Search

Dissecting cellulitis of the scalp (DCS) is a rare, primary neutrophilic cicatricial alopecia of unknown etiology. The disease follows a chronic, relapsing, and remitting course which may ultimately lead to scar formation and alopecia. The association of seronegative peripheral and/or axial spondyloarthritis in patients with hidradenitis suppurativa (HS) and acne conglobata (AC) is well established. However, the occurrence of spondyloarthropathy in patients with either isolated or combined DCS is relatively rare and therefore underrecognized by clinicians. We report a patient with DCS with inflammatory peripheral arthritis and asymptomatic radiographic sacroiliitis. Using PubMed, Ovid, and Google scholar, we searched for case reports of inflammatory arthritis in HS, AC, and DCS in the English literature from 1982 to present. We identified 12 patients with DCS who had associated spondyloarthropathy with adequate clinical details for a systematic analysis. We outline key clinical features, radiographic findings, and treatment utilized for these patients. Seronegative axial and peripheral spondyloarthritis may occur in the setting of isolated DCS as well with concomitant HS and AC. The inflammatory arthritis often develops during acute flares of the cutaneous disease. Choosing optimal drug therapy may be challenging. Current options include anti-TNF-α medications, which have been reported to be effective for both the cutaneous lesions and the associated spondyloarthritis. The complex pathophysiology of the conditions that comprise the follicular occlusion triad warrants further research into the potential role of additional biologic agents., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Coronary artery aneurysms are an uncommon manifestation of systemic lupus erythematosus (SLE), with only 14 cases reported previously in the literature. Herein, we report a 29-year-old woman with SLE who developed clinical and serologic evidence of an SLE flare and presented with chest pain and elevated serum troponin-T level. Cardiac computed tomography was performed and demonstrated fusiform aneurysmal enlargement of the proximal and middle portions of the coronary arteries and a beaded appearance of the distal coronary arteries. Extensive intercostal artery aneurysms were also noted. Several areas of abnormal myocardial perfusion were also noted. The patient improved after treatment with steroid pulses and cyclophosphamide. This case report is the first description of the appearance of lupus coronary vasculitis on cardiac computed tomography., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Azathioprine-induced aplastic anemia and fatal myelosuppression is a rare occurrence in patients with systemic lupus erythematosus (SLE). We report a case of a 53-year-old female with a normal thiopurine S-methyltransferase (TPMT) level who developed aplastic anemia within 4 weeks of azathioprine initiation, resulting in death. Physicians should be vigilant in monitoring routine blood work when administering azathioprine, a relatively common drug, in patients with SLE.

This article draws conclusions about pinpointing the actual onset of disease and when interventions should start to occur. The identification of necessary biomarkers will be discussed. We will also examine the incremental consequences of delaying therapy, particularly for 'preclinical' disease. Medical economic analyses can help us balance benefits and avoid some adverse outcomes for patients. To conclude, we will discuss the new roles that need developing for primary care physicians and non-physican providers., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Systemic lupus erythematosus (SLE), the prototypic systemic autoimmune disease, is a debilitating multisystem autoimmune disorder characterized by chronic inflammation and extensive immune dysregulation in multiple organ systems, resulting in significant morbidity and mortality. Here, we present a multidisciplinary approach resulting in the identification of neutrophil cytosolic factor 2 (NCF2) as an important risk factor for SLE and the detailed characterization of its causal variant. We show that NCF2 is strongly associated with increased SLE risk in two independent populations: childhood-onset SLE and adult-onset SLE. The association between NCF2 and SLE can be attributed to a single nonsynonymous coding mutation in exon 12, the effect of which is the substitution of histidine-389 with glutamine (H389Q) in the PB1 domain of the NCF2 protein, with glutamine being the risk allele. Computational modeling suggests that the NCF2 H389Q mutation reduces the binding efficiency of NCF2 with the guanine nucleotide exchange factor Vav1. The model predicts that NCF2/H389 residue interacts with Vav1 residues E509, N510, E556, and G559 in the ZF domain of Vav1. Furthermore, replacing H389 with Q results in 1.5 kcal/mol weaker binding. To examine the effect of the NCF2 H389Q mutation on NADPH oxidase function, site-specific mutations at the 389 position in NCF2 were tested. Results show that an H389Q mutation causes a twofold decrease in reactive oxygen species production induced by the activation of the Vav-dependent Fcγ receptor-elicited NADPH oxidase activity. Our study completes the chain of evidence from genetic association to specific molecular function.

Background: Leukemic synovitis is a rare complication of adult myeloid leukemias characterized by joint pain and swelling. It is important to recognize this diagnostic challenge as it may be the initial manifestation of leukemia or of relapse., Methods: A retrospective search of patient files from 2 teaching hospitals identified 4 adult patients who presented with large joint arthritis and concurrent or subsequent leukemic synovitis. All patients presented with inflammatory arthritis of large joints, and leukemic synovitis was identified by the presence of leukemic cells in the synovial fluid or infiltrating the synovial membrane seen at biopsy., Results: A leukemia of monocytic origin-acute myelomonocytic leukemia or chronic myelomonocytic leukemia-was diagnosed in all 4 patients. In 2 cases, leukemic synovitis was the initial manifestation of leukemia. In the third case, it was the first sign of relapse, and in the remaining case, it developed shortly after diagnosis of leukemia. All patients had either osteoarthritis or rheumatoid arthritis. One patient was diagnosed simultaneously with osteoarthritis and leukemia. The remaining patients had a prior history of arthritis., Conclusions: Adult leukemic synovitis occurs in association with leukemias of monocytic differentiation. Data presented here, and review of isolated case reports, support this association. The finding of large joint arthritis as a comorbidity in these 4 cases raises questions about the role of antecedent arthritis as a predisposing factor in the pathophysiology of leukemic synovitis.

In our earlier study, we utilized a Bayesian design to probe the association of approximately 1000 genes (approximately 10,000 single-nucleotide polymorphisms (SNPs)) with systemic lupus erythematosus (SLE) on a moderate number of trios of parents and children with SLE. Two genes associated with SLE, with a multitest-corrected false discovery rate (FDR) of <0.05, were identified, and a number of noteworthy genes with FDR of <0.8 were also found, pointing out a future direction for the study. In this report, using a large population of controls and adult- or childhood-onset SLE cases, we have extended the earlier investigation to explore the SLE association of 10 of these noteworthy genes (109 SNPs). We have found that seven of these genes exhibit a significant (FDR<0.05) association with SLE, both confirming some genes that have earlier been found to be associated with SLE (PTPN22 and IRF5) and presenting novel findings of genes (KLRG1, interleukin-16, protein tyrosine phosphatase receptor type T, toll-like receptor (TLR)8 and CASP10), which have not been reported earlier. The results signify that the two-step candidate pathway design is an efficient way to study the genetic foundations of complex diseases. Furthermore, the novel genes identified in this study point to new directions in both the diagnosis and the eventual treatment of this debilitating disease.

Objective: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility., Methods: Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case-control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated., Results: We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 x 10(-25)). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4., Conclusion: Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.

Soft tissue infections are common and potentially fatal conditions. Infections are a major cause of morbidity and mortality in patients who have rheumatic disease. Patients who have rheumatic diseases may be at increased risk for soft tissue infections because of various factors, including inherent immunologic defects, genetics, and use of immunomodulatory therapy, including biologic agents. Timely diagnosis and management with the institution of antibiotics with or without surgical intervention is imperative for effective resolution of infection. This article provides a review of recent literature on the presentation and clinical course of infectious tenosynovitis, septic bursitis, pyomyositis, and necrotizing fasciitis, especially in relation to patients who have rheumatic disease.

Serum antibodies reactive with the keratin layer of rat esophagus (AKA) were found in 46 of 80 (57.5%) rheumatoid arthritis (RA) patients. In contrast, AKA were present in only 7 of 82 (9.5%) patients with other types of rheumatic disorders and in 2 of 47 (4.2%) healthy subjects. AKA were not specific for RA, however, because in the former group, AKA were present in 4 of 20 (20%) systemic sclerosis patients and in 3 of 12 (25%) ankylosing spondylitis patients. AKA belong predominantly to the IgG class and are complement fixing. Although found in some RA joint fluids, AKA were not selectively concentrated in the joint fluid. Absorption of RA serum with type I human collagen or with human epidermal keratin did not remove AKA activity. The frequency of AKA in RA patients both negative and positive for DR4 was equal. There was no relationship between the frequency of AKA and the occurrence of other serum autoantibodies such as antibodies to intermediate filaments, smooth muscle, and nuclear antigens. Serum antibody reactive with human stratum corneum found in patients with psoriatic arthritis was shown to be different from AKA. Rabbit antiserum to human keratin did not inhibit the reaction of AKA against the keratin layer of rat esophagus. Autoimmunity to structural proteins including collagen, vimentin intermediate filaments, smooth muscle antigens, and keratin is a characteristic feature of RA.

Purpose of Review: Microscopic polyangiitis is a systemic necrotizing vasculitis that affects small vessels, resulting in a wide spectrum of organ involvement including the kidneys and the lungs. This paper reviews recent insights and observations into the pathogenesis, clinical manifestations, and treatment of pulmonary involvement in microscopic polyangiitis., Recent Findings: The spectrum of clinical presentations ranges from antecedent interstitial fibrosis to frank hemoptysis secondary to capillaritis. Computerized tomography imaging reveals a variety of pulmonary findings, including ground-glass attenuation, consolidation, thickening of bronchovascular bundles, and honeycombing. Antineutrophil cytoplasmic antibodies are important in diagnosis as well as in the pathogenesis and prognosis of microscopic polyangiitis. There is more evidence to support the various therapeutic modalities currently used in pulmonary manifestations of microscopic polyangiitis, including induction therapy with cyclophosphamide, the use of other novel pharmacologic agents such as the tumor necrosis factor-alpha blockers and rituximab, and nonpharmacologic modalities such as plasmapheresis and ventilatory management., Summary: The pulmonary manifestations of microscopic polyangiitis are diverse and often difficult to manage; however, as our understanding and experience grows so does our ability to successfully diagnose and treat these patients.

Metastatic spread of malignancy to the joints is rare and only a few cases of solid tumors have been reported. We describe a patient with inflammatory arthritis of the knee and ankle secondary to metastatic gastric adenocarcinoma to the joints and bone diagnosed by synovianalysis. Arthritis secondary to metastatic cancer is a poor prognostic sign. The diagnosis is based on a strong clinical suspicion, magnetic resonance imaging, and joint fluid cytology or synovial biopsy.

The rheumatic manifestations of sarcoidosis include inflammatory arthritis, periarticular soft tissue swelling, tenosynovitis, dactylitis, bone involvement and myopathy. Two types of arthritis that differ in clinical course and prognosis are recognized. Acute sarcoid arthritis is self-limiting and resolves without permanent sequelae. Chronic sarcoid arthritis although less common can progress to cause joint deformities. There are proliferative and inflammatory changes in the synovium and non-caseating granulomas are seen in half of patients. The pathogenesis of sarcoid arthritis is not well understood, however genetic and environmental factors are important. Drug therapy of sarcoid arthritis with nonsteroidal anti-inflammatory agents, corticosteroids, colchicine, antimalarials and/or immunosuppressive medications is based mainly on open label uncontrolled studies. This review focuses on the current knowledge on the various features of sarcoid arthritis including clinical presentation, course, imaging, and pathology. Recent developments in the usage of anti-tumor necrosis factor therapy for sarcoidosis will be reviewed.

Systemic sclerosis is a multisystem disorder of unknown etiology and involves organ systems such as the skin, peripheral vasculature, gastrointestinal tract, kidney, heart, and the lungs is observed quite frequently. In this review, we discuss the development of interstitial lung disease, one of the common pulmonary manifestations and a major cause of mortality and morbidity in this disorder. It is, however, under-recognized and diagnosed late in the course of the illness. Early use of pulmonary function tests followed by bronchoalveolar lavage in appropriate cases helps in early diagnosis. Recent studies emphasize the role of various profibrotic and inflammatory cytokines both locally in the lung and systemically in its pathogenesis. Treatment is helpful in arresting the progression if initiated early. Cyclophosphamide with or without corticosteroids given orally or as intravenous pulse may be helpful.

Systemic lupus erythematosis (SLE) is a heterogenous disease of unknown etiology. It is not uncommon to see pleuropulmonary involvement in isolation or along with the involvement of other organ systems in SLE. Pulmonary manifestations of SLE can involve the pleura, lung parenchyma, airways, pulmonary vasculature, and the respiratory muscles. In this review we discuss two important pulmonary manifestations of SLE: acute lupus pneumonitis and diffuse interstitial lung disease. These two conditions have a major impact on the mortality and morbidity of patients with SLE and it is essential to recognize and treat them appropriately. High-resolution computed tomographic scans of the chest and pulmonary function tests help to establish a diagnosis and aid long-term follow-up of these patients. High-dose corticosteroids are the mainstay of treatment for the two conditions, although other agents such as cyclophosphamide, azathioprine, intravenous gamma globulin, and plasmapheresis have been used with varying degrees of success.

Adult-onset Still's disease (AOSD) is a rare splenic disorder with an unknown cause. It is not uncommon for AOSD to involve other organs, such as the liver; the kidney; the bone marrow; and, less often, the lungs. In this review, we discuss the pulmonary complications of AOSD. Pulmonary involvement in AOSD usually consists of pleural effusion or transient pulmonary infiltrates, but it may become life threatening if it progresses to the adult respiratory distress syndrome. Chronic conditions, such as restrictive lung disease, have also been reported in patients with AOSD. The only treatment currently available is high-dose steroids, although other agents, such as intravenous immunoglobulin, cyclophosphamide, and azathioprine, have been tried with some success.

Systemic lupus erythematosus (SLE) is the prototype of human autoimmune diseases. Its genetic component has been suggested by familial aggregation (lambdas = 20) and twin studies. We have screened the human genome to localize genetic intervals that may contain lupus susceptibility loci in a sample of 188 lupus patients belonging to 80 lupus families with two or more affected relatives per family using the ABI Prism linkage mapping set which includes 350 polymorphic markers with an average spacing of 12 cM. Non-parametric multipoint linkage analysis suggests evidence for predisposing loci on chromosomes 1 and 18. However, no single locus with overwhelming evidence for linkage was found, suggesting that there are no 'major' susceptibility genes segregating in families with SLE, and that the genetic etiology is more likely to result from the action of several genes of moderate effect. Furthermore, the support for a gene in the 1q44 region as well as in the 1p36 region is clearly found only in the Mexican American families with SLE but not in families of Caucasian ethnicity, suggesting that consideration of each ethnic group separately is crucial.

We have recently reported that transforming growth factor-beta (TGF-beta) co-stimulates interleukin-2 (IL-2) activated CD8+ T cells to down-regulate antibody production. In SLE, lymphocyte production of both IL-2 and TGF-beta is decreased. Here we report that a brief treatment of PBMC from SLE patients with IL-2 and TGF-beta can result in marked inhibition of spontaneous polyclonal IgG and autoantibody production. Peripheral blood mononuclear cells (PBMC) from 12 patients with active SLE were exposed to IL-2 with or without TGF-beta for three days, washed and cultured for seven more days. The mean decrease in IgG secretion was 79%. The strongest inhibitory effect was observed in cases with the most marked B cell hyperactivity. Spontaneous production of anti-nucleoprotein (NP) antibodies was observed in four cases and cytokine treatment of PBMC decreased autoantibody production by 50-96%. IL-2 inhibited Ig production by either TGF-beta-dependent or independent mechanisms in individual patients. In a study of anti-CD2 stimulated IgG production in a patient with active SLE, we documented that IL-2 and TGF-beta reversed the enhancing effects of CD8+ T cells on IgG production and induced suppressive activity instead. These results raise the possibility that cytokine-mediated down-regulation of B cell hyperactivity in SLE may have therapeutic potential.

Objective: To determine whether genes participating in programmed cell death, including bcl-2, IL-10, Fas-L, and CTLA-4, may contribute to the genetic predisposition to systemic lupus erythematosus (SLE)., Methods: First, intragenic markers for the bcl-2, IL-10, Fas-L, and CTLA-4 genes were characterized and their extent of polymorphism in normal populations was determined. The allelic distribution of these gene markers in a large Mexican American SLE cohort of 158 patients and 223 ethnically matched controls was determined using fluorescent-labeled primers and semiautomated genotyping., Results: The bcl-2, Fas-L, and IL-10 loci showed significantly different allelic distribution in SLE patients compared with controls, indicating an association between these genes and SLE. No association was found between SLE and the CTLA-4 gene. Further analysis revealed a synergistic effect between susceptibility alleles of the bcl-2 and IL-10 genes in determining disease susceptibility. Alone, the presence of each of these alleles was associated with a moderate increase in SLE risk, while the occurrence of these alleles together increased the odds of developing SLE by more than 40-fold., Conclusion: The results suggest that individuals carrying specific genotypes of both bcl-2 and IL-10 are at significant risk of developing SLE.

Interstitial pulmonary fibrosis and tracheobronchial sicca are the most common presentation of pulmonary involvement in primary Sjögren's syndrome. There is wide spectrum of less common manifestations, including pulmonary arterial hypertension, pseudolymphoma, pulmonary lymphoma, lymphocytic interstitial pneumonitis, amyloidosis, and pleurisy. Pulmonary function test abnormalities showing a restrictive pattern and cellular abnormalities in bronchoalveolar lavage fluid for prevalent in patients without respiratory complaints and normal chest radiographs. Long-term prospective controlled studies are needed to determine the clinical course and significance of these findings.

Objective: To ascertain whether there are any geographic clusters of systemic lupus erythematosus (SLE), and critically review 2 previous reports of these clusters., Methods: A literature review of all epidemiologic surveys relevant to SLE published since 1966 was undertaken. This included a search of abstracts and reports, in addition to peer-reviewed publications., Results: Two geographic clusters were identified in the literature. A report purporting that contaminated ground water in southwest Tucson, Arizona was associated with significantly increased symptoms of SLE was flawed since no patients were examined, discarded criteria were used, and incorrect definitions were employed by the nonrheumatologist authors. Another study, which identified a cluster in Nogales, Arizona, used generally valid methodology. However, the authors' conclusion that a 94/100,000 prevalence of SLE was evidence of an excessive increase in this 92% Hispanic/Native American community is not consistent with published surveys among Hispanic and Native American populations., Conclusion: No valid claims of SLE geographic clusters have been published.

A patient with hyperglobulinemic purpura of Waldenstrom and systemic lupus erythematosus is reported. The coexistence of these two conditions which share a number of common clinical and laboratory features is rare. Treatment of the patient with prednisone, colchicine and hydroxychloroquine led to the improvement of the cutaneous vasculitis and a drop in ESR, serum gamma globulins and IgM and IgG rheumatoid factors. The features of nine other cases and the immunopathogenesis of the disease are reviewed.

Human immunodeficiency virus (HIV) infection can present with musculoskeletal syndromes including systemic vasculitis. We describe vasculitis resembling polyarteritis nodosa (PAN) in 2 HIV-infected individuals and review reported cases to emphasize clinical features. Our patients presented with digital gangrene and had vasculitis confirmed by angiography. In reports in the literature, patients have presented with digital ischemia and gangrene, peripheral neuropathy and constitutional symptoms. The diagnosis has been confirmed by angiography and by nerve and muscle biopsy. Treatment with systemic corticosteroids has afforded short term benefits to patients; however the effectiveness of alternative therapy and longterm prognosis remain unclear.

Budd-Chiari syndrome, hypertension, and thrombocytopenia developed in a 6-year-old girl as manifestations of primary antiphospholipid antibody syndrome (APS). She improved with systemic corticosteroid and anticoagulation therapy. Anticardiolipin antibodies were found in the patient, her mother and 3 siblings, suggesting the importance of genetic factors. The clinical features of an APS in children is reviewed.

To determine the utility of magnetic resonance imaging (MRI) of the brain in diagnosing active neuropsychiatric disease in systemic lupus erythematosus (NP-SLE), a prospective study of 51 hospitalized systemic lupus erythematosus (SLE) patients during 64 separate episodes of suspected NP-SLE was initiated. In addition to standard hematology, chemistry, and serological tests, the workup included MRI in all patients. A computed tomographic scan of the brain was obtained in patients enrolled in the first year of the study. Of the 64 neuropsychiatric episodes, 42 were attributable to NP-SLE and 22 were attributed to causes other than SLE. Neuropsychiatric complaints unrelated to lupus included depression (n = 6), seizures (n = 5), headache (n = 3), altered mental status (n = 2), aseptic meningitis (n = 2), cardiovascular accident (n = 2), transient ischemic attack (n = 1), and vertigo (n = 1). The MRI was abnormal in 34 of 64 (53%) episodes. MRI abnormalities were more common in patients with focal neurological deficits (19/26) than in those without focal findings (15/38; P = .008) and in patients with nephritis (19/24) than in those without renal disease (15/40; P = .002). MRI abnormalities were as frequent in NP-SLE (25/42) as in cases with non-NP-SLE-related causes (9/22). Periventricular increased signal (PIS) was a frequent MRI finding (10/64). Enlargement of the prepontine cistern, an MRI finding not previously described in NP-SLE, was seen (14/64). Both findings were associated with the presence of hypertension and lupus nephritis. PIS similar to that seen in our patients has been described in otherwise healthy elderly individuals with risk factors for stroke, suggesting that vascular abnormalities may be important in the etiology of these lesions. In conclusion, abnormalities in brain MRI occur frequently in NP-SLE, especially in patients with focal neurological deficits. However, the presence of similar MRI abnormalities in SLE patients with neuropsychiatric symptoms and findings with non-SLE-related causes limits the specificity of the MRI for diagnosing NP-SLE.

Lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine were studied in 18 female patients with systemic lupus erythematosus (SLE) with mild or inactive disease. Patients were case matched (200-400 mg hydroxychloroquine daily vs no hydroxychloroquine) on several factors including daily corticosteroid dose in this cross sectional study. All had normal menstrual cycles; none smoked, used alcohol, were taking lipid altering medications or had other concurrent diseases. Patients taking hydroxychloroquine had 35-54% lower total triglyceride, VLDL-triglyceride, LDL-triglyceride, HDL-triglyceride, VLDL-cholesterol, and apolipoprotein CIII levels (p < 0.03). These results are encouraging in that hydroxychloroquine, in addition to being useful for alleviating the primary symptoms of SLE, may also be useful for ameliorating the adverse effects of corticosteroid therapy on triglyceride-rich lipoprotein metabolism.

Background and Purpose: Delayed ischemic deficits contribute to the high morbidity and mortality rates associated with subarachnoid hemorrhage. We evaluated the potential usefulness of measuring coagulation and hemorheological variables and cardiolipin antibodies for prediction of delayed ischemic deficit after subarachnoid hemorrhage., Methods: Consecutive patients with subarachnoid hemorrhage were studied. Coagulation and hemorheological variables and cardiolipin antibodies were measured on admission, within 7 days of subarachnoid hemorrhage. A subset of patients was studied on admission and at two subsequent occasions., Results: Sixty-nine patients were studied. Sixty-one of these were without clinical manifestations of vasospasm at admission, and 16 developed delayed ischemic deficit during their hospitalization. None of the laboratory variables measured were significantly different between patients with or without later development of delayed ischemic deficit. Elevation of the fibrin fragment D-dimer was found in the group of eight patients admitted with ischemic symptoms and in 49% (34 of 69) of all patients, but this was not associated with delayed ischemic deficit. Sixteen patients were studied on three occasions; this group showed a significant decrease in hematocrit, an increased white blood cell count, and no change in fibrinogen concentration. Fibrin D-dimer levels rose significantly after surgery (from 5.01 +/- 0.69 to 5.53 +/- 0.58 ln-ng/ml, p less than 0.025) and after onset of delayed ischemic deficit (from 4.71 +/- 0.64 to 5.84 +/- 0.34 ln-ng/ml, p less than 0.01)., Conclusions: Hemostatic measurements, hemorheological variables, and cardiolipin immunoreactivity did not predict delayed ischemic deficit in this population.

We evaluated 50 consecutive patients with acute ischemic stroke to assess the prevalence of systemic infection preceding the neurological event. We analyzed the immunohematologic characteristics of patients with and without signs and/or symptoms of a preceding infectious process. Patients were examined less than or equal to 7 days after cerebral infarction and evaluated for fibrinogen, anticardiolipin antibodies, fibrin D-dimer (a fragment of cross-linked fibrin), plasminogen activator inhibitor-1, and protein S. Of the 50 patients, 17 had symptoms of infection beginning less than or equal to 1 month before the stroke (11 had upper respiratory tract infections, three urinary tract infections, two subacute bacterial endocarditis, and one pneumonia). Compared with patients without infection, patients with infection had significant increases in fibrin D-dimer concentration (5.3 +/- 1.1 versus 4.7 +/- 0.9 log-transformed ng/ml, p less than 0.05) and cardiolipin immunoreactivity, IgG isotype (1.8 +/- 1.3 versus 1.1 +/- 0.9 log-transformed phospholipid units, p less than 0.04), and, when studied less than or equal to 2 days after the stroke, increased fibrinogen levels (459 +/- 126 versus 360 +/- 94 mg/dl, p less than 0.05). In conclusion, infection-associated cerebral infarction is common and is associated with substantial immunohematologic abnormalities.

We describe a patient in whom nephrotic syndrome due to renal amyloidosis occurred 4 years into the course of severe ankylosing spondylitis with peripheral joint and extraarticular involvement. Treatment with colchicine was accompanied by reversal of proteinuria, and histologic regression of amyloid deposits was documented from bone marrow obtained from the femoral heads during total hip arthroplasties staged 1 year apart.

Alveolar septal deposits of immunoglobulins and complement were found in the lung biopsy of a patient with polymyositis and interstitial lung disease. Anti-Jo 1 antibody was present in the serum and in isolated mixed cryoglobulins of the patient, suggesting the role of immune complex deposition in the pathogenesis of lung disease. Significant amounts of cryoglobulins were found in 10 of 16 (62.5%) patients with polymyositis/dermatomyositis tested.

Rheumatoid pericarditis occurs in approximately one third of rheumatoid arthritis (RA) patients. However, clinically apparent rheumatoid pericarditis is infrequent. The authors found clinical pericarditis in 12 of 960 patients admitted for RA, 5 of whom had manifestations of cardiac compression. These 5 had longer duration of RA, worse functional class, and more extraarticular features than the patients without cardiac compression. Presenting features of cardiac compression included dyspnea, edema, chest pain, and pulsus paradoxus. Treatment of patients with cardiac compression due to rheumatoid pericarditis may include a trial of systemically administered corticosteroids, but this should not delay surgical intervention for impending tamponade. Pericardiocentesis should only be performed as an emergency, life-saving procedure. It may be followed by intrapericardiac injection of corticosteroids, but this does not prevent recurrence. Longer-lasting benefit is obtained by surgical decompression. Two-year mortality in patients with cardiac compression was 100%. The literature on the subject is reviewed.

The clinical course of chronic diffuse interstitial lung disease (ILD) was studied in 14 patients with SLE. The mean duration of follow-up was 7.3 years. All patients had dyspnea on exertion, pleuritic chest pain, chronic cough, and basilar rales. Chest roentgenogram showed diffuse or basilar infiltrates, pleural disease, and elevation of both diaphragms. Systemic corticosteroids were given early in the course of the illness for lung involvement and multisystem disease. Diffusing capacity for carbon monoxide (DLCO) and inspiratory vital capacity (IVC) improved or remained unchanged in the majority of patients. Respiratory complaints improved in all patients; however, two patients died of pulmonary fibrosis and another died of bacterial pneumonia. Alveolar septal deposits of immunoglobulins and complement were found. This study showed that while variability existed among individual subjects, the clinical progression of ILD was slow and tended to improve or stabilize with time.

The cellular requirements for B cell hyperactivity in systemic lupus erythematosus (SLE) were studied. Removal of either CD8+ or CD4+ lymphocyte markedly decreased the spontaneous in vitro production of polyclonal IgG and of antigen-specific (anti-double-stranded DNA and antinucleoprotein) antibodies by SLE peripheral blood mononuclear cells (PBMC). The CD8+ lymphocytes that sustained IgG production were CD3+, HLA-DR+, and their activity was abrogated by preincubation with anti-HLA-DR monoclonal antibody. When both CD4+ and CD8+ cells were removed, the readdition of either subset partially restored polyclonal IgG production, but both cell subsets were required to reconstitute autoantibody production. Purified SLE B cell cultures, which generated only 15% of the IgG produced by unseparated PBMC, were fully reconstituted only by mixtures of CD4+ with CD8+ cells, and with CD8-, CD4-, CD16+ cells. At least part of the support for spontaneous IgG production can be attributed to endogenous interleukin-2 and interleukin-6.

Eleven of 30 patients with MCTD, followed for a mean of 10 years, developed immune complex nephropathy (five membranous, two mesangial, one mixed, and one sclerosing) with NS in nine of 11. Another patient had membranous nephropathy at autopsy. Patients with renal disease tended to have more systemic manifestations than those without. NS was at times of abrupt onset, recurrent, and/or persistent. Anti-RNP and serum complement were not helpful in predicting nephritis. Seventy-two percent of nephropathy and 62% of NS episodes resolved or improved after corticosteroid therapy. Five patients became hypertensive, two developed chronic renal failure and required chronic dialysis, and one needed acute dialysis twice. One patient progressed to focal proliferative crescentic nephritis with necrotizing arteritis. Three patients with nephropathy died, two of pulmonary hypertension with acute cor pulmonale and one of overwhelming sepsis. Nephropathy is relatively common in MCTD, is associated with substantial morbidity, and with the risk of hypertension and chronic renal failure.

Serum antibodies reactive with the keratin layer of rat esophagus (AKA) were found in 46 of 80 (57.5%) rheumatoid arthritis (RA) patients. In contrast, AKA were present in only 7 of 82 (9.5%) patients with other types of rheumatic disorders and in 2 of 47 (4.2%) healthy subjects. AKA were not specific for RA, however, because in the former group, AKA were present in 4 of 20 (20%) systemic sclerosis patients and in 3 of 12 (25%) ankylosing spondylitis patients. AKA belong predominantly to the IgG class and are complement fixing. Although found in some RA joint fluids, AKA were not selectively concentrated in the joint fluid. Absorption of RA serum with type I human collagen or with human epidermal keratin did not remove AKA activity. The frequency of AKA in RA patients both negative and positive for DR4 was equal. There was no relationship between the frequency of AKA and the occurrence of other serum autoantibodies such as antibodies to intermediate filaments, smooth muscle, and nuclear antigens. Serum antibody reactive with human stratum corneum found in patients with psoriatic arthritis was shown to be different from AKA. Rabbit antiserum to human keratin did not inhibit the reaction of AKA against the keratin layer of rat esophagus. Autoimmunity to structural proteins including collagen, vimentin intermediate filaments, smooth muscle antigens, and keratin is a characteristic feature of RA.

Septic olecranon bursitis developed in three patients with systemic lupus erythematosus. Although promptly treated with systemic antibiotics, the clinical course in two patients became prolonged and eventually required bursectomy to eradicate the infection. The occurrence of septic bursitis was a manifestation of the general susceptibility of SLE patients to infections.

27 paired specimens of ascitic fluid and serum obtained from patients with alcoholic liver disease were tested for cryoproteins and immune complexes by the C1q binding assay. 20 sera (74%) and ten ascitic fluid (37%) had significant amounts of cryoproteins. The cryoproteins were of the 'mixed' type of cryoglobulins consisting of IgG, IgM, IgA, C3 and C1q. The C1q binding test was positive in 17 sera (63%) and in 16 ascitic fluid (59%). Intracytoplasmic inclusions of immunoglobulin and complement were found within the ascitic fluid leukocytes by direct immunofluorescence. The presence of immune complexes in the ascitic fluid may be important in the reduction of the complement level of cirrhotic ascitic fluid.

Three patients with systemic lupus erythematosus (SLE) and relapsing auricular and nasal chondritis are described. Chondritis in SLE is a rare event (less than 1% of our patients), was accompanied by clinical and laboratory evidence of SLE activity and resembled relapsing polychondritis in clinical presentation and pathology. Clinical involvement was limited, cartilage collapse did not occur and response to steroid therapy was prompt. Cartilage inflammation in two ear biopsies was relatively mild, with deposits of IgG and C3 in the chondrofibral junction and adjacent skin vessels. Immune complexes (cryoglobulins) were present in the serum. We postulate an immune complex pathogenesis of this rare manifestation of SLE.

The clinical course and cardiac pathology of three adults with MCTD who developed myocarditis and that of two other previously reported cases are reviewed. The patients presented with cardiomegaly, congestive heart failure, ventricular arrhythmias, and elevated serum CPK MB fraction. Except for more frequent episodes of serositis and less prevalent neuropsychiatric manifestations and hepatosplenomegaly, no distinguishing features were found in MCTD patients with myocarditis compared with those without myocardial involvement. The concomitant onset of proximal myositis and myocarditis in one patient suggests a common inflammatory pathologic process in the skeletal and cardiac muscles. Circulating antibodies to myocardium and to cardiac conduction tissue were found in nine of 23 (39%) MCTD patients, but the presence of these autoantibodies was not associated with the occurrence of clinical cardiac involvement. The clinical and pathologic features of the five MCTD patients were similar to that of SLE patients with myocarditis. Primary myocardial involvement in MCTD, as in SLE, was associated with a relatively poor prognosis.