Ten-Year Follow-Up of a DOCK8-Deficient Child With Features of Systemic Lupus Erythematosus

Abstract

Dedicator of cytokinesis 8 (DOCK8) deficiency is an innate error of adaptive immunity characterized by recurrent infections with viruses, bacteria, and fungi, typically high serum levels of immunoglobulin E, eosinophilia, and a progressive deterioration of T-and B-cell-mediated immunity. DOCK8 mutations are the second most common cause of hyper-immunoglobulin E syndromes (HIES). We report a case of DOCK8 deficiency associated with systemic lupus erythematosus (SLE). Association of SLE with HIES is very rare; to our knowledge, this is the sixth such case reported in the literature. A 10-year-old girl of consanguineous parents was followed in our clinic because of HIES since early childhood. She developed SLE with purpuric and necrotic skin lesions, diffuse arthritis, and glomerulonephritis. These autoimmune features were corroborated by the presence of antinuclear, anti-DNA, and antiphospholipid antibodies. The combination of HIES and autoimmunity makes treatment difficult, because the use of immunosuppressive drugs needed for SLE may worsen existing symptoms caused by the immunodeficiency. Our observation is the first case of association of SLE with HIES in the literature where the primary immune disease is genetically documented and labeled as DOCK8 deficiency.

Recent Advances in DOCK8 Immunodeficiency Syndrome

“…Cumulatively, these data establish that patients can be afflicted with a wide spectrum of microbes beyond the Staphylococcus aureus and herpes simplex virus, human papillomavirus, and molluscum contagiosum skin infections that predominate, leading to rarer presentations such as sclerosing cholangitis; that candidal infections are common but mild; and that chronic Epstein-Barr virus besides poorly controlled human papillomavirus infections likely contribute to the increased lymphoma and skin cancer risk. Additionally, these data also reinforce the observations that autoimmunity including autoimmune hemolytic anemia, lupus, and cerebral vasculitis are serious but rare complications (18); that vasculopathy can involve other large vessels outside the central nervous system (19, 20); and that connective tissue, dental, and skeletal abnormalities are features primarily of autosomal dominant STAT3-mutant hyper-IgE syndrome rather than DIDS.…”

DOCK8 deficiency: Insights into pathophysiology, clinical features and management

“…These include autoimmune hemolytic anemia, chorioretinitis/uveitis, hypothyroidism, as well as cytopenias and vasculitis [5,12,13,44]. Systemic lupus erythematosus (SLE) was reported in one patient with DOCK8 deficiency who developed purpuric and necrotic skin lesions, arthritis, and glomerulonephritis along with the presence of anti-nuclear, anti-DNA and antiphospholipid antibodies [16]. …”

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome

“…Some cases attributed to central nervous system vasculitis without obvious antecedent infection may be misattributed if based upon negative blood serologies, because pathogen testing can be negative in the blood while positive in the cerebrospinal fluid. One DIDS patient was reported as having systemic lupus erythematosus with nephropathy, which responded to immunosuppressive therapy . In some instances, clinical features of immunodysregulation can suggest other disorders, such as IPEX, but autoimmune gastrointestinal disease is not a feature of DIDS .…”