Immunoglobulin A Deficiency Clinical Presentation

Updated: May 15, 2018
  • Author: Marina Y Dolina, MD; Chief Editor: Michael A Kaliner, MD  more...
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Presentation

History

Previous studies based on analysis of blood donor banks have suggested that up to 90% of patients with selective immunoglobulin A deficiency (SIgAD) are asymptomatic. However, recent follow-up studies demonstrate that 80% of individuals with IgAD developed symptoms later in their life. [70] Symptomatic patients have a history significant for recurrent otitis media, sinusitis, bronchitis, pneumonia, GI tract infections, severe allergic reaction following infusions with immunoglobulins or blood transfusions, or, in children, failure to thrive.

  • Recurrent sinopulmonary infection is the most common illness associated with IgAD. Most upper and lower respiratory tract infections are caused by bacterial or viral pathogens characteristic of community-acquired pneumonia. Patients with concomitant IgG type 2 subclass deficiency may have a higher risk for recurrent infections from S pneumoniae, H influenzae, M catarrhalis, or Staphylococcus aureus.

  • Various GI tract infections with viruses, bacteria, and G lamblia parasites manifest as chronic diarrhea with or without malabsorption. Biopsy specimens may show nodular lymphoid hyperplasia with flattened villi.

  • Food allergy and other atopic disorders, such as allergic conjunctivitis, rhinitis, urticaria, atopic dermatitis, and asthma, are common in patients with IgAD.

  • Of patients with IgAD, 10-44% have anti-IgA antibodies, and these patients may have severe adverse reactions to IgA-containing materials such as blood, plasma, or immunoglobulin. [71]

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Physical

Patients present with various signs of recurrent respiratory tract infections; including swelling, pain, or tenderness upon palpation over the maxillary and frontal sinuses; chronic otorrhea and/or scarred or perforated tympanic membranes and decreased auditory acuity or even deafness; chronic nasal discharge; fever; nonproductive or productive cough; and dyspnea. GI findings may include abdominal distention, focal tenderness to direct palpation (without rebound), cramps after eating, diffuse pain, and increased peristalsis. [72, 73]

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Causes

The underlying causes of most cases of this heterogeneous disease remain unknown. Familial inheritance has been recognized in 25% of affected individuals, suggesting a strong genetic influence.

  • Case reports of some affected families indicate that inheritance may be autosomal dominant or recessive. In other families in which multiple members are affected, the pattern of inheritance does not conform to strict Mendelian rules.

    • In some families, the immunodeficiency can appear to skip generations; in others, one family member in a given generation may have IgAD, while another in the same generation may have common variable immunodeficiency (CVID), suggesting variable expressivity and penetrance of disease susceptibility gene(s).

    • Recent studies have shown that susceptibility to either CVID or IgAD may be linked to specific alleles of the major histocompatibility complex, suggesting that these alleles, or alleles of closely linked genes with which they are in linkage disequilibrium, are somehow involved in the pathogenesis of CVID and IgAD.

  • IgA deficiency is a particularly notable aspect of ataxia-telangiectasia and related disorders in which mutations in DNA processing/repair mechanisms interfere with rearrangements of immunoglobulin and T-cell receptor genes. Other signs of ataxia-telangiectasia should be carefully sought in children presenting with IgAD, particularly if they also have developmental delays. These manifestations may occur before the telangiectases are obvious.

  • In his 1991 report of 2 mothers with IgAD, de Laat suggests that transplacental passage of anti-IgA antibodies can also cause IgAD in an infant by inducing excessive IgA-specific T-cell suppressor activity. [74]

  • Certain drugs may also cause IgAD, but this form usually resolves once the medication is stopped. The following drugs have been implicated:

    • D-penicillamine

    • Sulfasalazine

    • Aurothioglucose

    • Fenclofenac

    • Gold

    • Captopril

    • Zonisamide

    • Phenytoin

    • Valproic acid

    • Thyroxine

    • Chloroquine

    • Carbamazepine

    • Hydantoin

    • Levamisole

    • Ibuprofen

    • Salicylic acid

    • Cyclosporin A

  • Infections may cause transient IgAD. The following have been recognized as causes:

  • IgAD can follow bone marrow transplantation from an IgA-deficient donor into a histocompatible sibling not previously deficient in IgA.

  • Occupational exposure to benzene: Workers maintaining cargo tanks that contain crude oil residues were exposed to benzene, as documented by blood and urine samples and exposure measurements. Tank workers showed a decline in IgA from baseline to pre-next shift, with suppression correlating with benzene concentrations in blood and urine and time spent in the tank. Declines in IgM and CD4 T cells were also noted. [75]

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