Mineharu Sugimoto

Usefulness of Endobronchial Ultrasonography for Transbronchial Lung Biopsies of Peripheral Lung Lesions

Background: Peripheral lung lesions are increasing in numbers. Endoscopic diagnosis is essential for the prevention of unnecessary operations. Conventional diagnostic procedures have limitations in availability and results. Objectives: Endobronchial ultrasonography (EBUS) was investigated as a means to guide transbronchial lung biopsy, to reduce the discomfort during the procedure and to improve diagnostic accuracy. Methods: In 50 cases, we performed transbronchial lung biopsy combined with EBUS and fluoroscopic guidance. The results were compared to 42 controls assessed by fluoroscopy only. Results: In 38 cases (76%), EBUS could describe the peripheral lesion (33 from inside, including 9 cases with difficulties in fluoroscopic observation, and 5 from an adjacent bronchus, indicating the correct location of the lesion). If successfully placed inside, a change in the patient’s position was not required, which helped to reduce patient discomfort. Lung cancer was diagnosed in 24 patients and benign disease in 25 patients; in 1 case diagnosis remained unknown. When the EBUS probe could be introduced inside the lesion, the sensitivity for cancer diagnosis and specificity for cancer exclusion were 100%, respectively (15/15, 18/18). Compared to the controls in whom the biopsy site was determined by fluoroscopy only, the sensitivity tended to be superior by EBUS, although it did not reach statistical significance (p = 0.06). However, specificity and accuracy were statistically significant (both p = 0.02). Conclusions: When the lesion can be correctly described by EBUS from inside the lesion, EBUS is useful to guide transbronchial lung biopsy, can contribute to a reduction in patient discomfort and improves the accuracy of diagnosis. Additional navigation tools to increase correct positioning of the EBUS probe are desirable.

Pneumocystis jirovecii infection: an emerging threat to patients with rheumatoid arthritis

Accompanying the increased use of biologic and non-biologic antirheumatic agents, patients with RA have been exposed to an increased risk of Pneumocystis jirovecii infection, which causes acute fulminant P. jirovecii pneumonia (PCP). Mortality in this population is higher than in HIV-infected individuals. Several guidelines and recommendations for HIV-infected individuals are available; however, such guidelines for RA patients remain less clear. Between 2006 and 2008 we encountered a clustering event of P. jirovecii infection among RA outpatients. Through our experience with this outbreak and a review of the recent medical literature regarding asymptomatic colonization and its clinical significance, transmission modes of infection and prophylaxis of PCP, we have learned the following lessons: PCP outbreaks among RA patients can occur through person-to-person transmission in outpatient facilities; asymptomatic carriers serve as reservoirs and sources of infection; and short-term prophylaxis for eradication of P. jirovecii is effective in controlling PCP outbreaks among RA outpatients.

Adult Chédiak‐Higashi syndrome presenting as parkinsonism and dementia

Chédiak‐Higashi syndrome (CHS) in children can be a fatal disease. We describe the oldest known CHS patient first seen with a neurologic disorder in early adult life. From the age of 22, this 39‐year‐old woman developed mental deterioration, parkinsonism including resting tremor at the tongue, mandible, and hands, oculogyric crisis, muscular atrophy of limbs, and loss of tendon reflexes. MRI showed marked temporal dominant brain atrophy and diffuse spinal cord atrophy. Partial albinism, panleukocytic giant granules, and profoundly decreased NK‐cell activity were compatible with childhood CHS, but apparently normal neutrophil function prolonged her survival. Stimulated proliferation of lymphocytes was less than 40% that of normal controls.

A followup study of asymptomatic carriers of Pneumocystis jiroveci during immunosuppressive therapy for rheumatoid arthritis.

Objective. To examine the preventive effects of prophylaxis against Pneumocystis jiroveci-induced pneumonia (PCP) in patients receiving immunosuppressive therapy for rheumatoid arthritis (RA) who are colonized by this organism. Methods. We performed molecular testing by polymerase chain reaction (PCR) for P. jiroveci on induced sputum or bronchoalveolar lavage fluids of 82 patients with RA. During primary prophylaxis, asymptomatic carriers of this organism were examined by high-resolution computed tomography and PCR every 2 weeks. RA patients who had developed PCP received PCR tests every week. Once negative results were obtained, PCR testing was scheduled at Months 1, 3, and 6, followed by reexaminations every 6 months. Results. We found 9 cases of asymptomatic carriage of P. jiroveci. All the carriers had received low doses of methotrexate. Upon introduction of PCP prophylaxis, 5 cases tested negative for PCR within 1 month. Three carriers developed PCP before starting prophylaxis, but these tested negative for PCR after short periods (1–2 weeks) of PCP treatment. Once P. jiroveci was eradicated, all cases maintained negative PCR results during followup without prophylactic intervention, even after resuming immunosuppressive therapy. One patient refused PCP prophylaxis, but no PCP developed. Conclusion. RA patients with asymptomatic carriage of P. jiroveci benefited from short-term prophylaxis against PCP. Positive PCR results appeared to be predictive of future development of PCP in RA patients. Identification of P. jiroveci carriers will encourage prompt introduction of PCP prophylaxis when rheumatologists consider immunosuppressive therapy for RA.

Comparative analysis of nucleotide sequences of the partial envelope gene (5′ Domain) among human T lymphotropic virus type I(HTLV-I) isolates

Human T-cell lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The nucleotide sequences of 640 bp of the proviral genome (positions 5158-5797) derived from 11 HTLV-I-infected persons were analyzed using the polymerase chain reaction and M13-based sequencing techniques. Patterns of single nucleotide substitutions were characterized from the extracellular domain of the envelope gene (gp46). Compared with other retroviruses, the nucleotide sequences of the HTLV-I external envelope gene are highly conserved among the genotypes studied. We found no evidence of dual infections with HTLV-II among the seropositive asymptomatic persons or in patients with either ATL or HAM/TSP. No unique sequence differences were observed in the envelope gene of the HTLV-I isolates derived from patients coinfected with human immunodeficiency virus type 1 (HIV-1). However, comparative analysis of these data and other published HTLV-I envelope sequences indicated the presence of four subtypes of HTLV-I in relation to their geographic origin.

A Cluster of Pneumocystis jirovecii Infection Among Outpatients with Rheumatoid Arthritis

To the Editor: Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PCP), well known to be one of the most frequent and serious complications occurring under immunocompromised conditions such as HIV infection. Accumulating reports have also shown the clinical significance of PCP in patients with malignancy, in transplant recipients, and in patients receiving immunosuppressive therapy. Indeed, a recent postmarketing surveillance report by the Japan College of Rheumatology indicated a high incidence of PCP in patients with rheumatoid arthritis (RA) receiving the anti-tumor necrosis factor-α agents infliximab and etanercept (0.4% and 0.2%, respectively). Despite recent advances in understanding human Pneumocystis infection, the exact mode of its transmission and acquisition remains unclear, and both the source and reservoir for infection in humans have not yet been established1. We describe a cluster of asymptomatic carriage of P. jirovecii and/or PCP occurring among outpatients with RA. Clinical and epidemiological data strongly suggest person-to-person transmission of P. jirovecii in our outpatient facility as the predominant route of acquisition. Kumamoto Saishunsou National Hospital is a 500-bed general hospital consisting of 3 buildings, located in the suburbs of Kumamoto City in western Japan. One building accommodates an outpatient clinic and a radiodiagnostic facility, which are both shared by all outpatients; about 200 outpatients from 12 clinical sections visit this building daily. Accordingly, patients with RA visit this building for regular checkups and … Address correspondence to Dr. Mori. E-mail: moris{at}saisyunsou1.hosp.go.jp

Pneumocystis jirovecii Pneumonia in Rheumatoid Arthritis Patients: Risks and Prophylaxis Recommendations

Pneumocystis jirovecii infection causes fulminant interstitial pneumonia (Pneumocystis pneumonia, PCP) in patients with rheumatoid arthritis (RA) who are receiving biological and/or nonbiological antirheumatic drugs. Recently, we encountered a PCP outbreak among RA outpatients at our institution. Hospital-acquired, person-to-person transmission appears to be the most likely mode of this cluster of P. jirovecii infection. Carriage of P. jirovecii seems a time-limited phenomenon in immunocompetent hosts, but in RA patients receiving antirheumatic therapy, clearance of this organism from the lungs is delayed. Carriers among RA patients can serve as sources and reservoirs of P. jirovecii infection for other susceptible patients in outpatient facilities. Development of PCP is a matter of time in such carriers. Considering the poor survival rates of PCP cases, prophylactic antibiotics should be considered for RA patients who are scheduled to receive antirheumatic therapy. Once a new case of PCP occurs, we should take prompt action not only to treat the PCP patient but also to prevent other patients from becoming new carriers of P. jirovecii. Short-term prophylaxis with trimethoprim-sulfamethoxazole is effective in controlling P. jirovecii infection and preventing future outbreaks of PCP among RA patients.

Is continuation of anti-tumor necrosis factor-α therapy a safe option for patients who have developed pulmonary mycobacterial infection?

Continuation of anti-tumor necrosis factor-α (TNFα) therapy generally has not been recommended for patients who have developed nontuberculous mycobacterial (NTM) diseases; in daily practice, however, we often encounter patients with refractory rheumatoid arthritis (RA) who experience uncontrollable flares following withdrawal of anti-TNFα agents. Here, we report a case of pulmonary NTM disease caused by Mycobacterium intracellulare occurring in a patient with refractory RA undergoing etanercept therapy. Since there was the concern of an exacerbation of RA symptoms, etanercept was continued during anti-NTM therapy. The patient’s pulmonary symptoms and radiological abnormalities were found to have markedly improved in a relatively short time period after beginning the anti-NTM therapy. Additionally, her RA symptoms were adequately controlled without the occurrence of any unexpected adverse events. The continuation of etanercept therapy may be a safe option during anti-NTM therapy if patients’ underlying diseases would otherwise be difficult to control. Strictly supervised anti-NTM therapy and patients’ informed consent are mandatory. We review the medical literature on NTM disease associated with anti-TNFα therapy for rheumatic diseases and discuss the safety of simultaneous use of anti-TNFα agents in patients during anti-NTM therapy.

Chemotactic Heterogeneity of Eosinophils in Idiopathic Pulmonary Eosinophilia

Heterogeneity in the chemotactic response of eosinophils to 5 T cell line eosinophilic chemotactic factors (ECFs) was assessed in 5 patients with idiopathic pulmonary eosinophilia. Eosinophils from 2

Detection of ALK rearrangement in an octogenarian patient with pleomorphic carcinoma of the lung

We herein present a rare case of ALK-positive pulmonary pleomorphic carcinoma in an octogenarian patient. A computed tomography scan of the thorax indicated a pulmonary nodule in the right upper lobe of an asymptomatic 87-year-old female. The surgical resection revealed that the disease was pleomorphic carcinoma with pathological T2aN0M0, stage IB. EML4-ALK was evaluated using immunohistochemistry and fluorescence in situ hybridization, and EGFR mutations were analyzed using the Cycleave method. While there were no EGFR mutations detected, she was positive for the ALK rearrangement. This is the first report of ALK rearrangement in an octogenarian patient with pleomorphic carcinoma of the lung.