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Background: Raynaud's phenomenon and the frequently ensuing digital ulcerations represent an early and very distressing symptom in patients with systemic sclerosis (scleroderma, SSc) causing significant limitations in the ability to work and quality of life. The use of vasoactive drugs (especially intravenous prostacyclin derivatives) is recommended to reduce the risk of hypoxic tissue damage up to the loss of fingers., Methods: In order to obtain information about the current state of treatment of patients with prostacyclin derivatives in routine clinical life in Germany, a survey was conducted among the centers affiliated to the German Network for Systemic Scleroderma (DNSS). In addition, a separate patient survey was conducted by the schleroderma self-help group (Sklerodermie Selbsthilfe e. V.), which only covered the symptoms Raynaud's syndrome, digital ulcers and the use of intravenous prostacyclin derivatives., Results: Of the 433 patients surveyed 56% stated that they had already been treated with prostacyclin derivatives (iloprost/alprostadil) because of their illness and symptoms. A total of 61% received the treatment for severe Raynaud's phenomenon and 39% for digital ulcerations. Most respondents not only experienced an improvement in Raynaud's phenomenon and digital ulcers but also a significant improvement of limitations in everyday life. They also needed significantly less outside help and absenteeism from work was much lower., Conclusion: Patients consistently reported a positive effect of treatment with prostacyclin derivatives on Raynaud's phenomenon, acral ulcerations, pain and daily restrictions and felt well and safely cared for during inpatient treatment. These positive effects in the patients' perceptions provide crucial information supporting and confirming the current European and international treatment recommendations.

Cold and White - Hypothenar Hammer Syndrome Abstract. Hypothenar hammer syndrome (HHS) is a condition caused by digital ischemia as a result of repeated trauma to the little finger. Routine diagnosis should include a detailed medical history and a physical examination including Allen's test. Imaging of vascular lesions can be done initially by acral plethysmography and duplex sonography, or directly in the context of angiography (gold standard). Early diagnosis enables effective therapeutic strategies and preventing permanent sequelae. The optimal treatment options are selected depending on the intensity of symptoms, ranging from conservative methods, secondary prevention, through a local thrombolysis up to operational measures.

Systemic scleroderma is a chronic autoimmune disease affecting the skin, internal organs and the musculoskeletal system. The presence of Raynaud phenomenon, anti-nuclear antibodies and pathologic capillaroscopy are early signs of the disease. Limited cutaneous SSc, diffuse cutaneous SSc and SSc-overlap syndromes are the main clinical subtypes. Multidisciplinary care is mandatory. Follow-up examinations should be performed at least annually in order to recognize in a timely fashion treatable organ involvement such as pulmonary arterial hypertension. Besides symptomatic treatment of organ involvement, immunosuppressive therapy is indicated for a progressive inflammatory course.

Leg ulcers may result in serious morbidity in patients with connective tissue diseases and Raynaud's phenomenon (RP). We describe a 35-year-old woman with mixed connective tissue disease who suffered from leg ulcers refractory to iloprost. When the patient was treated with the selective endothelin A receptor antagonist sitaxsentan for pulmonary arterial hypertension, the ulcers improved within 4 weeks and resolved completely thereafter. In addition, severity of RP ameliorated markedly. Further evaluation of sitaxsentan in patients with connective tissue diseases suffering from ischemic skin ulcers is required.

Phosphodiesterase type 5 (PDE5) induces the breakdown of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. Hence, PDE5 inhibitors promote vasodilative effects by enhancing intracellular cGMP levels. Three PDE5 inhibitors, sildenafil, vardenafil, and tadalafil, have been approved for the treatment of "erectile dysfunction" (ED). All three show an excellent effectiveness regarding ED therapy, but differ from one another regarding their pharmacokinetic properties. Recent experimental studies and clinical trials indicate that PDE5 inhibitors are also effective in the treatment of various other diseases such as pulmonary arterial hypertension (PAH), Raynaud's disease, gastrointestinal disorders, and stroke, and furthermore exert cardioprotective effects. This review describes the cardiovascular safety of PDE5 inhibitors and provides an overview of the current literature regarding potential novel indications.

Systemic sclerosis (SSc; syn. systemic scleroderma) is a rare autoimmune disorder with characteristic cutaneous manifestations. Prevalence in women is fivefold higher than in men. The course of the disease is slowly progressive with a variable degree of internal organ involvement due to fibrosis and obliteration of small vessels. The diffuse form shows more frequent and severe organ manifestations compared to the limited form. Increased mortality is particularly related to a cardiopulmonary involvement leading to a 5-year survival of around 75%. Treatment indications are dependent on the severity of the disease. In the acute state, immunosuppressive agents are needed in case of significant organ involvement. Vasodilative drugs are often used for the symptomatic treatment of Raynaud's phenomenon.

The connective tissue disease systemic sclerosis (SSc) is still a challenge to every rheumatologist. SSc is characterized by progressing fibrosis of the skin and internal organs, abnormal activation of the immune system and distinct changes in microcirculation. Although it is a rare disease with a prevalence of about 20:100,000 one may come across it in daily practice. SSc is classified into limited and diffuse forms. Both entities usually involve internal organs. Life expectancy is limited and depends predominantly on the extent of the organs involved. Therefore, it is essential to diagnose SSc early and to identify and closely monitor the organs involved.

Raynaud's syndrome has a prevalence of 3-5% in the general population. Despite its high frequency, the majority of available therapies have not been validated in randomized controlled trials. Effective therapies with a high level of evidence include the calcium channel blocker nifedipine. As analyzed by meta-analyses, nifedipine showed improvement of the peripheral circulation, as well as reduction of both the intensity and frequency of attacks in patients with primary and secondary Raynaud's syndrome as compared to placebo. Similar results in a metaanalysis were obtained for intravenous infusions of iloprost in patients with secondary Raynaud's phenomenon associated with systemic sclerosis. In addition, intravenous infusions of iloprost improved healing of fingertip ulcers in patients with systemic sclerosis. Therapies with significant effects in single randomized controlled trials include angiotensin II-receptor type 1 antagonists (losartan), the calcium channel blockers felodipine und amlodipine, serotonin-reuptake-inhibitors (fluoxetine) und phosphodiesterase-V-inhibitors (sildenafil, vardenafil). However, the results for these promising substances have to be confirmed in long-term trials with larger patient numbers.

History: A 65-year-old woman was admitted because of dyspnea at rest and peripheral edema due to scleroderma-associated pulmonary fibrosis and hypertension, as well as Raynaud's phenomenon., Diagnostic Features, Treatment and Course: She had a marked restrictive ventilatory disorder with severe impairment of diffusion capacity. Right heart catheterization demonstrated a mean pulmonary artery pressure of 50 mmHg. She was able to walk only 220 m. All usual methods of treatment failed to give satisfactory results so that sildenafil (phospherodiesterase type-5 |PDE-5| inhibitor; Viagra ((R)) was given, even though it is not licensed for this indications ("off-label", as a therapeutic attempt. This achieved definite reduction in pulmonary arterial pressure and significantly improved the clinical symptoms. In particular, it drastically reduced the level of atrial natriuretic peptide, an important prognostic marker in right heart failure. Sildenafil also significantly raised peripheral perfusion and the signs of Raynaud's syndrome., Conclusion: PDE-5 inhibitors are efficacious in scleroderma-associated pulmonary hypertension and may also provide a new option in the treatment of Raynaud's disease.

We report on an acral circulatory disorder of the hand, representing a Hypothenar-Hammer-Syndrome (HHS) with atypical symptoms. The patient suffered from a radial circulatory disorder of his right hand, clinically representing a secondary M. Raynaud. The symptoms occurred after a single severe trauma of the right hand and after using both hands like a hammer. Angiography showed a cork-screw sign of the A. ulnaris at the typical area and an open Arcus palmaris superficialis as well as occlusions of multiple finger arteries. Symptoms improved significantly after lysis. The most important differential diagnosis is endangiitis obliterans according to angiography. If symptoms occur again, histology is recommended to exclude vasculitis. Surgery should be discussed if the HHS is confirmed, since a cork-screw morphology of the A. ulnaris exists as well as perfusion of the fingers mainly via the A. ulnaris. Also a radial circulatory disorder of the hand combined with typical anamnesis may represent a HHS.

History and Findings: A 38-year-old woman, in her 13th week of pregnancy, presented for angiological investigation of repeated episodes of pain in the right index finger. She also reported painful paleness of the right nipple evoked particularly by cold. This was her fifth pregnancy; she had miscarried twice. The nipple pain occurred spasmodically and in three phases, while the left nipple was unaffected. The attacks lasted c. 15 min, progressing from an ischemic to a hyperemic phase, accompanied by unbearable pain. When first examined there was circumscribed, purplish network-patterned discoloration of the right hand with blackened discoloration of the distal nail-bed of the index finger., Investigations: Duplex-sonography revealed patency of the large arteries of the arm and hand. Transesophageal echocardiography showed a persistent foramen ovale and echo-density suspected to be a right atrial thrombus. Laboratory tests demonstrated anticardiolipin antibodies, suggesting an antiphospholipid syndrome., Treatment and Course: On administration of low-molecular heparin, its dosage weight-adjusted, and 100 mg aspirin daily the discoloration of the finger quickly disappeared, but Raynaud's syndrome remained unchanged until she had stopped breast feeding (left breast only) after 8 months. A healthy girl had been delivered by cesarean section in the 39th week, weighing 3100 g. There were no further thromboembolic complications., Conclusion: This very rare case of Raynaud's phenomenon in a nipple was associated with an anti-phospholipid syndrome.

Systemic sclerosis is an autoimmune disease of unknown origin affecting multiple organ systems. The management of this disease is challenging. Many therapeutic attempts have only been moderately successful. Iloprost, a stable prostacyclin analogue, with its antifibrotic effect can influence an important step in the pathogenesis of systemic sclerosis. In this review we analyze the published data for the optimal dose and duration of treatment. In three different studies, iloprost given for 5 days in the highest tolerated dose of 1-2 ng/kg/min provided a significant improvement of the disease measured by the number and intensity of Raynaud attacks, healing of digital ulcers, and digital perfusion. This improvement lasted for about one month. When the infusions were repeated once a month, treatment effect could be maintained. Although the effect of this treatment regimen should be proven in further long-term studies, we think that an intermittent continuous therapy with iloprost could result in an improvement or stabilization of systemic sclerosis.

The Raynaud phenomenon occurs in 90-100% of patients with systemic scleroderma. It is caused by dysregulation of the vascular tone between vasoconstrictive and vasodilatory influences. Early damage to the vascular endothelium and the activation of platelets lead to the release of vasoactive substances. Structural and function impairment of the perivascular neural fibers contributes to the vasospasm. New vasodilatory treatment strategies, e.g. infusions with calcitonin gene-related peptides, could be useful in the control of vasospasm in the peripheral extremities as well as internal organs in systemic scleroderma.

In-vivo videomicroscopy is one of the few noninvasive and clinically useful direct methods for evaluating the effect of a drug on microcirculation of normal and ischemic areas. By using nailfold videomicroscopy in conjunction with local exposure to cold air, the hemodynamic effects of ketanserine and nifedipine are reviewed in patients with primary Raynaud's disease.

A 45-year-old male patient presented with cold-induced generalized livedo reticularis, repeated acral ulcerations and purpura, Raynaud's phenomenon, and peripheral polyneuropathy. The patient also experienced malaise, vertigo, and transient amaurosis whenever he was exposed to low temperatures. Skin biopsies of the livedo reticularis revealed marked dilatation of the small dermal blood vessels and circumscribed leukocytoclastic vasculitis. Essential cryofibrinogenaemia was diagnosed on the basis of detection of this cryoprotein in the chilled blood plasma with increased viscosity. Pulsed therapy with dexamethasone and cyclophosphamide resulted in marked relief of the symptoms, and cryofibrinogen was no longer detectable in the patient's plasma.

Polymyositis is a primarily clinical diagnosis. In 30-40% of patients, however, the specific anti-Jo-1 antibody (anti-histidyl-tRNA-synthetase) can be found. These cases are often associated with interstitial lung disease and other typical clinical manifestations. This symptomatology is called Jo-1-syndrome. Prognosis depends on early diagnosis, since Jo-1 associated interstitial lung disease resulting in pulmonary fibrosis is favorably influenced by immunosuppressive therapy, especially with corticosteroids. The present report concerns a patient with Jo-1-syndrome and beginning pulmonary fibrosis who was treated with methotrexate and prednisolone with good initial response. After 1 year the patient's condition had deteriorated, so that the therapy was changed to cyclophosphamide. Longterm results under this therapy remain to be evaluated.

Raynaud's phenomenon often represents an early symptom of collagen diseases as well as of occlusive vascular disease; it can as well be due to vibration trauma following development of mechanical lesion of the acral capillary system. A rare case of professionally acquired vibration trauma in a miner who developed vasospastic ischaemia after 20 years subterranean work is reported. Non-invasive blood-flow measurements such as thermic relaxation time, transcutaneous O2-pressure, and laser-doppler perfusion rate, represent suitable means of diagnosis and observation of the course of the disease. Combination therapy including both primary inhibition of platelet aggregation as well as improvement of rheological properties has proved to be superior to other treatment plans.

Measurements of the whole-blood viscosity in patients with organic and functional disturbances of the acral blood supply were performed. In comparison with the whole-blood viscosity in normal persons patients with acral occlusive diseases showed a significantly increased viscosity. On the other hand, in patients with functional disturbances of the acral blood supply no differences could be established. In a therapy study the good efficacy of rheologically effective medicaments could be demonstrated particularly as combination therapy of pentoxifylline, acetylsalicylic acid and tolazoline in patients with acral occlusive diseases. These medicaments should by all means be used together with the basic therapy. In functional disturbances of the blood supply should predominantly be maintained physiotherapeutic methods of treatment.

Prostaglandin E1 was given intraarterially to twenty persons with severe peripheral ischaemia at risk of requiring amputation of a limb for ischaemic ulcers or necrosis. All patients had received conventional therapy without success before PG E1 treatment. An average dose of 6.14 ng/kg/min of PG E1 was given intraarterially for 2 hrs daily over a period of six days. In fifteen cases PG E1 therapy resulted in complete or partial healing of the ulcers and necrotic areas while the patients no longer suffered from pain at rest. No beneficial effects of PG E1 treatment were seen in five patients. In these cases cases multiple arterial occlusions, caused by arteriosclerosis and diabetes mellitus, existed, in more than three levels. Side effects like pain in the infused limb and swelling of the extremity occurred in fourteen patients, but were reversible in each case.

The ability of a single i. v. application of 40 micrograms alprostadil (PGE1, mean therapeutic dose 0.62 microgram/kg body weight) to cause changes in capillary microscopy parameters and tcpO2 was investigated in an open study in 15 patients with peripheral arterial occlusive disease, Fontaine stage II-IV (8 women and 7 men, average age 70.1 and 70.0 years, respectively). Capillary microscopy investigations and oxygen tension measurements were carried out before and immediately after i. v. infusion of PGE1 or a 5% solution of laevulose using an intra-individual comparison. PGE1 led to an increase in the number of erythrocyte-filled capillaries per mm2, an improvement in the initial condition of the capillaries evaluated according to Fagrell and to a significant increase in the tcpO2, whereas no haemodynamic changes occurred at all after laevulose. These findings substantiate the view that PGE1 is also effective when applied intravenously distal from the arterial occlusion.

The effectiveness of a new, nifedipine-like calcium antagonist (Bay K 9320) on the severity and frequency of episodic digital vasospasms was studied in a randomized double-blind trial of 24 patients (10 women, 14 men) with Raynaud's phenomenon. During the winter months the patients took one tablet three times daily for three weeks, each tablet either containing 20 mg of the calcium antagonist or a placebo. Three patients had collagen disease, 21 a primary form of Raynaud's phenomenon. Subjective improvement was reported by nine of twelve patients receiving the drug, while no improvement occurred in nine patients on the placebo. Light-plethysmography demonstrated under calcium antagonist treatment a reduction in the cold-provoked acral blood flow decrease more than four-fold compared with the unchanged value in the placebo group.

In 15 patients with progressive systemic sclerosis with Raynaud's phenomenon Papaverin hydrochloride retard (Panergon) therapy was used. The average age of 14 females and 1 male was 42 years (26-55). Panergon therapy lasted for 4 weeks, the daily dose being 450 mg. For the evaluation of the treatment, 3 instrumental methods were used: IR radiometry for measuring thermal changes in the hands, capillaroscopy of nailfold, and Doppler-ultrasonic examination for measuring the circulation in finger arteries. An increased temperature, particularly in the fingertips, was found by radiometric examination in 6 patients. We also observed the acceleration of capillary flow speed in 7 patients. The pulse wave in finger arteries was markedly increased in 5 patients. From the subjective point of view the Panergon therapy was judged to be successful in 12 patients. It was not necessary to interrupt the treatment because of unfavourable effects in any case. Panergon therapy seems to be an important step in the treatment of Raynaud's phenomenon in progressive systemic sclerosis.

During a 10-day hospitalization, 21 patients suffering from systemic sclerosis (SS) with Raynaud's phenomenon were treated intermittently with intravenous infusions of calcitonin for 5 hours daily. Telethermographically, we measured a significantly shortened rewarming period of the patients' hand after standardized cooling. Up to now, as many as 47 patients with SS have been treated in the same way during 152 10-day cycles of calcitonin infusion. Only 7 patients interrupted the calcitonin therapy because of transient headache or nausea. Allergic reactions have not been observed, so far.

In a single-blind trial 25 patients with progressive scleroderma and Raynaud's phenomenon intravenous infusions of iloprost, a prostacyclin derivative (carbaprostacyclin), were given daily for five hours during a six-day hospital stay, after a comparable initial single placebo infusion. Duration, frequency and intensity of Raynaud symptoms improved in more than 75% of the patients. This improvement was objectified by telethermometry which demonstrated acral hyperthermia and significantly briefer rewarming after standardized cooling of the hands. In addition, there was more rapid healing of ulcerations and necroses of the digital pulp. A significant inhibition of ADP- and collagen-dependent platelet aggregation was demonstrated during the iloprost infusion. Side effects, such as headache, nausea and tiredness occurred only transitorily during the infusion, were individually highly variable, and then only at higher concentrations. A dosage of 2 ng/kg X min was tolerated by all patients.

Twenty patients with primary or secondary Raynaud's phenomenon were, after a 4-week treatment-free interval, given captopril ( Lopirin ) at a dosage of 25 mg three times daily for 84 days. Marked subjective improvement was reported by 14 patients. Digital-artery pressure, blood flow at rest and blood flow during reactive hyperaemia increased. Blood flow at rest increased significantly after cooling (10 degrees C for three minutes).

Acute and subacute acral ischemia syndromes must be carefully distinguished from chronic intermittent acral disturbances of circulation because of the differences in the genesis, in the clinical picture and in the treatment. Vasoconstriction caused by cold or emotion and which disappears on warming is the principal feature of the chronic intermittent syndromes. Prestasis and stasis are the basis of the ischemia of acute and subacute syndromes, which cannot be relieved by warmth. Vasodilation measures have no effect, whereas the circulation can be restored by the improvement of the fluidity and the flow conditions of the blood.

In a number of patients with etiologically unexplained visual field loss, a vasospastic syndrome was found with the aid of capillaroscopic local cooling test on the fingers. After therapy with calcium entry blockers the visual field of the patients with vasospastic syndrome underwent a marked and statistically significant improvement. The control group showed a slight but statistically insignificant tendency towards improvement.

74 patients with arterial circulatory disorders have been treated with calcitonin in low dosages (0.25-0.5 mg s.c. or i.m. twice to three times weekly). In 3 women with Raynaud phenomenon in sclerodermia, previously refractory necroses of the finger-tips were cured. One woman with Raynaud disease became symptomfree. Marked improvements in the results of ergometric tests were observed in 8 out of 22 patients with intermittent claudication of the lower extremities. In 12 out of 31 patients with refractory angina pectoris, the attacks were practically eliminated. Remission of headaches of vascular origin was obtained in 6 out of 17 cases. Attacks of migraine were terminated in the incipient stage by treatment with 0.25 mg Cibacalcin.