Osteopontin is a glycosylated phosphoprotein that contains two distinct integrin binding domains and that has cleavage sites by thrombin and by matrix metalloprotease-3 (MMP-3) and MMP-7. Osteopontin structurally resembles a matrix protein and has well-characterized cytokine-like properties including the regulation of cellular adhesion and migration and cell-mediated immunity. Circulating ostenponin is a marker of disease activity in granulomatous disorders. Osteopotin expression is increased in alveolar macrophages, T cells and alveolar epithelial cells in a range of lung diseases such as sarcoidosis, tuberculosis, and lung fibrosis and has been shown to regulate aspects of pulmonary granuloma formation and fibrosis. Future investigations will explore the diagnostic and therapeutic potentials of modulating the function of osteopontin.

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We investigated clinical characteristics and therapeutic outcome of nine patients with bone involvement (6 males and 3 females) out of the 416 sarcoidosis cases (2.2%) visiting our clinic during the past decade. As four of them who were undergoing no treatment showed a new bone lesion, the affected sites totaled 14: seven hand phalanxes, five metatarsus, and two foot phalanxes. Almost all bone lesions appeared in company with worsening or new manifestation of other organ lesions. The chief complaints were pain in the affected regions in eight patients and deformity of hand fingers in one. As for diagnostic procedures, bone x-rays worked satisfactorily in all but one, revealing cystic or lacy lytic patterns. Bone scintigram and/or magnetic resonance imaging were sometimes more high resolution than x-rays. When patients having affected finger bones shake hands they frequently complain of finger pain. This “handshake sign” seems useful for suspecting finger bone involvement. As for treatment, five of the nine needed corticosteroids and four of them were successfully treated in a year or so to the point of ceasing medication or minimizing the dose. As corticosteroids give relief for persistent bone pain, we need not hesitate prescribing corticosteroid for them.

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The risk of cancer following sarcoidosis has long been an issue argued over but no conclusion has so far been drawn.
We found 19 patients diagnosed as having malignant tumors following sarcoidosis among the 355 sarcoidosis patients visiting Okayama University Hospital. They are classified into 14 types and 25 malignant tumors. Among them, 7 lung cancer cases were found. The average observation period from the diagnosis of sarcoidosis to the detection of lung cancer was 9.7 years (1.8-15.7 years). And the average age at the onset of the lung cancer was 68 years old (38-78 years old), being older than the national average.
We calculated the relative risk of malignant tumors based on the 355 patients with sarcoidosis for a total of 3, 340 personyears. The observed number of lung cancer cases was 7 per 100, 000 with the relative risk being 2.45 times (p<0.05) higher, than the expected number (2.86 per 100, 000 people).
As sarcoidosis appears to increase the risk of lung cancer, careful observation of sarcoidosis patients may be needed.

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We evaluated the clinical features of 32 sarcoidosis cases associated with asthma. In our clinic, 32 (10.6%) of the 301 sarcoidosis patients (108 male, 193 female, average observation period 7.5±4.2 years) had asthma. The association was found more frequently in females (25 cases-13.0%) than in males (7 cases-6.5%). The stage of chest X-ray and age-sex distribution were the same between those with and without asthma. Asthma appeared in 6 cases before sarcoidosis and in 26 cases after sarcoidosis: 7 cases in 2 years, 8 cases after 3-5 years, 8 cases after 6-9 years and 3 cases after 10 years or more. Asthma was diagnosed in 19 cases (17.9%) of the 106 cases whose sarcoidosis deteriorated or remained unchanged, and in 7 cases (3.7%) of the 189 cases whose sarcoidosis improved. From the present molecular-biological view, sarcoidosis is a Th1 disease, while asthma is a Th2 disease and we expected the two diseases might show a reversed trend. However, our experiences revealed that asthma occurred during the periods of either improvement or deterioration of sarcoidosis.

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The case of a 45-year-old man who was diagnosed to have pulmonary sarcoidosis at the age of 27, and bulla on the right upper lung fields at 35 is reported. A biopsy of a subcutaneous nodule confirmed sarcoidosis. An ophthalmological examination revealed iritis, vitreous opacities and hemorrhage at 36. At the age of 37, bully appeared in the left upper lung field. Since the age of 39, he has been given herb medicine as an out-patient. At age 44, he was on corticosteroids for iatrogenic eruptions. Thereafter, the wall of bulla on the left side became thick with manifestation of fungus ball and the diagnosis was aspergillosis. He was treated with anti-fungal agents. Though pulmonary aspergillosis is a well-known pulmonary complication of advanced pulmonary sarcoidosis, we reported this case, stressing the entire course of x-ray images of the gradually expanding bulla for 10 years since the infection.

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Bilateral enlargement of hilar lymph nodes on a chest radiograph was incidentally found in a 63-year-old woman in 1993. She was diagnosed to have sarcoidosis, and had periodic checkups by physicians without medication being prescribed. Thirst and polydipsia had developed a month before admission. On Sept. 10, 2004, she was admitted to our hospital for further examinations because of elevated levels of serum calcium and PTHrP with low PTH. Humoral hypercalcemia of malignancy was suspected, but malignancy was not found after extensive investigations including chest and abdominal CT, endoscopic examinations of gastrointestinal tracts and bone scintigram. Hypercalcemia in sarcoidosis is less common in Japan than in US and Europe, and has been considered to be derived from elevated levels of 1, 25-(OH)₂D₃. Since there have been few reports in the literatures of sarcoidosis with hypercalcemia caused by elevated levels of serum PTHrP, we herein report a patient with sarcoidosis associated with elevated levels of calcium and PTHrP.

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We report a case of a 42-year old man who had cervical and bilateral hilar lymphadenopathy with elevated serum ACE level diagnosed by a private physician in February 2001. He was referred to Teikyo University Hospital because of bilateral hydronephrosis in April 2004, and underwent nephrostomy followed by retrograde ureteral stent replacement. As the biopsy specimens from skin and lung revealed non-caseating epithelioid cell granuloma, the diagnosis of sarcoidosis was confirmed in reference to increased serum levels of calcium, angiotensin converting enzyme and lysozyme. The findings of abdominal computed tomography showed that right nephrolithiasis and left ureteral compression by retroperitoneal lymphadenopathy were responsible for bilateral hydronephrosis. Treatment with prednisolone after extracorporeal shock wave lithotripsy reduced serum calcium and creatinine levels accompanied with an improvement of lymphadenopathy and hydronephrosis.

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In April 2001, a 43-year-old female was admitted to our hospital after finding bilateral hilar lymphadenopathy on a chest radiograph. After clinical investigation, we diagnosed her as having pulmonary sarcoidosis. In November 2003, she complained of localized swelling of her left fifth finger and left second toe. Fifth finger swelling slowly progressed, and in January 2004, she complained of pain of the same lesion, and a bone radiograph revealed pathological fracture. Surgical operation for finger reconstruction was performed with the use of an iliac bone graft, and showed non-caseous granuloma from curetted specimen of left 5th finger. This result suggested that the pathological fracture was due to sarcoidosis. Because the second toe would break in the future, we started 30mg/day oral prednisolone.
Pathological bone fracture due to sarcoidosis is very rare, and we discuss this case in comparison with previously published cases.

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We experienced a case of sarcoidosis who developed T-cell lymphoma diagnosed by cervical lymph node biopsy. This 67y/o male was followed due to gastric cancer operation and ossification of posterior longitudinal ligament. He was found to have abnormal chest X-ray. Transbronchial lung biopsy revealed sarcoidosis. He noticed cervical lymph node swelling. Cervical lymph node biopsy revealed sarcoidosis. When he again noticed cervical lymph node swelling another lymph node biopsy revealed T-cell lymphoma. We reported this rare case of sarcoidosis accompanied with T-cell lymphoma.

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A 51-year-old female had chronic throiditis under treatment for 11 years. In June 2002, she was diagnosed as having progressive systemic sclerosis and Sjögren's syndrome with finger swelling and drying buccal cavity. She was referred to our hospital, as a chance x-ray revealed abnormalities. An x-ray showed bilateral hilar lymphadenopathy and a CT showed mediastinal and bilateral hilar lymphadenopathy and diffuse reticular opacities in bilateral lung fields. Bronchoalveolar lavage revealed elevated lymphocytes (44%) with high CD4/CD8 ratio (4.6). A transbronchial lung biopsy revealed noncaseating epithelioid cell granulomas compatible with sarcoidosis. She was already on 2.5mg of predonisolone every other day for Sjögren's syndrome. After 4 months, another chest x-ray showed slight improvement of bilateral hilar lymphadenopathy, Though the case reports of sarcoidosis in association with autoimmune disease have been on the increase, we report a rare case of sarcoidosis with two autoimmune diseases.

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A 55-year-old African male was admitted to our hospital complaining of a two-week history of productive cough and dyspnea on exertion. The patient had been diagnosed as HIV seropositive three years earlier and had been started with highly active antiretroviral therapy (HAART) two years prior to admission, which led to sufficient control of the disease. A computed tomographic scan revealed marked swelling of hilar and mediastinal lymph nodes, diffuse ground-glass attenuation of bilateral lung fields, and thickened bronchovascular bundles. Differential diagnoses included malignant lymphoma and Kaposi sarcoma. A positive “panda sign” on gallium scintigraphy suggested the possibility of sarcoidosis, which was confirmed by presence of noncaseating epithelioid granulomas in excised pretracheal lymph nodes, together with a negative tuberculin skin test, increased levels of ACE and lysozyme, and compatible broncheoalveolar fluid analysis results. This is the first case report of post-HAART immune restoration leading to coexistence of sarcoidosis and HIV infection.

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We retrospectively investigated the relationship between prognosis and patient's background, presence of renal disease, therapeutic regimen, and side effects of therapies in four cases of Wegener's granulomatosis followed for more than 20 years after diagnosis. As for prognosis, two had a complete remission, one had a complete remission but relapsed, and one didn't have a complete remission and eventually died. The patient who died had a limited form of Wegener's granulomatosis at the first visit, and fot the intitial eight years had a good response to azathioprine and predonisolone. When the lesion extended to a generalized form of Wegener's granulomatosis, azathioprine was replaced by cyclophosphamide. But the patient died of renal failure and infection 4 years after the administration of cyclophosphamide. The two completely remitted cases had limited forms and were given cyclophosphamide soon after the diagnosis without relapse. Early administration of cyclophosphamide may prevent the extension to renal involvement.

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