Human Herpesvirus-8 (HHV-8)-Positive Human Immunodeficiency Virus (HIV)-Negative Multicentric Castleman Disease With a Fulminant Course.

Multicentric Castleman disease (MCD) is a poorly understood, heterogeneous lymphoproliferative disorder with benign hyperplastic lymph nodes and systemic inflammatory symptoms. Human herpesvirus-8 (HHV-8) may be associated with MCD, whether or not the patient is infected with the human immunodeficiency virus (HIV). A 74-year-old man presented with anaemia, thrombocytopenia and bilateral axillary adenomegaly of unknown origin. The patient was admitted to the hospital two years ago with clinical signs of weight loss, asthenia, anorexia and a maculopapular rash on the trunk and back. Blood analysis showed pancytopenia (haemoglobin 7.7 g/dL, leucocytes 2.55 x 109/L and platelets 41 x 109/L), elevated acute phase reactants (such as C-reactive protein, erythrocyte sedimentation rate, ferritin and fibrinogen), hypoalbuminemia and hypergammaglobulinemia, and HIV serology was negative. Thoracic, abdominal and pelvic axial tomography showed generalised lymphadenopathy. The bone marrow biopsy showed only reactive changes, and the histology of an excisional biopsy of the adenopathy was consistent with the plasmablastic variant of MCD associated with HHV-8. The HHV-8 viral load was 3.8 x 104 copies/mL (4.5 log). He was started on prednisolone 60 mg/day and rituximab. He had a poor response to therapy, despite a reduction in the HHV-8 viral load, with clinical deterioration, transfusion-dependent anaemia and progression to multi-organ dysfunction leading to death three weeks after starting treatment. Our patient had a fulminant course of MCD despite treatment with rituximab. Further studies are needed to validate the different treatment modalities and to better understand the prognosis of this disease.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Kimura's Disease: A Literature Review Based on a Clinical Case.

Kimura's disease (KD) was first described in 1937. It is a rare, benign, and chronic immune-mediated inflammatory disorder affecting the subcutaneous tissue, salivary glands, and lymph nodes. The disease is more common in the second to third decades of life in middle-aged Southeast Asian countries. The cause of Kimura's disease remains unknown; some authors believe it is related to an autoimmune or delayed-type hypersensitivity reaction. It commonly presents as a solitary painless lymph node in the head and neck or generalized lymphadenopathy (67%-100%) associated with peripheral eosinophilia and elevated IgE levels. Renal involvement may occur in some patients. Diagnosis is made by histology. A 21-year-old Caucasian man with no relevant medical history presented with a non-tender swelling of the left hemiface without other associated symptoms. Laboratory investigations revealed a leukocyte count with eosinophilia (2.29×10^9/L- 26.5%) and elevated total IgE and IgG4. He had no renal dysfunction. He underwent surgical resection of the lesion in the jugal, infraorbital, and left nasolabial regions, and the anatomopathological examination revealed the characteristics of Kimura's disease. Three months after surgery, an MRI showed an increase in the size of the mass, and he was started on corticosteroids. Six months after surgery, he presented with a slight increase in the size of the mass and was started on Ciclosporin, which allowed a progressive reduction in the dose of corticosteroid with evidence of a progressive reduction in swelling. Ciclosporin was stopped due to toxic serum levels, and he was started on mycophenolate mofetil. The dose was increased because of the increase in facial mass; on mycophenolate mofetil 2500mg/day, the patient remains stable. KD is a chronic disorder of unknown etiology that mainly affects young people in Southeast Asia and is rare in Western countries, as in the case of this young man. Studies have shown no significant differences in region or race, complications, multiplicity, laterality, anatomical distribution, maximum size, eosinophil count, or IgE levels between age groups. There is no consensus on the optimal treatment for KD; several treatments have been used, including surgery, systemic corticosteroids, immunosuppressants, and radiation. Due to the tendency to relapse and the rarity of the disease, there is no consensus on treatment options for relapse.

Meglumine Antimoniate and Miltefosine Combined With Allopurinol Sustain Pro-inflammatory Immune Environments During Canine Leishmaniosis Treatment.

Canine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, TGF-ß, and IFN-γ by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-γ and downregulation of IL-2, IL-4, and TGF-ß, while gene expression of IL-12, TNF-α, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-γ gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery.

Canine leishmaniasis. Immunophenotypic profile of leukocytes in different compartments of symptomatic, asymptomatic and treated dogs.

Canine visceral leishmaniasis (CanL) is an emerging disease, expanding in various parts of the world. The infection caused by Leishmania, an intracellular protozoan parasite, can show different clinical manifestations, from asymptomatic or subclinical to symptomatic dogs, in which a wide spectrum of clinical signs is evident. The fact that the parasite replicates in different organs raises the hypothesis that each organ may have a specific immune response. The local immune responses should be evaluated and taken into consideration when developing prophylactic tools. Therefore, phenotypic characterization of peripheral blood, lymph node and bone marrow lymphocyte populations and the expression of class II molecules of major histocompatibility complex (MHCII) were performed in asymptomatic and symptomatic dogs and in dogs that had been diagnosed and treated for leishmaniasis. Our findings showed that blood and bone marrow lymphocytes from symptomatic dogs were highly activated. In bone marrow of asymptomatic and treated dogs, a high frequency of MHCII(+) lymphocytes was observed, as well as MHCII(+) monocytes in the treated group. These results show increased expression of MHCII molecules giving evidence for antigenic presentation mainly by lymphocytes. The symptomatic and treated dogs showed an expansion of CD4(+) T cells subpopulations in lymph nodes, revealing an important contribution of these cells in controlling local parasite replication. This study also underlines the eventual importance of CD3(+)CD4(-)CD8(-) (double negative) and CD3(+)CD4(+)CD8(+) (double positive) T cell subsets in sensing and controlling latent infections and their possible function in the immune dynamics during CanL. The specific cellular immune responses raised in different compartments where the parasite replicates seem to have variable effects on local parasite control, highlighting the complexity of the cellular immune response developed by the dog infected by Leishmania infantum.