Diffuse alveolar haemorrhage with suspected idiopathic pulmonary hemosiderosis and decrease in lung diffusing capacity and chronic respiratory failure.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown aetiology that causes recurrent episodes of diffuse alveolar haemorrhage (DAH). A male patient in his 50s had repeatedly experienced hemoptysis for the past 6 years, along with a decrease in the pulmonary diffusing capacity and chronic respiratory failure. After a 6-year follow-up, the patient experienced sudden exacerbation of hemoptysis and respiratory failure, and he was hospitalised. A CT of the chest revealed diffuse pulmonary infiltrates, whereas the bronchoalveolar lavage revealed hemosiderin-laden macrophages. Thus, the patient was diagnosed with DAH. As all diseases that cause DAH other than IPH were negative, the patient was suspected of IPH. He was treated with a combination of glucocorticoids and azathioprine, and his hemoptysis and chronic respiratory failure improved; however, the decrease in the pulmonary diffusing capacity did not improve. Treating adult-onset IPH with glucocorticoids and azathioprine might not improve pulmonary diffusing capacity.

Reactivation of cytomegalovirus predicts poor prognosis in patients on intensive immunosuppressive treatment for collagen-vascular diseases.

Reactivation of cytomegalovirus (CMV) occurs during intensive immunosuppressive therapies. However, the influence of CMV reactivation on prognosis in patients with immunosuppressive therapies for collagen-vascular diseases (CVD) is not fully understood. To determine whether CMV reactivation affects the prognosis of patients with CVD and to identify risk factors of CMV reactivation, we reviewed, retrospectively, the medical records of 109 CVD patients who were treated with glucocorticoid (prednisolone ≥20 mg/day) and were tested for CMV antigen (CMV-Ag). CMV-Ag was detected in 34 of the 109 patients. First-time CMV-Ag detection was within 50 days from the start of intensive immunosuppressive therapy in 82% of the patients. Common manifestations at first-time CMV-Ag detection were fever, arthralgia, and rash, although 52.9% of the patients were asymptomatic. The risk factors for CMV reactivation were old age (>65 years) and high-dose glucocorticoids (PSL ≥50 mg). During the 4-year study period, 18% of patients with positive CMV-Ag and 5% of those without CMV-Ag died. Patients with CMV-Ag (max CMV number ≥5/10(5) WBC) had a significantly poorer prognosis. Multivariate analysis confirmed CMV reactivation as an independent poor prognostic factor in CVD patients. Causes of death were exacerbation of pre-existing interstitial pneumonia and infection other than CMV. Our results demonstrate that CMV reactivation, particularly with a high CMV-Ag number, is a poor prognostic factor in CVD patients. Patients with older age and high-dose glucocorticoids have a high risk of CMV reactivation.

Autoantibodies against platelet-derived growth factor receptor alpha in patients with systemic lupus erythematosus.

Autoantibody against platelet-derived growth factor receptors (PDGFRs) has been reported in scleroderma (SSc). However, it remains unknown whether anti-PDGFRs antibody exists in collagen vascular diseases other than SSc. To answer the question, we developed an ELISA system and examined sera from patients with SLE (n = 75), SSc (n = 31), RA (n = 25) and control individuals. We also reviewed medical records to clarify clinical features of patients with anti-PDGFRα antibody. To examine the functions of anti-PDGFRα antibody in patients, fibroblasts were cultured and stimulated in the presence of purified IgG from patients, and their cell numbers were counted. Anti-PDGFRα antibody was detected in 29% of patients with SLE and in 21% of patients with SSc. Anti-PDGFRα antibody was found in 36% with active SLE, but in 10% in an inactive phase. Immunosuppressive therapy decreased the titer of the antibody. Patients with anti-PDGFRα antibody frequently developed a rash and hematological abnormalities, particular hemolytic anemia. Moreover, anti-PDGFRα antibody in SLE failed to demonstrate agonistic or antagonistic activities on PDGFR signaling. These findings indicate that nonfunctional anti-PDGFRα autoantibody exists in patients with SLE as well as those with scleroderma, and that the antibody could be a marker of disease activity and may be a marker of a subgroup of SLE.

Rituximab was effective on refractory thrombotic thrombocytopenic purpura but induced a flare of hemophagocytic syndrome in a patient with systemic lupus erythematosus.

We report the case of a patient with systemic lupus erythematosus (SLE) who first revealed hemophagocytic syndrome (HPS), which was treated successfully with glucocorticoid and intravenous cyclophosphamide. The patient then demonstrated refractory thrombotic thrombocytopenic purpura (TTP) with normal a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-13 activity that responded well to rituximab. After rituximab treatment, the patient showed a flare of HPS that was controlled by additional intravenous cyclophosphamide treatment. This case showed that TTP with normal ADAMTS-13 activity is B-cell dependent and indicated that B-cell depletion might exacerbate some autoimmune conditions in SLE.

[Various clinical symptoms in human parvovirus B19 infection].

Human parvovirus B19 infection causes erythema infectiosum in child, aplastic crisis in patients with chronic hemolytic anemia, chronic pure red cell aplasia in immunocompromised patients and hydrops fetalis. Human parvovirus B19 causes arthritis and acute glomerulonephritis due to immunological mechanism. Other disorders, rheumatoid arthritis, vasculitis and thrombotic microangiopathy, are linked in human parvovirus B19 infection. Parvovirus B19 infection causes choronic rheumatoid-like arthropathy. Autoantibody and low complement were seen in acute human parvovirus infection, and parvovirus B19 infection present clinically lupus like tableau.

Role of IgE in Th2 cell-mediated allergic airway inflammation.

Recent studies with gene knockout mice have demonstrated that T helper 2 (Th2) cell-derived cytokines, including IL-4, IL-5, and IL-13, play important roles in causing allergic airway inflammation. In addition to Th2 cytokines, IgE-dependent activation of mast cells has been suggested to play a role in allergic airway inflammation. In this review, we will discuss the role of IgE in Th2 cell-mediated allergic airway inflammation. We used IgE transgenic mice, which enabled us to investigate the role of IgE without the influence of activated T cells and other immunoglobulins. Whereas IgE cross-linking by antigens did not induce eosinophil recruitment into the airways or airway hyperreactivity, IgE cross-linking induced CD4+ T cell recruitment into the airways. In addition, when antigen-specific Th2 cells were transferred to IgE transgenic mice, IgE cross-linking significantly enhanced antigen-induced eosinophil recruitment into the airways. These findings suggest that IgE-dependent mast cell activation plays an important role in allergic airway inflammation by recruiting Th2 cells into the site of allergic inflammation.