Hypogammaglobulinemia
| Hypogammaglobulinemia | |
| ICD-10 | D80.0-D80.1 |
|---|---|
| ICD-9 | 279.00 |
| DiseasesDB | 6426 |
| MedlinePlus | 001307 |
| eMedicine | med/1120 ped/54 |
| MeSH | D000361 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Shyam Patel [2] Associate Editor(s)-in-Chief: Omer Kamal, M.D.[3] Vindhya BellamKonda, M.B.B.S [4]
Synonyms and keywords:
Overview
Hypogammaglobulinemia is a type of primary immune deficiency disease. "Hypogammaglobulinemia" is largely synonymous with "agammaglobulinemia". When the latter term is used (as in "X-linked agammaglobulinemia") it implies that gamma globulins are not merely reduced, but completely absent. Modern assays have allowed most agammaglobulinemias to be more precisely defined as hypogammaglobulinemias,but the distinction is not usually clinically relevant. "Hypogammaglobulinemia" is distinguished from dysgammaglobulinemia, which is a reduction in some types of gamma globulins, but not others.
Historical Perspective
- Dr. Robert A Good and March of dimes foundation maintained a close association for a quarter century in the fight against immunodeficiency diseases.[1]
- Immunodeficiency diseases such as ataxia telangiectasia have been described as early as 1920's, wiskott aldrich's during 1930's.
- Between 1950-1965, primary immunodeficiencies affecting all major levels of immune system were first described.[2]
- Use of immunoglobulins for the treatment of hypogammaglobulinemia was practised as early as 1950's.[3]
- Therapeutic results in the use of human serum gamma globulins have been published during the late 1950's. [4][5]
- Treatment of various infectious diseases with the use of gamma globulins started during the late 1950's. Whooping cough was treated with placental immunoglobulin during the year 1959.[6][7]
Classification
| Type[8] | OMIM[9] | Gene |
|---|---|---|
| AGM1 | 601495 | IGHM |
| AGM2 | 613500 | IGLL1 |
| AGM3 | 613501 | CD79A |
| AGM4 | 613502 | BLNK |
| AGM5 | 613506 | LRRC8A |
| AGM6 | 612692 | CD79B |
Pathophysiology
- Hypogammaglobulinemia may result from lack of production, excessive loss of immunoglobulins, or both.[10]
- Congenital disorders affecting B-cell development can result in complete or partial absence of one or more Ig isotypes. [11]
- The classic form of this type of disorder is Bruton agammaglobulinemia, also known as X-linked agammaglobulinemia (XLA).
- Because B, T, and natural killer (NK) cells share a common progenitor, defects occurring at early developmental stages may result in combined immunodeficiency involving all cell types, although defects further down the differentiation pathways may result in deficiencies of a single cell type only.
- The symptoms depend on the type and severity of the Ig deficiency and the presence or deficiency of cellular immunity. In general, hypogammaglobulinemia results in recurrent infections with a restricted set of microorganisms primarily localized to the upper and lower airways, although bacteremia and GI infections can also occur. Patients with associated defects in cellular immunity usually present with opportunistic viral, fungal, or parasitic infections.
Causes
Hypogammaglobulinemia is caused by:[12][13][14][14][15]
Differentiating Hypogammaglobulinemia from Other Diseases
Hypogammaglobulinemia must be differentiated from Bronchiectasis, complement deficiencies, and cystic fibrosis[16][17][18][19]
| Medical condition | Characteristic features |
|---|---|
| Complement deficiencies |
|
| Bronchiectasis |
|
| Cystic fibrosis |
|
| Staphylococcal associated glomerulonephritis |
|
Epidemiology and Demographics
- The incidence of primary immunodeficiency is approximately 10 per 100,000 individuals worldwide.[20][21]
- In children primary immunodeficiencies are more common in boys than in girls. Male to female ratio being 5:1.
- There is no racial predilection to Hypogammaglobulinemia
- Hypogammaglobulinemia affects men and women equally
Risk Factors
Common risk factors in the development of hypogammaglobulinemia include:[20]
- Family history of a primary immune deficiency disorder
- Medical therapy with drugs such as
- Bruton's agammaglobulinemia[23]
Screening
There is insufficient evidence to recommend routine screening for hypogammaglobulinemia.
Natural History, Complications, and Prognosis
Common complications of hypogammaglobulinemia include:[24]
- Recurrent infections
- Growth retardation (in children)
- Autoimmune disorders
- Increased risk of cancer
- Death due to serious infections
Diagnosis
Diagnostic Study of Choice
There is no established diagnostic study of choice for the diagnosis of hypogammaglobulinemia.
History and Symptoms
A clinical history of the following may be present:[25]
- Granulomatous disease, enteropathy (celiac-like/inflammatory), and autoimmune cytopenia may suggest common variable immunodeficiency (CVID).
- Infections in infancy (especially Pneumocystis jirovecii, respiratory syncytial virus, Candida, and bacteria)
- X-linked agammaglobulinemia (XLA/Bruton disease)
- Transient hypogammaglobulinemia of infancy
- Celiac disease
- Thymoma
- Recurrent infections
- Secondary causes such as nephrotic syndrome, malabsorption/gastroenteropathy (e.g., intestinal lymphangiectasia), myeloma, leukemia, lymphoma, or malnutrition.
- Medication history may reveal use of rituximab, carbamazepine, phenytoin, disease-modifying antirheumatic drugs, cytotoxic drugs, or immunosuppressive drugs).
- History of radiation therapy.
Symptoms may include
- Failure to thrive in children Chronic diarrhea
- Recurrent infections Shortness of breath
- Chronic cough Bronchiectasis
- Sinus pain Nasal discharge
- Diarrhea Steatorrhea
- Complications after receiving live vaccines
Physical Examination
Common physical examination findings of hypogammaglobulinemia include :[26]
- Growth retardation
- Paucity of tonsillar tissue
- Skin: rash, livedo reticularis
- Splenomegaly or hypersplenism in patients with common variable immunodeficiency.
- Pulmonary: Rales, rhonchi and wheezing
- Cardiovascular examination: Chronic respiratory insufficiency can result in pulmonary hypertension and right heart failure.
- Extremities: Digital clubbing
Laboratory Findings
Laboratory studies that may be helpful include the following:[26]
- Serum immunoglobulin[27]
- Antibody response after immunization
- Isohemagglutinins
- Peripheral blood lymphocyte immunophenotyping[28]
- Evaluation of cellular immunity (cutaneous delayed-type hypersensitivity)
- Renal studies
- GI studies (eg, alpha1-antitrypsin)
Electrocardiogram
There are no ECG findings associated with hypogammaglobulinemia.
X-ray
A chest x-ray may be helpful in the diagnosis of hypogammaglobulinemia. Findings on an x-ray may be suggestive of[29]
- Bronchiectasis
- Atelectasis
- Lung cysts
- Mediastinal lymphadenopathy
- Features of opportunistic infection e.g., P jiroveci pneumonia, aspergillus infection and aspergilloma
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with hypogammaglobulinemia.
CT scan
HRCT may show bronchial wall thickening, features of bronchiectasis, lobar and/or segmental collapse, scars, interstitial lesions and lobular air-trapping. [30]
MRI
There are no MRI findings associated with hypogammaglobulinemia
Other Imaging Findings
There are no other imaging findings associated with hypogammaglobulinemia
Other Diagnostic Studies
Other diagnostic studies for hypogammaglobulinemia include flow cytometry which demonstrates low levels of circulating memory B cells. Molecular analysis may also be used in some cases.
Treatment
Medical Therapy
Immune globulin therapy is the mainstay of treatment for a variety of primary immunodeficiency states. American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly established the "Practice parameter for the diagnosis and management of primary immunodeficiency." [31]
Surgery
Surgical intervention is not recommended for the management of hypogammaglobulinemia
Primary Prevention
There are no established measures for the primary prevention of hypogammaglobulinemia
Secondary Prevention
There are no established measures for the secondary prevention of hypogammaglobulinemia. Antibiotics and anti-inflammatory medications can help.
References
- ↑ Rose DW (2007). "Robert A. Good, the March of Dimes, and immunodeficiency: an historical perspective". Immunol. Res. 38 (1–3): 51–4. PMID 17917009.
- ↑ Stiehm ER (January 1993). "New and old immunodeficiencies". Pediatr. Res. 33 (1 Suppl): S2–7, discussion S7–8. doi:10.1203/00006450-199305001-00007. PMID 8433870.
- ↑ "USE OF immune globulins for the treatment of agammaglobulinemia or hypogammaglobulinemia". J Am Med Assoc. 162 (2): 117. September 1956. PMID 13357304.
- ↑ SOULIER JP, BADILLET M, HERZOG F (November 1958). "[Therapeutic results in the use of human serum gamma globulins; survey of 6, 602 cases. I. Main indications for their use in infections diseases]". Presse Med (in French). 66 (84): 1881–4. PMID 13623695.
- ↑ OLIVE BADOSA A (June 1958). "[Gamma globulin in immunological therapeutics: critical analysis]". Rev Clin Esp (in Spanish; Castilian). 69 (6): 361–4. PMID 13591696.
- ↑ LODODO KS, BAVAEVA SN (February 1959). "[Treatment of whooping cough with placental gamma-globulin]". Pediatriia (in Russian). 14 (2): 38–42. PMID 13645155.
- ↑ SAXL O (December 1958). "[Treatment of severe infections with gamma globulin]". Z Arztl Fortbild (Jena) (in German). 52 (24): 1030–3. PMID 13648484.
- ↑ Claman HN, Hartley TF, Merrill D (October 1966). "Hypogammaglobulinemia, primary and secondary: immunoglobulin levels (gamma-G, gamma-A, gamma-M) in one hundred and twenty-five patients". J Allergy. 38 (4): 215–25. PMID 4162597.
- ↑ Bryant A, Calver NC, Toubi E, Webster AD, Farrant J (August 1990). "Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2". Clin. Immunol. Immunopathol. 56 (2): 239–48. PMID 2165880.
- ↑ Artac H, Kara R, Gokturk B, Reisli I (November 2013). "Reduced CD19 expression and decreased memory B cell numbers in transient hypogammaglobulinemia of infancy". Clin. Exp. Med. 13 (4): 257–63. doi:10.1007/s10238-012-0200-y. PMID 22820757.
- ↑ Dorsey MJ, Orange JS (November 2006). "Impaired specific antibody response and increased B-cell population in transient hypogammaglobulinemia of infancy". Ann. Allergy Asthma Immunol. 97 (5): 590–5. doi:10.1016/S1081-1206(10)61085-X. PMID 17165264.
- ↑ Sneller MC (January 2001). "Common variable immunodeficiency". Am. J. Med. Sci. 321 (1): 42–8. PMID 11202479.
- ↑ Cunningham-Rundles C, Bodian C (July 1999). "Common variable immunodeficiency: clinical and immunological features of 248 patients". Clin. Immunol. 92 (1): 34–48. doi:10.1006/clim.1999.4725. PMID 10413651.
- ↑ 14.0 14.1 Conley ME, Howard V (October 2002). "Clinical findings leading to the diagnosis of X-linked agammaglobulinemia". J. Pediatr. 141 (4): 566–71. doi:10.1067/mpd.2002.127711. PMID 12378199.
- ↑ Ciesielka D (April 2004). "Clinical evaluation and treatment of the adult patient with suspected primary immunodeficiency disease: a case analysis". J Am Acad Nurse Pract. 16 (4): 158–65. PMID 15137474.
- ↑ Saffran DC, Parolini O, Fitch-Hilgenberg ME, Rawlings DJ, Afar DE, Witte ON, Conley ME (May 1994). "Brief report: a point mutation in the SH2 domain of Bruton's tyrosine kinase in atypical X-linked agammaglobulinemia". N. Engl. J. Med. 330 (21): 1488–91. doi:10.1056/NEJM199405263302104. PMID 8164701.
- ↑ Kornfeld SJ, Kratz J, Haire RN, Litman GW, Good RA (April 1995). "X-linked agammaglobulinemia presenting as transient hypogammaglobulinemia of infancy". J. Allergy Clin. Immunol. 95 (4): 915–7. PMID 7722175.
- ↑ Vetrie D, Vorechovský I, Sideras P, Holland J, Davies A, Flinter F, Hammarström L, Kinnon C, Levinsky R, Bobrow M (January 1993). "The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases". Nature. 361 (6409): 226–33. doi:10.1038/361226a0. PMID 8380905.
- ↑ Buckley RH (November 1992). "Immunodeficiency diseases". JAMA. 268 (20): 2797–806. PMID 1433695.
- ↑ 20.0 20.1 Robertson J, Elidemir O, Saz EU, Gulen F, Schecter M, McKenzie E, Heinle J, Smith E, Mallory G (September 2009). "Hypogammaglobulinemia: Incidence, risk factors, and outcomes following pediatric lung transplantation". Pediatr Transplant. 13 (6): 754–9. doi:10.1111/j.1399-3046.2008.01067.x. PMID 19067916.
- ↑ Casulo C, Maragulia J, Zelenetz AD (April 2013). "Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections". Clin Lymphoma Myeloma Leuk. 13 (2): 106–11. doi:10.1016/j.clml.2012.11.011. PMC 4035033. PMID 23276889.
- ↑ Christou E, Giardino G, Worth A, Ladomenou F (November 2017). "Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab". Int. Rev. Immunol. 36 (6): 352–359. doi:10.1080/08830185.2017.1346092. PMID 28800262. Vancouver style error: initials (help)
- ↑ Taneja A, Chhabra A. PMID 28846295. Missing or empty
|title=(help) - ↑ Parikh SA, Leis JF, Chaffee KG, Call TG, Hanson CA, Ding W, Chanan-Khan AA, Bowen D, Conte M, Schwager S, Slager SL, Van Dyke DL, Jelinek DF, Kay NE, Shanafelt TD (September 2015). "Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes". Cancer. 121 (17): 2883–91. doi:10.1002/cncr.29438. PMC 4545721. PMID 25931291.
- ↑ Kiliç SS, Tezcan I, Sanal O, Metin A, Ersoy F (December 2000). "Transient hypogammaglobulinemia of infancy: clinical and immunologic features of 40 new cases". Pediatr Int. 42 (6): 647–50. PMID 11192522.
- ↑ 26.0 26.1 Zaman M, Huissoon A, Buckland M, Patel S, Alachkar H, Edgar JD, Thomas M, Arumugakani G, Baxendale H, Burns S, Williams AP, Jolles S, Herriot R, Sargur RB, Arkwright PD (September 2018). "Clinical & laboratory features of seventy-eight UK patients with Good's syndrome (thymoma & hypogammaglobulinemia)". Clin. Exp. Immunol. doi:10.1111/cei.13216. PMID 30216434.
- ↑ Bogaert DJ, Dullaers M, Lambrecht BN, Vermaelen KY, De Baere E, Haerynck F (September 2016). "Genes associated with common variable immunodeficiency: one diagnosis to rule them all?". J. Med. Genet. 53 (9): 575–90. doi:10.1136/jmedgenet-2015-103690. PMID 27250108.
- ↑ Clerici M, Villa ML, Mantovani M, Rugarli C (November 1988). "NK cell activity and monocyte dysfunctions in a patient with common variable hypogammaglobulinemia". J Clin Lab Immunol. 27 (3): 143–7. PMID 2977623.
- ↑ Buckley CR (July 1998). "Agammaglobulinemia, by Col. Ogden C. Bruton, MC, USA, Pediatrics, 1952;9:722-728". Pediatrics. 102 (1 Pt 2): 213–5. PMID 9651432.
- ↑ Feydy A, Sibilia J, De Kerviler E, Zagdanski AM, Chevret S, Fermand JP, Brouet JC, Frija J (December 1996). "Chest high resolution CT in adults with primary humoral immunodeficiency". Br J Radiol. 69 (828): 1108–16. doi:10.1259/0007-1285-69-828-1108. PMID 9135465.
- ↑ Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, Keller M, Kobrynski LJ, Komarow HD, Mazer B, Nelson RP, Orange JS, Routes JM, Shearer WT, Sorensen RU, Verbsky JW, Bernstein DI, Blessing-Moore J, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CR, Schuller D, Spector SL, Tilles S, Wallace D (November 2015). "Practice parameter for the diagnosis and management of primary immunodeficiency". J. Allergy Clin. Immunol. 136 (5): 1186–205.e1–78. doi:10.1016/j.jaci.2015.04.049. PMID 26371839.