PLCG2-associated Antibody Deficiency & Immune Dysregulation (PLAID) – aka Familial Atypical Cold Urticaria (FACU) or FCAS3

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Acronym:
PLAID/FCAS3

SAID group:
PLCG2-associated

Gene:
Heterozygous genomic deletions within the PLCG2 gene. [64]

Inheritance:
Autosomal dominant.

Ethnicity:
Unknown. Most reported cases with European ancestry.

Frequency:
Unknown but rare.

Timing of symptoms:
Onset <5 minutes after exposure to cold air (evaporative cooling). [64] Frequent sinusitis or pneumonia, and respiratory infections. Concurrent autoimmune diseases. [64] [65]

Age of onset:
Onset in infancy-under 6 months of age. Lifelong symptoms, but some find the symptoms less severe in adulthood. [64] [65]

Skin cutaneous:
Cold-triggered. Cold urticaria, erythema and itching post cold exposure (air, wet skin, cold food). Some w/angioedema; chronic granulomata. Some with ulcerative and cutaneous lesions from cold exposure.[132] Negative Ice cube test. [64]

Neurologic:
Not noted. [64] [65] No fevers noted with cold-induced urticaria. [64] [65]

Auditory:
Not noted. [64] [65]

Ophthalamic:
Uncommon. [66]

Cardiopulmonary:
44% with recurrent sinus and/or respiratory infections, >50% with allergies, asthma and/or autoimmune diseases. [65]

Abdominal:
Not noted. Some have concurrent autoimmune diseases that may involve other organs. [65]

Lymphatic:
Not noted. Some need IVIG for low immunoglobulins & frequent infections. A few with combined variable immune deficiency (CVID). [65]

Joints bones muscles cartilage:
Not noted. [64] [65] Some have concurrent autoimmune diseases that may involve the joints, such as inflammatory arthritis or undifferenciated connective tissue diseases. [65]

Vasculitis:
Not noted. [64] [65]

Amyloidosis:
Not noted. [64] [65]

Abnormal labs:
High IgE. Low serum IgA, IgG, IgM. Decreased circulating CD19+ B cells, IgG+ & IgA+ memory B cells, NK cells. >60% +ANA. WBC normal. [64] [65]

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