an overview of infection prevention in patients with autoimmune disease focus on lupus

1. Rachmat Gunadi Wachjudi
Lahir di Garut 16 Januari 1955
Pendidikan
- Dokter umum FK UNSRI Palembang
-Internist FK UNPAD Bandung
-Subspesialis Reumatologi FK UI Jakarta
- Clinical Rheumatology and Osteoporosis
Training – Perth - WA
Pekerjaan
Ka Div Reumatologi
Departemen Ilmu Penyakit Dalam
Rumah Sakit dr Hasan Sadikin Bandung
Organisasi:
IDI, PAPDI, IRA, PEROSI, PERALMUNI
1

2. Preventing infection in patients
with autoimmune diseases
Illustrated in Lupus

3. 3

4. Causes of Autoimmunity
4

5. Pick an organ, any organ . . .
Autoimmunity can affect ANY organ/organ system in the human body
Autoimmune Uveitis Multiple Sclerosis
Sjogren’s Syndrome
Psoriasis
Systemic Lupus Erthematosus
Rheumatic Fever
Diabetes
Autoimmune Hepatitis
Addison’s Disease
Autoimmune Oophoritis Ulcerative Colitis
Rheumatoid Arthritis
Autoimmune hemolytic Anemia
5

6. Autoimmunity Classification
6

7. 7 7

8. Examples of Organ Specific
Lungs of a
patient with
Goodpasture’s
Hashimoto’s disease
(thyroiditis) Vitiligo
8

9. Autoimmune diseases…….
9

10. Examples of Systemic
Autoimmunity
SLE
10

11. Examples of Systemic Autoimmunity
Sjogren’s Syndrome
11

12. Rheumatoid Arthritis
12

13. Major Features of Active Autoimmune disease
• Constitutional – fatigue, malaise, fever, arthralgia, myalgia
• Variable organ involvement
– Arthritis, pleurisy, pericarditis
– Raynauds phemomenon, vasculitis, stroke
– Mucocutaneous – rashes, oral ulcers, sicca syndrome,
– Kidney, CKD, NS
– Neuropsychiatric – psychosis, seizures, transverse myelitis
• Variable abnormalities in laboratory testing
– High ESR, CRP, anemia, low WBC, platelets, abnormal urinalysis
– RF, ACPA, Anti Scl-70, anti-DNA, low complement levels (C3, C4)
13

14. The damages
• Disease damage
– CKD, cognitive dysfunction, ovarial failure
• Drug related
– Obesity, hypertension, diabetes
– osteoporosis, avascular necrosis
– Dyslipidemia
– Striae
• Premature atherosclerotic disease
– heart attack, stroke, heart failure
• Infection … opportunistic 14

15. Life threatening
15

16. Current Therapies
• Immunosuppressive drugs
- corticosteroids, azathioprine
- slows the proliferation of lymphocytes
 Cyclosporin A
• Biologic agents
• Thymectomy
• IvIg
• Plasmapheresis
16

17. Infections
• Are one of the most common causes of
– morbidity,
– hospitalization
– death
in patients with systemic lupus
erythematosus
17

18. Infection in SLE
• is complex, different populations
• Hospitalized and ambulatory cohorts
• Regional differences in pathogens.
• Opportunistic infections in SLE, may be underreported
• Guidelines for antimicrobial prophylaxis exist for persons with
HIV or patients undergoing hematopoietic stem-cell transplant
and have decreased incidence of death and hospitalization due
to opportunistic infections such as pneumocystis.
• Guidelines for Infection Prevention in SLE ?
18

19. Systematic strategy
• In the absence of definitive studies on the use of infection
prophylaxis in SLE, we propose a systematic strategy for
preventing opportunistic infections in SLE patients
 starting with their first clinical evaluation
19

20. Infections
• A major cause of mortality in systemic lupus erythematosus
• In a large multicentre European cohort of 1000 patients followed
over 10 years, infections represented the cause of death in 25%
of cases and active SLE in 26.5%.
• Bimodal distribution to death in SLE
– Infections and active disease causing death within the first 5
years of diagnosis,
– myocardial infarctions and thrombotic events occurring later
• Infections are also responsible for 14–50% of hospitalizations in
patients with SLE[and are a cause of significant morbidity. (46%
RSHS)
20

21. Risk factors for infection in systemic
lupus erythematosus
• Disease-associated risk factors
• Disease activity or organ damage
• Medications
• Laboratory findings
• Other risk factors
21

22. Immune defects seen in patients with systemic
lupus erythematosus and potential pathogens
• Hypocomplementemia : Neisseria species, Streptococcus
pneumoniae
• Hyposplenism: Streptococcus pneumonial , Haemophilus
influenzae , Neisseria meningitidis, Salmonella species
• Impaired phagocytic cell activity: Bacterial and fungal
infections (variety of potential organisms)
• Impaired T-cell activity: Herpes simplex and herpes zoster,
Epstein Barr virus and CMVHuman papillomavirus, Influenza,
Listeria monocytogenes , Nocardia species , Cryptococcus
neoformans , Mycobacterium tuberculosis , Nontuberculous
mycobacteria, Pneumocystis jirovici , Histoplasma capsulatum,
Coccidiodes immitis, Toxoplasma gondii
22

23. Glucocorticoids
• Broad effects on innate and adaptive immune system:
• Decreased cell-mediated immunity
• Decreased inflammatory response
• Decreased immunoglobulin synthesis
• Lysis of lymphoid follicles
• Broad variety of pathogens including
– Bacteria (Salmonella species, Listeria monocytogenes, Nocardia species)
– Viruses (herpes simplex virus, varicella zoster virus)
– Fungi (Pneumocsystis jiroveci,Candida species, endemic mycoses)
– Parasites: Strongyloides stercoralis
23

24. Other immunosuppressive agents:
• Azathioprine, cyclophosphamide, mycophenolate mofetil
 Lead to decline in numbers of B and T cells
– Bacteria (Salmonella species, Listeria monocytogenes,
Nocardia species)
– Viruses (herpes simplex virus, varicella zoster virus)
– Fungi (Pneumocsystis jiroveci,Candida species, endemic
mycoses)
– Parasites: Strongyloides stercoralis
24

25. Bacterial Infections
• The majority of reported infectious complications in patients with
SLE are bacterial
• The most frequent types of infections are respiratory, urinary
tract and soft tissue infections.
• Case series also suggest an increased risk of nontyphoid
salmonella infection.
• Prompt treatment of any identified or suspected infection is
recommended.
• Patients with SLE in which a delay in antimicrobial therapy (> 24
h)  a higher risk of mortality
25

26. Vaccination
• Pneumococcal Vacc considered well tolerated  recommended
for patients with SLE.
• Although disseminated Neisserial infections have been reported
in patients with SLE and some authors advocate for
meningococcal vaccination, no guidelines exist to date and there
is little research in this area.
26

27. Varicella Zoster Virus
• Most commonly reported viral infections in SLE, from
reactivation of latent varicella zoster virus.
• Disseminated disease in patients with SLE or may be
complicated by superinfection and postherpetic neuralgia.
• Annual incidence of 6.4 events/1000 patient years. (38 HZ case
in 69 SLE pts /5 yr)
• Herpes zoster is a late complication: 5 years after SLE diagnosis
• Commonly during periods of inactive or mild SLE disease
activity.
• Risk factors for herpes zoster include renal disease, concurrent
or prior malignancy and azathioprine and cyclophosphamide use
27

28. H zoster vaccination
• Centre for Disease Control Advisory Committee on Immunization
Practices recommends vaccination in
• patients over age 60, 2–4 weeks prior to any anticipated
immunosuppression, including high dose prednisone (≥20
mg/day lasting ≥2 weeks).
• At least 1 month after discontinuation of such therapy:
• Low doses of methotrexate (≤0.4 mg/kg/week) or azathioprine
(≤3.0 mg/kg/day) is not contraindicative to the administration of
zoster vaccine.
28

29. Human Papillomavirus
• A common viral infection in patients with SLE.
• HPV types 16 and 18 are associated with squamous
intraepithelial lesions (SIL) and cervical cancer.
• High numbers of patients with SLE have HPV infection and SIL
and women with SLE have a three-fold increase in the rate of
abnormal cervical cytology smears compared with the general
population.
• There are currently no recommendations or data regarding the
use of this vaccine in patients with SLE, but it should be offered
to patients meeting recommendations for the general population.
•
29

30. Cytomegalovirus
• Is common in the general population with seropositivity
estimated at 60–70%.
• Over 90% of SLE patients are seropositive for CMV,
antigenemia is detected in 18–44% of patients, whereas overt
clinical disease is rare but carries a high risk of mortality.
• Given the potential for morbidity in immunosuppressed patients
with SLE who develop end-organ disease, we recommend
vigilance on the part of the clinician in considering CMV as a
possible cause of unexplained cytopenias, persistent fevers,
colitis or retinitis in patients receiving immunosuppressive
medications for the treatment of SLE.
•
30

31. Influenza
• The annual incidence of influenza in the general population is 5–
20%; however, the rate of infection in SLE patients is not well
defined.
• The influenza vaccine is the most effective way to prevent
infection and reduce morbidity and mortality; however, it is
slightly less immunogenic in patients with SLE.
• Given the risk of potentially more severe presentations of
influenza in patients with SLE, yearly vaccination is
recommended.
•
31

32. Hepatitis B and C Virus Infection
• European League Against Rheumatism (EULAR) guidelines for
monitoring patients with SLE recommend screening of all
patients with specific risk factors for hepatitis B and C infection
at their first visit and serve as a useful guide for ensuring quality
of care in patients with SLE.
32

33. Myobacterium Tuberculosis
• The frequency of Mycobacterium tuberculosis (TB) infections in
patients with SLE in endemic countries is approximately 5%. TB
in SLE occurs commonly in extrapulmonary sites and may be
associated with more severe pulmonary involvement.
• In a study from California, 25% of SLE patients were found to
have latent TB infection.
• One of the most important risk factors for TB reactivation is
corticosteroid use.
•
33

34. American and Canadian guidelines
• Recommend that patients with prolonged therapy with
corticosteroids (prednisone >15 mg/day or equivalent for 2–4
weeks), who have a positive tuberculin skin test, indicating latent
TB infection, should be treated with preventive therapy.
• In endemic countries, use of isoniazid preventive therapy in
patients with rheumatic disease who are treated with prednisone
more than 15 mg/day for more than 3 months, independent of
tuberculin skin testing, can decrease the risk of developing TB
by 70%.
• Given the morbidity of TB, we recommend tuberculin skin testing
in patients from endemic areas prior to the initiation of
immunosuppressive therapy to identify patients with latent TB
infection who are candidates for INH preventive therapy.
34

35. Pneumocystis jiroveci
(Pneumocystis carinii)
• Is a common cause of pneumonia in immunosuppressed
individuals and is associated with a variety of immune deficits;
however, the main risk factors include cellular immune
deficiency resulting from corticosteroid and cytotoxic drug
therapy
• The attack rate of P jiroveci pneumonia (PJP) in patients with
connective tissue disease has been estimated at less than 2%,
although the exact incidence in SLE patients is difficult to
estimate.
• Infection occurred between 6 and 7 months after
immunosuppression had been initiated and had a mortality rate
of 20%. SLE patients infected with P jiroveci had a higher
disease activity and renal involvement was more common
35

36. Pneumocystis prophylaxis
• There is a higher rate of intolerance to TMP-SMX in SLE patients
with up to 52% of patients experiencing an adverse reaction,
usually cutaneous rashes.
• Sulfonamides may be associated with
– worsening SLE.
– risk of marrow suppression
– hemolysis and is not ideal in renal failure.
– hepatotoxicity, gastrointestinal intolerance and nephrotoxicity.
Lastly
• TMP-SMX may interact with a number of other immunosuppressive
medications including azathioprine, methotrexate and
mycophenolate mofetil and potentiate neutropenia
36

37. Pneumocystis
• Patients on at least 30 mg of prednisone daily are at higher risk
for pneumocystis and infection has been reported to occur after
a median of 12 weeks of therapy.
• Some experts recommended that PJP prophylaxis be
considered in patients on at least 16 mg of prednisone daily for
more than 8 weeks.
• Special consideration should be given to lupus patients who are
receiving combination therapy with prednisone and cytototoxic
agents such as cyclophosphamide.
37

38. Strongyloides stercoralis
• Is a nematode endemic in tropical and subtropical regions and it
infects up to 100 million people each year worldwide. Persons
chronically infected with S. stercoralis may be asymptomatic
• Disseminated strongyloidiasis has been described in patients
with SLE on immunosuppressive agents, especially
corticosteroids.
• The clinical presentation of the S. stercoralis hyperinfection
syndrome may be variable and may mimic some features of SLE
including pulmonary hemorrhage or vasculitis.
38

39. Srongiloides stercoralis
• It is recommended that patients from endemic areas (generally
tropical and subtropical areas) be screened with serologic
testing. Alternatively, microscopic evaluation of stool samples or
duodenal fluid for ova and parasites may yield positive results;
however, multiple samples may need to be obtained to
demonstrate infection.
• If infection is detected, Ivermectin should be prescribed to
eradicate infection.
39

40. Other Rare Infections
• Other rare opportunistic infections have been reported in SLE
patients including Mycobacterium avium
• Invasive fungal infections such as Cryptococcus
• Aspergillus and Candida species.
• No trials on prevention of these infections exist and diagnostic
vigilance is required.
40

41. Additional Strategies to Prevent
Infection
• Basic hygiene and sanitation including frequent hand washing
are the cornerstones of prevention of many infectious diseases
and bear mention.
• Judicious use of immunosuppressive therapy may lessen
infection risk.
• Interestingly, antimalarials may have protective effects against
infections, an observation which bears further study.
41

42. Conclusion
• Infections are a common cause of morbidity and
mortality in SLE and few guidelines exist on
preventing infections in SLE, especially
opportunistic infections.
42

43. A checklist to be utilized to identify
patients at risk
• Yearly influenza shot – give or recommend to family medical
doctor.
• Pneumococcal vaccination – give or recommend to family medical
doctor (every 5 years).
• Regular pap smears to screen for cervical dysplasia caused by
HPV – recommend to family medical doctor or gynaecologist.
There are currently no recommendations or data regarding the
use of the HPV vaccine in patients with SLE outside of
recommendations for the general population.
• TB skin test prior to starting immunosuppressive agents and
treatment with isoniazid (INH) for patients with latent TB infection.
43

44. Checklist
• Hepatitis B serology at baseline in all patients.
• Hepatitis C serology at baseline in patients with risk factors.
• HIV serology at baseline in patients with risk factors.
• Screening for strongyloides in patients from endemic areas
(strongyloides serology) prior to starting immunosuppressive
agents and treatment with ivermectin if infected.
• Vaccination against herpes zoster should also be considered
for patients with SLE who meet the criteria
44

45. Orchestration
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46. Further reading
• Curr Opin Rheumatol. 2011;23(4):358-365. © 2011
46

47. Thank you
For your
participation in
Reumatologi Klinik Bandung
9-10 Feb 2013