Criteria for the Clinical Use of Immune Globulin · 2018. 5. 31. · Suggested citation: Prairie Collaborative Immune Globulin Utilization Management Framework Project. Criteria for

Criteria for the Clinical Use of Immune Globulin

First Edition

April 2018

Suggested citation: Prairie Collaborative Immune Globulin Utilization Management Framework Project. Criteria for the clinical use of immune globulin. Alberta Ministry of Health, Shared Health Manitoba, and Saskatchewan Ministry of Health; 2018.

Prepared by the Inter-Provincial Medical Expert Committee and the Institute of Health Economics.

Suite 1200, 10405 Jasper Avenue Edmonton, AB Canada T5J 3N4

Phone (780) 448-4881 | Fax (780) 448-0018 [email protected] | www.ihe.ca

mailto:[email protected]

http://www.ihe.ca/


DISCLAIM

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Disclaimer: Important information about this document

This guideline reflects the best available data at the time the guideline was prepared. The recommendations are based, where possible, upon systematic review of the evidence. In the absence of published evidence, information and access criteria are based on clinical advice from the Guideline Development Group and individual clinical experts.

The information provided is not intended to be a definitive reference on any of the conditions. Patients and physicians should not use this document as a substitute for expert medical guidance and advice. The ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient after considering all of the circumstances presented by the individual patient, the known variability and biological behavior of the disease, and other relevant factors in each case.

Expert clinical opinion about treatment regimens should always be sought. The aim in each case is to find the minimal effective dose and optimize the treatment for each individual.


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TABLE OF CONTENTS BACKGROUND ............................................................................................................................ 1

Objectives .............................................................................................................................................................. 1

Target population .............................................................................................................................................. 1

Intended users ..................................................................................................................................................... 1

Conditions included .......................................................................................................................................... 2

Exclusions .............................................................................................................................................................. 2

Additional information ..................................................................................................................................... 2

SECTION 1: General Statements ........................................................................................... 3

Specialist assessment........................................................................................................................................ 3

Dosing ..................................................................................................................................................................... 3

Subcutaneous administration ....................................................................................................................... 4

Off-label use, including very rare diseases .............................................................................................. 4

Immune globulin in combination with other therapies ...................................................................... 4

Adverse effects .................................................................................................................................................... 4

SECTION 2: Dermatology Indications ................................................................................. 5

? Atopic dermatitis ................................................................................................................................... 5

Autoimmune blistering diseases ..................................................................................................... 5

? Chronic idiopathic urticaria ............................................................................................................... 6

? Livedoid vasculopathy ......................................................................................................................... 7

Pyoderma gangrenosum ................................................................................................................... 7

Scleromyxedema ................................................................................................................................... 7

Toxic epidermal necrolysis (TEN)/Stevens–Johnson syndrome (SJS) ............................... 8

SECTION 3: Hematology Indications .................................................................................. 9

Autoimmune cytopenias secondary to chronic lymphocytic leukemia .......................... 9

? Autoimmune hemolytic anemia (AIHA) ....................................................................................... 9

? Autoimmune neutropenia ................................................................................................................. 9

? Coagulation factor inhibitors ........................................................................................................... 9

Feto-maternal/neonatal alloimmune thrombocytopenia (FMAIT/NAIT) .................... 10

Hemolytic disease of the newborn (HDN) ............................................................................... 10

? Hemolytic uremic syndrome (HUS) ............................................................................................ 10

Heparin-induced thrombocytopenia (HIT) .............................................................................. 11

Hypogammaglobulinemia, acquired secondary to hematological malignancies .... 11


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Immune thrombocytopenic purpura (ITP) – adult ................................................................ 11

Immune thrombocytopenic purpura (ITP) – pediatric ........................................................ 12

? Neonatal hemochromatosis .......................................................................................................... 12

Neonatal thrombocytopenia secondary to maternal autoimmune disorders .......... 13

Post-transfusion purpura (PTP) .................................................................................................... 13

Pure red cell aplasia (PRCA) ........................................................................................................... 13

? Sickle cell disease, hyperhemolysis syndrome ....................................................................... 13

? Thrombotic thrombocytopenic purpura (TTP) ....................................................................... 14

SECTION 4: Immunology Indications .............................................................................. 15

Hypogammaglobulinemia, secondary ....................................................................................... 15

Primary immunodeficiency (PID) disorders ............................................................................. 16

SECTION 5: Infectious Disease Indications .................................................................... 17

Clostridium difficile infection (CDI), recurrent ......................................................................... 17

HIV/AIDS ................................................................................................................................................ 17

? Necrotizing fasciitis ........................................................................................................................... 17

Sepsis, neonatal prophylaxis ......................................................................................................... 17

Toxic shock syndrome (TSS) .......................................................................................................... 17

/ Varicella-zoster virus (VZV), prophylaxis .................................................................................. 18

SECTION 6: Transplant Medicine Indications (including infectious diseases in transplant recipients) ........................................................................................................ 19

/?/ Community-acquired respiratory virus (CARV), upper respiratory tract infection (URTI) ...................................................................................................................................................... 19

?/ Community-acquired respiratory virus (CARV), lower respiratory tract infection (LRTI)........................................................................................................................................................ 20

Cytomegalovirus (CMV) infection, prophylaxis ...................................................................... 20

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) ................................................................................................................................. 20

?/ Gastrointestinal viruses in solid organ transplant ................................................................ 21

Hematopoietic stem cell transplant (HSCT), allogeneic, Cytomegalovirus (CMV)-induced pneumonitis ........................................................................................................................ 21

Hematopoietic stem cell transplant (HSCT), allogeneic, graft-versus-host disease 21

Hematopoietic stem cell transplant (HSCT), autologous ................................................... 21

Hematopoietic stem cell transplant (HSCT) for primary immunodeficiency (PID) disorders ................................................................................................................................................ 22


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Kidney, active antibody-mediated rejection (ABMR) prevention and management ........................................................................................................................................ 22

? Kidney, acute/active T-cell mediated rejection (TCMR) management ......................... 23

? Kidney, non-active rejection management.............................................................................. 23

Pulmonary graft-versus-host disease ........................................................................................ 24

? Solid organ (other than kidney) ................................................................................................... 24

Solid organ (other than kidney), antibody-mediated rejection (ABMR) ...................... 24

SECTION 7: Neurology and Neuromuscular Indications .......................................... 25

Acute disseminated encephalomyelitis (ADEM) .................................................................... 25

? Acute flaccid myelitis ........................................................................................................................ 25

Acute optic neuritis ........................................................................................................................... 25

Adrenoleukodystrophy .................................................................................................................... 25

? Aicardi-Goutières syndrome .......................................................................................................... 26

Alzheimer disease .............................................................................................................................. 26

Anti-NMDA receptor encephalitis ............................................................................................... 26

Autism ..................................................................................................................................................... 26

? Childhood epilepsy, medically refractory/intractable ......................................................... 27

Chronic fatigue syndrome (myalgic encephalomyelitis) .................................................... 27

Chronic inflammatory demyelinating polyneuropathy (CIDP) ........................................ 27

Critical illness polyneuropathy (CIP) ........................................................................................... 28

? Diabetic amyotrophy ........................................................................................................................ 28

Guillain–Barré syndrome (GBS) ..................................................................................................... 28

? Hashimoto encephalopathy .......................................................................................................... 28

Lambert–Eaton myasthenic syndrome (LEMS) ....................................................................... 29

Motor neuron disease ...................................................................................................................... 29

Multifocal motor neuropathy (MMN) ........................................................................................ 29

/ Multiple sclerosis (MS) ..................................................................................................................... 30

Myasthenia gravis (MG), moderate to severe generalized ............................................... 30

? Myasthenia gravis (MG), ocular and/or mild generalized ................................................. 31

? Narcolepsy/cataplexy ....................................................................................................................... 31

? Neuromyelitis optica (Devic disease) ......................................................................................... 31

Neuropathic pain ............................................................................................................................... 32

/?/ Neuropathy associated with IgM paraproteinemia ............................................................. 32

? Opsoclonus-myoclonus ataxia (OMA) – adult ....................................................................... 33

Opsoclonus-myoclonus ataxia (OMA) – pediatric ................................................................ 33


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? Paraneoplastic neurological syndromes ................................................................................... 33

Paraneoplastic or sporadic autoimmune encephalitis ........................................................ 34

? Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) ........................................................................................................................... 34

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome ......................................................................................................... 35

? Postpolio syndrome .......................................................................................................................... 35

?/ Rasmussen syndrome ....................................................................................................................... 35

Stiff person syndrome (Moersch–Woltmann syndrome) ................................................... 35

/? Sydenham chorea .............................................................................................................................. 36

? Susac syndrome .................................................................................................................................. 36

? Transverse myelitis ............................................................................................................................ 37

SECTION 8: Rheumatology Indications ........................................................................... 38

Antiphospholipid syndrome (other than catastrophic) ...................................................... 38

Antiphospholipid syndrome, catastrophic ............................................................................... 38

Behçet disease ..................................................................................................................................... 38

? Congenital heart block, autoimmune (neonatal lupus) ...................................................... 38

Dermatomyositis – adult ................................................................................................................. 39

Dermatomyositis – pediatric ......................................................................................................... 39

Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss disease) ...... 39

? Immune-mediated uveitis .............................................................................................................. 40

/? Inclusion body myositis (IBM) ....................................................................................................... 40

? Kawasaki disease – adult ................................................................................................................. 41

Kawasaki disease – pediatric ......................................................................................................... 41

Livedoid vasculopathy ...................................................................................................................... 41

Macrophage activation syndrome (MAS) ................................................................................ 41

Polymyositis – adult .......................................................................................................................... 41

? Polymyositis – pediatric ................................................................................................................... 42

Rheumatoid arthritis ......................................................................................................................... 42

? Scleroderma ......................................................................................................................................... 42

? Sjogren syndrome .............................................................................................................................. 43

? Systemic juvenile idiopathic arthritis (JIA) (adult Still disease) ........................................ 43

? Systemic lupus erythematosus (SLE) .......................................................................................... 43

? Vasculitic syndromes ........................................................................................................................ 44


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SECTION 9: Other Indications ............................................................................................. 45

? Graves disease ..................................................................................................................................... 45

/? Hemophagocytic lymphohistiocytosis (HLH) syndrome .................................................... 45

Systemic capillary leak syndrome (SCLS) .................................................................................. 45

APPENDIX A: Categorization of Recommendations .................................................. 46

APPENDIX B: Evidence Sources ......................................................................................... 47

APPENDIX C: Participants in the Guideline Development Process ....................... 49

REFERENCES .............................................................................................................................. 51

References for reviewed seed guidelines .............................................................................................. 51

General references .......................................................................................................................................... 55

INDEX .......................................................................................................................................... 57


BACKGROU

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BACKGROUND The Prairie Collaborative Immune Globulin (IG) Utilization Management Framework project was initiated to establish criteria for IG therapy as a means to increase accountability for the quality, safety, and sustainability of the blood supply system and to demonstrate stewardship for the use of public funds. This project is a trilateral agreement between the Alberta, Manitoba, and Saskatchewan ministries of health and is founded on the following principles:

• IG treatment is considered after exploring all other safe, effective, and affordable alternative therapies.

• When IG is used, the lowest dose for the shortest duration required to achieve the desired outcome should be chosen.

• For ongoing therapy, the achievement of measurable clinical outcomes is a requirement; IG should not be continued in patients with no demonstrable benefit.

An Inter-Provincial Medical Expert Committee (IMEC) was established, hereafter referred to as the Guideline Development Group (GDG), to review existing best practice evidence and guidelines on IG. A full description of the methods used to develop this evidence-based guideline is available from: http://www.ihe.ca.

Objectives • Provide evidence-based recommendations on the effective, efficient, and clinically

appropriate use of IG.

• Provide evidence-based guidance for identifying the conditions and circumstances for which for IG is clinically appropriate and funded within the National Blood Program.

• Provide review criteria for demonstrating the effectiveness of IG use, adherence to the guidance, and appropriate clinical follow up of IG therapy.

Target population Pediatric and adult patients in any healthcare setting who require IG therapy.

Intended users The Criteria are intended for:

• Transfusion medicine professionals and clinicians (e.g., dermatologists, hematologists, immunologists, infectious disease specialists, neurologists, rheumatologists, transplant specialists) treating patients with conditions that require intravenous, subcutaneous, or oral preparations of human IG.

• Administrators assessing and reviewing clinically appropriate access to IG preparations.

http://www.ihe.ca/


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Conditions included IG is used for prophylaxis and treatment of a range of diseases and conditions across various medical specialties. In this document, the conditions considered for IG therapy are listed under the following broad categories: dermatology; hematology; immunology; infectious disease; neurology and neuromuscular medicine; rheumatology; transplant medicine; and other indications. See the index for a full list of conditions included in this document.

Exclusions • Review of criteria and utilization practices for fresh blood products and other

plasma products, including hyperimmune globulins, albumin products, and coagulation factors.

• Although some advice is provided with regard to particular adverse effects of intravenous IG (IVIG) administration, the guideline does not provide detailed guidance on the safe use of IG.

Additional information For additional information, please see the following indices:

• Appendix A – Categorization of Recommendations (i.e., explanations of , ?, and )

• Appendix B – Evidence Sources

• Appendix C – Participants in the Guideline Development Process

References and the index of conditions included can be found at the end of this document.


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SECTION 1: General Statements

Specialist assessment General The use of immune globulin (IG) requires understanding of the diagnosis and

pathophysiology of the disorder being treated. This includes monitoring and measuring outcomes to inform further treatment. A review by an appropriate specialist familiar with the product should occur prior to the initiation of IG therapy, whenever possible. Ongoing use of IG for chronic conditions should be done primarily by specialists with expertise in the particular disorder being treated, or in partnership with them. This is particularly important for recommendations in the “Do Not Know” category.

Dosing

General The dosing of IG will vary, depending on whether IG is for replacement therapy or immunomodulation and the individual patient’s condition, clinical presentation, comorbidities, concurrent therapy and response.

Calculations Unless otherwise indicated, use adjusted body weight for dosing calculations in overweight or obese adults as follows. Dosing Weight is an adjusted body weight (of overweight or obese patients):

Dosing Weight = IBW + [0.5 x (Actual - IBW)] Note: If actual body weight is less than IBW, then Dosing Weight = actual body weight.

Ideal Body Weight (IBW),1 Devine formula is: IBW (male) = 50.0 kg + 2.3 kg (each inch over 5 feet) IBW (female) = 45.5 kg + 2.3 kg (each inch over 5 feet)

In most circumstances, dosing for children is calculated based on actual body weight. An online calculator is available from: https://www.albertahealthservices.ca/webapps/labservices/IVIG_Dosing_Calculator.htm.

1. Pai MP, Paloucek FP. Annals of Pharmacotherapy 2000;34(9):1066-9.

Maximum Dose

The maximum daily dose of intravenous immune globulin (IVIG) is typically 1 g/kg adjusted body weight, as the risk of some side effects may increase with higher doses or infusion rates. However, it is reasonable to use a maximum daily dose of 2 g/kg adjusted body weight in specific clinical circumstances when clinical judgement deems that the benefit of treatment outweighs the risk. Note that some experts endorse the use of 1.6 g/kg adjusted body weight as a single dose, in lieu of 2 g/kg adjusted body weight administered over 2 days, in selected patients requiring longer term treatment who have demonstrated good tolerance for this approach. Specific doses are provided in the guideline when supported by the evidence.

Maintenance Therapy

For most chronic conditions, efforts should be made to reduce the dose once the patient’s condition has stabilized. Consider titrating the dose and/or the treatment interval to the lowest dose that continues to maintain the appropriate clinical effect for each patient. In some circumstances, the underlying condition may resolve completely and permit discontinuation of treatment.

https://www.albertahealthservices.ca/webapps/labservices/IVIG_Dosing_Calculator.htm


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Subcutaneous administration General Subcutaneous administration of immune globulin (SCIG) should be considered as an

alternative to IVIG in patients with primary and secondary immunodeficiencies.1 Where appropriate, SCIG may also be considered in other patients receiving long-term therapy.

1. Health Quality Ontario. Ontario Health Technology Assessment Series 2017;17(16):1-86.

Off-label use, including very rare diseases General In the event that a clinical decision is not covered by or in alignment with the guideline,

the clinician shall notify the relevant provincial blood coordinating program, or similar provincial authority, and provide details of the treatment including indication and rationale for use outside of guidelines, the dose, and the duration. The provincial program or alternate may require additional outcome measures be reported as appropriate.

Immune globulin in combination with other therapies General When IG will not be retained in circulation (e.g., massive bleeding or impending plasma

exchange), the timing or sequencing of IG administration should be given due consideration. In general, IG administration should follow plasma exchange. Note that IG may increase the clearance of rituximab and other monoclonal antibodies.

Adverse effects General It is important to assess individual patient risk for side effects when considering IG

treatment. The GDG notes the following two specific areas of concern related to IVIG:

• There is an increased risk of hemolysis in patients who have non-group O blood, receive a large cumulative IVIG dose, or have an underlying inflammatory or autoimmune disorder.1, 2

• Some sucrose-stabilized formulations of IVIG have shown nephrotoxicity and are best avoided in patients with pre-existing kidney impairment.3

Statements in italics in the recommendations relate to harm. Although some advice is provided with regard to particular adverse effects of IVIG administration, detailed guidance on the safe use of IG is beyond the scope of this document. Refer to the product monograph for more comprehensive guidance on the safe use of IG.

1. Branch DR, et al. Blood 2018;131(7):830-5. 2. Cherin P, et al. Autoimmunity Reviews 2016;15(1):71-81. 3. Dantal J. American Journal of Nephrology 2013;38:275-84.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cherin%20P%5BAuthor%5D&cauthor=true&cauthor_uid=26384525


LEGEND (see Appendix B for seed guideline references): CS – case series study; EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); IVIG – intravenous immune globulin; NR – non-systematic/narrative review; RCT – randomized controlled trial; SR – systematic review

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See Appendix A for category

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SECTION 2: Dermatology Indications

? Atopic dermatitis Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG may be considered in patients with atopic dermatitis who have:

• the most severe forms of eczema; • underlying immunodeficiency; • contraindications to standard immunosuppressive therapies; and/or • recurrent or life-threatening infections.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days. IVIG should be administered every 4 weeks initially, in addition to conventional immunosuppressive therapy, unless otherwise contraindicated. If clinical response is good, based on objective measures of effectiveness established at the outset of treatment, the interval between infusions can be gradually increased. IVIG should be administered for 3 to 6 months to assess efficacy. Some patients do not show a definitive sustained response until they have undergone up to 6 treatment cycles. In rare instances when longer term treatment is required (e.g., when disease recurs after withdrawal of IVIG and no other treatment options are available), regular washout periods should be attempted.

Review Criteria If clinical effectiveness has not been achieved after 6 treatment cycles, IVIG should be discontinued. Continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of long-term treatment and at least annually thereafter. If clinical effectiveness has not been achieved or sustained, IVIG should be discontinued.

Evidence Source RCT (G8); EO (G6, GDG)

Autoimmune blistering diseases Recommendation includes but is not limited to

o bullous pemphigoid o epidermolysis bullosa acquisita o IgA pemphigus o pemphigus herpetiformis o linear IgA disease

o mucous membrane pemphigoid/cicatricial pemphigoid

o paraneoplastic autoimmune multiorgan syndrome o pemphigus foliaceus o pemphigus vulgaris

Do Recommendation

IVIG is recommended in addition to standard corticosteroid and/or immunosuppressive therapy for all severe forms of autoimmune blistering diseases. It is not generally recommended as monotherapy, but this may be justified in isolated cases when other therapies are ineffective or contraindicated. The results are particularly good in pemphigus vulgaris, pemphigus foliaceus, mucous membrane pemphigoid, and epidermolysis bullosa acquisita. However, IVIG may also be indicated in severe forms of bullous pemphigoid, linear IgA disease, IgA pemphigus, and paraneoplastic autoimmune multiorgan syndrome.



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definitions

Autoimmune blistering diseases Dose 2 g/kg adjusted body weight divided over 2 to 5 days.

IVIG should be administered every 4 weeks initially, usually in addition to conventional immunosuppressive therapy. If clinical response is good, based on objective measures of effectiveness established at the outset of treatment, the interval between infusions can be gradually increased. IVIG should be administered for 3 to 6 months to assess efficacy. Some patients do not show a definitive sustained response until they have undergone up to 6 treatment cycles. In rare instances when longer term treatment is required (e.g., when disease recurs after withdrawal of IVIG and no other treat options are available), regular washout periods should be attempted.


Evidence Source SR (G8); CS (G7)

? Chronic idiopathic urticaria Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG may be considered as a last resort in patients with severe disease when conventional therapies are ineffective or contraindicated.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days. IVIG should be administered every 4 weeks initially. If clinical response is good, based on objective measures of effectiveness established at the outset of treatment, the interval between infusions can be gradually increased. IVIG should be administered for 3 to 6 months to assess efficacy. Some patients do not show a definitive sustained response until they have undergone up to 6 treatment cycles. In rare instances when longer term treatment is required (e.g., when disease recurs after withdrawal of IVIG and no other treat options are available), regular washout periods should be attempted.


Evidence Source NR (G8); EO (GDG)



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? Livedoid vasculopathy Do Not Know Recommendation

There is insufficient evidence to recommend for or against using IVIG. IVIG may be considered in exceptional circumstances when patients do not respond to primary standard therapy.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days. IVIG should be administered every 4 weeks initially. If clinical response is good, based on objective measures of effectiveness established at the outset of treatment, the interval between infusions can be gradually increased. IVIG should be administered for 3 to 6 months to assess efficacy. Some patients do not show a definitive sustained response until they have undergone up to 6 treatment cycles. In rare instances when longer term treatment is required (e.g., when disease recurs after withdrawal of IVIG and no other treat options are available), regular washout periods should be attempted.


Evidence Source EO (G8, GDG)

Pyoderma gangrenosum Do Recommendation

IVIG may be considered in patients with significant pyoderma gangrenosum, diagnosed by a dermatologist, when other therapies are ineffective or contraindicated.

Dose Induction: 2 g/kg adjusted body weight divided over 2 to 5 days. Maintenance: 1 to 2 g/kg adjusted body weight divided over 2 days, every 4 weeks for 4 to 6 cycles. If there is no clinical response after 3 to 6 treatment cycles, IVIG should be discontinued.

Review Criteria Patient response should be documented according to objective measures of effectiveness established at the outset of treatment.

Evidence Source CS (G1); EO (GDG)

Scleromyxedema Do Recommendation

IVIG may be considered in severe scleromyxedema when other therapies are ineffective or contraindicated.



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Scleromyxedema Dose 2 g/kg adjusted body weight divided over 2 to 5 days.

In the case of severe organ involvement, particularly kidney or heart, the treatment should be administered slowly (i.e., over 5 days). IVIG should be administered every 4 weeks initially. If clinical response is good, based on objective measures of effectiveness established at the outset of treatment, the interval between infusions can be gradually increased. IVIG should be administered for 6 months to assess efficacy.

Review Criteria Long-term therapy is recommended when there is a severe relapse after discontinuing IVIG. Continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of long-term treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued. Regular washout periods should be attempted.

Evidence Source CS (G1, G8)

Toxic epidermal necrolysis (TEN)/Stevens–Johnson syndrome (SJS) Do Recommendation

Early administration of IVIG is recommended as an option when other treatments are contraindicated and when the condition is life-threatening.

Dose One dose of 2 g/kg adjusted body weight, or 1 g/kg/day for 3 consecutive days. IVIG should be initiated as early as possible, preferably within 24 hours of diagnosis.

Qualifying Criteria

TEN or SJS/TEN with all of the following: 1. Consultation with a dermatologist or an allergist;

AND 2. Characteristic cutaneous and mucous membrane involvement;

AND 3. Evidence of rapid evolution.

Urgent skin biopsies for both routine histology and direct immunofluorescence should be performed, but should not delay IVIG therapy if indicated. The classification of disease is not always clear on initial presentation and the diagnosis may change during the first few days in hospital.


Evidence Source SR (G1); G (G2); EO (G36, GDG-SR)


LEGEND (see Appendix B for seed guideline references): CS – case series study; EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); HPA – human platelet antigen; IVIG – intravenous immune globulin; NR – non-systematic/narrative review; NRCS – non-randomized comparative study; SR – systematic review

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SECTION 3: Hematology Indications

Autoimmune cytopenias secondary to chronic lymphocytic leukemia See separate entries for immune thrombocytopenic purpura (ITP) and/or autoimmune hemolytic anemia (AIHA).

? Autoimmune hemolytic anemia (AIHA) Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG is not recommended for routine use, but may be considered as one of several options in urgent situations.

Dose 1 to 2 g/kg adjusted body weight divided over 2 to 5 days.


Evidence Source G (G2); EO (GDG)

? Autoimmune neutropenia Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG may be considered as one of several options in rare circumstances when standard therapy fails.

Dose There is insufficient evidence to recommend a dose.


Evidence Source G (G1, G2); EO (GDG)

? Coagulation factor inhibitors Recommendation includes but is not limited to

o acquired hemophilia o acquired von Willebrand disease

o inhibitors to factor VIII in hemophilia A o inhibitors to factor IX in hemophilia B

Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.

Dose Dosing regimens vary according to clinical context.

Review Criteria Continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.

Evidence Source EO (GDG)



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Feto-maternal/neonatal alloimmune thrombocytopenia (FMAIT/NAIT) Do Recommendation

IVIG is recommended for preventing or treating fetal or neonatal thrombocytopenia or hemorrhage. Treatment should be under the direction of a specialist with expertise in high-risk obstetrics.

Dose Maternal: 1 g/kg weekly throughout pregnancy, with starting time tailored to individual risk profile and history. Neonatal: Single dose of 1 g/kg. Occasionally more than one dose is required if thrombocytopenia persists.

Qualifying Criteria

Clinical suspicion of FMAIT/NAIT in the antenatal or neonatal setting based on clinical and laboratory features, including:

1. Thrombocytopenia or spontaneous hemorrhage in the fetus; OR

2. Thrombocytopenia with or without hemorrhage in the neonate; OR

3. Unexplained fetal death in a previous pregnancy and the presence of maternal platelet-specific alloantibodies that are known or suspected to cause this condition (most commonly anti-HPA-1a or anti-HPA-5b).


Evidence Source SR (G1); G (G2); EO (G36)

Hemolytic disease of the newborn (HDN) Do Recommendation

IVIG may be considered in selected cases in consultation with experts in feto-maternal medicine and transfusion medicine.

Dose Single dose of 1 g/kg. Dose may be repeated if clinically indicated.


Evidence Source SR (G1); EO (G36)

? Hemolytic uremic syndrome (HUS) Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.






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Heparin-induced thrombocytopenia (HIT) Do Recommendation IVIG may be considered as an option for severe HIT refractory to standard therapies.

Dose 2 g/kg adjusted body weight divided over 2 days.


Evidence Source EO (GDG-CS)

Hypogammaglobulinemia, acquired secondary to hematological malignancies Includes but is not limited to

o chronic lymphocytic leukemia o lymphoma

o myeloma o post-hematopoietic stem cell transplant (HSCT)

See entry for secondary hypogammaglobulinemia in the Immunology Indications section.

Immune thrombocytopenic purpura (ITP) – adult Do Recommendation

IVIG is recommended for: 1. Refractory ITP on the recommendation of an appropriate clinical specialist

Patients with severe thrombocytopenia (platelets less than 20x109/L) in whom other therapies are ineffective or contraindicated.

2. Acute ITP with life-threatening hemorrhage or immediate high risk for life-threatening hemorrhage Patients with acute, severe ITP and clinical evidence of a hemostatic defect (e.g., mucous membrane hemorrhage) or active bleeding.

3. ITP in pregnancy Pregnant patients with ITP and impending delivery.

4. Specific circumstances a. Planned surgery; b. Other concurrent risk factors for bleeding (e.g., concurrent anti-

coagulant therapy); c. Severe ITP (platelets less than 20x109/L) where corticosteroids and

other immunosuppressives are contraindicated; and/or d. Chronic ITP under the guidance of a clinical hematologist, in addition

to other therapies or where other therapies are ineffective or contraindicated.

5. HIV–associated ITP Patients unresponsive to antiviral therapy and:

a. Platelet count less than 20 x 109/L; or b. Less than 50 x 109/L with bleeding.

6. Lupus–associated ITP See separate entry for systemic lupus erythematosus (SLE).



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definitions

Immune thrombocytopenic purpura (ITP) – adult For each of these indications, consultation with a clinical hematologist is strongly recommended.

Dose Induction: 1 to 2 g/kg adjusted body weight divided over 2 to 5 days. Ongoing therapy: When indicated, 1 to 2 g/kg adjusted body weight in single or divided dose every 4 to 6 weeks, titrated as needed to achieve a clinical effect (it is unusual to give more than 1 g/kg in a single dose).

Review Criteria For acute treatment, patient response should be documented according to objective measures of effectiveness established at the outset of treatment. In rare instances when longer term treatment is required, continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.


Immune thrombocytopenic purpura (ITP) – pediatric Do Recommendation

Acute: IVIG may be considered in patients with a platelet count of less than 20 x 109/L as part of multimodal therapy when the patient has life-threatening bleeding or requires surgery. IVIG is not indicated for mild bleeding. While the effectiveness of IVIG is not disputed, clinical experts advise that most children with ITP do not require IVIG therapy. Consultation with a pediatric hematologist is advised. Chronic: IVIG may be considered.

Dose Acute or chronic ITP: Single dose of 0.8 to 1 g/kg adjusted body weight, with a second dose within 48 hours if the platelet count has not increased above 20 x 109/L. Acute ITP with life-threatening bleeding: 2 g/kg adjusted body weight divided over 2 days.



? Neonatal hemochromatosis Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG may be considered for pregnant women who have had a previous pregnancy affected by neonatal hemochromatosis.



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? Neonatal hemochromatosis Dose There is insufficient evidence to recommend a dose.


Evidence Source NRCS (G1); EO (GDG)

Neonatal thrombocytopenia secondary to maternal autoimmune disorders

Do Recommendation

IVIG is recommended in addition to other therapies, in consultation with a neonatologist.

Dose Neonatal: Single dose of 1 g/kg. Dose may be repeated if clinically indicated.


Evidence Source CS (G29); EO (G36)

Post-transfusion purpura (PTP) Do Recommendation

IVIG is recommended as standard first-line therapy for suspected or confirmed PTP with life-threatening bleeding.



Evidence Source G (G2); EO (G36)

Pure red cell aplasia (PRCA) Do Recommendation

IVIG is recommended for viral PRCA associated with proven parvovirus B19 in immunocompromised patients. IVIG may be considered for patients with immunological PRCA who have not responded to other therapies.

Dose 0.5 g/kg adjusted body weight weekly for 4 weeks.


Evidence Source G (G1, G2)

? Sickle cell disease, hyperhemolysis syndrome Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG may be considered as one of several options in urgent situations.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days.



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? Sickle cell disease, hyperhemolysis syndrome Review Criteria Patient response should be documented according to objective measures of

effectiveness established at the outset of treatment.

Evidence Source G (G2); EO (GDG-CS)

? Thrombotic thrombocytopenic purpura (TTP) Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.





LEGEND (see Appendix B for seed guideline references): EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); IG – immune globulin; IgG – immunoglobulin G; IV – intravenous; IVIG – intravenous immune globulin; NR – non-systematic/narrative review; NRCS – non-randomized comparative study; SC – subcutaneous; SCIG – subcutaneous immune globulin; SR – systematic review

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SECTION 4: Immunology Indications

Hypogammaglobulinemia, secondary See separate entries for Kawasaki disease in the Rheumatology Indications section; for necrotizing fasciitis and toxic shock syndrome (TSS) in the Infectious Disease Indications section; and for transplant-related immunomodulation (solid organ transplant) in the Transplant Medicine Indications section.

Do Recommendation

Immunoglobulin replacement is recommended for preventing recurrent, severe infection due to hypogammaglobulinemia (excluding paraprotein) related to other diseases or medical therapy.

Dose Aim to use the dose that achieves a significant reduction in the number of bacterial infections. Maintenance: 0.4 to 0.6 g/kg adjusted body weight IVIG every 4 weeks, or SCIG 0.1 to 0.5 g/kg adjusted body weight weekly, modified to achieve an IgG trough level of at least the lower limit of the age-specific serum IgG reference range, or as needed to achieve clinical effectiveness. Loading: One additional dose of 0.4 g/kg adjusted body weight may be given in the first month of therapy if the serum IgG level is markedly reduced. Chronic suppurative lung disease: 0.4 to 0.8 g/kg adjusted body weight IVIG or equivalent SCIG dose may be given if chronic suppurative lung disease is not adequately controlled at an IgG trough level at the lower limit of the age-specific serum IgG reference range.

Qualifying Criteria

Hypogammaglobulinemia secondary to underlying disease or medical therapy (including hematopoietic stem cell transplant [HCST]) with all of the following:

1. Serum IgG less than the lower limit of the reference range on two separate occasions AND

2. At least one of the following: a. One invasive or life-threatening bacterial infection (e.g., pneumonia,

meningitis, sepsis) in the previous year; b. Recurrent, severe bacterial infections; c. Clinically active bronchiectasis confirmed by radiology; d. Assessment by a physician specializing in immunodeficiency

indicating a significant antibody defect that would benefit from immunoglobulin replacement.

Review Criteria Continued use of IG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter by a physician specializing in immunodeficiency disorders. If clinical effectiveness has not been achieved, IG treatment should be discontinued. Cessation of IG treatment may be possible depending on the status of the underlying disease.

Evidence Source SR (G1); G (G2); EO (G36, GDG)


LEGEND (see Appendix B for seed guideline references): EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); IG – immune globulin; IgG – immunoglobulin G; IV – intravenous; IVIG – intravenous immune globulin; NR – non-systematic/narrative review; NRCS – non-randomized comparative study; SC – subcutaneous; SCIG – subcutaneous immune globulin; SR – systematic review

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Primary immunodeficiency (PID) disorders Do Recommendation Immunoglobulin replacement is recommended for preventing bacterial infection.

Dose Aim to use the dose that achieves a significant reduction in the number of bacterial infections. Maintenance: 0.4 to 0.6 g/kg adjusted body weight IVIG every 4 weeks or SCIG 0.1 to 0.5 g/kg adjusted body weight weekly, modified to achieve an IgG trough level of at least the lower limit of the age-specific serum IgG reference range, or as needed to achieve clinical effectiveness. Loading: One additional dose of 0.4 g/kg adjusted body weight may be given in the first month of therapy if the serum IgG level is markedly reduced. Chronic suppurative lung disease: 0.4 to 0.8 g/kg adjusted body weight IVIG or equivalent SCIG dose may be given if chronic suppurative lung disease is not adequately controlled at an IgG trough level at the lower limit of the age-specific serum IgG reference range. Specific antibody deficiency and IgG subclass deficiency: IVIG should be titrated based on clinical outcome alone as measurement of IgG trough levels is unhelpful in these conditions.

Qualifying Criteria

PID diagnosis must be established by a physician specializing in immunodeficiency disorders. Functional testing should be completed to establish diagnosis for:

a. Common variable immunodeficiency (CVID) and associated disorders b. Specific antibody deficiency c. IgG subclass deficiency

Evidence Source SR (G1); NRCS (G34); G (G2); EO (G36, GDG-SR)


LEGEND (see Appendix B for seed guideline references): AIDS – acquired immune deficiency syndrome; EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); HIV – human immunodeficiency virus; IVIG – intravenous immune globulin; RCT – randomized controlled trial; SR – systematic review

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SECTION 5: Infectious Disease Indications

Clostridium difficile infection (CDI), recurrent Do Not Do Recommendation

IVIG is not recommended in the absence of hypogammaglobulinemia (see separate entry for secondary hypogammaglobulinemia).

Evidence Source SR (G17)

HIV/AIDS Do Not Do Recommendation

IVIG is not recommended in the absence of hypogammaglobulinemia (see separate entry for secondary hypogammaglobulinemia).


? Necrotizing fasciitis For patients with hemodynamic compromise, see separate entry for toxic shock syndrome (TSS).

Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG in patients without hemodynamic compromise.




Sepsis, neonatal prophylaxis See separate entries for primary immunodeficiency (PID) disorders and secondary hypogammaglobulinemia in the Immunology Indications section.

Do Not Do Recommendation IVIG is not recommended.

Evidence Source RCT (G1)

Toxic shock syndrome (TSS) Do Recommendation

IVIG is recommended in addition to surgical intervention, antibiotic therapy, and other supportive measures for streptococcal TSS or staphylococcal TSS. Consultation with an infectious disease specialist is strongly recommended.

Dose Single dose of 2 g/kg adjusted body weight.


Evidence Source RCT (G1); G (G2); EO (GDG)


LEGEND (see Appendix B for seed guideline references): AIDS – acquired immune deficiency syndrome; EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); HIV – human immunodeficiency virus; IVIG – intravenous immune globulin; RCT – randomized controlled trial; SR – systematic review

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/ Varicella-zoster virus (VZV), prophylaxis When VZV immune globulin is available

Do Not Do Recommendation

IVIG is not recommended for varicella-susceptible immunocompromised patients with primary exposure to VZV when VZV immune globulin is available.

Evidence Source EO (G40)

When VZV immune globulin is unavailable

Do Recommendation

IVIG is a suitable alternative for varicella-susceptible immunocompromised patients when VZV immune globulin is unavailable within 96 hours after exposure.

Dose Single dose of 0.4 g/kg adjusted body weight, as soon as possible. Ideally the dose should be given within 96 hours after exposure, but administration up to 10 days post-exposure may be helpful. Patients who have received IVIG within the prior 3 weeks should be protected.

Evidence Source EO (G40, G41)


LEGEND (see Appendix B for seed guideline references): CS – case series study; EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); IG – immune globulin; IgG – immunoglobulin G; IVIG – intravenous immune globulin; NR – non-systematic/narrative review; NRCS – non-randomized comparative study; RCT – randomized controlled trial; SCIG – subcutaneous immune globulin; SR – systematic review

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SECTION 6: Transplant Medicine Indications (including infectious diseases in transplant recipients)

/?/ Community-acquired respiratory virus (CARV), upper respiratory tract infection (URTI)

Proven respiratory syncytial virus (RSV) in high risk patients*

Do Recommendation

IVIG may be considered in addition to antiviral therapy to prevent progression to lower respiratory tract infection.

Dose 0.5 g/kg adjusted body weight, daily, for 5 to 7 days.


Evidence Source EO (GDG-G)

Non-RSV in high risk patients*


There is insufficient evidence to recommend for or against IVIG. In some circumstances, IVIG may be considered in addition to antiviral therapy on a case-by-case basis to prevent progression to lower respiratory tract infection.




All other patient groups, including solid organ transplant (other than lung)



*Note The term “high risk patient”1 signifies: • Lung transplant patients, especially children; • Leukemia and/or allogeneic hematopoietic stem cell transplant patients with:

- Severe lymphopenia (absolute lymphocyte count less than 0.2 x 109/L); - Severe neutropenia (absolute neutrophil count less than 0.5 x 109/L); - Age greater than 60 years; - HLA mismatched or unrelated donor.

1. Beaird OE, et al. Transplant Infectious Disease 2016;18(2):210-5.



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?/ Community-acquired respiratory virus (CARV), lower respiratory tract infection (LRTI)

High risk patients*


There is insufficient evidence to recommend for or against IVIG. In some circumstances, IVIG may be considered in addition to antiviral therapy on a case-by-case basis.




All other patient groups, including solid organ transplant (other than lung)



*Note The term “high risk patient”1 signifies: • Lung transplant patients, especially children; • Leukemia and/or allogeneic hematopoietic stem cell transplant patients with:

- Severe lymphopenia (absolute lymphocyte count less than 0.2 x 109/L); - Severe neutropenia (absolute neutrophil count less than 0.5 x 109/L); - Age greater than 60 years; - HLA mismatched or unrelated donor.

1. Beaird OE, et al. Transplant Infectious Disease 2016;18(2):210-5.

Cytomegalovirus (CMV) infection, prophylaxis Recommendation includes o hematopoietic stem cell transplant (HSCT) o solid organ transplant


Evidence Source SR (G28); EO (GDG-NR)

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD)

Recommendation includes o hematopoietic stem cell transplant (HSCT) o solid organ transplant

Do Not Do Recommendation IVIG is not recommended for prophylaxis or treatment.




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?/ Gastrointestinal viruses in solid organ transplant Refractory and persistent Norovirus or Rotavirus diarrhea


There is insufficient evidence to recommend for or against IG. Oral IG should be considered for persistent, proven Norovirus or Rotavirus in immunosuppressed transplant recipients where reduction of immunosuppression is contraindicated.

Dose Maximum dose of 360 mg, given as single oral doses of 25 mg to 45 mg, four times daily, for at least 2 days.


Evidence Source EO (GDG-NR)

Refractory and persistent viral gastroenteritis syndromes (other than Norovirus or Rotavirus)

Do Not Do Recommendation IG is not recommended.


Hematopoietic stem cell transplant (HSCT), allogeneic, Cytomegalovirus (CMV)-induced pneumonitis

Do Recommendation

IVIG is recommended, in addition to appropriate antiviral chemotherapy, for proven or probable1 CMV-induced pneumonitis following allogeneic HSCT.

1. Ljungman P, et al. Clinical Infectious Diseases 2017;64(1):87-91.


Evidence Source G (G2); EO (GDG-NRCS)

Hematopoietic stem cell transplant (HSCT), allogeneic, graft-versus-host disease

Do Not Do Recommendation IVIG is not recommended for preventing graft-versus-host disease in allogeneic HSCT.

Evidence Source EO (GDG-SR)

Hematopoietic stem cell transplant (HSCT), autologous Do Not Do Recommendation

IVIG is not recommended unless the patient has established humoral deficiency (see separate entry for secondary hypogammaglobulinemia).




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Hematopoietic stem cell transplant (HSCT) for primary immunodeficiency (PID) disorders

Do Recommendation

IVIG is recommended to reduce baseline community-acquired encapsulated Gram-positive bacterial infections.

Dose 0.4 to 0.6 g/kg adjusted body weight, every 4 weeks or SCIG 0.1 to 0.5 g/kg adjusted body weight weekly, modified to achieve an IgG trough level of at least the lower limit of the age-specific serum IgG reference range, or as needed to achieve clinical effectiveness. Requirements may change and IVIG should be titrated based on clinical outcome.

Evidence Source G (G2); EO (GDG)

Kidney, active antibody-mediated rejection (ABMR) prevention and management

Do Recommendation

Pre-transplant: IVIG is recommended when an antibody or antibodies might preclude transplantation (e.g., donor specific anti-human leukocyte antigen (HLA) antibody or anti-blood group antibody). IVIG may be continued for up to 3 months post-transplant. Post-transplant: IVIG may be used to treat active ABMR1 when other therapies are ineffective.

1. Haas M, et al. American Journal of Transplantation 2018;18:293-307.

Dose IVIG with plasma exchange: 0.1 g/kg adjusted body weight after each plasma exchange, to a maximum total dose of 2 g/kg. IVIG alone: 2 g/kg adjusted body weight divided over 2 to 5 days. When IVIG is used alone, further doses may be indicated every 4 weeks for a further 3 cycles, depending on clinical response or biopsy findings. Thereafter, additional treatment cycles (often together with other treatment modalities) may be indicated, but only when biopsy findings and/or clinical response demonstrate ongoing/recurrent active ABMR or chronic active ABMR.1 Demonstration of ongoing/recurrent active ABMR or chronic active ABMR should precede each treatment cycle. Note: Some sucrose-stabilized formulations of IVIG have shown nephrotoxicity and are best avoided in patients with pre-existing kidney impairment.2 Some nephrologists recommend that IVIG infusions be capped at 140 g/day to reduce the risk of nephrotoxicity.

1. Haas M, et al. American Journal of Transplantation 2018;18:293-307. 2. Dantal J. American Journal of Nephrology 2013;38:275-84.

Review Criteria Patient response to each treatment cycle should be documented according to objective measures of effectiveness established at the outset of treatment.

Evidence Source SR (G1); G (G2); EO (GDG)



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? Kidney, acute/active T-cell mediated rejection (TCMR) management Do Not Know Recommendation

There is insufficient evidence to recommend for or against using IVIG. It may be considered in exceptional cases when other therapies are ineffective or contraindicated.

Dose There is insufficient evidence to recommend a particular dosing regimen. Most centres report short-term treatment (1 to 4 doses), rather than long-term administration. Note: Some sucrose-stabilized formulations of IVIG have shown nephrotoxicity and are best avoided in patients with pre-existing kidney impairment.1 Some nephrologists recommend that IVIG infusions be capped at 140 g/day to reduce the risk of nephrotoxicity.

1. Dantal J. American Journal of Nephrology 2013;38:275-84.


Evidence Source SR (G1); G (G2); EO (GDG)

? Kidney, non-active rejection management Do Not Know Recommendation

There is insufficient evidence to recommend for or against using IVIG. It may be considered in exceptional cases when other therapies are ineffective or contraindicated. However, it is generally discouraged due to the lack of evidence of effectiveness in the absence of active disease, weighed against the known toxicity (including nephrotoxicity), administrative burden to the patient, and cost. If used, it should be given according to an established protocol that enables subsequent evaluation of its overall efficacy as a management strategy.

Dose There is insufficient evidence to recommend a particular dosing regimen. Most centres use short-term protocols (1 to 4 doses), often as part of a multi-modality treatment protocol, rather than long-term administration. In long-term protocols, once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness. Note: Some sucrose-stabilized formulations of IVIG have shown nephrotoxicity and are best avoided in patients with pre-existing kidney impairment.1 Some nephrologists recommend that IVIG infusions be capped at 140 g/day to reduce the risk of nephrotoxicity.

1. Dantal J. American Journal of Nephrology 2013;38:275-84.

Review Criteria For short-term treatment, patient response should be documented according to objective measures of effectiveness established at the outset of treatment. In rare instances when long- or indefinite-term treatment is given, continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least semi-annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.



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? Kidney, non-active rejection management Evidence Source SR (G1); G (G2); EO (GDG)

Pulmonary graft-versus-host disease Do Not Do Recommendation IVIG is not recommended.


? Solid organ (other than kidney) Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG may be considered in:

• highly sensitized patients awaiting transplantation; • transplant recipients with acute T-cell mediated rejection (TCMR) and clinical

evidence of graft dysfunction; • transplant recipients as treatment or prophylaxis for rejection when

conventional immunosuppressive therapy is contraindicated.



Evidence Source CS (G1); EO (GDG-NR)

Solid organ (other than kidney), antibody-mediated rejection (ABMR) Do Recommendation

IVIG is recommended in addition to plasma exchange. Where appropriate, biopsy evidence of rejection should be sought.

Dose 0.1 g/kg adjusted body weight after each plasma exchange, to a maximum dose of 2 g/kg total.


Evidence Source CS (G1); EO (G36, GDG)


LEGEND (see Appendix B for seed guideline references): CR – case report; CS – case series study; EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); IgA – immunoglobulin A; IgG – immunoglobulin G; IVIG – intravenous immune globulin; MAG - myelin-associated glycoprotein; NR – non-systematic/narrative review; qSR – quasi-systematic review; RCT – randomized controlled trial; SR – systematic review

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SECTION 7: Neurology and Neuromuscular Indications

Acute disseminated encephalomyelitis (ADEM) Do Recommendation

IVIG is recommended for: 1. ADEM unresponsive to steroid therapy or where steroids are contraindicated. 2. Recurrent or multiphasic ADEM unresponsive to steroid therapy or where

steroid therapy has become intolerable or is contraindicated.

Dose Induction: 2 g/kg adjusted body weight divided over 2 to 5 days. Maintenance (for recurrent or multiphasic ADEM only): 0.4 to 2 g/kg adjusted body weight every 4 to 6 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.


Evidence Source CS (G1)

? Acute flaccid myelitis Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.




Acute optic neuritis See separate entry for neuromyelitis optica (Devic disease).


Evidence Source RCT (G1)

Adrenoleukodystrophy Do Not Do Recommendation IVIG is not recommended.




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? Aicardi-Goutières syndrome Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.



Evidence Source EO (GDG-CR)

Alzheimer disease Do Not Do Recommendation IVIG is not recommended.


Anti-NMDA receptor encephalitis Do Recommendation IVIG may be considered as an option with expert consultation.



Evidence Source EO (GDG-qSR)

Autism Do Not Do Recommendation IVIG is not recommended.




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? Childhood epilepsy, medically refractory/intractable Recommendation includes but is not limited to

o Infantile spasms o Landau–Kleffner syndrome o Lennox–Gastaut syndrome


There is insufficient evidence to recommend for or against IVIG. IVIG should be considered only when conventional therapies are ineffective, with previous full assessment by a pediatric epileptologist. If IVIG is used, a therapeutic trial should be conducted, under the supervision of a pediatric epileptologist:

• Infantile spasms: one dose only • Landau–Kleffner syndrome: one dose only • Lennox–Gastaut syndrome: one dose every 4 weeks, up to 6 cycles

If the therapeutic trial is effective, IVIG can be used long term.

Dose 0.4 to 2 g/kg adjusted body weight divided over 2 to 5 days, every 4 weeks for 4 to 6 cycles.


Evidence Source EO (G1, G36, GDG-CS)

Chronic fatigue syndrome (myalgic encephalomyelitis) Do Not Do Recommendation IVIG is not recommended.

Evidence Source EO (G1, GDG-RCT)

Chronic inflammatory demyelinating polyneuropathy (CIDP) Recommendation includes but is not limited to

o Demyelinating neuropathy associated with IgG and IgA paraproteinemia

Do Recommendation

IVIG is recommended for first-line treatment, to be initiated when progression is rapid, walking is compromised, or there is significant functional impairment. The diagnosis of CIDP is complicated, particularly in patients with concurrent diabetes. Evaluation by a neurologist with expertise in neuromuscular disease is required.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days, every 4 weeks. IVIG should be administered for 3 to 6 months to assess efficacy. Some patients do not show a definitive sustained response until they have undergone up to 6 treatment cycles. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



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Chronic inflammatory demyelinating polyneuropathy (CIDP) Review Criteria Regular review by a neurologist is required: frequency as determined by the clinical

status of the patient. If clinical effectiveness has not been achieved after 6 treatment cycles, IVIG should be discontinued. Continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment, in consultation with a neurologist. For stable patients, these measures should be assessed, in consultation with a neurologist, no later than 6 months after initiation of long-term treatment and at least annually thereafter. If clinical effectiveness has not been achieved or sustained, IVIG should be discontinued.

Evidence Source SR (G1); EO (GDG)

Critical illness polyneuropathy (CIP) Do Not Do Recommendation IVIG is not recommended.


? Diabetic amyotrophy Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG may be considered in exceptional circumstances with expert consultation.


Review Criteria In rare instances when longer term treatment is required, continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.

Evidence Source EO (G1, GDG-SR)

Guillain–Barré syndrome (GBS) Do Recommendation IVIG is recommended in patients with significant disability and progression.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days. A second course of IVIG may be considered in patients with clearly demonstrated secondary deterioration, after assessment by a neurologist.


? Hashimoto encephalopathy Do Not Know Recommendation

IVIG is not recommended as first-line treatment because preferable alternative treatment is available. IVIG may be considered in exceptional circumstances where there is progressive neurologic decline despite appropriate steroid therapy.



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? Hashimoto encephalopathy Dose Single dose of 2 g/kg adjusted body weight.



Lambert–Eaton myasthenic syndrome (LEMS) Do Recommendation

IVIG is recommended as an option for initial treatment. IVIG may be considered in patients who show objective evidence of clinical improvement with IVIG therapy but have incomplete response to oral maintenance therapies.

Dose Induction: 2 g/kg adjusted body weight divided over 2 to 5 days. Maintenance: Maximum dose of 2 g/kg adjusted body weight, every 4 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.


Evidence Source G (G2); EO (G36, GDG)

Motor neuron disease See separate entry for multifocal motor neuropathy (MMN).

Recommendation includes but is not limited to

o amyotrophic lateral sclerosis (ALS)



Multifocal motor neuropathy (MMN) Do Recommendation

IVIG is recommended as first-line treatment. Diagnosis should be made by a neuromuscular specialist with specific electrodiagnostic expertise.

Dose Induction: 2 g/kg adjusted body weight divided over 2 to 5 days. Maintenance: 0.4 to 2 g/kg adjusted body weight every 2 to 6 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



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Multifocal motor neuropathy (MMN) Review Criteria Continued use of IVIG should be based on objective measures of effectiveness

established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.

Evidence Source SR (G1); G (G2)

/ Multiple sclerosis (MS) Short-term therapy

Do Recommendation

IVIG is recommended for short-term therapy in patients with clinically definite relapsing/remitting MS,1,2 confirmed by a neurologist, and one of the following indications:

1. Pregnancy and the immediate post-partum period when other immunomodulation is contraindicated;

2. Young patients with severe relapsing/remitting disease in whom other therapies are ineffective;

3. Severe relapse with no response to high-dose methylprednisolone.

1. Thompson AJ, et al. Lancet Neurology 2018;17(2):162-73. 2. Krupp LB, et al. Multiple Sclerosis 2013;19(10):1261-7.

Dose Induction: 1 to 2 g/kg adjusted body weight divided over 2 to 5 days. Maintenance for indications 1 and 2: 0.4 to 1 g/kg adjusted body weight every 4 to 6 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



Long-term therapy



Myasthenia gravis (MG), moderate to severe generalized Do Recommendation

IVIG is recommended as: 1. An alternative to plasma exchange in acute exacerbation (myasthenic crisis) or

before surgery and/or thymectomy. 2. Maintenance therapy for moderate to severe generalized MG when other

treatments are ineffective or have caused intolerable side effects.



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Myasthenia gravis (MG), moderate to severe generalized Dose Induction, before surgery, or during myasthenic crisis: 1 to 2 g/kg adjusted body

weight divided over 2 to 5 days. Maintenance: 0.4 to 1 g/kg adjusted body weight every 4 to 6 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



? Myasthenia gravis (MG), ocular and/or mild generalized Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.

Dose There is insufficient evidence to recommend a dose. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



? Narcolepsy/cataplexy Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG may be considered in exceptional circumstances with expert consultation.


Review Criteria In rare circumstances when long-term treatment is required, continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.

Evidence Source EO (G1, GDG-qSR)

? Neuromyelitis optica (Devic disease) Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.



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GY & N

EURO

-M

USCU

LAR IND

ICATION

S

?


definitions

? Neuromyelitis optica (Devic disease) Dose There is insufficient evidence to recommend a dose.


Evidence Source NR (G1)

Neuropathic pain Do Not Do Recommendation IVIG is not recommended.


/?/ Neuropathy associated with IgM paraproteinemia Demyelinating neuropathy without anti-MAG antibodies

Do Recommendation

IVIG is recommended for neuropathy associated with IgM and features consistent with CIDP, in the absence of anti-MAG antibodies.

Dose 2 g/kg divided over 2 to 5 days, every 4 weeks. IVIG should be administered for 3 to 6 months to assess efficacy. Some patients do not show a definitive sustained response until they have undergone up to 6 treatment cycles. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.

Review Criteria Regular review by a neurologist is required: frequency as determined by the clinical status of the patient. If clinical effectiveness has not been achieved after 6 treatment cycles, IVIG should be discontinued. Continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment, in consultation with a neurologist. For stable patients, these measures should be assessed, in consultation with a neurologist, no later than 6 months after initiation of long-term treatment and at least annually thereafter. If clinical effectiveness has not been achieved or sustained, IVIG should be discontinued.

Evidence Source SR (G1, G2); EO (GDG)

Demyelinating neuropathy with anti-MAG antibodies

Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.




33

NEU

ROLO

GY & N

EURO

-M

USCU

LAR IND

ICATION

S

?


definitions

/?/ Neuropathy associated with IgM paraproteinemia Review Criteria Continued use of IVIG should be based on objective measures of effectiveness

established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.


Axonal neuropathy



? Opsoclonus-myoclonus ataxia (OMA) – adult Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.




Opsoclonus-myoclonus ataxia (OMA) – pediatric Do Recommendation

IVIG is recommended for acute and long-term treatment, in consultation with a neurologist, in addition to other tumour therapies, as applicable.

Dose Induction: 1 to 2 g/kg adjusted body weight divided over 2 to 5 days. Maintenance: 0.4 to 1 g/kg adjusted body weight every 4 to 6 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



? Paraneoplastic neurological syndromes Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG for paraneoplastic neurological syndromes that are not otherwise specified.



34

NEU

ROLO

GY & N

EURO

-M

USCU

LAR IND

ICATION

S

?


definitions

? Paraneoplastic neurological syndromes Dose Dosing regimens vary according to clinical context.

Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



Paraneoplastic or sporadic autoimmune encephalitis See separate entries for anti-NMDA receptor encephalitis and Rasmussen syndrome.


o potassium channel antibody-associated encephalopathy

Do Recommendation

IVIG should be considered for both paraneoplastic and sporadic autoimmune encephalitis. IVIG may play a role in maintenance therapy.

Dose Induction: 2 g/kg adjusted body weight divided over 2 to 5 days. Maintenance: 0.5 to 2 g/kg adjusted body weight, every 4 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.


Evidence Source EO (G36; GDG-qSR)

? Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS)


There is insufficient evidence to recommend for or against IVIG. The utility of IVIG appears to be limited to patients with a confirmed diagnosis, including evidence of recent streptococcal infection. Diagnosis of PANDAS requires expert consultation.



Evidence Source G (G2); EO (G36, GDG-RCT)



35

NEU

ROLO

GY & N

EURO

-M

USCU

LAR IND

ICATION

S

?


definitions

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome



? Postpolio syndrome Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG for routine treatment. While IVIG may be considered in exceptional circumstances for postpolio muscular atrophy, experts generally advise against the use of IVIG in this context.


Review Criteria In rare instances when long-term treatment is required, continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.

Evidence Source RCT (G25); EO (GDG)

?/ Rasmussen syndrome Short-term therapy


There is insufficient evidence to recommend for or against IVIG. IVIG is an option as a short-term, temporizing measure.



Evidence Source G (G2); EO (G36, GDG)

Long-term therapy


Evidence Source G (G2)

Stiff person syndrome (Moersch–Woltmann syndrome) Do Recommendation

IVIG is recommended for treatment of significant functional impairment in patients who have stiff person syndrome, verified in consultation with a neurologist.



36

NEU

ROLO

GY & N

EURO

-M

USCU

LAR IND

ICATION

S

?


definitions

Stiff person syndrome (Moersch–Woltmann syndrome) Dose Induction: 2 g/kg adjusted body weight divided over 2 to 5 days.

Maintenance: 1 to 2 g/kg adjusted body weight, every 4 to 6 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



/? Sydenham chorea Short-term therapy

Do Recommendation

The use of a single dose of IVIG is reasonable to provide short-term improvement in symptoms for children with moderate to severe Sydenham chorea associated with significant impairment.




Long-term therapy


There is insufficient evidence to recommend for or against IVIG in the long-term therapy of children with moderate to severe Sydenham chorea.




? Susac syndrome Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.

Dose 1 to 2 g/kg adjusted body weight divided over 2 to 5 days, every 4 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



37

NEU

ROLO

GY & N

EURO

-M

USCU

LAR IND

ICATION

S

?


definitions

? Susac syndrome Review Criteria Continued use of IVIG should be based on objective measures of effectiveness

established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued. Effectiveness of IVIG therapy may be difficult to determine due to the fluctuating course of disease.


? Transverse myelitis Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.





LEGEND (see Appendix B for seed guideline references): CS – case series study; EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); IVIG – intravenous immune globulin; NR – non-systematic/narrative review; qSR – quasi-systematic review; RCT – randomized controlled trial; SR: systematic review

38

RHEU

MATO

LOGY

IND

ICATION

S

?


definitions

SECTION 8: Rheumatology Indications

Antiphospholipid syndrome (other than catastrophic) See separate entry for catastrophic antiphospholipid syndrome.


Evidence Source EO (G1, GDG-qSR)

Antiphospholipid syndrome, catastrophic See separate entry for antiphospholipid syndrome other than catastrophic.

Do Recommendation

IVIG is recommended for catastrophic antiphospholipid syndrome, characterized by widespread small vessel thrombosis leading to multiorgan failure.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days. A single treatment is usually sufficient. The potential pro-thrombotic effect of IVIG should be considered in this indication.

Qualifying Criteria

All of the following criteria must be met: 1. Evidence of rapidly evolving thrombosis involving two or more organs; 2. Unequivocal laboratory evidence of antiphospholipid antibodies (lupus

anticoagulant and/or anticardiolipin antibodies and/or beta 2 glycoprotein I antibodies); and

3. Other causes of thrombotic microangiopathy are considered less likely. Confirmation by histopathology of thrombotic small vessel occlusion in at least one organ or tissue is desirable but should not delay IVIG therapy if indicated.


Behçet disease Do Not Do Recommendation IVIG is not recommended.


? Congenital heart block, autoimmune (neonatal lupus) Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.






39

RHEU

MATO

LOGY

IND

ICATION

S

?


definitions

Dermatomyositis – adult Do Recommendation

IVIG should be considered for patients who do not respond to first-line therapies. In severe or life-threatening situations, e.g., dysphagia, it may be part of first line therapy.

Dose 2 g/kg adjusted body weight divided over 2 days, every 4 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.


Evidence Source EO (GDG-RCT)

Dermatomyositis – pediatric Do Recommendation

IVIG should be considered: • in addition to corticosteroids and/or immunosuppressives:

o at the outset of treatment; or o when the response is suboptimal;

• for persistent skin disease when the muscle disease is otherwise well controlled.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days, every 2 weeks for 3 to 5 cycles, and then every 4 weeks.1 Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.

1. Huber AM, et al. Journal of Rheumatology 2017;44(1):110-6.



Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss disease)

Do Recommendation

IVIG may be considered for patients with nervous system or cardiac disorders who do not respond to primary standard therapy.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days, every 4 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



40

RHEU

MATO

LOGY

IND

ICATION

S

?


definitions

Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss disease)


Evidence Source EO (G31, GDG-NR)

? Immune-mediated uveitis Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. IVIG may be considered for exceptional cases of immune-mediated, sight-threatening uveitis with persistent activity despite corticosteroid and immunosuppressive therapy.

Dose 1 to 2 g/kg adjusted body weight, in single or divided dose, every 4 weeks for 3 months (it is unusual to give more than 1 g/kg in a single dose). In rare circumstances, longer term therapy may be required.

Review Criteria In rare circumstances when long-term treatment is required, continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 3 months after initiation of long-term treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.


/? Inclusion body myositis (IBM) IBM without dysphagia



IBM with dysphagia


There is inconclusive evidence to recommend for or against IVIG in patients with IBM who have dysphagia affecting function. Given the modest effect identified in a small number of reported patients, expert opinion advises against the use of IVIG in this context.1

1. Dalakas MC, et al. Neurology 1997;48(3):712-6.





41

RHEU

MATO

LOGY

IND

ICATION

S

?


definitions

/? Inclusion body myositis (IBM) Evidence Source EO (GDG-SR)

? Kawasaki disease – adult Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.




Kawasaki disease – pediatric Do Recommendation IVIG is recommended early in Kawasaki disease to prevent coronary artery pathology.

Dose 2 g/kg adjusted body weight over 10 to 12 hours unless cardiac function necessitates the administration of a prolonged or divided treatment dose. A single treatment is usually sufficient. One additional dose may be given if there is ongoing inflammation. A third dose of IVIG is not recommended.

Qualifying Criteria

Clinical diagnosis of Kawasaki disease by a pediatrician, rheumatologist, or immunologist.

Evidence Source SR (G1, G37)

Livedoid vasculopathy See entry in the Dermatology Indications section.

Macrophage activation syndrome (MAS) Do Recommendation IVIG may be used in addition to other therapies.




Polymyositis – adult Do Recommendation IVIG is recommended for patients who do not respond to first-line therapies.



42

RHEU

MATO

LOGY

IND

ICATION

S

?


definitions

Polymyositis – adult Dose 2 g/kg adjusted body weight divided over 2 to 5 days, every 4 weeks.

Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



? Polymyositis – pediatric Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.




Rheumatoid arthritis Do Not Do Recommendation IVIG is not recommended.


? Scleroderma Do Not Know Recommendation

There is insufficient evidence to recommend for or against IVIG. It may be considered in exceptional circumstances when patients do not respond to primary standard therapy.



Evidence Source CS (G8); EO (GDG-qSR)



43

RHEU

MATO

LOGY

IND

ICATION

S

?


definitions

? Sjogren syndrome Do Not Know Recommendation There is insufficient evidence to recommend for or against IVIG.




? Systemic juvenile idiopathic arthritis (JIA) (adult Still disease) See separate entry for macrophage activation syndrome (MAS).


There is insufficient evidence to recommend for or against IVIG. IVIG may be considered in exceptional circumstances when patients do not respond to primary standard therapy.




? Systemic lupus erythematosus (SLE) Do Not Know Recommendation

There is insufficient evidence for or against IVIG. IVIG may be considered in exceptional circumstances for SLE when no other treatment options are effective or appropriate. Care should be taken in the setting of connective tissue disease as the infusion of IVIG in patients with high titre rheumatoid factor (RF) has been associated with renal damage.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days. Long-term therapy can be recommended only in exceptional cases. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.





44

RHEU

MATO

LOGY

IND

ICATION

S

?


definitions

? Vasculitic syndromes See separate entries for Behçet disease, eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss disease), and Kawasaki disease.


o granulomatosis with polyangiitis (Wegener granulomatosis)

o IgA-associated small vessel vasculitis (Henoch–Schonlein purpura)

o microscopic polyangiitis


There is insufficient evidence to recommend for or against IVIG. IVIG may be considered as an option when primary standard therapy is ineffective or contraindicated.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days. In rare circumstances, longer term therapy may be required.

Review Criteria In rare circumstances when long-term treatment is required, continued use of IVIG should be based on objective measures of effectiveness established at the outset of treatment. These measures should be assessed no later than 6 months after initiation of treatment and at least annually thereafter. If clinical effectiveness has not been achieved, IVIG should be discontinued.



LEGEND (see Appendix B for seed guideline references): CS – case series study; EO – expert opinion; G – guideline; GDG – guideline development group (IMEC); IVIg – intravenous immunoglobulin; qSR – quasi-systematic review

45

OTH

ER IN

DICATIO

NS

?


definitions

SECTION 9: Other Indications

? Graves disease Do Not Know Recommendation

IVIG is not recommended as first-line treatment because preferable alternative treatment is available. IVIG may be considered in exceptional circumstances when steroids are ineffective or contraindicated.

Dose 2 g/kg adjusted body weight divided over 2 to 5 days, every 3 to 4 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.



/? Hemophagocytic lymphohistiocytosis (HLH) syndrome Without thrombocytopenia



With thrombocytopenia


There is insufficient evidence to recommend for or against IVIG. IVIG may be considered in exceptional circumstances with appropriate consultation.




Systemic capillary leak syndrome (SCLS) Do Recommendation IVIG may be considered for prophylaxis, in addition to other therapies.

Dose 1 to 2 g/kg adjusted body weight divided over 2 to 5 days, every 4 weeks. Once the patient’s condition has stabilized, consider titrating the dose and/or the treatment interval to the lowest dose necessary to maintain clinical effectiveness.


Evidence Source CS (G1); EO (GDG-qSR)


APPEND

IX A

46

APPENDIX A: Categorization of Recommendations

Summary of Criteria to Determine the Categorization of Recommendations

Do

• The Guideline Development Group (GDG) accepted the original recommendation (from the seed guideline), which provided a prescriptive direction to perform the action or used the term “effective” to describe it.

• The GDG supplemented a recommendation or created a new one, based on their collective professional opinion (with or without additional research evidence), which supported the action.

Do Not Know

?

• The GDG accepted the original recommendation, which did not recommend for or against the action or stated that there was “no evidence,” “insufficient or conflicting evidence,” or “no good evidence” to support its use.

• The GDG supplemented a recommendation or created a new one, based on their collective professional opinion (with or without additional research evidence), which was equivocal with respect to supporting the action.

o “Inconclusive evidence to recommend for or against”: the additional research evidence comprised at least one systematic review presenting conflicting or equivocal results or stating that the evidence in relation to the action was “limited,” “inconclusive,” “inconsistent,” or “insufficient.”

o “Insufficient evidence to recommend for or against”: the additional research evidence did not include a systematic review.

Do Not Do

• The GDG accepted the original recommendation, which provided a prescriptive direction not to perform the action, used the term “ineffective” to describe it, or stated that the evidence does “not support” it.

• The GDG supplemented a recommendation or created a new one, based on their collective professional opinion (with or without additional research evidence), which did not support the action.


APPEND

IX B

47

APPENDIX B: Evidence Sources This guideline was developed by a multidisciplinary Inter-Provincial Medical Expert Committee (IMEC), referred to as the Guideline Development Group (GDG) throughout this document. Recommendations are based on a review of 45 “seed” guidelines (referenced as G1 to G45; published between January 2012 and September 2017) and additional systematic review evidence, or were created by the GDG based on their collective professional opinion and an analysis of relevant evidence. Note that only some (n=18) of these guidelines were directly used by the GDG to formulate recommendations. The references for the “seed” guidelines are available at the end of this document. A full description of the methods used to develop this evidence-based guideline is available from: http://www.ihe.ca.

Each recommendation in the guideline came from one or more seed guidelines or was created by the GDG, based on their collective professional opinion and an analysis of additional evidence on immune globulin. The Evidence Source row of the recommendations provides information on the seed guideline(s) that were used to develop the guideline recommendations and the design of the studies referenced by the seed guideline(s) and the GDG in support of their recommendations. The following evidence sources were considered:

• Systematic review (SR), quasi-systematic review (qSR) (a review that does not include a critical appraisal of the included studies), randomized controlled trial (RCT), non-randomized comparative study (NRCS), case series study (CS), guideline (G), narrative review (NR), case report (CR).

• Expert opinion (EO) – as cited by the seed guideline(s) or when no evidence was provided by the seed guideline in support of the recommendation.

• EO (GDG) – the GDG examined the individual studies cited by the seed guideline(s) or additional evidence on immune globulin, as identified by a supplementary literature search, and drafted a new recommendation based on their collective EO.

o When EO (GDG) recommendations were based on specific studies, the study design of the evidence was listed, e.g., EO (GDG-SR), EO (GDG-RCT). For a full listing of these studies, please see: http://www.ihe.ca.

For evidence cited by the seed guideline(s) or the GDG, only the highest level of evidence was listed for each indication. For example, when the evidence cited from SRs and studies of other design (i.e., qSR, RCT, NRCS, CS, G, NR, or CR), only SR is listed as the source. When no SR was referenced in the seed guideline or by the GDG, the evidence source is indicated in the following order: qSR, RCT, NRCS, CS, G, NR, CR, EO. For recommendations combining multiple indications, the level of evidence was listed for each indication according to the rules stated above.

http://www.ihe.ca/

http://www.ihe.ca/


APPEND

IX B

48

The general statements were sourced from the seed guidelines or were created by the GDG, based on their collective professional opinion and an analysis of relevant evidence referenced by the members of the GDG or provided by the research team, such as recently published systematic reviews or studies/trials not captured by the literature searches.

Statements in italics relate to harm. These statements were sourced from the recommendations or elsewhere in the seed guidelines, or were created by the GDG.


APPEND

IX C

49

APPENDIX C: Participants in the Guideline Development Process A full listing of participant affiliations is available from: http://www.ihe.ca.

STEERING COMMITTEE

Rume Djebah, MBBS, MHA Project Coordinator Alberta Health, Alberta, Canada Judy Hoff, BSc CLS Saskatchewan Ministry of Health, Saskatchewan, Canada Glenna Laing, BN, MA Steering Committee Co-chair Alberta Health, Alberta, Canada

Wendy Peppel, BN (until October 2017) Manitoba Health, Manitoba, Canada Sheila Rutledge Harding, MD, MA, FRCPC Steering Committee Co-Chair IMEC Chair and Subcommittees Co-chair Saskatoon Health Authority, Saskatchewan, Canada Robert Shaffer, BSc (from November 2017) Manitoba Health, Manitoba, Canada

DERMATOLOGY

P. Régine Mydlarski, MD, FRCPC University of Calgary, Alberta, Canada

HEMATOLOGY

Charles Musuka, MBChB, FRCPC, FRCPath University of Manitoba, Manitoba, Canada Bruce Ritchie, MD, FRCPC University of Alberta, Alberta, Canada

Matthew Seftel, MD, MPH, FRCPC, FRCP Subcommittee Co-chair CancerCare Manitoba, Manitoba, Canada Meer-Taher Shabani-Rad, MD, FRCPC University of Calgary, Alberta, Canada

IMMUNOLOGY

Jennifer Grossman, MD, FRCPC Subcommittee Co-chair Alberta Health Services, Alberta, Canada

Chrystyna Kalicinsky, MD, FRCPC University of Manitoba, Manitoba, Canada

INFECTIOUS DISEASE AND TRANSPLANT MEDICINE

Eric Bow, MD, MSc, D. Bacteriol, FRCPC University of Manitoba and CancerCare Manitoba, Manitoba, Canada

Karen Doucette, MD, FRCPC University of Alberta, Alberta, Canada Jeffrey Curtis Ma, MD, FRCPC University of Calgary, Alberta, Canada

NEUROLOGY

Juan Pablo Appendino, MD, CSCN (EEG), FAES Alberta Children’s Hospital, Alberta, Canada Helly Goez, MD, FRCPC University of Alberta and Glenrose Rehabilitation Hospital, Alberta, Canada Werner Ilse, MD, MSc, FRCPC, DAAEM University of Manitoba, Manitoba, Canada

Hanna Kolski, MD, FRCPC Subcommittee Co-chair University of Alberta, Alberta, Canada Kerri Schellenberg, MD, FRCPC, CSCN (EMG), MMedEd University of Saskatchewan, Saskatchewan, Canada Chris White, MD, FRCPC University of Calgary, Alberta, Canada

http://www.ihe.ca/


APPEND

IX C

50

RHEUMATOLOGY

Keltie Anderson, MD, BSc, BA, FRCPC University of Saskatchewan, Saskatchewan, Canada Janet Ellsworth, MD, FRCPC University of Alberta, Alberta, Canada Mehul Jariwala, MD, DNB (Pediatrics) University of Saskatchewan, Saskatchewan, Canada Nadia Luca, MD, FRCPC University of Calgary and Alberta Children's Hospital, Alberta, Canada

David Robinson, MD, FRCPC Subcommittee Co-chair University of Manitoba, Manitoba, Canada Anthony Russell, MB BCh, FRCPC University of Alberta, Alberta, Canada Heinrike Schmeling, MD, PhD, FRCPC University of Calgary and Alberta Children’s Hospital, Alberta, Canada

RESEARCH TEAM

Stefanie Kletke, MA, BSc, BA (Hons) Project Coordinator Institute of Health Economics, Alberta, Canada

Carmen Moga, MD, MSc Institute of Health Economics, Alberta, Canada Ann Scott, BSc (Hons), PhD Institute of Health Economics, Alberta, Canada


REFERENCES

51

REFERENCES References for reviewed seed guidelines The guidelines are not presented in any specific order. G1, G2, etc., are randomly assigned and for the purpose of organization only.

Only those guidelines directly used by the GDG to formulate recommendations (n=18*) are cited as evidence sources in the document.

G1* Australia

Jurisdictional Blood Committee, for and on behalf of the Australian Health Ministers’ Conference. Criteria for the clinical use of intravenous immunoglobulin in Australia. Second Edition. Canberra: Commonwealth of Australia; 2012.

G2* Canada

Ontario Regional Blood Coordinating Network. Ontario intravenous immune globulin (IVIG) utilization management guidelines Version 2.0. Toronto: Ontario Regional Blood Coordinating Network; 2012.

G3 USA

Ringold S, Weiss PF, Beukelman T, DeWitt EM, Ilowite NT, Kimura Y, et al. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: Recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis and Rheumatism 2013;65(10):2499-512.

G4 Japan

Research Committee of the Japanese Society of Pediatric Cardiology; Cardiac Surgery Committee for Development of Guidelines for Medical Treatment of Acute Kawasaki Disease. Guidelines for medical treatment of acute Kawasaki disease: Report of the Research Committee of the Japanese Society of Pediatric Cardiology and Cardiac Surgery (2012 revised version). Pediatrics International 2014;56(2):135-58.

G5 Australia, New Zealand

RHDAustralia (ARF/RHD writing group), National Heart Foundation of Australia, Cardiac Society of Australia and New Zealand. Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease (2nd edition). Casuarina, Australia: RHDAustralia; 2012.

G6* USA

Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis. Section 3. Management and treatment with phototherapy and systemic agents. Journal of the American Academy of Dermatology 2014;71(2):327-49.

G7* United Kingdom

Venning VA, Taghipour K, Mohd Mustapa MF, Highet AS, Kirtschig G. British Association of Dermatologists' guidelines for the management of bullous pemphigoid 2012. British Journal of Dermatology 2012;167(6):1200-14.

G8* Europe

Enk AH, Hadaschik EN, Eming R, Fierlbeck G, French LE, Girolomoni G, et al. European Guidelines (S1) on the use of high-dose intravenous immunoglobulin in dermatology. Journal of the European Academy of Dermatology and Venereology 2016: doi:10.1111/jdv.13725.

G9 United Kingdom

Oscier D, Dearden C, Erem E, Fegan C, Follows G, Hillmen P, et al. Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia. London, United Kingdom: British Society for Haematology; 2012.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Research%20Committee%20of%20the%20Japanese%20Society%20of%20Pediatric%20Cardiology%5BCorporate%20Author%5D

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cardiac%20Surgery%20Committee%20for%20Development%20of%20Guidelines%20for%20Medical%20Treatment%20of%20Acute%20Kawasaki%20Disease%5BCorporate%20Author%5D

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cardiac%20Surgery%20Committee%20for%20Development%20of%20Guidelines%20for%20Medical%20Treatment%20of%20Acute%20Kawasaki%20Disease%5BCorporate%20Author%5D

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sidbury%20R%5BAuthor%5D&cauthor=true&cauthor_uid=24813298

https://www.ncbi.nlm.nih.gov/pubmed/?term=Davis%20DM%5BAuthor%5D&cauthor=true&cauthor_uid=24813298

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cohen%20DE%5BAuthor%5D&cauthor=true&cauthor_uid=24813298

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cordoro%20KM%5BAuthor%5D&cauthor=true&cauthor_uid=24813298

https://www.ncbi.nlm.nih.gov/pubmed/?term=Berger%20TG%5BAuthor%5D&cauthor=true&cauthor_uid=24813298

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bergman%20JN%5BAuthor%5D&cauthor=true&cauthor_uid=24813298

https://www.ncbi.nlm.nih.gov/pubmed/?term=Highet%20AS%5BAuthor%5D&cauthor=true&cauthor_uid=23121204

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kirtschig%20G%5BAuthor%5D&cauthor=true&cauthor_uid=23121204

https://www.ncbi.nlm.nih.gov/pubmed/?term=Enk%20AH%5BAuthor%5D&cauthor=true&cauthor_uid=27406069

https://www.ncbi.nlm.nih.gov/pubmed/?term=Hadaschik%20EN%5BAuthor%5D&cauthor=true&cauthor_uid=27406069

https://www.ncbi.nlm.nih.gov/pubmed/?term=Eming%20R%5BAuthor%5D&cauthor=true&cauthor_uid=27406069

https://www.ncbi.nlm.nih.gov/pubmed/?term=Fierlbeck%20G%5BAuthor%5D&cauthor=true&cauthor_uid=27406069

https://www.ncbi.nlm.nih.gov/pubmed/?term=French%20LE%5BAuthor%5D&cauthor=true&cauthor_uid=27406069

https://www.ncbi.nlm.nih.gov/pubmed/?term=Girolomoni%20G%5BAuthor%5D&cauthor=true&cauthor_uid=27406069


REFERENCES

52

G10 United Kingdom

National Collaborating Centre for Cancer. Myeloma: diagnosis and management. London (UK): National Institute for Health and Care Excellence (NICE); 2016.

G11 USA

Monagle P, Chan AK, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Göttl U, et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141(2 Suppl):e737S-801S.

G12 Australia

Queensland Maternity and Neonatal Clinical Guidelines Program. Neonatal jaundice. Brisbane: Queensland Health; 2012.

G13 Canada

Barrington KJ, Sankaran K; Canadian Paediatric Society, Fetus and Newborn Committee. Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants. Paediatrics & Child Health 2007;12(Suppl B):1B-12B. Reaffirmed 2016.

G14 Italy

Romagnoli C, Barone G, Pratesi S, Raimondi F, Capasso L, Zecca E, et al. Italian guidelines for management and treatment of hyperbilirubinaemia of newborn infants ≥ 35 weeks' gestational age. Italian Journal of Pediatrics 2014;31;40(1):11.

G15 United Kingdom

NHS Blood and Transplant (NHSBT) Services. Neonatal alloimmune thrombocytopenia. London: NHSBT; 2014.

G16 USA

Rajasekhar A, Gernsheimer T, Stasi R, James AH. 2013 Clinical practice guide on thrombocytopenia in pregnancy. Washington, DC: American Society of Hematology; 2013.

G17* USA

Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. American Journal of Gastroenterology 2013;108(4):478-98.

G18 Spain

Working Group of the Clinical Practice Guideline on the Management of Invasive Meningococcal Disease. Clinical practice guideline on the management of invasive meningococcal disease. Madrid (Spain): Ministry of Health, Social Services and Equality; Aragon Institute for Health Sciences; 2013.

G19 United Kingdom

Royal College of Obstetricians and Gynaecologists (RCOG). Bacterial sepsis in pregnancy. London, United Kingdom: RCOG; 2012.

G20 United Kingdom

Royal College of Obstetricians and Gynaecologists (RCOG). Bacterial sepsis following pregnancy. London, United Kingdom: RCOG; 2012.

G21 Belgium

Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO clinical practice guideline for glomerulonephritis. Kidney International Supplements 2012;2(2):139-274.

G22 Canada

Kantor PF, Lougheed J, Dancea A, McGillion M, Barbosa N, Chan C, et al. Presentation, diagnosis, and medical management of heart failure in children: Canadian Cardiovascular Society guidelines. Canadian Journal of Cardiology 2013;29(12):1535-52.

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G23 USA

Go CY, Mackay MT, Weiss SK, Stephens D, Adams-Webber T, Ashwal S, et al. Evidence-based guideline update: medical treatment of infantile spasms: report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2012;78(24):1974-80.

G24* Europe

EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis, Andersen PM, Abrahams S, Borasio GD, de Carvalho M, Chio A, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) – revised report of an EFNS task force. European Journal of Neurology 2012;19(3):360-75.

G25* USA

Patwa HS, Chaudhry V, Katzberg H, Rae-Grant AD, So YT. Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2012;78(13):1009-15.

G26 United Kingdom

Dignan FL, Scarisbrick JJ, Cornish J, Clark A, Amrolia P, Jackson G, et al. Organ-specific management and supportive care in chronic graft-versus-host disease. British Journal of Haematology 2012;158(1):62-78.

G27 USA

Cincinnati Children's Hospital Medical Center. Evidence based clinical practice guideline for management of EBV-associated post-transplant lymphoproliferative disease (PTLD) in solid organ transplant. Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2012.

G28* United Kingdom

Emery V, Zuckerman M, Jackson G, Aitken C, Osman H, Pagliuca A, et al. Management of cytomegalovirus infection in haemopoietic stem cell transplantation. British Journal of Haematology 2013;162(1):25-39.

G29* United Kingdom

Nottingham Neonatal Service. Neonatal thrombocytopenia. Nottingham, United Kingdom: Nottingham University Hospitals NHS Trust; 2016.

G30 USA

Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017;27(3):315-89.

G31* Japan

Ichinose M, Sugiura H, Nagase H, Yamaguchi M, Inoue H, Sagara H, et al. Japanese guidelines for adult asthma 2017. Allergology International 66(2017):163-89.

G32 Europe

Straube A, Bronstein A, Straumann D. Nystagmus and oscillopsia. European Journal of Neurology 2012;19(1):6-14.

G33* Europe

Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, et al. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica 2016;101(7):803-11.

G34* USA

Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al.; Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. Journal of Allergy and Clinical Immunology 2015;136(5):e1-78.

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https://www.ncbi.nlm.nih.gov/pubmed/?term=Weiss%20SK%5BAuthor%5D&cauthor=true&cauthor_uid=22689735

https://www.ncbi.nlm.nih.gov/pubmed/?term=Stephens%20D%5BAuthor%5D&cauthor=true&cauthor_uid=22689735

https://www.ncbi.nlm.nih.gov/pubmed/?term=Adams-Webber%20T%5BAuthor%5D&cauthor=true&cauthor_uid=22689735

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ashwal%20S%5BAuthor%5D&cauthor=true&cauthor_uid=22689735

https://www.ncbi.nlm.nih.gov/pubmed/?term=Borasio%20GD%5BAuthor%5D&cauthor=true&cauthor_uid=21914052

https://www.ncbi.nlm.nih.gov/pubmed/?term=de%20Carvalho%20M%5BAuthor%5D&cauthor=true&cauthor_uid=21914052

https://www.ncbi.nlm.nih.gov/pubmed/?term=Chio%20A%5BAuthor%5D&cauthor=true&cauthor_uid=21914052

https://www.ncbi.nlm.nih.gov/pubmed/?term=Chaudhry%20V%5BAuthor%5D&cauthor=true&cauthor_uid=22454268

https://www.ncbi.nlm.nih.gov/pubmed/?term=Katzberg%20H%5BAuthor%5D&cauthor=true&cauthor_uid=22454268

https://www.ncbi.nlm.nih.gov/pubmed/?term=Dignan%20FL%5BAuthor%5D&cauthor=true&cauthor_uid=22533889

https://www.ncbi.nlm.nih.gov/pubmed/?term=Scarisbrick%20JJ%5BAuthor%5D&cauthor=true&cauthor_uid=22533889

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cornish%20J%5BAuthor%5D&cauthor=true&cauthor_uid=22533889

https://www.ncbi.nlm.nih.gov/pubmed/?term=Clark%20A%5BAuthor%5D&cauthor=true&cauthor_uid=22533889

https://www.ncbi.nlm.nih.gov/pubmed/?term=Amrolia%20P%5BAuthor%5D&cauthor=true&cauthor_uid=22533889

https://www.ncbi.nlm.nih.gov/pubmed/?term=Jackson%20G%5BAuthor%5D&cauthor=true&cauthor_uid=22533889

https://www.ncbi.nlm.nih.gov/pubmed/?term=Emery%20V%5BAuthor%5D&cauthor=true&cauthor_uid=23647436

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zuckerman%20M%5BAuthor%5D&cauthor=true&cauthor_uid=23647436

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https://www.ncbi.nlm.nih.gov/pubmed/?term=Aitken%20C%5BAuthor%5D&cauthor=true&cauthor_uid=23647436

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https://www.ncbi.nlm.nih.gov/pubmed/?term=Pagliuca%20A%5BAuthor%5D&cauthor=true&cauthor_uid=23647436

https://www.ncbi.nlm.nih.gov/pubmed/?term=Styczynski%20J%5BAuthor%5D&cauthor=true&cauthor_uid=27365460

https://www.ncbi.nlm.nih.gov/pubmed/?term=van%20der%20Velden%20W%5BAuthor%5D&cauthor=true&cauthor_uid=27365460

https://www.ncbi.nlm.nih.gov/pubmed/?term=Fox%20CP%5BAuthor%5D&cauthor=true&cauthor_uid=27365460

https://www.ncbi.nlm.nih.gov/pubmed/?term=Engelhard%20D%5BAuthor%5D&cauthor=true&cauthor_uid=27365460

https://www.ncbi.nlm.nih.gov/pubmed/?term=de%20la%20Camara%20R%5BAuthor%5D&cauthor=true&cauthor_uid=27365460

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cordonnier%20C%5BAuthor%5D&cauthor=true&cauthor_uid=27365460


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G35 Europe

Hirsch HH, Martino R, Ward KN, Boeckh M, Einsele H, Ljungman P. Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clinical Infectious Diseases 2013;56(2):258-66.

G36* Canada

Saskatchewan IVIG Optimization Program. Saskatchewan immune globulin (IVIG) optimization program guidelines. Saskatoon: Saskatchewan IVIG Optimization Program; 2015.

G37* USA

McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation 2017;135:e927-99.

G38* Japan

Murai H. Japanese clinical guidelines for myasthenia gravis: putting into practice. Clinical and Experimental Neuroimmunology 2015;6:21-31.

G39 United Kingdom

Creamer D, Walsh SA, Dziewulski P, Exton LS, Lee HY, Dart JKG, et al. UK guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis in adults 2016. Journal of Plastic, Reconstructive & Aesthetic Surgery 2016:69(6):e119-53.

G40* USA

Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-infected children. New York, NY: National Institutes of Health; 2017.

G41* United Kingdom

Baker RJ, Mark PB, Patel RK, Stevens KK, Palmer N. Renal association clinical practice guideline in post-operative care in the kidney transplant recipient. BMC Nephrology 2017;18(1):174.

G42 USA

National Comprehensive Cancer Network®. The NCCN Clinical Practice Guidelines in Oncology. Chronic lymphocytic leukemia/small lymphocytic lymphoma (Version 2.2018). Fort Washington, PA: National Comprehensive Cancer Network; 2017.

G43 United Kingdom

Sussman J, Farrugia ME, Maddison P, Hill M, Leite MI, Hilton-Jones D. Myasthenia gravis: Association of British Neurologists' management guidelines. Practical Neurology 2015; 15:199-206.

G44 Canada

BC Transplant. Clinical guidelines for kidney transplantation. Vancouver, Canada: Provincial Health Services Authority; 2017.

G45 USA

National Comprehensive Cancer Network®. The NCCN Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related infections (Version 2.2017). Fort Washington, PA: National Comprehensive Cancer Network; 2017.

https://www.ncbi.nlm.nih.gov/pubmed/?term=McCrindle%20BW%5BAuthor%5D&cauthor=true&cauthor_uid=28356445

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rowley%20AH%5BAuthor%5D&cauthor=true&cauthor_uid=28356445

https://www.ncbi.nlm.nih.gov/pubmed/?term=Newburger%20JW%5BAuthor%5D&cauthor=true&cauthor_uid=28356445

https://www.ncbi.nlm.nih.gov/pubmed/?term=Burns%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=28356445

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bolger%20AF%5BAuthor%5D&cauthor=true&cauthor_uid=28356445

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gewitz%20M%5BAuthor%5D&cauthor=true&cauthor_uid=28356445

https://www.ncbi.nlm.nih.gov/pubmed/?term=Creamer%20D%5BAuthor%5D&cauthor=true&cauthor_uid=27287213

https://www.ncbi.nlm.nih.gov/pubmed/?term=Walsh%20SA%5BAuthor%5D&cauthor=true&cauthor_uid=27287213

https://www.ncbi.nlm.nih.gov/pubmed/?term=Dziewulski%20P%5BAuthor%5D&cauthor=true&cauthor_uid=27287213

https://www.ncbi.nlm.nih.gov/pubmed/?term=Exton%20LS%5BAuthor%5D&cauthor=true&cauthor_uid=27287213

https://www.ncbi.nlm.nih.gov/pubmed/?term=Lee%20HY%5BAuthor%5D&cauthor=true&cauthor_uid=27287213

https://www.ncbi.nlm.nih.gov/pubmed/?term=Dart%20JKG%5BAuthor%5D&cauthor=true&cauthor_uid=27287213




https://www.ncbi.nlm.nih.gov/pubmed/?term=Baker%20RJ%5BAuthor%5D&cauthor=true&cauthor_uid=28571571

https://www.ncbi.nlm.nih.gov/pubmed/?term=Mark%20PB%5BAuthor%5D&cauthor=true&cauthor_uid=28571571

https://www.ncbi.nlm.nih.gov/pubmed/?term=Patel%20RK%5BAuthor%5D&cauthor=true&cauthor_uid=28571571

https://www.ncbi.nlm.nih.gov/pubmed/?term=Stevens%20KK%5BAuthor%5D&cauthor=true&cauthor_uid=28571571

https://www.ncbi.nlm.nih.gov/pubmed/?term=Palmer%20N%5BAuthor%5D&cauthor=true&cauthor_uid=28571571



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Branch DR, Hellberg Å, Bruggeman CW, Storry JR, Sakac D, Blacquiere M, et al. ABO zygosity, but not secretor or Fc receptor status, is a significant risk factor for IVIG-associated hemolysis. Blood 2018 131(7):830-5.

Cherin P, Marie I, Michallet M, Pelus E, Dantal J, Crave JC, et al. Management of adverse events in the treatment of patients with immunoglobulin therapy: A review of evidence. Autoimmunity Reviews 2016;15(1): 71-81.

Dalakas MC, Sonies B, Dambrosia J, Sekul E, Cupler E, Sivakumar K. Treatment of inclusion-body myositis with IVIg: A double-blind, placebo-controlled study. Neurology 1997;48(3):712-6.

Dantal J. Intravenous immunoglobulins: In-depth review of excipients and acute kidney injury risk. American Journal of Nephrology 2013;38:275-84.

Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D, et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell–mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. American Journal of Transplantation 2018;18:293-307.

Health Quality Ontario. Home-based subcutaneous infusion of immunoglobulin for primary and secondary immunodeficiencies: a health technology assessment. Ontario Health Technology Assessment Series 2017;17(16):1-86. Available from: http://www.hqontario.ca/evidence-to-improve-care/journal-ontario-health-technology-assessment-series (accessed 8 February 2018).

Huber AM, Kim AS, Reed AM, Carrasco R, Feldman BM, Hong SD, et al. Childhood Arthritis and Rheumatology Research Alliance consensus clinical treatment plans for juvenile dermatomyositis with persistent skin rash. Journal of Rheumatology 2017;44(1):110-6.

Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: Revisions to the 2007 definitions. Multiple Sclerosis 2013;19(10):1261-7.

Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, et al. Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clinical Infectious Diseases 2017;64(1):87-91.

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Pai MP, Paloucek FP. The origin of the "ideal" body weight equations. Annals of Pharmacotherapy 2000;34(9):1066-9.

Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurology 2018;17(2):162-73.


IND

EX

57

INDEX acute disseminated encephalomyelitis (ADEM), 25 adrenoleukodystrophy, 25 Aicardi-Goutières syndrome, 26 Alzheimer disease, 26 amyotrophic lateral sclerosis (ALS), 29 amyotrophy, diabetic, 28 anemia

autoimmune hemolytic (AIHA), 9 pure red cell aplasia (PRCA), 13

antiphospholipid syndrome catastrophic, 38 other than catastrophic, 38

arthritis juvenile idiopathic (JIA), systemic, 43 rheumatoid, 42

autism, 26 autoimmune hemolytic anemia (AIHA), 9 Behçet disease, 38 blistering diseases, autoimmune, 5

bullous pemphigoid, 5 epidermolysis bullosa acquisita, 5 IgA pemphigus, 5 linear IgA disease, 5 mucous membrane pemphigoid, 5 paraneoplastic autoimmune multiorgan

syndrome, 5 pemphigus foliaceus, 5 pemphigus herpetiformis, 5 pemphigus vulgaris, 5

bullous pemphigoid, 5 cataplexy, 31 chronic inflammatory demyelinating

polyneuropathy (CIDP), 27 chronic spontaneous urticaria. See chronic

idiopathic urticaria chronic suppurative lung disease, 15, 16 Churg-Strauss disease. See eosinophilic

granulomatosis with polyangiitis (EGPA) cicatricial pemphigoid. See mucous membrane

pemphigoid Clostridium difficile infection (CDI), recurrent, 17

with hypogammaglobulinemia. See hypogammaglobulinemia, secondary

coagulation factor inhibitors, 9

hemophilia, acquired, 9 inhibitors to factor IX in hemophilia B, 9 inhibitors to factor VIII in hemophilia A, 9 von Willebrand disease, acquired, 9

common variable immunodeficiency (CVID), 16 community-acquired respiratory virus (CARV)

lower respiratory tract infection (LRTI), 20 hematopoietic stem cell transplant (HSCT), 20 leukemia, 20 solid organ transplant, 20

upper respiratory tract infection (URTI), 19 hematopoietic stem cell transplant (HSCT), 19 leukemia, 19 respiratory syncytial virus (RSV), 19 solid organ transplant, 19

congenital heart block, autoimmune, 38 critical illness polyneuropathy (CIP), 28 Cytomegalovirus (CMV)

-induced pneumonitis in hematopoietic stem cell transplant (HSCT), 21

infection, prophylaxis of in hematopoietic stem cell transplant (HSCT),

20 in solid organ transplant, 20

cytopenias, autoimmune, secondary to chronic lymphocytic leukemia. See immune thrombocytopenic purpura (ITP); autoimmune hemolytic anemia (AIHA)

dermatitis, atopic, 5 dermatomyositis

adult, 39 pediatric, 39

Devic disease. See neuromyelitis optica eczema. See dermatitis, atopic encephalitis

anti-NMDA receptor, 26 paraneoplastic or sporadic autoimmune, 34

potassium channel antibody-associated encephalopathy, 34

Rasmussen. See Rasmussen syndrome encephalomyelitis

acute disseminated (ADEM), 25 myalgic. See chronic fatigue syndrome

encephalopathy Hashimoto, 28


IND

EX

58

potassium channel antibody-associated, 34 steroid-responsive, associated with autoimmune

thyroiditis. See Hashimoto encephalopathy eosinophilic granulomatosis with polyangiitis

(EGPA), 39 epidermolysis bullosa acquisita, 5 epilepsy, childhood, medically

refractory/intractable, 27 infantile spasms, 27 Landau-Kleffner syndrome, 27 Lennox-Gastaut syndrome, 27

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative

disorders (PTLD), 20 Evans syndrome. See autoimmune hemolytic

anemia (AIHA); immune thrombocytopenic purpura (ITP)

gastroenteritis syndromes. See gastrointestinal viruses, in solid organ transplant

gastrointestinal viruses, in solid organ transplant gastroenteritis syndromes other than Norovirus or

Rotavirus, 21 Norovirus or Rotavirus, 21

graft-versus-host disease in hematopoietic stem cell transplant (HSCT), 21 pulmonary, 24

granulomatosis with polyangiitis, 44 Graves disease, 45 Guillain–Barré syndrome (GBS), 28 Hashimoto encephalopathy, 28 hemochromatosis, neonatal, 12 hemolytic disease of the newborn (HDN), 10 hemolytic uremic syndrome (HUS), 10 hemophagocytic lymphohistiocytosis (HLH)

syndrome, 45 hemophilia

A, inhibitors to factor VIII, 9 acquired, 9 B, inhibitors to factor IX, 9

hemorrhage, fetal/neonatal. See thrombocytopenia, alloimmune

Henoch-Schonlein purpura. See IgA-associated small vessel vasculitis

heparin-induced thrombocytopenia (HIT), 11 HIV/AIDS, 17 hyper IgE. See immunodeficiency disorders,

primary (PID)

hyperhemolysis syndrome, in sickle cell disease, 13 hypogammaglobulinemia

acquired secondary to hematological malignancies. See hypogammaglobulinemia, secondary

secondary, 11, 15, See also immunodeficiency disorders, primary (PID) to hematopoietic stem cell transplant (HSCT),

15 iatrogenic immunodeficiency. See

hypogammaglobulinemia, secondary IgA paraproteinemia, neuropathy associated with,

27 IgA pemphigus, 5 IgA-associated small vessal vasculitis, 44 IgG paraproteinemia, neuropathy associated with,

27 IgG subclass deficiency, 16 IgM paraproteinemia, neuropathy associated with,

32 immune globulin (IG), administration

intravenous (IV) adverse effects, 4

hemolysis, 4 nephrotoxicity, 4

assessment by specialist, 3 dose, 3

adjusted body weight, calculations for, 3 maintenance therapy, 3 maximum, 3

in combination with other therapies, 4 off-label use, 4 rare diseases, use in, 4 rituximab, clearance of, 4 timing/sequencing of, 4

subcutaneous (SC), 4 immune thrombocytopenic purpura (ITP)


immunodeficiency disorders primary (PID), 16

hematopoietic stem cell transplant (HSCT) for, 22

inclusion body myositis (IBM), 40 infantile spasms, 27 juvenile idiopathic arthritis (JIA), systemic, 43, See

also macrophage activation syndrome (MAS) Kawasaki disease


IND

EX

59


Lambert-Eaton myasthenic syndrome (LEMS), 29 Landau-Kleffner syndrome, 27 Lennox-Gastaut syndrome, 27 leukemia

chronic lymphocytic, 9, 11 community-acquired respiratory virus (CARV)

lower respiratory tract infection (LRTI), 20 upper respiratory tract infection (URTI), 19

linear IgA disease, 5 livedoid vasculopathy, 7 lupus, neonatal. See congenital heart block,

autoimmune Lyell syndrome. See toxic epidermal necrolysis

(TEN) lymphoma, 11 macrophage activation syndrome (MAS), 41 microscopic polyangiitis, 44 Moersch-Woltmann syndrome. See stiff person

syndrome motor neuron disease, 29 mucocutaneous lymph node syndrome. See

Kawasaki disease mucous membrane pemphigoid, 5 multifocal motor neuropathy (MMN), 29 multiple sclerosis (MS), 30 myasthenia gravis (MG)

mild generalized, 31 moderate to severe generalized, 30

myasthenic crisis, 30 ocular, 31

myelitis acute flaccid, 25 transverse, 37

myeloma, 11 myositis

dermato- adult, 39 pediatric, 39

inclusion body (IBM), 40 poly-


narcolepsy, 31 necrotizing fasciitis, 17

with hemodynamic compromise. See toxic shock syndrome (TSS)

NEMO (nuclear factor kB essential modulator) syndrome. See immunodeficiency disorders, primary (PID)

neuritis, acute optic, 25, See also neuromyelitis optica

neuromyelitis optica, 31 neuropathy

associated with IgM paraproteinemia, 32 axonal, 32 demyelinating with anti-MAG, 32 demyelinating without anti-MAG, 32

multifocal motor (MMN), 29 neuropathic pain, 32 poly-

chronic inflammatory demyelinating (CIDP), 27 associated with IgA paraproteinemia, 27 associated with IgG paraproteinemia, 27

critical illness (CIP), 28 polyneuropathy, organomegaly,

endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome, 35

neutropenia, autoimmune, 9 Norovirus. See gastrointestinal viruses, in solid

organ transplant ophthalmopathy. See Graves disease opsoclonus-myoclonus ataxia (OMA)


PANDAS. See pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS)

paraneoplastic syndromes autoimmune multiorgan, 5 neurological, 33

pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS), 34

pemphigus foliaceus, 5 pemphigus herpetiformis, 5 pemphigus vulgaris, 5 POEMS syndrome. See polyneuropathy,

organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome

polymyositis adult, 41 pediatric, 42


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60

polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome, 35

postpolio syndrome, 35 post-transfusion purpura thrombocytopenia (PTP),

13 pretibial myxedema. See Graves disease pure red cell aplasia (PRCA), 13 pyoderma gangrenosum, 7 Rasmussen syndrome, 35 rejection

antibody-mediated (ABMR) kidney transplant, 22 solid organ (other than kidney) transplant, 24

non-active kidney transplant, 23

T-cell mediated (TCMR) kidney transplant, 23 solid organ (other than kidney) transplant, 24

rheumatoid arthritis, 42 Rotavirus. See gastrointestinal viruses, in solid

organ transplant scleroderma, 42 scleromyxedema, 7 sepsis, neonatal, prophylaxis of, 17 severe combined immunodeficiency (SCID). See

immunodeficiency disorders, primary (PID) sickle cell disease, hyperhemolysis syndrome in, 13 Sjogren syndrome, 43 specific antibody deficiency, 16 Stevens-Johnson syndrome (SJS), 8 stiff person syndrome, 35 Still disease, adult. See juvenile idiopathic arthritis

(JIA), systemic Susac syndrome, 36 Sydenham chorea, 36 systemic capillary leak syndrome (SCLS), 45 systemic lupus erythematosus (SLE), 43 thrombocytopenia

alloimmune feto-maternal (FMAIT), 10 neonatal (NAIT), 10

heparin-induced (HIT), 11 immune thrombocytopenic purpura (ITP)

adult, 11 acute, 11 chronic, 11

HIV-associated, 11 in pregnancy, 11 lupus-associated. See lupus erythematosus refractory, 11

pediatric, 12 acute, 12 chronic, 12

in hemophagocytic lymphohistiocytosis (HLH) syndrome, 45

neonatal, secondary to maternal autoimmune disorders, 13

post-transfusion purpura (PTP), 13 thrombotic thrombocytopenic purpura (TTP), 14

thrombotic thrombocytopenic purpura (TTP), 14 thyroiditis, autoimmune,steroid-responsive

encephalopathy associated with. See Hashimoto encephalopathy

toxic epidermal necrolysis (TEN), 8 toxic shock syndrome (TSS)

staphylococcal, 17 streptococcal, 17

transplant hematopoietic stem cell (HSCT), 11, 15

allogeneic Cytomegalovirus (CMV)-induced

pneumonitis, 21 graft-versus-host disease, 21

autologous, 21 with humoral deficiency. See

hypogammaglobulinemia, secondary community-acquired respiratory virus (CARV)


Cytomegalovirus (CMV) infection, prophylaxis of, 20

Epstein-Barr virus (EBV), 20 for immunodeficiency disorders, primary (PID),

22 kidney

antibody-mediated rejection (ABMR), 22 non-active rejection, 23 T-cell mediated rejection (TCMR), 23

solid organ community-acquired respiratory virus (CARV)


Cytomegalovirus (CMV) infection, prophylaxis of, 20

Epstein-Barr virus (EBV), 20 gastrointestinal viruses, 21


IND

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61

solid organ (other than kidney), 24 antibody-mediated rejection (ABMR), 24 graft dysfunction, 24 sensitized, 24 T-cell mediated rejection (TCMR), 24

transverse myelitis, 37 urticaria

chronic idiopathic, 6 severe autoimmune-mediated, 6

uveitis, immune-mediated, 40 varicella-zoster virus (VZV), prophylaxis of, 18 vasculitic syndromes, 44

Behçet disease, 38 eosinophilic granulomatosis with polyangiitis

(EGPA), 39 granulomatosis with polyangiitis, 44

IgA-associated small vessel vasculitis, 44 Kawasaki disease


microscopic polyangiitis, 44 von Willebrand disease, acquired, 9 Wegener granulomatosis. See granulomatosis with

polyangiitis WHIM (warts, hypogamma-globulinemia,

immunodeficiency, myelokathexis) syndrome. See immunodeficiency disorders, primary (PID)

Wiskott-Aldrich syndrome. See immunodeficiency disorders, primary (PID)

X-linked agammaglobulinemia (XLA). See immunodeficiency disorders, primary (PID)

Criteria for the Clinical Use of Immune Globulin · 2018. 5. 31. · Suggested citation: Prairie Collaborative Immune Globulin Utilization Management Framework Project. Criteria for

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