An Unusual Case of Sarcoidosis with a Prolonged Fever and Progressive Arthropathy.

A 70-year-old man had developed a high fever and arthralgia in his right elbow 6 months prior. Loxoprofen improved the symptoms temporarily, but arthropathy developed in other joints. Long-term recurrent arthropathy and the fever caused activity reduction and progressive debilitation. We performed fluorine-18 fluorodeoxyglucose-positron emission tomography and detected a positive accumulation in multiple joints and lymph nodes. A lymph node biopsy revealed epithelioid cell granulomas, which, along with elevated angiotensin-converting enzyme levels, led to the diagnosis of sarcoid arthropathy. After prednisolone administration, the fever and arthralgia resolved, and his activities of daily living improved. Clinicians should be aware of this type of sarcoid arthropathy.

Lifestyle Factors Associated With Erosive Esophagitis in Japanese Individuals With and Without Obesity Undergoing Health Checkups.

BACKGROUND: Several lifestyle factors have been reported to be associated with erosive esophagitis (EE). Many studies examined the associated factors for EE independent of obesity. However, lifestyle factors associated with EE might differ depending on sex or the presence of obesity. This study thus aimed to investigate the lifestyle risk factors for EE stratified by obesity and sex. METHODS: A cross-sectional survey was conducted among Japanese people who underwent an annual health checkup at the Oita Health Checkup Center between 2019 and 2021. Multivariate analysis was performed to determine the factors associated with EE in participants stratified by sex and the presence of obesity. RESULTS: EE was diagnosed in 676 of 5240 participants (12.9%) who were analyzed, and occurred most often in males (601 cases). The percentage of obesity based on body mass index was significantly higher among EE than non-EE participants (50.3% and 26.5%, P < .001). In obese males, eating just before bedtime (OR = 1.34, 95% CI 1.01-1.78) and hiatal hernia (OR = 3.42, 95% CI 2.57-4.54) were significantly associated with EE in multivariate analysis. In non-obese males, current smoking (OR = 1.48, 95% CI 1.07-2.04), alcohol consumption of 40 to 60 g/day (OR = 1.60, 95% CI 1.11-2.30), and hiatal hernia (OR = 3.63, 95% CI 2.79-4.73) were significantly associated with EE. CONCLUSIONS: We found that factors associated with EE were different between obese and non-obese males. In obese males, avoiding going to bed within 2 h after dinner might contribute to preventing the occurrence of EE. In non-obese males, prevention of obesity, quitting smoking, and avoiding heavy alcohol consumption might be important for preventing the development of EE.

A Case of Tumor-Induced Osteomalacia Detected by Venous Sampling.

Tumor-induced osteomalacia (TIO) can cause osteomalacia due to excessive production of fibroblast growth factor 23 (FGF23) by the tumor. Since TIO is a very rare disease, it is often misdiagnosed as intervertebral disc herniation, spondyloarthritis, or osteoporosis. We report a 65-year-old man who developed generalized arthralgia and difficulty walking two years ago and was diagnosed with multiple fractures throughout his body. He was initially diagnosed with osteoporosis and was treated with calcitriol. However, he was referred to our hospital since his symptoms did not improve. We diagnosed tumor-induced osteomalacia based on low serum phosphorus, high bone-type alkaline phosphatase, high FGF23 levels, and the presence of two tumors. The responsible tumor was identified using FGF23 levels in venous sampling. As the location of the tumor made surgical resection difficult, we selected treatment with burosumab, a human monoclonal antibody against FGF23, leading to improvement in the hypophosphatemia and pain, such that he was able to walk with a cane. In cases of osteoporosis with hypophosphatemia, general physicians should keep TIO in mind, and attempt to identify the responsible tumor lesion.

Disseminated nontuberculous mycobacterial infection in a patient with idiopathic CD4 lymphocytopenia and IFN-γ neutralizing antibodies: a case report.

BACKGROUND: Disseminated nontuberculous mycobacterial (NTM) infection usually occurs in immunodeficient patients, such as those with human immunodeficiency virus infection and idiopathic CD4 lymphopenia. However, disseminated NTM diseases have also been reported in immunocompetent patients. Autoantibodies to interferon-gamma (IFN-γ) are known to be involved in disseminated NTM disease, although anti-IFN-γ antibodies are mainly seen in immunocompetent patients rather than those with immunodeficiency. Here, we report a rare case of disseminated NTM patient with idiopathic CD4 lymphopenia and anti-IFN-γ antibodies. CASE PRESENTATION: A 64-year-old Asian male presented with fever, back pain, anorexia and weight loss. Physical examination revealed subcutaneous masses in the forehead, sternoclavicular joint, and right inguinal region. Computed tomography showed multiple osteosclerotic changes with soft structures and osteolytic changes. Both blood and sputum cultures were positive for Mycobacterium intracellulare, confirming the presence of disseminated NTM infection. Histopathological evaluation of the subcutaneous mass in the right inguinal region showed numerous granulomas consisting of epithelioid cells with Langhans-type giant cells. He was diagnosed with idiopathic CD4 lymphocytopenia. Interestingly, he also had anti-IFN-γ autoantibodies with suppression of IFN-γ-dependent signal transducer and activator of transcription 1 (STAT1) phosphorylation. Two-drug combination therapy with clarithromycin and ethambutol was started for the NTM infection, which resulted in a favorable disease course. CONCLUSIONS: In patients with disseminated NTM infection, idiopathic CD4 lymphocytopenia and anti-IFN-γ autoantibody-positive immunodeficiency can be coexisted. It is necessary to clarify the pathogenesis and clinical course of CD4 lymphocytopenic conditions and IFN-γ neutralizing antibody-positive in the disseminated NTM disease.

A case of maoto-induced interstitial pneumonia.

A 64-year-old man was prescribed maoto, a prevailing Chinese herbal, for a cold with upper respiratory inflammation. Two days later, he developed a high fever, progressive dyspnea and pulmonary infiltration on chest high-resolution computed tomography (HRCT) including diffuse ground-glass opacity mainly around bronchovascular bundles and partial distribution of subpleural cysts resembling honeycombing. Despite the administration of azithromycin and pazufloxacin, the pulmonary infiltration and hypoxemia has rapidly progressed, so he was referred to our hospital. Although fulminant pneumonia or the acute exacerbation of idiopathic pulmonary fibrosis (IPF) was considered, his respiratory symptoms and pulmonary infiltration immediately improved and oxygen therapy was not needed on the fifth hospital day. Based on the clinical course, laboratory findings and the chest imaging findings, drug induced interstitial lung disease was suspected. The drug-induced lymphocyte test (DLST) as well as a scratch test against maoto demonstrated positive results. This is the first case report of maoto-induced interstitial pneumonia that was diagnosed based on the patient's clinical course, chest imaging findings and laboratory findings.

Significant elevation of the levels of B-cell activating factor (BAFF) in patients with sarcoidosis.

B-cell activating factor (BAFF) plays an important role in the survival and differentiation of B-cells and production of antibodies. Recent studies show that the serum BAFF levels are elevated in patients with sarcoidosis; however, they have not studied the relationship of the finding with the clinical features of the disease. The purpose of the present study is to analyze the BAFF and to elucidate the relationship between BAFF levels and the disease activity or severity of sarcoidosis. Eighty-eight patients with sarcoidosis and 21 healthy volunteers were enrolled in the present study. The BAFF levels were measured by an enzyme-linked immunosorbent assay. To assess the disease severity, we examined the number of affected organs, Schadding stages, respiratory function impairment (RFI), and the scoring system developed by Wasfi et al. The serum BAFF levels in sarcoidosis patients were significantly higher than those in healthy volunteers (median 1553.0 vs 984.6 pg/ml, p < 0.001). There were positive correlations between the serum BAFF level and disease activity markers. In addition, there were positive correlations between the BAFF levels and the disease severity score in both the serum (R = 0.367, p < 0.001) and bronchoalveolar lavage fluid (BALF) (R = 0.376, p < 0.001). This study demonstrated that the BAFF levels in both the serum and BALF were positively correlated with the disease activity markers and disease severity. BAFF may be useful as an indicator of both the disease activity and severity.

Intrascrotal and osseous sarcoidosis mimicking intrascrotal organ cancer and bony metastasis.

We report a case of sarcoidosis with concomitant epididymis, testes, and phalanxes involvement mimicking intrascrotal organ cancer and metastatic bony disease. A 23-year-old man developed blurred vision and hyperemia of the left eye, and was diagnosed as having left iritis. A chest computed tomography scan detected bilateral hilar lymphadenopathy and lung nodular shadows. A transbronchial lung biopsy revealed a non-caseating granuloma and he was diagnosed with sarcoidosis. One year after the onset of his eye symptoms, he noticed enlargement of his right scrotum. Magnetic resonance imaging detected lesions of the right epididymis, bilateral testes, and bilateral phalanxes. A technetium-99m scintigram revealed a high accumulation in the bilateral bones of extremities. These radiological findings mimicked intrascrotal organ cancer and metastatic bony disease. Pathologic evaluation following the right epididymectomy revealed non-caseating granulomas compatible with sarcoidosis. Three and half years after the appearance of intrascrotal and bony lesions, they improved spontaneously. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 373-376).

Familial Mediterranean Fever with Rheumatoid Arthritis Complicated by Pulmonary Paragonimiasis.

A 42-year-old woman presented with an intermittent fever and chest and back pain, and an abnormal chest shadow was detected. She was diagnosed with paragonimiasis caused by Paragonimus westermani. Praziquantel therapy improved the abnormal chest shadow, but did not relieve her symptoms. She was also diagnosed with familial Mediterranean fever (FMF), and colchicine therapy resolved her symptoms. She subsequently developed arthralgia and morning stiffness in her hands. We also diagnosed the patient with rheumatoid arthritis (RA), and corticosteroid and salazosulfapyridine therapy improved her symptoms. The existence of paragonimiasis complicated the diagnosis of FMF. The coexistence of FMF and RA is very rare, but does exist.

Angiopoietin-2 expression in patients with an acute exacerbation of idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: We hypothesized that increased pulmonary vascular permeability may play a role in the pathogenesis of an acute exacerbation of the idiopathic interstitial pneumonias (AE-IIPs). Angiopoietin-2 (Ang-2) promotes endothelial activation, destabilization, and inflammation. The purpose of this study was to examine whether Ang-2 expression was associated with the pathogenesis of AE-IIPs. METHODS: Twenty-three patients with AE-IIP patients, 18 acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, 37 idiopathic pulmonary fibrosis (IPF) patients, and 33 healthy volunteers (HVs) were enrolled. The serum level of Ang-2 was measured by an enzyme-linked immunosorbent assay. RESULTS: The serum levels of Ang-2 were higher in AE-IIPs and ALI/ARDS patients than in IPF patients and HVs; the BALF levels of Ang-2 were also higher than in IPF patients. There was a positive correlation between the serum level of Ang-2 and the CRP in patients with AE-IIP patients, whereas a significant positive correlation was found between the serum Ang-2 level and the CRP or SOFA scores of the ALI/ARDS patients. Although the baseline Ang-2 level was not related to survival, the Ang-2 levels significantly declined in survivors during treatment, while they did not change in non-survivors. CONCLUSIONS: Increased pulmonary vascular permeability and inflammation due to Ang-2 may play a role in the pathogenesis of AE-IIPs.

Interventricular septal thickening as an early manifestation of cardiac sarcoidosis.

We report an unusual case of cardiac sarcoidosis demonstrated by interventricular septal thickening. A 64-year-old woman was diagnosed with sarcoidosis involving the lungs, eyes, and skin. Three years later, renal dysfunction was detected during a periodic examination and a renal biopsy revealed non-caseating granulomas. Electrocardiogram results were normal, but an echocardiogram revealed thickening of the interventricular septum. Abnormal accumulation of gallium-67 and a perfusion defect in tecnetium-99-methoxyisobutylisonitrile scintigrams occurred in the interventricular septum. Magnetic resonance images showed T2-high intensity in the lesion. We considered the thickening to represent cardiac involvement of sarcoidosis. Oral prednisolone therapy diminished the interventricular septal thickening.

Tracheal ulcer due to Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

A 74-year-old man was referred to our hospital because of a tracheal stenosis circumscribed with soft tissue density and a left pulmonary nodule. Open biopsy of a right submandibular lymph node revealed diffuse large B-cell lymphoma, and the malignant cells were positive for Epstein-Barr virus gene products. Bronchofiberscopy revealed a tracheal necrotizing ulcer. After chemotherapy, the tracheal ulcer resolved. To our knowledge, this is the first report of a case of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly with a tracheal ulcer.

Hard metal lung disease successfully treated with inhaled corticosteroids.

We herein report a case of hard metal lung disease that was successfully treated with inhaled corticosteroids. A 46-year-old man was admitted to our hospital due to coughing and an abnormal shadow on a chest radiograph. He had worked as a hard metal tool sharpener for five years. Chest computed tomography scans showed centrilobular micronodules and areas of ground-glass opacity in the bilateral lung fields. Video-associated lung biopsy specimens revealed bronchocentric interstitial pneumonia and cellular bronchiolitis. A high-energy dispersion X-ray microanalysis detected tungsten. The patient was diagnosed with hard metal lung disease. Inhaled corticosteroid therapy (800 µg of ciclesonide hydrofluoroalkane daily) resolved the patient's symptoms, elevated KL-6 level, abnormal areas of chest opacity and obstructive, restrictive and diffusion impairments.

Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangitis in the course of idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary fibrosis is a manifestation of microscopic polyangitis (MPA), and often precedes the detection of MPA. The prevalence and sequence of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and MPA in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) have not been precisely elucidated. METHODS: We enrolled 61 consecutive patients with IPF and measured the MPO-ANCA titers at initial presentation and during the follow-up period. Clinical, radiologic and histologic features of MPO-ANCA-positive cases were examined. RESULTS: Of 61 patients, 3 (4.9%) had positive MPO-ANCA titers at the initial presentation of IPF. During the disease course, MPO-ANCA-positive conversion occurred in 6 patients and the prevalence of ANCA increased to 14.8%. Among the nine patients positive for MPO-ANCA, two patients developed MPA during follow-up. Histologic features of MPO-ANCA-positive pulmonary fibrosis were compatible with the usual interstitial pneumonia pattern in which alveolar hemorrhage and capillaritis were not observed. The patients with MPO-ANCA-positive conversion showed increased percentages of bronchoalveolar lavage eosinophils and more frequent complication of pulmonary emphysema compared to those with MPO-ANCA-negative IPF. CONCLUSIONS: The findings of the present study demonstrated that patients with an initial diagnosis of IPF occasionally acquire MPO-ANCA, which develops to MPA during the disease course of IPF. The presence of pulmonary eosinophilia and low attenuation areas on computed tomography scans might be predictive of MPO-ANCA positive conversion.

Incidentally discovered primary malignant melanoma of the trachea.

Primary malignant melanoma of the trachea is extremely rare. We report here the first case of primary tracheal malignant melanoma in the asymptomatic stage. Incidentally, this 73-year-old man was found to have a flat tumor at the upper trachea on chest computed tomography scans. The tumor was surgically resected with end-to-end anastomosis and was diagnosed to be primary malignant melanoma of the trachea. Four months after the surgical resection, cervical lymph node metastasis was found. Despite the resection of metastatic lymph nodes and six courses of chemotherapy, he died of cachexia approximately two years after the discovery of the tracheal tumor.

Increase in salivary cysteinyl-leukotriene concentration in patients with aspirin-intolerant asthma.

BACKGROUND: Cysteinyl-leukotrienes (CysLTs; LTC4, LTD4, and LTE4) play a considerable role in the pathophysiology of aspirin-intolerant asthma (AIA). Saliva has recently been validated as novel, simple, and noninvasive method for investigating inflammation in patients with asthma. The aim of this study is to clarify the molecular species of CysLT in saliva and to evaluate the CysLT and LTB4 concentrations in saliva in AIA patients. We also examined how the CysLT concentration in saliva reflects that of their corresponding urinary metabolite. METHODS: We preformed an analytical cross-sectional study. CysLT and LTB4 concentrations in saliva were quantified by enzyme immunoassay (EIA) following purification by high-performance liquid chromatography (HPLC). RESULTS: 1. When analyzed by EIA in combination with HPLC, saliva was found to consist of LTC4, LTD4 and LTE4 in similar amounts. 2. In saliva analysis among the three groups (AIA patients, aspirin-tolerant asthma [ATA] patients, and healthy subjects), both the concentrations of CysLTs and LTB4 were significantly higher in AIA patients than in ATA patients and healthy subjects. 3. We found significant correlations between CysLT concentration and LTB4 concentration in saliva in each group. 4. No significant correlation was found between the concentration of LTE4 in urine and that of CysLTs in saliva. CONCLUSIONS: In this study, we found higher concentrations of CysLTs and LTB4 in saliva from AIA patients than in saliva from ATA patients, suggesting that the quantification of CysLT and LTB4 concentrations in saliva may be another diagnostic strategy for AIA.

Osteopontin levels are elevated in patients with eosinophilic pneumonia.

BACKGROUND AND OBJECTIVE: Osteopontin is a key cytokine involved in pro-inflammatory T helper type 1 (Th1)-associated immune responses, which has recently been implicated in allergic diseases. We investigated the pathogenic role of osteopontin in eosinophilic pneumonia. METHODS: The concentrations of osteopontin and Th1- or Th2-associated cytokines were measured in BAL fluid (BALF) from 41 patients with eosinophilic pneumonia, including those with acute (AEP, n = 12), chronic (CEP, n = 16), or drug-induced eosinophilic pneumonia (DEP, n = 13). The results were compared with those from patients with other interstitial lung diseases. Immunocytochemistry and double immunofluorescence labelling were performed to determine the cellular source of osteopontin. RESULTS: Osteopontin was significantly elevated in BALF from patients with eosinophilic pneumonia as compared with BALF from patients with drug-induced interstitial pneumonia, hypersensitivity pneumonitis, idiopathic interstitial pneumonia, or sarcoidosis, and also compared with BALF from healthy volunteers. Osteopontin concentrations elevated at the time of exacerbation decreased during clinical improvement, either spontaneously or as a result of corticosteroid therapy. Elevated concentrations of CXCL10, CCL17 and IL-10 were also detected in BALF from patients with eosinophilic pneumonia. Osteopontin concentrations in BALF of AEP patients were correlated with IL-5, as well as IL-10, CCL11, CCL17 and CXCL10 concentrations. In AEP and DEP patients, serum osteopontin concentrations were also elevated. Double immunofluorescence labelling showed that in patients with eosinophilic pneumonia, osteopontin was expressed in lung eosinophils. CONCLUSIONS: Osteopontin is likely to contribute to the development of inflammation in patients with eosinophilic pneumonia.

Hypertrophic pulmonary osteoarthropathy as a paraneoplastic manifestation of lung cancer.

INTRODUCTION: This study examined the frequency of hypertrophic pulmonary osteoarthropathy (HPO) and the clinical characteristics of lung cancer with HPO. METHODS: The results of 2625 lung cancer patients who underwent bone scintigraphy were reviewed to identify patients with HPO, which was diagnosed when the bone scintigram showed a diffuse, symmetric pattern of bilateral increased uptake in the long tubular bones. Clinical characteristics were investigated based on the clinical and pathologic records. RESULTS: Nineteen patients (0.72%) were found to have HPO: 17 were men, 17 were heavy smokers, and 13 had clinical stage IIIB or IV disease. Ten patients complained of pain or edema in the extremities, and seven of them had stage IIIB or IV disease. In four patients with clinical stage IIIB or IV disease, HPO was not detected at the first presentation, and the diagnosis was made after disease progression. The symptoms of HPO improved in two patients who underwent surgical resection but in only three of five patients who received chemotherapy. The HPO findings on the bone scintigram improved in 2 of 3 patients who underwent surgical resection and 5 of 11 patients who received chemotherapy. CONCLUSIONS: Less than 1% of the lung cancer patients developed HPO as a paraneoplastic manifestation. Males, heavy smokers, and advanced disease predominated in lung cancer patients with HPO. The symptoms and bone scintigram findings of HPO improved in half of the patients on treating the lung cancer.

CD203c expression on human basophils is associated with asthma exacerbation.

BACKGROUND: CD203c is a basophil cell surface marker used to diagnose and monitor various allergic diseases, but its relationship to asthma is not clear. OBJECTIVE: We determined whether CD203c expression levels are associated with stable and exacerbated asthma. METHODS: We used flow cytometry to compare spontaneous expression levels of surface markers on basophils from patients with stable or exacerbated asthma and from healthy subjects. Longitudinal changes in these expression levels were measured after basophil stimulation by IgE-dependent or IgE-independent mechanisms and compared with patients' asthma status. RESULTS: Spontaneous expression levels of CD203c were significantly higher on basophils from patients with asthma exacerbation than patients with stable asthma or healthy subjects. In contrast, no differences in spontaneous expression levels of CD63 or CD69 were observed among the 3 groups. Anti-IgE-induced expression of CD203c significantly increased in basophils during asthma exacerbation (P = .005). Low concentrations of Dermatophagoides pteronyssinus or IL-3 induced higher expression levels of CD203c during asthma exacerbation than during clinical improvement; induction of CD203c expression by these antigens therefore correlates with asthma control. In the patients with clinical improvement, there was a correlation between spontaneous CD203c expression levels and the percent predicted values of FEV(1) (r = -0.761; P = .022). CONCLUSION: Asthma exacerbation was accompanied by increased expression of CD203c on basophils that decreased significantly during remission. Basophil expression levels of CD203c might therefore be used to monitor asthma in patients.

Significance of serum vascular endothelial growth factor level in patients with idiopathic pulmonary fibrosis.

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, which has been implicated in the pathogenesis of fibrotic lung diseases, including idiopathic pulmonary fibrosis (IPF). The aim of this study was to examine the clinical significance of the serum VEGF level for evaluating disease severity and progression. The levels of VEGF in serum were measured in 41 patients with IPF, 14 patients with lung cancer, and 43 healthy volunteers. We measured the serum levels of CRP, LDH, KL-6, SP-D, and the parameters obtained from arterial blood gas analysis and pulmonary function tests. High-resolution computed tomography (HRCT) was performed to determine the extent of the interstitial and the alveolar opacities. The ability of each biomarker to predict disease severity was estimated by measuring the area under the receiver operating characteristic curve (AUC). The VEGF levels of IPF patients with high alveolar-arterial difference of oxygen (AaDO(2)) levels were significantly elevated than those with low AaDO(2) levels and those of healthy volunteers. When examined within the IPF group, a significant positive correlation was found between the VEGF levels and the HRCT interstitial score (p = 0.027) and the KL-6 levels (p = 0.037). Among several serum biomarkers, VEGF showed the largest AUC for predicting disease severity as defined by a high AaDO(2) value. There was an inverse correlation between the baseline VEGF level and the monthly change in percent predicted vital capacity. The serum VEGF level may reflect the severity of IPF and offer clinical benefits to predict the disease's progression.

Increased serum ADAM8 concentration in patients with drug-induced eosinophilic pneumonia-ADAM8 expression depends on a the allergen route of entry.

BACKGROUND: ADAM8 (a disintegrin and a metalloprotease 8) has been linked to asthma and eosinophilic pneumonia (EP). ADAM8 cleaves a variety of substrates and is a sheddase for CD23, the low affinity IgE receptor. The concentration of soluble ADAM8 (sADAM8) is increased in bronchoalveolar lavage fluid (BALF) from patients with smoking-induced acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP), but not drug-induced EP (Drug-EP). In AEP, the BALF sADAM8 concentration significantly correlates with the soluble CD23 concentration (sCD23). METHODS: To evaluate the involvement of ADAM8 in the pathogenesis of eosinophilic pneumonia, we measured the concentrations of sADAM8 and its substrate, soluble CD23 (sCD23), in serum from patients with AEP, CEP, and Drug-EP. We also measured the change in the sADAM8 concentration after a provocation test. RESULTS: In contrast to the BALF findings, serum sADAM8 concentrations were increased in Drug-EP (mean+/-SEM; 639.6+/-49.15) and serum ADAM8 levels correlated positively with the serum sCD23 levels in patients with Drug-EP (P=0.0080, R(2)=0.8465). Serum sADAM8 concentrations were also increased in AEP (409+/-76.91) and CEP (644.7+/-87.03). Serum ADAM8 concentrations were also elevated after the provocation test. CONCLUSION: Serum ADAM8 concentrations were elevated in Drug-EP, although the sADAM8 concentrations were not increased in the BALF in Drug-EP. Thus, the pathogenesis of AEP and Drug-EP may be distinct with regard to allergen exposure; AEP may be caused by the inhalation of antigens, whereas Drug-EP may be caused by bloodstream antigens. These findings indicate that ADAM8 levels reflect the route of eosinophilic inflammation in EP.