Adult-onset Still's disease: analysis of a monocentric cohort of patients.

OBJECTIVE: Adult-onset Still's disease (AOSD) is a multigenic autoinflammatory disease with a severe systemic involvement. Because of the rarity of the disease, most published cohorts are multicentric. The aim of this report is to describe a monocentric cohort of AOSD patients, reporting clinical features and response to therapy in a long follow-up. METHOD: Thirty-eight patients, attending the Clinical Immunology Unit and fulfilling Yamaguchi, Fautrel, or Daghor-Abbaci classification criteria for AOSD, were recruited for this study. In all patients, clinical and serological data were collected at diagnosis and every 6 months thereafter. The Pouchot score was calculated at every visit. RESULTS: Fever, arthromyalgia, and skin rash were the most frequent manifestations, followed by lymphadenopathy, sore throat, arthritis, splenomegaly, hepatic involvement, pleuropericarditis, and weight loss. As far as the disease course is concerned, 25% presented a monocyclic and 35% a polycyclic pattern, and 40% developed chronic articular involvement. Severe complications were observed at disease onset in 21% of the patients. All of the patients were treated with steroids; 74% also received conventional synthetic disease-modifying anti-rheumatic drugs (methotrexate in most cases) and 71% biological disease-modifying anti-rheumatic drugs (interleukin-1 inhibitors in most cases). Therapeutic switching for lack/loss of efficacy or adverse drug reactions was necessary in 66%. CONCLUSION: The analysis of this cohort confirms that AOSD is a complex, severe, and heterogeneous disease. However, despite long-term treatment and comorbidities, therapies are effective and well tolerated. The therapeutic armamentarium now available allows long-lasting remission with low immunosuppression to be achieved in most patients.

The use of rituximab in idiopathic inflammatory myopathies: description of a monocentric cohort and review of the literature.

Rituximab (RTX), a chimeric monoclonal antibody targeted against CD20, has been used to treat refractory inflammatory myopathies (IIM). The primary objective of this study was to retrospectively assess the efficacy of RTX in reducing disease activity in patients with IIM refractory to conventional therapy. Secondary aim was the evaluation of adverse events (AE) during the treatment period. We examined 26 patients with a diagnosis of IIM, referred to our Rheumatology Unit and treated with RTX for active refractory disease. Patients were treated with RTX 1000 mg i.v., twice, with a 2-week interval. RTX treatment was associated with a significant reduction of creatine kinase (p=0.001) after six months compared to the baseline, an improved muscular strength measured with MMT8 (p<0.001) and a reduction of the extramuscular activity of the disease measured with MYOACT (p<0.001). In particular, RTX improved DM skin rash, arthritis and pulmonary manifestations. Autoantibody positivity (in particular antisynthetase, anti- SRP and antiRo/SSA), and a disease duration <36 months at the moment of the treatment are associated with a better response rate. Treatment with RTX was also associated with a reduction of the mean daily dose of steroids needed to control disease activity (p=0.002). Our results have confirmed that RTX is efficacious in the treatment of refractory IIM. Ad hoc controlled trials are needed to better clarify the specific subset of patients who may better respond to the treatment and the optimal therapeutic schedule.

Health-related quality of life in severe cryoglobulinaemic vasculitis and improvement after B-cell depleting therapy.

OBJECTIVES: To study the health-related quality of life (HRQOL) in severe cryoglobulinaemic vasculitis (CV) associated with hepatitis C virus infection (HCV) and to describe the effect of rituximab on HRQOL. METHODS: HRQOL was evaluated with the Medical Outcomes Study Short Form 36 (SF-36). Health Survey questionnaire was submitted to 15 patients with severe CV. SF-36 questionnaire was evaluated at baseline and after rituximab. Physical Health Composite Summary (PCS) and Mental Health Composite Summary (MCS) scores were calculated according to standard protocols, and normalised to healthy controls. SF-36 summary scores were compared with those of HCV positive patients without CV, and other vasculitis published in the literature. European Quality of Life-5 dimensions (EQ5D) scores were also derived. RESULTS: Physical and mental domain scores were all reduced if compared with those of the healthy population, with physical domains being greatly affected. HRQOL of CV was comparable with HRQOL reported for the other small vessel vasculitis. The development of CV in HCV positive patients worsened PCS rather than MCS score. Birmingham Vasculitis Activity Score (BVAS) did not correlate with HRQOL, while the presence of peripheral neuropathy was associated with a worse HRQOL. Early rituximab treatment improved both PCS and MCS scores, with long-term effects. CONCLUSIONS: PCS rather than MCS was affected in HCV positive patients when CV is present. Rituximab improved both physical and mental domains, thus supporting its use before antiviral therapy in severe HCV-related CV. The cost/benefits ratio of a sequential therapy may be supported.

A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis.

OBJECTIVE: To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV). METHODS: Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months. RESULTS: Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated. CONCLUSION: RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.

Bosentan and sildenafil: successful treatment in a sclerodermic patient with refractory ulcers.

Systemic sclerosis is an inflammatory disease of the connective tissue characterized by vasculopathy and accumulation of collagen and other components of the connective matrix, affecting the skin and internal organs. The appearance of skin ulcers as a result of vascular damage is very common in the history of the disease. Skin ulcers, painful and slow healing due to atrophy and local ischemia, get worse the quality of life of patients. Often, the use of conventional therapies (such as calcium channel blockers and prostanoids) does not cause the complete healing of the lesions. We report the case of a patient in whom therapeutic association between endothelin antagonist (bosentan) and phosphodiesterase-V inhibitor (sildenafil) resulted in complete healing of old ulcers both to upper and lower limbs and allowed the interruption of intravenous therapies.

Preliminary classification criteria for the cryoglobulinaemic vasculitis.

BACKGROUND: To develop preliminary classification criteria for the cryoglobulinaemic syndrome or cryoglobulinaemic vasculitis (CV). METHODS: Study part I developed a questionnaire for CV to be included in the formal, second part (study part II). Positivity of serum cryoglobulins was defined by experts as an essential condition for CV classification. In study part II, a core set of classification items (questionnaire, clinical and laboratory items, as agreed) was tested in three groups of patients and controls-that is, group A (new patients with the CV), group B (controls with serum cryoglobulins but lacking CV) and group C (controls without serum cryoglobulins but with features which can be observed in CV). RESULTS: In study part I (188 cases, 284 controls), a positive response to at least two of three selected questions showed a sensitivity of 81.9% and a specificity of 83.5% for CV. This questionnaire was employed and validated in study part II, which included 272 patients in group A and 228 controls in group B. The final classification criteria for CV, by pooling data from group A and group B, required the positivity of questionnaire plus clinical, questionnaire plus laboratory, or clinical plus laboratory items, or all the three, providing a sensitivity of 88.5% and a specificity of 93.6% for CV. By comparing data in group A versus group C (425 controls), the same classification criteria showed a sensitivity 88.5% and a specificity 97.0% for CV. CONCLUSION: Classification criteria for CV were developed, and now need validation.

Mortality rate and outcome factors in mixed cryoglobulinaemia: the impact of hepatitis C virus.

OBJECTIVES: Mixed cryoglobulinaemia (MC) is a chronic small-vessel vasculitis. Shortly after the discovery of hepatitis C virus (HCV) in 1989, an association between HCV infection and MC was being increasingly reported, suggesting the potential pathogenetic implication of HCV in most of the cases that had been previously diagnosed as essential MC. A number of studies have pointed out prognostic factors linked to mortality in this disorder. None of them, however, have clarified the impact of HCV discovery on the natural history of the disease. The aim of the present study was to evaluate mortality in MC after the discovery of HCV infection. METHODS: We retrospectively collected clinical and serological data in 70 unselected HCV-positive patients being followed up at our unit from 1990. Clinical and prognostic factors linked to poor outcome were evaluated. RESULTS: Chronic hepatitis, renal involvement, and intestinal vasculitis were the most frequent causes of death. CONCLUSION: Compared to other series, the outcome in our MC seemed to be better. Factors linked to a poor outcome were renal involvement, widespread vasculitis, male sex, and cryocrit.

[Long term outcome of treatment of diffuse proliferative glomerulonephritis with pulse steroids and short course pulse cyclophosphamide]. / Outcome a lungo termine di pazienti con glomerulonefrite lupica proliferativa diffusa trattati con boli di steroidi e un breve ciclo di ciclofosfamide.

OBJECTIVES: To evaluate the long- term outcome of a group of systemic lupus erythematosus (SLE) patients with diffuse proliferative glomerulonephritis (DPGN) treated with pulse steroids and a short course of pulse cyclophosphamide (Cyc) in order to find out baseline predictor variables of disease outcome at the end of the follow-up. METHODS: Female SLE patients fulfilling ACR criteria with active DPGN treated with pulse steroids and pulse Cyc were enrolled in the study and retrospectively analyzed with particular interest to renal flares and poor renal outcome at the end of follow- up as outcome measures. RESULTS: 30 female patients with DPGN were included, of these 20 (66,7%) patients are actually in follow-up at our unit, 4 (13.3%) died and 6 (20%) were lost during the follow-up. Fourteen patients (46.6%) presented at least one renal flare (RF) during the follow up for a total of 21 flares. At our last observation, 18 (60%) presented a good renal outcome while 12 (40%) had a poor outcome. Lower age at kidney biopsy resulted an important prognostic factor for the occurrence of both RF and poor long- term renal outcome; additionally, a poor renal outcome resulted significantly correlated with an inadequate response at the end of the protocol and with the number of renal flares after remission. CONCLUSIONS: These data suggest that, in general, a short course therapy with Cyc might be effective in controlling disease activity but demonstrated high rate of RF and poor renal outcome over time; however, this protocol might represent an effective therapeutic strategy in a subgroup of patients with specific epidemiological and clinical characteristics and suggest the possibility of tailoring immunosuppressive therapy on the basis of prognostic factor at baseline.

How HCV has changed the approach to mixed cryoglobulinemia.

Mixed cryoglobulinemia is a systemic disease due to a small vessel immune-complex mediated vasculitis. The discovery of a viral origin of the disease has launched a great expectancy among researchers and the years after this finding have been characterized by the effort to reach viral eradication in the hope of obtaining disease remission. Moreover, the use of immunosuppressives has been discouraged for many years as they could favour viral replication, and HCV infection has represented a contraindication to the more recent biological drugs directed against cytokines. The trials with antiviral agents in this disorder, however, has not met the expectations, especially when challenged with some of the most severe complications of the disease; moreover, these medications were not devoid of unexpected side effects, such as the occurrence of peripheral neuropathies. Since lymphoproliferation is one of the features of the disease, this has focused the attention of investigators on the potential benefit of newly targeted therapies specifically directed against B-lymphocytes (such as rituximab). Preliminary results on the use of these medications are promising. Furthermore, the use of biological agents in small open trials in HCV positive arthritis patients has demonstrated an acceptable safety profile. All these empirical observations should probably induce the scientific community to reconsider the therapeutical approach to HCV-related mixed cryoglobulinemia. Indeed, the use of aggressive chemotherapy treatments in the era preceding HCV discovery has not been associated with significant liver toxicities and standard chemotherapy during HCV-related lymphoma carried out a unexpected low rate of severe liver damage. Future efforts should probably focus on the potential benefit of a multi-step, combined anti-viral and cytotoxic therapy (both with standard regimens and new medications).

[Churg-Strauss syndrome: outcome and long-term follow-up of 38 patients from a single Italian centre]. / Caratteristiche clinico-sierologiche e dati di out come di una casistica monocentrica di pazienti affetti da sindrome di Churg-Strauss.

OBJECTIVE: This study was aimed at verifying any potential correlation between anti-myeloperoxidase antineutrophil cytoplasmic antibodies (ANCA-MPO) and clinical features and outcome indices in Churg-Strauss Syndrome (CSS). METHODS: Thirty-eight Churg-Strauss syndrome patients were selected from the medical records of all vasculitis patients attending the Rheumatology and Immunology Unit at the Department of Internal Medicine of the University of Pisa in the decades between 1989 and 2008. Data were analysed retrospectively. Statistical analyses of the results were carried out using the Mann-Whitney test to determine the correlations between the clinical and serological parameters. Qualitative variables were compared using contingency table analysis and Fisher's exact test. RESULTS: ANCA-MPO were detected in15/38 (39%) patients. Positive ANCA status was associated with peripheral neuropathy (p=0.0006), whereas negative ANCA status was associated with lung involvement (p=0.002). Relapses were strongly associated with positive ANCA status (p=0.01) and with an increase in- or a reappearance of ANCA-MPO levels (p=0.006). Finally, ANCA-MPO were significantly associated with neurological damage (p=0.003). CONCLUSIONS: The presence or absence of ANCA-MPO identify different clinical subsets in CSS. Overall, ANCA-MPO appears as a useful tool in the monitoring of CSS and in particular a good predictor of CSS relapses.

Mixed cryoglobulinemia and mortality: a review of the literature.

Mixed cryoglobulinemia is a highly heterogeneous clinical syndrome in terms of clinical presentation, extent and severity of organ involvement, immunological abnormalities and clinical course. Modern management began with the discovery of the close association between this syndrome and hepatitis C virus (HCV) infection. In this review we examined previously published studies on mortality in different series of patients with mixed cryoglobulinemia (MC). Patients with mixed cryo-globulinemia have higher mortality rates, predicted by age, renal involvement, intestinal vasculitis, widespread vasculitis and type of cryoglobulins.

[Churg-Strauss vasculitis and idiopathic hypereosinophyl syndrome: role of molecular biology in the differential diagnosis of hypereosinophyl syndrome]. / Vasculite di Churg-Strauss e sindrome ipereosinofila idiopatica: ruolo della biologia molecolare nella diagnosi differenziale delle sindromi ipereosinofile.

OBJECTIVE: Hypereosinophilic syndromes are a heterogeneous group of uncommon disorders characterized by the presence of marked peripheral blood eosinophilia, tissue eosinophilia, or both, resulting in a wide variety of clinical manifestations, often without an identifiable cause. Churg-Strauss syndrome is a systemic vasculitis characterized by prominent peripheral eosinophilia, asthma and systemic involvement. The presence of mild to severe eosinophilia and systemic involvement raise the search of many trigger factor that need to be ruled out. Distinguishing CSS from idiopathic hypereosinophilic syndrome may be particularly challenging, especially in ANCA negative patients. METHODS: The aim of the present study was to present a small case series of patients referred to a Rheumatology Unit for mild to severe eosinophilia and signs and symptoms of systemic involvement and to outline the clinical significance of molecular biology in the work-up of hypereosinophilia. RESULTS: Eleven patients with moderate to severe peripheral eosinophylia, were referred to our Unit from 1996 to 2007. Female to male ratio was 7/4, mean age 40.54 (range 22-75). Three out of eleven patients resulted positive for molecular biology. The diagnosis of idiopathic hypereosinophylia was confirmed in one out of three on the basis of the clinical picture and bone marrow biopsy. CONCLUSIONS: Molecular biology may be useful in the screening and in the follow-up of a new hypereosinophylic patient.

[Fibronectin gene polymorphisms and clinical manifestations of mixed cryoglobulinemic syndrome: increased risk of lymphoma associated to MspI DD and HaeIII AA genotypes]. / Polimorfismi del gene della fibronectina e manifestazioni cliniche della sindrome crioglobulinemica: aumentato rischio di linfoma legato ai genotipi MspI DD e HaeIII AA.

OBJECTIVE: To analyse FN gene polymorphisms in type II mixed cryoglobulinemic syndrome (MCsn), an immune-complex mediated systemic vasculitis linked to hepatitis C virus (HCV) infection and characterized by rheumatoid factor (RF) positive B-cell proliferation at high risk for the progression into non Hogkin's lymphoma (NHL). METHODS: Samples from eighty-one patients, with MCsn (type II serum cryoglobulins and clinical signs of vasculitis were studied. Sixty-five (65/81, 80.3%) patients were HCV-positive. Twenty-one (25.9%) patients had developed a B-cell NHL during the course of MCsn. Seventy-two patients with HCV-negative and MC-unrelated NHL and 110 healthy blood donors (HBDs) were taken as controls. HaeIIIb and MspI FN gene polymorphisms were analysed by ELISA, whenever possible. RESULTS: HaeIIIb and MspI allele and genotypic frequencies did not differ between MCsn patients and HBDs. Of note, the DD-MspI allele and genotype frequencies did not differ between MCsn patients and HBDs. Of note, the DD-MspI (OR = 5.56; DI = 1.67-18.51, p = 0.0046) and the AA-HaeIIIb (OR = 5.54, CI = 1.64- 18.76, p = 0.0066) homozygosis appeared significantly and independently associated with the development of B-cell NHL in MCsn patients, with the HaeIIIbA allele possibly conferring an increased risk of NHL in the general population (OR = 1.72, CI = 1.128-2.635, p = 0.0133). In contrast, the major vasculitic manifestations, such as peripheral neuropathy, skin ulcers and glomerulonephritis tended to be associated with the counterpart MspI C allele. No association between FN plasma levels and FN genotypes was found. CONCLUSION: Genotyping for MspI and HaeIIIb FN gene polymorphisms may be clinically relevant to define the predisposition to the major clinical manifestations in MCsn.

Functional and isokinetic assessment of muscle strength in patients with idiopathic inflammatory myopathies.

OBJECTIVE: To assess muscle strength in patients with idiopathic inflammatory myopathies (IIM) using neuromuscular scales and isokinetic testing. METHODS: Muscle function was evaluated in 27 IIM patients being followed at the Rheumatology Unit of the University of Pisa using: (i) a modified version of the grading system used to assess Duchenne dystrophy, (ii) the four-stage grading system of Henriksson and Sandstedt, (iii) an isokinetic muscle strength test (Kin Com, Chatanooga) and (iv) the Health Assessment Questionnaire (HAQ). RESULTS: The neuromuscular scales showed normal or only mildly impaired muscle strength in 60% (Duchenne scale) and 80% (Henriksson and Sandstedt scale) of the patients, respectively, whereas isokinetic testing detected moderate to severe reductions in muscle strength in almost 70% of the patients. No correlations were observed between muscle strength and disease activity, therapy, age at evaluation and disease duration. There was a correlation between the results of the HAQ and neuromuscular testing, but not the isokinetic test. CONCLUSIONS: Although less easy and more expensive to administer, isokinetic testing appears to be a more sensitive instrument than the standard neuromuscular tests for assessing muscle function in IIM patients. In particular, it can detect small reductions in muscle strength.

[Primary Sjogren's syndrome: clinical and serological feature of a single centre]. / Sindrome di Sjogren primitiva: descrizione clinica e sierologica di una casistica monocentrica.

OBJECTIVE: To describe clinical and serological features of a large series of patients affected by primary Sjogren's syndrome (pSS), assessing the evolution of the disease in a long-term follow-up study. METHODS: Clinical and laboratory data of 250 patients with pSS attending our Unit for a mean follow-up period of 140 months were retrospectively collected and analysed. In all the cases the diagnosis was made according with the recent international criteria. RESULTS: Glandular involvement was almost universally present, typically as the first manifestation of the disease and a slow progression of the salivary and lachrymal dysfunction was seen during the observation period. Extraglandular involvement was mild, quite rare and delayed. The respective percentages for muscle-skeletal disease, urogenital, haematological, skin, pulmonary, gastrointestinal, neurological and renal involvement were 60%, 40%, 24%, 20%, 11%, 7%, 8% and 3%. Only 6 patients developed a lymphoma. The serological pattern of the majority of patients remained constant throughout the follow-up period. CONCLUSIONS: pSS is often a benign condition. Since some patients may develop lymphoid malignancies, clinical follow-up is recommended.

A novel nonsense mutation (Q509X) in three Italian late-infantile neuronal ceroid-lipofuscinosis children.

We identified a novel nonsense CLN2 mutation (Q509X) in three Italian children with classical late-infantile neuronal ceroid lipofuscinosis (LINCL) from two unrelated families. The mutation introduced a premature stop codon in exon 12 of the CLN2 gene, resulting in a protein lacking the last 54 residues. Haplotype analysis suggested independent origin of the mutation in our families. The protein truncation test was employed to verify the functional consequences of the novel Q509X mutation. In Patient 1, the mutant alleles were transcribed but translated in a shorted peptide suggesting that the Q509X mutation is likely to interfere with CLN2p function. While expanding the list of genetic variants in LINCL, our findings represent the first molecular characterization of LINCL patients in South Europe.

A simple method for the biochemical purification of Ro/SS-A antigen.

In the present study, Ro/SS-A antigen has been isolated from human spleen by a two-step procedure. In the first step most of the non-antigenic material was removed by means of ammonium sulphate precipitation and ion exchange chromatography. The final purification was obtained by passing the Ro/SS-A-containing fractions twice through a Mono Q ion exchange fast protein liquid chromatography (FPLC) column. The purified antigen showed identical immunoreactivity with crude material on CIE and was composed of two polypeptides with a molecular weight of approximately 60,000 and 55,000 respectively on SDS-PAGE, both reacting on Western blotting with a panel of anti-Ro/SS-A antisera. This system permits milligrams of highly purified antigen to be obtained from grams of human spleen.

Evaluation of S-adenosylmethionine in primary fibromyalgia. A double-blind crossover study.

The effect of S-adenosylmethionine (SAMe) and placebo was evaluated in a short-term crossover study of 17 patients with primary fibromyalgia. Eleven of 17 patients had a significant depressive state as assessed by either the Hamilton Depression Rating Scale or the Scala di Autovalutazione per la Depressione (SAD) rating scale. The number of trigger points plus painful anatomic sites decreased after administration of SAMe (p less than 0.02) but not after placebo treatment. In addition, scores on both the Hamilton and SAD rating scales improved after SAMe administration (p less than 0.05 and p less than 0.005, respectively), whereas they did not significantly change after placebo treatment. In all the patients, there was a good correlation between scores on the Hamilton rating scale and the number of trigger points. Thus, this preliminary study confirms the close relationship between primary fibromyalgia and psychologic disturbances, particularly with regards to a depressive state. SAMe treatment, by improving the depressive state and reducing the number of trigger points, seems to be an effective and safe therapy in the management of primary fibromyalgia.

Low-antigen-content diet in the treatment of patients with mixed cryoglobulinemia.

PURPOSE: The effects of a low-antigen-content diet (LAC diet) versus a standard normocaloric diet on the signs and symptoms of mixed cryoglobulinemia (MC) were compared in a crossover randomized study. PATIENTS AND METHODS: The study consisted of 24 outpatients with MC, and was carried out in a 48-week period. After 18 weeks of either the LAC or the placebo diet, patients returned to a totally unrestricted diet for 12 weeks (washout period) and crossed over to the second half of the study for the other 18 weeks. RESULTS: After three weeks of the restricted LAC diet, the cryocrit decreased from 3.5 +/- 3.4% (mean +/- SD) to 2.3 +/- 2.0% (p less than 0.01), and the circulating immune complex levels decreased from 48 +/- 30% to 39 +/- 34% (p less than 0.01). At the same time, the purpura score (p less than 0.05), glutamic pyruvic transaminase level (p less than 0.01), and gamma glutamyl transferase level (p less than 0.001) significantly improved. Splenic reticuloendothelial function, measured as the half-life of heat-damaged autologous red cells, decreased from 41 +/- 21 minutes to 21 +/- 10 minutes (p less than 0.005). In contrast, no significant parallel clinical, biochemical, and immunologic changes occurred in the same patients during the placebo (standard normocaloric) diet. CONCLUSION: These data show that an LAC diet decreases the amount of circulating immune complexes in MC and can modify certain signs and symptoms of the disease. These effects of the LAC diet may be explained by postulating a functional restoration of the mononuclear phagocytic system.