Search

We present a case of the multicentric plasma cell variant of Castleman's disease (CD) with two rare manifestations. The patient consulted us because of cutaneous vasculitis of the lower limbs, while constitutional symptoms were nearly absent. Imaging studies also revealed pulmonary parenchymal involvement. Furthermore, our patient is the first case in whom association of ankylosing spondylitis with CD is reported. In addition, we present a review of the literature with emphasis on the clinical presentation of CD and its difficult discrimination from autoimmune and infectious disorders. An overview of the therapeutic options is also provided.

Introduction: Osteoarthritis (OA) of the knee joint is caused by genetic and hormonal factors and by inflammation, in combination with biomechanical alterations. It is characterized by loss of articular cartilage, synovial inflammation and subchondral bone sclerosis. Considerable evidence indicates that the menisci, ligaments, periarticular muscles and the joint capsule are also involved in the OA process. This paper will outline the theoretical framework for investigating the infrapatellar fat pad (IPFP) as an additional joint tissue involved in the development and progression of knee-OA., Methods: A literature search was performed in Pubmed from 1948 until October 2009 with keywords InFrapatellar fat pad, Hoffa fat pad, intraarticular adipose tissue, knee, cartilage, bone, cytokine, adipokine, inflammation, growth factor, arthritis, and OA., Results: The IPFP is situated intracapsularly and extrasynovially in the knee joint. Besides adipocytes, the IPFP from patients with knee-OA contains macrophages, lymphocytes and granulocytes, which are able to contribute to the disease process of knee-OA. Furthermore, the IPFP contains nociceptive nerve fibers that could in part be responsible for anterior pain in knee-OA. These nerve fibers secrete substance P, which is able to induce inflammatory responses and cause vasodilation, which may lead to IPFP edema and extravasation of the immune cells. The IPFP secretes cytokines, interleukins, growth factors and adipokines that influence cartilage by upregulating the production of matrix metalloproteinases (MMPs), stimulating the expression of pro-inflammatory cytokines and inhibiting the production of cartilage matrix proteins. They may also stimulate the production of pro-inflammatory mediators, growth factors and MMPs in synovium., Conclusion: These data are consistent with the hypothesis that the IPFP is an osteoarthritic joint tissue capable of modulating inflammatory and destructive responses in knee-OA., (Copyright 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

We describe the case of a 39-year-old Caucasian woman who was admitted to the University Hospital of Antwerp with a clinical picture suggestive of adult Still's disease. Even though a transoesophageal echocardiography showed endocarditis of the aortic valve, blood cultures remained negative. Additional serological testing revealed a positive result for Bartonella henselae. Histology of the supraclavicular lymph node showed a reactive lymph node with a positive polymerase chain reaction (PCR) for Bartonella henselae. Prednisolone treatment was started in a dosage of 10 mg per day and rifampicin 600 mg/d in combination with doxycyclin 200 mg/d was given for 6 months. During therapy the patient gradually improved and signs of endocarditis disappeared on echocardiography.

Objective: Bisphosphonates have been reported to possess anti-inflammatory and cartilage protective effects in animal arthritis models but not much is known about their direct effect on chondrocytes. In this study we evaluate the effect of bisphosphonates on nitric oxide (NO) production by activated chondrocytes., Methods: Isolated bovine chondrocytes and bovine cartilage explants were used. In the second part of the study human cartilage explants (osteoarthritis (OA) and non-OA cartilage) were used. The isolated chondrocytes and cartilage explants were pre-incubated with clodronate, pamidronate or risedronate and stimulated with IL-1 and TNF-alpha (10 ng/mL, 48 h). NO production was quantified using the Griess assay., Results: In bovine cultures, clodronate (10(-4)mol/L) and pamidronate (10(-6)mol/L) showed a small inhibition of NO production (up to 15 % and 25% respectively), whereas risedronate had no effect. In the human cartilage cultures no effect of BPs on the NO production was detected except for the highest concentration of clodronate tested (10(-4)mol/L) which demonstrated a small enhancement (19%) in NO production reaching significance in the non-OA group., Conclusion: BPs have a modest effect on NO production by inflammatory activated chondrocytes only in the higher concentrations, indicating that the clinical relevance of these effects is probably negligible.

The destruction of cartilage is an important characteristic of rheumatoid arthritis (RA). Immune complexes (IC) are usually found in high amounts in RA synovial fluids (SF) and in the superficial layers of RA cartilage. The objective of this study was to investigate if IC have a direct influence on proliferation, survival and production of nitric oxide (NO) of cytokine-activated chondrocytes. Primary bovine chondrocytes were incubated with cytokines (huIL-1alpha, bovIFN-gamma, huTNF-alpha) and IC containing precipitates of peripheral blood (PB) and/or synovial fluid (SF) of 14 RA patients, 5 osteoarthritis (OA) patients and 10 healthy age and sex-matched controls. After 48 h, chondrocyte viability, proliferation, apoptosis, NO production and oxygen radical levels were measured. Staining with May-Grünwald-Giemsa after incubation with IC of RA PB and SF, showed apoptotic chondrocytes with condensation of the nuclei. The proliferation rates of cytokine-activated chondrocytes, incubated with sera and SF IC of RA patients were significantly decreased compared to chondrocytes, incubated with sera and SF IC of OA patients and compared to sera of controls. Quantitative evaluation of apoptotic cells by annexin-V/propidium iodide and TUNEL assays revealed a significant increase after incubation with sera and SF IC of RA patients, compared to control sera and OAs sera and SF. In all TUNEL positive samples, active-caspase-3-positive cells were found. There was a significant increase of chondrocyte NO production, after incubation with SF IC of RA patients, compared to OA SF. These results support the hypothesis that IC, present in serum and SF of RA patients, have a profound influence on chondrocyte growth, NO production and apoptosis, contributing to cartilage destruction in RA.

Objective: In addition to their cholesterol-lowering action, statins have been suggested to exert anti-inflammatory activities. In this study we evaluate whether simvastatin could influence the production of pro-inflammatory cytokines (interleukin (IL)-6 and IL-8) and nitric oxide (NO) by activated human chondrocytes., Methods: Human isolated chondrocytes and cartilage explants were pre-incubated with simvastatin (0.5, 5, 10 and 50 micromol/L) for 48 h. Then the cultures were stimulated with a mixture of IL-1Beta and TNF-alpha (10 ng/mL) and co-incubated with simvastatin for an additional 48 h. A flow cytometric microsphere-based immunoassay was performed to detect cytokine secretion in the supernatants. NO production was quantified using the Griess assay., Results: Simvastatin demonstrated significant dose-dependent inhibition of IL-6 and IL-8 production of isolated chondrocytes and cartilage explants up to 99% for IL-6 and up to 88% for IL-8 (p < 0.01). At the higher concentrations simvastatin decreased NO production by both isolated chondrocytes (up to 43%, p < 0.01) and cartilage explants (up to 30%, p < 0.01)., Conclusion: This study demonstrates anti-inflammatory properties of simvastatin in chondrocytes in vitro, suggesting a potential cartilage-protective role for statins in arthritis.

The objective of this study was to evaluate the effect of bisphosphonates (BPs) and simvastatin on chondrocyte lipid peroxidation. For this purpose, a flow cytometrical method using C11-BODIPY(581/591) was developed to detect hydroperoxide-induced lipid peroxidation in chondrocytes. Tertiary butylhydroperoxide (t-BHP) induced a time and concentration dependent increase in chondrocyte lipid peroxidation. Addition of a Fe2+/EDTA complex to t-BHP or hydrogen peroxide (H2O2) clearly enhanced lipid peroxidation. The lipophilic simvastatin demonstrated a small inhibition in the chondrocyte lipid peroxidation. None of three tested BPs (clodronate, pamidronate, and risedronate) had an effect on chondrocyte lipid peroxidation induced by t-BHP. However, when Fe2+/EDTA complex was added to t-BHP or H2O2, BPs inhibited the lipid peroxidation process varying from 25% to 58%. This study demonstrates that BPs have antioxidant properties as iron chelators, thereby inhibiting the chondrocyte lipid peroxidation. These findings add evidence to the therapeutic potential of bisphosphonates and statins in rheumatoid arthritis.

Objective: To investigate whether anti-TNF therapy could have an effect on dendritic cells (DCs) and regulatory T cells in rheumatoid arthritis (RA) patients., Methods: A four-colour flow cytometric technique was used to measure CD4+CD25+ T cells i.e. CD4+CD25high+ (regulatory T cells) and CD4+CD25low+ (activated T cells)), DCs as well as the in vitro, intracellular, lipopolysaccharide-stimulated cytokine production of DCs., Results: Clinical and laboratory parameters of disease activity decreased after anti-TNF treatment. Before anti-TNF therapy, RA patients demonstrated a decreased count of Th2-promoting lymphoid DCs as compared to controls and after anti-TNF therapy this decrease was sustained. Intracellular cytokine production was only found in the myeloid DCs population and there was a higher production of TNF-alpha and IL1-b as compared to healthy controls. Treatment did not alter this cytokine production. Before anti-TNF therapy, the percentage CD4+CD25+ T cells was significantly elevated in RA patients than in healthy controls., Conclusion: These results demonstrate anti-TNF to be a potent anti-inflammatory drug, as mirrored by the decrease in clinical and biological parameters as well as the decrease in activated CD4+ T cells. However, in this study no demonstrable effect on DCs and regulatory T cells was found.

Bisphosphonates have anti-inflammatory effects in rheumatoid arthritis and chondroprotective effects in animal arthritis models but their influence on chondrocytes is not known. The aim of this study is to investigate whether bisphosphonates could influence the production of pro-inflammatory cytokines by activated chondrocytes. Therefore human articular cartilage explants were incubated at 48 h with clodronate, pamidronate or risedronate (10(-6) and 10(-8)mol/L), and dexamethasone (10(-8)mol/L). Subsequently, cultures were stimulated with IL-1, 10 ng/mL (n=6) or 1 ng/mL (n=10) for 48 h. Co-incubation was performed with or without bisphosphonates or dexamethasone. A flow cytometric microsphere-based immunoassay was used for the detection of the pro-inflammatory cytokines IL-6, IL-8, TNF-alpha, IL-1 and the regulatory cytokines IL-12p70 and IL-10 in the supernatants. Stimulation with IL-1 resulted in a dose dependent induction of IL-6 and IL-8, but no production of the other cytokines could be demonstrated. This production of IL-6 and IL-8 was neither inhibited nor enhanced by bisphosphonates. Only dexamethasone caused an inhibition of IL-6 production. In conclusion, there is no evidence on the level of articular cartilage cells that bisphosphonates would suppress or enhance IL-6 and IL-8 mediated joint destruction.

Collagen vascular diseases and malignancies have common systemic and immune features. We report a case of a 21 year old female patient with constitutional symptoms, polyserositis, spontaneous rupture of the spleen, leukocytoclastic vasculitis and acute renal failure. The tentative diagnosis of SLE was made because she developed a positive antinuclear factor (1/640), with anti-SSA antibodies and a positive lupus anticoagulans. Two months later a cervical lymphadenopathy occurred while recieving treatment with prednisolone. A lymph node biopsy revealed morphologic features of a SLE, similar to those observed in multicentric Castleman's disease (MCD). MCD is a distinct type of a lymphoproliferative disorder of unknown etiology. The difficulties in differential diagnosis of these two diseases are discussed.

The aim of this study was to investigate the in vitro antioxidant profile of different bisphosphonates. Bisphosphonates were tested for their xanthine oxidase and microsomal lipid peroxidation inhibiting capacity. Furthermore, the effect of these different compounds on DPPH, a stable radical, was investigated. Clodronate, risedronate, and pyrophosphate were further tested for their hydroxyl radical scavenging activity. None of the tested compounds showed xanthine oxidase inhibiting activity or DPPH scavenging activity. All the tested bisphosphonates exhibited inhibiting capacities on the microsomal lipid peroxidation. The hydroxyl radical scavenging activity was dependent on the order of adding the different reagents and was highest for risedronate. Bisphosphonates possess an inhibiting activity on the microsomal lipid peroxidation and the Fenton reaction. In these reactions iron plays an important role suggesting that the selective in vitro antioxidant properties of the bisphosphonates are due to their iron chelating characteristics.

We present a patient who had one episode of prepatellar bursitis and subsequently several episodes of arthritis of his right knee. Cultures of several punctures of his knee remained sterile, but the patient had been taking oral antibiotics on each of these occasions against our medical advice. Ultimately a diagnostic puncture revealed growth of Staphylococcus aureus. An X-ray demonstrated an osteolytic lesion of the patella, but no defect in the articular surface of the patella could be visualised. MRI demonstrated a communication between the osteomyelitic focus through the medial retinaculum to the bursa suprapatellaris and the knee joint. Osteomyelitis of the patella is mainly a disease of childhood. This case is, to our knowledge, the first report on the association between bursitis, osteomyelitis of the patella and recurrent septic arthritis of the knee in an adult. The literature is reviewed and discussed briefly.

Objective: Cytokines produced by inflammatory cells play a pivotal role in synovial inflammation and joint destruction in rheumatoid arthritis. To investigate the influence of pro-inflammatory cytokines (IL-1 alpha, IL-6, TNF-alpha, IFN-gamma) and subsequently the possible beneficial role of an anti-inflammatory cytokine (IL-4) on chondrocyte viability (necrosis/apoptosis), proliferation and nitric oxide (NO) production., Methods: Primary bovine chondrocytes were cultured until monolayers were obtained. Cells were incubated with cytokines (IL-1 alpha, IFN-gamma, TNF-alpha, IL-4, IL-6) at 0.1, 1, 10 and 100 ng/mL. After 48 h, the viability of the chondrocytes was measured flow cytometrically with propidium iodide. Proliferation was determined by the incorporation of tritiated thymidine. The morphology of the chondrocytes, including presence of apoptotic nuclei, was evaluated by a May-Grünwald-Giemsa staining. In addition, the number of apoptotic chondrocytes was detected flow cytometrically with a TUNEL technique and annexin-V/propidium iodide staining. NO production was evaluated using a spectrophotometric assay, based upon the Griess reaction., Results: The viability and proliferation of bovine chondrocytes decreased after incubation with 100 ng/mL IL-1 alpha, TNF-alpha or IFN-gamma. In contrast, incubation of chondrocytes with IL-4 or IL-6 had no influence on the viability or the proliferation of cells. IL-1 alpha was able to enhance NO production in a dose dependent manner. IFN-gamma and TNF-alpha induced NO production only at the highest concentration (100 ng/mL), whereas IL-4 and IL-6 did not. There was a dose dependent increase in apoptosis of bovine chondrocytes cultured in the presence of IL-1 alpha and TNF-alpha. This effect could not be prevented by preincubation with IL-4. Preincubation with IL-4 diminished IL-1 alpha and TNF-alpha induced NO production and increased proliferation of chondrocytes. In an additional experiment, incubation of human chondrocytes with anti-Fas did not induce apoptosis as measured by annexin-V/propidium iodide staining., Conclusions: Pro-inflammatory cytokines are able to induce apoptosis, whereas IL-4 as an anti-inflammatory cytokine can inhibit the effect of IL-1 alpha and TNF-alpha on NO production and proliferation of bovine chondrocytes.

Introduction: It has been shown that T lymphocytes and monocytes/macrophages, producing pro-inflammatory cytokines, play a pivotal role in the pathophysiology of rheumatoid arthritis (RA). In recent placebo-controlled double-blind randomized studies, chimeric (human/mouse) tumour necrosis factor-alpha (TNFalpha) antibodies (cA2) proved to be very effective in improving clinical disease activity and reducing inflammatory parameters in RA., Objective: To investigate whether anti-TNFalpha therapy influences the in vitro intracellular cytokine production in peripheral blood monocytes and T lymphocytes of RA patients after one single (24 h) and multiple intravenous infusions (6 months)., Methods: An intracellular flow cytometric technique was applied to measure interleukin 1beta (IL-1beta), IL-6, TNFalpha, IL-10 and IL-12 in monocytes and IL-2, IL-4 and interferon-gamma in T lymphocytes of 15 patients, before, after 24 h and after 6 months of therapy with monoclonal chimeric anti-TNFalpha antibodies (3 mg/kg, bimonthly i.v.). All patients were on stable therapy with methotrexate (15-20 mg/week i.m.). Cytokine content in monocytes was measured directly after blood sampling (basal levels), after 8 h of culture (spontaneous production) and after 8 h of stimulation with lipopolysaccharides (LPS-stimulated production)., Results: Basal levels and production (after 8 h) of IL-1beta, IL-6 and TNFalpha were significantly decreased 24 h after the first administration of anti-TNFalpha (for IL-1beta P < 0.01; for IL-6 P < 0.01; for TNF P < 0.003) and after 6 months of therapy (for IL-1beta P < 0.02; for IL-6 P < 0.03; for TNFalpha P < 0.001). For IL-12, basal levels were significantly decreased 24 h and 6 months after the start of therapy with anti-TNFalpha antibodies (P=0.0001; P=0.003, respectively). In contrast, IL-10 production increased significantly after 24 h and after 6 months (P=0.02; P=0.01). The T(H2)/T(H1) cytokine ratio in CD4+ T cells was significantly increased after 24 h and after 6 months of anti-TNFalpha therapy (P=0.003; P=0.0007)., Conclusion: Anti-TNFalpha therapy might down-regulate the monocytic capacity to produce pro-inflammatory cytokines and induces a shift to a more pronounced anti-inflammatory T(H2) cytokine production.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disease with predominance of type I cytokine [interleukin 2 (IL-2), interferon-gamma (IFN-gamma)] production. In this prospective study, we evaluated the influence of longterm therapy with methotrexate (MTX) in combination with low dose corticosteroids on the type 1/type 2 cytokine balance in RA., Methods: Peripheral blood mononuclear cells were isolated from 10 controls and 20 patients with RA before therapy and after 12 mo of therapy with MTX in combination with low dose corticosteroids. Using flow cytometry, the intracellular production of IL-2, IFN-gamma, and IL-4 was measured in CD4+ and CD8+ T lymphocytes., Results: Compared with healthy controls, patients with RA before therapy showed an increased percentage of IL-2 positive CD4+ and CD8+ T cells (p = 0.002, p = 0.01, respectively). An increased percentage of IFN-gamma positive CD8+ T cells was found (p = 0.0006) compared with the control group. After 12 months of therapy, a significantly decreased percentage of IL-2 positive CD4+ T cells and IFN-gamma positive CD4+ and CD8+ T lymphocytes was observed (p = 0.0003, p = 0.0007, p = 0.001). The percentage of IL-4/IFN-gamma positive CD4+ and CD8+ T cells was significantly higher after 12 months of therapy (p = 0.01, p = 0.02). There was a positive correlation between the percentage of IFN-gamma positive CD4+ T cells and disease activity variables (Ritchie Index and number of swollen joints) in RA patients before therapy (r = 0.6, p = 0.04 and r = 0.4, p = 0.05)., Conclusion: Longterm therapy with MTX in combination with low dose corticosteroids for RA influenced the predominance of type 1 cytokines toward normalization of the cytokine balance in both CD4+ and CD8+ T lymphocytes.

Objectives: The aim of this work was to evaluate in a randomised double-blind prospective study the effect of pamidronate on intracellular monocytic cytokine profiles (IL-1, IL-6, TNF-alpha) and bone density in rheumatoid arthritis patients., Methods: Twenty rheumatoid arthritis patients were treated for one year with methotrexate and a low dose of prednisolone. Double blind randomisation was performed for either i.v. pamidronate (at 3-month intervals) or placebo. The effect of pamidronate was evaluated on intracellular cytokine profiles (IL-1, IL-6, TNF-alpha), disease activity and bone mass measurements. The human monocytic cell line THP-1 was used to evaluate in vitro apoptosis by pamidronate., Results: Spontaneous production of interleukin-1 beta by patient blood monocytes was lower in the pamidronate group and was associated with an increase in bone density of the spine after 12 months of therapy. In vitro a dose-related increase in pamidronate induced apoptosis was found in THP-1 cells., Conclusions: This prospective double-blind randomised study demonstrated that pamidronate therapy resulted in an increase of bone density despite treatment with steroids. This rise is associated with a suppression of interleukin-1 beta production in monocytes of patients treated with pamidronate. Our in vitro experiments suggest that this anti-inflammatory effect could be due to an increase in the apoptosis of monocytic cells.

The stingray is one of the most dangerous fishes for man. The sting is poisonous and causes a painful wound. Fatalities are reported. Most injuries due to stingrays occur in coast regions of the tropics and subtropics. Therefore, physicians in countries with a moderate climate are less informed about the management about these kinds of injuries. The characteristics, treatment and prevention are discussed in connection with a case that occurred in Belgium in a devotee of aquarium fishes.

The clinical manifestations of hypoparathyroidism are mainly characterised by increased neuromuscular irritability as a consequence of hypocalcaemia. Occasionally, elevation of the muscle enzymes may mimic polymyositis. Reduced parathyroid hormone production, but also vitamin D treatment and calcium supplementation, may contribute to the increased bone mass found in patients with postsurgical hypoparathyroidism. We report the case of a 36-year-old woman with untreated idiopathic hypoparathyroidism and a high bone mass despite severe muscle impairment due to hypocalcaemic myopathy.

Experimental data suggest that pro-inflammatory cytokines such as interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) are important in the pathogenesis of osteoporosis in rheumatoid arthritis. Therefore we compared the production of these cytokines by monocytes in 10 rheumatoid arthritis patients and 10 controls. Cytokine levels in rheumatoid arthritis patients were related to disease activity parameters, bone mineral density (BMD) corrected for age and sex (Z scores) and osteocalcin as a laboratory parameter of bone remodelling. Cytokines were determined by a flow cytometrical technique. There was a tendency for higher IL-1beta levels in patients compared with controls. A positive correlation between erythrocyte sedimentation rate and spontaneous production of monocytic cytokines was found. Z scores of the lumbar spine showed a negative correlation with spontaneous production of IL-1beta and IL-6. Plasma osteocalcin levels were positively correlated with spontaneous production of IL-1beta, IL-6 and TNF-alpha. In conclusion, the correlation of the levels of these cytokines with parameters of bone metabolism and osteoporosis suggest that especially IL-1beta and IL-6 are associated with more pronounced osteoporosis in active rheumatoid arthritis., (Copyright 1999 Academic Press.)

Ochronosis is a rare disease caused by an inherited lack of homogentisic acid oxidase. Alkaptonuria is the presence of homogentisic acid in urine. Ochronosis is characterized by the deposition of a dark pigment in tissues rich in collagen. A wide spectrum of clinical manifestations is described. The most important signs are ochronotic arthropathy, ocular and cutaneous pigmentation, genitourinary tract obstruction by ochronotic calculi and cardiovascular ochronosis, especially calcification and stenosis of the aortic valve. The constellation of these clinical signs should suggest the diagnosis which is confirmed by the detection of homogentisic acid in urine. There is no cure for the disease and treatment is based on symptomatic measures.

Adult-onset Still's disease is an uncommon rheumatological syndrome with a diversity of signs and symptoms. Pulmonary manifestations described are pleuritis and usually transient radiologic infiltrations. The patient presented in this case report had biopsy-proven lung fibrosis when adult-onset Still's disease was diagnosed. Three years after diagnosis, the patient developed clinical signs of the interstitial lung disorder. Radiological and histological progression was observed. Other causes of interstitial lung disorders were excluded. Clinicians should be aware that interstitial lung disease can be a complication of adult-onset Still's disease and can compromise the clinical status of the patient.

A 72-year-old rheumatoid arthritis patient is described presenting with acute dyspnoea and peripheral oedema. A pericardial effusion with signs of tamponade was diagnosed. Examination of the pericardial fluid revealed the presence of cholesterol crystals and IgE-containing immune complexes. The significance of these findings in the differential diagnosis of pericardial disease is discussed.

Two cases of eosinophilic fasciitis are described, in which magnetic resonance imaging (MRI) clearly demonstrated thickening of the fascia and increased signal intensity in the superficial muscle fibers correlating with inflammation. MRI is a useful noninvasive imaging technique in the diagnosis of eosinophilic fasciitis and can guide biopsy of selected abnormal areas.

A 39-year-old Ugandan student is described presenting with general malaise, fever and a pulmonary infiltrate. Open lung biopsy showing infarction and positive ANCA lead to a diagnosis of Wegener's granulomatosis and a treatment with immunosuppressive drugs was instituted. Five weeks after admission, however, sputum cultures turned out to be positive for Mycobacterium tuberculosis. The importance of ANCA-interpretation and the possibility of false positive results is discussed.

IgE-containing circulating immune complexes (IgE-CIC) were determined with a 2.5% PEG-precipitation assay in 98 patients with classical or definite rheumatoid arthritis (RA). Of the 45 IgE-CIC positive sera, only 4 had elevated total serum IgE. IgE-CIC positive patients had more active disease than patients without IgE-CIC, as determined by their more swollen joints and higher Ritchie indices (p less than 0.04 and 0.02, respectively). Apart from IgE, other immunoglobulin isotypes, rheumatoid factor (RF) of the IgG-, IgA- and IgM-classes, C3 and antinuclear antibodies could be demonstrated in the IgE-containing PEG-precipitates. IgE-RF could not be demonstrated in serum or in IgE-CIC. Anti-IgE of the IgM-class (IgMaIgE) were frequently found (28/45 patients) in the IgE-positive PEG-precipitates. All 14 patients positive for IgGaIgE in the IgE-CIC were also positive for IgMaIgE in the CIC. As in the serum, there was a good correlation in the CIC between the level of IgGaIgE and the level of IgMaIgE (r = 0.64). The correlation between the respective levels of IgGaIgE and IgMaIgE in serum and in CIC was high (r = 0.93 and 0.79, respectively). On the other hand, only 1 patient was positive for IgAaIgE in the IgE-CIC. We conclude that IgE and aIgE of the IgM- and IgG-classes are frequently present in the immune complex form in RA and that they are correlated with the clinical activity of arthritis.