Fethi MELLOULI, Registry National Center for Bone Marrow of Tunis. Tunisia.
Translated by Jeddane L (Morocco)

Primary immunodeficiencies (PID) are a large family of 200 diseases of which 176 are currently characterized genetically. [1] Polyvalent immunoglobulins are prominent in their care. They are the cure of the predominant antibody deficiencies. What are the main forms of immunoglobulins?How to administrate them? How effective are they? What are the main complications associated with their use? And how to fix it?

Main forms of immunoglobulins:

Immunoglobulin preparations consist of Human immunoglobulin G (IgG) obtained from a pool of plasmas from over thousand healthy individuals. Several routes of administration are possible. [2] Historically, the intramuscular route was the first to be used. It has the disadvantage of the small amount that can be injected and above all, the local proteolytic degradation in muscle immunoglobulins, rendering it ineffective. The second path and the most used is the intravenous route. It has the advantage of acting immediately, without volume limits to be injected. Currently, we are seeing the use of increasingly widespread subcutaneous immunoglobulin in developed countries. They are used at home either by subcutaneous bolus or by subcutaneous infusion pump. This route has the advantage of stable IgG levels in the blood, to be well tolerated and to improve the quality of life by reducing the number of hospitalizations [3]. However, their initiation requires certain conditions such as education of patient and his entourage, keeping a health record booklet, knowledge of major adverse events (AEs) and the immediate conduct in their occurrence and above all, presence of a referent physician clearly identified and quickly available when needed.

Administration of IV immunoglobulins:

After a loading dose of 0.8 to 1 g / kg / week for 2 weeks [2], the average maintenance doses of immunoglobulins are of 400 mg / kg / dose every 3 to 4 weeks. These doses are then adjusted, depending on the clinical efficacy and through of residual IgG. The immunoglobulin infusion should be slow. We must start with low flow rates of 0.5 ml / kg / hour, which will increase thereafter to reach cruising speed, which should never exceed the rate of 4 ml / kg / hour. These IV immunoglobulins are often very well tolerated. [4]

Effectiveness of IV immunoglobulins:

The effectiveness of immunoglobulins is assessed on the clinic (number of infectious episodes that required the use of antibiotics, days of hospitalization, trophic state of the patient, ...), biology (persistent inflammatory disease) and radiology (CT of the lungs and sinuses, in assessing the stabilization of bronchiectasis or chronic sinusitis). For the efficiency of this replacement therapy, the through levels of IgG must be greater than 6 g / l [5]. This rate should be higher (greater than 8 g / l) if bronchiectasis or chronic sinusitis is associated.

Major complications associated with the use of IV immunoglobulin:

Adverse events (AEs) associated with IV immunoglobulin occur in a small proportion of patients [6-9]. They are usually moderate to minor [6-8]. Some AEs occur occasionally [9], such as headache, fever, chills, nausea, vomiting, hypo- or hypertension, back pain, arthralgia, myalgia. Other AEs were uncommon or rare, such as eczema-like skin reactions, regressive hemolysis and / or hemolytic anemia, leuco-neutropenia, transient increase in transaminases (very rare).

Severe AEs are represented by increased creatinine level [10], aseptic meningitis reaction [6], anaphylactic shock [6-8], and deep vein or arterial thrombosis [11]. Rare cases of acute renal failure (ARF) have been reported during treatment with IVIg. Their incidence is estimated at less than 1% [12]. The role of the stabilizer is often mentioned and IgG containing sucrose are more likely to cause ARF, however the IV IgG stabilized with sucrose are also the most commonly used [13].

How to manage these complications?

Most side effects are predictable because they are dependent on the rate of infusion. Indeed, if that rate is greater than 4 ml / kg / hour, AEs, such as chills, fever, headache, occur more frequently.

Risk factors of adverse effects are especially identified for severe AEs, e.g, anaphylactic shock occurs mostly in IgA deficient patients with antibodies against IgA. Aseptic meningitis are favored by a history of migraine [6-8.14], low blood pressure [6-8], or dehydration [7]. Thrombosis is favored by hyper blood viscosity status, thrombosis history, thrombophilia, reduced mobility and situations at risk of dehydration.

Prevention of minors AEs is through the adjustment of the infusion rate according to the clinical tolerance [8,9]. In patients with primary immunodeficiency with complete IgA deficiency, it is necessary to search for IgA antibodies prior to administration of the first infusion of IVIg. If present, it is then necessary to prescribe IVIG devoid of IgA, perform the infusion with a emergency trolley at the bedside and adjust the infusion rate. The prevention of thrombosis and aseptic meningitis pass by hyper hydration of the patient 2 to 3 hours before and after the perfusion with normal saline, adjusting the rate of infusion and fractionation of the dose on 5 days if possible.

To prevent the occurrence of ARF in patients at risk [12], you should measure the clearance of creatinine before IVIG, temporarily stop any diuretic, ensure good hydration, avoid concomitant use of other nephrotoxic drugs, reduce the rate of infusion of IVIg by half, reaching 1-2 ml / kg / hour maximum, space IVIG treatments if possible. These ARF are regressive in more than 90% of cases.


  1. Al Herz W, Bousfiha A, Casanova JL et al. Primary immunodeficiency diseases : an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front immunol 2011 ;2:54.
  2. Mellouli F. le traitement des déficits immunitaires primitifs. Revue de médecine pratique 2014 ;37:28-9.
  3. Gardelf A, Cicolary U, Math D et al. Children and adults with primary antibody deficiencies gain quality of life by subcutanous IgG self infusions at home. J Allergy Clin Immunol 2004 ;115:936-42.
  4. Brennan VM, Salomé Bentley NJ, Chapel HM. Prospective audit of adverse reactions occuring in 459 primary antibody deficient patients receiving intra venous immunoglobulin. Clin Exp Immunol 2011 ;133 :247-51.
  5. Ksouri H, Mellouli F, Barbouche R et al. Apport du traitement substitutif par immunoglobulines au cours des agammaglobulinémies : à propos de 10 cas. Arch Pédiatr 2006 ;13 :1034-9.
  6. Looney RJ, Huggins J. Use of intravenous immunoglobulin. Best Practice & Reseach Clincal Haemotology 2006 ;19 :2-251.
  7. Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Trasfusion Medicine Reviews2003 ;17(4) :241-51.
  8. Hamrock DJ. Adverse events associated with intravenous immunoglobulin therapy. Int Immunopharmacol2006 ;6 :535-42.
  9. Misbah SA, Chapel HM. Adverse effects of intravenous Immunoglobulin. Drug safety 1993 ;9(4) :254-62.
  10. Fakhouri F. Immunoglobulines intraveineuses et insuffisance rénale aigue : mécanisme et prévention. Rev Med Interne2007 ;28 :4-6.
  11. Marie I, Levesque H. Risque thrombogène des immunoglobulines intraveineuses : mythe ou réalité ? Rev Med Interne2006 ;27(12) :905-8.
  12. Fakhouri Hors série n 1 Revue de médecine interne Mai 2007.
  13. Schiavotto C, Ruggeri M, Rodeghiero F. Adverse reactions after high dose intravenous immunoglobulin : incidence in 83 patients treated for idiopathic thrombocytopenic purpura (ITP) and review of the literature. Haematologica1993 ;8 :35-40.
  14. Sekul EA, Cupler EJ, Dalakas MC. Aseptic meningitidis associated with high dose intravenous immunoglobulin therapy : frequency and risk factors. Ann Intern Med1994 ;121 :259-62.


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