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.