Mahmoud Abu-Shakra

Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies

OBJECTIVES To review the autoimmune and rheumatic manifestations of patients with malignancy. METHODS A Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes. RESULTS Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of (a) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1, D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated antigens (RNP, Sm). The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes (anti-Hu syndrome and others). (b) Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. (c) Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy. CONCLUSION Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.

Gastrointestinal Manifestations of Systemic Sclerosis

Gastrointestinal (GI) manifestations of systemic sclerosis (SSc) were found in 82% of 262 patients followed up prospectively. Esophageal dysmotility, lower esophageal sphincter laxity, bacterial overgrowth, and wide mouth diverticuli were the most common findings. The disease is usually diffuse with multiple levels of involvement. Gastrointestinal involvement was not significantly correlated with gender, age at SSc diagnosis or disease type (limited or diffuse scleroderma). Upper GI symptoms develop early in the course of SSc and may not correlate with objective findings. Various investigations, treatment regimens, and less frequent disease manifestations are reviewed and discussed.

The Effect of Balneotherapy at the Dead Sea on the Quality of Life of Patients with Fibromyalgia Syndrome

Abstract: Fibromyalgia (FS) is an idiopathic chronic pain syndrome defined by widespread non-articular musculoskeletal pain and generalised tender points. As there is no effective treatment, patients with this condition have impaired quality of life (QoL). The aim of this study was to assess the possible effect of balneotherapy at the Dead Sea area on the QoL of patients with FS. Forty-eight subjects participated in the study; half of them received balneotherapy, and half did not. Their QoL (using SF-36), psychological well-being and FS-related symptoms were assessed prior to arrival at the spa hotel in the Dead Sea area, at the end of the 10-day stay, and 1 and 3 months later. A significant improvement was reported on most subscales of the SF-36 and on most symptoms. The improvement in physical aspects of QoL lasted usually 3 months, but on psychological measures the improvement was shorter. Subjects in the balneotherapy group reported higher and longer-lasting improvement than subjects in the control group. In conclusion, staying at the Dead Sea spa, in addition to balneotherapy, can transiently improve the QoL of patients with FS. Other studies with longer follow-up are needed to support our findings.

Osteonecrosis in patients with SLE

Osteonecrosis is a clinical entity characterized by death of bone marrow and trabecular bone as a result of disruption of blood supply to the bone (1,2). Other aspects of this condition include avascular necrosis, aseptic necrosis, and osseous ischemic necrosis of bones.Osteonecrosis is classified into two main forms; post-traumatic and nontraumatic. The post-traumatic form of osteonecrosis usually develops as a result of traumatic displacement of bone fragments, which leads to impaired blood supply and ischemia to the affected bone. Osteonecrosis of the femoral head is common following fracture of the femoral neck.A variety of systemic diseases and clinical conditions are associated with nontraumatic osteonecrosis. These include autoimmune rheumatic diseases, alcoholism, pregnancy, Gauchers disease, thrombophilia, corticosteroid therapy, Sickle-cell anemia, pancreatitis, inflammatory bowel diseases, and use of cytotoxic drugs and others. Idiopathic forms of osteonecrosis have also been reported (2–4).Among the rheumatic diseases, osteonecrosis is strongly associated with systemic lupus erythematosus (SLE) (5). However, osteonecrosis has been diagnosed in patients with primary antiphospholipid syndrome (APS) (6), rheumatoid arthritis (7), and systemic vasculitis (8).This article reviews the causes, clinical and epidemiological features, diagnosis, and treatment options for osteonecrosis among patients with SLE.

Influenza Virus Vaccination of Patients with SLE: Effects on Generation of Autoantibodies

Abstract: The sera of 24 women with SLE who received influenza vaccine were tested by ELISA for anti-DNA, anticardiolipin, anti-Sm, anti-Sm/RNP, anti-Ro and anti-La. Blood samples were withdrawn at the time of vaccination and 6 and 12 weeks after vaccination. The mean age at enrolment into the study was 46.1 years. The mean disease duration was 9.1 years. SLEDAI scores were 6.6 at vaccination, 4.9 at 6 weeks and 5.1 at week 12. The vaccine was not associated with the generation of anti-DNA. At time of vaccination a single patient had anti-Sm, four patients had anti-Sm/RNP antibodies, none of the patients had anti-La antibody and six had anti-Ro antibodies. Six weeks after vaccination four, eight, nine and three patients had autoantibodies reacting with Sm, Sm/RNP, Ro and La, respectively. Twelve weeks after vaccination none of the patients had anti-Sm, three had anti-Sm/RNP, five had anti-Ro and two had anti-La antibodies. Following vaccination six and three patients developed IgG and IgM anticardiolipin antibodies, respectively. In summary, although the influenza virus vaccine is clinically safe for patients with SLE it may trigger the generation of autoantibodies. This effect is usually short term and has no clinical significance.

Autoantibodies profile in the sera of patients with Sjogren's syndrome: the ANA evaluation--a homogeneous, multiplexed system.

Background: Flow-based, multiplex bead arrays (MBA) have been developed for a variety of applications including the detection of antibodies to extractable nuclear antigens (ENA). It offers a rapid and sensitive method to assess multiple analyses in a single tube/well. Purpose: To evaluate the Athena Multi-Lyte ANA Test System utilizes Luminex Corporations MBA technology for the detection of antinuclear antibodies (ANA) and ENA antibodies in the sera of patients with Sjogrens syndrome (SS). Methods: MBA assay was used to detect ANA and ENA antibodies in the sera of 37 patients with SS and 96 sera from healthy subjects. Results: All patients were women. Their mean age was 48.7 years and the mean disease duration was 7.27 years. ANA was found in 3 (3%) sera of healthy subjects by the AtheNA system and in 2 (2%) sera by the ELISA kit. A 99% concordance between the 2 assays was found. A 94.6% concordance between the 2 assays was found by testing the sera of patients with SS for ANA. By the AtheNA system, none of the sera of 37 patients with SS had autoantibodies reacting with Sm, Jo-1, dsDNA or histones. Anti-RNP antibody was found in 5.4% of the sera and 2.7% of the sera reacted with Scl-70 and histones. Anti-SS/A and anti-SS/B were identified in 84 and 76% of the sera, respectively. Conclusion: The AtheNa Multi-Lyte ANA Test System offers a sensitive and specific result for the detection of ANA and ENA antibodies in the sera of patients with SS.

Clinical and radiographic outcomes of rheumatoid arthritis patients not treated with disease-modifying drugs.

OBJECTIVE To compare the radiographic and clinical features of rheumatoid arthritis (RA) patients who were not given disease-modifying antirheumatic drugs (DMARDs) with those of RA patients who were followed up and treated with DMARDs at a rheumatology clinic. METHODS The population of this case-control study includes a series of RA patients who immigrated to Israel from the previous Union of Soviet Socialist Republics and who were treated only with nonsteroidal antiinflammatory drugs. Control patients who were followed up and treated with DMARDs at our rheumatology clinic were matched by sex, disease duration, number of actively inflamed joints, and the presence of serum rheumatoid factor. The outcome measures were the number of deformed and radiographically damaged joints. Radiographic damage was evaluated by the methods of Steinbrocker and Sharp. RESULTS The study population consisted of 22 RA patients (15 women, 7 men) who were not treated with DMARDs and 22 patients (15 women, 7 men) who were treated with DMARDs. The mean disease duration was 16.2 years for the study patients and 14.3 years for the controls. Compared with the matched controls, RA patients who were not treated with DMARDs were found to have a significantly higher mean number of deformed joints (13.8 versus 7.2), a higher mean number of damaged joints (24.4 versus 15.5), and a higher overall damage score by the Sharp criteria (146.1 versus 65.7). CONCLUSION RA patients who were not given DMARDs had a 1.57-fold increased number of radiographically damaged joints and a 2.22-fold increased overall Sharp damage score compared with patients who were treated with second-line agents.

The significance of anticardiolipin antibodies in patients with lupus nephritis.

The objective of this study was to determine whether anticardiolipin antibodies (ACL) in SLE patients are associated with a specific pattern of lupus nephritis and/or with renal microvascular changes. Patients with SLE, followed prospectively between June 1991-May 1994 at The Wellesley Hospital Lupus Clinic, who underwent a renal biopsy were included. The ACL was measured by the ELISA according to international standardized method. Renal biopsy morphology was assessed using the WHO criteria for the classification of lupus nephritis. Renal vascular changes included glomerular hyaline thrombi, intimal fibro sis and intraluminal thrombi of renal arterioles. There were 23 SLE patients. The mean age at diagnosis of SLE was 28.2 years and the mean disease duration was 6.3 years. Of these 10 (43%) had high levels of ACL. No difference in the frequency of severe nephritis (Class III and IV) was identified amongst patients with and without ACL. Mesangial nephritis was more common in patients with ACL 40% vs 0, p = 0.02). Glomerular hyaline thrombi occurred in 3 (13%) patients. None of them had positive ACL. Renal vascular lesions included intimal proliferation in 4 (ACL + , 1) occluded lumens by thrombi in 2 (ACL + 1). Our data indicate that the development of glomerular and/or microvascular changes is not related to the presence of ACL.Chloroquine and hydrocychloroquine have been evaluated in 30 noninfectious disorders and conditions other than rheumatoid arthritis or lupus erythematosus; 12 of these have been subjected to well-designed controlled trials. It is concluded that chloroquines are safe and effective first line therapies for selected patients with porphyria cutanea tarda, cutaneous sarcoidosis, cutaneous manifestations of dermatomyositis, hyperlipidemias and thromboembolic prophylaxis for patients with antiphospholipid antibodies. Published experience with these and other diseases or syndromes are critically reviewed.

Therapy with mud compresses for knee osteoarthritis: comparison of natural mud preparations with mineral-depleted mud.

Mud pack therapy is an alternative mode of treatment for rheumatic diseases. It is based on the application of heated mud packs to the entire body or to specific areas, such as over joints. The aim of the current study was to evaluate the efficacy of treatment with mud compresses at patients’ homes for osteoarthritis of the knee.Fifty-eight patients with osteoarthritis of the knee were enrolled in a prospective, double-blinded, controlled study. Forty patients were treated with natural mineral-rich mud compresses and 18 patients were treated with mineral-depleted mud compresses. Mud compresses were applied 5 times each week during 3 weeks for a total of 15 treatments. Patients were assessed at baseline, at completion of the 3-week treatment period, and twice after the conclusion of the treatment period—after 1 month and after 3 months.The main outcome measures were the Lequesne Index of severity of knee osteoarthritis, patient self-assessment of pain, and severity of knee pain on a visual analog scale. A reduction of 20% or more in the pain scores was considered clinically significant.In the group treated with natural mud compresses, a significant reduction in knee pain was observed at all assessments. Similarly, improvement in the Lequesne Index was seen at the end of therapy and a month after treatment. In the control group, given mineral-depleted mud compresses, no significant change in knee pain was seen at any assessment. Improvement in the Lequesne Index was seen 1 and 3 months after completion of the therapy, but not at the end of therapy. Seventy-two percent of the patients in the treatment group had an improvement of >20% in self-assessment of knee pain, compared with 33% in the control group (p = 0.005).The data suggest that treatment with mud compresses, but only in their natural form, temporarily relieves pain in patients with osteoarthritis of the knees. We believe that treatment with mud compresses might augment conventional medical therapy in these patients.

Fibromyalgia in systemic lupus erythematosus: prevalence and clinical implications.

Fibromyalgia (FM) is common in SLE patients, and is the source of many of the symptoms and much of the disability in these patients. The association of FM and SLE may pose diagnostic dilemmas.Fibromyalgia does not correlate with SLE disease activity, but the clinical features of FM in these patients may contribute to a misinterpretation of lupus activity. The recognition of the association between SLE and FM is relevant to every physician who treats lupus patients.