pp 329 –339
DOI 10.1002/acr.21930
© 2013, American College of Rheumatology
SPECIAL ARTICLE

ACR Top 5Choosing Wisely: The American College of 333

Rheumatology’s Top 5 List of Things
Physicians and Patients Should Question
JINOOS YAZDANY,1 GABRIELATable 1.1 The 1American
SCHMAJUK, College
MARK ROBBINS, 2
of Rheumatology’s
DAVID Top
DAIKH,1 ASHLEY 5 list*
BEALL, 3

EDWARD YELIN, JENNIFER BARTON, ADAM CARLSON, MARY MARGARETTEN, JOANN ZELL,4
1 1 1

LIANNE S. GENSLER,1 VICTORIA KELLY,5 KENNETH SAAG,6 CHARLES KING,7 AND

Do not test ANA
THE subserologies
AMERICAN COLLEGE without a positive ANA
OF RHEUMATOLOGY COREand clinical suspicion
MEMBERSHIP GROUP of immune-mediated disease.
Tests for ANA subserologies (including antibodies to double-stranded DNA, Sm, RNP, SSA, SSB, Scl-70, and centromere) are
usually negative
Objective. if thetoANA
We sought is anegative.
develop Exceptions
list of 5 tests, treatments, orinclude anti–Jo-1,
services commonly usedwhich can be practice
in rheumatology positivewhose
in some forms of myositis, or
necessity or value should be questioned and discussed by physicians and patients.
occasionally,
Methods. Weanti-SSA in the setting
used a multistage process of lupus or
combining Sjögren’s
consensus syndrome.
methodology Broad testing
and literature reviews of autoantibodies
to arrive at the should be avoided;
instead, the
American choice of
College of autoantibodies
Rheumatology’s (ACR)should be
Top 5 list. guided by the
Rheumatologists specific
from diverse disease under
practice settings consideration.
generated
using the Delphi method. Items with high content agreement and perceived high prevalence advanced to a survey of ACR
items

members, who comprise >90% of the US rheumatology workforce. To increase the response rate, a nested random sample
of 390 rheumatologists received more intensive survey followup. The samples were combined and weighting procedures
Do not test for Lyme disease as a cause of musculoskeletal symptoms without an exposure history and appropriate
were applied to ensure generalizability. Items with high ratings underwent literature review. Final items were then
examination findings.
selected and formulated by the task force.
Results. One hundred five unique items were proposed and narrowed down to 22 items during the Delphi rounds. A total
The musculoskeletal manifestations of Lyme disease include brief attacks of arthralgia or intermittent or persistent episodes of
of 1,052 rheumatologists (17% of those contacted) participated in the member-wide survey, whereas 33% of those in the
nested random sample participated; respondent characteristics were similar in both samples. Based on survey results and
arthritis in 1 or a few large joints at a time, especially the knee. Lyme testing in the absence of these features increases the
available scientific evidence, 5 items (relating to antinuclear antibodies, Lyme disease, magnetic resonance imaging, bone
absorptiometry, and biologic therapy for rheumatoid arthritis) were selected for inclusion.
likelihood of false-positive results and may lead to unnecessary followup and therapy. Diffuse arthralgias, myalgias, or
Conclusion. The ACR Top 5 list is intended to promote discussions between physicians and patients about health care
https://www.aacc.org/-/media/Files/Transcripts/Pearls-of-Laboratory-Medicine/2018/Slides/Antinuclear-Antibody-Testing-
Tacker-Slides.pdf?la=en&hash=62020F086AFE9BC2A849FB5FAB4CC8B1AC4EAAAF
Pertanyaan 3
Apakah test ANA perlu diulang untuk evaluasi tatalaksana?
A. Ya
B. Tidak
World Health Organization/Arthritis Foundation/Centers for
Disease Control and Prevention autoantibody standardising
committee.

4. ANA testing is primarily intended for

diagnostic purposes, and not for monitoring
disease progression

Agmon-Levin N, et al. Ann Rheum Dis 2014;73:17–23. doi:10.1136/annrheumdis-2013-203863

 Ilustrasi Kasus 2

• Nama : Ny.T
• Usia : 21tahun
Identitas Pasien
• Nama : Ny.T
• Usia : 21tahun
• Dikonsulkan oleh GP pasca test MCU dengan hasil ANA IF : 1:100
• Saat ini pasien mengaku tidak ada keluhan apapun
Pertanyaan 4
Apakah ANA perlu diulang pada pasien ini untuk memastikan hasil
yang positif?
A. Ya
B. Tidak
World Health Organization/Arthritis Foundation/Centers for
Disease Control and Prevention autoantibody standardising
committee.

2. ANA, anB-dsDNA and anB-ENA tesBng should be

included in the autoanBbodies detecBon as part of the
diagnosBc work-up of SARD as well as some other
autoimmune diseases

Agmon-Levin N, et al. Ann Rheum Dis 2014;73:17–23. doi:10.1136/annrheumdis-2013-203863

Applying ANA to Clinical Diagnosis
Pertanyaan 5
Kondisi berikut mana yang mungkin menyebabkan hasil ANA test
positif?
A. Infeksi virus
B. Orang sehat
C. TBC
D. Keganasan
E. Semua benar
 Diseases and Related Conditions Associated
With Anti-nuclear Antibodies

Kelley Rheumatology.2020
 Ilustrasi Kasus 3

• Nama : Ny.A
• Usia : 21tahun
 RIWAYAT PENYAKIT SEKARANG
6 bulan SMRS
Pasien mengeluh nyeri di sendi-sendi jari tangan, pergelangan tangan, dan siku kedua tangan.
Nyeri terutama dirasakan saat pasien istirahat, membaik jika pasien mulai menggerakkan kedua
tangan. Keluhan disertai dengan kaku di jari-jari tangan terutama pagi hari saat bangun tidur.
Kaku dirasakan sekitar 2 jam, membaik jika pasien mulai menggerakkan jari-jari tangan. Keluhan
lain tidak ada. Pasien kemudian berobat ke SpPD di Lombok, dikatakan penyakit autoimun
namun belum tau jenis apa.

1 Minggu SMRS
Pasien pindah domisili ke Jakarta. Pasien ingin melanjutkan pengobatan di Jakarta. Saat ini
pasien mengeluh nyeri-nyeri sendi masih ada, namun sudah membaik dengan menggunakan
obat metilprednisolon. Keluhan selain nyeri sendi tidak ada
 Riwayat Penyakit
• Riwayat penyakit dahulu:
– Riwayat penyakit stroke, jantung, hati, dan ginjal disangkal

• Riwayat penyakit keluarga:

– Tidak ada anggota keluarga yang menderita penyakit autoimun, penyakit jantung, hati,
hipertensi, ginjal, dan keganasan

• Riwayat Sosial Ekonomi:

– Pasien sudah menikah, memiliki 4 orang anak
– Pasien seorang ibu rumah tangga
– Riwayat minum alkohol, IVDU dan promiskuitas disangkal
– Pembiayaan JKN
Pemeriksaan FISIK
 Pemeriksaan fisik

Kesadaran : Kompos menDs

Tekanan darah : 119/ 79 mmHg G Normal

Frekuensi Nadi : 95 x/menit A Tender joint PIP 2-5 bilateral, wrist bilateral, elbow kanan.
Swollen joint PIP 2 dan 5 bilateral
Frekuensi Nafas : 16 x/menit L Tidak ada tenderness maupun swollen joint
S Normal
Suhu : 36.2 C

SpO2 : 99% oksigen ruangan

BB : 59kg kg, TB : 168cm cm, BMI : 20.9

 Pemeriksaan Fisik

Mata: konjungtiva tidak pucat, sklera

tidak ikterik.
Jantung : S1-S2 reguler, murmur dan
Leher: ;dak teraba pembesaran KGB gallop ;dak ada

Pulmo: bunyi napas vesikuler bilateral,

ronkhi dan wheezing tidak ada
Abdomen: supel, bising usus posi;f,
hepar dan lien ;dak teraba

Ekstremitas : akral hangat, CRT<2s, tidak ada

edema
 Pemeriksaan penunjang

ANA IF 1:100

Ro Manus
Foto manus kanan dan kiri tidak tampak fraktur /
dislokasi / degenerative disease
Pertanyaan 6
Pemeriksaan penunjang yang sebaiknya Anda mintakan, kecuali?
A. CRP
B. RF
C. Anti-CCP
D. ANA-IF
E. ANA profile
 Kapan memintakan ANA profile

19. In case of a positive ANA test during the diagnostic work-up

(depending on pattern, titre and/or clinical setting), it is
recommended to perform specific tests for anti-ENA antibodies
Contoh ANA
profile
 Pemeriksaan penunjang

RF NegaBf
CRP 20 (high)
Pertanyaan 7
Apa diagnosis yang paling mungkin pada kasus ini?
A. SLE
B. RA
C. Gout
D. OA
Kriteria klasi8ikasi Rheumatoid Arthritis
Hasudungan A. Rheumatoid Arthritis Patophysiology. 2016. https://www.youtube.com/watch?v=ld8PhyAHov8
Indonesian Rheumatology Association. Artritis Reumatoid. 2021
Pada pasien dilakukan pemeriksaan anti CCP

AnB-CCP IgG 249.9 (high)

Pertanyaan 8
Apakah masih dibutuhkan pemeriksaan ANA profile untuk
diagnostik?
A. Masih
B. Tidak perlu
TERIMA KASIH