Paul Katz

Increased risk of neisserial infections in systemic lupus erythematosus.

Survival in systemic lupus erythamatosus (SLE) continues to improve because of better ancillary care, earlier diagnosis, and earlier treatment. However, infection remains a leading cause of morbidity and mortality in this disease. Although corticosteroids and immunosuppresives increase the risk of opportunistic infection, the SLE patient is still most at risk from common bacterial pathogens. As the prototypic immune-complex disease, patients with active SLE have low circulating complement as well as a reticuloendothelial system (RES) saturated with immune complexes. It seems intuitive that SLE patients should be most at risk for organisms dependent for their removal on the RES or complement for opsonization or bacteriolysis. The current series presents four patients with SLE and disseminated neisseria infection and brings to 14 the number of patients in the literature with disseminated neisserial infection. They are typically young, female, with renal disease, and either congenital or acquired hypocomplementemia, and may present with all features of a lupus flare. Surprisingly, they are not all on corticosteroids or immunosuppressives and have some features that are unusual for non-SLE patients with these infections. There seems to be an over-representation of Nisseria meningitidis (despite potential reporting bias), and there ironically may be better tolerance with fewer fulminant complications in patients who have complement deficiencies. The best approach for the physician treating SLE is to immunize all SLE patients with available bacterial vaccines to N meningitidis and Streptococcus pneumonia, have a low threshold of suspicion for the diagnosis of disseminated neisserial or other encapsulated bacterial infection in the SLE patient who is sick, and to treat empirically with third generation cephalosporins after appropriate cultures.

Rheumatoid vasculitis: Experience with 13 patients and review of the literature

Rheumatoid vasculitis is an uncommon but potentially catastrophic complication of RA. There are few current extensive experiences and no consensus regarding the clinical, laboratory, histologic features, and management or prognosis of rheumatoid vasculitis. We therefore reviewed selected observations in 13 patients followed over the past decade and compared them with patients reported and with results of a survey of North American Rheumatologists. Our patients were seven men and six women (age, 33 to 70 years) who had had active RA for 4 to 36 years. They exhibited sensory neuropathy, mononeuritis multiplex, Felty syndrome, cutaneous lesions, leg ulcers, gangrene, anemia, leukocytosis, eosinophilia, high titers of RF, hypocomplementemia, and CICs or cryoglobulinemia approximately as frequently as other reported patients with rheumatoid vasculitis, but they displayed constitutional symptoms, subcutaneous nodules, ischemic changes, and proteinuria rather less consistently than in other series. These observations were not necessarily as expected by survey respondents. We, as in other series and suggested by survey respondents, tended to select penicillamine or cytotoxic drugs (or plasmapheresis) for patients with mononeuritis, gangrene, or leg ulcers, and nonsteroidal antiinflammatory drugs, antimalarials, gold, or penicillamine for sensory neuropathy or digital lesions. Four patients died, two deteriorated, and seven were stable or improved, a finding that was also similar to the experiences of others. Rheumatoid vasculitis is an uncommon, potentially catastrophic syndrome with varying clinico-pathologic features that have different prognostic implications and should be managed individually.

Rheumatoid vasculitis: diagnostic and therapeutic decisions

SummaryRheumatoid vasculitis is an uncommon but potentially catastrophic complication of RA. There are few extensive experiences recorded in the current literature and there is no consensus regarding the clinical features, laboratory findings, histologic pattern, prognosis, or appropriate management of this syndrome. We therefore surveyed 1,947 North American ARA members for their perceptions of rheumatoid vasculitis. Fourhundred twenty-eight surveys were returned, of which 290 were suitable for analysis. The majority of respondents were within 10 years of fellowships and were even distributed among private practice, and parttime and full-time academic positions. The respondents saw 15–50 rheumatoid arthritis (RA) patients weekly and less than five RA vasculitis patients annually. The majority correctly diagnosed two actual and complex case histories from patients with and without autopsy-proven vasculitis. Respondents associated the following features most strongly with rheumatoid vasculitis — mononeuritis multiplex, digital gangrene, digital ischemic lesions, nailfold ischemic lesions, non-healing leg ulcers, palpable purpura, fingertip nodules, sensory neuropathy, scleromalacia perforans, high titer rheumatoid factor, positive visceral angiography, cryoglobulinemia, hypocomplementemia, circulating immune complexes, and histologic necrotizing vasculitis or vascular transmural neutrophilia. Digital lesions or sensory neuropathy alone were not viewed as portending an ominous prognosis by most respondents and would have been treated with nonsteroidal anti-inflammatory drugs, antimalarials, gold salts, or D-penicillamine. Other clinical manifestations considered as reflecting rheumatoid vasculitis (gangrene, mononeuritis multiplex, ulcers) were thought to worsen prognosis and would have been managed more often with corticosteroids, D-penicillamine, cytotoxic agents or plasmapheresis. Rheumatoid vasculitis is viewed as a heterogeneous group of syndromes with varying clinical and histopathologic features, which have different prognostic implications, and therefore should be managed differently. While these data do not substitute for an extensive recorded series of patients, they provide useful information about community perceptions of an uncommon but difficult clinical problem. They identify the need for additional data to examine the validity of these attitudes.

Characterization of corticosteroid receptors in natural killer cells: comparison with circulating lymphoid and myeloid cells

Lymphocytes mediating natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities are relatively refractory to the changes in circulatory traffic and intrinsic function induced in other cell types by in vivo and in vitro corticosteroids (CS). To investigate if such drug resistance could be attributed to differences in the CS receptor number of affinity (Kd) of these cells, these characteristics were determined in purified populations of large granular lymphocytes (LGL), monocytes, neutrophils (PMN), and T cells. All cell types displayed a single class of CS receptor of uniform affinity; however, LGL resembled monocytes and PMN in receptor number and Kd while T cells had significantly fewer sites per cell with lower Kd. These studies suggest that the unresponsiveness of NK activity to CS is not secondary to differences in CS receptor capacity or affinity.

In vitro immunoglobulin production by mononuclear cells in rheumatoid arthritis.

Since patients with rheumatoid arthritis (RA) exhibit serum hypergammaglobulinemia and autoantibody (rheumatoid factor) production, we compared elaboration and control of in vitro RA mononuclear cell (MNC), Ig assayed by enzyme-linked immunoassays or by hemolytic plaque formation, in 37 RA patients and 17 normal subjects. We found (1) RA spontaneous plaque-forming cells were significantly reduced (RA 344 vs normal 627 PFC/10(6) MNC, P less than 0.002); (2) RA spontaneous IgG and IgM (but not IgA) elaboration was significantly diminished (IgG RA 339, normal 776; IgM RA 255, normal 869 ng/ml, P less than 0.001; IgA RA 87, normal 124); (3) RA stimulated IgG and IgM production (but not IgA) was also decreased (IgG RA 2434, normal 3862, P less than 0.06; IgM RA, 1676, normal 3323, P less than 0.005; IgA RA 1859, normal 2315); (4) reduced RA Ig elaboration was not clearly due to altered numbers of T or non-T cells, age, medications, clinical features of disease, or response kinetics; (5) relative improvement of RA in vitro IgG, but not usually IgM, secretion followed removal of adherent cells, addition of indomethacin or addition of mitomycin C-treated T cells; (6) MNC from synovial fluids, but not bone marrows, exhibited spontaneous Ig production in excess of stimulated synovial fluid cellular or peripheral blood Ig elaboration. These observations indicate selective impairment of peripheral blood MNC IgG and, particularly, IgM secretion in RA. This defect appears to reflect accessory cell influences which differ from normal as well as the sequestration of primed or activated cells in the synovial fluid.

IgM rheumatoid factor elaboration by blood, bone marrow, and synovial mononuclear cells in patients with rheumatoid arthritis

IgM rheumatoid factor (RF) elaboration by rheumatoid arthritis (RA) synovial, bone marrow, and blood mononuclear cells (MNC) is reported. IgM RF was prepared from RF-positive sera by sequential euglobulin precipitation, Sephacryl S300 gel filtration, and IgG-Sepharose affinity chromatography. Purified material, which contained no detectable IgG or IgA, was used in an enzyme-linked immunosorbent assay (ELISA) to quantitate cellular elaboration of IgM RF. Excellent standard curves (r2 = 0.98) were obtained without nonspecific binding of samples or antisera to IgG-coated microtiter plates and without cross-reactivity of standards with antisera other than anti-IgM. We found RA blood MNC (11 patients) spontaneously averaged 15 ng/ml IgM RF (6% of total IgM produced), but elaborated 254 ng/ml IgM RF following pokeweed mitogen (PWM) stimulation (22 patients), exceeding that of 13 normal controls. Bone marrow MNC spontaneously (4 patients) produced 71 ng/ml IgM RF and secreted 78 ng/ml IgM RF with PWM stimulation (9 patients). In contrast synovial fluid MNC (5 patients) spontaneously elaborated 6652 ng/ml IgM RF, significantly (P less than 0.05) more than blood or bone marrow MNC; PWM-stimulated synovial fluid MNC (5 patients) produced 5472 ng/ml IgM RF. These observations confirm selective localization of activated, IgM RF-producing cells to the rheumatoid synovial space.

Necrotizing granulomatous vasculitis with eosinophilic infiltrates limited to the prostate: Case report and review of the literature

A 67-year-old white man presented with recurrent bladder outlet obstruction due to allergic granulomatous prostatitis, with no evidence of asthma, allergies, or systemic vasculitis. He is currently doing well on a slowly tapering course of prednisone therapy and has had no recurrence of bladder outlet obstruction. This entity, although rare, must be promptly recognized in order that the proper studies can be performed to search for systemic vasculitis, and the appropriate therapy can be initiated to avoid further bladder outlet obstruction and loss of renal function.

Detection and quantitation of circulating immune complexes in arterial blood of patients with rheumatic disease

We developed antigen-nonspecific enzyme-linked immunoassays (ELISA) to quantitate IgG-C3- and IgM-C3-containing circulating immune complexes (CIC) in venous and arterial blood from rheumatic disease patients. Standards were diethylaminoethyl (DEAE)-purified, heat-aggregated IgG incubated with fresh human serum (for IgG-C3 CIC) and IgM rheumatoid factor-rich serum incubated with reduced, alkylated IgG and then with fresh human serum (for IgM-IgG-C3 CIC). Venous serum and plasma IgG-C3 and IgM-C3 CIC correlated closely (P less than 0.01). Rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) patients had elevated levels of venous IgM-C3 CIC (P less than 0.0001) but not IgG-C3 CIC; patients with vasculitis, inflammatory rheumatic diseases, or noninflammatory rheumatic diseases had mean values similar to normal individuals. Venous IgG-C3 and IgM-C3 CIC did not correlate. Paired venous and arterial samples from 16 rheumatic disease patients averaged comparable amounts of IgG-C3 and IgM-C3 CIC, respectively; venous and arterial IgM-C3 CIC levels in patients significantly exceeded normals (P less than 0.05). Venous and arterial IgG-C3 CIC levels correlated closely (P less than 0.01) as did venous and arterial IgM-C3 levels (P less than 0.05). Thus, arterial CIC offered no advantage over venous determinations for rheumatic disease patients. IgM-C3 CIC were elevated in patients with RA and SLE when IgG-C3 CIC were not. Ig isotype-specific CIC quantitation may be useful for certain rheumatic diseases.