Livedo reticularis associated with increased titers of anticardiolipin antibodies in systemic lupus erythematosus

Seventy-eight consecutive patients with systemic lupus erythematosus were assessed for the presence of livedo reticularis. The possible association of livedo reticularis with other clinical and laboratory features including anticardiolipin antibodies was explored. Thirty-eight patients had livedo reticularis. Four cases were severe, 11 moderate, and 23 mild. There was a statistically significant association between the combined moderate and severe livedo reticularis group and elevated levels of anticardiolipin antibodies. The recognized association of anticardiolipin antibodies with thrombotic events suggests a possible pathogenetic role. The presence or history of central nervous system disease, renal disease, vasculitis, or lupus inhibitor was significantly associated with the moderate and severe livedo reticularis group. Livedo reticularis may be a cutaneous marker for the later development of important systemic events in systemic lupus erythematosus.     

Livido racemosa in detection of anti-phospholipid antibodies

Livedo reticularis and antiphospholipid antibodies have previously been found to be associated with a subgroup of patients with systemic lupus erythematosus. We present a case of livedo reticularis accompanied by antiphospholipid antibodies, in which no other signs of any systemic or cutaneous disease could be detected.     

The anticardiolipin syndrome. A new way to slice an old pie, or a new pie to slice?

Students of systemic lupus erythematosus have long been confused by the paradoxical association of atypical clinical features such as recurrent thrombosis and spontaneous abortion with the lupus anticoagulant and biologic false-positive VDRL reaction. The recent development of sensitive, solid-phase immunoassays for quantitating the autoantibody response to phospholipids holds the promise of illuminating the basis for this seeming enigma. It is now apparent that antiphospholipids antibodies such as anticardiolipin might well play a role in mediating the elements of this paradox. In addition, other cutaneous vascular conditions as diverse as livedo reticularis and Degos' disease might also be related to this type of autoimmune response.     

Livedo reticularis, cerebrovascular disorders and mitral disease: a new cause of Sneddon's syndrome?

Sneddon's syndrome consists of livedo reticularis and cerebral vascular accidents with no evidence of systemic disease responsible for the livedo. The syndrome has been assimilated to a subgroup of systemic lupus erythematosus (SLE) with presence of antibodies directed against phospholipids. Recently, a significant increase in the frequency of cardiac valve diseases has been demonstrated in some SLE patients with livedo reticularis, cerebral vascular accidents and antiphospholipid antibodies. We report the case of a 26-year old woman who had been presenting for 6 years with idiopathic livedo reticularis. Her history was remarkable for the occurrence of 2 cerebral ischaemic accidents at the ages of 23 and 26 years, generalized convulsive seizures at 22 years, and hypertension of pregnancy with 2 miscarriages. Biopsy of the livedo showed normal histological patterns, but electron microscopy detected an obliterating endothelial proliferation and endothelial cells with numerous Weibel-Palade bodies. Laboratory signs of SLE, as well as antiphospholipid antibodies were absent. At the age of 26 years, cardiac abnormalities were heard at auscultation for the first time, and echocardiography showed that they were due to a fairly loose mitral stenosis. According to Burton's criteria our patient had all the typical features of Sneddon's syndrome. The finding of mitral stenosis--an emboligenic cardiopathy that is potentially responsible for cerebral vascular accidents--raises the problem of its relationship with Sneddon's syndrome. The association does not seem to be fortuitous, since our case is very similar to the cases of SLE or antiphospholipid antibody syndrome associated with cardiac valve lesions. However, this case is particular in that 6 years after the onset of the disease there was still no sign of SLE and of antiphospholipid antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Livedo racemosa, secondary to drug-induced systemic lupus erythematosus

We present a 40-year-old man with erythematous-to-violaceous, broken, reticulated patches on the upper chest, back, and extremities, which is consistent with livedo racemosa. The cutaneous findings appeared after an increase in dilantin dose and subsequently improved after a reduction in dilantin dose. Furthermore, antinuclear antibodies and antihistone antibodies were detected. We therefore believe that the livedo racemosa is a cutaneous manifestation of a drug-induced systemic lupus erythematosus. We review the distinctive features of livedo racemosa as well as its associations with several disorders. Although there are no effective treatments for livedo racemosa, patients often are placed on low-dose aspirin and counseled to avoid smoking in an effort to protect against their increased risk of stroke and arterial thrombosis.     

False positive VDRL (BFP-STS) and systemic lupus erythematosus; new data in clinico-laboratory associations

AIM: To investigate the relationships between clinical features and serological parameters in systemic lupus erythematosus (SLE) patients with false positive venereal disease research laboratory (VDRL) test (BFP-STS) and those without. METHODS: The records of 74 patients with SLE were reviewed. These were divided on the basis of the presence of a biologically false positive serological test (BFP-STS) (n = 18) or its absence (n = 56). The clinical features and serological parameters were subsequently evaluated in each group. RESULTS: A biologically false positive serological test was found in 18 patients (24.5%). Clinically, they had a significantly higher frequency of malar rash (P < 0.02), hemolytic anaemia (P < 0.02) and SLE-related antiphospholipid (APL) syndrome (P < 0.02). Neuropsychiatric lupus was more frequent in the group without BFP-STS. Moreover, subacute cutaneous LE (SCLE), Raynaud's phenomenon, livedo reticularis (LR) and cardiopulmonary complications were present only in the latter group. There was no significant association between BFP-STS and other autoantibodies including Extractable nuclear antigen (ENAs), however, there was a significant association with C3 hypocomplementemia (P < 0.05). Half of the patients with BFP-STS were positive for anticardiolipin antibodies (aCL Abs) vs. 28% in the negative group (P = NS). CONCLUSIONS: The study suggests that the clinical and serological relevance of BFP-STS in lupus patients may vary from those described in relation to other antiphospholipid determinants. Our patients appeared to have sparing of certain major organ systems, yet there was a greater tendency to developing Antiphospholipid (APL) syndrome and hemolytic anaemia.     

Cutaneous Thrombosis, Cerebrovascular Thrombosis, and Lupus Anticoagulant—the Sneddon Syndrome

Ten patients with circulating lupus anticoagulant who presented with cutaneous vascular disease and Cerebrovascular disease are presented. Cutaneous manifestations were gangrene, thrombophlebitis, ulcers, and livedo reticularis. All 10 patients had cerebral infarction. The relationship between the cerebral and cutaneous vascular changes and the presence of lupus anticoagulant is supported by a common noninflammatory vascular thrombosis histologically in these patients and by the presence of similar pathologic and clinical findings in patients with the lupus anticoagulant syndrome.     

Cutaneous thrombosis, cerebrovascular thrombosis, and lupus anticoagulant--the Sneddon syndrome. Report of 10 cases

Ten patients with circulating lupus anticoagulant who presented with cutaneous vascular disease and cerebrovascular disease are presented. Cutaneous manifestations were gangrene, thrombophlebitis, ulcers, and livedo reticularis. All 10 patients had cerebral infarction. The relationship between the cerebral and cutaneous vascular changes and the presence of lupus anticoagulant is supported by a common noninflammatory vascular thrombosis histologically in these patients and by the presence of similar pathologic and clinical findings in patients with the lupus anticoagulant syndrome.     

Thrombotic cutaneous nodules and hepatic vein thrombosis in the anticardiolipin syndrome

A patient with the anticardiolipin syndrome presented with hepatic vein thrombosis (Budd-Chiari syndrome) and non-ulcerating, thrombotic, cutaneous nodules. This cutaneous manifestation of the anticardiolipin syndrome has not been described before, though its histological appearances resemble those of previously reported cutaneous complications, such as chronic ulceration, livedo reticularis and distal cutaneous ischaemia. Recognition of the skin lesion could allow the prevention of major systemic complications.     

SYSTEMIC LUPUS ERYTHEMATOSUS: A REPORT OF FORTY-FIVE CASES WITH UNUSUAL CLINICAL AND IMMUNOLOGICAL FEATURES

SUMMARY.— Forty five cases of systemic lupus erythematosus in Hong Kong are reviewed.
Of common occurrence were hyperkeratotic follicular papules, which in some cases resembled pityriasis rubra pilaris and keratosis pilaris, hyperkeratosis of the palms and soles, and psoriasiform lesions. Less frequent cutaneous manifestations included chilblains, livedo reticularis, and scleroderma-like changes. Biological false positive serological tests for syphilis were not encountered.
The possible significance of these deviations from the familiar clinical and immunological picture is discussed.     

HEPARIN-ASSOCIATED THROMBOCYTOPENIA AND THROMBOSIS (HATT) PRESENTING WITH LIVEDO RETICULARIS

Background. Heparin-associated thrombocytopenia and thrombosis (HATT) is an infrequently encountered syndrome characterized by ischemic necrosis of soft tissue and vital organs following anticoagulation with heparin. The syndrome is thought to be due to heparin-dependent platelet aggregation and thrombosis, which is mediated by pathologic immunoglobulins. Case Report. A 60-year-old man developed truncal livedo reticularis and ischemic necrosis of the left foot associated with thrombocytopenia, disseminated intravascular coagulopathy (Die), and microangiopathic hemolytic anemia during intravenous heparin therapy. Skin biopsy from an area of livedo reticularis revealed fibrin thrombi in dermal blood vessels, which is characteristic of HATT. The diagnosis of HATT prompted discontinuation of heparin and a resulting rapid resolution of the livedo reticularis and hematologic abnormalities. No other potential causes of Die were identified, and, other than stopping heparin, no specific therapy was employed. Conclusions. Periodic monitoring of platelets should be performed on all patients receiving treatment with heparin, as early detection of heparin-induced thrombocytopenia followed by discontinuation of the drug may prevent life threatening thrombotic complications. HATT should be included in the differential diagnosis of patients with livedo reticularis that occurs during heparin therapy.     

Acquired haemophilia in a patient with systemic lupus erythematosus

INTRODUCTION: In patients with lupus, the most common acquired circulating anticoagulant is antiprothrombinase which is responsible for thrombosis. The presence of antibodies directed against factor VIII is rarely found in systemic lupus erythematosus. A case of acquired haemophilia in a patient with lupus is reported. CASE REPORT: A 30 year-old woman with systemic lupus erythematosus developed a right coxalgia and ecchymotic skin lesions which were prominent on the right arm and forearm. Laboratory values were as follows: positive antinuclear antibodies > 1: 2 560, anti-DNA antibodies (300 IU/ml), prolonged activated partial thromboplastin time, reduced factor VIII activity (1 p. 100) and the presence of antibodies against factor VIII. Magnetic nuclear resonance of the right hip confirmed the presence of an intramuscular hematoma. The patient was initially treated with intravenous pulse and oral corticosteroids, intravenous immunoglobulins and intravenous cyclophosphamide. Clinical and biological improvement was promptly obtained. DISCUSSION: In our patient with systemic lupus erythematosus, bleeding revealed acquired haemophilia with antibodies against factor VIII. It should be pointed out that the association between lupus and haemophilia is uncommon and that at present no standardized treatment can be recommended.     

Epidermolysis bullosa acquisita preceding the development of systemic lupus erythematosus

In most cases of epidermolysis bullosa acquisita that occur in patients with systemic lupus erythematosus, the diagnosis of systemic lupus erythematosus is made before the development of blistering. We observed three patients with well-documented epidermolysis bullosa acquisita that developed several years before the onset of systemic lupus erythematosus. One patient was producing anti-U1RNP autoantibodies at the time epidermolysis bullosa acquisita was diagnosed, and all five produced this antibody during the systemic lupus erythematosus phase of their illness. In addition, in all five cases of epidermolysis bullosa acquisita with systemic lupus erythematosus antibodies to double-stranded DNA ultimately developed, and severe systemic lupus erythematosus and lupus nephritis developed in four patients. Sera from 15 other patients with epidermolysis bullosa acquisita without overt systemic lupus erythematosus were analyzed for systemic lupus erythematosus-related autoantibodies. Four patients were found to have at least one such autoantibody. These findings further document an association between epidermolysis bullosa acquisita and systemic lupus erythematosus and suggest that patients with systemic lupus erythematosus who present with epidermolysis bullosa acquisita may represent a subset of lupus erythematosus that puts the patient at increased risk for the development of more severe systemic illness. Patients presenting with epidermolysis bullosa acquisita, especially those who are black or Hispanic, should be monitored for the development of potentially life-threatening systemic lupus erythematosus.     

The lupus anticoagulant in systemic lupus erythematosus

The lupus anticoagulant was found in six of 41 unselected patients with systemic lupus erythematosus (14%). Three of these six patients had episodes of thrombosis. Thrombosis occurred in only one patient in the remainder of the series without the lupus anticoagulant. The lupus anticoagulant should be considered as one of the criteria for the diagnosis of systemic lupus erythematosus, and it may be a useful marker for those patients at risk from thromboembolism. It should be looked for in young adults with thrombotic episodes.     

Cutaneous manifestations associated with antiphospholipid antibodies

BACKGROUND: Primary Antiphospholipid Antibody Syndrome (PAAS) is characterized by detection of antiphospholipid antibodies associated with venous or arterial thrombosis and/or miscarriages by patients with no other associated disease such as systemic lupus erythematosus (SLE). Primary Antiphospholipid Antibody Syndrome has many clinical manifestations of which dermatological ones are probably the most common. The purpose of this study was to determine the frequency of each cutaneous lesion, describing clinical features essential for diagnosis, in patients with Antiphospholipid Antibody Syndrome (AAS) attending Walter Cantídio University Hospital. METHODS: Sixty patients with clinical findings suggestive of AAS were screened, and submitted for clinical and laboratory evaluations including lupus anticoagulant (KCT), anticardiolipin antibodies (IgG and IgM: ELISA), routine laboratory tests and screening tests for possible associated conditions. RESULTS: Twenty-five cases of primary and 14 cases of secondary AAS were diagnosed by clinical and laboratory evidences. Persistent elevated antiphospholipid antibodies without history of thromboembolic events or miscarriages were demonstrated in 21 patients. Forty percent of the patients with AAS had a cutaneous feature as the major complaint. These were dermographism (15), acrocyanosis (13), urticaria (9), diffuse alopecia (9), livedo reticularis (seven), Raynaud's phenomenon (three), purpura (two), ulcers and necrosis (four), nodules (four), pterygium ungueum (one) and subungual hemorrhage (one). CONCLUSIONS: Dermatological complaints are very frequent in patients with AAS and may be the first clue to the syndrome. Therefore a careful history and detailed physical examination are essential to diagnose AAS. All dermatologists should investigate the possibility of AAS when facing cutaneous findings related to venous or arterial thrombosis or microthrombosis.     

Antiphospholipid antibody syndrome (Hughes' syndrome)

ABSTRACT: A wide variety of dermatologic manifestations have been described in the antiphospholipid syndrome (APS). The most common is livedo reticularis, which is associated not only with cerebrovascular events but also with systemic hypertension and heart valve abnormalities. Its mechanism remains unclear and no treatment is effective. Lower limb ulcers may be related to deep vein or skin vessel thrombosis with clinical features of livedoid vasculitis. The latter frequently persist despite antiplatelet therapy, thus requiring anticoagulation. The pseudovasculitis lesions are frequently misdiagnosed if skin biopsies are not performed, especially in systemic lupus erythematosus-related APS. Antiplatelet therapy is prescribed in the absence of large vessel thrombosis. Widespread cutaneous necrosis and digital gangrenes may be life threatening. They require full anticoagulation. When these lesions appear concomitantly to multiple vascular occlusions in the setting of "catastrophic" APS, steroids and therapy which can achieve a prompt reduction of antiphospholipid antibodies titers should probably be added to anticoagulation.     

Initial cutaneous manifestations associated with histopathological leukocytoclastic vasculitis in two patients with antiphospholipid antibody syndrome

Antiphospholipid antibody syndrome (APS) is a multisystem disorder associated with a variety of circulating autoantibodies that target different phospholipid protein complexes. APS is sometimes lethal as a result of severe sequelae, which may be primary or secondary to the underlying disease. We report two women who presented histopathologically with leukocytoclastic vasculitis as the first cutaneous manifestation and were subsequently diagnosed with APS associated with systemic lupus erythematosus (SLE). Patient 1 presented with widespread cutaneous necrosis (WCN) with rapidly spreading pain down the lower extremities. Skin biopsy specimens from her leg purpura and WCN revealed perivascular infiltrates with neutrophils consistent with leukocytoclastic vasculitis and thromboses of small-sized dermal vessels. Patient 2 exhibited livedo reticularis, painful cutaneous nodules with necrosis, ulcer, and erythematous macules on her lower extremities, shoulder, and face. Skin biopsies of her right knee showed intravascular thrombosis of small dermal vessels and infiltration of perivascular tissues with necrotizing granulomatous vasculitis in the dermis. We found that these various cutaneous manifestations with leukocytoclastic vasculitis were present at an early stage of APS. Although progression to leukocytoclastic vasculitis in patients with APS is uncommon, our data suggest that the association between microvascular occlusions and cutaneous vessel vasculitis has a predictive value for the pathogenesis. It is important for dermatologists to recognize these cutaneous signs to permit early and accurate diagnosis and treatment.     

Clinical course and prognosis of cutaneous lupus erythematosus

Classical variants of specific cutaneous LE lesions are chronic discoid LE (CDLE) and subacute cutaneous LE (SCLE). CDLE and SCLE may appear at any age; however, the most common age of onset is between 20 and 40 years, with a female predominance of 3:1 in CDLE and 3-6:1 in SCLE. Nonspecific LE skin lesions such as generalized or acrolocalized vasculitis (4-30%), livedo reticularis (22-35%), and alopecia (38-78%) are frequently seen in patients with cutaneous LE. Other typical cutaneous LE subsets such as LE profundus/panniculitis, LE tumidus, urticaria vasculitis, hypertrophic LE, and bullous LE are rather rare variants. Butterfly rash and/or macular exanthema are characteristic skin lesions of systemic lupus erythematosus (SLE) rarely found in patients with cutaneous LE.     

Thalidomide and thrombosis

BACKGROUND: Teratogenicity and neuropathy are the well known serious side effects induced by thalidomide. We describe 5 cases of thrombotic events occurring within a brief delay after the onset of thalidomide in a manner that suggests that thalidomide could have acted as a precipiting or as a starting factor in these events. OBSERVATIONS: Five patients including 4 patients with lupus erythematosus (1 discoid lupus, 1 subacute lupus and 2 systemic lupus erythematosus) and one patient with a severe atopic dermatitis, all without previous history of vascular events, developed an arterial thrombosis (2 cases) or a venous thrombosis (3 cases), severe in 4 cases, few days or weeks after the onset of thalidomide treatment (50 to 100 mg daily). DISCUSSION: All the patients had risk factors of thrombosis: the presence of antiphospholipids and/or anticardiolipin antibodies in lupus erythematosus patients and a trauma in the atopic case. However the absence of a previous story of thrombosis, its rapid occurrence after the onset of thalidomide and its severity are intriguing. In addition, recent studies demonstrate that thalidomide has various effects that would act, among other things, on angiogenesis. Thus, we think that a doubt exists on a negative effect of thalidomide in thrombosis risk factors patients and that this hypothesis has to be confirmed.     

Erythema elevatum diutinum--a rare variant of skin changes in systemic lupus erythematosus

It is reported on 5 patients with erythema elevatum diutinum, in 2 of these cases exists a systemic lupus erythematosus and another patient suffers from cutaneous lupus erythematosus. This information can be considered as a possibility that cutaneous alterations similar to erythema elevatum diutinum could be the first symptoms of systemic lupus erythematosus when the usual treatment is inefficient.