Sterling G. West

Association of psychiatric manifestations with antibodies to ribosomal p proteins in systemic lupus erythematosus

PURPOSE The goal of this study was to determine whether elevated serum levels of antibodies to ribosomal P proteins (anti-P antibodies) are associated with neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE). Additional experiments examined characteristics of these antibodies that might be associated with pathogenicity. PATIENTS AND METHODS A large number of serum samples were collected from patients with SLE, control subjects with other rheumatic diseases, and normal individuals. At the time serum samples were obtained, patients with SLE were categorized according to the presence of psychosis, depression, and other manifestations of central nervous system (CNS) involvement. Serum anti-P antibody activity was quantitated by an enzyme-linked immunosorbent assay utilizing a synthetic peptide corresponding to the major P protein epitope. RESULTS In a group of 79 normal individuals, mean (+/- SE) IgG anti-P activity was 0.01 +/- 0.003 and no individuals had values greater than 3 SD above the mean. Similar results were obtained measuring IgM anti-P activity. Normal levels were found in all sera from 21 patients with rheumatoid arthritis. Of 119 patients demonstrating various patterns of antinuclear and anticytoplasmic antibody activity, elevated anti-P levels were found only in patients with SLE. Overall, 19% of 269 patients with SLE demonstrated elevated levels of IgG or IgM anti-P antibodies, including 14% of 187 patients without and 29% of 82 patients with neuropsychiatric manifestations. The frequency of positive test results varied greatly depending on the nature of the CNS involvement. The frequency in patients with severe depression (n = 8) and psychosis (n = 29) was 88% and 45%, respectively, compared with only 9% in patients with nonpsychiatric neurologic disease (n = 45). For the entire SLE group, the odds ratio for the association of anti-P antibodies and severe psychiatric manifestations was 7.63 with a 95% confidence interval of 3.61 to 16.14. In a review of 187 patients with SLE originally classified as not having severe psychiatric disease, seven of 10 patients being treated with antidepressant medications had elevated levels of anti-P antibodies. In serial studies, the serum level of anti-P antibodies appeared to correlate with the activity of psychiatric disease and did not correlate with the activity of other manifestations of SLE. Anti-P antibodies in nearly all patients were IgG and directed primarily to the C-terminal 11 amino acids of the P protein. No difference in these characteristics was observed when patients with and without psychiatric manifestations were compared. Paired serum and cerebrospinal fluid (CSF) samples were also obtained from eight patients with active neuropsychiatric disease. Even when expressed as a fraction of the total IgG present, anti-P activity was markedly lower in CSF than in serum. CONCLUSIONS Elevated levels of autoantibodies to the C-terminal region of ribosomal P proteins appear to be a specific marker for SLE, and are associated with both severe depression and psychosis in this disease. This assay is easily reproducible and may help distinguish SLE-induced psychiatric disease from that caused by other processes.

Neuropsychiatric lupus erythematosus: A 10-year prospective study on the value of diagnostic tests

PURPOSE To evaluate which serologic, cerebrospinal fluid (CSF), and neuroradiographic tests alone or in combination are most useful in the diagnosis of neuropsychiatric lupus erythematosus (NPLE). PATIENTS AND METHODS Prospective study of patients with systemic lupus erythematosus (SLE) hospitalized with neuropsychiatric disease between January 1982 and December 1991. Special tests evaluated as part of this study included serum antinuclear antibodies, complement levels, serum and CSF antineuronal antibodies, CSF special protein studies (immunoglobulin G [IgG] index and oligoclonal bands), serum antiribosomal-P antibodies, serum antiphospholipid antibodies, and cranial magnetic resonance imaging (MRI). Diagnostic sensitivity, specificity, and positive predictive value (PPV) were determined for single tests and combinations of tests. RESULTS Fifty-two NPLE patients were categorized by neuropsychiatric presentation (32 diffuse, 10 focal, and 10 complex presentations) and compared to 14 SLE control patients. Each NPLE patient with a diffuse or complex presentation had abnormal CSF IgG index/oligoclonal bands, elevated CSF antineuronal antibodies, and/or serum antiribosomal-P antibodies, yielding a sensitivity of 100%, specificity of 86%, and PPV of 95% for this combination of tests. Nine of 10 patients with focal presentations and all with complex disease had evidence of vasculitis/livedo reticularis, antiphospholipid antibodies, and/or a cranial MRI with multiple lesions, giving a sensitivity of 95%, specificity of 86%, and a PPV of 90% for this battery of tests. These combinations of tests correctly diagnosed all nine SLE patients whose initial diagnosis proved to be incorrect based on subsequent clinical course. Abnormal test results frequently normalized or improved with successful therapy. CONCLUSIONS Specific tests for CSF antibodies are most useful diagnostically in diffuse NPLE, implicating autoantibodies in the pathogenesis of this NPLE presentation. In those patients with diffuse NPLE who present with primarily psychiatric disease, serum antiribosomal-P antibodies appear to be helpful. In contrast, focal NPLE appears to be mostly secondary to vascular occlusion, and the presence of dermal vasculitis/livedo reticularis, antiphospholipid antibodies, and/or an abnormal cranial MRI are most helpful diagnostically. Patients with complex presentations demonstrate abnormalities characteristic of both diffuse and focal NPLE. Abnormal tests can be followed serially and appear to correlate with clinical responses to therapy.

Intracranial plasma cell granuloma

The first case of an intracranial plasma cell granuloma is presented. An associated polyclonal gammopathy was another remarkable feature. Routine and special stains of histologic sections as well as electron microscopy characterized such lesions. Immunofluorescent studies revealed a heterogeneous population of plasma cells. When the granuloma was removed, the polyclonal gammopathy resolved, and neither have recurred with eight months of follow‐up. It is suggested that prior reports of meningiomas with conspicuous plasma cell‐lymphocytic components may in reality be plasma cell granulomas and could be differentiated by electron microscopy.

Sleep apnea in male patients with the fibromyalgia syndrome

PURPOSE Fibromyalgia is a common pain syndrome that is often associated with sleep disturbances. The most characteristic pattern noted on formal sleep study is alpha-wave intrusion on delta-wave 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, 2.2% (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.

Sacral insufficiency fractures in rheumatoid arthritis.

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.

Covert hypothyroidism presenting as a cardiovascular event

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.

Retinal vasculopathy associated with systemic light chain deposition disease.

A 35-year-old black male with the abrupt onset of blurred vision and decreased visual acuity was found to have severe retinal vasculopathy associated with systemic light chain deposition disease. While ocular manifestations are frequently reported in other plasma cell dyscrasias, ophthalmologic symptoms have not been previously reported in systemic light chain deposition disease alone. A possible mechanism of light chain deposition and damage to the retinal vasculature is proposed.

Henoch-Schonlein Purpura Followed by Wegener's Granulomatosis

A 13-year-old girl was evaluated for polyarthritis, abdominal pain, and palpable purpura of the lower extremities. Findings of a complete blood count, blood chemistries, liver enzymes, and coagulation studies were all normal. Urinalysis revealed 2+ proteinuria, with 705 mg of protein per 24 hours (0.705 g/dL) . The Wintrobe erythrocyte sedimentation rate (ESR) was 30 mm/hr. To rule out other vasculitic processes, tests were performed for rheumatoid factor, antinuclear antibody, rapid plasma reagin (RPR), hepatitis B surface antigen, anti-neutrophil cytoplasmic antibody (C-ANCA), complement (C3, C4, and CH5o), cryoglobulins, and