Dedicator of Cytokinesis 8 Immunodeficiency Syndrome Presenting as Extensive and Giant Lesions of Molluscum Contagiosum in a Child

Madam, Dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome is an autosomal recessive (AR) disorder caused by mutations in the gene DOCK8 which functions as a regulator of the cytoskeleton. It is characterized by recurrent bacterial and viral infections, allergies, and certain cancers. Some patients may also experience complications such as autoimmune hemolytic anemia, vasculitis, or vasculopathy. We report a 3-year-old female child born of a second-degree consanguineous marriage presenting with complaints of multiple asymptomatic skin-colored raised lesions on face, neck, upper trunk, and fingers for 2 years. Cutaneous examination revealed multiple umbilicated pearly white papules and nodules over face, neck, back, and chest [Figure 1a-d]. Genital examination showed yellowish discharge from labia majora and minora [Figure 2].Figure 1: Multiple pearly white small umbilicated papules seen on the face, neck, and chest with giant nodule on the right upper eyelid (a), umblicated papules and nodules on ear, chin, and neck (b), on upper back (c), on chest (d)Figure 2: Yellowish greenish discharge from the vulvaInvestigations revealed severe anemia and leukocytosis with marked eosinophilia. Lymphocyte subpopulation assay showed increased CD19 B lymphocyte count and raised serum immunoglobulin E (IgE) level [Table 1]. Ultrasonography of the abdomen and pelvis showed cystitis and mesenteric lymphadenopathy. Enzyme-linked immunosorbent assay for HIV was nonreactive. Bacterial culture of pus swab from the labia showed growth of Enterobacter species. DNA test report of primary immunodeficiency panel genes revealed homozygous deletion of contiguous region corresponding to exons 10–27 of the DOCK8 gene, suggesting the diagnosis of DOCK8 immunodeficiency syndrome.Table 1: Laboratory investigations of the patientThe patient was treated with oral and topical antibiotics, zinc, and multivitamin supplements. Parents were counseled about the nature of disease and prognosis. Giant lesions of molluscum contagiosum over eyelids, obstructing the vision, were removed by curettage. Hyper IgE syndrome (HIES) is an autosomal dominant disease characterized by eczema, recurrent skin abscesses, pneumonias, and elevated serum IgE. Mutations in DOCK8 underlie most cases of AR HIES and are associated with reduced numbers of T cells, B cells, and natural killer (NK) cells, with impaired CD8 T cell proliferation and activation. The human DOCK8 gene, consisting of 46–48 exons, is spread over ~250 kb on the chromosome 9p24.3. It is highly expressed within the immune system, especially by lymphocytes.[1] Clinical presentation of DOCK8 deficiency includes recurrent cutaneous viral infections, respiratory and gastrointestinal infections, atopic manifestations including atopic dermatitis and food allergies, and increased risk of squamous cell carcinomas. Distinctive clinical feature of DOCK8 deficiency is the occurrence of severe cutaneous viral infections. These infections are extensive, difficult to control, and often occur concurrently. The most common viruses involved are molluscum contagiosum virus (MCV), herpes simplex virus (HSV), human papillomavirus (HPV), and varicella-zoster virus (VZV). Chronic orolabial or ulcerative anogenital HSV infections, as well as herpes simplex keratitis and eczema herpeticum, are typically observed. Warts due to HPV infection are often disfiguring flat and verrucous. MCV lesions are often confluent, and VZV can present with increased severity or with recurrent episodes.[2] Differential diagnosis include other immunodeficiency disorders such as HIES and Wiskott-Aldrich syndrome. Differentiating features of these immunodeficiency disorders are discussed in Table 2.Table 2: Differential diagnosis of dedicator of cytokinesis 8 immunodeficiency disordersCommon immunological features include raised serum IgE levels, raised absolute eosinophil count, lymphopenia, decrease in T lymphocyte subsets (CD3, CD4, CD8), and NK cells (CD16/56).[3] Genetic sequencing of the DOCK8 gene and examination of DOCK8 protein expression by flow cytometry confirm the diagnosis of DOCK8 deficiency.[4] Management of DOCK8 immunodeficiency includes treatment of eczematous rash, cutaneous, and systemic infections with appropriate antibiotic, antifungal, and antiviral therapy. Patients with impaired specific antibody responses may benefit from intravenous immunoglobulin therapy. Hematopoietic stem cell transplantation represents a promising therapeutic option for DOCK8-deficient patients. Role of transplantation in the prevention of malignancies is unknown.[5] Patient with DOCK8 deficiency syndrome may not have all the clinical features, especially in early childhood, and may present with only cutaneous features. Follow-up of these patients is important in view of the high risk of early death from opportunistic infections or malignancy. Development of substantial numbers of molluscum contagiosum should raise suspicions about this condition. Declaration of patient consent The authors certify that they have obtained all appropriate consent forms, duly signed by the parent of the patient. In the form, the parent has given his consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child/children will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.