DOCK8 primary immunodeficiency syndrome.

A 3-year-old boy presented to our dermatology department in July, 2013, with a history of moderate atopic dermatitis, food allergy to cow’s milk protein and hen’s egg, and a 4 week history of very extensive molluscum contagiosum. Initial treatment with topical cantharidin and imiquimod had been unsuccessful. The family had no history of immunodefi ciency. Investigations showed lymphopenia with abnormal T-cell subsets (CD4 lymphocyte count of 0·384 × 109 cells per L [normal range 0·5–2·4 × 109 cells per L], CD3 lymphocyte count of 0·462 × 109 cells per L [0·9–4·5 × 109 cells per L], and CD8 lymphocyte count of 0·074 × 109 cells per L [0·3–1·6 × 109 cells per L]), increased IgE (2567 kIU/L [ 3%). Pneumococcal antibody serotypes, except 23F, were detected at negligible concentrations, despite previous vaccination. Clinical examination showed extensive sheets of molluscum on the trunk, genital region, ears, and eyelids with occipital and submandibular lymphadenopathy (fi gure). Naso pharyn geal swabs detected adenovirus DNA. The molluscum did not improve with two intravenous infusions of cidofovir in July, 2013. Because the clinical manifestations and the initial immunology screen suggested DOCK8 immuno defi ciency syndrome we ordered Sanger sequencing that subsequently identifi ed two compound heterozygous mutations in the DOCK8 gene on chromosome 9q24. Mutations in DOCK8 underlie most cases of autosomal recessive hyper-IgE syndrome and are associated with reduced numbers of T cells, B cells, and natural killer cells, with impaired CD8 T-cell proliferation and activation. Aff ected individuals have increased susceptibility to viral, bacterial, and fungal infections and have atopic manifestations including atopic dermatitis and food allergies. In our patient, the unusual severity of the molluscum infection along with the mild atopic dermatitis and food allergy suggested the diagnosis of DOCK8 primary immunodefi ciency syndrome, prompting further work-up. Presentation is characterised by recurrent infections with staphylococcus, cutaneous herpes, or human papillomavirus, respiratory and gastrointestinal infections, and an increased risk of squamous-cell carcinomas. Development of substantial numbers of molluscum contagiosum should raise suspicions about this condition. Management of DOCK8 immunodefi ciency includes prophylactic antibiotic, antifungal, and antiviral therapy. In view of the high risk of early death from opportunistic infection or malignancy, we have transplanted fi ve patients with DOCK8 defi ciency, all of whom are alive and well and free of all symptoms. In January, 2014, our patient received an HLA-identical sibling donor bone marrow transplant. He developed grade 2 skin graft versus host disease which resolved by 1 year after the transplantation, with complete clearance of the molluscum lesions and good immune reconstitution with 100% donor chimerism.