Delayed reaction to cow's milk proteins: a case study

Area of Science:

• Immunology
• Allergology
• Clinical Medicine

Background:

• Cow's milk allergy involves immunological reactions to milk proteins, with onset classified as immediate or delayed.
• Delayed-type hypersensitivity reactions to cow's milk proteins can manifest hours to days after ingestion.

Observation:

• An 18-year-old male presented with chronic, late-onset respiratory symptoms (rhinorrhea, sneezing, nasal blockade) 12-48 hours after milk intake.
• Standard allergy tests (skin prick, intradermal) were negative, but patch tests were positive for whole milk and alpha-lactalbumin.
• Elevated total IgE, positive IgG4 to milk fractions (alpha-lactalbumin, beta-lactoglobulin, casein), and positive histamine release test (HRT) for casein were observed.

Findings:

• A single-blind placebo-controlled milk challenge confirmed late respiratory symptoms, occurring 10 hours post-ingestion.
• Precipitating antibodies to milk fractions were detected, alongside positive IgG4 levels, suggesting a complex immune response.
• The findings indicate a role for IgG4 antibodies, potentially as blocking or anaphylactic antibodies, or reflecting a persistent antigenic stimulus.

Implications:

• This case underscores the complexity of cow's milk allergy diagnosis, particularly for delayed-type reactions.
• Patch testing and assessment of IgG4 may be valuable in diagnosing non-immediate hypersensitivity to cow's milk.
• Understanding the role of IgG4 in delayed reactions is crucial for accurate diagnosis and management of milk protein hypersensitivity.