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.