Druggable monogenic immune defects hidden in diverse medical specialties: Focus on overlap syndromes

Table 2 Clinical and laboratory red flags

Clinical red flags

Early onset in childhood: The development of complex inflammatory disorders before puberty and particularly before early childhood rises suspicion of a congenital immune dysregulation

Overlap of symptoms in distinct specialties: A clinical history of distinct rheumatologic and non-rheumatologic conditions is not common in pediatrics, addressing a monogenic disorder

Lymphoproliferative manifestations: The presence of splenomegaly and/or lymphadenopathy in association with inflammatory or autoimmune diseases suggests an underlying inborn error of immunity.

Recurrent infections: The recurrence of severe or atypical infections (especially candidiasis) in association with inflammatory or autoimmune diseases is rarely a consequence of immunomodulatory therapies in children, but it does suggest an immunological defect

Familiarity with autoimmunity: The clustering of autoimmune disorders in families acknowledges a likely monogenic cause

Laboratory red flags

Hypogammaglobulinemia

Hypergammaglobulinemia

Leukopenia

Hypereosinophilia

Wide positivity of autoantibodies

Positive interferon signature