Neurosarcoidosis

Signs and symptoms of neurosarcoidosis are variable and depend on location and size of granulomas. Clinical studies suggest a rate of 5% and autopsy results a rate of more than 25% of central nervous system (CNS) involvement in sarcoidosis. Statistical analysis of 57,789 patients admitted to the Department of Medicine in Lucerne over an 11-year period revealed 51 patients (0.9/1000) with the diagnosis of sarcoidosis. Six of these (12%) had sarcoidosis affecting the CNS. Neurosarcoidosis presented as: leptomeningeal granulomas, cranial nerve palsy, hypothalamic-pituitary syndrome, diabetes insipidus, pareses, paresthesia, pyramidal signs, dementia, urine retention, and asymptomatic granulomas. Neurosarcoidosis has predilections for the base of the brain, cranial nerves (facial nerve palsy is the most common) and meninges, but any part of the CNS may be affected. Therefore, the diagnosis of neurosarcoidosis may be extremely difficult, especially when it occurs as an isolated finding. Positive findings in transbronchial biopsy and lavage may demonstrate asymptomatic pulmonary involvement in as many as 50% of patients with neurosarcoidosis. Angiotensin-converting enzyme levels may be raised in the blood or cerebrospinal fluid in some 50% of cases. Kveim test has a low sensitivity in neurosarcoidosis and thus is of little use. Gallium uptake may demonstrate extracranial granuloma available for biopsy. All these tests, and also computed tomography and magnetic resonance imaging, may be helpful. However, when in selected cases with isolated CNS disease standard investigations are not conclusive, meningeal or cerebral biopsy may be required in order to exclude other causes such as other granulomatous disorders, tumor metastasis, lymphoma, vasculitis, Sj?gren syndrome, infection, neurologic disease such as multiple sclerosis, or systemic diseases such as Whipple's disease. CNS involvement in the acute phase of the disease has a favorable prognosis, while chronic courses respond less well to therapy. Treatment is initiated most frequently with corticosteroids (0.5-1 mg/kg body weight/day or pulses of 1 g/day of methylprednisolone in severe cases). Improvement is seen within 1-2 months. Side effects of corticosteroids, aggressive disease or frequent recurrences may require other immunosuppressive drugs (methotrexate, azathioprine, chlorambucil, cyclosporine A). Cerebral irradiation may be successful in some cases when other treatments fail.     

Scintigraphy with gallium-67 citrate in patients with AIDS: pathologic extrapulmonary uptake

67Gallium citrate can accumulate in different inflammatory and neoplastic lesions. The mechanisms of 67Gallium uptake in abnormal tissue are still partially unknown and the tracer is considered a nonspecific indicator of disease. In AIDS patients, 67Gallium citrate is used in the diagnosis and characterization of opportunistic pulmonary infections and especially of Pneumocystis carinii pneumonia. From June 1989 through December 1992 in our Department 140 67Gallium scans were performed on 103 AIDS patients, referred for evaluation of pulmonary symptoms. All studies were carried out 72 hours after i.v. administration of 185 MBq 67Gallium citrate, with anterior and posterior views of head, chest and abdomen. The images were evaluated with conventional diagnostic criteria and site, number and intensity of abnormal foci of extrapulmonary uptake were recorded. Abnormal extrapulmonary uptake was found in 17 patients (12%): gastric (3, two of which also exhibited abnormal intestinal uptake), esophageal (1) hepatic (1), intestinal (2) renal (4), nodal (3), ocular (1), cutaneous (1), sinusal (1) localizations. In all cases clinical, endoscopic, bioptic or microbiological demonstration of the possible cause of 67Gallium uptake was obtained. An intriguing finding in our series was the lower incidence of gastric uptake (two patients with miliary tuberculosis and one patient with gastric candidiasis) than in the literature. This finding could be explained by clinical and epidemiologic differences between different patient populations. However, the scan interval after tracer administration should be also taken into account, since in our study scans were always performed at 72 hours, while in other series the interval ranged 24-48 hours. The relatively high incidence of abnormal extrapulmonary uptake confirms the opportunity of whole body exploration after 67Gallium administration in the patients with such multisystemic disease as AIDS, even when the patients are referred mainly for respiratory problems.     

Studies in diagnosis of choroidal melanoma: use of 67Gallium

A series of clinically suspected malignant melanomas was used to test the usefulness of 67Gallium citrate using external counting techniques. The comparison was made with angiograms, 32P uptake, and clinical examinations. 67Gallium citrate uptkae proved to be an unreliable diagnostic tool with the described techniques. However, sufficient tissue concentration was obtained tin the tumor to suggest that improved probe counting systems with better resolution of ocular from extraocular tissue may allow this to become a useful technique in differentiating tumor from nontumor ocular pathology. A good indirect and direct ophthalmoscopic examination, along with periodic observation, were the most useful techniques for diagnosis in these cases. 32P uptake was extremely reliable (100%) and quite helpful in assuring the proper diagnosis.     

Sarcoidosis of the heart

Myocardial involvement in sarcoidosis occurs in about 27% of patients. Clinical manifestations include ventricular arrhythmias, conduction abnormalities, and sudden death. Diagnosis requires clinical suspicion and may be supported by electrocardiography, echocardiography, thallium imaging, gallium-67 scanning, and myocardial biopsy. Steroids seem to be beneficial in the treatment of myocardial sarcoidosis. Those who do not respond to medical treatment may benefit from cardiac transplantation.     

Ileal ureter

Clinically apparent involvement of the heart and nervous system occurs in a relatively small number of patients with sarcoidosis. The diagnosis of myocardial and neurological sarcoidosis is difficult because anatomic presence of granulomas without clinical dysfunction is an important feature of sarcoidosis. The chest radiography is abnormal in 8 of every 10 patients with myocardial or neurosarcoidosis. Serum angiotensin-converting enzyme and gallium uptake studies may provide some indication of the extent and severity of the granulomatous process. Corticosteriods are the mainstay of therapy but chloroquine or hydroxychloriquine, methotrexate, and azathioprine are also effective. Prognosis of myocardial and neurological sarcoidosis is poor.     

Sarcoidosis in a cicatrix: apropos of 5 cases

The authors report 5 cases of sarcoidosis developed on scars. Sarcoidosis may be isolated (1 case); it may precede (1 case) or accompany systemic sarcoidosis, or occur during a relapse (3 cases). Dermatologists who observe cicatricial changes always suspect sarcoidosis. It is therefore important that physicians should examine the scars of their patients with suspected sarcoidosis, since biopsy of these scars is easily performed, confirms the diagnosis and avoids more invasive explorations.     

Intense muscle uptake of gallium-67 in a patient with sarcoidosis

Sarcoidosis has been associated with muscle involvement. In general, this involvement remains asymptomatic. The following case report demonstrates a patient with a 4-mo history of sarcoidosis who reported severe fatigue and slight muscular complaints at a regular checkup. Gallium scintigraphy indicated unexpected and unusually extensive muscular localizations of the disease. The latter findings were confirmed by examination of biopsy specimens. The importance of gallium scintigraphy lies in the possibility of wholebody screening for inflammation localizations, particularly when physical, laboratory, lung function and radiographic examinations fail to provide convincing evidence of active sarcoidosis. Furthermore, it can be helpful in the follow-up of the effect of supportive treatment.     

Corticosteroid therapy in cardiac sarcoidosis

Corticosteroid treatment of cardiac sarcoidosis is not conclusive, although sarcoid granulomas in the heart may be more responsive to steroid therapy than in other organs. Healing of sarcoidosis lesions in the heart results in fibrosis and sinning of the myocardium, which may lead to aneurysm formation causing congestive heart failure or sudden death. Congestive heart failure is the leading cause of death in patients with cardiac sarcoidosis in Japan. It is reasonable to initiate steroid therapy as soon as the diagnosis of cardiac sarcoidosis is established in order to prevent fibrosis. Early initiation of steroid therapy with conventional treatment for specific cardiac manifestations (antiarrhythmic therapy, pacemaker implantation and heart failure medication) should bring improvement in the left ventricular systolic and diastolic function with prevention from malignant arrhythmias. Systemic disorder represents a contraindication to organ transplantation, but heart transplantation is now a feasible treatment for patients with end-stage cardiac sarcoidosis with congestive heart failure.     

Renal manifestations in sarcoidosis

Clinically distinct renal disease is said to be rare in sarcoidosis, but autopsy reveals an incidence of renal involvement is 23 or 26% in Japanese studies. There are three categories of renal disease in sarcoidosis: 1) renal changes by abnormal calcium metabolism, 2) interstitial nephritis or granulomatous nephritis and 3) glomerulonephritis. Some investigators add renal angiitis to the three categories. In some patients without clinical renal disorders, renal involvement is discovered by chance at the time of autopsy or renal biopsy. Renal disease may develop during the course of sarcoidosis, preceding the diagnosis of sarcoidosis, or may be found simultaneously with extrarenal involvements at the time of diagnosis. Renal involvement should always be considered for exact diagnosis and appropriate treatment.     

Sarcoidosis with nasal obstruction and septal perforation

Although sarcoidosis is predominantly a pulmonary disorder, it often produces disease in the head and neck. For this reason, otolaryngologists should be comfortable in evaluating and treating the disease. The diagnosis of sarcoidosis often can be made with a biopsy of conjunctival or oral mucosa, even when disease manifestations are not apparent in those parts of the body. In a case of sarcoidosis involving the nose, a 54-year-old black man had a proliferation of small lumps on the tip of his nose. For many years, he had had daily epistaxis, anosmia and severe difficulty breathing through this nose. The bridge of his nose was deformed, and he had a large anterior septal perforation. Physical examination revealed palpable bilateral cervical lymphadenopathy. Laboratory test results were, for the most part, normal; however, fine-needle aspiration of one of the cervical lymph nodes showed multiple epithelioid granulomas with interspersed lymphocyte, and an incisional biopsy of the nasal tissue was highly suggestive of sarcoidosis. Unenhanced computed tomography also revealed widespread nasal inflammation and an abnormal soft tissue mass anterior to the maxilla consistent with chronic osteomyelitis. The patient's condition dramatically improved following treatment with oral prednisone; however, he considered undergoing reconstructive surgery for the noticeable nasal septal deformity.     

Diabetes insipidus, Sheehan''s syndrome and pregnancy

We diagnosed a case of primary cardiac lymphoma using transthoracic needle biopsy. A 70-year-old man was admitted because of dyspnea. Magnetic resonance imaging revealed a tumor mass in the right ventricular free wall. We performed ultrasound guided transthoracic needle biopsy using an 18-G needle, and diagnosed as malignant lymphoma by the biopsy specimen. This method may be useful for the diagnosis of cardiac lymphoma.     

Increased subglottic gallium uptake in relapsing polychondritis

Gallium scintigraphy was performed on a 14-yr-old girl with subglottic airway narrowing that caused wheezing and dyspnea. The study showed increased gallium uptake in the neck. A biopsy was performed on the subglottic region, and the histology was compatible with relapsing polychondritis. After treatment with steroids, laboratory data that had indicated active inflammation soon normalized. Repeat gallium scintigraphy showed diminished uptake, although the subglottic stenosis did not improve. These results suggest that gallium scintigraphy is valuable for evaluating inflammatory activity in relapsing polychondritis.     

Technetium-99m-tetrofosmin uptake in sarcoidosis stage I

The uptake of 99mTc-tetrofosmin in enlarged lymph nodes, of the lung hilus, in the case of sarcoidosis Stage I (histopathologically confirmed by mediastinoscopic biopsy) is demonstrated. On a routine chest radiograph of a 78-yr-old woman, hilar lymphadenopathy was first detected. In the following mammography, disseminated micro calcifications were found in the left breast and a 99mTc-tetrofosmin study was performed for detection of breast cancer. Scintigraphy using 99mTc-tetrofosmin showed clear uptake in the hilar lymph nodes, but not in the left breast. The 99mTc-tetrofosmin uptake in the hilar lymph nodes was due to sarcoidosis confirmed by histology. Therefore, 99mTc-tetrofosmin scintigraphy may be useful in patients with suspected sarcoidosis, especially in Stage I.     

Ganciclovir treatment of active hepatitis B virus infection in a heart transplant patient

We report a 51-year-old woman with alopecia caused by sarcoidosis. The lesion enlarged within 4 years and only repeated biopsies enabled the diagnosis. The medical work-up revealed that the patient had asymptomatic pulmonary involvement. Scarring alopecia is a rare complication of sarcoidosis and biopsy from the active margin may lead to the diagnosis.     

Sarcoidosis in children. Epidemiology in Danes, clinical features, diagnosis, treatment and prognosis

This paper reviews current knowledge of childhood sarcoidosis with regard to the epidemiology in Danes, clinical presentation, diagnostic procedures, treatment and prognosis. Sarcoidosis is a granulomatous disease of unknown aetiology, with multiorgan involvement. The diagnosis is confirmed by the demonstration of epitheloid cell granulomas in tissue biopsy specimens. During the period 1980-92, three cases of childhood sarcoidosis were recorded in Copenhagen County, which has a total population of 610,000. The approximate incidence of clinically recognized sarcoidosis in Danish children younger than 15 y of age was 0.22-0.27/100,000 children per year, corresponding to approximately three new cases in Denmark each year. The true incidence is unknown, since the disease is often asymptomatic and resolves without a clinical diagnosis being made. In children younger than 5 y of age, the disease is characterized by involvement of skin, eyes and joints, whereas in older children involvement of lungs, lymph nodes and eyes predominate. The mainstay of treatment consists of oral corticosteroids. The risk/benefit ratio of using long-term corticosteroids needs to be evaluated in each individual patient. Some patients may benefit from additional therapy with methotrexate. The long-term prognosis is not well established, but it seems to be poorer in children younger than 5 y. Older children appear to have as favourable a prognosis as young adults.     

Digital color imaging colposcopy: a matter of choice

PURPOSE: The objective of this study was to correlate the findings of sarcoidosis on high resolution CT (HRCT) with indexes of disease activity as measured with 67Ga scan, bronchoalveolar lavage (BAL), and serum angiotensin-converting enzyme (SACE) assay. METHOD: Twenty-nine patients with proven sarcoidosis underwent HRCT scan, 67Ga scan, BAL, and SACE assay within a 1 month period. The extent of parenchymal involvement by nodules, consolidation, ground-glass attenuation, and linear opacities was quantified to the nearest 10% of surface area affected on the CT examination. Whole-lung gallium uptake was quantified and the percentage of BAL-recovered lymphocytes (BAL-%LC) and SACE levels obtained by chart review. CT scores of disease extent were correlated with measured indexes of activity using the Spearman rank correlation coefficient. RESULTS: The mean extent of nodules, consolidation, ground-glass attenuation, and linear opacities on HRCT images was 15.1 +/- 16.6, 1.6 +/- 4.0, 17.5 +/- 25.4, and 7.6 +/- 9.6%, respectively. The extent of nodules and consolidation correlated with the intensity of lung gallium uptake (r = 0.46, p < 0.02), BAL-%LC (r = 0.50, p < 0.01), and SACE levels (r = 0.38, p < 0.05). No significant correlation was found between extent of ground-glass attenuation or linear opacities with any indexes of disease activity. CONCLUSION: On HRCT scan, nodules and consolidation in sarcoidosis reflect disease activity as measured by 67Ga scan, BAL, and SACE assay.     

Association of sarcoidosis, low-grade B-lymphoma and epidermoid carcinoma

We report on a case of the so-called sarcoidosis-lymphoma syndrome in a 65-years-old man diagnosed as having sarcoidosis and, four years later, neurosarcoidosis. The diagnoses of epidermoid carcinoma of the skin and of stage IV monocytoid, small cell lymphocytic lymphoma were made five and seven years, respectively, after the initial diagnosis of sarcoidosis. It has been suggested that the increased mitotic activity of lymphocytes observed in sarcoidosis, favours their malignant transformation. Hypothetically, sarcoidosis might also influence the development of epidermoid carcinomas by depletion of circulating T4 lymphocytes and decreased resistance to oncogenic viruses that could lead to decreased tumour rejection in the epithelia exposed to carcinogenic stimuli.     

Chronic beryllium disease: uncommon disease, less common diagnosis

Chronic beryllium disease (CBD) is typically considered only when occupational exposure to beryllium is a certainty; however, CBD has also occurred in occupational and environmental settings where exposure was unexpected. When the etiology of a case of granulomatous pulmonary disease is not determined, sarcoidosis is the "diagnosis of exclusion." This diagnosis does not communicate much information about the patient's prognosis, the disease's etiology, or even what disease etiologies were specifically excluded. Some cases of CBD have been called sarcoidosis, allowing exposure to continue for the patient and (at times) other individuals. The granulomatous changes of sarcoidosis are thought to result from an abnormal immune response. While the etiologic agents that can initiate this response are largely unknown, the immunopathogenesis of CBD has been well described, and laboratory methods are available in a few centers that can (if used) identify beryllium hypersensitivity. The potential for exposure and disease to be widely separated in time and location makes it important for health-care and environmental health professionals to be aware of these new diagnostic methods.     

Trial of new intraocular lens power calculation following phototherapeutic keratectomy]

Thirty-one men (age range, 46-76 years; mean age, 64.8 years) with intrathoracic masses suggesting possible malignancy on the basis of chest radiography or CT underwent preoperative Tc-99m MIBI SPECT examinations. Diagnosis was confirmed on pathologic examinations of samples obtained either at thoracotomy, esophagectomy, or by biopsy. Twenty-five patients had primary lung cancer, including squamous cell carcinoma, large cell carcinoma, adenocarcinoma, and small cell carcinoma. Two patients had lymphomas with spread to the mediastinum, and three patients had extrathoracic primary cancers (one squamous cell carcinoma of esophagus, one squamous cell carcinoma originating from a head and neck tumor, and one metastatic mediastinal leiomyosarcoma). One patient with a tuberculoma had negative results of the Tc-99m MIBI examination. Tc-99m MIBI had a 86.7% sensitivity rate, a 0% false-positive rate, and a 100% positive predictive value to detect malignant intrathoracic masses. There was a 13% false-negative rate, however, suggesting that MIBI-SPECT may underdiagnose malignant lesions. SPECT findings of these 31 patients can be classified as 1) mass with increased uptake, n = 23; 2) ring-like appearance of increased uptake, n = 3; 3) mass with absent uptake, n = 4; and 4) photon-deficient mass, n = 1. Absent uptake in patients with mass lesions could be explained by necrosis of the lesion (caseation necrosis or massive tumor necrosis with or without bleeding). Most malignant intrathoracic masses are Tc-99m MIBI avid and may be detected with a high degree of sensitivity and with an excellent positive predictive value. A positive MIBI scan may help in the clinical diagnosis of malignancy. The use of Tc-99m MIBI could serve not only as a tumor imaging agent, but also may be used to determine the extent of spread and potentially the chemotherapeutic responsiveness of a tumor.     

Pseudotumor forms of neurosarcoidosis in children. Diagnostic difficulties and therapeutic management

In systemic sarcoidosis, neurologic manifestations are possible and occurred in 5 p. 100 of cases. The diagnosis is easier when sarcoiddosis is known, but in half case neurologic symptoms are inaugural. In these cases, involvement of other sites (liver, lung, eyes or skin) by the disease is needed to confirm sarcoidosis. Main manifestations in neurosarcoidosis are cranial nerve palsy, diabetes insipidus or chronic aseptic meningitis, but sometimes sarcoidosis can present as an intracranial mass. The diagnosis of neurosarcoidosis may be difficult and could be confused with infection (such tuberculosis or mycosis), with inflammatory diseases (such multiple sclerosis) or with neoplasm, particularly in case of oedema. Brain biopsy may be necessary in isolated neurosarcoidosis if no peripheral histology evidence of noncaseating granulomas has been obtained. Treatment with steroids alone is the best choice for initial therapy but must be prolonged. It is difficult to predict accurately the response to steroids and relapse may be possible after a long time. Other immunosuppressive therapeutics or radiotherapy have been used in patient with refractory neurosarcoidosis. Sequential magnetic resonance imaging is the useful mean for the follow-up of neurosarcoidosis.