Frits van Rhee, MD, PhD: Treatment Options

What are the potential treatment options?

Frits van Rhee, MD, PhD, University of Arkansas for Medical Sciences, says that in this patient one would like to exclude that the Herpesvirus type 8 is not active. Molecular testing is a necessity, which detects replicating virus in the peripheral blood. Ten to 20% of the American population is infected with this virus, and it’s dormant, asleep, and not causing problems. The antibody test may be positive for this virus in 10-20% of patients, and it’s not informative. What one must look for is either replicating virus, dividing virus in the peripheral blood, or stain the lymph node for active virus. These tests were negative in this patient. That would point to a diagnosis of HHV negative, or what’s also referred to now as idiopathic multicentric Castleman’s disease. The term idiopathic in medicine is used to indicate that it is truly known as to what is causing the disease.

Guess the Diagnosis: Case 2

Mark F. is a 25-year-old law school student from Florida with a 3-week history of severe fatigue, night sweats, and weight loss; he has also reported high fevers for the past week. He did not complain of joint pain.

• He presents to the emergency department complaining of abdominal pain. His past medical history is notable for enlarged thyroid incidentally found 5 years before; family history relevant for an aunt with rheumatoid arthritis
• Physical exam was notable for generalized lymphadenopathy (1-2 cm), hepatosplenomegaly, bilateral pleural effusions, ascites, and 4+ peripheral edema. Laboratory findings show anemia (7 gm/dL), elevated CRP (150 mg/L), ESR (120mm/hr), creatinine (3.0 mmol/L), Albumin of 2.1 g/dL and normal immunoglobulin levels (IgG: 1100 mg/dL, IgA: 300 mg/dL, IgM 200 mg/dL), low platelets (50,000/mL), positive ANA 1:160 with a speckled pattern. RhF was negative. Coagulation screen was not suggestive of DIC. LDH was normal

The patient was admitted for further assessment.

• Regressed germinal centers, scattered hyperplastic follicles, preserved architecture with patent peripheral sinuses and florid interfollicular plasmacytosis with no light chain restriction
• Rheumatologist diagnosed the patient with SLE and treated with high-dose steroids; this did not result in a major improvement in symptoms, laboratory parameters or lymphadenopathy

Mark’s SLE diagnosis was reviewed and further testing was performed:

• The patient was believed to be too sick to be taken to the OR to undergo a lymph node biopsy, so a bone marrow biopsy was performed. Bone marrow showed a hypercellular marrow with mild increase in polyclonal plasma cells and moderate reticulin fibrosis
• Laboratory work: Negative dsDNA, anti-Smith and anti-phopsholipid antibodies with normal complement levels; ANCA and anti-streptolysis O titer are negative. No M protein on protein electrophoresis. 24-hour urine showed mild proteinuria. Monospot negative. TSH, T4, and T3 normal. Normal thyroglobulin and thryoid peroxidase antibodies. Urinary sediment is negative as are urine and blood cultures. IL-6 is 6 pg/mL
• CT-PET: generalized lymphadenopathy with low-positive FDG uptake
• Without a clear diagnosis, a lymph node biopsy was performed of the cervical chain: Regressed germinal centers, scattered hyperplastic follicles, preserved architecture with patent peripheral sinuses; florid interfollicular plasmacytosis, prominent vascularization with absence of light chain restriction. Negative LANA-1, IgG4, and EBER stains. Negative PCR for B-cell clonality