Human herpesvirus 8 (HHV-8) infection is associated with Kaposi's sarcoma, primary effusion lymphomas and HIV-1-associated multicentric Castleman's disease (Cesarman & Knowles, 1997). A PCR-based study also suggested an association between HHV-8 and multiple myeloma which could not be confirmed using anti-HHV-8 antibody detection (Rettig et al, 1997; Marcelin et al, 1997). The POEMS syndrome is a rare multisystem disorder characterized by the association of polyneuropathy, organomegaly, endocrinopathy of various forms, monoclonal immunoglobulin component in serum and skin changes (Soubrier et al, 1994). The histological hallmarks of POEMS syndrome are osteosclerotic myeloma in bone and plasmacytic multicentric Castleman's disease in lymph nodes. We retrospectively looked for antibodies to HHV-8 in 13 patients with POEMS syndrome (Soubrier et al, 1994). All patients (four female, nine male; aged 55 ± 10 years) had polyneuropathy meeting the criteria for chronic demyelinating neuropathy, endocrinopathy, skin changes, and a monoclonal component containing lambda light chain in serum. Osteosclerotic bone lesions were disclosed in seven patients. We also tested 10 patients with classic Kaposi's sarcoma as positive controls. Immunofluorescence assay was done on PEL cell line latently infected with HHV-8 but not with Epstein-Barr virus (BCP-1, provided by P. S. Moore, New York, U.S.A.) (Simpson et al, 1996). HHV-8 antibodies could be detected in only one out of 13 patients with POEMS syndrome and 10/10 Kaposi's controls. The 57-year-old female patient with POEMS syndrome and anti-HHV-8 antibodies in serum had peripheral lymphadenopathy with features of Castleman's disease. Among the 12 POEMS syndrome patients with no detectable anti-HHV8 antibodies in serum, four also had Castleman's disease proven by lymph node or spleen biopsy. None of the five patients with POEMS syndrome and Castleman's disease had HIV infection. Because multicentric Castleman's disease is a distinctive feature of the POEMS syndrome, HHV-8 was a strong candidate for aetiopathogenesis in this syndrome. Moreover, the HHV-8 genome contains numerous open reading frames with homology to known cellular genes, including a viral IL-6 which is functionally active on human myeloma cells (Burger et al, 1998). Interestingly, overproduction of proinflammatory cytokines (tumour necrosis factor-alpha, IL-1-beta, IL-6) and vascular endothelial growth factor has been demonstrated in POEMS syndrome (Soubrier et al, 1997). Unlike other human herpesviruses, with the exception of herpes simplex virus type 2, infection with HHV-8 is not widespread. On the basis of antibody reactivity, HHV-8 seroprevalence is estimated at about 5% in the U.K., 10–35% in Mediterranean countries and up to 25% in the U.S.A. (Simpson et al, 1996). Hence, HHV-8 seroprevalence in POEMS syndrome (7.6%) does not seem to differ from the general population. One could argue that serological testing provides only indirect evidence for HHV-8 infection. Serological data on HHV-8 infection have been shown to correlate reliably with virus detection by PCR or Southern blot hybridization in Kaposi's sarcoma, body-cavity based lymphomas and HIV-related Castleman's disease lesions (Cesarman & Knowles, 1997). Of note, HHV-8 infection of bone marrow dendritic cells, which has been claimed to occur in multiple myeloma, could not be corroborated by serological testing and was not confirmed by other groups using highly sensitive PCR methods (Rettig et al, 1997; Marcelin et al, 1997; Cull et al, 1998). In conclusion, HHV-8 infection does not appear to relate to Castleman's disease in the setting of POEMS syndrome.
Although experience remains limited and uncontrolled, intravenous immunoglobulin (IVIg) therapy probably has a place in the management of selected patients with the antiphospholipid syndrome. It seems effective for the prevention of recurrent pregnancy losses when conventional strategies using subcutaneous heparin and low-dose aspirin have failed. IVIg are currently investigated in the treatment of recurrent in vitro fertilization failure associated with antiphospholipid antibodies. In patients with severe thrombocytopenia, IVIg usually induce a prompt but transient remission. Finally, IVIg associated with steroids and heparin might improve survival in the rare but life-threatening catastrophic antiphospholipid syndrome.
The authors report their experience with 45 cases of inferior vena cava thrombosis. Diagnosis was delayed for an average of 55 days. One-third of cases were revealed by an embolic complication. Inflammatory diseases were the most common causes (Behcet disease: seven cases, systemic lupus erythematosus: 5 cases). Malignancies accounted for 20% of cases. Abnormalities of coagulation were uncommon: antithrombin III deficiency in one patient and protein C deficiency in another. Estrogen-progestogen combinations could be incriminated in 4 cases. Outcome was fatal in 20% of cases, usually as a result of the underlying disease. Functional status was good in two-thirds of patients without malignancy followed up for an average of 27 months. In 14 patients a clip was inserted to ensure total (3 cases) or partial (11 cases) interruption of vena cava blood flow because of a free thrombus and/or recurrent pulmonary embolism. Three patients had thrombectomy. After clip insertion two embolisms were recorded, one of which occurred in the immediate post-operative period.
Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares. [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up. Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12). Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.
