The lupus anticoagulant in systemic lupus erythematosus and systemic sclerosis

The lupus anticoagulant is an acquired IgG or IgM antibody directed against specific phospholipids involved in the formation of prothrombin activators. It is identified by coagulation tests. The partial thromboplastin time and kaolin clotting time are prolonged and these abnormalities cannot be corrected by the addition of normal plasma, as in simple clotting factor deficiency. The thrombin time is normal.
Five out of 36 unselected patients with systemic lupus erythematosus (SLE) showed the presence of lupus anticoagulant (14%). The duration of SLE was from 2 to 38 years. Three of the five patients gave a history of thrombosis. The only male patient suffered from myocardial infarction and venous thromboses in his twenties and is an example of a group of young males with major thrombotic episodes. One patient had a Coombs-positive haemolytic anaemia. Thrombocytopenia is sometimes associated with the lupus anticoagulant but was not found in the present series. Anticardiolipin antibodies were not measured, but none of the patients had false-positive serology.
The lupus anticoagulant is a useful marker for those patients with SLE at risk for thrombosis.
The lupus anticoagulant was not found in 24 unselected patients with systemic sclerosis and is therefore not a factor in the pathogenesis of the vascular phenomena in this disease.     

Chronic lupus erythematosus presenting as acneiform lesions

BACKGROUND: Cutaneous manifestations of lupus erythematosus are numerous but usually permit easy diagnosis. However, there are atypical lesions that can mimic benign dermatologic disorders. We report on a patient with lesions of acne leading to the diagnosis of chronic lupus erythematosus, and who subsequently developed systemic lupus erythematosus. CASE REPORT: A 30-year-old woman presented with inflammatory lesions and comedos on the face. The eruption started after her last pregnancy and was refractory to local and general treatment. She also complained of arthralgia, Raynaud's phenomenon and diffuse alopecia. Cutaneous biopsy was characteristic of chronic lupus erythematosus. Immunofluorescence microscopy of lesional skin showed a lupus band deposit. Antinuclear antibodies were highly positive. The patient was successfully treated with chloroquine. Three years later, the patient presented with photodistributed eruption. Antinuclear antibodies were still positive and in addition anticardiolipin antibodies were found. Final diagnosis was systemic lupus erythematosus. DISCUSSION: Acneiform lesions are rarely reported in lupus erythematosus. Only three similar cases were reported in literature. Atypical and treatment-resistant eruptions should attract attention. Furthermore, the occurrence of systemic lupus in chronic lupus erythematosus is not an unfrequent phenomenon and the oestrogen-dependance of chronic lupus lesions may predict this association.     

Pemphigoid and acquired hemophilia

INTRODUCTION: The association of bullous pemphigoid and acquired haemophilia is reported. CASE-REPORT: A 74 year-old man developed a bullous pemphigoid after decreasing corticotherapy, ecchymosis and haematomas revealing a high level of acquired anti-VIII antibodies (110 Bethesda UB units; TCA 98 s). Immunosuppressive treatment (cyclosporine, prednisone, azathioprine and bolus of cyclophosphamide) did not stop the disease. Perfusion of recombinant factor VIIa, human immunoglobulins and prednisone-azathioprine association permitted clinical and biological remission. DISCUSSION: Acquired haemophilia is idiopathic half the time. It can appear in autoimmmune diseases. Mortality is high. Only 4 cases of association with bullous pemphigoid have been reported in the literature. At the haemorrhagic phase, porcine factor VIII or more recombinant activated factor VII with human immunoglobulins are necessary. Immunosuppressive treatment is used to decrease production of anti-factor VIII antibodies.     

系统性红斑狼疮患者继发获得性血管性血友病1例

患者女,25岁。诊断为系统性红斑狼疮6年,下腹痛、恶心、呕吐伴有黑便半月。入院时肛门指检示子宫后可触及8cm×7cm×6cm大小的囊性包块。B超引导下经腹盆腔穿刺,抽出暗红色不凝血约2mL。予泼尼松50mg/d、来氟米特20mg/d及注射用奥美拉唑钠等治疗,症状好转。但不久全身出现散在的指尖到蚕豆大小不等瘀点、瘀斑。查血常规示血小板289×109/L,血浆因子Ⅷ促凝活性为0.9%,von Willebrand因子抗原水平为2.3%,瑞斯托霉素诱导的血小板凝集试验结果为3.8%。诊断为系统性红斑狼疮继发获得性血管性血友病。加用人免疫球蛋白冲击治疗(400mg/kg×5d),补充新鲜血浆及血浆因子Ⅷ等治疗后,症状缓解。随访1年,患者系统性红斑狼疮病情稳定,泼尼松逐渐减量至20mg/d,未出现出血征象,复查血浆因子Ⅷ促凝活性为79.6%,von Willebrand因子抗原水平为92.1%,瑞斯托霉素诱导的血小板凝集试验结果为112.6%。     

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.     

Bullous systemic lupus erythematosus: revised criteria for diagnosis

Summary Blistering in systemic lupus erythematosus has been divided into three groups.¹ A specific subgroup of ‘bullous systemic lupus erythematosus’ has been defined by Gammon et al. on the basis of a number of criteria.² From our experience of seven patients with bullous systemic lupus erythematosus, and after reviewing the literature, we suggest that the current classification is too narrow. Our patients displayed clinical and immunohistolegical (based on direct and indirect immunofluorescence and Western immunoblotting) heterogeneity. Sera from two patients bound to epidermal epitopes in sodium chloride-split skin, but immunoblotting was negative. In neither of these patients could the target antigen be type VII collagen, the only antigen identified as pathogenic in this disease. Patients with epidermal binding should not be excluded from a diagnosis of bullous systemic lupus erythematosus. SLE is a disease in which there is a genetic predisposition to form antibodies to type VTI collagen, along with other autoantibodies, many of which may be implicated in blistering. We suggest that the criteria for the diagnosis of BSLE should be revised. We define this disease as an acquired subepidermal blistering disease in a patient with SLE, in which immune reactants are present at the basement membrane zone on either direct or indirect immunofluorescence.     

Bullous Lupus: An Unusual Initial Presentation of Systemic Lupus Erythematosus in an Adolescent Girl

Abstract: Bullous systemic lupus erythematosus is a subepidermal blistering disease that occurs only rarely in a subset of patients with systemic lupus erythematosus and even less commonly in pediatric patients. Autoimmunity in bullous systemic lupus erythematosus is characterized by the presence of circulating anti‐type VII collagen antibodies. We report here a case of a child whose initial systemic lupus erythematosus presentation was a diffuse bullous eruption.     

Cutaneous lupus erythematosus and cardiolipin antibodies. Incidence and clinical significance]

In recent years, the importance of antiphospholipid antibodies in systemic lupus erythematosus and various other dermatological and internal diseases has been recognized. Characteristic symptoms associated with these antibodies are venous and arterial thrombosis, recurrent fetal loss, thrombocytopenia, and haemolytic anaemia. Two antiphospholipid antibody subgroups that are clinically relevant can be discerned: anticardiolipin antibodies and lupus coagulant. In this study, 51 clinically well-characterized patients with predominantly cutaneous lupus erythematosus were screened for the presence of anticardiolipin antibodies. Anticardiolipin antibodies could be detected in only three patients. These data suggest that, in patients with cutaneous lupus erythematosus, anticardiolipin antibodies should be measured only in the presence of symptoms associated with antiphospholipid antibodies.     

Lupus erythematosus associated with genetically determined deficiency of the second component of the complement

BACKGROUND: The gene deletion responsible for the type I human complement C2 deficiency was reported in 1992. The purpose of our study is to evaluate clinical and immunological characteristics of 11 patients with lupus erythematosus and type I C2 deficiency. OBSERVATIONS: We observed 5 patients with a homozygous C2 deficiency and 6 with a heterozygous C2 deficiency. Eight patients had systemic lupus erythematosus, 2 had subacute cutaneous lupus erythematosus, and 1 had chronic lupus erythematosus. Photosensitivity was present in 73% of the patients, and 64% tested positive for anti-Ro (SSA) antibodies. Renal involvement that required immunosuppressive therapy was present in 54% of the patients. Ninety percent of the patients tested positive for antinuclear antibodies, and 54% tested positive for anti-double-stranded DNA antibodies. Phenotyping of the fourth component of the complement was performed in 82% of the patients and showed a C4A4B2 phenotype, which is suggestive for the type I C2 deficiency. CONCLUSIONS: Most patients with lupus erythematosus associated with C2 type I deficiency are photosensitive, and this is probably related to the presence of anti-Ro (SSA) autoantibodies. The prognosis for those patients is not better than that for patients with lupus erythematosus in general.     

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.     

Neonatal lupus erythematosus presenting as papules on the feet

We describe a case of neonatal lupus erythematosus in a 4‐week‐old male baby presenting with nodules/papules on the plantar surface of both feet. Skin histology of the right foot papule was consistent with lupus erythematosus. Annular lesions more typical of this condition then appeared later and maternal antibodies were positive for speckled antinuclear antibodies (1:5120), anti‐Ro/SSA and anti‐La/SSB(+), rheumatoid factor 1380.0 IU/mL. The patient had no evidence of cardiac, haematological or hepatobilary involvement. Although the mother was asymptomatic, the maternal grandmother had recently been diagnosed with Sjögren's syndrome.     

Systemic lupus erythematosus presenting with 'rheumatoid nodules'

A patient with systemic lupus erythermatosus who presented with subcutaneous nodules over the flexor aspect of the fingers in association with arthritis and Raynaud's phenomenon is described. Histopathological examination of the nodules showed appearances consistent with rheumatoid nodules. Further investigations revealed leucopenia and circulating anti-nuclear antibody but negative rheumatoid factor. Immunofluorescence studies of normal non-light exposed skin showed the presence of IgM deposits at the dermo-epidermal junction consistent with systemic lupus erythematosus. The nodules almost disappeared following treatment with hydroxychloroquine. Rheumatoid-like nodules have been reported in systemic lupus erythematosus, although rarely.¹ However, the distribution of the nodules and the patient's clinical course differ from the few cases previously reported in the literature. ^1,2     

Photosensitivity in lupus erythematosus

BACKGROUND: Lupus erythematosus is a systemic disease process that may manifest with a variety of internal and cutaneous findings. Photosensitivity is one the most common manifestations of lupus erythematosus. In patients with lupus erythematosus, there is a relationship between exposure to ultraviolet light, autoantibodies, genetics and other factors in the development of photosensitivity. METHODS: Literature was reviewed on the topics of lupus erythematosus and photosensitivity discussed together and separately. The suggested mechanisms for their relationship were reviewed and analyzed. RESULTS: Photosensitivity's relationship to and influence on the systemic manifestations of lupus remain to be defined. Mechanisms for photosensitivity might include: modulation of autoantibody location, cytotoxic effects, apoptosis induction with autoantigens in apoptotic blebs, upregulation of adhesion molecules and cytokines, induction of nitric oxide synthase expression and ultraviolet-generated antigenic DNA. Tumor necrosis factor alpha also seems to play a role in the development of photosensitivity. CONCLUSION: The basis for photosensitivity in lupus has yet to be fully defined. It is more commonly associated with subacute and tumid lupus erythematosus than with other variants. Anti-Ro antibodies appear to relate to photosensitivity. Tumor necrosis factor alpha polymorphisms appear to be important in some variants of lupus with photosensitivity. There is no sine qua non antibody or mutation of photosensitivity in lupus. In patients with lupus, more work needs to be done to define the mechanisms of photosensitivity.     

Coexistence of pemphigus herpetiformis and systemic lupus erythematosus

A female patient with coexistence of pemphigus herpetiformis and systemic lupus erythematosus is described. She presented to our Department with pruritic vesicles on her trunk and extremities, which were later accompanied with butterfly like erythema on her face and with central nervous system (CNS) manifestations. The diagnosis of pemphigus herpetiformis was based on the clinical picture and immunofluorescence finding, because the histopathologic finding is not always typical for the diagnosis. The diagnosis of systemic lupus erythematosus was based on positive ANA and anti-dsDNA, presence of butterfly-like erythema on her face, and CNS manifestations. The patient was treated by corticosteroids in combination with immunosuppressants, which should ensure good control of both diseases. The coexistence of pemphigus herpetiformis and systemic lupus erythematosus has not been reported in recent literature.     

Simultaneous onset of pemphigoid and factor VIII antibody hemophilia

A 47-year old patient who had been suffering from hypertension and chronic renal failure for many years developed progressive extensive haemorrhagic erosions of the mouth within 3 months and less severe erosions of the genital and nasal mucosa. Additionally, subcutaneous haematomas developed spontaneously. Laboratory investigations demonstrated circulating antibodies against factor VIII while direct and indirect immunofluorescent microscopy showed discrete tissue-bound and circulating IgG reactive with the epidermal basement membrane in a pemphigoid-like fashion. Immunoblot analysis of the patient's serum revealed an "atypical" IgG reactivity against a central portion of the extracellular domain of the BP180 antigen. These findings were unexpected, since the clinical aspect showed striking resemblance to (paraneoplastic) pemphigus. The patient developed life-threatening complications. Eventually, reduction of circulating autoantibodies by a combination of plasmapheresis and subsequent immunosuppressive therapy led to a stable remission of both autoimmune bullous skin disorder and acquired haemophilia.     

SLE患者外周血单核细胞TNFα及其受体P55和P75表达

目的 探讨单核细胞在ＳＬＥ发病中的作用。方法 应用免疫组化技术对活动期ＳＬＥ患者外周血单核细胞ＴＮＦα及其受体Ｐ５５和Ｐ７５表达进行检测。结果 活动期ＳＬＥ患者单核细胞ＴＮＦα及其受体Ｐ５５和Ｐ７５表达明显增加（ｔ分别为１１．４３、５．８３和３．９３,Ｐ分别小于０．００１、０．００１和０．００２）。结论 ＳＬＥ和ＴＮＦα及其受体Ｐ５５和Ｐ７５表达增高,单核细胞可能参与ＳＬＥ的发病过程。e     

Anti-Ribosomal P Protein Antibodies in a Japanese Patient with Systemic Sclerosis

A 56-year-old Japanese woman developed Raynaud's phenomenon and digital ulcerations at the age of 50. She showed rapid and diffuse skin sclerosis; visceral involvement was mild. She showed no symptoms or laboratory findings suggestive of other collagen diseases, including systemic lupus erythematosus and Sjögren's syndrome. Based on the clinical and histological findings, she was diagnosed as having diffuse cutaneous systemic sclerosis (SSc). The patient's serum produced nucleolar and cytoplasmic staining by indirect immunofluorescence analyses on HEp-2 cell substrate and reacted with P0, P1 and P2 proteins in immunoblotting using purified ribosomal antigens. She was negative for anti-topoisomerase I, centromere, and U1RNP antibodies. Anti-ribosomal P protein antibodies are considered highly specific for systemic lupus erythematosus; this is the first case report of an SSc patient with anti-ribosomal P protein antibodies. The clinical features of SSc patients with these antibodies need to be clarified by an accumulation of cases.     

Palisading granuloma presenting in a patient with systemic lupus erythematosus

A patient with systemic lupus erythematosus who developed a distinctive nodular eruption demonstrating typical features of palisading granuloma is presented herein. A 60-year-old woman was admitted complaining of an elastic-hard, indurated nodule on the right dorsal aspect of the metacarpophalangeal joint of her third finger with a history of several years. She was successfully treated for her lupus nephritis with oral predonisolone. She had experienced erythema on her cheeks after sun exposure and polyarthralgia for a decade. Laboratory examination revealed positive results for antinuclear antibody and rheumatoid factor. Peripheral blood cell counts showed leukocytopenia and lymphocytopenia. Results of hand X-ray were unremarkable. Histological examination of the skin biopsy specimen from the nodule revealed a structure composed of a central area of fibrinoid necrosis, surrounded by a middle zone of palisading cells and an outer zone of chronic lymphocyte infiltrate. These findings led us to the histological diagnosis of palisading granuloma. She was diagnosed as having systemic lupus erythematosus complicated with a rheumatoid nodule. She is currently under treatment with cyclophosphamide (50 mg/day) without exaggeration of her systemic lupus erythematosus and nodule.     

Morbus Basedow

Graves disease is a frequent cause (30-40%) of hyperthyroidism. In addition to the classic clinical triad (goiter, exophthalmos and tachycardia), symptoms relating to other organ systems may be found at presentation. Cutaneous manifestations play an important role and may initially be the only clue to the endocrine disorder. A 40-year-old woman with Graves disease presented with features of systemic lupus erythematosus. She had a malar rash, as well as marked hematological changes (thrombocytopenia and leukocytopenia) and antinuclear antibodies (1:640). She also had hyperthyroidism and Graves disease-specific thyroid autoantibodies (TSIg). Her symptoms improved after initiation of antithyroid therapy. Because of overlapping clinical and laboratory criteria, Graves disease can mimic systemic lupus erythematosus. The differentiation requires careful laboratory evaluation. Moreover, both autoimmune diseases may occur in the same patient.     

Sclerodermic linear lupus panniculitis: report of two cases

Lupus erythematosus panniculitis is a rare disease characterized by deep subcutaneous nodules, most commonly localized on the upper limbs and face. Unique clinical presentations, such as linear configuration or 'overlap' forms between lupus erythematosus panniculitis and localized scleroderma have been reported. We present here the clinical characteristics, course and laboratory findings of 2 patients having linear lupus erythematosus panniculitis with localized scleroderma-like changes. The 2 patients (of the 14 patients with lupus erythematosus panniculitis seen by us since 1990) were females with a young age at the onset of disease (median, 25 years). In 1 case, evolution into systemic lupus erythematosus with severe renal involvement occurred whereas the other patient, who had a spontaneous abortion and exhibited anticardiolipin antibodies, should be followed and screened for the emergence of antiphospholipid syndrome. Thus, the clinical behavior of this variant seems to be more aggressive, as compared with the usual course of lupus erythematosus panniculitis, which is considered to be a benign disease, although some reports have suggested that its prognosis is not always favorable. The linear distribution could be the clinical hallmark of such a unique, 'sclerodermic' subset of lupus erythematosus panniculitis.