Use of anti-tumor necrosis factor biologics in the treatment of rheumatoid arthritis does not change human T-lymphotropic virus type 1 markers: a case series.

Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.

Proviral loads of human T-lymphotropic virus Type 1 in asymptomatic carriers with different infection routes.

High human T-lymphotropic virus Type 1 (HTLV-1) proviral DNA load (PVL) has been reported to be one risk factor for the development of adult T-cell leukemia/lymphoma (ATL). ATL is also believed to develop in HTLV-1 carriers who acquire infection perinatally. ATL cells have been reported to frequently harbor defective provirus. In our study, PVLs for three different regions of HTLV-1 provirus (5'LTR-gag, gag and pX) were measured in 309 asymptomatic carriers with different infection routes. PVLs for the pX region in 21 asymptomatic carriers with maternal infection was significantly higher than in 24 carriers with spousal infection. Among 161 carriers with relatively high pX PVLs (equal to or greater than 1 copy per 100 peripheral blood mononuclear cells), 26 carriers (16%) had low gag PVL/pX PVL (less than 0.5) and four (2%) had low 5'LTR-gag PVL/pX PVL (less than 0.5). Low gag PVL/pX PVL ratio, which reflects deficiency and/or polymorphism of HTLV-1 proviral DNA sequences for the gag region, was also associated with maternal infection. These data suggest that HTLV-1 carriers with maternal infection tend to have high PVLs, which may be related to provirus with deficiency and/or the polymorphism of proviral DNA sequences. In addition, there is a possibility that this ratio may be used as a tool to differentiate the infection routes of asymptomatic HTLV-1 carriers, which supports the need for a large scale study.

[Overwhelming postsplenectomy infection 22 years after splenectomy].

A 25-year-old man undergoing splenectomy at 3 years of age to treat idiopathic thrombocytopenic purpura but no history of Streptococcus pneumonia vaccination, and reporting high fever, nausea, and headache developed purpura, confusion, and hypotension the next day and was admitted. Detailed examination showed disseminated intravascular coagulation and multiple-organ dysfunction. Chest X-ray and computed tomography (CT) showed pneumonia and pleural effusion. Blood culture was positive for S. pneumoniae. Gram staining of sputa yielded numerous white blood cells and gram-negative rods, and sputa culture was positive for Pasteurella multocida and Haemophilus influenzae. The medical history and presence of these organisms yielded a diagnosis of overwhelming postsplenectomy infection (OPSI), and the patient responded to treatment with a combination of benzylpenicillin, cefotaxime, and meropenem. This case suggests that patients with a history of splenectomy may benefit from vaccination for S. pneumoniae and adequate education on OPSI.

[A case of disseminated nontuberculous mycobacteriosis during purpura associated with hypergammaglobulinemia and hepatitis type C].

A 74-year-old woman with hepatitis due to hepatitis C virus followed up using oral predonisolone (3 mg/day) for two years because of hypergammaglobulinemia-associated purpura reported fever and lumbago in February 2005. Upon admission in June, she was found in chest-computed tomography to have atelectasia in the right middle lung lobe and a nodule with a cavity in the right lower lobe. She tested positive for tuberculous glycolipid antibody. Gallium scintigraphy showed an abnormal accumulation in the lower lumbar vertebra. Magnetic resonance imaging showed abnormal enhancement at L4, L5, and their intervertebral disc. Mycobacterium intracellulare (M. intracellulare) was detected in blood culture, bronchoalveolar lavage, and a biopsy specimen from the intervertebral disc, yielding a diagnosis of disseminated nontuberculous mycobacteriosis (NTM) due to M. intracellulare. She was treated with clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP), but EB and RFP were discontinued due to of the fever they induced. She was then treated with a combination of CAM, levofloxacin, and streptomycin and followed up as an out patient. Based on case reports of disseminated NTM infection in Japan, the prognosis is poor and a protocol must be established for its treatment.

Crystalglobulinemia with fulminant course with cylinder-like bodies on peripheral blood smear.

A 63-year-old woman presented to our hospital with fever, purpura and pain in both legs and died 4 days after admission. Her blood smear and skin biopsy showed cylinder-like bodies (20×120 µm). She was diagnosed to have monoclonal gammopathy (IgG, lambda type). An autopsy revealed cylinder-like bodies in the vasculature of various organs. We noted a proliferation of atypical plasma cells in her bone marrow, suggesting pre-existing myeloma. Crystalglobulinemia is a rare manifestation of hypergammaglobulinemia that can cause multiple embolisms of the small vessels, and this resulted in the patient's fulminant course. The identification of cylinder-like bodies in the peripheral blood may help in reaching a diagnosis in such cases.

[18F]fluorodeoxyglucose positron emission tomography is a useful tool to diagnose the early stage of Takayasu's arteritis and to evaluate the activity of the disease.

Takayasu's arteritis (TA) is a rare disease that can be difficult to diagnose in its early stage. A young woman with a fever and neck pain was thought to have TA, although computed tomographic angiography did not show any specific changes of the arteries. [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) was performed to detect the source of the inflammation. Specific accumulation of [(18)F]FDG-6-phosphate in the thoracic aorta and its direct branches was observed, leading to a diagnosis of TA. [(18)F]FDG-PET is therefore considered to be useful for the diagnosis of early-stage TA.