Prolonged improvement of Raynaud's phenomenon and scleroderma after recombinant tissue plasminogen activator therapy

We describe a patient with systemic sclerosis (SSc; scleroderma) characterized by severe Raynaud's phenomenon, cutaneous sclerosis, and digital ulceration and subsequent amputation who was treated with recombinant tissue plasminogen activator (rt-PA) after acute myocardial infarction. She showed prompt improvement of the Raynaud's phenomenon and healing of the digital ulceration. After 18 months of followup, the Raynaud's phenomenon has remained mild, and there has been improvement in the cutaneous sclerosis. Since the pathophysiology of SSc has been associated with disorders of fibrinolysis and coagulation, this patient represents an interesting index case that might prompt further evaluation of rt-PA therapy in carefully selected patients.     

Cardiological aspects of the antiphospholipid syndrome. Part I. Valvular lesions in the primary and secondary antiphospholipid syndrome and systemic lupus erythematosus

AIM. To assess prevalence of cardiac valvular lesions in patients with primary (P) antiphospholipid syndrome (APLS) and systemic lupus erythematosus (SLE) with and without secondary APLS. MATERIAL AND METHODS. Patients with PAPLS (n=56, 15 men and 41 women), SLE and APLS (n=88, 23 men, 65 women) and SLE without APLS (n=51, 19 men, 32 women) were followed up for 9 years. Serological markers of APLS were anticardiolipin antibodies and lupus anticoagulant. RESULTS. Prevalence of various heart defects was the highest in PAPLS (43%) compared with SLE with APLS (c2=5.6, p=0.001) and SLE without APLS (c2=9.3, p=0.0002). In secondary APLS prevalence of valvular involvement was 27% what was substantially more than in SLE without APLS (4%) (c2=7.2, p=0.0007). Changes of mitral valve cusps and mitral regurgitation were found in 33, 41 and 50% of patients with SLE, SLE with APLS and PAPLS, respectively. Pronounced mitral regurgitation and valve defects were significantly more frequent in patients with any APLS compared with those with SLE without APLS. Thickening of aortic cusps was significantly more frequent in patients with PAPLS compared with patients with SLE (with and without APLS). Changes of tricuspid valve were significantly more frequent in patients with any APLS. Progression of valvular pathology was observed in 2 patients with SLE and APLS after 4 and 5 years of follow up. During 9 years thrombotic complications developed in 8 patients with APLS and valvular lesions (6 strokes, 2 retinal thromboses). CONCLUSION. An association exists between presence of APLS and various cardiac valvular lesions. Lesions of aortic valve are associated with PAPLS. Development of valvular pathology in patients with SLE and PAPLS during follow up dictates the necessity to monitor echocardiographical parameters and titers of anticardiolipin antibodies.     

Potential therapeutic effect of simvastatin on progressive renal failure and nephrotic-range proteinuria caused by renal cholesterol embolism

We report our experience with a 62-year-old Japanese man with cholesterol crystal embolism after angiographic procedures performed because of intermittent claudication. In addition to progressive renal failure and nephrotic-range proteinuria, cutaneous ischemia, consisting of livedo reticularis in the lower limbs and digital necrosis at the tip of the right toe, and fundoscopic findings showing several white spots in the branches of retinal artery were also observed. Progressive renal failure and nephrotic-range proteinuria were halted just after treatment with simvastatin. Thus, simvastatin can exert a beneficial therapeutic effect on renal cholesterol embolism.     

Redirection of cutaneous sensation from the hand to the chest skin of human amputees with targeted reinnervation

Amputees cannot feel what they touch with their artificial hands, which severely limits usefulness of those hands. We have developed a technique that transfers remaining arm nerves to residual chest muscles after an amputation. This technique allows some sensory nerves from the amputated limb to reinnervate overlying chest skin. When this reinnervated skin is touched, the amputees perceive that they are being touched on their missing limb. We found that touch thresholds of the reinnervated chest skin fall within near-normal ranges, indicating the regeneration of large-fiber afferents. The perceptual identity of the limb and chest was maintained separately even though they shared a common skin surface. A cutaneous expression of proprioception also occurred in one reinnervated individual. Experiments with peltier temperature probes and surface electrical stimulation of the reinnervated skin indicate the regeneration of small diameter temperature and pain afferents. The perception of an amputated limb arising from stimulation of reinnervated chest skin may allow useful sensory feedback from prosthetic devices and provides insight into the mechanisms of neural plasticity and peripheral regeneration in humans.     

Syndrome RACAND associé à une cirrhose biliaire primitive

The acronym RACAND means the association of Raynaud's phenomenon, anticentromere antibodies and digital necrosis without digital sclerosis. It is a rare syndrome recently individualised. The association with primary biliary cirrhosis has never been previously reported, and leads to discuss its nosology. A 57-year-old woman with a history of Raynaud's phenomenon, presented with recurrent episodes of fingers and toes necrosis. Clinical examination did not evidence digital sclerosis. Anticentromere antibody titer was high. There was no oesophageal or lung involvement. A liver biopsy performed because of moderate increase in liver enzymes showed histological lesions of primary biliary cirrhosis. Treatment with iloprost, platelet aggregation inhibitors and anticalcic drugs could not avoid amputation of several toes. It is possible that anticentromere antibodies are directly toxic to vascular endothelial cells and result in a diffuse or localized vasculopathy. The association with primary biliary cirrhosis is in favour of autoimmune condition of both vascular and ductular endothelial cells.     

Anti-oxidized low-density-lipoprotein (OxLDL) antibodies in systemic lupus erythematosus with and without antiphospholipid syndrome

The aim of this study was to examine potential links between antiOxLDL antibodies and the clinical and biological features of secondary antiphospholipid syndrome (II APLS) associated with systemic lupus erythematosus (SLE). A cohort study was done of 98 SLE patients followed-up for 1 y, including 18 with definite II APLS and 13 patients with definite primary APLS (I APLS). IgG anticardiolipin, IgG anti beta2 GPI, lupus anticoagulant, VDRL and IgG antiOxLDL were measured in all 98 study subjects. High antiOxLDL titers were found in seven (39%) of the 18 patients with II APLS vs 10 (12.5%) of the 80 patients without APLS (P < 0.01; OR = 4.45; 95% CI = 1.4-14.1) and none of the 13 patients with I APLS (P < 0.02). The mean antiOxLDL titer was not significantly higher in the SLE patients with than without II APLS (P > 0.05). A high antiOxLDL titer was correlated with deep venous thrombosis (P < 0.01; OR = 5.77; 95% CI = 0.54-61) but not with arterial thrombosis (P > 0.05; OR = 1; 95% CI = 0.29-3.09), thrombocytopenia, central nervous system involvement, livedo reticularis, or a positive Coombs test. The antiOxLDL antibody titer was correlated with the IgG anticardiolipin antibody titer (r = 0.235; P = 0.02) and with the IgG anti-beta2 GPI antibody titer (r = 0.224; P = 0.026). AntiOxLDL elevation was found in 17% of SLE patients and was significantly associated with II APLS and venous thrombosis. We found no evidence suggesting that antiOxLDL may be associated with atherosclerosis.     

Immune-mediated pathology following hepatitis B vaccination. Two cases of polyarteritis nodosa and one case of pityriasis rosea-like drug eruption

The association of hepatitis B virus infection and vasculitis or other immune-mediated manifestations is well documented. Reports on such manifestations in relation to hepatitis B vaccination are scarce, however. We report 2 patients who developed polyarteritis nodosa following vaccination against hepatitis B. In one patient this resulted in an ischemic and necrotic digital ulcus, necessitating surgical amputation. The other patient presented with typical cutaneous polyarteritis nodosa which responded well to corticosteroid treatment. A third patient developed a severe pityrias rosea-like eruption. He was treated with topical steroids with healing of the lesions, leaving only post-inflammatory hyperpigmentation. The literature on these associations is reviewed.     

Antiphospholipid antibody profile-based outcome of purely vascular and purely obstetric antiphospholipid syndrome

Antiphospholipid syndrome (APLS) is caused by antiphospholipid autoantibodies, and manifests with vascular and/or obstetric complications. The factors associated with initial disease presentation and course are unknown. We assessed the antibody profile associated with disease presentation and with the development of vascular and obstetric complications in women with initially vascular or initially obstetric APLS. A review of records of APLS women at childbearing age followed at one center during 2006–2015. Of 126 women, median age at diagnosis 29 [23–37] years, 62 were initially diagnosed with purely obstetric APLS and 64 with purely vascular APLS. Baseline characteristics and antibody profile did not differ according to the initial diagnosis. At a mean follow-up duration of 61?±?23 months, 19 (30.6%) with initially obstetric disease, and 20 (31.3%) with initially vascular disease, developed vascular and obstetric complications, respectively (P?=?1.0). Among those with triple positivity [lupus anticoagulant (LAC)+, anticardiolipin (ACL)+, anti beta2-glycoprotein I (AB2GPI)+], a higher proportion developed both obstetric and vascular complications, compared to those with single or double positivity (42.3 vs. 16.4%, P?=?0.002). In multivariate analysis, the presence of LAC (P?=?0.008), ACL IgG (P?=?0.009) or AB2GPI IgG (P?=?0.01) was the only independent predictor of the development of both obstetric and vascular complications. Almost one-third of women with initially vascular or initially obstetric APLS developed mixed disease. The antibody profile was the only prognostic marker for disease course. The association found between LAC, ACL IgG or AB2GPI IgG, and patient outcomes could contribute to risk stratification and individualized patient management.     

Cardiovascular surgical outcomes in patients with the antiphospholipid syndrome--a case-series

BACKGROUND: Patients with the antiphospholipid syndrome (APLS) have severe involvement of the cardiovascular apparatus and often need surgical interventions to correct these manifestations. Few studies that have looked at the outcomes of cardiothoracic surgeries in APLS patients have reported high rates of perioperative mortality and thromboembolic events. OBJECTIVE: Our goal was to examine the outcomes of adult APLS patients undergoing coronary artery bypass surgery (CABG) and/or valvular surgery. We also wanted to determine whether aggressive anticoagulation therapy could prevent life threatening thromboembolic complications in these patients. METHODS: We retrospectively reviewed medical records of nine patients with primary APLS undergoing cardiothoracic surgery between 1985 and 2005 at our institution. Patient demographics, operative procedures and one-year clinical outcomes were obtained. RESULTS: Forty-five percent of our patients had more than three cardiovascular risk factors other than APLS. There were no mortalities in our case series. However, 89% of our patients developed major complications. Despite aggressive anticoagulation, 37.5% developed thromboembolic events including cerebrovascular accidents, myocardial infarctions and vena caval thrombosis. Other complications included heparin-induced thrombocytopenia, redo of CABG surgery and sepsis. CONCLUSION: Despite aggressive anticoagulation and lack of significant pre-operative co-morbidities, APLS patients undergoing cardiothoracic surgery appear to have high rates of post-operative clinical events.     

Severe vascular complications in patients affected by systemic sclerosis cyclically treated with iloprost

The objective of this study was to evaluate the incidence of the most severe vascular complications, such as pulmonary arterial hypertension, scleroderma renal crisis, and digital necrosis requiring amputation, in a monocentric group of systemic sclerosis (SSc) patients cyclically treated with intravenous iloprost. We reviewed the record-charts of 115 patients affected by SSc (18 men and 97 women, mean age 58.9.1?±?14.2?years) regularly receiving iloprost for at least 3?years; the mean duration of the treatment was 98.8?±?37.5?months (a total of 946.8?years of therapy). Demographic and clinical features were recorded. None of the patients died of SSc-associated vascular complications. After iloprost administration digital gangrene requiring amputation developed in 2 patients who had concomitant peripheral arterial disease (a total of 3 episodes; annual incidence of 0.31 for 100?years of iloprost therapy). Four patients were diagnosed with pulmonary arterial hypertension during iloprost treatment (annual incidence of 0.42 for 100?years of drug therapy); in none of the cases did the complication show a progressive course. No cases of scleroderma renal crisis were observed. With the limits of an observational study and in the absence of a control group, our experience suggests that prolonged cyclic iloprost therapy may limit the incidence/progression of severe digital and visceral SSc-vasculopathy.     

Digital ischaemia aetiologies and mid-term follow-up: A cohort study of 323 patients

Upper extremity digital ischaemia (UEDI) is a rare heterogeneous condition whose frequency is 40 times less than that of toe ischaemia. Using a large cohort, the aim of this study was to evaluate aetiologies, prognosis and midterm clinical outcomes of UEDI.All patients with UEDI with or without cutaneous necrosis in a university hospital setting between January 2000 to December 2016 were included. Aetiologies, recurrence of UEDI, digital amputation and survival were analyzed retrospectively.Three hundred twenty three patients were included. UEDI due to cardio-embolic disease (DICE) was the highest occurring aetiology with 59 patients (18.3%), followed by DI due to Systemic Sclerosis (SSc) (16.1%), idiopathic causes (11.7%), Thromboangiitis obliterans (TAO) (9.3%), iatrogenic causes (9.3%), and cancer (6.2%). DICE patients tended to be older and featured more cases with arterial hypertension whereas TAO patients smoked more tobacco and cannabis. During follow-up, recurrences were significantly more frequent in SSc than in all other tested groups (P < .0001 vs idiopathic and DICE, P = .003 vs TAO) and among TAO patients when compared to DICE patients (P = .005). The cumulated rate of digital amputation was higher in the SSc group (n = 18) (P = .02) and the TAO group (n = 7) (P = .03) than in DICE (n = 2).This retrospective study suggests that main aetiologies of UEDI are DICE, SSc and idiopathic. This study highlights higher frequency of iatrogenic UEDI than previous studies. UEDI associated with SSc has a poor local prognosis (amputations and recurrences) and DICE a poor survival. UEDI with SSc and TAO are frequently recurrent.     

Comparison of infrared thermography and laser speckle contrast imaging for the dynamic assessment of digital microvascular function

ObjectivesLaser speckle contrast imaging (LSCI) is a novel non-invasive microvascular imaging modality. The present study evaluates the validity and reliability of LSCI by comparison with infrared thermography (IRT) for the dynamic assessment of digital microvascular function in healthy volunteers.MethodsSubjects attended on 3 occasions. Simultaneous assessment of cutaneous perfusion at 3 distinct regions of interest (ROI) within the hands was undertaken using LSCI and infrared thermography (IRT) at baseline, and at 13 s intervals over 15 min following a standardised local cold challenge. Endpoints for evaluation included absolute measurements at baseline and following cold stress, in addition to the characteristics of the re-warming curves (maximum % recovery and maximum gradient). Visits 1 and 2 were undertaken in identical conditions (ambient temperature 23 °C) to assess reproducibility, whereas visit 3 was undertaken at a lower ambient room temperature of 18 °C to evaluate responsiveness to reduction in ambient room temperature.ResultsFourteen healthy participants completed the study. There was greater variability in the data generated using LSCI compared with the highly damped IRT, reflecting greater sensitivity of LSCI to physiological variation and movement artefact. LSCI and IRT correlated well at baseline and following cold challenge for all endpoints (r_s for pooled data between 0.5 and 0.65, p < 0.00005). Reproducibility of both IRT and LSCI was excellent (ICCs > 0.75) for absolute assessments but lower for re-warming curve characteristics. LSCI provides greater spatial resolution than IRT identifying variation in cutaneous perfusion within the hands most likely associated with the presence of arteriovenous anastamoses. Both techniques were responsive to reduction in ambient room temperature. Effect sizes were greatest for IRT than LSCI (e.g. ? 1.17 vs. ? 0.85 at ROI 1 at baseline) although this may represent heat transfer rather than altered vascular perfusion.DiscussionIn the dynamic assessment of digital vascular perfusion, LSCI correlates well with IRT, is reproducible and responsive to reduction in ambient room temperature. Absolute measurements appear preferable to parameters derived from re-warming curve characteristics when assessing digital perfusion following cold challenge. The greater temporal and spatial resolution of LSCI compared with IRT may facilitate the development of novel assessment tools of autonomic function and digital cutaneous perfusion.     

Successful plasma exchange combined with rituximab therapy in aggressive APS-related cutaneous necrosis

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis or recurrent fetal loss associated with the presence of antiphospholipid antibodies and/or a lupus anticoagulant. The skin appears to be an important target organ and many cases of APS may present with skin manifestations. These lesions may be manifold and may take the form of livedo reticularis, livedo racemosa, ulcerations, digital gangrene, subungeal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis, or primary anetoderma. We report a case of fulminant APS-related cutaneous necrosis. A 38-year-old Caucasian male with a past history of APS, multiple deep vein thrombi/pulmonary emboli, presented with necrotic lesions on his right upper and right lower extremities. Initially, baseline anticoagulation was increased without improvement. Subsequently, plasma exchange was initiated on a daily schedule. Furthermore, rituximab 1,000 mg IV was administered on days 1 and 15. After six consecutive daily sessions of plasma exchange, there was significant regression of the necrotic lesions. After a 22-day hospital stay, the patient was discharged to home on fondaparinux. The patient presented approximately 2 months later after missing follow-up appointments. At the time, his initial lesions looked remarkably improved.

     

Digital vasculitis: a late complication of anti-tumour necrosis factor alpha therapy

Anti-tumour necrosis factor alpha therapy has led to significant advancement in the treatment of rheumatological disease. Rarely, anti-TNFα antagonists have been associated with vasculitis, predominantly cutaneous leukocytoclastic vasculitis. We present the first case of angiographically-confirmed digital vasculitis occurring as a late complication of etanercept therapy. Our case adds to the limited repertoire of case reports of anti-TNFα induced vasculitis and highlights the potential risk of this serious complication occurring up to several years after initiation of these agents.     

Acute ischemia of the extremities and drug addiction

It is not unusual to find ischemia of limbs in drug addicts and two new cases are reported, together with a literature review, allowing analysis of physiopathologic mechanisms and therapeutic modalities. The first case was a 20 year old man who presented with sensory-motor ischemia of the right hand after injection of heroin into the radial artery. Arteriography showed partial occlusion of the deep palmar arch and all collateral arteries of fingers. Regression of ischemia followed administration of thrombolytics, heparin and vasodilators, arteriography showing restoration of palmar arch and digital arteries flow apart from that of the 4th finger. The latter developed distal necrosis which required, in spite of thoracic sympathectomy, amputation of the 3rd phalanx. Histology of amputation piece showed presence of intra-arterial foreign bodies. The second case was a 30 year old man who presented with an acute sensory-motor ischemia of left calf and foot after injection of heroin into the retromalleolar groove. Arteriography showed absence of opacification of vascular axes in the middle third of leg and an atheromatous plaque in left main iliac artery. Heparin therapy plus lumbar sympathectomy resulted in reheating of the foot, but ischemia recurred one month later. A repeat arteriography with oblique images demonstrated that the plaque in the main iliac artery was larger than it appeared in frontal images and that an embolus had developed in the deep femoral artery. Final treatment in this patient involved an inter-femoral saphenous vein bypass and amputation of 4th toe. Histology of amputation piece showed only a banal arterial thrombosis without foreign body.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous immunoglobulins as treatment of severe cutaneous polyarteritis nodosa

We describe three patients with severe refractory cutaneous polyarteritis nodosa, resulting in painful ulcers involving the lower limbs and causing toe necrosis. Due to the severity of the cutaneous manifestations, the three patients received intravenous immunoglobulins at a dose of 1 g/kg/day for 2 days monthly. After the second intravenous immunoglobulin infusion, skin signs dramatically improved and completely healed after the third intravenous immunoglobulin infusion. Our findings indicate that intravenous immunoglobulins can be included in a therapeutic strategy to treat refractory cutaneous polyarteritis nodosa.     

Catastrophic antiphospholipid syndrome after ovulation induction

INTRODUCTION: The catastrophic antiphospholipid syndrome (CAPS) is a rare expression of the antiphospholipid syndrome (APLS). The all predicting factors of happening of CAPS are not yet discovered. Some women presenting an APLS with infertility have recourse to ovulation induction (OI). EXEGESIS: After an OI, a woman is admitted for acute renal failure, hypertension, seizures, respiratory failure. History and immunologic tests are in favour of APLS. Renal biopsy highlights a thrombotic microangiopathy. Diagnosis of CAPS is made. Patient improves after respiratory assistance, parenteral treatment for hypertension and anticoagulant therapy. CONCLUSION: IO seems to be on of the factors which leads to CAPS. To avoid such consequences, it's essential to know the history and the immunological status of the patients having recourse to this treatment to take care of these risked pregnancies.     

Vasopressin-related bullous disease of the legs

We report a 33-year-old man who developed cutaneous necrosis of the lower extremities with extensive bulla formation after i.v. administration of vasopressin for the treatment of bleeding esophageal varices. Due to its potent nonselective vasoconstrictive action, vasopressin not only may induce cardiac and gastrointestinal ischemia, but cutaneous ischemia as well. As in our patient, this may lead to extensive necrotic skin lesions at sites distant from the infusion.     

High resolution 3 Tesla contrast-enhanced MR angiography of the hands in Raynaud’s disease

Raynaud’s disease is associated with disorders in blood circulation of the hands. The gold standard to visualise pathology of digital arteries is catheter angiography. Contrast-enhanced MR angiography (CE MRA) has developed even more as an alternative non-invasive method to digital subtraction angiography, mostly for pelvic or lower limb vessels. We report a case of primary Raynaud’s disease with high-grade stenosis and an occlusion of the digital arteries. This case illustrates the benefit and efficiency of CE MRA at high fields in depicting location and extension of peripheral arterial alterations.