Early diagnosis of cardiac involvement in systemic sclerosis by 123I-MIBG neurotransmitter scintigraphy.

Cardiac involvement of systemic sclerosis (SSc) is associated with a poor prognosis. Arrhythmias and conduction disturbances are a known feature of SSc. From histopathological examinations, it is known that the conducting system is secondarily involved as a result of focal fibrosis of the myocardium. Fibrotic changes are believed to be related to vasospasms, such as Raynaud's phenomenon. The sympathetic nervous system is very sensitive to ischaemia, impairing the energy-dependent uptake of intraneuronal norepinephrine. 123I-metaiodobenzylguanidine (123I-MIBG) is a metabolic analogue of norepinephrine and can therefore be used as a marker of norepinephrine depletion. The aim of the study was to evaluate the incidence and extent of SSc-associated ischaemic damage due to primary cardiac involvement by assessing intraneuronal 123I-MIBG uptake and distribution. Supplementary myocardial stress and rest perfusion scintigraphy, together with cardiological examinations (including an exercise stress test, Holter ECG and echocardiography), were performed in 18 patients. None of the patients showed evidence of ischaemia upon myocardial perfusion stress SPET or exercise stress. ECG at rest detected pathological conductance disturbances in one patient (6%). Holter ECG evoked pathological arrhythmias in three patients (17%). The echocardiograms of four patients (22%) showed a slight impairment of left ventricular diastolic function. 123I-MIBG scintigraphy revealed an inhomogeneous reduction of norepinephrine content in 15 patients (83%). It would appear that 123I-MIBG scintigraphy is able to detect cardiac SSc involvement prior to cardiological investigations.

Chronic venous insufficiency - a potential trigger for localized scleroderma.

Localized scleroderma is a cutaneous disease that is characterized by an initial inflammatory response, followed by sclerosis of the skin. The cause of localized scleroderma has not yet been determined. Seifarth et al. reported two cases of localized scleroderma at sites of chronic venous insufficiency. We document here three more patients in whom localized scleroderma was located at insufficient veins. Treatment of underlying chronic venous insufficiency (CVI) leads to a substantial clinical improvement of scleroderma at the site of insufficient veins, but not elsewhere. Experimental data support the concept of chronic venous insufficiency creating a microenvironment, which may lead to localized scleroderma. Local hypoxaemia, which is present in CVI, induces the release of endothelium-derived cytokines, such as IL-1. Subsequently, expression of endothelial adhesion molecules and consequently leucocyte extravasation are induced. Infiltrating leucocytes secrete a number of inflammatory mediators, including transforming growth factor beta, which is a potent stimulus for collagen synthesis. Therefore, it may well be that CVI is a potential trigger factor for localized scleroderma. In addition, localized scleroderma may only develop if a certain amount of trigger factors are present - and resolves if one or more of the contributing factors (i.e. CVI) can be treated.

[Lung manifestation of progressive systemic scleroderma. Computerized tomographic findings]. / Lungenmanifestation der progressiven systemischen Sklerodermie. Computertomographische Befunde.

Progressive systemic scleroderma (PSS) is caused by generalized connective tissue disorder. The most frequent visceral manifestations are pulmonary and oesophageal involvement. Early detection of such visceral manifestations, which are sometimes life-limiting, is of paramount importance in any diagnostic procedures. The sensitivity of the methods differs and depends on the stage of the disease. Modified high-resolution computed tomographic scans (HRCT) were obtained in 28 patients with early forms of PSS and showed pulmonary involvement in 79% and signs of oesophageal involvement in 54%. HRCT is much more sensitive than chest radiography, lung scintigraphy and lung function tests even at an early stage of the disease. Classification of PSS should take account of the clinical type of sclerosis and of immunological and other parameters of prognostic importance.

[Detection of the Köbner phenomenon of the skeleton of patients with psoriasis]. / Zur Kenntnis des Köbner-Phänomens am Skelett des Psoriatikers.

Psoriasis is a humorally controlled systemic disease. The degree of "eruptive strength" of manifestation results from hereditary factors (disposition) and environmental factors (provocation). We were able to demonstrate that the well-known Köbner phenomenon of the skin also occurs on the skeleton of patients suffering from psoriasis. We analysed 83 patients in whom bone scans were carried out. Our results indicate that provocation factors such as bacterial foci and/or trauma correlate with a significantly higher number of pathological scintigraphic findings, ranging up to "hot spots". Furthermore, not only did bone fractures remained scintigraphically positive for an unusually long time, traumas of the end phalanx could be demonstrated in 70% of psoriatic patients compared with 21% of a control group. Obviously, one factor alone or a combination of factors triggers the involvement of the skeleton as a "deep Köbner phenomenon". In psoriatic patients the response of bone metabolism to disturbance differs from that of non-psoriatic patients in that there is a long-lasting dysregulation. This explains the high correlation between skin and skeletal manifestation in psoriatics. Therefore the manifestation of psoriatic disease is due not to a single-stranded linear causal interrelation but to a multicausal "network pathogenesis". Bone scintigraphy is the diagnostic method of choice in patients with psoriatic osteoarthropathy and allows an objective evaluation of therapeutic success.

[Psoriatic osteoarthropathy and bone scintigraphy]. / Psoriatische Osteoarthropathie und Skelettszintigraphie.

Psoriasis is a generalized disease that affects bone as well as skin. Three patterns of bone involvement can be differentiated in psoriatic arthritis distal, central, and distal combined with central. Distal involvement is more specific for psoriatic arthritis, with radial and/or transverse involvement of the distal interphalangeal joints. The progression dynamic and the pattern of distribution are different from those pattern of rheumatoid arthritis: psoriatic arthritis originates in the periarticular bone and extends towards the synovia, whereas in rheumatoid arthritis it extends in the opposite direction. In psoriatic arthritis anterior chest wall syndrome, insertion tendinopathies, and localized or diffuse bone disease are often observed. Bone scintigraphy is more sensitive in the diagnosis of psoriatic bone involvement than clinical examination or conventional radiological imaging, allowing earlier diagnosis through the visualization and documentation of specific patterns and presence of disease in multiple sites. It also allows more discriminating selection of subsequent X-ray examinations to limit radiation exposure. Thus, bone scintigraphy is now the most important diagnostic tool in the assessment of psoriatic arthritis.

[Early syphilis and the skeletal system]. / Frühsyphilis und Skelettsystem.

Eleven patients with early syphilis were selected at the University Dermatology Clinik in Frankfurt/M, and bone scintigraphy was performed to check for bone lesions as sign of a systemic character of the disease. The 99mTc-methylene diphosphonate scintigrams were compared with those in a control group of 50 patients. Focal hot spots indicating early metabolic changes in bone were found in all 11 patients with early syphilis. The difference between the two groups was statistically significant. The most frequent sites of hot spots were the joints of the palmar and plantar first digits. Foci were also found at the tibial tuberosities. The results support the hypothesis that reactive focal osteitis is caused by penetrating treponemes in the very early stages of syphilis. Also, we can confirm the high sensitivity of bone scintigraphy for the early detection of metabolic changes in bone compared with conventional X-ray images.

[The significance of hot spots in psoriatic skeletal involvement]. / Die Bedeutung von "hot spots" bei der psoriatischen Skelettbeteiligung.

Bone scintigraphy is a modern method of low specificity but very high sensitivity in determining early changes in bone metabolism. There is a relationship between excessive skeletal metabolic disorders of the bone and the appearance of foci of maximum radionuclide uptake, or "hot spots". This distribution of radionuclide uptake has a specific character. In a retrospective study, we investigated the distribution of hot spots in 92 patients with various forms of psoriatic disease. Hot spots were found at and near to joints only. In enthesopathies hot spots are not found, because of lack of substance. They do, however, show signs suggesting a major disorder in collagen metabolism. Hot spots indicate a rather acute degree of skeletal involvement in psoriatic disease and are also frequently found in very active phases of psoriatic disease. Therapy-induced regression is possible. Spontaneous regression was observed only in the case of hot spots of short duration. The correlation of scintigraphic findings with X-rays shows that hot spots are signs of maximal focal metabolic activity. In a high percentage of cases they are leading up to a state of destruction, which can be shown on X-rays later. Among other parameters, they indicate the likelihood of skeletal involvement in psoriatic disease. Moreover, they indicate a high risk of "psoriatic arthritis".

Leg ulcers in Klinefelter's syndrome--further evidence for an involvement of plasminogen activator inhibitor-1.

An abnormality in platelet aggregability or fibrinolysis, namely elevated activity of plasminogen activator inhibitor-1 (PAI-1), has been recently documented in patients suffering from Klinefelter's syndrome associated with leg ulceration without underlying venous insufficiency. To determine whether increased PAI-1 activity is a general feature of Klinefelter's syndrome, or more specifically associated with leg ulceration, we investigated PAI-1 influencing parameters and PAI-1 activity in two groups of patients: (i) Klinefelter patients suffering from leg ulceration (n = 7); and (ii) Klinefelter patients without leg ulceration (n = 6). On analysing PAI-1 influencing parameters such as age, body mass index, triglycerides, C-reactive protein, testosterone, smoking behaviour, the presence of diabetes mellitus, and arterial hypertension, respectively, we found no statistically significant differences between the two groups. However, PAI-1 activity in group 1 was highly significantly elevated compared with that in group two patients (P < 0.005). We conclude that (i) PAI-1 activity is not elevated in Klinefelter's syndrome in general; (ii) elevation of PAI-1 activity in patients suffering from Klinefelter's syndrome does not appear to be secondary to PAI-1 influencing parameters; and (iii) elevation of PAI-1 activity may play a crucial role in the pathogenesis of leg ulceration in Klinefelter's syndrome. Therefore, a therapy for leg ulceration in Klinefelter's syndrome that aims to return the elevated PAI-1 activity to normal should be explored.