Genetically transitional disease: conceptual understanding and applicability to rheumatic disease.

In genomic medicine, the concept of genetically transitional disease (GTD) refers to cases in which gene mutation is necessary but not sufficient to cause disease. In this Perspective, we apply this novel concept to rheumatic diseases, which have been linked to hundreds of genetic variants via association studies. These variants are in the 'grey zone' between monogenic variants with large effect sizes and common susceptibility alleles with small effect sizes.

Genetic variations in NLRP3 and NLRP12 genes in adult-onset patients with autoinflammatory diseases: a comparative study.

Objectives: Cryopyrin-associated periodic syndrome or NLRP3-associated autoinflammatory disease (NLRP3-AID) and NLRP12-AID are both Mendelian disorders with autosomal dominant inheritance. Both diseases are rare, primarily reported in the pediatric population, and are thought to be phenotypically indistinguishable. We provide the largest cohort of adult-onset patients and compared these diseases and the gene variant frequency to population controls.

The Complement System and C1q in Chronic Hepatitis C Virus Infection and Mixed Cryoglobulinemia.

The complement system bridges innate and adaptive immunity against microbial infections, with viral infection being a major trigger. Activation of the classical, alternative, and lectin pathways have been reported in chronic hepatitis C virus (HCV) infection and/or cryoglobulinemia. HCV infection leads to dysregulation of complement-mediated immune responses.

Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial.

Importance: Familial amyloid polyneuropathy, a lethal genetic disease caused by aggregation of variant transthyretin, induces progressive peripheral nerve deficits and disability. Diflunisal, a nonsteroidal anti-inflammatory agent, stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro.

Objective: To determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy.

Rheumatoid factor, complement, and mixed cryoglobulinemia.

Low serum level of complement component 4 (C4) that occurs in mixed cryoglobulinemia (MC) may be due to in vivo or ex vivo activation of complement by the classical pathway. Potential activators include monoclonal IgM rheumatoid factor (RF), IgG antibodies, and the complexing of the two in the cold, perhaps modulated by the rheology and stoichiometry of cryocomplexes in specific microcirculations. There is also the potential for activation of complement by the alternative and lectin pathways, particularly in the setting of chronic infection and immune stimulation caused by hepatitis C virus (HCV).

Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis.

Objective: Amyloid A protein quantification in fat tissue is a new immunochemical method for detecting AA amyloidosis, a rare but serious disease. The objective was to assess diagnostic performance in clinical AA amyloidosis.

Methods: Abdominal subcutaneous fat tissue of patients with AA amyloidosis was studied at the start of an international clinical trial with eprodisate (NC-503; 1,3-propanedisulfonate; Kiacta), an antiamyloid compound.

Eprodisate for the treatment of renal disease in AA amyloidosis.

Background: Amyloid A (AA) amyloidosis is a complication of chronic inflammatory conditions that develops when proteolytic fragments of serum amyloid A protein (SAA) are deposited in tissues as amyloid fibrils. Amyloid deposition in the kidney causes progressive deterioration in renal function. Eprodisate is a member of a new class of compounds designed to interfere with interactions between amyloidogenic proteins and glycosaminoglycans and thereby inhibit polymerization of amyloid fibrils and deposition of the fibrils in tissues.

In normal rat, intraventricularly administered insulin-like growth factor-1 is rapidly cleared from CSF with limited distribution into brain.

Background: Putatively active drugs are often intraventricularly administered to gain direct access to brain and circumvent the blood-brain barrier. A few studies on the normal central nervous system (CNS) have shown, however, that the distribution of materials after intraventricular injections is much more limited than presumed and their exit from cerebrospinal fluid (CSF) is more rapid than generally believed. In this study, we report the intracranial distribution and the clearance from CSF and adjacent CNS tissue of radiolabeled insulin-like growth factor-1 after injection into one lateral ventricle of the normal rat brain.

Rheumatologic illnesses: treatment strategies for older adults.

Basic objectives of arthritis therapy are to reduce musculoskeletal pain, slow progression of disease, maintain and improve function and quality of life, and avoid adverse drug reactions. Both nonpharmacologic and pharmacologic approaches may be taken. The former include patient education, cognitive therapy, high-intensity progressive-resistance or strength training, weight control, cold therapy, heat, massage, relaxation and distraction techniques.

Geriatric autoimmune diseases: systemic lupus erythematosus, Sjogren's syndrome, and myositis.

Systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), and dermatomyositis (DM)/polymyositis (PM) may be encountered in geriatric patients due to improved survival rates in patients with younger ages of onset or from elderly-onset (EO) disease. EO disease accounts for up to 20% of patients affected by these disorders, and is typically insidious rather than acute. Whereas SS and DM/PM are considered autoimmune diseases with distinct organ specificity, SLE is a systemic disorder that may affect multiple organ systems.

Crystal arthritis. Gout and pseudogout in the geriatric patient.

Gout and pseudogout are inflammatory arthritides due to monosodium urate and calcium pyrophosphate dihydrate crystal formation. Both are prevalent among geriatric patients, and can present as acute mono- or oligoarticular disease, or as a chronic polyarthropathy resembling osteoarthritis or rheumatoid arthritis. Gout in the geriatric patient is a disease affecting women, commonly associated with diuretic usage, often involves the fingers, may be complicated by the development of masses of uric acid crystals (tophi) in soft tissues, and is frequently polyarticular.

Osteoarthritis. A review of musculoskeletal aging and treatment issues in geriatric patients.

Musculoskeletal disease is extraordinarily prevalent among geriatric patients, with an incidence that is increasing with the growth of this segment of the population. It is a major cause of disability, dependency, dysmobility, pain, and depression. Rheumatologic evaluation of the geriatric patient provides challenges to the clinician in the proper interpretation of pain, the effect of comorbidities and multiple medications, and the need to consider an interdisciplinary approach that includes the recognition of cognitive deficits, functional evaluations, and treatment of muscle atrophy.

Autoimmune disease complicating antiviral therapy for hepatitis C virus infection.

Objective: To review autoimmune disease complicating therapy with type I interferons (IFNs), specifically in the setting of hepatitis C virus (HCV) infection.

Methods: This study describes 13 reported cases of drug-induced systemic lupus erythematosus (SLE) associated with IFN therapy for the period reported during 1990-2002 by searching MEDLINE. In addition, 2 additional patients are presented, 1 with SLE and 1 with an antineutrophil cytoplasmic antibody (ANCA)-positive nephritis, with long-term follow-up.