Unusual infections in SLE - SGPGIsgpgi.edu.in/pdf/Unusal infections in SLE.pdf · •Unusual infections are not so unusual? •Index cases of different spectrum of infections? •

Unusual infections in SLE

Jyoti Ranjan Parida

My task today

• Why infection is important in SLE ?

• Why SLE patient develop more infection?

• What are the usual infections ?

• Unusual infections are not so unusual?

• Index cases of different spectrum of infections?

• Can we prevent infection?

My task today





• Index case of different spectrum of infections?

• Can we prevent infection

Mortality in SLE

Group Year

Since Dx

Death

Rate per

1000 p-

yrs

Number of deaths due to specific causes

SLE Cancer Infection Vascular

Total

< 2

2- 5

5-10

10+

11.3

8.5

10.4

15.4

1

2

2

9

0

1

5

6

6

5

8

6

0

3

2

13

Caucasian

s

< 2

2- 5

5-10

10+

5.5

5.8

8.5

12.0

0

1

0

3

0

1

4

0

1

2

3

1

0

0

1

6

Af-Amer

< 2

2- 5

5-10

10+

18.5

11.7

13.7

20.0

1

1

2

6

0

0

1

6

4

2

5

5

0

3

1

7

N. Kasitanon, L. Magder, M. Petri ACR 2008

Impact on Mortality

Morbidity related to Infection

• Hospitalization due to infection: 15% of SLE / year

• Infection: 57% of all hospitalisation (Mexico)

• SLE patients admitted for other reasons

– 12.5% develop nosocomial infection

• Risk of major infection in SLE is 60% higher than other chronic diseases

Incidence in OPD – Prospective study

200 Mexican SLE Followed 2 yrs 32% infection

Hospitalized Patients

Hospitalized patients

Lupus (2010) 19, 43–48.

My task today







My task today







My task today







Unusual infections?

• No standard definition

• Uncommon

• Mainly case report

• Often delayed diagnosis

• High index of suspicion

My task today







Case 1

50/F

1997: Diagnosed as minor organ SLE

2001 : ILD, Rx 6 IV CP bolus →AZA

Pneumonia : AZA stopped, only on Prednisolone 7.5 mg/d

2008: Transient AF, Moderate MR with TR Rx Acitrom, Carvedilol, Amiodarone

2009 : Skin rash, no evidence of vasculitis , Pred10 mg/d

50/F PG 2010

C/o –

• Partial seizure (3 episodes)

• Forgetfulness 15 days

• Irrelevant talk

• No h/o aura/ incontinence/ Todd’s palsy

• No h/o trauma/TIA/seizure disorder

• No h/o fever/new skin rash/ oral ulcer/alopecia/joint pain

• On Phenytoin and stopped Acitrom

Examination

• PR 92/min, BP 110/70

• Inability to do simple calculation

• Unable to understand meaning of simple paragraph

• B/L papilledema

Possibilities

1. Intracerebral hemorrhage ( Acitrum induced)

2. NPSLE

3. ICSOL ( Malignancy, infective etc)

Investigations

• Hb 10.5 gm%

• TLC 7700/cmm

• DC N70L26E2M2

• Platlet 2.12 lac/cmm

• ESR 70 mm/hr

• CRP <0.32

• dsDNA <6.25

• C3 130

• C4 23.4

• Serum protein 7.0 mg%

• Serum albumin 3.6 mg%

• Tot Bilirubin 0.8 mg%

• Dir Bilirubin 0.2 mg%

• SGOT 29 U/L

• SGPT 12 U/L

• ALP 106 U/L

• Creatinine – 0.88 mg%

• Urine NAD

• Urine P/C 0.25

MRI Brain

Hospital course

• Surgical drainage : 15 ml thick pus aspirated and abscess cavity washed with saline -antibiotic

• Rx : Inj Cotrimoxazole + Amikacin

• Symptoms recovered – No seizure

• Discharged after 2 wks – Tab Cotrimaxazole + antiepileptic

• Review MRI after 1 month – significant ↓ in abscess size

Learning from the case

• Infection can mimic disease activity

• When in doubt, do Imaging for CNS symptoms

• Unusual infections are not so unusual in lupus

• CRP may be normal

Our experience with Nocardiosis

Organs involved PRDN at

diagnosis

Immunosuppressive drugs

Case 1Mr GCP Brainabscess,

pulmonary nodule

Subcutaneous

abscess

40 mg IVMonthly cyclophosphamide

X 3 dose

Case 2 Mrs SG Empyema

Brain abscess

Subcutaneous

abscess

25 mg IVmonthly cyclophosphamide

X 4 dose

Case 3 Mrs. PP Brain abscess 10 mg

1. Nocardia sepsis in a multigravida with SLE and autoimmune hepatitis.

Anaesth Intensive Care 2007;35(4):601–4. 2. Nocardia brain abscesses in a male patient with SLE: successful outcome despite delay in diagnosis. Clin Rheumatol 2007;26(6):1020–2.

3. Disseminated nocardiosis with initial manifestation mimicking disease flare-up of systemic lupus erythematosus in an SLE patient. Am J Med 2005;118(11):1297–8. 4. Systemic lupus erythematosus associated with pulmonary nocardiosis. Arch Intern Med 1967;119:202–5.

Recent Case Reports

Treatment

Combination (Cotrimoxazole +amikacin +ceftriaxone or imipenem) Clinical improvement - After 1–2 weeks of therapy After definite clinical improvement, 1 oral drug Antimicrobial Susceptibility whenever available Duration of Rx Most systemic infection – 6 -12 months Localized disease – 2-4 months HIV with CD4<200 - Indefinite

Harrison’s Principle Int Med 18th Ed

Case 2

17 year old female

April 2009

Fever

Oral ulcers

Malar rash

Photosensitivity

Painful rash on tips of fingers and toes

Past H/O choroiditis 2 year ago

Recovered with Prednisolone

1 month

Investigations

Hb 9 g/dl

TLC 5200/ccm

DLC P80L20

PLT 146000/ccm

Retic 1.5%

Total protein 8.3 g/dl

Albumin/globulin 3.5/4.8 g/dl

SGPT/SGOT 43/26 IU/ml

Creatinine 0.7mg/dl

Urine NAD CXR NAD

ANA 2+ positive

Anti dsDNA >200 IU/dl

IgM ACL 5.6 GPL

IgG ACL 0 MPL

C3 30.6 mg/dl

C4 <5.4 mg/dl

SLE with Cutaneous Vasculitis

SLE with Cutaneous Vasculitis

Prednisolone -0.5mg/kg

HCQ- 200mg

Prox Muscle weakness Muscle enzymes –N

EMG- Myopathy

SLE myositis

Azathioprine added

↑Prednisolone -1 mg/kg

HCQ- 200mg

Painful loss of vision R eye

SLE choroiditis

Headache, psychomotor

slowing & seizure

CSF Protein 233

Cells 28 Diagnosed as

NPSLE

IV Methyl Pred X2 + Cylophosphamide

3 April 09 27th April 09 15 May 09 27 May 09

31 May 2009: SGPGI

Recurrence of GTCS followed by unconscious

Examination

PR 112/min

BP 110/70 mm Hg

Comatose

B/L crepitations

Initiated on mechanical ventilation

Treated with Antibiotics and Steroids

Investigations

Hb 6.9 g/dl

TLC 1700/ccm

DLC P65L35

PLT 88000/ccm

Total protein 4.1 g/dl

Albumin 2.0 g/dl


S Cr 0.6mg/dl

Urine NAD CXR NAD CT Head NAD

Anti dsDNA 14.4 IU

C3 31.7 mg/dl

C4 7.53 mg/dl

CSF

Protein 163 mg

Glucose 67 mg

Cells 26 all Lympho

Course

• Day2: Confused, weakness in all 4 limbs LL>UL Rx with IVIG thinking of myositis

• Day 10: Extubated, HZV –V2 and C2, Rx with Acyclovir

• Day15: Persistent diarrhea Rx with antibiotics No improvement in weakness

• Day20: shifted to ward

Course in the ward

• Fever • Abdominal pain, Intermittent diarrhea • Persistent neurological deficit • Disoriented

UL LL Power Grade 3 Grade 0 Pain sensation normal absent DTR normal absent Extensor Plantars Bowel and bladder incontinence

Further evaluation

Stool Examination Normal microscopy, No opportunistic pathogen,

normal flora on culture, Cl difficile antigen negative CT abdomen (to r/o mesentric vasculitis) Normal

Seen by neurologist

?Anoxic encephalopathy with Critical care neuropathy NCV normal MRI Brain few hyper intensities in basal ganglion T2

Unexplained neurological deficit

UMN+LMN findings

Motor weakness

Absent DTR LL

Normal DTR -UL

Extensor plantar

Sensory loss LL

Normal NCV

Myeloradiculopathy

Chorioditis

Prolonged pancytopenia

Transaminitis

Prolonged diarrhea

Severely immunosuppressed

CSF Protein 28 mg/dl Sugar 34mg/dl (RBS -76mg/dl) Cells 10 cells, all lymphocytes AFB Negative CMV PCR Positive Toxo Negative

Anatomically consistent with Myeloradiculopathy

SLE with CMV myeloradiculopathy

Hospital course

0

1

2

3

4

5

MR

C G

rad

ing

of

LL

mu

scle

p

ow

er

No of days since hospitalisation

Lower Limb Muscle power

Day 25 Day 40 Day 50 Day 80

Started on Gancyclovir

Gradual tapering of Steroid

Follow up

• Completely Recovered

• Completed Graduation

• Regular OPD attendance with a big smile on her face

CMV infection in SLE Retrospective review of 88 acute viral infections in SLE

Excluded HIV/HTLV/HBV/HCV

Medicine 2008

CMV PCR +ve Bx- No inclusion bodies

IV Ganciclovir IV IG

After 5 wks- Follow up CT

On MMF CD4 T cell 59/µl Retinal necrosis with flame haemorrhages - central macula

MMF stopped Intravitreal Gancyclovir * 6 month

Regression of CMV retinitis Improvement of Vision CD4 T cell 394/µl Ganciclovir stopped

Reactivation of CMV Retinitis Reintroduction of Intravitreal ganciclovir

Eye 2006; 20(5):618–21.

Case 3

27 year old female

August 2009

Fever

Oral ulcers

Malar rash

Photosensitivity

Polyarthritis , alopecia 1 month

7 month

Investigations

Hb 8.3 g/dl

TLC 6200/ccm

DLC P68L30L2

PLT MCV

28900/ccm 78.3 Total protein 5.1 g/dl

Albumin 3.6 g/dl


S Cr 0.9mg/dl

Urine NAD

Anti dsDNA >200 IU

C3 68 mg/dl

C4 17 mg/dl

DCT +ve ICT -ve Retic count 1%

SLE with DCT +

anemia

Prednisolone -0.5mg/kg

HCQ- 200mg

Pedal edema,HTN Urine protein 2+

24 hr urine Prot 2 gm Renal Bx Class III A

nephritis

SLE nephritis

Started on NIH protocol

↑Prednisolone -1 mg/kg

HCQ- 200mg Mycophenolate

3 gm/d

Urine RBC 20-30/hpf Protein 4+

MMF resistant

2nd dose of Cyclo

SOB CXR B/l diffuse

haziness

H1N1 positive

Oseltamivir

NIH discontinued On Wysolone 1

mg/kg

8 August 09 29th Sept 09 30 july 10 31 Aug 10

Herpes Zoster

25th Oct 2010

Progressive decrease in urination Fall in Hb to 4 gm% (2 unit BT outside) 1 episodes of seizure with altered sensorium Investigation Sever metabolic acidosis Sr Creat 4.4, urine prot 4+, RBC 20-30/hpf dsDNA >200, C3 <18.3, C4 10.6 Treatment Hemodialysis Started on EUVAS Protocol Sr creat decreased to 1.4 and urination improved

07/12/2010

Fever (High grade) Headache (Holocranial) Vomiting No neck pain/diplopia/altered sensorium/cranial nerve

deficit or FND/Seizure No papilledema CSF :High opening pressure, Protein 38 150 cells with 95% lymphocytes Cryptococcal budding yeasts + CRAG titre > 1:64 Rx: Inj Amphotericin B with repeated CSF tap

5 days

-Death in 7 of which Cryptococcus neoformans (6) -Dose of prednisolone prior to fungal infection tended to correlate with 1 yr mortality after diagnosis of SLE

Meningitis in 5 cases

1 pulmonary cryptococcosis - Died from Resp failure

Induction with amphotericin B

Maintanaince- oral fluconazole indefinitely

None of them has had relapses

Indefinite maintenance therapy with fluconazole is

recommended in SLE patients with cryptococcosis

Tuberculosis

• Not unusual in our country

• 11.5% in our center

• Can we prevent it ?

Take home message

• Unusual infections are not so unusual

• Can mimic disease activity

• Early diagnosis and treatment is key

• Need good Microbiology Support

• Most gratifying to treat

Unusual infections in SLE - SGPGIsgpgi.edu.in/pdf/Unusal infections in SLE.pdf · •Unusual infections are not so unusual? •Index cases of different spectrum of infections? •

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