Juvenile diffuse systemic sclerosis/systemic lupus erythematosus overlap syndrome—a case report

We report a rare case of diffuse systemic sclerosis (SSc) evolving into diffuse SSc/systemic lupus erythematosus (SLE) overlap syndrome. A 15-year-old boy was diagnosed as diffuse SSc with initial presentations of Raynaud’s phenomenon and skin tightening. He underwent Chinese herbal treatment and clinical symptoms deteriorated in the following 3?years. On admission to our ward, serositis with pleural effusion, severe pulmonary fibrosis with moderate pulmonary hypertension, swallowing difficulty, and polyarthritis were observed. Autoantibody profiles revealed concurrence of anti-double-stranded DNA, anti-Smith, anti-topoisomerase I, and anti-ribonucleoprotein antibodies. The patient fulfills the criteria for both diffuse SSc and SLE. After drainage for pleural effusion accompanied by oral prednisolone and sildenafil, there were improvement of respiratory distress, swallowing difficulty, and pulmonary hypertension. In conclusion, connective tissue diseases may overlap with each other during the disease course. Serial follow-up for clinical symptoms as well as serological changes is recommended.     

The overlap of Sjögren's syndrome with other systemic autoimmune diseases

OBJECTIVE: To analyze the main diagnostic problems caused by the overlap between Sj?gren's syndrome (SS) and other systemic autoimmune diseases (SAD). METHODS: We performed a MEDLINE search for articles published between January 1966 and December 2005 that specifically analyzed the overlap between SS and other SAD. We identified a list of diagnostic problems in patients with primary SS who had features considered typical of other SAD. RESULTS: Clinically, the main diagnostic problems occur in SS patients presenting with arthritis, Raynaud phenomenon, cutaneous features (subacute cutaneous lupus erythematosus, purpura, livedo reticularis, erythema nodosum), interstitial pulmonary disease, and cytopenias (leukopenia, thrombocytopenia). Immunologically, antiphospholipid antibodies (aPL) and antineutrophil cytoplasmic antibodies (ANCA) are the most frequent atypical autoantibodies found in primary SS, with a prevalence ranging between 10 and 20%. However, coexisting antiphospholipid syndrome or systemic vasculitis is only detected in around 10% of SS patients with aPL or ANCA. Anti-DNA and anticentromere antibodies have a prevalence of 5 to 10%, but are more closely related to clinical and/or laboratory data suggestive of associated systemic lupus erythematosus and limited systemic sclerosis, respectively, leading to the fulfillment of classification criteria for these diseases in more than 25% of cases. CONCLUSION: The wide variety of clinical and immunological manifestations of patients with primary SS often overlap with other SAD, making the differentiation between primary SS, SS associated with SAD, and SS-like presentations of some other SAD difficult. This overlap suggests that the current classification criteria are useful in differentiating between autoimmune and non-autoimmune processes but fail to clearly differentiate among SAD.     

Right Atrial Thrombus Mimicking Myxoma with Pulmonary Embolism in a Patient with Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome

Antiphospholipid syndrome is a well-defined entity that is characterized by spontaneous abortion, thrombocytopenia, and recurrent arterial and venous thromboses. A partially calcified right atrial thrombus mimicking myxoma with recurrent pulmonary embolism has not been previously reported in a patient who also had systemic lupus erythematosus and secondary antiphospholipid syndrome.Herein, we describe the case of a 37-year-old woman with systemic lupus erythematosus and secondary antiphospholipid syndrome who was admitted to the hospital with progressive exertional dyspnea. Ventilation-perfusion scanning showed multiple parenchymal defects in the lungs that portended pulmonary embolism. In addition, the scanning revealed normal regional ventilation. Transthoracic and transesophageal echocardiography showed a right atrial mass that was highly suggestive of myxoma, and the patient subsequently underwent surgery. A histologic examination showed an organized, partially calcified thrombus.Intracardiac thrombus has been rarely reported as a complication of antiphospholipid syndrome. In our patient, the preoperative investigations could not differentiate the partially calcified right atrial thrombus from a myxoma, and the diagnosis was made postoperatively.Key words: Antibodies, anticardiolipin/blood; antiphospholipid syndrome/complications; autoimmune diseases/complications; coronary thrombosis/complications/diagnosis/epidemiology/radiography/surgery; heart atria; heart neoplasms/diagnosis; lupus erythematosus, systemic/complications; myxoma/diagnosis; recurrence; thrombosis/complications/diagnosis/etiology/pathology/prevention & control/surgeryAntiphospholipid syndrome is characterized by spontaneous abortion, thrombocytopenia, and recurrent arterial and venous thromboses in association with medium-to-high titers of antiphospholipid antibodies or positive lupus anticoagulant test results. The disorder is referred to as primary antiphospholipid syndrome when it occurs alone¹; however, it can also be found in association with systemic lupus erythematosus (SLE). Less well known is the association between antiphospholipid antibodies and primary intracardiac thrombosis.Right atrial thrombus mimicking myxoma with recurrent pulmonary embolism (PE) has not, to the best of our knowledge, been previously reported in a patient who also had SLE and secondary antiphospholipid syndrome. Here, we report the case of a 37-year-old woman who presented with these conditions.     

DETECTION OF ANTIRIBOSOMAL P PROTEIN ANTIBODIES IN PATIENTS WITH SYSTEMIC SCLEROSIS

This study investigated the prevalence and clinical significanceof anti-ribosomal P protein (anti-P) antibodies in patientswith systemic sclerosis (SSc). Serum samples from 150 patientswith SSc were examined by indirect immunofluorescence, ELISAand immunoblotting. Anti-P antibodies were detected in four(3%) patients with SSc. Three of the four patients showed SSc/SLE(systemic lupus erythematosus) overlap syndrome, but psychiatricdisorders were not observed in these patients. By longitudinalimmunoblotting analysis one patient, who was initially diagnosedwith SSc, later developed anti-P antibodies along with clinicalmanifestations of SLE. Our data suggest that anti-P antibodiesare uncommon in SSc and that the presence of anti-P antibodiesin patients with SSc indicates an overlap with SLE. KEY WORDS: Anti-ribosomal P protein antibodies, Systemic sclerosis, Systemic lupus erythematosus     

Vocal cords palsy in systemic lupus erythematosus patient: diagnostic and therapeutic difficulties

Vocal cords palsy is a rare complication in the course of systemic lupus erythematosus (SLE). A 38-year-old female patient with a history of SLE presented with chronic voice hoarseness resistant to standard treatment. High levels of antinuclear antibodies including dsDNA, Ro52, SSA, SSB were confirmed, while antiphospholipid antibodies were absent. While other causes of voice hoarseness were excluded, bilateral vocal cords palsy was diagnosed. Moreover, the patient revealed features of obvious Hashimoto thyroiditis with high levels of antithyroid antibodies and also developed a convergent squint as a result of fatigability of oculomotor muscles. Electrophysiology test of peripheral nerves detected myasthenic type nerve-muscle conduction impairment which was suspected as the cause of reported symptoms. Possible reasons for emerging signs and symptoms of neuropsychiatric systemic lupus erythematosus were discussed as well as the presence of vasculitis, neuropathy, significance of thyroiditis and coexistence of myasthenia. All that reasons of similar autoimmune background were also raised in this case report.     

Marked saggital sinus dilatation and thrombi without thrombosis in a patient with systemic lupus erythematosus

Superior saggital sinus thrombosis (SSST), which has a strong causal link with antiphospholipid syndrome, rarely occurs in patients with systemic lupus erythematosus (SLE). We describe a 34-year-old woman with SLE whose clinical problem was mild headache. Her serology indicated negative antiphospholipid, anticardiolipin antibodies and lupus anticoagulants. However, marked dilatation of the entire saggital sinus with scattered thrombi was observed in enhanced-, surface- and three-dimensional reconstructed CTs (3D-CTs) without abnormal intra-axial signal in brain MRI. The enhanced-, surface- and 3D-CTs are useful to detect silent dural sinus dilatation with scattered thrombi in a patient with SLE without any symptoms of SSST.     

Bilateral avascular necrosis of both hips and both shoulders in a case with systemic lupus erythematosus: What should we blame,steroid or secondary antiphospholipid syndrome?

A 38‐year‐old female patient was diagnosed as a case of systemic lupus erythematosus (SLE) in 1994. Her initial presentation was nephritis which remitted on combination of steroid, azathioprine and pulse cyclophosphamide therapy. One year later the patient developed bilateral avascular necrosis (AVN) both hips and underwent bilateral hip replacement. In 2003 the patient developed bilateral AVN of both shoulders. In view of this uncommon presentation the patient screened for hidden secondary antiphospholipid syndrome and surprisingly investigations revealed negative anticardiolipin antibodies, weakly positive lupus anticoagulant test and positive reactivity against β2 glycoprotein 1. Although steroid is well know for its major role in AVN in patients with SLE, the presence of hidden secondary antiphospholipid syndrome augments the deleterious effects of steroid on bone and leads to AVN in uncommon sites. It is suggested that in SLE patients with positive lupus anticoagulant and negative antiphospholipid antibodies, testing for reactivity against β2 glycoprotein 1 is mandatory.     

Tetraplegia as a presenting feature of systemic lupus erythematosus complicated by pulmonary hypertension.

A 28-year-old woman presenting with subacute onset of a tetraplegia is described who was shown to have active systemic lupus erythematosus in association with high circulating anticardiolipin binding and lupus anticoagulant activity. The patient later developed severe symptomatic systemic and pulmonary hypertension and required emergency resuscitation. This case provides further support for an association between antiphospholipid antibodies and the clinical features of central nervous system (CNS) involvement and pulmonary hypertension in SLE.     

Antiphosphatidylethanolamine antibody as the sole antiphospholipid antibody in systemic lupus erythematosus with thrombosis.

A previously healthy 34-year-old woman, was diagnosed as having systemic lupus erythematosus (SLE), with membranous glomerulopathy which improved rapidly. Neither lupus anticoagulant nor anticardiolipin antibodies were detected in her plasma. After three months of total remission, she developed a severe pulmonary thromboembolism for which no specific biological cause was found. Her plasma was analysed for different antiphospholipid antibodies: lupus anticoagulant and anticardiolipin antibodies were again negative. Using an ELISA prepared with either five different anionic phospholipids or zwitterionic phosphatidylethanolamine, solely an anti-phosphatidylethanolamine IgG was discovered in her plasma. In lupus patients, the presence of antiphospholipid antibodies is now well recognized as a high risk factor for repeated thrombosis and/or recurrent abortions. This case suggests that the presence of antiphosphatidylethanolamine antibody should be investigated in cases of unexplained thrombosis in SLE, where the usual clinical and biological investigations have failed to shed light.     

Double heart valve replacement disclosing antiphospholipid syndrome]

In patients with systemic lupus erythematosus (SLE) heart valve lesions are usually discovered at echocardiography; their haemodynamic repercussions are uncommon, and valve replacement is exceptional. We report the case of a woman who had undergone aortic and mitral valve replacement before antiphospholipid antibodies were found associated with 4 ARA criteria of SLE. Histopathological examination confirmed the diagnosis of Libman-Sachs specific endocarditis. The presence of antiphospholipid antibodies leads to a discussion of their role in the physiopathology of the heart valve lesions and vascular accidents that occurred in this patient. The overlap observed between the diagnostic criteria of SLE and those of primary antiphospholipid syndrome is discussed. Heart valve lesions may be one of the modes of access to the antiphospholipid syndrome.     

Primary antiphospholipid syndrome associated with postoperative primary adrenal failure

Abstract. A 51-year-old Caucasian male without previous history of thromboembolic disease developed Coomb's positive haemolytic anaemia, thrombocytopenia, transient paranoid psychosis and bilateral adrenal haemorrhage with primary adrenal failure after surgery for inguinal hernia. The activated partial thromboplastin time was spontaneously prolonged, and lupus anticoagulant and anticardiolipin antibodies were detected. In the absence of criteria for classification of systemic lupus erythematosus (SLE), the entity was classified as a primary antiphospholipid syndrome. Despite the persistence of the serological abnormalities, the patient remains well after substitution with cortisone. Primary adrenal failure due to adrenal haemorrhage can be associated with the primary antiphospholipid syndrome.     

Systemic sclerosis sine scleroderma associated with antiphospholipid syndrome

The antiphospholipid syndrome (APS) can be primary, when it occurs alone, or secondary, when it is associated with another autoimmune disease, mainly systemic lupus erythematosus and rarely other autoimmune diseases. Cases described in literature (Medline 1966 to December 2009) associate the presence of antiphospholipid antibodies with the presence of APS and systemic sclerosis (SS). Currently, however, no cases of the SS variant sine scleroderma with APS have been described. In this study, the authors describe the case of a patient with APS characterised by thrombosis of the retinal veins, in May 2006, the presence of lupus anticoagulant and an anticardiolipin IgG antibody. In May 2007, this patient developed Raynaud’s phenomenon, a lack of oesophageal motility and nailfold capillaroscopy with a scleroderma pattern. The patient was positive for the anti-centromere antibody but lacked any evidence of cutaneous thickening or involvement. In summary, the authors describe the first case of a patient with APS associated with SS sine scleroderma.     

A rare case of systemic autoimmune disease with intricate features of systemic sclerosis, lupus, polymyositis and rheumatoid arthritis. Overlap syndrome or mixed connective tissue disease?

We report an unusual case of connective tissue disease characterized by the coexistence of signs, symptoms and immunological features of 4 defined autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM) and rheumatoid arthritis (RA). A 53-year-old female was admitted in our clinic with massive polyserositis (pretamponade) as well as skin, joint, muscular lesions and altered general status. The problem we found was the difficulty of including this case in a known clinical entity; SSc/SLE/PM//RA overlap syndrome and mixed connective tissue disease were the two most plausible diagnoses. We discuss the particularities of these clinical and immunological associations and the appropriate therapeutic options used in this kind of patients.     

Association of cerebral vasculitis with a lupus anticoagulant. A case with brain pathology

Summary The authors report the case of a sixty-five year old woman initially suffering from a thrombocytopenia. The patient was diagnosed as having an autoimmune disease with a lupus anticoagulant, positive antinuclear antibodies and negative anti-DNA antibodies. She then developed an encephalopathy which was fatal despite corticosteroids. Brain pathology revealed a vasculitis with some giant cells, evoking a granulomatous angiitis of the central nervous system. These clinical and biological features suggest a systemic lupus erythematosus with vasculitis or a primary granulomatous angiitis of the central nervous system. Taking into account the clinical manifestations and the presence of a lupus anticoagulant, we finally preferred to identify it as a primary antiphospholipid antibodies syndrome, despite absence of anticardiolipin antibodies. Contrary to thrombosis, vasculitis is rarely associated with an anticardiolipin antibody or a lupus anticoagulant. However, vasculitis in the course of primary antiphospholipid antibodies syndrome has been reported previously as in this case report.     

Pulmonary hypertension in a lupus clinic: experience with twenty-four patients

The clinical and serological findings on 24 patients with pulmonary hypertension (PHT) seen at the Lupus Clinic of St. Thomas' Hospital, London are presented. Twenty-two patients had systemic lupus erythematosus (SLE), one other a primary antiphospholipid syndrome and another an SLE/progressive systemic sclerosis (PSS) overlap syndrome. In 21 of the 24 patients, the disease resembled the primary idiopathic variety with clear lung fields and no clinical evidence of pulmonary thromboembolism, although angiography and nuclear perfusion scans were not performed. Two patients clearly suffered from thromboembolic PHT, one with SLE and one with an antiphospholipid syndrome. One patient with SLE/PSS overlap syndrome developed pulmonary fibrosis. The frequency of antiphospholipid antibodies (lupus anticoagulant and antibodies to cardiolipin was 68% which appears to be higher than generally found in patients with SLE, and the clinical significance of this finding is unknown. Other associated features of the antiphospholipid syndrome in this group were uncommon. Death occurred in 13 of the 24 patients, 4 were lost to followup and 7 are known to be alive. The cause of death was circulatory failure in the majority; sudden death once this complication occurred was particularly common. One patient died from adult respiratory distress syndrome and one from hemorrhagic shock while undergoing heart/lung transplantation. Two patients underwent successful heart/lung transplantation. One, however, died of a mesenteric occlusion and bowel infarction following a second lung transplantation because of rejection of the first heart/lung transplantation after one year. The other patient is alive and well 2 years later.     

Prevalence of anticardiolipin antibodies in subacute cutaneous lupus erythematosus.

We examined the prevalence of the antibodies to cardiolipin measured by solid-phase enzyme immunoassay during a prospective study of patients with subacute cutaneous lupus erythematosus (SCLE). Seven of 44 (16%) consecutive patients with SCLE had positive anticardiolipin antibodies; of these only three satisfied the American Rheumatism Association's revised criteria for the classification of systemic lupus erythematosus. Clinical findings probably associated with the positive anticardiolipin antibodies were found in four cases, including clotting abnormalities, thrombocytopenia, hemolytic anemia, livedo reticularis, chilblain lupus erythematosus lesions, migraine, leg venous thrombosis and pulmonary embolism after surgery, and spontaneous abortion. Our data suggest that it is reasonable to screen SCLE patients for these antibodies to confirm the presence of the antiphospholipid syndrome.     

Autoimmune-mediated atherothrombosis

Autoimmune vascular inflammation and oxidative stress (lipid peroxidation) are common in systemic autoimmune diseases and contribute to the oxidative modification of low-density lipoprotein (oxLDL) and oxLDL/beta2GPI complex formation. Circulating oxLDL/beta2GPI complexes have been detected in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The presence of antibodies to oxLDL/beta2GPI complexes indicates that these complexes are immunogenic, and the coexistence of complexes and antibodies has pointed to an active proatherogenic role in the development of autoimmune vascular complications. Immunohistochemical staining of atherosclerotic lesions suggest that these complexes are formed in the arterial wall and released into circulation. The in vitro macrophage uptake of oxLDL/beta2GPI complexes was significantly increased in the presence of antiphospholipid antibodies, either beta2GPI-dependent anticardiolipin or anti-beta2GPI antibodies, suggesting that macrophage Fcgamma receptors are involved in lipid intracellular influx and foam cell formation. These findings provide an explanation for the accelerated development of atherosclerosis seen in SLE and APS. The presence of circulating oxLDL/beta2GPI complexes and IgG antibodies to these complexes indicate significant vascular injury and oxidative stress as well as an active role in autoimmune-mediated atherothrombosis.     

Long-term membranous glomerulonephritis as the presenting manifestation of systemic lupus erythematosus in a patient with human immunodeficiency virus infection

The coexistence of human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE) is unusual, but the occurrence of SLE after HIV infection is even less common. Both conditions share similar clinical features including constitutional symptoms, facial rash, oral ulcers, alopecia, arthralgias, arthritis, seizures, cytopenias, glomerulonephritis, and antinuclear and antiphospholipid antibodies. This clinical overlap makes the diagnosis of SLE in a patient with pre-existing HIV infection difficult. Furthermore, immune complex glomerulonephritis with features resembling lupus nephritis has been described in HIV-positive patients. We present the case of a 45-year-old Hispanic woman with long-standing HIV infection who developed membranous glomerulonephritis with histological features of lupus nephritis. Five years after onset of renal disease she developed clinically evident SLE.     

New insights into pregnancy-related complications in systemic lupus erythematosus

Pregnancy in patients with systemic lupus erythematosus (SLE) presents an additional risk to an already complex clinical situation—overlap in symptoms between changes of pregnancy and SLE, presence of antiphospholipid antibodies, and need for potentially teratogenic medications can all complicate the management of pregnant patients with SLE. Studies demonstrate that, with careful planning, the majority of patients with lupus can complete pregnancy without serious complications. Recent developments are modified instruments to measure disease activity in pregnancy, increasingly common continuation of hydroxychloroquine during pregnancy, more frequent use of in vitro fertilization, and more aggressive fetal monitoring in patients positive for anti-Sjögren’s syndrome (SS)-A/Ro or anti- SS-B/La antibody.