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Neuropsychiatric manifestations of systemic lupus erythematosus (SLE) are frequent, vary from mild to severe, and are often difficult to diagnose and distinguish from those of other diseases. Any location in the nervous system may be affected, with symptoms and signs ranging from mild cognitive dysfunction to seizures, strokes, and coma. At the initial development of neuropsychiatric manifestations, many patients have other medical conditions or are receiving medications that can affect the central nervous system or the peripheral nervous system. The challenge to the clinician is to determine the exact cause of the nervous system dysfunction and to institute the appropriate therapy. This chapter describes the classification, clinical signs and symptoms, laboratory and neuroimaging findings, differential diagnosis, and treatment of SLE involving the nervous system.

Many patients with an idiopathic interstitial pneumonia (IIP) have clinical features that suggest an underlying autoimmune process but do not meet established criteria for a connective tissue disease (CTD). Researchers have proposed differing criteria and terms to describe these patients, and lack of consensus over nomenclature and classification limits the ability to conduct prospective studies of a uniform cohort. The “European Respiratory Society/American Thoracic Society Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease” was formed to create consensus regarding the nomenclature and classification criteria for patients with IIP and features of autoimmunity. The task force proposes the term “interstitial pneumonia with autoimmune features” (IPAF) and offers classification criteria organised around the presence of a combination of features from three domains: a clinical domain consisting of specific extra-thoracic features, a serologic domain consisting of specific autoantibodies, and a morphologic domain consisting of specific chest imaging, histopathologic or pulmonary physiologic features. A designation of IPAF should be used to identify individuals with IIP and features suggestive of, but not definitive for, a CTD. With IPAF, a sound platform has been provided from which to launch the requisite future research investigations of a more uniform cohort. ERS/ATS task force provides nomenclature and classification criteria for patients with IIP and autoimmune features

Rheumatoid arthritis is the most common chronic inflammatory polyarthritis characteristically involving the small joints of the hands, wrists, and feet in a symmetric distribution. The primary site of pathology is the synovium of diarthrodial joints. Most patients have rheumatoid factor and/or anti-citrullinated protein antibodies in their serum. Extra-articular manifestations may occur and most commonly involve the skin, lungs, heart, eye, and hematologic system. If untreated joint destruction with deformity and significant organ dysfunction leading to disability and death can occur. The etiology is unknown, but recurrent environmental exposures inciting an autoimmune response in a genetically predisposed individual has been proposed. Over the past two decades, there have been several major advancements in the diagnosis and management of this disease.

Many patients with systemic lupus erythematosus (SLE) have working memory deficits. Few studies have evaluated working memory performance and neurometabolite profile using magnetic resonance spectroscopy in SLE.We gave the Paced Auditory Serial Addition Test (PASAT), a measure of working memory, to 73 patients with SLE. We calculated total score, dyads, chunking, and cognitive fatigue. Using magnetic resonance spectroscopy, we determined the ratio of choline to creatine (Ch/Cr) in normal-looking right and left frontal lobe white matter.Twenty-nine percent of patients showed impaired working memory on the PASAT. Total PASAT score inversely correlated with right and left frontal white matter Ch/Cr. Left frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. Right frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. There was no relationship between cognitive fatigue and either left or right frontal white matter Ch/Cr. Longer disease duration was associated with higher left frontal white matter Ch/Cr. Correlations remained significant when we considered disease duration and left frontal white matter Ch/Cr against total PASAT score and total dyads.Patients with SLE were impaired on the PASAT. Lower total PASAT score and fewer dyads correlated with higher left frontal microstructural white matter damage, while cognitive fatigue did not. This pattern suggests that early white matter damage interferes with working memory in SLE and provides further insight into the neurobiological basis of mild cognitive dysfunction related to microstructural white matter injury.

Purpose Approximately 14–54% of patients with systemic lupus erythematosus without a history of major neuropsychiatric syndromes (nonNPSLE) have cognitive deficits. Elevated N-methyl-D-aspartate (NMDA) receptor antibodies (anti-NR2) have been reported in 35% of patients with SLE, but few studies have utilized controls or a composite memory index. We hypothesized that serum anti-NR2 would be elevated in nonNPSLE compared to healthy controls, and that elevated anti-NR2 would be associated with memory dysfunction and depression. Methods Subjects included 43 nonNPSLE patients with a mean age of 36.5 (SD = 9.0) and mean education level of 14.7 years (SD = 2.5). Twenty-seven healthy control subjects with similar demographic characteristics were also enrolled in this study. A global Cognitive Impairment Index (CII) and a Memory Impairment Index (MII) were calculated using impaired test scores from the ACR–SLE neuropsychological battery. Serum samples were analyzed using a standard ELISA for anti-NR2. Results Elevations of serum anti-NR2 were found in 14.0% of the nonNPSLE and 7.4% of the controls (p = 0.47). There was no relationship between elevated anti-NR2 status and higher CII or performance on the MII. No relationship between levels of depressive symptoms and anti-NR2 was found. Conclusions The frequency of elevated anti-NR2 was low (14.0%) in this sample of SLE patients and not significantly different from controls. A relationship was not found between the presence of anti-NR2 in serum and global cognitive or memory indices, or with depression. Results suggest that serum anti-NR2 is not likely related to mild cognitive dysfunction in SLE patients without a prior history of NPSLE.

This commentary highlights the present dilemmas surrounding the classification of a patient with interstitial pneumonia who has clinical features suggesting an associated connective tissue disease but the features fall short of a clear diagnosis of connective tissue disease-associated interstitial lung disease under the current rheumatologic classification systems. This commentary illustrates what we perceive to be the limitations in the present approach to the classification of this group of patients and discusses problems with redefining the diagnosis of undifferentiated connective tissue disease to encompass patients with interstitial pneumonia. Finally, we advocate not only for a multidisciplinary approach to evaluation, but also disease classification and offer a proposal to define them as a distinct phenotype—lung-dominant CTD—for which prognostic, therapeutic, and pathobiologic implications can be tested in future, hopefully multiinstitutional, studies.

We compared the frequency of life stress and coping styles using self-report measures in patients with systemic lupus erythematosus (SLE) and healthy controls. We also explored the relationship between cognition, life stress and coping. Thirty-one SLE patients with overt neuropsychiatric (NPSLE) symptoms, 22 SLE patients without overt neuropsychiatric (non-NPSLE) symptoms and 25 healthy controls completed measures of cognition, life events and coping skills. SLE patients (NP and non-NP) showed greater use of negative, disengaging coping scales (p = 0.002) and more negative life stress events over the past 6 months (p = 0.018) and past 6–12 months (p = 0.004) compared with controls. NPSLE and non-NPSLE subjects were higher on a cognitive impairment index (CII) than controls (p < 0.001). Only the NPSLE subjects had significant correlations between CII and negative life events 0–6 months (p < 0.001), negative life events 0–12 months (p < 0.001) and negative coping styles (p = 0.007). SLE patients demonstrated greater negative life events over the past 12 months and tend to utilise greater negative disengaging coping skills. NPSLE patients demonstrate a potential relationship between negative life events, negative coping and cognitive dysfunction. The associations between cognitive changes and life stress and coping suggest the need for integrated behavioural strategies for treatment. Copyright © 2009 John Wiley & Sons, Ltd.

This study examined white matter (WM) structural and metabolic alterations in relation to cognition in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE).SLE can produce cognitive impairment even without overt neuropsychiatric features, but the pathogenesis of this dysfunction is not well understood. Our preliminary study of non-NPSLE found evidence correlating cognitive impairment with increased choline/creatine (Ch/Cr) in frontal lobe WM.Subjects included 60 non-NPSLE patients and 24 controls. Magnetic resonance imaging and magnetic resonance spectroscopy were performed, and a battery of neuropsychologic tests was administered. Structural and metabolic measures were analyzed and correlated with neuropsychologic data.No significant differences were found in total brain, gray matter, and WM volumes, or in frontal WM N-acetylaspartate/Cr, but the non-NPSLE group had significantly increased Ch/Cr in frontal WM. A WM cognitive score (WMCS) that included the Paced Auditory Serial Addition Task, Letter Fluency, and Animal Naming was found to correlate with total WM volume, and lower WMCS correlated with higher left frontal WM Ch/Cr.Non-NPSLE patients had frontal WM metabolic changes that correlated with cognitive impairment, whereas no cerebral atrophy or WM axonal damage was evident. These data confirm and extend our previous observations supporting the role of microstructural WM changes in the cognitive impairment of non-NPSLE patients. The data also suggest that the WMCS may be sensitive to cognitive dysfunction from myelin damage that develops before axonal injury.

OBJECTIVES To discuss the clinical manifestations and possible pathogenic mechanisms of the unusual syndrome of diffuse alveolar hemorrhage (DAH) and pulmonary capillaritis without thrombosis in the setting of the primary antiphospholipid antibody syndrome (PAPS). METHODS Four men with DAH and capillaritis in the setting of PAPS are identified. Their clinical presentations, laboratory, radiographic, and pathologic findings are reviewed as is their clinical course and response to therapy. In addition, the literature regarding DAH and pulmonary capillaritis in the setting of PAPS is reviewed. RESULTS The patients presented with dyspnea, hemoptysis, fever, hypoxia, and diffuse alveolar infiltrates; none had evidence of acute thromboembolic disease. All secondary causes of DAH were ruled out. All patients had positive testing for the lupus anticoagulant and high-titer anticardiolipin antibodies, including antibodies against the beta-2-glycoprotein I antigen. Three cases had lung biopsies that revealed pulmonary capillaritis and DAH with no evidence of thrombosis. All patients improved with high-dose corticosteroids. Recurrent disease in the setting of aggressive immunosuppression responded to intravenous immunoglobulin. Antiphospholipid antibody-mediated endothelial cell activation in the absence of thrombosis may induce capillaritis as seen in these cases. CONCLUSIONS The syndrome of DAH and pulmonary capillaritis is further defined. Evidence supports a causative relationship between PAPS, pulmonary capillaritis, and DAH in the absence of thromboembolic disease. Further elucidation of a possible nonthrombotic mechanism of antiphospholipid antibody-mediated pathology is needed to guide future therapies for this unusual manifestation of PAPS.

Abnormalities of inflammatory and hormonal measures are common in SLE patients. Although cognitive dysfunction has been documented in SLE patients, the biological mechanism of these deficits has not been clarified. The goal of this study was to explore the relationship between inflammatory and hormonal activity and measures of learning, fluency, and attention in systemic lupus erythematosus patients without neuropsychiatric symptoms (non-CNS–SLE), patients with rheumatoid arthritis (RA), and healthy controls (HC). Fifteen non-CNS–SLE patients, 15 RA patients and 15 HC participants similar in age, education, and gender (female) were compared on tests of cognition, depression, and plasma levels of interleukin-6 (IL-6), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S) and cortisol. Non-CNS–SLE patients demonstrated lower learning and poorer attention. Furthermore, non-CNS–SLE and RA patients had significantly lower levels of DHEA and DHEA-S than HC participants. Hierarchical regression analysis demonstrates that DHEA-S and IL-6 accounts for a unique portion of the variance in subject performance on measures of learning and attention after controlling for depression and corticosteroid treatment. This data highlights the value of hierarchical analyses with covariates, and provides evidence in humans of a relationship between peripheral cytokine levels and cognitive function. (JINS, 2001, 7, 745–754.)

Objective To investigate cerebral magnetic resonance imaging (MRI) abnormalities in relation to cognitive functioning in systemic lupus erythematosus (SLE) patients without a history of central nervous system (CNS) disease. Methods Ventricle-to-brain ratios (VBRs) and the total number of white matter hyperintensities (WMHIs) were computed in 20 female patients with non-CNS SLE using established MRI computer-generated quantification procedures. Comprehensive neuropsychological test scores across 8 domains were also obtained. Results A mean VBR of 2.83% (SD = 0.7) occurred in the non-CNS SLE patients compared with a VBR of 1.36% in a normative sample. The average number of WMHIs was 4.95 (SD = 6.0). Using a combined rating scale (VBR >2.25%, WMHIs >5), 7 of 20 MRI scans (35%) were classified as abnormal. Increased VBRs and larger numbers of WMHIs showed a trend association with longer duration of SLE. Thirty-five percent of the non-CNS SLE patients demonstrated neuropsychological deficits. No significant correlations were found between the VBR, total WMHIs, and cognitive scores. Comparisons of cognitively impaired and nonimpaired patients with non-CNS SLE revealed no significant differences across clinical characteristics or MRI values. Conclusion Quantified MRI analyses indicated atypical brain structure and an increased number of WMHIs in a subset of non-CNS SLE patients. However, these MRI abnormalities were not associated with functional abnormalities determined by comprehensive neuropsychological testing. Therefore, MRI analyses are not likely to provide additional clinical information on cognitively impaired SLE patients who have no other evidence of CNS involvement.

Neuropsychiatric symptoms are recognized to occur in a significant percentage of systemic lupus erythematosus patients and to be a leading cause of morbidity and morality in lupus. Recent findings regarding the clinical presentation, diagnosis, pathogenesis, and treatment of neuropsychiatric lupus erythematosus are reviewed. The study of neurocognitive deficits and psychosocial functioning in systemic lupus erythematosus patients continues to be an area of great research interest worldwide. Severe neuropsychiatric manifestations can be divided into diffuse, focal, and seizure presentations, which can each have a different etiopathogenesis. New techniques for magnetic resonance imaging and single-photon emission CT of the brain may improve the utility and sensitivity of these neuroradiographic tests. Certain combinations of serologic, cerebrospinal fluid, and neuroimaging tests appear to be most useful diagnostically when ordered based on the patient's neurologic presentation. The role of complement, cytokines, and endothelial cell activation in causing the vascular pathology observed in the brains of neuropsychiatric lupus erythematosus patients is an area of promising research. Treatment remains empiric, but intravenous pulse cyclophosphamide and intrathecal administration of immunosuppressive medications are new approaches that have been used successfully to treat patients with severe and refractory symptoms.

The effect of low dose methotrexate (MTX) on postoperative complications in rheumatoid arthritis patients undergoing elective total joint arthroplasty was observed prospectively in 32 patients. Patients were assigned to discontinue MTX the week prior to and during the week of surgery (Group 1, n=19) or to continue MTX throughout the perioperative period (Group 2, n=13). Nineteen patients in Group 1 had 26 procedures, with no postoperative infections. Thirteen patients in Group 2 had 16 procedures, with 4 postoperative infections: 2 infected prostheses, 1 infected joint fusion, and 1 deep wound infection (P=.03). No patient had a postoperative flare of rheumatoid arthritis. Temporary discontinuation of MTX prior to joint arthroplasty appears to decrease the risk of postoperative infection.

Background Mild cognitive dysfunction (MCD) is common in patients with systemic lupus erythematosus (MCD-SLE) but few studies have investigated potential site differences. Methods SLE patients from Denver, CO, and New York, NY, were enrolled in two different cognition studies employing similar screening methods. Using the resulting neuropsychological scores, cognitive impairment was calculated using a cognitive impairment index (CII). Results The rate of MCD-SLE was 24% at the Denver, CO, site and 60% at the New York, NY, site. The mean CII was 2.6 ± 2.3 versus 4.4 ± 2.7, respectively ( p = 0.005). The NY participants had a significantly longer disease duration ( p = 0.13) and higher American College of Rheumatology SLE criteria scores ( p > 0.001). NY participants had a higher frequency of impairment in semantic verbal fluency ( p = 0.005), visuomotor speed ( p = 0.013), and motor sequencing ( p = 0.001). A correlation was found between cognitive impairment and SLE disease duration ( p = 0.03). Conclusions The rate of MCD-SLE was greater in SLE patients from New York, NY, compared to patients in the Denver, CO, area. The greater duration of disease and higher prevalence of medical complications in the NY group might contribute to this difference. Findings suggest that MCD-SLE may differ by site, but future studies that better evaluate site or selection bias are recommended.

Objective. To test the usefulness and cost savings resulting from application of the new American College of Rheumatology (ACR) guidelines for assessing the risk for the development of clinically significant liver disease in rheumatoid arthritis (RA) patients treated with methotrexate (MTX). Methods. One-hundred twelve MTX-treated RA patients were prospectively followed up for MTX hepatotoxicity and underwent liver biopsies according to modified guidelines of the Psoriatic Task Force (PTF). All biopsies were graded according to the Roenigk classification. The new ACR recommendations were then retrospectively applied to test their usefulness and cost-effectiveness in this cohort. Results. Based on the PTF guidelines, 66 patients underwent liver biopsies; a total of 110 liver biopsies were performed. Two patients had biopsy-related complications. Five patients were found to have Roenigk grade IIIB or IV histologic abnormalities. The total cost for this group was $111,380. Applying the new ACR criteria, only 15 patients would have undergone liver biopsies; there would have been a total of 18 biopsies, with no complications. Four of the 5 patients with Roenigk grade IIIB or IV liver abnormalities would have been identified. One patient with insulin-dependent diabetes mellitus (IDDM) who was found to have cirrhosis (Roenigk grade IV) on liver biopsy as a result of use of the PTF guidelines would have been missed with use of the ACR guidelines. The total cost for the group receiving biopsies based on the ACR guidelines would have been $16,956. Overall, the new ACR guidelines had 80% sensitivity and 82% specificity and resulted in a cost savings of $1,430 per patient. Conclusion. The new ACR guidelines on MTX monitoring and biopsy surveillance appear to be clinically useful and result in considerable cost savings. However, 1 IDDM patient with significant liver histologic abnormalities would have been missed. We suggest that IDDM be added to the ACR guidelines as a risk factor for MTX hepatotoxicity.

Ochronosis is the bluish-black discoloration of tissues typically due to the rare autosomal-recessive metabolic disorder alkaptonuria, caused by a mutation of the HGD gene on chromosome 3. This gene mutation results in a deficiency of homogentisate 1,2-dioxygenase, leading to the accumulation and deposition of homogentisic acid in cartilage and other connective tissues. …

Objective. To determine the prevalence of magnetic resonance imaging (MRI) lesions in systemic lupus erythematosus (SLE) patients without a history of neuropsychiatric symptoms and to correlate any MRI abnormalities with the patient's other disease manifestations or treatment. Methods. Prospective study of 32 consecutive patients with SLE without a history of neuropsychiatric symptoms, from inpatient and outpatient rheumatology services, who underwent MRI scan during a 3-year period. Results. Five patients had MRI abnormalities consisting of white matter lesions or periventricular hyperintensities; this is similar to the prevalence of these abnormalities in the general population. Conclusion. The prevalence of silent brain MRI abnormalities is not increased in SLE patients who do not have a history of neuropsychiatric manifestations.

Methods All patients with rheumatoid arthritis (RA) attending an outpatient rheumatology clinic at a major military medical center over 6 years were included in follow-up for the development and subsequent course of sacral insufficiency fractures. Results Sacral insufficiency fractures developed in 4 of 386 patients. Consistent with the literature, patients were female, elderly, and/or postmenopausal, had severe or long-standing disease, and were taking corticosteroids. The correct diagnosis was initially delayed because radiographs were normal but was later established with bone scan and sacral computerized tomography. Each patient improved with calcitonin and/or physical therapy over time. Conclusions Patients with RA represent a unique subgroup predisposed to insufficiency fractures because of multiple osteoporotic risk factors. Patients who have RA and acute low back or buttock pain should be evaluated aggressively for sacral insufficiency fractures with bone and/or computed tomography scans regardless of normal plain radiographs.

Objective. To ascertain the effects of low-dose methotrexate (MTX) on bone metabolism and histomorphometry in rats. Methods. Female Sprague-Dawley rats (6 months old, n = 42) were divided into the following 4 groups: intraperitoneal (IP) injections of MTX, with and without ovariectomy, and IP saline (controls), with and without ovariectomy. Injections were given for 16 weeks. The MTX dose was equivalent to a standard dose for rheumatoid arthritis in humans that would yield similar serum MTX levels (0.6 ± 0.1 μmoles). Results. Bone formation (assessed by serum alkaline phosphatase and osteocalcin levels and histomorphometry) was significantly lower in the MTX groups, and bone resorption (assessed by urinary hydroxyproline levels and histomorphometry) was increased in the MTX groups. Bone mass was significantly diminished in the MTX groups. Conclusion. Prolonged administration of lowdose MTX in rats causes significant osteopenia via suppression of osteoblast activity and stimulation of osteoclast recruitment, which results in increased bone resorption.

Objective: This study examined the relationship between immune, cognitive and neuroimaging assessments in subjects with systemic lupus erythematosus (SLE) without histories of overt neuropsychiatric (NP) disorders. Methods: In total, 84 subjects with nonNPSLE and 37 healthy controls completed neuropsychological testing from the American College of Rheumatology SLE battery. Serum autoantibody and cytokine measures, volumetric magnetic resonance imaging, and magnetic resonance spectroscopy data were collected on a subset of subjects. Results: NonNPSLE subjects had lower scores on measures of visual/complex attention, visuomotor speed and verbal memory compared with controls. No clinically significant differences between nonNPSLE patients and controls were found on serum measures of lupus anticoagulant, anticardiolipin antibodies, beta 2-glycoproteins, or pro-inflammatory cytokines (interleukin (IL)-1, IL-6, interferon alpha (IFN-alpha), and interferon gamma (IFN-gamma)). Higher scores on a global cognitive impairment index and a memory impairment index were correlated with lower IFN-alpha. Few associations between immune functions and neuroimaging parameters were found. Conclusions: Results indicated that nonNPSLE patients demonstrated cognitive impairment but not immune differences compared with controls. In these subjects, who were relatively young and with mild disease, no relationship between cognitive dysfunction, immune parameters, or previously documented neuroimaging abnormalities were noted. Immune measures acquired from cerebrospinal fluid instead of serum may yield stronger associations.

Objective: Memory impairment is common in patients with systemic lupus erythematosus (SLE). This study examined hippocampal volumes and neurometabolic alterations in relation to memory function in SLE patients without a history of neuropsychiatric syndromes (nonNPSLE). Methods: Subjects included 81 nonNPSLE patients and 34 healthy controls. Volumetric magnetic resonance imaging and magnetic resonance spectroscopy of the right and left hippocampal areas (RH, LH) were performed. Verbal and visual memory tests were administered and a Memory Impairment Index (MII) was derived from standardized tests. Results: Higher memory impairment (MII) was correlated with lower RH glutamate + glutamine/creatine ( p = 0.009) and lower RH N-acetylaspartic acid/creatine ( p = 0.012) in nonNPSLE patients. A trend for a negative correlation between RH and LH volumes and MII was evident for absolute hippocampal volumes. Lower RH glutamate + glutamine/creatine was also correlated with worse performance in a mean visual memory index ( p = 0.017). Conclusions: An association between reduced memory and lower N-acetylaspartic acid/creatine in the RH suggests neuronal damage in nonNPSLE patients with very mild and early disease. Alterations in glutamate + glutamine/creatine further indicate early metabolic changes in nonNPSLE are related to memory impairment, a finding that might suggest that memory impairment relates to presynaptic glutamatergic dysfunction in the hippocampus.

purpose: Fibromyalgia is a common pain syndrome that is often associated with sleep disturbances. The most characteristic pattern noted on formal steep study is α-wave intrusion on δwave sleep. This nonrestorative sleep pattern may be endogenous, or caused by any of a number of sleep disturbances. Our goal was to determine the frequency of sleep apnea and its relationship to a nonrestorative sleep pattern in our patients with fibromyalgia syndrome. patients and methods: All new fibromyalgia patients seen in the Rheumatology Clinic at Fitzsimons Army Medical Center were screened using history and physical examination for suspicion of sleep apnea. When this condition was suspected, the patients underwent formal polysomnography to delineate any sleep disturbance. results: Four of 92 women, and 13 of 25 men with the new diagnosis of fibromyalgia syndrome underwent polysomnography. Of the women, 22% (2 of 92) had significant sleep apnea at formal evaluation; both were obese and had obstructive findings. In contrast, 44% (11 of 25) of the men had significant sleep apnea. conclusions: Sleep apnea is not a significant cause of fibromyalgia symptoms in females. In male patients with fibromyalgia, sleep apnea was observed in a large percentage. Fibromyalgia may be a marker for occult sleep apnea in males.

Objective. Familial associations of the antiphospholipid antibody syndrome (APS) offer the opportunity to study genetic mechanisms of autoantibody production and disease, but are unusual. We identified a family, including identical twins and their mother, in which all members had systemic lupus erythematosus (SLE) and presented with different manifestations of the APS. Methods. Review of case histories and clinical laboratory results, antiphospholipid antibody (aPL) studies, complement C4 protein and gene analysis, and HLA typing of family members were performed. Results. Each of the 3 family members presented with a different clinical association of the APS. These various clinical presentations were closely temporally related. No particular aPL activity could be separated out that would account for the different manifestations, although the twin with thrombocytopenia and livedo reticularis had a strikingly high IgM anticardiolipin antibody level. C4A or C4B deficiencies could not be implicated in the autoimmune process. However, the mother and the twins shared the HLA haplotype that included the class II antigens DR4, DRw53, and DQw7, which has previously been associated with aPL production. Conclusion. This family study emphasizes the different clinical associations of aPL production in SLE. In addition to genetic influences that appear to include HLA class II antigens, the clinical presentations also suggest an environmental trigger.

We describe, to our knowledge for the first time in the English literature, the successful use of cadaveric dura mater in reinforcing the sclera in a rheumatoid arthritis patient with scleromalacia perfora ns.

• Background.— Microscopic polyarteritis is a systemic small-vessel vasculitis that primarily involves the kidneys but may also affect the skin and other organ systems. This unique vasculitis represents one of the vasculitides with antineutrophil cytoplasmic antibodies, usually of the perinuclear immunostaining pattern (P-ANCA, antimyeloperoxidase antibodies). The objective of this case report is to describe microscopic polyarteritis, the use of antineutrophil cytoplasmic antibodies, and the unique cutaneous histopathologic features of our patient. Observations.— We describe a patient with clinical findings consistent with microscopic polyarteritis, the presence of antimyeloperoxidase antibodies, and a specific cutaneous leukocytoclastic vasculitis. This report further characterizes the histopathologic features by demonstrating that the anatomic location of the cutaneous vasculitic lesions is at the level of the dermal arteriolar vessels and postcapillary venules. Conclusions.— Cutaneous arteriolar leukocytoclastic vasculitis may prove to be a histologic hallmark of microscopic polyarteritis when it presents in the skin. However, further case comparisons and histopathologic investigations are needed. The consequences of this systemic vasculitis, if not adequately treated, may be life threatening. Recognition of clinical features, use of antineutrophil cytoplasmic antibodies, and demonstration of a cutaneous arteriolar leukocytoclastic vasculitis may aid in the diagnosis and subsequent treatment of patients followed up by dermatologists for vasculitic ulcers. ( Arch Dermatol. 1992;128:1223-1228)

Hypothyroidism presenting with classic signs and symptoms is generally easily recognized. Less often, patients with hypothyroidism may present with symptoms and laboratory abnormalities suggestive of cardiovascular disease. In this article, we describe six such patients. Hypothyroidism was suspected when creatine phosphokinase (CPK) levels were persistently elevated. The diagnosis was confirmed by thyroid function tests, and thyroid hormone therapy resulted in resolution of symptoms and CPK elevations. Persistently elevated CPK levels associated with cardiovascular symptoms but without demonstrable myocardial damage should prompt consideration of covert hypothyroidism.

While studying the alpha beta T cell receptor repertoire in rheumatoid arthritis (RA) patients, we found that the frequency of V beta 14+ T cells was significantly higher in the synovial fluid of affected joints than in the peripheral blood. In fact, V beta 14+ T cells were virtually undetectable in the peripheral blood of a majority of these RA patients. beta-chain sequences indicated that one or a few clones dominated the V beta 14+ population in the synovial fluid of individual RA patients, whereas oligoclonality was less marked for other V beta's and for V beta 14 in other types of inflammatory arthritis. These results implicate V beta 14-bearing T cells in the pathology of RA. They also suggest that the etiology of RA may involve initial activation of V beta 14+ T cells by a V beta 14-specific superantigen with subsequent recruitment of a few activated autoreactive v beta 14+ T cell clones to the joints while the majority of other V beta 14+ T cells disappear.

Subcutaneous sarcoidosis and sarcoid tenosynovitis are unusual manifestations of systemic sarcoidosis. We report two Japanese women with disseminated sarcoidosis presenting with subcutaneous and tenosynovial involvement demonstrated by computed tomography and magnetic resonance imaging. Sarcoidosis must be considered in the differential diagnosis of unexplained subcutaneous nodulosis or tenosynovitis in patients with or without a previous diagnosis of sarcoidosis.

Objective To examine neuropsychological and neurologic functioning in systemic lupus erythematosus (SLE) patients without histories of overt neuropsychiatric disorders (non-NPSLE patients). Methods Sixty-seven non-NPSLE patients and 29 healthy controls were administered a standardized neurologic examination and measures of cognition, depression, and self-reported cognitive functioning. Results Non-NPSLE patients scored lower than controls on the total score of the neurologic examination (P < 0.0001). Item analysis indicated that the physician's description of mentation and mood was the only item that differed significantly between patients with SLE and controls (P = 0.004). Compared with controls, non-NPSLE patients had significantly higher rates of impairment on logical reasoning (P = 0.012) and verbal memory (P = 0.03), and trends toward greater impairment on visual attention (P = 0.06) and working memory (P = 0.098). There were no significant differences between non-NPSLE patients and controls on a cognitive impairment index (CII): 20.9% of non-NPSLE patients and 13.8% of controls were impaired. Patients with SLE scored higher on depressive symptoms (P < 0.0001) and perceived cognitive difficulties (P = 0.001) compared with controls. Conclusion The utility of a standardized neurologic examination in SLE for excluding overt neurologic dysfunction and assuring a non-NPSLE group selection was demonstrated. In contrast to our earlier study, we did not find differences between non-NPSLE patients and controls on the CII. Slightly lower CII scores in non-NPSLE patients and higher CII scores in controls may have reduced cognitive differences between these groups. Non-NPSLE patients demonstrate specific decline in the areas of attention, memory, and reasoning; continued studies of associated brain regions are warranted.