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By taking a careful patient history, conducting a thorough physical examination, knowing the clinical features of vasculitis, and using selected laboratory tests, the physician can diagnosis vasculitis tentatively. Recognizing the pattern of organ involvement provides a clue to the type of vasculitis present. Serologic laboratory tests for ANCAs or hepatitis B or C may help confirm the presence of the underlying vasculitis, and a definitive diagnosis can be confirmed by a biopsy of involved tissue or by angiography.

Background: Neutrophilic and lymphocytic vascular inflammation is common in vasculitis associated with connective tissue disease (CTD). We recently identified eight patients with CTD and eosinophilic vasculitis., Objective: The purpose of this study was to characterize a variant form of vasculitis in CTD with eosinophilic infiltration., Methods: Of 98 CTD patients with cutaneous necrotizing vasculitis, eight were found with predominantly eosinophilic vascular infiltration. Nine CTD patients with cutaneous neutrophilic vasculitis were identified for comparison. Clinical and laboratory findings were reviewed and compared. Indirect immunofluorescence for eosinophil granule major basic protein (MBP), neutrophil elastase, and mast cell tryptase was performed on lesional tissue. MBP levels and eosinophil survival enhancing activity were assayed in sera from three patients., Results: The patients with eosinophilic vasculitis had depressed serum complement levels and peripheral blood eosinophilia; MBP levels were elevated in serum and eosinophil survival was prolonged. Immunofluorescence of tissue showed marked angiocentric eosinophil MBP staining with peripheral neutrophil elastase staining; mast cell tryptase staining was notably absent. The patients with neutrophilic vasculitis were variably hypocomplementemic and did not have peripheral blood eosinophilia. Immunofluorescence showed marked angiocentric neutrophil elastase staining with scattered eosinophil MBP staining; mast cell tryptase staining showed normal mast cell numbers., Conclusion: Patients with eosinophilic vasculitis, CTD, and hypocomplementemia show vessel wall destruction in association with vessel wall deposition of cytotoxic eosinophil granule MBP, which suggests that eosinophils mediate vascular damage in this disease process. In addition, perivascular mast cells appear diminished, thereby suggesting that mast cell degranulation occurs.

There are few controlled trials of immunosuppressive therapy for vasculitis, making the further study of long-term outcome of these diseases with contemporary modes of management necessary. Relapse is frequent in many forms of vasculitis. The consequences of immunosuppressive therapy, including opportunistic infection, have been emphasized. Novel forms of therapy have been described in small series and case reports, although the precise role of such therapies in the treatment of vasculitis in general is far from certain in the absence of collaborative, multicenter controlled studies. The relationship between vasculitis and hepatitis C virus has prompted the use of interferon therapy in the treatment of vasculitic complications resulting from this infection.

We tested sera from 56 patients to determine the seroprevalence of antibodies to hepatitis C virus (HCV) in polyarteritis nodosa (PAN), to assess the specificity of these antibodies for hepatitis C virus encoded antigens, and to evaluate the clinical features in patients with HCV infection and PAN. Eleven (20%) were positive for anti-HCV by an enzyme immunoassay. Three (5%) had specific antibodies to HCV encoded antigens detected by recombinant immunoblot assay (RIBA II) and had HCV RNA detected by polymerase chain reaction. Patients with HCV infection were more likely to have liver and skin involvement and a diminished serum complement.

Objective: To explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis., Design: Case series of patients with seropositive rheumatoid arthritis., Setting: The outpatient clinic of the Division of Rheumatology, Mayo Clinic., Patients: One hundred and two patients with seropositive, erosive rheumatoid arthritis and a minimum disease duration of 3 years., Measurements: Patients were genotyped for both HLA-DRB1 alleles and were categorized according to the expression of one or two disease-linked HLA-DRB1 alleles. Identification of HLA-DRB1 alleles was done by the polymerase chain reaction and subsequent oligonucleotide hybridization. Homozygosity for allelic variants was confirmed by sequence analysis. Immunogenetically defined patient subgroups were retrospectively evaluated for joint destruction and patterns of disease manifestation, including rheumatoid organ disease., Results: Of 102 patients, 98 (96%) expressed the disease-linked sequence polymorphism. Forty-seven patients (46%) carried a double dose of the relevant sequence stretch: Twenty-eight patients expressed HLA-DRB1*04 variants on both alleles, and 19 combined an HLA-DRB*04 variant with HLA-DRB1*0101 or DRB1*1402. Nodular disease was present in 100% of patients typed as HLA-DRB1*04/04 and in 59% of patients typed as HLA-DRB1*04 and who had inherited only a single dose of the disease-linked sequence polymorphism (P < 0.0001). Major organ systems were involved in 61% and 11% of these two patient groups, respectively (P < 0.0001); and joint surgery was required in 61% and 25% (P < 0.002), respectively. Patients typed as HLA-DR*04/01 had intermediate clinical courses., Conclusion: Genotyping patients with rheumatoid arthritis for both HLA-DRB1 alleles identifies clinical subsets with distinct profiles of disease manifestations.

A large variety of vasculopathic syndromes are uncommonly associated with malignancies. Vasculitis is usually manifested by skin lesions and is generally associated with hematologic malignancies rather than solid tumors. Evidence of autoantibodies, immune complexes, and complement consumption is typically absent. Myelodysplastic syndromes can be confidently linked to vasculitis on the basis of recent literature. The temporal relationship of malignancy to vasculitis development is variable except that vasculitis generally follows the discovery of hairy cell leukemia and splenectomy. Vasculitis may occasionally be a complication of chemotherapy, radiation therapy, and bone marrow transplantation. Occasionally, malignant disorders may mimic vasculitic syndromes. The etiopathogenesis of vasculitis in patients with malignant disorders is unknown. The recent literature on vasculitis and malignancy addresses predominantly case reports and small patient cohorts and identifies clinical characteristics rather than pathogenic mechanisms.

The myelodysplastic syndromes are characterized by ineffective hematopoiesis with possible transformation to acute nonlymphocytic leukemia. We describe a patient with refractory anemia with excess blasts with unusual rheumatic manifestations of vasculitis, migratory synovitis, arthralgias, and myalgias. A retrospective review over a 6-month period of 162 patients with myelodysplastic syndromes found 16 patients (10%) with several rheumatic manifestations. We divided these manifestations into 4 different categories: cutaneous vasculitis, "lupus-like syndrome," neuropathy, and patients with both a rheumatic disease and a myelodysplastic syndrome. There were 7 with cutaneous vasculitis including leukocytoclastic vasculitis and other individual cases of urticarial vasculitis and panniculitis; 3 with lupus-like manifestations with histological evidence of an inflammatory process; 3 with neuropathic manifestations including peripheral neuropathy, mononeuritis with foot drop, and chronic inflammatory demyelinating polyneuropathy; and 3 patients in which their myelodysplastic syndrome was diagnosed after their rheumatic disease was known, including rheumatoid arthritis. Sjögren's syndrome and mixed connective tissue disease. The class with refractory anemia with excess blasts had 9 patients with rheumatic manifestations but also had the largest number of patients in the study (46/162 or 29%). Three of the 16 patients died, all from the refractory anemia with excess blasts class, reflecting the known mortality in this group of patients. We believe there is a significant association between myelodysplastic syndromes and rheumatic manifestations.

Vasculitis may accompany rheumatoid arthritis. One must distinguish between vascular involvement associated with the pathogenesis of rheumatoid arthritis, isolated digital vasculitis, and the syndrome of clinical rheumatoid vasculitis. The cause of clinical rheumatoid vasculitis is unknown. High titers of rheumatoid factor, cryoglobulins, diminished circulating complement, an increased prevalence of HLA-DR4, and the pathologic findings suggest an immune etiology. However, similar, but perhaps less pronounced, abnormalities occur in uncomplicated rheumatoid arthritis, and these findings are not universal in complicating vasculitis. Classic cutaneous clinical manifestations include ischemic ulcers, digital gangrene, and palpable purpura. Mononeuritis multiplex is another classic presentation of rheumatoid vasculitis. Small digital infarctions may accompany other manifestations in clinical vasculitis or may occur alone as isolated digital arteritis, in which case the prognosis is relatively favorable. Weight loss, pleuritis, pericarditis, ocular inflammation, splenomegaly, hepatomegaly, and Felty's syndrome have also been reported in association with rheumatoid vasculitis. Although renal involvement has been considered unusual in rheumatoid vasculitis, several studies suggest that this may be more common than previously recognized. Ideally, a biopsy or an angiogram confirms the diagnosis of rheumatoid vasculitis, but often the diagnosis rests upon the clinical picture. In general, blind biopsies are not helpful, although one series indicated that a blind rectal biopsy may be an exception to this rule. An elevated erythrocyte sedimentation rate, increased C-reactive protein level, anemia, thrombocytosis, hypoalbuminemia, and a positive rheumatoid factor are common laboratory findings. Leukocytosis, hypergammaglobinemia, leukocytopenia, an elevated creatinine level, and minimal abnormalities of the urinary sediment also occur in patients with rheumatoid vasculitis. However, these abnormalities overlap in patients with uncomplicated rheumatoid arthritis, and their role in distinguishing rheumatoid vasculitis from uncomplicated rheumatoid arthritis is limited. Other immunologic tests have no established clinical role in diagnosing rheumatoid vasculitis. Therapy depends upon the clinical manifestation of rheumatoid vasculitis. Uncomplicated rheumatoid arthritis deserves appropriate therapy, and general attention to nutrition, cessation of tobacco, and control of blood pressure are indicated for all patients. Isolated digital vasculitis generally requires no more than the usual treatment for uncomplicated rheumatoid arthritis. Appropriate dermatologic management is indicated for ischemic ulcers. Most clinical experience in managing more symptomatic rheumatoid vasculitis has focused on glucocorticosteroids, D-penicillamine, and cytotoxic immunosuppressive drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Polyarteritis is reviewed in detail including a discussion of the cause of arteritis and the effect on blood vessel physiology. The clinical feature of polyarteritis and an approach to the diagnosis are discussed. The controversies in the management of polyarteritis are reviewed, and new approaches to the management are introduced.

Several second-line antirheumatic agents possess both immunosuppressive and antimicrobial properties. Rifampin is an antimicrobial agent recently found to exhibit immunosuppressive activity in both animal and human studies. Intraarticular rifamycin SV, a rifampin derivative, has been reported to cause dramatic improvement in gonarthritis in 15 patients with rheumatoid arthritis (RA). These reports along with the personal observation of spontaneous improvement of arthritic symptoms in 2 patients with RA treated with rifampin at our institution, prompted us to conduct a pilot study using oral rifampin at 600-1200 mg daily in 8 patients with active, adult onset, seropositive RA. Although, no clinically important or statistically significant improvement occurred in any of the outcome variables measured (p greater than 0.12), the power of this study to detect such differences was limited. Alkaline phosphatase increased modestly in 7 patients. One patient developed an acute, drug induced, flu-like syndrome with marked elevation of liver enzymes which resolved promptly with drug withdrawal. We conclude that the potential effectiveness of oral rifampin therapy in RA is doubtful.

Rheumatoid arthritis (RA) was differentiated from systemic lupus erythematosus (SLE) by direct immunofluorescent techniques on skin specimens, using monospecific antisera for IgG, IgM, C3, C1q, properdin, and fibrin. Of 30 patients with RA studied, 20 had dermal vessel deposits of immunoglobulins and complement components in unaffected skin without the characteristic dermal-epidermal junctional fluorescence of SLE. Of 24 SLE patients studied, 24 had granular deposits of immunoglobulins and complement components in unaffected skin at the dermal-epidermal junction.

Five patients with Wegner's granulomatosis were found to have significantly raised serum immunoglobulin E (IgE) levels. The rise in IgE was not related to the extent of clinical involvement, was not part of a generalized serum immunoglobulin rise, and was not associated with eosinophilia. Raised serum IgE may be a clue to the pathogenesis of this disease.

Since 1973, we have identified and collected follow-up data on 16 patients with hypocomplementemic urticarial vasculitis. Preliminary diagnostic criteria are the presence of typical urticarial skin lesions and low levels of serum complement (all components), plus two of the following: dermal venulitis, arthritis, glomerulo-nephritis, episcleritis or uveitis, recurrent abdominal pain, and C1q precipitin in plasma. Exclusions are systemic lupus erythematosus, mixed cryoglobulinemia, elevated antinuclear antibody titer, hereditary deficiency of a complement component or of C1 esterase inhibitor, and presence of anti-native DNA or hepatitis B antigen. The renal involvement is relatively benign, and generally the patients do well and respond to specific treatment when this is indicated. Eight of 10 smokers studied had evidence of chronic obstructive pulmonary disease, 1 of whom died of this complication. In three patients, severe chronic obstructive pulmonary disease developed at a young age after relatively low pack-year cigarette smoking histories. Lung disease probably results from the interaction of two major risk factors-smoking and an immunologically mediated process that has not been identified.

We describe the clinical and laboratory characteristics of 52 patients with rheumatoid vasculitis whose condition was diagnosed at a tertiary care center between 1974 and 1981, and we report their survival and the factors that were associated with decreased survival. The patients with rheumatoid vasculitis had decreased survival in comparison with an age-, sex-, and region-matched general population. Their survival was also decreased in comparison to that of an incidence cohort of community patients with rheumatoid arthritis. In the latter cohort, decreased survival was confined to those patients with classic but not definite rheumatoid arthritis. After partial correction for referral bias, we found no difference in survival between the cohort with rheumatoid vasculitis and the cohort with classic rheumatoid arthritis. We found that the age at diagnosis of rheumatoid vasculitis, the therapeutic decisions before and at diagnosis, and the referral distance were the best predictors of survival. Abnormal urinary sediment and hypergammaglobulinemia also predicted poor survival, but because of a lack of specificity in a small number of clinically abnormal values, we urge a cautious interpretation of their importance.

Forty-one patients with rheumatoid arthritis, including 6 with acute vasculitis, 13 with chronic vasculitis, and 22 without vasculitis, were studied for evidence of intravascular coagulation and fibrinolysis (ICF). The mean plasma fibrinogen levels were elevated in all groups. The fibrinogen, platelet count, and fibrin split products were usually elevated in acute vasculitis. Fewer patients on corticosteroids had abnormal coagulation tests. Active plasmin was detected in 12 patients primarily with chronic vasculitis. Plasminogen activator activity was not diminished in vascular endothelium of normal appearing skin of those patients with or without vasculitis. None of the patients demonstrated decompensated intravascular coagulation and fibrinolysis. The results suggest overcompensated ICF occurring in rheumatoid arthritis, but rheumatoid patients with vasculitis cannot be clearly distinguished from those without vasculitis on the basis of the usual tests performed for coagulation and fibrinolysis abnormalities.

A study to determine the presence of immune deposits in the cutaneous vessels of normal-appearing skin was made in 39 patients with rheumatoid arthritis. Immune deposits in skin vessels were found in 20 of the 32 patients with seropositive rheumatoid arthritis. The frequency of such immune deposits was only slightly higher in patients with clinical vasculitis than in those without such vasculitis. There was an association among the presence of immune deposits in skin vessels, presence of antinuclear antibodies, and elevated serum levels of IgM and IgA. The major immunoreactants detected were IgM and C3. The presence of immune deposits in skin vessels does not differentiate seropositive rheumatoid aptients who have clinical vasculitis from those who do not have clinical vasculitis.

Fifty-three patients with polyarteritis who were followed up for at least 2 years were defined clinically and studied retrospectively to determine the influence of clinical factors and treatment on the prognosis. There was a spectrum of severity of disease, and the 5-year survival in the group was 55%. A small number of patients had evidence of ongoing immune-complex disease, as indicated by the presence of cryoglobulins or hepatitis Bs antigen or by diminished serum complement. These markers were not associated with distinct clinical features and did not influence prognosis. Organ involvement that most adversely affected prognosis was that of the gut and the kidneys. Six of 8 patients with bowel infarction or serious gastrointestinal bleeding died, and 6 of 10 patients with renal insufficiency died. Hypertension and peripheral neuropathy did not influence the prognosis. Thirty-six patients were treated with corticosteroids alone and 14 with a combination of corticosteroids and cytotoxic agents (3 received no treatment); the outcome was the same in both groups. Twenty-two in the steroid-alone group and six in the combination group were alive when last seen. Early deaths were usually due to complications directly related to the vasculitis, and late deaths were often due to cerebrovascular or cardiovascular complications. At the last follow-up, 18 patients were in remission, and 13 had inactive vasculitic disease and were on maintenance treatment.

We conducted a prospective study of captopril therapy in patients with scleroderma and combined hypertension and renal insufficiency. In all seven patients studied during a 1-year period, control of blood pressure was achieved, and in six of the seven, renal function stabilized or improved. The total daily dosage of captopril ranged from 32 to 100 mg, divided into doses taken every 6 to 8 hours. Although one patient had a suspected captopril-induced rash for a short time, none of the other patients had any adverse side effects. Renal biopsies were performed in six patients; in three of them, specimens were obtained both at the beginning and at the end of the study. The initial biopsy specimens showed changes that were similar to those described in other reports. Findings on repeat biopsies were unchanged except for evidence of chronicity. In the six patients with controlled blood pressure and improved or stabilized renal function, the improvement was maintained for 1 1/2 to nearly 3 years on this drug therapy. Using specific measurements of skin compliance and vascular blood flow in the upper extremities, we could detect no evidence, however, of concomitant improvement in these other features of the disease. Although the blood pressure was controlled with captopril, one patient had progressive skin induration, one had progressive pulmonary insufficiency, and another had progressive renal failure.

In a randomized, double-blind, controlled study, 28 patients with early scleroderma received dipyridamole (225 mg/day) and aspirin (975 mg/day) or placebo for 1-2 years. No significant clinical or objective laboratory improvement was noted in either group. Platelet survival time, plasma renin activity, and coagulation tests were not predictive of disease course. Biomechanical and vascular tests of the hands correlated with clinical extent of skin induration and presence of finger ulcers, respectively.

Thirty-four patients with systemic vasculitis were studied to determine the possible type and frequency of associated immunologic abnormalities. The patients were divided into three clinical groups--those with systemic vasculitis without respiratory tract involvement, those with systemic vasculitis with respiratory tract involvement (particularly Churg-Strauss vasculitis and Wegener's granulomatosis), and those with limited vasculitis without visceral involvement. A diminished level of serum complement was found in half the patients with systemic vasculitis without respiratory tract involvement. These patients usually had diffuse skin disease that often was associated with the presence of rheumatoid factor and cryoglobulinemia and most likely represented an immune-complex induced disease. The serum IgE often was elevated in patients who had systemic vasculitis with respiratory tract involvement, particularly those with Churg-Strauss vasculitis and Wegener's granulomatosis, and may be a clue to the pathogenesis in this group of patients.

Adult onset Still's disease is an acknowledged cause of fever of unknown origin. Eight patients with adult onset Still's disease each had a lymph node biopsy as part of their initial evaluation. Seven of 8 biopsies exhibited intense, somewhat atypical, paracortical immunoblastic hyperplasia. This nodal histology, while not specific for the disorder, appears distinct from that associated with rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus. This paracortical cellular proliferation with apparent nodal effacement, along with atypical immunoblasts, can simulate lymphoma. Adult onset Still's disease should be added to the differential consideration of benign lymph node histology simulating lymphoma.

The systemic necrotizing vasculitides are classified into vasculitic syndromes on the basis of the pattern of clinical and pathologic involvement. The vasculitides have certain common clinical and laboratory abnormalities. Systemic necrotizing vasculitis is diagnosed on the basis of clinical features, and the vascular nature of the disease is determined by biopsy of involved tissue or angiography. The outcome is dependent on the extent of visceral involvement. Vascular inflammation influences the physiologic features of the vessel and may trigger vasoconstriction. Although glucocorticoids combat the inflammation, they may augment vasoconstriction and platelet aggregation. These effects must be considered in designing a management approach and in evaluating the cause and management of ischemic complications.

The clinical and autopsy records of 65 patients with either polymyositis (24) or dermatomyositis (41) and pulmonary disease were reviewed. Pulmonary symptoms were recorded in 43 of the cases and included dyspnoea in 31, cough in 23, and chest pain in six. Interstitial lung disease was noted at autopsy in 27 patients; almost half of these had arthritis. Bronchopneumonia was found in 35 patients, 31 of these had received prednisone. Dysphagia was present in a similar proportion of patients with and without pneumonia. Pulmonary vasculitis was seen in five patients; pulmonary symptoms, arthritis, and raised erythrocyte sedimentation rate were present in four of these cases and all five had associated interstitial lung disease. Other pulmonary manifestations included pulmonary oedema, primary pulmonary malignancy, diffuse alveolar damage, fibrinous pleuritis, pulmonary emboli, and diaphragmatic atrophy. The mean survival after disease onset was 29 months but was much less for those with interstitial lung disease and pulmonary vasculitis.

A subgroup of patients with rheumatoid arthritis (RA) whose sera agglutinated sensitized sheep erythrocytes used for total hemolytic complement determination has been identified. These patients have higher titers of rheumatoid factor (RF) and more severe rheumatoid disease compared to controls. The agglutination of sensitized sheep erythrocytes by sera of some patients with RA may be related to qualitative or quantitative variations in their RF.

Systemic vasculitis is an unusual but recently recognized complication of hairy cell leukemia. We studied this relationship further in an attempt to better understand pathogenetic mechanisms of vasculitis. We examined the records of 129 cases of hairy cell leukemia seen at the Mayo Clinic between 1976 and 1983, and identified 2 cases with evidence of systemic vasculitis. The first of these cases is discussed in detail. Immunologic studies were performed but we were unable to demonstrate the presence of shared antigen on hairy cells and endothelial cells. The literature is reviewed and reports of this association are summarized. Possible mechanisms of vascular injury are discussed.

Study of involved and uninvolved skin from patients with necrotizing vasculitis revealed diminished tissue fibrinolytic activity deposition of immunoreactants in involved skin. In these patients, the depletion of tissue fibrinolytic activity is probably the result of vessel injury secondary to the local deposit of immunoreactants. In addition, there was diminished tissue fibrinolytic activity in uninvolved skin from patients with and without clinical skin involvement, unassociated with the deposition of immunoreactants. The precise mechanism for diminished tissue lytic activity in these latter patients is not known, but it may be associated with generalized activation of the coagulation and fibrinolytic mechanisms that result in local depletion of tissue fibrinolytic activity. These local changes may aggravate the clinical course of the disease as well as inhibit the healing of the lesions.

Glucocorticoids are potent anti-inflammatory agents that play an important role in the therapy of many patients with connective tissue diseases, including systemic lupus erythematosus, polymyalgia rheumatica, various types of vasculitis, and complications of rheumatoid arthritis. Glucocorticoids reduce the number and influence the function of lymphocytes, monocytes, and eosinophils in peripheral blood. Prolonged high doses of glucocorticoids result in decreased levels of immunoglobulins, particularly IgG. Granulocytes are increased in the peripheral blood, but their migration to sites of inflammation is diminished. Glucocorticoids inhibit release of lysosomal enzymes. Although they have no effect on the factor or factors that initiate inflammation, glucocorticoids have proved to be effective in the treatment of inflammatory manifestations of disease. Among significant adverse effects of glucocorticoid therapy are osteoporosis, aseptic necrosis of bone, and steroid myopathy.

In the three major morphologic groups of lupus nephritis--diffuse, focal proliferative, and membranous--glomerular deposition of immunoglobulins is usually a combination of IgG, IgM, and IgA and is not a good indicator of initial renal severity or outcome. In this study of 60 patients with systemic lupus erythematosus and nephritis, patients with exclusive or predominant glomerular deposition of IgG did not have more severe renal disease or a worse prognosis than those with combined IgG-IgM deposition.

Ankylosing spondylitis and rheumatoid arthritis share many common features. However the presence of rheumatoid factor, histologically classic rheumatoid nodules, and the histocompatibility cell wall antigen (HLA-B27) helps distinguish one from the other. Two cases are reported in which these features established the coexisting diagnoses of ankylosing spondylitis and rheumatoid arthritis.

Among 65 patients with necrotizing vasculitis, 45 had systemic and 20 had nonsystemic vasculitic neuropathy. In nonsystemic vasculitic neuropathy, clinically only nerves are affected; there are no, or few, constitutional symptoms or serological abnormalities. The clinical and pathological features are those of an ischaemic neuropathy caused by a necrotizing vasculitis of small arterioles. These 20 patients had neuropathic symptoms for a median time of 11.5 yrs (range 1-35 yrs). The clinical pattern of neuropathy was that of multiple mononeuropathy in 13, asymmetric neuropathy in 4, distal polyneuropathy in 3, and sensory polyneuropathy in 1. As compared with their initial evaluation, 8 are now worse, 5 are better, 4 are approximately the same, and 3 are dead from unrelated causes. Prednisone was thought to prevent the development of new lesions in some cases. By contrast, of the 41 patients with systemic necrotizing vasculitis whose outcome is known, 12 are dead (median time, 1.5 yrs, range 3 months-8 yrs) and 29 are alive (median time, 6 yrs, range 6 months-22 yrs).

Sjögren's syndrome (dryness of eyes, mouth, and other mucous membranes) may be associated with disease of joints, blood, internal organs, skin, and central and peripheral nervous systems. We reviewed 33 cases of primary Sjögren's syndrome and peripheral neuropathy evaluated by neurologic examinations and EMG at the Mayo Clinic from 1976 to 1988, and studied sural nerve biopsy specimens in 11 of them. Symmetric sensorimotor polyneuropathy occurred most frequently, followed by symmetric sensory neuropathy. Autonomic neuropathy, mononeuropathy, or cranial neuropathy (especially trigeminal neuropathy) was superimposed on generalized neuropathy in approximately one-fourth of patients. The course generally was slowly progressive, except for a few patients who may have improved with prednisone therapy. Although spinal ganglion involvement might have accounted for some of the clinical and neurophysiologic findings, we found evidence that necrotizing vasculitis was involved in fiber degeneration. All nerve biopsies revealed perivascular inflammatory infiltrates and other vessel abnormalities, which were diagnostic in two cases and strongly suggestive of necrotizing vasculitis in six cases. Axonal degeneration predominated over demyelination and sometimes was focal or multifocal. In neuropathy of unknown cause, particularly if it is sensory, autonomic, or involves trigeminal nerve, consider Sjögren's syndrome.

To evaluate the relationship between clinical manifestations and serologic markers in patients with systemic lupus erythematosus (SLE) and patients with an overlap syndrome, we reviewed the charts of 247 such patients who had been examined between 1975 and 1979. All patients with an overlap syndrome had a high frequency of arthritis and Raynaud's phenomenon and a low frequency of renal disease regardless of the presence or absence of antibody to nuclear ribonucleoprotein (anti-nRNP) and antibody to Sm antigen (anti-Sm). The presence or absence of anti-nRNP and anti-Sm did not distinguish whether a patient had SLE or an overlap syndrome and could not be used to predict clinical manifestations of disease.

The courses of 18 patients with arthritis and vasculitis in the first 2 years after onset of disease (mean follow-up, 54 months) were studied. The patients were categorized as having rheumatoid vasculitis, systemic vasculitis, and undifferentiated connective tissue syndrome. These patients cannot be distinguished on basis of organ involvement by vasculitis or histopathologic findings on biopsy, but can be separated clinically by the extent of joint involvement and the presence or absence of rheumatoid factor and antinuclear antibody. Early onset of vasculitis is associated with a poor outcome, especially in patients with rheumatoid arthritis, with rapid progression to vasculitic involvement of the viscera, resulting in death. On the basis of the 54-month follow-up period involving this selected series, the prognosis of patients with systemic vasculitis and undifferentiated connective tissue syndrome appears more favorable than that of patients with rheumatoid vasculitis.

Most of the patients with the Felty syndrome suffer from such complications as fevers, infections, cutaneous ulcers, and vasculitis. Unfortunately, there are no therapeutic interventions that are predictably beneficial. We report our experience with 20 patients who received parenteral gold therapy for 2 to 114 months (mean, 23.6 months). All had complications of the Felty syndrome. On parenteral gold therapy, 60% had a complete response, 20% had a partial response, and 20% were unresponsive by preselected criteria. No serious complications were encountered. We think that parenteral gold therapy should be considered early, before other agents, in the treatment of this condition.

A retrospective review was undertaken to ascertain whether there are distinctive histopathologic features of the lymphoid neoplasms that occur in patients with previous connective tissue disease. Of 29 patients studied, 12 had malignant lymphoma with diffuse large-cell cytomorphology. Only 1 of these 12 had an immunoblastic cell type. The remaining 17 patients had neoplasia of a widely diverse nature. Six had lymphocytic lymphoma (one nodular poorly differentiated, three diffuse poorly differentiated, and three diffuse well differentiated), two had Hodgkin's disease, three had plasma cell myeloma, and six had chronic lymphocytic leukemia. Data fail to confirm a relationship between lymphoid proliferations with immunoblastic morphology and connective tissue diseases.

Eight patients with Felty's syndrome who had associated fevers, cutaneous ulcers, or infections were treated with parenteral gold. A satisfactory response was noted in 7 of the 8 patients. Improvement in leukopenia (7/8), decrease in infections (5/8) and fevers (7/8), and healing of ulcers (4/5) were noted. We conclude that gold has a role in the treatment of this complication of rheumatoid arthritis.