Case Report
A 10-year-old male with giant lobular capillary hemangiomas in the ear,
neck and gluteal areas, was referred to our clinic. He was the son of a
Syrian refugee family, born of a consanguineous marriage. His history
revealed that his lesions was first appeared as a mass in his right
eyelids at four years of age. The lesions were progressive. After
excision, they rapidly recurred. He had multiple lesions on his neck,
iliac region and perianal areas (Figure-1A, 1B). When he admitted to our
hospital, he had fever and multiple masses. He also was experiencing
severe itching. The patient experienced surges of fever over 39 ̵̊C once a
day, for the following days. He had hepatomegaly and mild splenomegaly
on physical examination. He also had multiple maculopapular lesions on
his trunk; suggestive of epidermodysplasia verruciformis (Figure-1C).
Broad spectrum antibiotics for possible secondary bacterial infection
and acyclovir treatments were started empirically.
Human immunodeficiency virus (HIV) serology was negative.
Immunohistochemical studies were negative for human herpes virus 8
(HHV8) and cytomegalovirus (CMV). Human papillomavirus (HPV) and herpes
simplex virus (HSV) PCR were negative. Common etiological drivers were
tested and ruled out. Additionally, we decided to test him for orf
virus. Orf virus PCR samples were taken. Interestingly, the results came
strongly positive for the virus (Figure-2). It was noticed that after
scratching his perineal area, he would auto-inoculate the lesions by
touching another body area (neck, scalp).
Our patient was anemic (hemoglobin was 8,6 gr/dl), had hypoalbuminemia
(1,9 gr/dl), elevated CRP (53 mg/L) and ESR (44 mm/hour), had
thrombocytosis (801 k/microL) suggesting a hyperinflammatory response.
The patient’s serum alkaline phosphatase (ALP) levels were high (Table
1).
Bone survey was done and revealed lytic lesions at the first metacarpal
bone of the right hand. Craniocervical, abdominal, and pelvic magnetic
resonance imaging (MRI) scans and thorax computed tomography (CT) were
performed in order to check for additional masses. Cervical and thoracic
lymphadenopaties were noted. Abdominal MRI showed multiple conglomerated
lymphadenopathies in the parailiac region. T2 signal hyperintensity and
contrast material enhancement were present at the medial clavicula and
sternum.
An excisional biopsy was performed from the iliac lesion. Pathologic
evaluation revealed lobular capillary hemangioma. The patient was given
2 mg/kg/day propranolol (p.o.), considering the effect on infantile
hemangiomas.
Punch biopsy from the widespread maculopapular lesions on his trunk
revealed epidermodysplasia verruciformis. Susceptibility to viral skin
infections suggested an underlying combined immunodeficiency syndrome or
an agent specific primary immunodeficiency. Immunological studies were
remarkable for elevated serum IgE level and eosinophilia (Table 1-3).
Sanger sequencing of the DOCK8 gene was done and showed homozygous
mutation in NM_203447.3 c.2007+1G>T
(IVS17+1G>).
Laparotomy and abdominal lymph node dissection were performed. Lymph
node biopsy was compatible with the Castleman disease, hyaline vascular
type including regressed/ atrophic germinal centers and lollipop
appearance in some germinal centers, plasmacytosis in the
interfollicular spaces, negative staining for CMV, EBV or HHV-8.
Considering the multicentric lymphadenopathies, together with the
histopathologic features, laboratory criteria (elevated CRP, anemia,
thrombocytosis, hypoalbuminemia), clinical criteria (fever,
hepatosplenomegaly) and excluding HHV-8 and HIV infection, and not
detecting polyneuropathy, endocrinopathy, or monoclonal plasma cell
disorder, iMCD-NOS was diagnosed. Corticosteroids and rituximab
treatments were started. Due to the severity and dissemination of
disease, the treatment changed to R-CHOP regimen. R-CHOP therapy was
proved to be very effective, and our patient’s lesions regressed
dramatically after first and second cycles of chemotherapy (Figure
1D-E). Unfortunately, our patient was died because of RSV (respiratory
syncytial virus) pneumonia and subsequent P. aureginosa sepsis
after the second R-CHOP cycle.