SYSTEMIC LUPUS ERYTHEMATOSUS

AND INFECTION

RAKHMA YANTI HELLMI

Div. Reumatologi RSUP DR Kariadi /FK UNDIP, Semarang

 Systemic Lupus Erythematosus(SLE) : chronic
autoimmune disease with diverse manifestations,with
pathogenesis unclear & complicated

Infection & SLE are similar in that both cause

inflammatory reactions

INTRODUCTI
ON Infection is common trigger factor for SLE

Immunosuppressive therapy and abnormalities of the

immune system in SLE causes highly suspectible
infection

Amy D, Robert S, , GC Tsokos Systemic Lupus Erythematosus and Infection. Basic, Aplied, Clinical Aspect.2016. 403-10
 Infection : major cause of
morbidity and mortality in SLE

EPIDEMIOLO Hospitalization rates for serious

infections 12 times higher than
GY in patients without SLE

25% of SLE patients die due to

infections

Amy D, Robert S, , GC Tsokos Systemic Lupus Erythematosus and Infection. Basic, Aplied, Clinical Aspect.2016. 403-10
Interaction of
infection and
SLE

J Y Jung, C H Suh, Infection in SLE, similarities, and differences with lupus flare. 2016
 SLE Immune Humoral Immunity
Dysfunction  Hypo𝜸globulinemia& Ig
Cytokine dysregulation
o Decreased IL-2 production
Predisposing subclass defeciencies
o Increased TNF 𝛼 production
to Infection  Fc 𝜸 receptor antibodies
o Increased IL-10
 B-cell maturation flaws

Cellular immunity Complement system

 Impaired T cell cytotoxic  Hypocomplementemia
capability  Mannose binding lectin
 Lymphopenia pathway polymorphisms
 NK-cell dysregulation  Complemen C1-q deficiency

Phagocyte impairment
 Superoxide deficits
 Defective phagocytosis

Amy D, Robert S, , GC Tsokos Systemic Lupus Erythematosus and Infection. Basic, Aplied, Clinical Aspect.2016. 403-10
 Impaired Processes in SLE associated infection

J A James, A L Sestak, E S Vista. SLE & Infections. Dubois’Lupus Erythematosus and related syndrome. 8 th. 2013
 Disease activity

High anti-DNA titers

Low complement levels

Nephritis

PREDICTORS Leucopenia

Antiphospholipid antibodies

Prednisone-equivalent doses over 7,5-10

mg/day

MP high dose pulse

Cyclophosphamid high dose regimens

A Danza, GR Irastorza.Infection risk in systemic erythematosus patients; susceptibility factors and preventive strategies.2013
2019 update of the EULAR recommendations for
the management of systemic lupus erythematosus
 Proportions of the immunosuppressive drug
Drugs Total Infection case Control

Azathioprine, n(%) 101 (28,1) 35(29,2) 66 (27,5)

MMF, n(%) 37 (10,3) 12 (10,0) 25(10,4)

Tacrolimus, n(%) 31 (8,6) 16 (13,3) 15 (6,3)

Methotrexate, n(%) 29(8,1) 13 (10,8) 16 (6,7)

Cyclophosphamid, n(%) 27(7,5) 12 (10,0) 15 (6,3)

J Y Jung, D Yoon, Y Choi, Associated clinical factors for serious infections in patients with SLE.2019
 Organisms identified in patients with SLE

• Sample : 3815 patients

• 1321 (34%) were diagnosed with infection
• Caused: bacterial infection (50,6%), viral infection (36,4%), fungal infection
(12,5%)
• Frequently isolated bacteria : E Coli(24,6%), Acinetobacter baumannii(13,4%),
Staphylococcus (13,4%)
• Most common fungus: Candida spp, Aspergillus, Crytococcus neoformans
• 48 patients (2,2%) died of infection

Dongying C, Jingyi X, Haihong C, et al Infection in Soutthern Chinese Patients with Systemic Lupus Erythematosus: Spectrum, Drug
Site of infection and microorganism most frequently involved in SLE
Bacterial infections
Respiratory tract Streptococcus pneumoniae,Mycobacterium tuberculosis
Urinary tract Escheria coli, Kleibsella spp, Pseudomonas spp
Skin and soft tissues Staphylococcus aureus
Bacteremia/sepsis Escheria coli, Staphylococcus aureus, Salmonella spp
Viral infection
Skin Hespes Zoster
Respiratory tract Cytomegalovirus
Gastrointestinal tract
Central nervous system
Lupus flare like manifestation
Cervix Human papilloma virus
Fungal infections
Upper gastrointestinal tract Candida spp
Respiratory tract Pneumocystis jirovecii
Central nervous system Cryptococcus neoformans
 Prevalence of infection
• E Coli (uropathogen 76,6%)
• Mycobacterium tuberculosis (5-30%)(7x)
• S pneumoniae (6-18%)
• Salmonella

Dongying C, Jingyi X, Haihong C, et al Infection in Soutthern Chinese Patients with Systemic Lupus Erythematosus: Spectrum,
 Febrile,flare or infection?

• Deciding on a course therapy a febrile patient with SLE is often difficult

• No definite parameter are sufficiently reliable to distinguish a lupus flare or

acute infection

• Evaluation disease activity for assessment scales ( BILAG, SLAM, SLEDAI,

ECLAM)

FE Ospina, A Echeverri, D Zambrano, et al.Distinguishing infections vs flare in patients with systemic lupus erythematosus. 2016
 Using SLE biomarkers to differentiate
between infection and disease flare

hsCRP (cut off 6 mg/dL, associated with active infection, 84% specificity )

Procalsitonin (> 0,38ng/ml has Sensitivity 74,5%,Specificity 95,5%, high

positive predictive value of 92,1 %, not useful for TB or viral infection)
Mannose binding lectin(>0,5 mg/ml, has Sensitivity 82%,Specificity 82%, 98%
predictive value)

FE Ospina, A Echeverri, D Zambrano, et al.Distinguishing infections vs flare in patients with systemic lupus erythematosus. 2016
 Using SLE biomarkers to differentiate
between infection and disease flare
CD 64 (>2,2 good predictor of bacterial infection, sensitivity 63%, specificity
89%)
CD 27 ++

sTREM-1 (soluble level of Triggering Receptor Expressed in Myeloid cell 1)

(>53,2 pg/ml, has Sensitivity 100 %,Specificity 66%)
2’5’-oligoadenylate synthetase (OAS)

Delta neutrophil index(2,8% , Sensitivity 54,3%, specificity 87,7%)

FE Ospina, A Echeverri, D Zambrano, et al.Distinguishing infections vs flare in patients with systemic lupus erythematosus. 2016
 Flare vs Sepsis
• nCD64 & hsCRP

 Abnormal (probability sepsis 92%), normal

( diagnosis sepsis excluded with probability 99%)
(76% sensitivity and 98 specificity)

• BioScore (sTREM-1, Procalsitonin, nCD64)

FE Ospina, A Echeverri, D Zambrano, et al.Distinguishing infections vs flare in patients with systemic lupus erythematosus. 2016
 Preventative Strategies
• Do not administer live virus vaccines in immunosuppressed
patients
• Select stable disease periodes for vaccination
• Yearly influenza vaccine
• Pneumococcal vaccine / 5 years
• Anti tetanic vaccine
• Hepatitis A/B vaccines in high risk patients
• Test baseline immunoglobulin levels before rituximab

A Danza, G Ruiz I, Infection ris in SLE patients: suspectibility factors and preventive strategies. Lupus 2013,1286-94
 Preventative Strategies
• Screening test for latent tuberculosis
• INH prophylaxis ( if screening +, and is taking moderate-high doses of
prednisone)
• Avoid BCG vaccine
• Do not use long term prednisone > 5 mg/day
• Use low dose MP pulses
• Use cyclophosphamide low regimens (500 mg)
• Give HCQ to all patients

A Danza, G Ruiz I, Infection ris in SLE patients: suspectibility factors and preventive strategies. Lupus 2013,1286-94
 Management
• Varied report, individual factors

• Screening infection before imusupressive therapy

• IVIg ( in hypogammaglobulinemia/specific antibody deficiency/recurrent infection)

• Prophylaxis

 no great deals

Valganciclovir in CMV

Endocarditis prophylaxis for invasive dental/genitourinary procedures

Penisillin V for patients may have had splenectomy

Trimethoprim-sulphamethoxazole (PJP prophylaxis on SLE with Cyclophosphamide, severe

lecopenia, lymphopenia, high dose steroid, hypocomplement, Higher SLEDAI)
Thank you