Consistent with recommendations of the Working Group on Antiretroviral Therapy of the National Pediatric HIV Resource Center IVIG is considered medically necessary in children with HIV-infection who meet any of the following criteria:

1. Those with hypogammaglobulinemia, i.e., serum IgG concentration less than 250 mg/dL;  
2. Those with recurrent serious bacterial infections, i.e., defined as two or more infections such as bacteremia, meningitis, or pneumonia in a 1-year period;  
3. Those who fail to form antibodies to common antigens, such as measles, pneumococcal, and/or Haemophilus influenzae type b vaccine;  
4. Those living in areas where measles is highly prevalent and who have not developed an antibody response after two doses of measles, mumps, and rubella virus vaccine live;  
5. Single dose for HIV-infected children who are exposed to measles;  
6. HIV-infected children with chronic bronchiectasis that is suboptimally responsive to antimicrobial and pulmonary therapy.

Symmetric or focal neurologic deficits with slowly progressive or relapsing course over 2 months or longer (with neurophysiological abnormalities). 

Note:  A metaanalysis comparing the efficacy if IVIG, plasma exchange, and oral glucocorticoids found equivalence between all three, at least within the first 6 weeks of therapy (Van Schaik, et al., 2002). IVIG is considered under accepted guidelines as the preferred treatment, particularly in children, when there is difficulty with venous access for plasmapheresis, and those susceptible to the complications of long-term corticosteroid therapy (Orange, et al., 2006).

Persons typically respond to IVIG or plasma exchange within the first several weeks of treatment and may demonstrate sustained improvement for many weeks or months.  Relapses may require periodic isolated treatments with a single dose of IVIG or single plasma exchange.  If a person responds successfully to infrequent booster treatments of either IVIG or plasma exchange, it is reasonable to maintain this form of treatment rather than adding corticosteroids or other immunosuppressants.

IgG level less than 600mg/dL; and:

1. 1 severe bacterial infection within preceding 6 months or 2 or more bacterial infections in one year; or  
2. Evidence of specific antibody deficiency.

Dermatomyositis, Polymyositis

(includes Juvenile)

1. Members presenting at least one item from the 1st criterion and four items from the 2nd through 9th criteria are said to have dermatomyositis.  Patients presenting no items from the 1st criterion and at least four items from the 2nd through 9th criteria are said to have polymyositis.

   1. Skin lesions 

      1. Heliotrope rash (red purple edematous erythema on the upper palpebra) 
      2. Gottron's sign (red purple keratotic, atrophic erythema, or macules on the extensor surface of finger joints) 

      3. Erythema on the extensor surface of extremity joints: slightly raised red purple erythema over elbows or knees 

   2. Proximal muscle weakness (upper or lower extremity and trunk) 
   3. Elevated serum CK (creatine kinase) or aldolase level 
   4. Muscle pain on grasping or spontaneous pain 
   5. Myogenic changes on EMG (short-duration, polyphasic motor unit potentials with spontaneous fibrillation potentials) 
   6. Positive anti-Jo-1 (histadyl tRNA synthetase) antibody 
   7. Non-destructive arthritis or arthralgias 
   8. Systemic inflammatory signs (fever: more than 37° C at axilla, elevated serum CRP level or accelerated ESR of more than 20 mm/h by the Westergren method) 

   9. Pathological findings compatible with inflammatory myositis (inflammatory infiltration of skeletal evidence of active regeneration may be seen

   AND

2. Member has severe active illness; and

3. Member is intolerant or refractory to 1st and 2nd line therapies:  

   1. 1st line therapy - Corticosteroids (e.g., prednisone);  
   2. 2nd line therapy - Immuno-suppressants (e.g., methotrexate, azathioprine, cyclophosphamide, and cyclosporine).  

Maternal and paternal platelet typing reveals the father has a platelet antigen that the mother lacks and the mother has detectable antibodies to this antigen (to HPA 1a are the most common cause of FAIT); and

1. At 20 weeks or later, cordocentesis reveals fetal platelets less than 20 x 1000/mL(3); or  
2. Previous pregnancy affected by FAIT.

Guillain Barre Syndrome (GBS) - a.k.a. acute infective polyneuritis (includes GBS variants: Miller-Fisher syndrome [MFS], pan autonomic polyneuropathy,

acute pandysautonomia, acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN))

1. Severe GBS with significant weakness such as inability to stand or walk without aid, respiratory or bulbar weakness, or Miller-Fisher syndrome (MFS); and  
2. The disorder has been diagnosed during the first 2 weeks of the illness; and  
3. IVIG is initiated within one month of symptom onset.  Note: Based on the 2003 AAN guidelines, IVIG should usually be initiated within 2 weeks and no longer than 4 weeks of onset of neuropathic symptoms.

HIV-associated Thrombocytopenia

- Adult

1. Significant bleeding in thrombocytopenic patients or platelet count less than 20,000/ul; and  
2. Failure of RhIG in Rh-positive patients.

HIV-associated Thrombocytopenia

- Pediatric

Infants and children < 13 years of age whose IgG level is < 400 mg/dL; and

1. 2 or more bacterial infections in a 1-year period despite antibiotic chemoprophylaxis with TMP-SMZ or another active agent; or  
2. Child has received 2 doses of measles vaccine and lives in a region with a high prevalence of measles; or  
3. Member has HIV-associated thrombocytopenia despite antiretroviral therapy; or  
4. Member has chronic bronchiectasis that is suboptimally responsive to antimicrobial and pulmonary therapy; or  
5. T4 cell count is greater than or equal to 200/mm3.

1. Other causes of thrombocytopenia have been ruled out by history and peripheral smear; and

   Unresponsive to corticosteroid therapy; and

   Management of acute bleeding due to severe thrombocytopenia (platelet counts less than 30,000/ul); or  

2. To increase platelet counts prior to invasive major surgical procedures (e.g., splenectomy), or  
3. To defer or avoid splenectomy; or  
4. In members with severe thrombocytopenia (platelet counts less than 20,000/ul) considered to be at risk for intracerebral hemorrhage.

Acute ITP:

1. IVIG as initial therapy if platelet count < 20,000/ul, especially when member has emergency bleeding or is at risk for severe life-threatening bleeding; or  
2. Persons with severe thrombo-cytopenia (platelet counts less than 20,000/ul) considered to be at risk for intracerebral hemorrhage.

Note:  IVIG not indicated if only mild manifestations of bleeding.

Chronic ITP:

In high risk persons when platelet count low or person symptomatic; and

1. Failure of other therapies, or  
2. Member is a high risk for post-splenectomy sepsis.

1. Age of 10 years or older; and  
2. Duration of illness of greater than six months; and  
3. No concurrent illness/disease explaining thrombocytopenia; and   
4. Prior treatment with corticosteroids and splenectomy has failed or member is at high risk for post-splenectomy sepsis. 

1. Refractory to steroids with platelet counts < 10,000/ul in the third trimester; or  
2. Platelet counts < 30,000/ul associated with bleeding before vaginal delivery or C-section; or  
3. Pregnant women who have previously delivered infants with autoimmune thrombocytopenia; or  
4. Pregnant women who have platelet counts less than 50,000/ul during the current pregnancy; or  
5. Pregnant women with past history of splenectomy.

To prevent or modify recurrent bacterial or viral infections (e.g., CMV) in members with iatrogenically induced, or disease associated immunosuppression (IgG < 400 mg/dL) with one of the following:

1. Solid organ transplants or extensive surgery with immunosuppression (Note: In particular, IVIG may be medically necessary in persons undergoing multiple courses of plasmapheresis as a treatment for allograft rejection or for other indications; these persons may receive IVIG at the completion of therapy if their IgG level is less than 400 mg/dL); or
2. Hematological malignancy; or  
3. Extensive burns; or  
4. Collagen-vascular disease.

Diagnosis must be established - no specific lab test - diagnosis is established by meeting the following criteria:

1. Fever present for at least five days; and  

2. Four of the following five conditions are met:  

   1. Mucous membrane changes such as a red tongue and dry fissured lips;  
   2. Swelling of the hands and feet;  
   3. Enlarged lymph nodes in the neck;  
   4. Diffuse red rash covering most of the body;  
   5. Redness of the eyes.

No response to anticholinesterases and Diaminopyridine); and

1. Used as an alternative to plasma exchange if weakness is severe; or  
2. When there is difficulty with venous access for plasmapheresis. 

1. Treatment of acute myasthenic crisis with decompensation (respiratory failure, or disabling weakness requiring hospital admission); and
2. Other treatments have been unsuccessful or are contraindicated (e.g., azathioprine, cyclosporine, and cyclophosphamide).

Note: For management of myasthenic crises, IVIG is administered over 2 to 5 days.  Use of IVIG as maintenance therapy is considered experimental and investigational.

1. Presence of Anti-GAD antibody; and  
2. Benzodiazepines (e.g., Valium) and/or Baclofen, phenytoin, clonidine, tizanidine have failed.

1. "Plateau Phase" MM (> 3 months since diagnosis); and 
2. IgG level < 600mg/dL; and  
3. 2 or more significant infections in last year or a single life threatening infection; or 

Evidence of specific antibody deficiency.

Multiple Sclerosis (MS) -  Relapsing-remitting

(not primary or secondary progressive MS)

1. Severe manifestations of relapsing-remitting MS (not primary or secondary progressive MS); and  
2. Standard approaches (i.e., interferons – Betaseron, Avonex, Rebif) have failed, become intolerable, or are contraindicated.

Erythrovirus (formerly parvovirus) B19 Infection, Chronic, with Severe Anemia

(Pure Red Cell Aplasia)

1. The diagnosis has been proven by biopsy and confirmed by pathology report; and  
2. The condition is rapidly progressing, extensive or debilitating; and  
3. Corticosteroids, immuno-suppressive agents have failed or the member has experienced significant complications from standard treatment, such as diabetes or steroid-induced osteoporosis. 

1. Decreased platelets (usually < 10,000/ul); and 
2. 2 - 14 days post transfusion with bleeding.

Primary Humoral Immunodeficiencies

1. Selective IgM Immunodeficiency  
2. Congenital hypogamma-globulinemia  
3. Immunodeficiency with near/normal IgM (absent IgG, IgA) – a.k.a. Hyper IgM syndrome  
4. Other deficiency of humoral immunity  
5. Severe combined immunodeficiency disorders (e.g., X-SCID, jak3, ZAP70, ADA, PNP, RAG defects, Ataxia Telangiectasia,  DiGeorge syndrome, common variable immunodeficiency

1. Agammaglobulinemia (total IgG < 200 mg/dL or infants with BTK gene and/or absence of B lymphocytes)); or  
2. Persistent hypogammaglobulinemia(total IgG < 400 mg/dL) with recurrent bacterial infections and/or lack of response to protein or polysaccharide antigens (inability to make IgG antibody against diphtheria and tetanus toxoids, pneumococcal polysaccharide vaccine, or both):
   
   
   1. Serum antibody titres to tetanus and/or diphtheria should be obtained prior to immunization with diphtheria and/or tetanus vaccine and three to four weeks after immunization. An inadequate response is defined as less than a fourfold rise in antibody titre and lack of protective antibody level (as defined by laboratory performing the assay); and
   2. Serum antibody titres to pneumococcus should be measured prior to immunization and three to six weeks after immunization with polyvalent pneumococcal polysaccharide vaccine (e.g., Pneumovax).  An inadequate response is defined as less than a 4-fold rise in titer over baseline in at least one serotype tested and lack of protective antibody level (i.e., specific IgG concentration less than 1.3 mcg/ml); or  
      
      
3. Selective IgG subclass deficiency (see criteria below); or
4. Normal total IgG levels with severe polysaccharide nonresponsiveness and evidence of recurrent severe difficult-to-treat infections (e.g., recurrent otitis media, bronchiectasis, recurrent infections requiring IV antibiotics, multiple antibiotic hypersensitivities, chronic or recurrent sinusitis) (see table below) with a documented requirement for antibiotic therapy:
   
   
   1. Member has unexplained recurrent or persistent severe bacterial infections despite adequate treatment, including all of the following:
      
      
      1. Aggressive management of other conditions predisposing to recurrent sinopulmonary infections (eg, asthma, allergic rhinitis);
      2. Prophylactic antibiotics;
      3. Increased vigilance and appropriate antibiotic therapy for infections; and
      4. Immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines.
         
         
   2. Serum antibody titres to pneumococcus should be measured prior to immunization and three to six weeks after immunization with polyvalent pneumococcal polysaccharide vaccine (e.g., Pneumovax); at least 14 polysaccharide antigens should be tested. 
   3. Polysaccharide nonresponsiveness is defined as less than 4-fold rise in antibody titer and lack of protective antibody titer (specific IgG antibody titer less than 1.3 mcg/ml) in greater than 30 percent of antigens tested (more than 50 percent in children ages 2 to 5 years).
   4. Further evidence of infection, including sinus and lung imaging, complete blood counts, C-reactive protein measurement, and erythrocyte sedimentation rate determination, may be required to support the need for IVIG supplementation.
   5. IVIG should be discontinued and the medical necessity of IVIG should be reevaluated 1 year after initiating therapy and every two years thereafter by reassessing immune response to protein and polysaccharide antigens. Immune response should be reevaluated at least 5 months after discontinuation of IVIG.  IVIG should also be discontinued at that time if the number and/or severity of infections have not been reduced, as not all persons with polysaccharide nonresponsiveness benefit from IVIG.

The use of IVIG may not be beneficial in certain secondary immunodeficiency states; correction of the underlying condition is the preferred approach.

For children whose symptoms do not improve with antiepileptic drugs and corticosteroids.

1. Deficiency of one or more IgG subclasses to levels less than two standard deviations below the age-specific mean (see table below). These levels should be assessed on at least two occasions while the patient is free of infections; and
2. Member has unexplained recurrent or persistent severe bacterial infections despite adequate treatment, including all of the following:
   
   
   1. Aggressive management of other conditions predisposing to recurrent sinopulmonary infections (eg, asthma, allergic rhinitis);
   2. Prophylactic antibiotics;
   3. Increased vigilance and appropriate antibiotic therapy for infections; and
   4. Immunization with conjugate vaccines in patients who have not responded to polysaccharide vaccines.
      
      
3. Member has demonstrated an inability to mount an adequate response to protein and polysaccharide antigens, as determined by the following criteria:
   
   
   1. Member has documented inability to mount an antibody response to protein antigens:  Serum antibody titres to tetanus and/or diphtheria should be obtained prior to immunization with diphtheria and/or tetanus vaccine and three to four weeks after immunization. An inadequate response is defined as less than a fourfold rise in antibody titre  and lack of protective antibody level (as defined by laboratory performing the assay); and
   2. Member has documented inability to mount an adequate antibody response to polysaccharide antigens.  Serum antibody titres to at least 14 pneumococcus serotypes should be measured prior to immunization and three to six weeks after immunization with polyvalent pneumococcal polysaccharide vaccine (e.g., Pneumovax).  An inadequate response is defined as less than a 4-fold rise in titer over baseline in at least 30 percent of serotypes tested (in at least 50 percent of serotypes tested in children ages 2 to 5 years) and lack of protective antibody level (i.e., specific IgG concentration less than 1.3 mcg/ml).

   Note: Response to polysaccharide antigens is not reliable in children less than 2 years of age.

4. IVIG should be discontinued and the medical necessity of IVIG should be reevaluated 1 year after initiating therapy and every two years thereafter by reassessing immune response to protein and polysaccharide antigens. Immune response should be reevaluated at least 5 months after discontinuation of IVIG.  IVIG should also be discontinued at that time if the number and/or severity of infections have not been reduced, as not all persons with selective IgG subclass deficiencies benefit from IVIG. 

Members with severe active SLE for whom first- and second-line therapies have been unsuccessful, have become intolerable, or are contraindicated.  

Note: Standard first-line therapy of active SLE include non-steroidal anti-inflammatory drugs, followed by low-dose corticosteroids and antimalarial compounds. Second-line therapeutic alternatives are the cytotoxic agents methotrexate, azathioprine, or cyclophosphamide.

Acquired factor VIII inhibitors
Acquired von Willebrand's disease
Acute lymphoblastic leukemia
Acute myeloid leukemia
Acute optic neuritis
Adrenoleukodystrophy
Alzheimer’s disease
Amyotrophic lateral sclerosis
Angioedema
Antiphospholipid syndrome
Aplastic anemia
Asthma
Autism
Autoimmune autonomic neuropathy
Autoimmune chronic urticaria
Autoimmune inner ear disease
Autoimmune liver disease
Behçet's syndrome
Cardiomyopathy, acute
Chronic fatigue syndrome
Chronic sinusitis
Clostridium difficile colitis
Congenital heart block
Convulsive syndromes
Critical illness polyneuropathy
Cystic fibrosis
Dermatosis, autoimmune
blistering
Diabetes mellitus
Diamond-Blackfan anemia
Dysautonomia, acute idiopathic
Eczema
Encephalopathy
Endotoxemia
Epilepsy

Goodpasture’s syndrome
Hemolytic transfusion reaction
Hemolytic-uremic syndrome
Hemophagocytic syndrome
HTLV-1 associated myelopathy
Idiopathic lumbosacral
plexopathy
Immune-mediated neutropenia
Inclusion body myositis
Intractable seizures
Leukemia, acute lymphoblastic
Lower motor neuron syndrome
Malignancy, non-hematologic
Multiple sclerosis - primary
progressive or secondary types
Myalgia, myositis, unspecified
Myalgic encephalomyelitis
Myelopathy, HTLV-I associated
Necrotizing enterocolitis
Neonatal lupus syndromes
Neonatal sepsis (prophylaxis)
Nephritic syndrome
Nephropathy, membranous
Nephrotic syndrome
Neuromyelitis optica (Devic’s
disease)
Neuromyotonia (Isaacs’ syndrome)
Neurosarcoidosis
Non-immune thrombocytopenia
Ophthalmopathy, euthyroid
Oral use of IVIG for any
indication
Orthostatic tachycardia syndrome
Otitis media, recurrent
Paraneoplastic cerebellar
degeneration
Paraneoplastic syndromes other than neuroblastoma
Paraproteinemic neuropathy (IgM variant
Parkinson’s disease

Pediatric autoimmune
neuropsychiatric disorders
associated with streptococcal
infection (PANDAS)
POEMS syndrome **
Polyarteritis nodosa
Polyneuritis cranialis
Progressive lumbosacral
plexopathy
Pyoderma gangrenosum
Radiculoneuritis, Lyme
Recurrent otitis media
Recurrent fetal loss
Red cell aplasia not due to erythrovirus B19
Rheumatic fever, carditis
Refractoriness to platelet
transfusion
Reiter's syndrome
Renal failure, acute
Rheumatoid arthritis (adult and
juvenile)
Scleroderma
Selective isolated IgA immunodeficiency
Sensory neuropathy
Still's disease
Sydenham's chorea
Systemic vasculitides
Thrombocytopenia (non-immune)
Thrombotic thrombocytopenic
purpura (TTP)
Tic disorders
Transverse myelopathy/myelitis
Uveitis
Vasculitis associated with other
connective tissue diseases
Viral myocarditis
Vogt-Koyanagi-Harada syndrome
Wegener’s granulomatosis