2025 – PAGE 111 – ALLERGY & IMMUNOLOGY

COMMON VARIABLE IMMUNE DEFICIENCY (CVID)

In Common Variable Immune Deficiency (AKA CVID), B-cells fail to transform into plasma cells. This results in a deficiency of all of the Ig subtypes. CVID can also have some T-cell membrane defects. Symptoms include recurrent upper and lower respiratory tract infections (recurrent pneumonias!). Patients can have recurrent herpes and recurrent Zoster (VZV) infections. There is a risk of EBV-associated lymphoma. Treat by giving IV Immunoglobulin (IVIG) in an effort to raise the patient’s level of antibodies to “normal.”

HYPER IGM SYNDROME

In hyper IgM syndrome, the IgM to IgG class switch does not occur due to a missing signal from T-cells to B-cells. There is LYMPHOcytosis and NEUTROPENIA. This is a T-cell abnormality but results in a functional B-cell deficiency. Therefore, it shares features of both B-cell and T-cell deficiencies, but the presentations are more similar to B-cell deficiencies. Patients frequently have sinusitis, otitis media and pneumonia with the “HNS” encapsulated organisms mentioned in the B-cell deficiencies section (Haemophilus influenzae, Neisseria meningitides, and Streptococcus pneumoniae). It usually starts around 6 months of age. Because of the T-cell abnormality, there is an increased risk of lymphoma/cancer. Patients can also get diarrhea and opportunistic infections from Pneumocystis jirovecii, Histoplasma and Cryptosporidium. For treatment, give IVIG to make up for the missing immunoglobulins and Trimethoprim-Sulfamethoxazole (AKA Bactrim) for PCP prophylaxis.

MNEMONIC:

Bactrim is used for PCP prophylaxis

MNEMONIC: Think of the LYMPHOcytosis as a compensatory mechanism in which there are high numbers of LYMPHOcytes circulating and releasing elevated levels of IgM to “make up” for the lack of IgG, IgE and IgA. Also, think of the neutropenia as being a relative “lack of neutrophils” on the WBC resulting from an excess of lymphocytes.

PEARL: Infections are similar to agammaglobulinemia, but the CBC looks different. Also, these patients can get PCP so suspect this diagnosis in any HIV-negative patient diagnosed with PCP.

B-CELL DEFICIENCIES

PEARLS:

• A pure B-cell deficiencywill usually present with recurrent bacterial infections (AKA pyogenic infections) starting around 6 months of age.
• Encapsulated organisms are very high on the differential, so keep in mind the “HNS” organisms (Haemophilus influenzae, Neisseria meningitides, and Streptococcus pneumoniae).
  • (DOUBLE TAKE) MNEMONIC: A complete list of encapsulated organismscan be recalled by remembering that “Some Nasty Killers Have Some Capsule Protection”: Streptococcus pneumoniae, Neisseria meningitidis, Klebsiella pneumoniae, Haemophilus influenzae, Salmonella typhi, Cryptococcus neoformans, and Pseudomonas aeruginosa. Bruton’s agammaglobulinemia and sickle cell patients are especially susceptible to encapsulated organisms.
• Because of problems with antibody production, you will NOT FIND THE EXPECTED TITERS for bacteria we typically immunize against, including Tetanus, Diphtheria, and Streptococcus (AKA pneumococcus). If you suspect a B-cell deficiency, test for it by obtaining TITERSfor something the child was already immunized against, such as TETANUS (an ABP favorite when testing for knowledge of Agammaglobulinemia). Low titers may indicate B-cell deficiency. Do not get confused with getting SKIN TESTING for tetanus, Candida, Mumps, or PPD, which all test for Delayed type-hypersensitivity, Type IV, T-cell mediated reactions.
• There are NOT as many viral or fungal infections as seen in T-cell deficiencies.
• MNEMONICS:
  • The age of presentation (6 months) happens to be around the same age when the mother’s immunoglobulins/antibodies begin to wane!
  • During well-child checks, we inject numerous vaccines to help B-cells make immunoglobulins against various organisms. Most of these are against BACTERIA. So, try to tie B-cell problems with recurrent BACTERIAL infections. Remember especially the enCAPSulated HNS organisms that have CAPS on them that need to be popped off with antibodies. (Antibodies look kind of like a bottle opener.)