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A 40-year-old Japanese woman was admitted to Oita University Hospital with progressive dyspnea, consciousness disturbance and severe cytopenias. Her chest roentgenogram showed diffuse bilateral infiltrates. She was therefore forced to receive mechanical ventilation. Bone marrow aspiration disclosed numerous hemophagocytic histiocytes, thus suggesting her condition to be hemophagocytic syndrome. In addition, she also developed myocarditis and renal failure. Pulsed methylprednisolone, gamma-globulin, granulocyte colony-stimulating factor and sivelestat sodium hydrate were administrated, and thereafter the patient recovered from cytopenia and organ failure. Afterwards, influenza A H3N2 was detected from bronchial extracts. We should recognize that an influenza A virus infection can induce hemophagocytic syndrome and acute respiratory failure as the initial manifestations of multiple organ failure.

In an attempt to understand the role of interleukin-18 (IL-18) in the pathogenesis of sarcoidosis, we examined the expression of IL-18 in normal muscle and in muscle biopsies from six patients with muscular sarcoidosis. Western blot analysis demonstrated that IL-18 was identified only in homogenates of granulomatous muscle tissues, but not in normal muscle tissue homogenates. By immunohistochemistry, strongly IL-18-positive cells were distributed predominantly at the boundary zone of the granulomas. They were recognized as activated macrophages by double staining with anti-CD68. Epithelioid cells showed only faint reactivity. Serum IL-18 levels of patients with sarcoidosis were significantly increased compared to those of healthy volunteers. Unlike protein expression, IL-18 mRNA expression was detected even in normal muscles. Our results coupled with those of previous investigations demonstrating activity of IL-18 in inducing interferon-gamma production suggest a significant role of IL-18 in the pathogenesis of sarcoidosis.

A 47-year-old female was diagnosed to have pulmonary, ocular, and nodular-type muscular sarcoidosis. Seven years later, nodules developed in all limb muscles. She received minocycline 200 mg daily, which resulted in an obvious reduction of the muscular sarcoidosis with a significant decrease in the serum angiotensin-converting enzyme level. Nine months later, the minocycline was discontinued, thus resulting in a rapid recurrence of the disease. The immediate readministration of minocycline again resulted in a prompt improvement. We detected Propionibacterium acnes within the granulomas in the affected muscle by an immunohistochemistry. More interestingly, we found a decrease in the circulating levels of interleukin-12 p40 and interferon-inducible protein-10 during the minocycline therapy. The minocycline therapy may be effective for sarcoidosis and the fact that the disease rapidly relapsed after discontinuation of the minocycline administration suggests that the mechanism of action in this case may be immunomodulating but not antimicrobial effect.

A 68-year-old woman presenting dyspnea on exertion was admitted. Hypoxemia and a considerably elevated level of serum KL-6 were noted. Chest high-resolution computed tomography (HRCT) scans demonstrated panlobular ground-glass opacities with a mosaic distribution and hilar and mediastinal lymphadenopathy. Bronchoalveolar lavage revealed an increased percentage of lymphocytes and an elevated CD4/CD8 ratio, implicating a diagnosis of sarcoidosis. However, as we could not exclude other diffuse lung diseases because of unusual HRCT pattern in sarcoidosis, video-assisted thoracoscopic lung biopsy was performed. The histology of epithelioid cell granulomas in the specimens of the lung and the lymph nodes confirmed a diagnosis of sarcoidosis. The lung specimens corresponding to areas of increased opacity demonstrated diffuse alveolitis with minimal fibrosis between individual granulomas. Immunohistochemistry for KL-6 provided positive results on alveolar lining cells in areas of alveolitis but not on granulomas. After steroid treatment, the ground-glass opacities disappeared and the serum KL-6 level normalized. We discuss this rare case of pulmonary sarcoidosis presenting panlobular ground-glass opacities with mosaic distribution.

Background The presentation of acute eosinophilic pneumonia (AEP) closely resembles that of acute lung injury (ALI)/ARDS, including its idiopathic form, acute interstitial pneumonia (AIP). AEP usually lacks peripheral eosinophilia at the acute phase; therefore, the establishment of serum biomarkers for AEP would be clinically useful. Methods We measured the levels of thymus- and activation-regulated chemokine (TARC)/CCL17, eotaxin/CCL11, KL-6, and surfactant protein-D (SP-D) in serum for patients with acute parenchymal lung diseases including AEP (n = 17), AIP (n = 13), pneumonia-associated ALI/ARDS (n = 12), and alveolar hemorrhage (n = 7). To evaluate diagnostic ability, each marker was estimated by measuring the area under the receiver operating characteristic curve (AUC). Results Serum TARC/CCL17 levels of AEP patients were much higher than those of patients in other disease groups. More importantly, high circulating TARC/CCL17 levels were observed in AEP even at acute phase when peripheral eosinophilia was absent. TARC/CCL17 showed the largest AUC, and the TARC/CCL17 levels with cutoff points from 6,259 to 7,039 pg/mL discriminated AEP from other syndromes with sensitivity and specificity of 100%. The KL-6 level was low in most patients with AEP, and the sensitivity was 81.6% in cutoff with 100% specificity. The AUC for eotaxin/CCL11 and SP-D was small, with values of 0.73 (95% confidence interval [CI], 0.60 to 0.86) and 0.53 (95% CI, 0.31 to 0.64), respectively. Conclusions This study indicates that the measurement of circulating TARC/CCL17 and KL-6 is useful for discriminating AEP from other causes of ALI.

A 52-year-old woman visited a local hospital with a high fever, non-productive cough and general fatigue. Her chest X-ray showed infiltrate in the right middle lung field. Computed tomography scans revealed ground-glass opacity and surrounding ring-shaped air-space consolidation, the "reversed halo sign". Cefpirom was administered, but her symptoms persisted and the infiltrate migrated to the left upper lobe. As cryptogenic organizing pneumonia was suspected, she was then treated with intravenously pulsed methylprednisolone followed by prednisolone. Despite these therapies, acute respiratory failure occurred and she was therefore transferred to our hospital. On admission, severe hypoxemia and diffuse bilateral infiltrates on chest images suggested acute respiratory distress syndrome. As we obtained information that a parakeet had recently died at her home, minocycline was administered, resulting in prompt improvement of the symptoms, respiratory insufficiency and pulmonary infiltrates. Finally, elevated antibody titers against Chlamydophila psittasi confirmed a diagnosis of Psittacosis. Sequential chest computed tomography scans in this case indicate that absorption of marginal air-space consolidation with extended central ground glass attenuation in concordance with a new infiltrate on another lung field appeared to create wandering infiltrate. Wandering infiltrate on chest X-ray in psittacosis may be a sign of disease progression.

A 66-year-old man had been given bepridil for the treatment of atrial fibrillation since April 28, 2002. The patient developed exertional dyspnea with hypoxemia in the middle of June 2002 and was admitted to our hospital. The chest X-ray and chest CT scans showed diffuse reticulonodular infiltrates in the lower lung fields. Pulmonary function tests revealed depletion of diffusion capacity for carbon monoxide. Bronchoalveolar lavage fluid contained increased percentages of lymphocytes, neutrophils and eosinophils, and a CD4/8 ratio was low. The transbronchial lung biopsy specimens demonstrated alveolar septal thickening with infiltration of mononuclear cells and intraalveolar organization. As drug-induced pneumonitis was suspected, bepridil was discontinued, resulting in improvement of dyspnea and hypoxemia. The patient was then treated with corticosteroid, which led to complete resolution of infiltration on chest X-ray. According to the clinical data consistent with drug-induced pneumonia, the prompt improvement after cessation of bepridil and the absence of other possible causes, we diagnosed this case as bepridil-induce pnemonitis.

A 17-year-old adolescent was admitted to Oita University Hospital with non-productive cough and exertional dyspnea. She had been smoking approximately 10 cigarettes per day for two years. When the patient was three years old, she underwent surgical removal of skull tumor of Langerhans cell histiocytosis. Initial chest CT scans showed coalescing thick-walled air cysts surrounded by micronodules in both lungs, most predominantly in the middle and upper lung fields. Bronchoalveolar lavage fluid contained 2.3% of CD1a-positive cells and video-assisted thoracoscopic lung biopsy disclosed granulomatous lesions consisting of histiocytic cells containing S-100 protein but without CD68 antigen allowing a diagnosis of pulmonary Langerhans cell histiocytosis. She stopped smoking, resulting in spontaneous resolution of the coalescing air cysts which were replaced by funicular scarring within two years. In case of extra-pulmonary Langerhans cell histiocytosis in children, the close relationship between cigarette smoking and pulmonary involvement should be informed to the parents to prevent the patient starting smoking in the future.

Amyopathic dermatomyositis (ADM) is occasionally complicated by rapidly progressive interstitial pneumonia (RPIP), and in such cases, diffuse alveolar damage (DAD) is usually diagnosed at autopsy. Here, we present three patients with RPIP accompanied by ADM in whom lung disease was assessed at an early stage. High-resolution computed tomography (HRCT) carried out before the onset of dyspnoea revealed uniformly subpleural reticular opacity with faint ground-glass attenuation. At that stage, surgical lung biopsies from two patients showed histological patterns typical of cellular nonspecific interstitial pneumonia (NSIP). Despite pulse methylprednisolone and subsequent high-dose oral administration of prednisolone, lung disease progressed in all patients, with extensive areas of ground-glass opacity and consolidation observed in HRCT scans. DAD was confirmed histologically in one case. Additional administration of cyclosporine, pulse cyclophosphamide or high-dose intravenous administration of immunoglobulin rescued all patients. Our data suggest that ADM-associated interstitial pneumonia takes an aggressive course even when the radiological and histological features are consistent with NSIP. Aggressive combination therapy with high-dose steroids and immunosuppressive agents is required as early as possible for patients with this life-threatening disorder.

Thymus- and activation-regulated chemokine (TARC/CCL17) is a lymphocyte-directed CC chemokine, which plays a role in the recruitment of CC chemokine receptor-4 positive T helper 2 (Th2) cells. In this study, we measured concentrations of TARC and Th2 cell-derived cytokines in bronchoalveolar lavage (BAL) fluid, as well as TARC concentrations in serum from patients with eosinophilic pneumonia and other interstitial lung diseases. TARC was significantly elevated in BAL fluids from patients with eosinophilic pneumonia (median, 240 pg/ml), whereas TARC was undetectable (< 7 pg/ml) in most cases of hypersensitivity pneumonitis, sarcoidosis, and idiopathic pulmonary fibrosis, as well as in healthy control subjects. Also, when present, quantities were less than 20 pg/ml. Elevated concentrations of interleukin (IL)-4, IL-5, and IL-13 were also detected in BAL fluid from patients with eosinophilic pneumonia. Interestingly, TARC concentrations in BAL fluids were closely correlated with the concentrations of IL-5 and IL-13. A serial examination showed that elevated TARC in BAL fluid rapidly fell to below detectable limits preceding decreases in IL-5 concentration and eosinophil percentage. Our results, in concordance with previous studies, demonstrate the potential activity of TARC for recruiting Th2 cells to the lungs and suggest a significant role for TARC in the pathogenesis of eosinophilic pneumonia.

Summary Background In sarcoidosis, the T helper type 1 (Th1) response tends to predominate at affected disease sites; however, whether Th1/Th2 polarization occurs in the peripheral circulation is unknown. Methods Fifty-two patients with sarcoidosis and 21 healthy volunteers were investigated. The concentrations of interferon-inducible protein 10 (IP-10)/CXCL10 and thymus- and activation-regulated chemokine (TARC)/CCL17 in the serum, bronchoalveolar lavage fluid (BALF) and culture supernatant were measured by an enzyme-linked immunosorbent assay. The circulating CXCR3+ CD4+ T cells and CCR4+ CD4+ T cells were assessed by flow cytometry. Results The CXCR3- or CCR4-positive ratios among CD4+ T cells were both higher in sarcoidosis than in healthy volunteers. The serum levels of both IP-10 and TARC of the patients with sarcoidosis were significantly higher than those of the healthy volunteers. In patients with sarcoidosis, a larger amount of IP-10 was generated by the BALF cells, whereas IP-10 production by peripheral blood mononuclear cells did not increase in comparison to the control subjects. The TARC levels produced by peripheral blood mononuclear cells of sarcoidosis patients were significantly higher than those of the controls, while no difference existed between the 2 groups regarding TARC production by BALF cells. Conclusion IP-10 is mainly produced at the lung and TARC in the peripheral circulation in sarcoidosis patients. Both IP-10 and TARC cooperatively play a role in the pathogenesis of sarcoidosis.