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IMPORTANT NOTE:

 The electronic

 version of these 

 guidelines is the

 version currently in use.

 Any printed version

 cannot be assumed to

 be current.

 

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Authors:

Dr Jackie Yan, Elizabeth Wilson, Emma Best

Service: Paediatric Rheumatology & Paediatric Infectious Diseases
Editor: Dr Raewyn Gavin Date Reviewed: April 2010

 

IMMUNOSUPPRESSION & INFECTION IN RHEUMATOLOGY PATIENTS

 

 

 

                  Click here for print version (pdf)

 

 

Common Medications in Paediatric Rheumatology        é

 

  • Corticosteroids (Prednisone, Prednisolone, Methylprednisolone)

Up to 1-2mg/kg/day (maximum 60mg daily)

Pulsed IV methylprednisolone 10 - 30 mg/kg/dose (maximum 1g daily) x 3 days

 

  • The medications listed below have immunosuppressive effects.  This depends on the agent and dose used.  The disease modifying anti-rheumatic drugs (DMARDs I*) in the first column, when used singly, are considered less immunosuppressive, than those in the other three columns.

  

DMARDs I*

DMARDs II

Biologics

Cytotoxics

Methotrexate

Leflunomide (*Arava)

Sulphasalazine

Hydroxychloroquine

 

 

 

Cyclosporine

Azathioprine (*Imuran)

Mycophenolate mofetil

Etanercept (*Enbrel)

Infliximab (*Remicaide)  Adalimumab (*Humira)

Anakinra (*Kineret)

Tocilizumab

Rituximab (*Mabthera)

Abatacept

Cyclophosphamide

 

 

Screening prior to immunosuppressive therapy        é

 

1. All patients

 

    - Serology for VZV, Measles, Hep A, B, C

    - Consider HIV

 

2. Tuberculosis

 

    - ALL patients before biologic or cytotoxic therapy

    - Selected patients with HIGH risk families

    - Screening tests:  Mantoux, TB Quantiferon gold, CXR

 

Paediatric Rheumatology patients are considered significantly immunosuppressed if they are on the following medication:

 

1.  Prednisone             2mg/kg/day for more than 1 week, or

                                  1mg/kg/day for more than 1 month

 

AND/OR

 

2.  Medication listed in the DMARDs II, biologics or cytotoxics columns (as listed above)

  • If on combinations of DMARDs, biologics or cytotoxics

  • If on steroids as well as single or multiple DMARDs

 

3.  Clinical indications e.g. unusual and/or persistent infections

 

The value of additional immune testing on patients taking these medications is unknown

 

 

Immunisations        é

 

Vaccination pre-immunosuppression:

 

  • Routine immunisations, including HPV vaccine if applicable, at least TWO  WEEKS prior to immunosuppression (HPV vaccine currently licensed from 9 years of age)

  • MMR and Varicella vaccination at least ONE MONTH prior to immunosuppression, if no history of illness or VZV IgG negative

  • Pneumococcal vaccine in SLE patients

    • <2yrs Conjugate vaccine, as per schedule

    • >2yrs  If no prior pneumococcal vaccine, then 2 doses two months apart Prevenar (conjugate), then Pneumovax 2 months later. 

    • >2yrs  If prior conjugate vaccine given as per schedule, then single dose of Pneumovax.

    • Repeat Pneumovax every 5 years if continued immunosuppression.

  • Influenza vaccine yearly for patient and household

 

Vaccination if on immunosuppression:

 

  • No live vaccines (e.g. MMR, varicella, BCG), but can receive other inactivated vaccines

  • All should receive influenza vaccine, HPV vaccine if age appropriate

  • Meningococcal vaccines

    • <2yr consider conjugate Men C vaccine, then when

    • >2yrs quadrivalent meningococcal polysaccharide vaccine (A,C,Y,W135)

    • Adolescents – advise quadrivalent meningococcalpolysaccharide vaccine (A,C,Y,W135)

 

After immunosuppression, routine vaccinations (see Worksheets A, B)

 

As per Starship Haematology/Oncology Immunisation policy

  • When off therapy 6 months, check baseline immunisation titres (VZV/measles/mumps/rubella/Hep A, Hep B, diphtheria, tetanus, haemophilus B) and yearly for tetanus to consider need for booster doses

  • Commence re-immunisation schedule, provided lymphocyte count > 1.0. 

  • If serology shows preservation of previous vaccine antibodies to all tested, polio/pertussis vaccines do not need to be re-administered

  • Immune globulin interferes with antibody responses to live vaccines (MMR/Varicella) only. MMR and/or varicella vaccines should be delayed until at least 6 months after measles or VZ immunoglobulin given

 

 

Antimicrobial & antifungal prophylaxis        é

 

  • Have high index of suspicion for opportunistic infections, especially if other unusual infections e.g. fungal, etc., investigate for infection and treat as appropriate

  • Evaluate on case-by-case basis

 

Indications for PCP Prophylaxis

  • Intravenous cyclophosphamide for juvenile dermatomyositis, SLE, vasculitides

  • Consider prophylaxis if additional other immunosuppressants, steroids

  • Consider prophylaxis depending on condition of patient e.g. pulmonary pathology

  • Routinely in Wegener’s granulomatosis as on regular oral steroids and oral cyclophosphamide

  • Prophylaxis with co-trimoxazole

    • Recommended oral regimen:  trimethoprim 150mg/m2 per day with sulphamethoxazole 750mg/m2 per day in divided doses twice a day, three times a week, on consecutive days  e.g. co-trimoxazole 240mg BD Fri, Sat, Sun

    • If allergic to co-trimoxazole, give dapsone

 

 

Chickenpox        é

 

  • Check Varicella zoster IgG prior to immunosuppression

    - If negative, immunise with chickenpox vaccine 1 month prior to immunosuppression

  • If IgG negative, should receive VZIG within 72 hours of exposure

  • If time of presentation >72 hours from exposure, consider starting acyclovir for 7 -14 days after initial contact (high dose oral or IV) after discussion with ID consultant

    - Oral acyclovir 80mg/kg/day in 4 divided doses commencing day 7 following exposure and continue for 7 days

 

Age

Dose Acyclovir

<2 years

200mg qid

2-6 years

400mg qid

>6 years

800mg qid

 

 

 

 

 

  • If IgG positive, all pts who fit the definition of being significantly immunosuppressed (see above), should still receive VZIG within 72 hours of exposure and be treated with IV acyclovir if chickenpox develops (see RCH Paediatric Pharmacopoeia for dose)

 

Significant exposure (for which VZIG indicated in susceptible patients as described above) includes the following

  • Same household

  • Playmate – face to face indoor play or classroom

  • Same hospital room or visitors

 

Chickenpox and IVIG

  • Protection from IVIG and VZIG last for about 4 weeks after last infusion

  • Immunise with live vaccines ≥ 6 months after last IVIG infusion, and after 11 months if high dose IVIG used (e.g. for Juvenile Dermatomyositis, Kawasaki or ITP), otherwise likely no or poor response

 

 

Measles         é

 

  • Check Measles Ig G prior to immunosuppression. If negative, immunise with MMR vaccine 1 month prior to immunosuppression

  • If IgG negative, should receive immunoglobulin within 6 days of exposure

  • If IgG positive, all pts who fit the definition of being significantly immunosuppressed (see above) should still receive immunoglobulin within 6 days of exposure (see Measles guideline)

 

Measles and IVIG

  • Protection from IVIG and measles immunoglobulin last for about 4 weeks after last infusion

  • Immunise with live vaccines ≥ 6 months after last IVIG infusion, and after 11 months if high dose IVIG used (e.g. for JDM, Kawasaki or ITP), otherwise likely no or poor response

 

 

Changing immunosuppressive therapy in serious infection        é

 

  • Please discuss ALL proposed changes with Rheumatology consultant

 

  • If on biologic therapy e.g. Etanercept (Enbrel), stop until infection is under control. If infection suspected, then immunosuppressive should be delayed.

 

  • If on combinations of immunosuppressives, consider stopping one and/or increasing intervals between doses

    - If on leflunomide and severe infection, consider using cholestyramine to enhance clearance from body

 

  • If on chronic steroids

    • Consider reducing steroid dose if possible, but also

    • Consider HPA-axis suppression and risk of adrenal crisis. Do not discontinue steroids and ensure that patient receives stress doses, especially if fever >38°C or has operative procedure (see below)

    • Patients need IV fluids and IV hydrocortisone if not tolerating oral fluids

 

 

Corticosteroid Stress Doses        é

 

 

 

Corticosteroid Stress doses  =   5 -10 times maintenance

 

i.e. Cortisone 50 mg/m2/day PO, or, if severe 100mg/m2/day PO or IV

 

Note:  Prednisone potency =  5 x cortisone potency

          Continuous IV infusion of hydrocortisone is preferable to IV boluses

 

Suggested doses:

       Prednisone         10 mg/m2/day PO or

       Hydrocortisone  100mg/m2/24hr by continuous IV infusion 

  

 

 

Worksheet A - Immunisation of Children off significant immunosuppressive therapy aged < 7 years        é

 

Click here for Print Version

 

 

Checklist:

 

 

Baseline ‘End of Treatment’ antibodies:

Immune

(yes/no)

Off therapy 6 months

 

 

Hepatitis B

 

Lymphocyte count >1:0

 

 

Measles

Text Box: If “no” to any of these immunise with MMR as per schedule below 

  

Date of last IVIG

 

 

Mumps

 

Date of last VZIG

 

 

Rubella

 

 

 

 

Varicella Zoster

 

 

 

 

Diphtheria

 

 

 

 

Tetanus

 

 

 

 

Haemophilus (Hib)

 

 

Immunise as below omitting any vaccines to which immune

 

 

Date given

Vaccines

Notes

Nurse notes

1st Dose

 

DTaP-IPV-Hep B/Hib

(=Infanrix Hexa)

or

DTaP -IPV plus

monovalent Hib

 

 

 

If Hep B immune

 

PCV-7 (Prevenar)

 

 

+ 6 wks

 

DTaP -IPV

(Infanrix-IPV)

 

 

Hep B

Omit if Hep B immune

 

PCV-7

or

23 PPV

If < 5 years

 

If > 5 yrs, and booster

after 3-5 yrs

 

+ 6 wks

 

DTaP -IPV

 

 

Hep B

Omit if Hep B immune

 

MMR

Notes     ?

 

+ 6 wks

 

MMR

Notes     ?   ?

 

Varicella

Omit if immune.

Notes  ?  ?

 

23 PPV

If > 2 yrs and not given prior, then booster

after 3-5 yrs

 

 

 

 

Age 4 yrs

 

DTaP -IPV

 

 

 

Age 11 yrs

 

dTap

(=Boostrix)

 

 

Age 12 yrs

(girls only)

 

Gardasil (HPV)

3 doses at zero, two and six months

 

 

Note        Omit only if immune to all three (measles, mumps and rubella)

? Not to be given within 5 months of VZIG or 8 months of IVIG

? MMR and varicella vaccines are both live and so must either be given both on the same day or

     separated by at least 4 weeks

 

 

Worksheet B - Immunisation of Children off significant immunosuppressive therapy aged > 7 years        é

 

Click here for Print Version

 

Checklist:

 

 

Baseline end of treatment antibodies:

Immune

(yes/no)

Off therapy 6 months

 

 

Hepatitis B

 

Lymphocyte count >1:0

 

 

Measles

Text Box: If “no” to any of these immunise with MMR as per schedule below 

  

Date of last IVIG

 

 

Mumps

 

Date of last VZIG

 

 

Rubella

 

 

 

 

Varicella Zoster

 

 

 

 

Diphtheria

 

 

 

 

Tetanus

 

 

 

 

Haemophilus (Hib)

 

 

 

 

 

 

  

Immunise as below omitting any vaccines to which immune

 

 

Date given

Vaccines

Notes

Nurse notes

1st Dose

 

dTap-IPV

(= Boostrix-IPV)

 

 

Hep B

Omit if immune

 

PCV-7 (Prevenar)

 

 

+ 6 wks

 

dTap-IPV

 

 

 

Hep B

Omit if immune

 

Pneumovax (=23PPV)

with booster after

3-5 years

 

+ 6 wks

 

dTap-IPV

 (= Boostrix-IPV)

 

 

Hep B

Omit if immune

 

MMR

Notes     ?  ?

 

Varicella

Omit if immune

Notes ?     ?

 

+ 6 wks

 

Varicella

2nd dose if

>13 yrs at 1st dose

Notes  ?    ?

 

MMR

Notes    ?   ?

 

Age 11 yrs

 

dTap (=Boostrix )

 

 

Age 12 yrs

(girls only)

 

Gardasil (HPV)

3 doses at zero, two and six months

 

 

Note        omit only if immune to all three (measles, mumps and rubella)

? not to be given within 5 months of VZIG or 8 months of IVIG

? MMR and varicella vaccines are both live and so must either be given both on the same day or separated by at least 4 weeks

 

 

References        é

 

Immunisation of the Immunocompromised Child – Best Practice Statement, February 2002, Royal College of Paediatrics and Child Health (www.rcpch.ac.uk )

 

Immunisation policy – Starship paediatric Haematology/Oncology

 

Consultation with Prof Lori Tucker, Paediatric Rheumatologist, BC Children’s Hospital, Vancouver, BC

 

Red Book 2006 – Report of Committee on Infectious Diseases, American Academy of Pediatrics

 

2011 National Immunisation Schedule