Introduction
Castleman disease (CD) is a rare lymphoproliferative disorder, generally seen in adults with HIV infection, and small case series has been reported in the pediatric population [1]. Patients often have systemic symptoms due to hyperinflammation, lymphocyte polyclonality, plasma cell proliferation and fatal multiorgan dysfunction. Castleman disease is classified according to the histopathological findings, number of lymph nodes involved and presence of human herpes virus 8 (HHV-8) infection [2]. Types of CD are identified as unicentric Castleman disease (UCD), HHV-8 associated multicentric Castleman disease, HHV-8 negative/ idiopathic multicentric Castleman disease (iMCD) and polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS)-associated MCD [2]. Two subgroups of iMCD are identified as: iMCD with thrombocytopenia, ascites, reticulin fibrosis, renal dysfunction, organomegaly (iMCD-TAFRO) and iMCD-not otherwise specified (iMCD-NOS) [2]. Several mechanisms thought to be etiological drivers such as elevated levels of human IL-6 or viral IL-6 encoded by HHV-8, other infectious or immunologic mechanisms [2]. The etiology, pathogenesis and relationship between immunodeficiencies of UCD and iMCD are poorly understood [2].
DOCK8 (dedicator of cytokinesis 8) deficiency is a rare autosomal recessive primary immunodeficiency. It is more common in populations with increased consanguineous marriages. Biallelic loss of function leads to the defect in DOCK8, which encodes guanine nucleotide exchange factor that is highly expressed in lymphocytes and regulates the actin cytoskeleton [3]. Classical findings are recurrent infections, allergic diseases including eczema and food allergy, autoimmunity and virus associated cancers [4]. Patients with DOCK8 deficiency suffer from especially cutaneous viral infections, varicella zoster, molluscum contagiosum, herpes simplex and human papillomaviruses [5]. There is no relationship shown to date that DOCK8 deficiency may cause susceptibility to orf virus infection. Orf virus is a member ofParapoxvirus genus, responsible for a highly contagious zoonotic viral infection that affects sheep and goats. In healthy individuals, this virus rarely causes systemic involvement and usually causes local infections, commonly orf nodules in hands. It may, however, cause more generalized illness in primary immunodeficiency patients. There are examples of orf virus-induced lobular capillary hemangiomas after thermal burns in literature. Local immunosuppression related to the burns is possible disease mechanism [13-15]. Orf infection is rarely seen in otherwise healthy individuals [6]. We present a rare case of DOCK8 deficient patient who had iMCD-NOS and orf virus infected giant lobular capillary hemangiomas.