Surgical management for instability and paraplegia caused by spinal sarcoidosis. A case report

STUDY DESIGN: Report of a patient with paraplegia caused by vertebral sarcoidosis. OBJECTIVES: To report a rare case of vertebral sarcoidosis accompanied by progressive neurologic symptoms from the lower extremities, and to discuss the diagnostic and therapeutic approach to its management. SUMMARY OF BACKGROUND DATA: Vertebral sarcoidosis is a rare condition, and only a few case reports exist in the literature. A needle or open biopsy is required to establish the diagnosis. In most cases, treatment with steroids improves associated neurologic symptoms. Operative intervention is necessary in cases with progressive vertebral destruction, spinal instability, and impending or progressive neurologic deterioration. METHODS: Operative treatment by a two-stage anterior vertebrectomy and fusion followed by posterior stabilization was given to a patient with vertebral sarcoidosis and progressive neurologic deterioration of the lower extremities. RESULTS: After surgery, the patient had a complete neurologic recovery and satisfactory spinal fusion. CONCLUSIONS: In the absence of any spinal instability, neurologic symptoms associated with vertebral sarcoidosis respond satisfactorily to nonoperative treatment with steroids. Progressive neurologic deterioration or spinal instability caused by bone destruction requires operative intervention. Anterior vertebrectomy and fusion combined with posterior stabilization provided a satisfactory result for the patient in this report.     

Lung transplantation for pulmonary sarcoidosis

Patients with end-stage sarcoidosis have now undergone lung transplantation successfully with good short-term and intermediate-term results. Lung transplantation for sarcoidosis requires several considerations unique to this disease. Selection of pulmonary sarcoidosis patients for transplantation requires that medical therapy has been exhausted. This may involve the use of corticosteriods and alternative medications. Causes of pulmonary dysfunction other than pulmonary sarcoidosis, such as bronchiectasis and myocardial sarcoidosis, must be excluded before candidates are considered for transplantation. The extent and severity of extrapulmonary disease must also be assessed and may preclude lung transplantation. The presence of mycetomas is considered a relative contra-indication by some transplant centres and an absolute contra-indication by others. Relatively few patients with pulmonary sarcoidosis have undergone transplantation and, therefore, there are few data on outcome. Sarcoidosis frequently recurs in the allograft, but rarely causes symptoms or pulmonary dysfunction. More severe acute rejection episodes may occur in sarcoidosis transplant recipients, although at present there is no evidence of an increased risk of obliterative bronchiolitis or increased mortality.     

Brain tumors in patients with Fanconi''s anemia

OBJECTIVES: To study whether an association between polyglandular autoimmune (PGA) syndrome type III [including autoimmune thyroid disease (ATD) and insulin-dependent diabetes mellitus (IDDM)], coeliac disease and sarcoidosis, exists. DESIGN: In patients with documented sarcoidosis, the presence of the disease constellation of ATD, IDDM and coeliac disease was examined. SETTING: The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, Lund University Clinics, General Hospital, Malm?, Sweden. SUBJECTS: Of all patients (n = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 patients (44 males, 34 females: median age at the time of the study 48 years, range 22-81 years: median observation time since the diagnosis of sarcoidosis 120 months, range 1-468 months) were examined in the present study. RESULTS: Amongst the 78 patients with documented sarcoidosis, one female patient was found with PGA syndrome type III, coeliac disease and sarcoidosis. CONCLUSIONS: This present patient further indicates the existence of an association between polyglandular autoimmune (PGA) syndrome type III, coeliac disease and sarcoidosis. To determine whether this disease constellation might constitute a new syndrome, further studies on larger groups of patients with sarcoidosis are demanded.     

Analysis of restriction fragment length polymorphism for the HLA-DR gene in Japanese patients with sarcoidosis

BACKGROUND: It is commonly assumed that some immunological disorder may play a part in the pathogenesis of sarcoidosis. Previous studies by several groups have shown a significant association with HLA-DR antigens in patients with sarcoidosis. In this study, restriction fragment length polymorphism (RFLP) analysis of the HLA-DR gene was designed to confirm the association at the gene level and to look for a gene rearrangement which may influence susceptibility to sarcoidosis. METHODS: Thirty two unrelated Japanese patients with sarcoidosis were tested for HLA antigens and subjected to RFLP analysis after digestion with Eco RI, Pst I, Bam HI, Pvu II, and Hind III by using an HLA-DR beta cDNA probe. A group of 47 unrelated healthy Japanese subjects served as controls. Frequencies of each restriction fragment were compared between the patients and the control subjects. Correlation between fragment frequencies and clinical features were also analysed. RESULTS: No restriction fragments of HLA-DR beta gene were found specific to the patients with sarcoidosis. The RFLP analysis could detect polymorphism of HLA-DR beta genes that was not distinguishable by conventional serological methods. Several restriction fragments of the DR beta gene were seen only in DRw52 positive individuals, and showed higher frequencies in the patients than in control subjects. The patients with these DNA fragments were likely to have limited stage disease with no ophthalmic involvement. CONCLUSIONS: An association between HLA and sarcoidosis was noted at the DNA level, although no restriction fragments were specific for this disease. RFLP analysis of the HLA gene is a more useful method than the usual HLA typing, and should be the first step in identifying the gene sequence which is connected with susceptibility to sarcoidosis.     

Detection of antibodies to Borrelia species among patients with confirmed sarcoidosis in a region where Lyme disease is nonendemic

BACKGROUND: Lyme disease is a multisystemic disorder caused by the spirochete Borrelia burgdorferi, while sarcoidosis is a multisystemic granulomatous disease of unknown etiology. The purpose of this study was to evaluate the relationship between Lyme disease and sarcoidosis. METHODS: We examined the seroprevalence of antibody to Borellia species in patients with sarcoidosis. We performed the enzyme-linked immunosorbent assay, using three Japanese Borrelia species in addition to B. burgdorferi, and dotblot analysis using purified Borrelia-specific proteins in 38 patients with histopathologically confirmed sarcoidosis and 80 healthy controls. RESULTS: Two patients (5.3%) were positive for antibodies to Borrelia species according to one or both assays, and one (1.2%) healthy control was positive. In both patients it was suspected that Borrelia infection had developed prior to the development of sarcoidosis. CONCLUSION: Borrelia species were thought not to be responsible for the development of sarcoidosis in a nonendemic region in Japan. Since clinical manifestations of Lyme disease share certain similarities with those seen in sarcoidosis, ophthalmologists should be aware of the need to differentiate between the two diseases and the need for prompt treatment in each case.     

The diagnosis of pericardial effusion and cardiac tamponade by 12-lead ECG. A technology assessment

Two types of receptor for tumour necrosis factor-alpha (TNF-R), the 55-kD receptor (TNF-RI) and the 75-kD receptor (TNF-RII), have been identified. Soluble TNF-RI (sTNF-RI) and soluble TNF-RII (sTNF-RII) can be measured in culture supernatants and biological fluids, and the role of sTNF-R has been suggested. In the present study, we measured plasma sTNF-RI and sTNF-RII levels in 19 patients with active sarcoidosis by ELISA in order to assess the state of both types of receptors in this disease. Both plasma sTNF-RI and sTNF-RII levels in patients with active sarcoidosis were significantly higher than those in normal control subjects. A longitudinal evaluation of plasma sTNF-RI and sTNF-RII levels showed that the magnitude of changes in sTNF-RII was closely related with the clinical course of sarcoidosis. These results suggest that plasma sTNF-RII levels may be useful parameters for monitoring the clinical course of sarcoidosis as well as markers for identifying disease activity.     

Prevalence and relevance of coronary artery anomalies

A patient with scar sarcoidosis and Crohn's disease is described. The possibility of patients with Crohn's disease being more prone to develop sarcoidosis is discussed.     

Sarcoidosis: 25-year clinical follow-up

Based on the follow-up of 1,600 patients with sarcoidosis from 1971 to 1996, the authors analyzed the value of various methods for identifying the disease, the frequency and nature of misdiagnoses. They showed the efficiency of basic treatments in patients with sarcoidosis: corticosteroidal hormones, nonhormonal antiinflammatory drugs, plasmapheresis, and physiotherapy. Recurrencies and progression were seen in 23.85% of patients. The likely causes of recurrent sarcoidosis are considered. It is concluded that recurrencies are one of the important problems of modern sarcoidosis.     

Nonpainful swelling of the palate and loosening of the maxillary incisors

Bone lesions in the maxilla have rarely been described in relation to sarcoidosis. This patient exhibited many of the classic signs of sarcoidosis, including lack of symptoms at the time of presentation, which resulted in the diagnosis of sarcoidosis being made serendipitously. The presence of musculoskeletal lesions is often regarded as a poor prognostic sign and, in general, sarcoidosis follows a more virulent course in black patients. Sadly, the course of the disease in this patient continues to march onward despite a 1-year therapeutic trial of corticosteroids.     

The Norwegian Polio Study 1994: a nation-wide survey of problems in long-standing poliomyelitis

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease of unknown etiology, while Lyme borreliosis is a multisystemic disorder caused by Borrelia burgdorferi. The purpose of this study is to evaluate the relationship between sarcoidosis and Lyme borreliosis in a region of Japan where Lyme borreliosis is endemic. METHODS: We determined the seroprevalence of anti-Borrelia burgdorferi antibodies as well as antibodies three Japanese Borrelia strains by enzyme-linked immunosorbent assay and dotblot assay using purified Borrelia-specific proteins in 46 patients with confirmed sarcoidosis and 150 controls (50 disease controls and 100 healthy controls) in Hokkaido, the affected region. RESULTS: Fifteen patients with sarcoidosis (32.6%) tested positive for Borrelia spirochete in both assays, compared with two disease controls (4.0%) and two healthy controls (2.0%). The seroprevalence of anti-Borrelia antibodies in patients with sarcoidosis was much higher in the affected region than in the region in our previous study were Lyme borreliosis is non-endemic. CONCLUSION: In a region where Lyme borreliosis is endemic, Borrelia infection may be partially associated with sarcoidosis.     

Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Beh?et's disease involving the nervous system

A retrospective study of CSF and serum analysis from a total of 43 patients with sarcoidosis, 20 with systemic lupus erythematosus, and 12 with Beh?et's disease with neurological involvement found local synthesis of oligoclonal IgG using isoelectric focusing and immunoblotting in 51%, 25%, and 8% respectively at some stage in their disease. Blood-brain barrier breakdown, when assessed with an albumin ratio found 47% of patients with sarcoidosis, 30% of those with systemic lupus erythematosus, and 42% of patients with Beh?et's disease exhibiting abnormal barrier function at some time. Serial CSF analysis showed that clinical relapses were associated with worsening barrier function and in some patients the development of local oligoclonal IgG synthesis; conversely steroid treatment led to a statistically significant improvement in barrier function, and in two patients a loss of oligoclonal IgG bands. A higher proportion of patients had MRI abnormalities than oligoclonal IgG or blood-brain barrier breakdown, MRI being abnormal in 16 of 19 patients with sarcoidosis, three of four patients with systemic lupus erythematosus, and seven of nine patients with Beh?et's disease, although this may have been due to temporal factors. In the differential diagnosis of chronic neurological disorders, locally synthesised oligoclonal IgG cannot distinguish between diseases, but the loss of bands seen in two patients contrasts with what is seen in multiple sclerosis, and thus may be a useful diagnostic clue.     

Clinical correlates of granulomas in muscle

We evaluated the clinical and myopathological features of all patients with granulomas in muscle biopsy specimens identified over a 5-year period (1992-1996) at the Washington University Medical Center. Ten patients were found to have granulomas in their muscle biopsy specimens. Of these, eight patients had myopathic changes. Seven had dysphagia as a major functional difficulty during the course of their disease. None had elevated levels of serum creatine kinase (CK). Four of the patients with myopathy had systemic sarcoidosis and relatively severe proximal weakness with functional disability. Treatment with corticosteroids was followed by marked improvement in strength and functional disability. The four other patients with myopathy had no systemic signs of sarcoidosis. Weakness was especially prominent distally in three of these patients. The two patients in this group treated with corticosteroids did not improve. The final two patients, who had granulomas in muscle but no myopathic changes, had clinical syndromes of mononeuritis multiplex and eosinophilic fasciitis (Shulman syndrome). We conclude that granulomatous myopathy, in the presence or absence of systemic sarcoidosis, is commonly associated with dysphagia (87%) and a normal serum CK. Clinical features in patients with sarcoidosis included severe proximal weakness with functional disability that often responded to corticosteroid treatment. Granulomatous myopathy without systemic sarcoidosis was associated with milder, but more predominantly distal weakness.     

Lung transplantation for respiratory failure resulting from systemic disease

BACKGROUND: Lung transplantation for pulmonary failure resulting from systemic disease is controversial. We reviewed our transplant experience in patients with sarcoidosis, scleroderma, lymphangioleiomyomatosis, and graft-versus-host disease. METHODS: This retrospective review examined the outcome of 23 patients who underwent pulmonary transplantation for these systemic diseases. Group 1 included 15 patients with pulmonary hypertension who underwent transplantation (9 for sarcoidosis, 6 for scleroderma), and group 2 included 8 patients with normal pulmonary artery pressures who underwent transplantation (5 for lymphangioleiomyomatosis, 3 for graft-versus-host disease). The incidences of infection and rejection, pulmonary function, and survival were measured and compared with those of patients who underwent transplantation for isolated pulmonary disease. RESULTS: Although there were no differences in the rate of infection between patients who underwent transplantation for systemic versus isolated disease, patients with pulmonary hypertension who underwent transplantation for systemic disease had significantly lower rates of rejection. Four patients with sarcoidosis and 2 with lymphangioleiomyomatosis demonstrated recurrence in the allograft. Survival was similar between patients who underwent transplantation for systemic versus isolated disease. CONCLUSIONS: Patients with respiratory failure resulting from these systemic diseases can undergo transplantation with outcomes comparable to those obtained in patients who undergo transplantation for isolated pulmonary disease.     

Noninvasive assessment of the direct action of oral nifedipine and nicardipine on left ventricular contractile state in patients with systemic hypertension: importance of reflex sympathetic responses

BACKGROUND: Alveolar macrophages from patients with sarcoidosis were analyzed for their ability to secrete tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1-beta), and interleukin-6 (IL-6). RESULTS: Constitutive release of all three monokines in these patients was concomitantly increased in the active state of disease in comparison with inactive sarcoidosis or healthy control subjects. Alveolar macrophages from patients with inactive sarcoidosis compared with cells from healthy subjects showed increased spontaneous secretion of TNF-alpha and IL-6 only, whereas the constitutive release of IL-1-beta was similar as in healthy volunteers. In vitro stimulation of alveolar macrophages from healthy control subjects with lipopolysaccharide or pokeweed mitogen led to a time- and dose-dependent enhanced secretion of TNF-alpha, IL-1-beta, and IL-6. In a similar manner, with corresponding cells from patients with sarcoidosis the secretion of all three cytokines could be further increased by stimulation with lipopolysaccharide or pokeweed mitogen. CONCLUSIONS: The data presented indicate that an increased release of TNF-alpha, IL-1-beta, and IL-6 correlates to disease activity and may play a critical part in the pathogenesis of sarcoidosis.     

Somatostatin receptor imaging in patients with sarcoidosis

Granulomatous diseases can be visualized in vivo after the injection of indium-111-DTPA-octreotide (111In-pentetreotide), a radiolabelled somatostatin analogue. We evaluated whether somatostatin receptor imaging reflects disease activity, whether certain scintigraphic characteristics can predict the disease prognosis and whether repeat scintigraphy correlates with the clinical course in patients with sarcoidosis. 111In-pentetreotide was injected in 46 patients and images were obtained 24 h later. Known mediastinal, hilar and interstitial disease was recognized in 36 of 37 patients. Also, such pathology was found in seven other patients who had normal chest X-rays. In five of these, somatostatin receptor imaging pointed to interstitial disease. Frequently, accumulation of radioactivity in parotid glands and supraclavicular lymph nodes was found. Neither the degree of radioactive accumulation in the thorax nor a specific pattern of pathological uptake was correlated with disease severity or clinical course. The degree of uptake of radioactivity in the parotid glands was correlated with significantly higher serum angiotensin-converting enzyme (ACE) levels. Somatostatin receptor imaging was repeated in 13 patients. In five of six patients in whom chest X-ray monitored improvement of disease activity, the pentetreotide scintigram also showed a decrease in pathological uptake. In two of five patients in whom the chest X-ray was unchanged, but serum ACE concentrations had decreased and lung function improved, normalization on pentetreotide scintigrams was found. It is concluded that: (1) somatostatin receptor imaging can demonstrate active granulomatous disease in patients with sarcoidosis; (2) pathological uptake of radioactivity in the parotid glands during somatostatin receptor imaging is correlated with higher serum ACE concentrations; (3) the value of somatostatin receptor imaging in the follow-up of patients with sarcoidosis will have to be determined in a prospective longitudinal study.     

Synthesis and biological activity studies of 3-arylaminomethyl-7H-6-(6 substituted-3-coumarino)-S-triazolo-[3,4-b][1,3,4]thiadiazines

Sarcoidosis (S) is a systemic disease affecting above all lymph nodes and lung tissue. Skeletal involvement is reported to occur in 14% of patients, the most common manifestations is cystoid osteitis, an asymptomatic lesion localized to the small bones of hand and feet. Lytic lesions are rare and usually accompanied by visceral involvement, the lesions may be detected in vertebral bodies and in long bones, pelvis and scapulae. MRI may be a good diagnostic tool, but open biopsy is often necessary. Joints are involved in about 89% of patients with acute sarcoidosis. Arthritis is localized more frequently to knees and ankles, is polyarticular, a little painful, migratory and transient, often accompanied by erythema nodosum. Clinical manifestations disappear in a few weeks, chronic and erosive disease is rare and always associated with systemic involvement. In these patients it may be useful to perform gallium citrate 67 scintigram and evaluation of serum ACE. Synovial biopsy lacks of specificity and sensibility, and in some cases it is necessary to perform open biopsy. S is a disease that may spontaneously regress and therapy may be unnecessary. In some cases, methotrexate may be useful in addition to prednisone. Chloroquine and hydroxychloroquine are effective in cases of skeletal involvement.     

Role of the flocculus of the cerebellum in motor learning of the vestibulo-ocular reflex

Inhalation of metal dust or fume can cause granulomatous lung disease that mimics sarcoidosis. Particular metals that possess antigenic properties which promote granuloma formation include aluminum, barium, beryllium, cobalt, copper, gold, rare earths (lanthanides), titanium, and zirconium. The occupational and environmental exposure history holds the key to linking such metals with seemingly idiopathic disease. We propose clinicians use a systematic approach to investigating the occupational and environmental history and immunologic responses of patients with sarcoidosis, in order to discriminate metal-induced granulomatosis from sarcoidosis.     

Single lung transplantation in patients with systemic disease

OBJECTIVE: To report functional results and survival in patients undergoing single lung transplantation (SLT) for pulmonary involvement associated with systemic disease or prior malignancy, criteria traditionally considered contraindications to SLT. DESIGN: Case series. SETTING: The University of Texas Health Science Center at San Antonio. PATIENTS: Nine patients who have undergone SLT for end-stage lung disease: four patients with sarcoidosis; two patients with limited scleroderma; and three patients with prior malignancies (two with prior lymphoma and bleomycin-induced pulmonary fibrosis and one who received two bone marrow transplants for acute lymphocytic leukemia and subsequently developed chemotherapy-induced pulmonary fibrosis). MEASUREMENTS: Pulmonary function testing, exercise oximetry, quantitative ventilation-perfusion lung scanning. Actuarial survival. RESULTS: All patients had marked improvement in pulmonary function, exercise oximetry, and quantitative ventilation perfusion to the SLT. One patient with scleroderma died 90 days postoperatively from Pseudomonas pneumonia with a sepsis syndrome. One patient with sarcoidosis died 150 days postoperatively from disseminated aspergillosis. At autopsy, there was no evidence of recurrent fibrosis or sarcoidosis in the transplanted lungs in either of these two patients. The seven surviving patients have returned to work or school and are conducting all activities of daily living without pulmonary disability. The 1- and 2-year actuarial survival rates in these nine patients is 68.6 percent as compared with the 1- and 2-year actuarial survival rates of 66.3 percent and 55.8 percent in the remainder of our SLT group as a whole (n = 49). Despite pharmacologic immunosuppression, there is no evidence of recurrent malignancy in the 3 patients with prior malignancies. CONCLUSIONS: We conclude that carefully selected patients with end-stage lung involvement related to systemic disease or chemotherapy-induced fibrosis may benefit from SLT.     

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.     

Inhibition of nitric oxide synthesis increases adenosine production via an extracellular pathway through activation of protein kinase C

At the time of diagnosis, many sarcoidosis patients have no clinical indication for corticosteroid therapy, and prognostic parameters predicting deterioration are missing. In the present study, we investigated parameters derived from bronchoalveolar lavage (BAL) and serum in 77 patients with recently diagnosed sarcoidosis to test their predictive value. Patients were divided into a group with (Group A, n = 37) and a group without (Group B, n = 40) indications for therapy, and the course of the disease was evaluated after 5.7 +/- 0.4 mo. The CD4+/CD8+ lymphocyte ratio and percentage of BAL lymphocytes were of no predictive value. Release of tumor necrosis factor-alpha (TNF-alpha) from cultured alveolar macrophages (AM) was significantly increased in both groups (Group A = 1,872 +/- 428 pg/ml; Group B = 1,561 +/- 449 pg/ml) as compared with controls (220 +/- 37 pg/ml). In Group B, however, patients with a high level of TNF-alpha release had a significantly greater risk of disease progression than did those with normal TNF-alpha release (43.8% versus 8.3%, respectively). From the serologic parameters investigated, consisting of neopterin, angiotensin converting enzyme (ACE), and soluble interleukin-2 receptor (sIL-2R), only the last was of significant predictive value; 42.1% of sarcoidosis patients in Group B with a high level of sIL-2R experienced disease progression, whereas none of those with a normal level did. We conclude that TNF-alpha release and sIL-2R are suitable parameters for predicting disease progression in sarcoid patients who have no indication for therapy at the time of disease diagnosis.