Makindo Medical Notes.com

HHV-8 is the well-established cause of HHV-8-associated MCD, which accounts for approximately 50% of all cases of MCD

About

• Castleman disease originally described in a case published in 1954
• Rare condition that affects the lymph nodes and related tissues
• Two main forms: unicentric CD and multicentric CD
• AKA angiofollicular or benign giant lymph node hyperplasia

Aetiology

• Exact underlying cause of CD is currently unknown
• Some have HIV and/or HHV-8 infection
• Interleukin (IL) 6 in UCD
• Interleukin (IL) 6 and human herpesvirus (HHV) 8 in MCD
• Dysregulated and overproduced IL-6, particularly with MCD
• IL-6 stimulates the production of acute phase reactants in the liver
• IL-6 stimulates plasma cells

Clinical Types

• Unicentric CD is a "localized" condition that is generally confined to a single set of lymph nodes
• Multicentric CD is a "systemic" disease that affects multiple sets of lymph nodes and other tissues throughout the body.

Pathological Types

• Hyaline-vascular type 90% of cases . There are germinal follicles with hyalinized vessels surrounded by concentric layers of small lymphocytes with proliferative interfollicular vascular stroma
• Plasma cell type. Characterized by a paucity of follicular hyalinized vessels in the germinal follicles, although the interfollicular tissues are composed of sheets of dense plasma cells with less vascular stroma.

Associated conditions which patient may develop

• Large B-cell lymphomas
• Polyneuropathy, organomegaly,endocrinopathy, monoclonal gammopathy and skin abnormality (POEMS) syndrome
• Follicular dendritic cell sarcomas
• Paraneoplastic pemphigus
• Kaposi sarcoma seen with MCD due to a common viral pathogenesis
• Eruptive cherry haemangiomatosis or violaceous papules
• Lymphocytic interstitial pneumonitis.

Clinical

• B symptoms: Fever, sweats, and weight loss
• UCD: presents in the third and fourth decade of life, with the mean age of diagnosis being 34 years. Females slightly more. Painless lymphadenopathy chest (30%), neck (23%), abdomen (20%), retroperitoneum (17%), and, rarely, the axilla (5%), groin (3%), or pelvis (2%). May have B symptoms.
• MCD: Presents in the 50s. Those with HIV/HHV8 maybe younger. A slight male predominance. Generalized lymphadenopathy and hepatosplenomegaly, fluid retention with gravitational oedema, pleural and pericardial effusions, ascites. B symptoms.

Investigations

• FBC:anaemia. CRP: elevated CRP and ESR, low/high platelets
• Hypergammaglobulinemia
• Hypoalbuminemia
• U&E: Renal impairment
• Elevated IL-6 and IL-10.
• HIV test, HHV8 serology
• Plasma levels of HHV-8 DNA correlate with clinical symptoms and predict relapse rates in HIV-associated MCD
• CT./MRI : may show enlarged lymph nodes as well as liver and spleen enlargement

Management

• Unicentric form is typically of the hyaline-vascular type and amenable to surgical treatment. Radiation therapy is also an option due to its high rates of objective response.
• Multicentric typically belongs to the plasma cell type and is associated with more complicated systemic manifestations. Rituximab monotherapy is the mainstay of therapy; however, novel therapies targeting interleukin 6 may represent a treatment option in the near future. Antiviral strategies as well as single-agent and combination chaemotherapy with glucocorticoids is established systemic therapy. Those with HIV should be started on HAART. Prednisone 1 mg/kg daily or its equivalent may be added to rituximab until systemic inflammatory symptoms are adequately controlled and then tapered off. Cytotoxic agents such as oral etoposide, vinblastine, cyclophosphamide, cladribine, chlorambucil, and liposomal doxorubicin have been used. Rituximab may be used in those with are HIV negative. Anti-Interleukin 6 Therapy: Siltuximab and tocilizumab are monoclonal antibodies targeting IL-6and its receptor (IL-6R), respectively. The US Food and Drug Administration (FDA) has approved siltuximab for the treatment of patients with HIV negative, HHV-8negative MCD, where it shows significant clinical activity, resulting in control of IL-6–dependent systemic symptoms and laboratory abnormalities
• The management of Castleman disease also requires careful attention to potential concomitant infections, malignancies, and associated syndromes.

Algorithm

References

• Castleman's disease
• Castleman's disease Radiology