Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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1450620 | Three cases of malignant neoplasm, pneumonitis, and pancytopenia during treatment with low | 1992 Oct | A 77-year-old man with chronic obstructive pulmonary disease was treated with low-dose methotrexate (7.5-15 mg per week). After 15 months a diagnosis of urothelial carcinoma of the bladder was made; after a further 6 months pneumonitis and pancytopenia developed. The patient died due to massive pulmonary hemorrhage. A malignant teratoma was diagnosed in a 65-year-old asthmatic man 16 months after initiation of methotrexate therapy (15 mg per week). The patient died 4 months later due to fulminant progression of the neoplasm. A third malignant neoplasm (dermal squamous cell carcinoma) was seen in a 64-year-old woman with rheumatoid arthritis after 13 months treatment with 7.5 mg methotrexate per week. These three cases, while obviously not proving a causal relationship between long-term treatment with low-dose methotrexate and development of malignant neoplasm, do call for stringent treatment criteria, close surveillance, and prospective studies. | |
1426857 | In situ characterization of mononuclear cell phenotype in intrahepatic lymphoid follicles | 1992 Oct | The author examined liver biopsy specimens obtained from 596 patients with chronic viral hepatitis to clarify the role of lymphoid follicle formation in the portal spaces. Lymphoid follicles were observed more frequently in chronic hepatitis non-A non-B than in chronic hepatitis B and were also common in patients with anti-hepatitis C virus-positive non-A non-B hepatitis. Immunohistology revealed that these hepatic lymphoid follicles resembled the lymphoid follicles of synovial tissue in rheumatoid arthritis. In situ hepatitis B virus markers were examined in 40 patients with chronic hepatitis B showing lymphoid follicles. Among these, hepatitis B surface antigen (HBsAg) was detected in liver cells as well as in the center of the follicles in 19 patients (47.5%). By immune electron microscopy, the author confirmed the HBsAg-positive cells in the lymphoid follicles as follicular dendritic cells. These cells appeared to be a site for antigen trapping in the follicles, therefore, the intrahepatic lymphoid follicles are suggested to play a role in immune response to HBsAg in chronic hepatitis B. | |
1400804 | High-performance liquid chromatographic determination of naproxen, ibuprofen and diclofena | 1992 Jul 24 | High-performance liquid chromatographic assay procedures have been developed for naproxen, ibuprofen and diclofenac in human plasma and synovial fluid samples. A single liquid-liquid extraction procedure was used to isolate each compound from acidified biological matrix prior to the quantitative analysis. A Spherisorb ODS column (12.5 cm x 4.6 mm I.D.) was used for all the chromatography. Naproxen was eluted with a mobile phase of methanol-Sörensen's buffer at pH 7 (37:63, v/v). Ibuprofen and diclofenac were eluted using mobile phases of methanol-water at pH 3.3 (65:35, v/v and 63:37, v/v, respectively). Diphenylacetic acid was used as the internal standard for the assay of naproxen and flurbiprofen was used in the analysis of ibuprofen and diclofenac. Inter- and intra-day coefficients of variation were less than 7%. The assays were used in clinical studies of the three drugs in osteo- and rheumatoid arthritis patients. | |
1358348 | Evaluation of the A-60 IgG ELISA serodiagnostic test for tuberculosis in Taiwan. | 1992 Jun | To assess the applicability of a serologic test of specific IgG antibody for tuberculous infection in the Taiwan population, serum samples obtained from 118 subjects were analyzed by an ELISA test using mycobacterial antigen 60. There were 50 patients with a documented active infection caused by Mycobacterium tuberculosis (39 pulmonary tuberculosis, five pleurisy, three cervical lymphadenitis and three miliary tuberculosis with extrapulmonary involvement). Of these 50 patients, 42 (84%) showed a positive ELISA test (titer > 200 U). Of the 19 patients with inactive pulmonary tuberculosis, seven (37%) had a positive titer. Of the 22 patients with pulmonary disease other than tuberculosis, four (18%) showed a false-positive. In eight patients with autoimmune diseases, only the patient with rheumatoid arthritis had a positive reaction. One of the 19 healthy controls (5.3%) showed a false-positive result. The overall false-positive rate for the nontuberculous group was 12%. Follow-up examinations in 20 patients with active tuberculosis one month after treatment revealed that seven had an elevation in titers (three of them were initially negative and became positive later), five remained high and eight decreased in titers. Further examinations in six patients two months after treatment showed a decrease in titers. We conclude that this ELISA assay of specific IgG antibody is a valuable serologic test for diagnosis of M. tuberculosis infection. It may be useful in areas with a high prevalence of M. tuberculosis infection. | |
1328632 | Peripheral neuropathy in mixed cryoglobulinemia: clinical and electrophysiologic investiga | 1992 Jun | Peripheral neuropathy has been described in different rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus and systemic vasculitis, but usually in limited numbers of patients. Nerve injury is more frequently reported in mixed cryoglobulinemia. In earlier studies generally performed in small series of patients, prevalence of peripheral neuropathy varied widely. We evaluated prevalence of peripheral neuropathy in 33 unselected patients with mixed cryoglobulinemia (25 women, 8 men, aged from 45-71 years). Neurologic involvement was detected using a complete clinical and electrophysiologic assessment, including sensory motor conduction velocities, F wave and H reflex. Neurologic examination revealed a neuropathy in 48% of subjects, while electrophysiologic variables were altered in 82%; a percentage similar to that of subjective symptoms (91%). Among electrophysiologic investigations, F wave was altered in 22/33 subjects (67%); therefore, this variable seems to be the most reliable for the detection of neurologic involvement. Cryocrit levels were significantly higher in patients with peripheral neuropathy: abnormal examination (p less than 0.01), sensory motor conduction (p less than 0.04), and F wave alterations (p less than 0.008). In addition, hemorheological abnormalities seem to contribute to the pathogenesis of nerve injury. Our results indicate that peripheral neuropathy, to a variable degree, is present in the majority of patients with mixed cryoglobulinemia, and a complete clinical and electrophysiologic investigation can be useful for an early and correct diagnosis. | |
19078063 | Connective tissue disease in people exposed to organic chemical solvents: systemic scleros | 1996 Aug | The etiology of connective tissue disease appears to be multifactorial and includes genetic factors, autoimmune responsiveness and environmental elements. This survery in a clinical rheumatology practice has investigated the relationship of environmental occupational organic solvent exposure and the presence of connective tissue disease. Two hundred and seventynine consecutive patients with various connective tissue diseases were classified according to the American College of Rheumatology criteria for systemic lupus erythematosus, systemic sclerosis (scleroderma), and rheumatoid arthritis and clinically as dermatomyositis/polymyositis, mixed connective tissue disease, and Sjogren's syndrome. Comprehensive questionnaires were used regarding diagnosis, occupational history and chemical and other substance exposure.There was a striking increase in exposure to organic chemical solvents in the population of people with systemic sclerosis. Twelve of 33 people with scleroderma gave a history of organic chemical exposure versus 22 of the other 246 people (p = .00001); 3 of 33 with systemic sclerosis were exposed to perchloroethylene versus 2 of the other 246 (p = .00076), 2 scleroderma patients to trichloroethane versus 1 of the other 246 (p = .0031), and 2 scleroderma patients each to petroleum solvent and fluorocarbon solvent versus 0 of the other 246 (p = .00011) for each. Four of these 33 scleroderma patients worked in dry cleaning plants versus one of the other 246 (p < .00001), and 2 scleroderma subjects had been cleaning airplane parts versus 2 of the other 246 (p = .00076).These observations support a hypothesis for a role of occupational exposure in some patients with scleroderma. Prospective epidemiologic studies are needed. Clinicians should question new patients about such exposures and may wish to counsel them about avoiding exposures. However, no data have yet suggested that stopping the exposures made patients healthier. | |
12179257 | [Non-contraceptive benefits of contraception]. | 1995 Oct | ||
1587165 | Anterior surgery of the upper cervical spine. | 1992 Jan | The authors report the results obtained in a series of more than 80 cases submitted to 76 operations of the upper cervical spine by transoral approach with a minimum follow-up of two years. The cases include: 15 unstable fractures or non-union of the odontoid processes; 28 cases of post-traumatic instability of C1-C2 level without fracture of the odontoid process; 13 cases of rheumatoid arthritis with instability at C1-C2; 14 cases of severe anomalies of the craniovertebral junction, often associated with basilar impression and spinal cord compression, of which 7 cases presented with tetraparesis; 6 malignant tumors. The method used involves an anterior transoral approach, more often without tracheotomy, and with exposure of the anterior aspect of the atlas and of the odontoid process by means of a midline incision of the posterior wall of the pharynx. When spinal cord lesion was present, decompression and reconstruction by bone grafts taken from the iliac crest were performed. In nearly all of the cases osteosynthesis with an anterior plate was used. Complications were mild. There were two cases of infection, observed at the onset of our experience, which were resolved after removal of the instrumentation. There was loosening of a screw in three cases; this was eliminated through the digestive tube with no consequences. There were no early intra- or postoperative deaths. Consolidation was obtained in most of the patients, and only in three cases did we observe a loss of postoperative reduction. Among patients affected with tetraparesis we observed many cases of neurological recovery.(ABSTRACT TRUNCATED AT 250 WORDS) | |
8981890 | Hybrid total hip arthroplasty: a 7- to 11-year followup. | 1996 Dec | A consecutive series of 125 hybrid total hip arthroplasties were performed in 120 patients by a single surgeon and were observed for an average of 8.6 years (range, 7-11 years). There were 38 men and 82 women with an average age of 71 years (range, 25-87 years) at the time of surgery. The diagnoses included primary and secondary osteoarthritis in 112 patients, osteonecrosis in 5 patients, and rheumatoid arthritis in 3 patients. All acetabular components were modular and had a Ti shell fixed with an average of 3 screws. The cemented femoral component was either Precoat or Precoat Plus with a 28-mm modular CoCr femoral head. The patients were prospectively observed clinically using the Harris hip score and radiographically using the Hip Society methods. Of the 125 total hip arthroplasties, 123 were followed for the entire observation period. The average preoperative Harris Hip Score was 37 (range, 15-55) and at the latest followup was 92 (range, 65-100). One acetabular component was revised for recurrent dislocations 3 years after surgery, and 1 stem was revised for mechanical loosening and 1 stem was radiographically loose. There was no evidence of cup migration of more than 1 mm. There were no radiolucencies around any of the screws. Two sockets had polyethylene wear of 2 mm. Localized pelvic osteolysis was noted in 5 hips (4%). The results of this study suggested that hybrid total hip replacement is an excellent procedure for reconstruction of the arthritic hip with minimal evidence of polyethylene wear and pelvic osteolysis. | |
8942447 | Genetic association of the HLA DRB1 gene locus on chromosome 6p21.3 with schizophrenia. | 1996 Dec | OBJECTIVE: The authors investigated the human leukocyte antigen (HLA) DRB1*04 gene in schizophrenic patients because it is positively associated with rheumatoid arthritis, an autoimmune disease that exhibits a strong negative association with schizophrenia. The HLA DQB1*0602 allele was also studied because of previous reports of genetic association between it and schizophrenia. Maternal HLA was investigated because of the reported association between prenatal influenza and schizophrenia and the central role of HLA molecules in the immune response to viral infections. METHOD: Polymerase chain reactions and sequence-specific oligonucleotide probes were used to genotype 94 unrelated patients with DSM-III-R schizophrenia, 92 mothers of schizophrenic offspring who were not related either to each other or to the 94 patients, and 177 healthy comparison subjects. RESULTS: The frequency of DRB1*04 alleles was significantly lower in both the schizophrenic patients and the unrelated mothers of schizophrenic offspring than in the healthy comparison subjects. No significant differences were found for DQB1*0602. CONCLUSIONS: DRB1*04 alleles may partially account for the genetic predisposition to schizophrenia. The association reported here may be explained by genetic linkage or by an autoimmune pathophysiology for a proportion of schizophrenia cases. Alternatively, it may be that maternal B lymphocytes that do not express the DR4 antigen encoded by DRB1*04 respond to influenza virus by producing antibodies that perturb neurodevelopment, thus underpinning a proportion of schizophrenia cases. | |
8978964 | Etiological factors and underlying conditions in patients with leucocytoclastic vasculitis | 1996 Nov | This study concerns a retrospective analysis of 63 consecutive patients presenting with leukocytoclastic vasculitis at the Departments of Dermatology or Rheumatology of the University Hospital Ghent (Belgium) (period 1988-1993). The diagnosis of leukocytoclastic vasculitis was confirmed by histopathology in all cases. All patients were screened for underlying causes, including drugs, infection, systemic autoimmune disease or neoplasia. In 34 patients, an etiological factor was identified: drugs (5 patients), infection (6 patients), drugs or infection (4 patients), systemic autoimmune disease (10 patients), Henoch Shönlein (6 patients), neoplasia (2 patients) and cryoglobulinemia (1 patient). In the group of patients with leukocytoclastic vasculitis in the context of systemic autoimmune disease, 4 patients suffered from systemic lupus erythematosus, 2 from Wegener's disease, 2 from Behçet's disease, 1 from polyarteritis nodosa and 1 from rheumatoid arthritis. In the remaining 29 patients, no cause for the vasculitis could be identified. | |
8751472 | Aggressive acute CD3+, CD56- T cell large granular lymphocyte leukemia with two stages of | 1996 Sep | In the majority of clonal expansions of CD3+ large granular lymphocytes (LGL), referred to as T-LGL leukemia, patients have a chronic disease, often manifested by severe neutropenia, rheumatoid arthritis, and mild to moderate splenomegaly. The characteristic leukemic phenotype is CD3+, CD8+, CD16+, CD57+ and CD56-. Here we report an unusual case of T-LGL (CD3cyt+, CD3surface-, CD16+, CD56-) with clinicopathological features (acute presentation, large tumor mass, and systemic illness with highLGL counts at diagnosis) similar to those described for patients with CD3-natural killer (NK)-LGL leukemia. Two distinct stages of maturation arrest were observed: in the lymph node abnormal cells were CD4+, CD8+ whereas the majority of circulating leukemic cells expressed only CD8. TCR gamma (TCR gamma) gene configuration demonstrated that these originated from the same T cell clone, suggesting a maturation process between the two populations, or preferential passage of CD8 single positive cells into the blood. | |
8839774 | CD4-reactive antibodies in systemic lupus erythematosus. | 1996 Aug | An important place in the immune network is reserved for specific interactions between regulatory antibodies (Ab) and their ligands on T and B lymphocytes. Several lines of evidence indicate that the CD4 glycoprotein may be recognized by such Ab. High levels of CD4-reactive Ab occur in approximately 10-20% of HIV-infected patients. Moreover, between 20 and 30% SLE patients have Ab preferentially reactive with the CD4+ T cells. In relation to this, we have done studies aimed at demonstrating the existence and characteristics of Ab directly targeting CD4 in patients with SLE in comparison with rheumatoid arthritis and normal controls. Assessment of the CD4-reactive Ab by different approaches revealed a several-fold increase in serum concentration of anti-CD4 Ab restricted to a subset of SLE patients (n = 15/87, 17.2%). Enhanced binding was shown to occur specifically both on native CD4 (by immunofluorescence) and on recombinant CD4 (by ELISA and Western blot). Anti-CD4 Ab belonged to IgM and/or IgG isotypes. The overall binding of immunoglobulins to the CD4 molecule was not significantly contributed by DNA/anti-DNA and other circulating immune complexes, and there was no restriction in the usage of kappa and lambda light chains. Clinically, high CD4 reactivity occurred in SLE patients with active disease, as measured by the SLEDAI, and was associated with particular clinical manifestations, including neuropsychiatric disease and lymphopenia. | |
10160476 | Is there scope for improving the cost-effective prescribing of nonsteroidal anti-inflammat | 1996 Jun | Nonsteroidal anti-inflammatory drugs (NSAIDs) are used widely throughout the world to relieve the symptoms of musculoskeletal disorders, in particular osteoarthritis and rheumatoid arthritis. These drugs have significant adverse effects, including gastrointestinal ulceration and the associated complications of perforation and bleeding. The relative toxicity of competing forms of branded and generic NSAIDs varies considerably. Their acquisition cost also varies considerably, sometimes with relatively more toxic drugs being more expensive. Thus, it may be possible to reduce both adverse effects and pharmaceutical expenditures associated with NSAIDs, if doctors' prescribing behaviour can be changed. A tentative exploration of alternative patterns of NSAID use demonstrates that it may be possible to reduce expenditures on NSAIDs in the UK to below the 1994 level, and reduce adverse events. If prescribing of NSAIDs was reduced by 25%, average dosage reduced by 10% and patients switched to less toxic NSAIDs, up to 86 million pounds sterling could be saved per year in the UK, the number of serious adverse events per year reduced by 189 (from a baseline figure of around 500) and the annual number of gastrointestinal complications reduced by 127 (from a baseline figure of around 315). Such results may be achieved without reductions in the quality of life of patients using these drugs. The available clinical and economic information about NSAIDs is limited, and the publication of numerous poor quality studies has corrupted the knowledge base. Despite these problems, there appears to be enough evidence to indicate that expenditure on NSAIDs could be considerably reduced and significant adverse effects could be avoided if general practitioners were persuaded to change their prescribing behaviour. Inefficient and inappropriate prescribing of these often beneficial, but sometimes dangerous, drugs appears to be wasting scarce UK National Health Service resources and harming patients. | |
8991539 | Dendritic cells: origin and differentiation. | 1996 Mar | Dendritic cells (DC) are bone marrow-derived cells that are specialized to take up, process and present antigen, and have the capacity to stimulate resting T cells in the primary immune response. DC are a unique population that is likely to derive from a myeloid precursor cell. DC differentiation from bone marrow precursors in enhanced by the cytokines GM-CSF and tumor necrosis factor-alpha. In contrast, it has been proposed that thymic DC and T cells arise from a common stem cell, and that these DC play a specific role in the negative selection of thymic T cells. A number of post-bone marrow differentiation stages can be defined phenotypically and functionally. Undifferentiated DC have very active endocytic pathways, including receptor-mediated endocytosis involving a mannose/beta glucan receptor, and macropinocytosis of soluble antigen. In contrast, later stages of maturation are associated with a decreased ability to take up and process antigen, and increasing expression of major histocompatibility complex, adhesion and costimulatory molecules. Finally, activation of DC for full antigen-presenting cell function can be identified by the expression of CD28 ligands. The inflammatory site in rheumatoid arthritis is a human model of DC differentiation in response to a chronic antigenic stimulus. The features of this DC model are discussed. | |
8821775 | Additive effects of suboptimal doses of estrogen and cortisone on the suppression of T lym | 1996 Jan | Many immune-mediated inflammatory diseases are treated with corticosteroids. This type of treatment is, however, often afflicted with side-effects such as osteoporosis and atherosclerosis. During the last decades also sex steroids, such as estrogens, have been shown to have immunoregulatory properties. In this report we studied the effect of combined treatment with suboptimal doses of dexamethasone and estradiol on T lymphocyte mediated delayed type hypersensitivity (DTH), granulocyte-mediated inflammatory responses, immunoglobulin production and antigen specific antibody responses in mice. The results show that the two hormones display additive effects on suppression of DTH. In contrast, such additive effects were not observed in granulocyte-mediated inflammation. B lymphocyte activity, measured by immunoglobulin production and antigen-specific antibody responses, were increased after exposure to estradiol and suppressed by dexamethasone. In mice treated with both hormones the up regulation of B lymphocytes was still evident. The results could indicate the potential to use combinations of corticosteroids and estrogen in the treatment of T lymphocyte dependent rheumatic diseases such as rheumatoid arthritis (RA). In addition, the B lymphocyte stimulation by estrogen in cortisone exposed mice stimulate to future studies in humans if estrogen containing contraceptives or post menopausal hormone treatment could have triggering effects in patients with immune complex mediated diseases also when they are on corticosteroid treatment. | |
8770235 | Antioxidant activity of Chinese ant extract preparations. | 1995 Dec | Chinese ant extract preparations (CAEP) are a Chinese traditional medicine which is mainly used as a health food or drink for the treatment of rheumatism, rheumatoid arthritis, chronic hepatitis, sexual hypofunction, and antiaging in China. The effects on free radicals were examined by electron spin resonance spectrometry using the spin trapping agent 5.5-dimethyl-1-pyrroline-1-oxide (DMPO). Superoxide radicals (3.35 x 10(15) spins/ml) were quenched 50% by the extract at 0.5 mg/ml. The CAEP extract at 0.7 mg/ml inhibited 50% of hydroxyl radicals (52.0 x 10(15) spins/ml) generated by the Fenton reaction. Against DPPH radical, the scavenging action of CAEP was observed at 1.8 mg/ml of the extract and 50% of the DPPH radicals (8.14 x 10(15) spins/ml) were quenched. In vitro tests showed that CAEP inhibited the production of thiobarbituric acid-reactive substances, an index of lipid peroxidation, in rat brain homogenate. | |
8562547 | Cataract patients in a defined Swedish population 1986-90: VII Inpatient and outpatient st | 1995 Dec | AIMS: Cataract surgery has at times been said to correlate with an increased death risk. We have therefore analysed the standardised death ratio in a population based cohort of patients that had undergone cataract surgery. METHODS: Data for all patients undergoing cataract surgery from 1986 up to and including 1990 in the Lund Health Care District were prospectively recorded, and 5120 were retrieved for analysis. Death dates and primary death diagnoses for each patient were obtained from the Swedish Bureau of Census up to and including 1991. Standardised mortality ratios were calculated for all patients, subdivided into a number of categories: inpatients, outpatients, sex, age < 75 years, age > or = 75 years, patients with heart and circulatory diseases, with malignant tumours, and with diabetes. The cut off age was set at 74 because this divided the patients into two approximately equal groups. Using time dependent survival regression, the relative risk for dying were estimated for sex, age, and for postoperative YAG laser capsulotomy, and also for diabetic patients and patients with rheumatoid arthritis. RESULTS: Inpatients almost always show an increased standardised mortality ratio compared with outpatients. Young patients and diabetic patients also showed an increased standardised mortality ratio, compared with the normal population, but not older patients, who constitute the majority. Cardiovascular death diagnoses were overrepresented among the young. CONCLUSIONS: Cataract surgery is correlated with an increased standardised mortality ratio only in young patients and in patients with certain complicating diseases like diabetes and cardiovascular diseases. | |
7673286 | Discoid lateral meniscus in children. Long-term follow-up after excision. | 1995 Sep | We retrospectively reviewed the results for fifteen patients, eight girls and seven boys, who had had a total of eighteen meniscectomies performed for a discoid meniscus at The Hospital for Special Surgery between January 1, 1955, and December 31, 1983. The average age was ten and a half years (range, six to sixteen years) at the time of the operation and twenty-eight years (range, twenty to thirty-six years) at the time of follow-up. The average duration of follow-up was seventeen years (range, eight to twenty-eight years). The primary indication for the meniscectomy was continuing pain in fourteen knees and locking or snapping in three. One patient had tenderness and walked with a limp. A meniscal tear was found in twelve knees at the time of the operation. According to the scale of Ikeuchi, the result was excellent for ten knees, good for three, and fair for five. Of the five patients (five knees) who had a fair result, four had mild intermittent discomfort after strenuous physical activity as well as clicking (three knees) or swelling (one knee), and one had clicking. One of these five patients was subsequently found to have rheumatoid arthritis, and two subsequently had a patellar realignment. No degenerative changes were evident on the roentgenograms of the eight patients (nine knees) for whom they were made at the latest follow-up evaluation. | |
7554562 | Blood dehydroepiandrosterone sulphate (DHEAS) levels in pemphigoid/pemphigus and psoriasis | 1995 May | Serum dehydroepiandrosterone sulphate (DHEAS) levels and diagnostic autoantibody titers were measured in patients with pemphigoid/pemphigus [n = 46/4; 21 men and 29 women, 42 to 93 years of age (mean 79)]. Twenty-four patients were either on peroral Prednisolone (n = 11), or topical treatment with betamethasone (n = 13), and the other 26 were either receiving non-steroidal drugs or were untreated. Their DHEAS levels were compared to those of 20 patients with psoriasis, and to 23 patients with secondary osteoarthritis (OA). Assessing the patients by group, the mean DHEAS level was markedly lower in the pemphigoid/pemphigus than in the psoriasis and OA patients (geometric mean 600 vs. 2130 and 2100 nmol/l, respectively; p < 0.001). This difference was independent of steroid treatment. No correlation was found between the DHEAS levels and antibody titers. The low levels found in pemphigoid/pemphigus are concordant with those reported for systemic lupus erythematosus, rheumatoid arthritis and polymyalgia rheumatica/giant cell arteritis. DHEAS deficiency is a permanent feature in these autoimmune diseases, and may contribute to their etiology and/or pathophysiology. |