- Author: Terry W Chin, MD, PhD; Chief Editor: Harumi Jyonouchi, MD more...
Further Outpatient Care
Avoid live viral vaccines for patients with agammaglobulinemia and any siblings or other children in the household because the attenuated virus is excreted and poses a threat to immunodeficient patients. The risk of vaccine-associated paralytic poliomyelitis increases 7000 times more than the normal risk of 1 case per 750,000. If the patient has been exposed to a live viral vaccine, or if the live poliovirus has been given, obtain a stool culture to determine if the patient has the attenuated virus. Although most laboratories can determine the presence of an enterovirus, poliovirus identification requires sending the viral specimen to a state referral laboratory. Administer intravenous immunoglobulin (IVIG) and maintain serum immunoglobulin (Ig)G levels higher than 500 mg/dL.
Frequent monitoring of the patient's pulmonary status is important because the main long-term complication continues to be chronic lung disease. Regular measurements of pulmonary lung function should be obtained and high-resolution CT scanning of the lungs should be performed since bronchiectasis can develop (even in patients on chronic IVIG therapy). If end-stage lung disease develops, lung transplantation has been performed in patients with agammaglobulinemia using intensive IVIG administration (every 48 h during the first 10 d after transplant).
Extensive diagnostic tests including cerebrospinal fluid (CSF) analyses with polymerase chain reaction (PCR) for viral genomes, neuroimaging, and electrophysiologic studies need to be pursued to evaluate for infectious or autoimmune complications.
Successful cure has been reported using stem cells from either cord blood or bone marrow from human leukocyte antigen (HLA)-matched siblings.
Further Inpatient Care
Hospitalization has become unusual for patients with antibody deficiencies because home health organizations can provide intravenous antibiotics, pulmonary care, and nutritional interventions on an outpatient basis. Ig replacement therapy with either IVIG administered in outpatient clinics or SCIG at home to minimize interruptions of daily living is the mainstay of medical treatment.
The rationale for hospitalizing patients with immunodeficiency who are receiving IVIG replacement is usually to provide an adequate workup of a puzzling infection, to manage severe GI issues, to address acute pulmonary decompensation in the presence of chronic pulmonary disease, or to assess and treat severe autoimmune disorders.
Compared with others, patients who are treated have fewer acute overwhelming infections that require hospitalization.
Inpatient & Outpatient Medications
Administer IVIG to every patient with agammaglobulinemia. In rare circumstances (eg, temporary lack of venous access), intramuscular IgG can be given. Subcutaneous administration of IVIG is an option depending on individual preferences. A survey revealed that 90% of 1243 (1119) patients with primary immunodeficiencies in 16 countries receive IVIG in an inpatient setting, whereas 7% (87) are treated with subcutaneous Ig (SCIG), mainly at home. However, this survey was performed before the SCIG preparation was available.
Because these patients risk developing unusual infections, attempt to identify any pathogens in either the respiratory or gastrointestinal tracts. More modern techniques using PCR helped diagnose Mycoplasma pneumoniae osteomyelitis in a patient with hypogammaglobulinemia with repeatedly sterile pus cultures.
For patients to have refractory Campylobacter jejuni infection longer than 2 years is not unusual, despite therapy with various antibiotics and IVIG preparations.
In patients with respiratory symptoms, analyzing bronchial samples obtained during bronchoscopy using traditional culture as well as PCR may help determine the various viruses and bacteria present.
Maintain IVIG and aggressively treat pneumonias with antibiotics to avoid chronic lung disease. Recurrent infections may eventually cause either obstructive disease alone or combined obstructive and restrictive lung disease. Aerosol treatments with bronchodilators and chest physiotherapy, such as postural drainage, may prevent further damage in these patients.
Although most children with agammaglobulinemia or early onset hypogammaglobulinemia develop recurrent bacterial respiratory tract infections during infancy, 20% of cases are diagnosed in children aged 3-5 years, reflecting the widespread use of antibiotics. Unfortunately, permanent damage to the lungs with bronchiectasis may have already occurred.
This could be reflected in continued decline in pulmonary function testing. However, increasing the dose may blunt this decline. As much as 42% of humoral or antibody deficiency may have bronchial hyperreactivity as measured by methacholine challenge testing. The presence of bronchiectasis has also been found to correlate with continued risk for developing pneumonia despite immunoglobulin replacement therapy.
No good studies have examined the effectiveness of aerosol treatments in these patients, although one may speculate that mobilization of secretions should help. Similarly, no good studies have examined the usefulness of prophylactic antibiotics, either systemically or topically (ie, aerosolized).
Unusual pulmonary disorders such as recurrent pulmonary alveolar proteinosis, which is not associated with any known infectious agent, have been seen in patients treated with IVIG.
Chronic sinusitis may also result from repeated infections and subsequent structural changes. Chronic ear infections may result in hearing loss. A study indicated that as many as 38% of patients with primary antibody deficiency developed sensorineural hearing loss and as many as 73% may have conductive hearing loss. The prophylactic use of antibiotics was possibly associated with lower rates of audiological complications. Finally, watch for the development of mastoiditis.
Patients with low or absent Ig levels have increased risk of malignancy, especially in the lymphoreticular and GI organs, which may be the result of altered immune surveillance. The risk for malignancy in certain patients with immunodeficiency is estimated to be 100-300 times higher than in the general population. In one survey in Japan, approximately 2.7% of patients with primary immunodeficiency diseases developed malignant disorders. Most are diagnosed when the patient is younger than 10 years, except for those whose immunodeficiencies developed later in life (eg, common variable immunodeficiency disease [CVID]).
The association of hypogammaglobulinemia with thymoma is well recognized and is known as Good syndrome.
Reports of progressive neurodegeneration in patients with primary immunodeficiency on IVIG treatment are concerning.[93, 94] Extensive diagnostic tests including CSF analyses with PCR for viral genomes, neuroimaging, and electrophysiologic studies need to be pursued to evaluate for infectious or autoimmune complications.
Autoimmune diseases (eg, inflammatory bowel disease, atrophic gastritis, pernicious anemia) are also observed in patients with agammaglobulinemia or hypogammaglobulinemia. Their occurrence suggests that the altered immune system, with its low resistance to infectious pathogens, may cause an inappropriate hyperfunction toward self-antigens that cause autoimmune disorders.
Treatment of autoimmune complications may consist of increasing the dose of immunoglobulin replacement and/or steroids or rituximab.
The outcome of patients with agammaglobulinemia or hypogammaglobulinemia depends on the underlying disease.
For patients with agammaglobulinemia, overall prognosis is good when patients comply with their IVIG or SCIG therapy and attend to the possible complications of chronic infections in the upper and lower respiratory tracts.
In a 10-year prospective study of children younger than 4 years with hypogammaglobulinemia, Dalal et al identified 3 groups: (1) those who developed normal Ig levels with specific antibody production, (2) those who developed normal IgG levels but only transient antibody production, and (3) those with persistently low IgG levels. In a similar study with 8-year follow-up, Kidon et al (2004) found that 75% of children with hypogammaglobulinemia normalized their serum Ig levels (and were therefore diagnosed with transient hypogammaglobulinemia of infancy). Finally, Kutukculer and Gulez followed a group of 37 patients with hypogammaglobulinemia and found 49% spontaneously corrected their immunoglobulin abnormalities with IgG or IgM levels reaching normal levels at about 5 years of age and IgA levels by about 6 years of age.
Cases of so-called "reversible hypogammaglobulinemia" have been reported in which adult patients on IVIG therapy resume immunoglobulin production.
In studies of patients before IVIG treatment was developed, 75% of patients older than 20 years had developed chronic lung disease, and 5-10% had cor pulmonale.
Patients can be expected to attend school and hold jobs.
Two organizations offering scholarships to patients with immune disorders are the Immune Deficiency Foundation and the Jeffrey Modell Foundation. They are also excellent resources for the parents of a child with an immune deficiency disorder.
York NR, de la Morena MT. 50 years ago in the journal of pediatrics: a decade with agammaglobulinemia. J Pediatr. 2012 May. 160(5):756.
Khan WN. Colonel Bruton's kinase defined the molecular basis of X-linked agammaglobulinemia, the first primary immunodeficiency. J Immunol. 2012 Apr 1. 188(7):2933-5. [Medline].
Samson M, Audia S, Lakomy D, et al. Diagnostic strategy for patients with hypogammaglobulinemia in rheumatology. Joint Bone Spine. 2011 May. 78(3):241-5. [Medline].
Nelson KS, Lewis DB. Adult-onset presentations of genetic immunodeficiencies: genes can throw slow curves. Curr Opin Infect Dis. 2010 Aug. 23(4):359-64. [Medline].
Conley ME, Famer DM, Dobbs AK, et al. A minimally hypomorphic mutation in Btk resulting in reduced B cell numbers but no clinical disease. Clin Exp Immunol. 2008. 152:39-44.
Litzman J, Brysova V, Gaillyova R, et al. Agammaglobulinaemia in a girl with a mosaic of ring 18 chromosome. J Paediatr Child Health. 1998 Feb. 34(1):92-4. [Medline].
Ohga S, Nakao F, Narazaki O, et al. Hypogammaglobulinaemia in a patient with ring chromosome 21. Arch Dis Child. 1997 Sep. 77(3):252-4. [Medline].
Revy P, Busslinger M, Tashiro K, et al. A syndrome involving intrauterine growth retardation, microcephaly, cerebellar hypoplasia, B lymphocyte deficiency, and progressive pancytopenia. Pediatrics. 2000 Mar. 105(3):E39. [Medline].
Roifman CM. Antibody deficiency, growth retardation, spondyloepiphyseal dysplasia and retinal dystrophy: a novel syndrome. Clin Genet. 1999 Feb. 55(2):103-9. [Medline].
Stewart DM, Tian LL, Notaranelo LD, Nelson DL. X-linked hypogammaglobulinemia and isolated growth hormone deficiency: an update. Immunol Rev. 2008. 40:262-70. [Medline].
al-Attas RA, Rahi AH. Primary antibody deficiency in Arabs: first report from eastern Saudi Arabia. J Clin Immunol. 1998 Sep. 18(5):368-71. [Medline].
Bousfiha AA, Jeddane L, El Hafidi N, Benajiba N, Rada N, El Bakkouri J, et al. First Report on the Moroccan Registry of Primary Immunodeficiencies: 15 Years of Experience (1998-2012). J Clin Immunol. Mar 2914. E PUB. [Medline].
Leal RC, Bertelli EC, Soler ZA. Recurrent pneumonia caused by genetic immunodeficiency: a prophylactic and rehabililtative approach. Braz J Infect Dis. 2007. 11:307-10. [Medline].
Lam DS, Lee TL, Chan KW, et al. Primary immunodeficiency in Hong Kong and the use of genetic analysis for diagnosis. Hong Kong Med J. 2005 Apr. 11(2):90-6. [Medline].
Wang LL, Jin YY, Hao YQ, et al. Distribution and clinical features of primary immunodeficiency diseases in Chinese children (2004-2009). J Clin Immunol. 2011 Jun. 31(3):297-308. [Medline].
de Silva NR, Gunawardena S, Rathnayake D, Wickramasingha GD. Spectrum of primary immunodeficiency disorders in Sri Lanka. Allergy Asthma Clin Immunol. Dec 2013. 9:50. [Medline].
Schatorjé EJ, Gathmann B, van Hout RW, de Vries E; PedPAD consortium. The PedPAD study: Boys predominate in the hypogammaglobulinemia registry of the ESID Online Database. Clin Exp Immunol. Feb 2014. Epub. [Medline].
van den Bruele T, Mourad-Baars PE, Claas EC, et al. Campylobacter jejuni bacteremia and Helicobacter pylori in a patient with X-linked agammaglobulinemia. Eur J Clin Microbiol Infect Dis. 2010 Nov. 29(11):1315-9. [Medline]. [Full Text].
Vancikova Z, Freiberger T, Vach W, Trojanek M, Rizzi M, Janda A. X-linked agammaglobulinemia in community-acquired pneumonia cases revealed by immunoglobulin level screening at hospital admission. Klin Padiatr. Nov 2013. 225:339-42. [Medline].
Shaghaghi M, Parvaneh N, Ostad-Rahimi P, Fathi SM, Shahmahmoodi S, Abolhassani H, et al. Combined immunodeficiency presenting with vaccine-associated paralytic poliomyelitis: a case report and narrative review of literature. Immunol Invest. 2014. 43:292-8. [Medline].
Rudge P, Webster AD, Revesz T, et al. Encephalomyelitis in primary hypogammaglobulinaemia. Brain. 1996 Feb. 119 ( Pt 1):1-15. [Medline].
Katamura K, Hattori H, Kunishima T, et al. Non-progressive viral myelitis in X-linked agammaglobulinemia. Brain Dev. 2002 Mar. 24(2):109-11. [Medline].
Wildenbeest JG, van den Broek PJ, Benschop KS, et al. Pleconaril revisited: clinical course of chronic enteroviral meningoencephalitis after treatment correlates with in vitro susceptibility. Antivir Ther. 2012. 17(3):459-66. [Medline].
Sveinsson O, Matell H, Herrman L. Progressive multifocal leukoencephalopathy in a patient with Good's syndrome. BMJ Case Rep. Jul 2013. 284(1-2):2013. [Medline].
Mancuso A, Gentiluomo M, Vangeli M, Torre MD, Belli LS. Diarrhea as sole presentation of Good's syndrome mimicking Crohn's disease. Clin Immunol. Apr 2013. 147:9-10. [Medline].
Agarwal S1, Mayer L. Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency. Clin Gastroenterol Hepatol. Sep 2013. 11:1050-63. [Medline].
Gavrilova T, Capitle E. A case of relapsing polychondritis and hypogammaglobulinemia. Ann Allergy Asthma Immunol. Aug 2013. 111:147-8.
Wynes J, Harris W 4th, Hadfield RA, Malay DS. Subtalar joint septic arthritis in a patient with hypogammaglobulinemia. J Foot Ankle Surg. Mar-Apr 2013. 52:242-8. [Medline].
Sato H, Iino N, Ohashi R, Saeki T, Ito T, Saito M, et al. Hypogammaglobulinemic patient with polyarthritis mimicking rheumatoid arthritis finally diagnosed as septic arthritis caused by Mycoplasma hominis. Intern Med. 2012. 51:425-9. [Medline].
Bonkowsky JL, Bohnsack JF, Pennington MJ, et al. Leukoencephalopathy, arthritis, colitis, and hypogammaglobulinemia (LACH) in two brothers: a novel syndrome?. Am J Med Genet A. 2004. 128:52-6. [Medline].
Farmer DG, Kattan OM, Wozniak LJ, Marcus E, Ponthieux S, Hwang V, et al. Incidence, timing, and significance of early hypogammaglobulinemia after intestinal transplantation. Transplantation. May 2013. 95:1154-9. [Medline].
Mozer-Glassberg Y, Shamir R, Steinberg R, Kadmon G, Har-Lev E, Mor E, et al. Hypogammaglobulinemia in the early period after liver transplantation in children. Clin Transplant. May-Jun 2013. 27:E289-94. [Medline].
Chambers DC, Davies B, Mathews A, Yerkovich ST, Hopkins PM. Bronchiolitis obliterans syndrome, hypogammaglobulinemia, and infectious complications of lung transplantation. J Heart Lung Transplant. Jan 2013. 32:36-43. [Medline].
Carbone J, Sarmiento E, Del Pozo N, Rodriguez-Molina JJ, Navarro J, Fernandez-Yañez J, et al. Restoration of humoral immunity after intravenous immunoglobulin replacement therapy in heart recipients with post-transplant antibody deficiency and severe infections. Clin Transplant. May-Jun 2013. 26:e277-83. [Medline].
Akman S, Guven AG, Ince S, et al. IgG and IgG subclasses deficiency in children undergoing continuous ambulatory peritoneal dialysis and its provocative factors. Pediatr Int. 2002 Jun. 44(3):273-6. [Medline].
Rehman S, Bytnar D, Berkenbosch JW, et al. Hypogammaglobulinemia in pediatric ICU patients. J Intensive Care Med. 2003 Sep-Oct. 18(5):261-4. [Medline].
Dotta L, Tassone L, Badolato R. Clinical and genetic features of Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome. Curr Mol Med. 2011 Jun. 11(4):317-25. [Medline].
Agarwal S, Cunningham-Rundles C. Thymoma and immunodeficiency (Good syndrome): a report of 2 unusual cases and review of the literature. Ann Allergy Asthma Immunol. 2007. 98:185-90. [Medline].
Sawada A, Takihara Y, Kim JY, et al. A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans. J Clin Invest. 2003 Dec. 112(11):1707-13. [Medline].
Lougaris V, Vitali M, Baronio M, Moratto D, Tampella G, Biasini A, et al. Autosomal Recessive Agammaglobulinemia: The Third Case of Igβ Deficiency Due to a Novel Non-sense Mutation. J Clin Immunol. Apr 2014. epub. [Medline].
Khalili A1, Plebani A, Vitali M, Abolhassani H, Lougaris V, Mirminachi B, et al. Autosomal Recessive Agammaglobulinemia: A Novel Non-sense Mutation in CD79a. J Clin Immunol. Feb 2014. 34:138-41. [Medline].
Boisson B, Wang YD, Bosompem A, Ma CS, Lim A, Kochetkov T, et al. A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells. J Clin Invest. Nov 2013. 123:4781-5. [Medline].
Hugle B, Hoffman H, Bird LM, et al. Hoffman syndrome: New patients, new insights. Am J Med Genet A. 2011 Jan. 155A(1):149-53. [Medline].
Zhang ZY, Zhao XD, Jiang LP, et al. Clinical characteristics and molecular analysis of 21 Chinese children with congenital agammaglobulinemia. Scand J Immunol. 2010 Nov. 72(5):454-9. [Medline].
Onigbanjo MT, Orange JS, Perez EE, Sullivan KE. Hypogammaglobulinemia in a pediatric tertiary care setting. Clin Immunol. 2007. 125:52-9. [Medline].
Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections. Clin Lymphoma Myeloma Leuk. Apr 2013. 13:106-11. [Medline].
Besada E, Bader L, Nossent H. Sustained hypogammaglobulinemia under rituximab maintenance therapy could increase the risk for serious infections: a report of two cases. Rheumatol Int. Jun 2013. 33:1643-4. [Medline].
Ozaras N, Goksugur N, Eroglu S, Tabak O, Canbakan B, Ozaras R. Carbamazepine-induced hypogammaglobulinemia. Seizure. Apr 2012. 21:229-31. [Medline].
Okumura A, Tsuge I, Kamachi Y et al. Transient hypogammaglobulinemia after antileptic drug hypersensitivity. Pediatr Neurol. 2007. 36:342-4. [Medline].
Boccara O, Valevrie-Allanore L, Crickx B et al. Association of hypogammaglobulinemia with DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Eur J Dermatol. 2006. 16:666-8. [Medline]. [Full Text].
Kawano T, Matsuse H, Obase Y, et al. Hypogammaglobulinemia in steroid-dependent asthmatics correlates with the daily dose of oral prednisolone. Int Arch Allergy Immunol. 2002 Jul. 128(3):240-3. [Medline].
Kitamura A, Takiguchi Y, Tochigi N, et al. Durable hypogammaglobulinemia associated with thymoma (Good syndrome). Intern Med. 2009. 48(19):1749-52. [Medline].
Yong PF, Aslam L, Karim MY, Khamashta MA. Management of hypogammaglobulinaemia occurring in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2008 Sep. 47(9):1400-5. [Medline].
Carneiro-Sampaio M, Liphaus BL, Jesus AA, Silva CA, Oliveira JB, Kiss MH. Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies. J Clin Immunol. 2008 May. 28 Suppl 1:S34-41. [Medline].
Lankisch P, Laws HJ, Weiss M, Borkhardt A. Agammaglobulinemia and lack of immunization protection in exudative atopic dermatitis. Eur J Pediatr. Jan 2014. 173:117-9. [Medline].
Ghoshal UC, Goel A, Ghoshal U, et al. Chronic diarrhea and malabsorption due to hypogammaglobulinemia: a report on twelve patients. Indian J Gastroenterol. 2011 Jul. 30(4):170-4. [Medline].
Furtado AK, Cabral VL, Santos TN, Mansour E, Nagasako CK, Lorena SL, et al. Giardia infection: protein-losing enteropathy in an adult with immunodeficiency. World J Gastroenterol. May 2012. 18:2430-3. [Medline].
Orange JS, Geha RS, Bonilla FA. Acute chylothorax in children: selective retention of memory T cells and natural killer cells. J Pediatr. 2003. 143:243-9. [Medline].
Bezrodnik L, Raccio AC, Canil LM, Rey MA, Carabajal PC, FOssati CA, et al. Hypogammaglobulinemia secondary to cow-milk allergy in children under 2 years of age. Immunology. 2007. 122:140-6. [Medline].
Ricci G, Piccinno V, Giannetti A, et al. Evolution of hypogammaglobulinemia in premature and full-term infants. Int J Immunopathol Pharmacol. 2011 Jul-Sep. 24(3):721-6. [Medline].
Ozen A, Baris S, Karakoc-Aydiner E, et al. Outcome of hypogammaglobulinemia in children: immunoglobulin levels as predictors. Clin Immunol. 2010 Dec. 137(3):374-83. [Medline].
Kainulainen L, Vuorinen T, Rantakokko-Jalava K, Osterback R, Ruuskanen O. Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol. 2010 Jul. 126(1):120-6. [Medline].
Bondioni MP, Duse M, Plebani A et al. Pulmonary and sinusal changes in 45 patients with primary immunodeficiencies: computed tompgraphy evaluation. J Comput Assist Tompgr. 2007. 31:620-8. [Medline].
Gharagozlou M, Ebrahimi FA, Farhoudi A, et al. Pulmonary complications in primary hypogammaglobulinemia: a survey by high resolution CT scan. Monaldi Arch Chest Dis. Jun 2006. 65:69-74.
Tavakol M, Kouhi A, Abolhassani H, Ghajar A, Afarideh M, Shahinpour S, et al. Otological findings in pediatric patients with hypogammaglobulinemia. Iran J Allergy Asthma Immunol. Jun 2014. 13:166-73. [Medline].
Chinen J, Shearer WT. Subcutaneous immunoglobulins: alternative for the hypogammaglobulinemic patient?. J Allergy Clin Immunol. 2004. 114:934-5. [Medline].
Ochs, HD, Gupta S, Kiseeling P et al. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006. 26:265-73. [Medline].
Gustafson R, Gardulf A, Hansen S et al. Rapid subcutaneous immunoglobulin administration every second week results in high and stable serum immunoglobulin G levels in patients with primary antibody deficiencies. Clin Exp Immunol. 2008. 152:274-9. [Medline].
Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: A meta-analysis of clinical studies. Clin Immunol. 2010 Oct. 137(1):21-30. [Medline].
Berger M. Incidence of infection is inversely related to steady-state (trough) serum IgG level in studies of subcutaneous IgG in PIDD. J Clin Immunol. 2011 Oct. 31(5):924-6. [Medline].
Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug Information Handbook 2008-2009. 16th edition. Cleveland, OH: Lexi-Comp Inc; 2008.
Hooper JA. Intravenous immunoglobulins: evolution of commercial IVIG preparations. Immunol Allergy Clin North Am. 2008 Nov. 28(4):765-78, viii. [Medline].
Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health Syst Pharm. 2005 Aug 15. 62(16 Suppl 3):S5-11. [Medline].
Siegel J. The Product: All intravenous immunoglobulins are not equivalent. Pharmacother. 2005. 25(11 Pt 2):78S-84S.
Shaghaghi M, Parvaneh N, Ostad-Rahimi P, Fathi SM, Shahmahmoodi S, Abolhassani H, et al. Combined immunodeficiency presenting with vaccine-associated paralytic poliomyelitis: a case report and narrative review of literature. Immunol Invest. Mar 2014. 43:292-8. [Medline].
Gonzalo-Garijo MA, Sánchez-Vega S, Pérez-Calderón R, Pérez-Rangel I, Corrales-Vargas S, Fernández de Mera JJ, et al. Renal amyloidosis in a patient with X-linked agammaglobulinemia (Bruton's disease) and bronchiectasis. J Clin Immunol. Jan 2014. 34:119-22. [Medline].
Howard V, Myers LA, Williams DA, et al. Stem cell transplants for patients with X-linked agammaglobulinemia. Clin Immunol. 2003 May. 107(2):98-102. [Medline].
Quinti I, Pierdominici M, Marziali M, et al. European surveillance of immunoglobulin safety--results of initial survey of 1243 patients with primary immunodeficiencies in 16 countries. Clin Immunol. 2002 Sep. 104(3):231-6. [Medline].
Buckley RH. Pulmonary complications of primary immunodeficiencies. Paediatr Respir Rev. 2004. 5 (Suppl A):S225-33. [Medline].
Chen Y, Stirling RG, Paul E, et al. Longitudinal decline in lung function in patients with primary immunoglobulin deficiencies. J Allergy Clin Immunol. 2011 Jun. 127(6):1414-7. [Medline].
Ozcan C, Metin A, Erkoçoğlu M, Kocabas CN. Bronchial hyperreactivity in children with antibody deficiencies. Allergol Immunopathol (Madr). Jan 2014. Epub. [Medline].
Quinti I, Soresina A, Guerra A, et al. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011 Jun. 31(3):315-22. [Medline].
Patiroglu T, Akyildiz B, Patiroglu TE, Gulmez IY. Recurrent pulmonary alveolar proteinosis secondary to agammaglobulinemia. Pediatr Pulmonol. 2008 Jul. 43(7):710-3. [Medline].
Berlucchi M, Soresina A, Redaelli De Zinis LO, et al. Sensorineural hearing loss in primary antibody deficiency disorders. J Pediatr. 2008 Aug. 153(2):293-6. [Medline].
Tavakol M, Kouhi A, Abolhassani H, Ghajar A, Afarideh M, Shahinpour S, et al. Otological findings in pediatric patients with hypogammaglobulinemia. Iran J Allergy Asthma Immunol. Jun 2014. 13:166-73. [Medline].
Ishimura M, Takada H, Doi T, et al. Nationwide survey of patients with primary immunodeficiency diseases in Japan. J Clin Immunol. 2011 Dec. 31(6):968-76. [Medline].
Brosens LA, Tytgat KM, Morsink FH et al. Multiple colorectal neoplasms in X-linked agammaglobulinemia. Clin Gastroenterol Hepatol. 2008. 6:115-9. [Medline].
Slotta JE, Heine S, Kauffels A, et al. Gastrectomy with isoperistaltic jejunal parallel pouch in a 15-year-old adolescent boy with gastric adenocarcinoma and autosomal recessive agammaglobulinemia. J Pediatr Surg. 2011 Sep. 46(9):e21-4. [Medline].
Ziegner UH,, Kobayashi RH, Cunningham-Rundles C, et al. Progressive neurodegeneration in patients with primary immunodeficiency disease on IVIG treatment. Clin Immunol. 2002. 102:19-24. [Medline].
Papapetropoulos S, Friedman J, Blackstone C et al. A progressive, fatal dystonia-Parkinsonism syndrome in a patient with primary immunodeficiency receiving chronic IBIG therapy. Mov Disord. 2007. 22:1664-6. [Medline].
Dalal I, Reid B, Nisbet-Brown E, Roifman CM. The outcome of patients with hypogammaglobulinemia in infancy and early childhood. J Pediatr. 1998 Jul. 133(1):144-6. [Medline].
Kidon MI, Handzel ZT, Schwartz R, et al. Symptomatic hypogammaglobulinemia in infancy and childhood - clinical outcome and in vitro immune responses. BMC Fam Pract. 2004 Oct 21. 5:23. [Medline].
Desar IM, Weemaes CM, van Deuren M et al. Reversible hypogammaglubulinaemia. Neth J Med. 2007. 65:381-5. [Medline].
Aghamohammadi A, Moin M, Farhoudi A, et al. Efficacy of intravenous immunoglobulin on the prevention of pneumonia in patients with agammaglobulinemia. FEMS Immunol Med Microbiol. 2004 Mar 8. 40(2):113-8. [Medline].
Baumgart KW, Britton WJ, Kemp A, et al. The spectrum of primary immunodeficiency disorders in Australia. J Allergy Clin Immunol. 1997 Sep. 100(3):415-23. [Medline].
Black C, Zavod MB, Gosselin BJ. Haemophilus influenzae lymphadenopathy in a patient with agammaglobulinemia: clinical-histologic-microbiologic correlation and review of the literature. Arch PatholLab Med. 2005. 129:100-3. [Medline].
Buehring I, Friedrich B, Schaaf J, et al. Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies. Clin Exp Immunol. 1997 Sep. 109(3):468-72. [Medline].
Conley ME. Early defects in B cell development. Curr Opin Allergy Clin Immunol. 2002. 2:517-22. [Medline].
Conley ME, Broides A, Hernandez-Trujillo V, et al. Genetic analysis of patients with defects in early B-cell development. Immunol Rev. 2005. 203:216-34. [Medline].
Conley ME, Dobbs AK, Farmer DM, et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol. 2009. 27:199-227. [Medline].
Dittrich AM, Schulze I, Magdorf K, et al. X-linked agammaglobulinaemia and Pneumocystis carinii pneumonia--an unusual coincidence?. Eur J Pediatr. 2003 Jun. 162(6):432-3. [Medline].
Eijkhout HW, van Der Meer JW, Kallenberg CG, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. 2001 Aug 7. 135(3):165-74. [Medline].
Eley BS, Hughes J, Cooper M, Pienaar S, Beatty DW. Primary immunodeficiency diseases at Red Cross War Memorial Children's Hospital. S Afr Med J. 1997 Dec. 87(12):1684-8. [Medline].
Ferrari S, Lougaris V, Caraffi S, et al. Mutations of the Igbeta gene cause agammaglobulinemia in man. J Exp Med. 2007 Sep 3. 204(9):2047-51. [Medline].
Feydy A, Sibilia J, De Kerviler E, et al. Chest high resolution CT in adults with primary humoral immunodeficiency. Br J Radiol. 1996 Dec. 69(828):1108-16. [Medline].
Fijolek J, Wiatr E, Demkow U, Orlowsk TM. Immunological disturbances in Good's syndrome. Clin Invest Med. 2009 Aug 1. 32(4):E301-6. [Medline].
Halsey NA, Pinto J, Espinosa-Rosales F et al. Search for poliovirus carriers among people with primary immune deficiency diseases in the United States, Mexico, Brazil and the United Kingdom. Bull World Heatlh Organ. 2004. 82:3-8. [Medline].
Kainulainen L, Nikoskelainen J, Vuorinen T, et al. Viruses and bacteria in bronchial samples from patients with primary hypogammaglobulinemia. Am J Respir Crit Care Med. 1999 Apr. 159(4 Pt 1):1199-204. [Medline].
Kano Y, Inaoka M, Shiohara T. Association between anticonvulsant hypersensitivity syndrome and human herpes 6 reactivation and hypogammaglobulinemia. Arch Dermatol. 2004. 140:183-8. [Medline].
Kutukculer N, Gulez N. The outcome of patients with unclassified hypogammaglobulinemia in early childhood. Pediatr Allergy Immunol. 2009 Nov. 20(7):693-8. [Medline].
Mila J, Matamoros N, Pons de Ves J, et al. [The Spanish Registry of Primary Immunodeficiencies. REDIP-1998]. Sangre (Barc). 1999 Apr. 44(2):163-7. [Medline].
Morales P, Hernandez D, Vicente R, et al. Lung transplantation in patients with x-linked agammaglobulinemia. Transplant Proc. 2003 Aug. 35(5):1942-3. [Medline].
Mueller BU, Pizzo PA. Cancer in children with primary or secondary immunodeficiencies. J Pediatr. 1995 Jan. 126(1):1-10. [Medline].
Ozdoba C, Ramelli G, Schroth G. MRI in a patient with congenital agammaglobulinaemia. Neuroradiology. 1998 Aug. 40(8):516-8. [Medline].
Plebani A, Soresina A, Rondelli R, et al. Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study. Clin Immunol. 2002 Sep. 104(3):221-30. [Medline].
Quartier P, Debre M, De Blic J, et al. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr. 1999 May. 134(5):589-96. [Medline].
Raynaud M, Ronce N, Ayrault AD, et al. X-linked mental retardation with isolated growth hormone deficiency is mapped to Xq22-Xq27.2 in one family. Am J Med Genet. 1998 Mar 19. 76(3):255-61. [Medline].
Skull S, Kemp A. Treatment of hypogammaglobulinaemia with intravenous immunoglobulin, 1973-93. Arch Dis Child. 1996 Jun. 74(6):527-30. [Medline].
Teramoto T, Kaneko H, Funato M, et al. Progressive multifocal leukoencephalopathy in a patient with X-linked agammaglobulinemia. Scand J Infect Dis. 2003. 35(11-12):909-10. [Medline].
Tokuda K, Nishi J, Miyanohara H, et al. Relapsing cellulitis associated with Campylobacter coli bacteremia in an agammaglobulinemic patient. Pediatr Infect Dis J. 2004 Jun. 23(6):577-9. [Medline].
Wang LJ, Yang YH, Lin YT, Chiang BL. Immunological and clinical features of pediatric patients with primary hypogammaglobulinemia in Taiwan. Asian Pac J Allergy Immunol. 2004. 22:25-31. [Medline].
|Brand(Manufacturer)||Manufacturing Process||pH||Additives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs].)||Parenteral Form and Final Concentrations||IgA Content (mcg/mL)|
|Kistler-Nitschmann fractionation; pH 4 incubation, nanofiltration||6.4-6.8||6% solution: 10% sucrose, < 20 mg NaCl/g protein||Lyophilized powder 3%, 6%, 9%, 12%||Trace|
|Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization||5.1-6||Sucrose free, contains 5% D-sorbitol||Liquid 5%||< 50|
|Gammagard Liquid 10%
|Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation||4.6-5.1||0.25M glycine||Ready-for-use liquid 10%||37|
|Cohn-Oncley fraction II/III; ultrafiltration; pasteurization||6.4-7.2||5% solution: 5% sucrose, 3% albumin, 0.5% NaCl||Lyophilized powder 5%||< 20|
|Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation||4-4.5||Contains no sugar, contains glycine||Liquid 10%||46|
|Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation||4.8-5.1||Contains sorbitol (40 mg/mL); do not administer if fructose intolerant||Ready-for-use solution 5%||< 10|
|Cohn-Oncley fraction II/III; ultrafiltration; pasteurization||6.4-7.2||5% solution: 5% glucose, 0.3% NaCl||Lyophilized powder 5%||< 10|
(Baxter Bioscience for the American Red Cross)
|Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated||6.4-7.2||5% solution: 0.3% albumin, 2.25% glycine, 2% glucose||Lyophilized powder 5%, 10%||< 1.6 (5% solution)|
9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events
|Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization||5.1-6||10% maltose||Liquid 5%||200|
(Swiss Red Cross for the American Red Cross)
|Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration||6.6||Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl||Lyophilized powder 3%, 6%, 9%, 12%||720|
|pH 4 incubation; octanoic acid fractionation, depth filtration, and virus filtration||4.6-5||10% solution; Preservative-free, sucrose-free, and maltose-free||Ready-to-use solution 10%||< 25|
|Brand(Manufacturer)||Manufacturing Process||pH||Additives||Parenteral Form and Final Concentrations||IgA Content mcg/mL|
|Cold ethanol fractionation, pasteurization||6.4-7.2||2.25% glycine, 0.3% NaCl||Liquid 16% (160 mg/mL)||< 50 mcg/mL|