Peripheral blood lymphocyte cell surface markers during the course of systemic lupus erythematosus.

Peripheral blood lymphocytes from 23 patients with active systemic lupus erythematosus (SLE) were serially studied. Changes in bone marrow-derived lymphocytes (B cells), as measured by surface Ig receptors and C3 receptors, and in thymus-derived cells (T cells) measured by rabbit T-cell-specific antiserum and E-binding techniques, were correlated with fluctuations in clinical disease activity and treatment. In normal controls B- and T-cell percentages remained relatively stable, although the situation in SLE was much more labile. A relative and absolute decrease in T lymphocytes and cells bearing a receptor for C3 was found in active lupus. Absolute numbers of cells bearing surface Ig were decreased to a lesser extent, whereas the proportion of these cells was increased. It is postulated that the increase in autoantibody formation and diminished delayed hypersensitivity seen in systemic lupus may be due to a loss of T-lymphocyte function.

Studies of T- and B-lymphocytes in patients with connective tissue diseases.

Peripheral blood lymphocytes from normal subjects as well as patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and active tuberculosis were studied for the relative distribution of bone marrow-derived lymphocytes (B-cells) and thymic-derived T-cells. B-cells were identified by direct immunofluorescence of surface Ig markers; T-cells were studied using rabbit antisera to pooled human fetal thymocytes absorbed with chronic lymphatic leukemia lymphocytes as a source of B-cells. In normal subjects, the sum of percentages of peripheral blood lymphocytes staining for surface Ig (B-cells) plus the percentage of cells staining with the absorbed antithymocyte antiserum closely approximated 100%. The mean value for percent B-cells among 51 normals tested was 22.9%+/-7.1; mean T-cells value was 75.3+/-13.95%. T-cell-specific antiserum stained 18% of normal human bone marrow lymphocytes, 42.5% of lymphocytes from normal spleens, and 98% of cells obtained from thoracic duct drainage of patients with RA. Specificity of antihuman thymocyte antiserum appeared to depend on the use of living cells. When patients with RA were examined, a wide range (14-98%) of peripheral blood T-cell values was found. Values for low percentages of peripheral blood T-cells appeared to correlate to some extent with severe clinical disease. In 11 of 36 RA patients, the sum of identifiable B- plus T-cells accounted for only 34-55% of peripheral blood lymphocytes. The identity of the remaining "null" cells could not be identified.3 of 24 SLE patients studied showed low percentages of peripheral blood T-cells, but no correlation could be drawn between T- to B-cell ratios and clinical disease activity. Among 21 patients with active tuberculosis, one had a low value for identifiable T-cells. No significant differences from normals in range or proportion of B-cells was identified in patients with active tuberculous infection.

Subjective and clinical oral symptoms in patients with primary Sjögren's syndrome.

OBJECTIVE: To study subjective and clinical oral symptoms and their possible correlations in patients with primary Sjögren's syndrome (1 degree SS). METHODS: In 40 cases fulfilling the Copenhagen as well as the San Diego criteria for 1 degree SS, different subjective symptoms were registered during an interview and by using a questionnaire and visual analogue scales (VAS). A clinical examination was performed to record the salivary parameters, dental status, candidosis, other mucosal lesions, and oral dysfunction. RESULTS: Subjectively, dryness was reported by 98%, soreness by 63%, angular lesions by 70%, and mucosal ulcerations by 40% of the patients. Frequent carious lesions were a major subjective complaint. Clinically, the dental status did not differ from that of the Swedish general population except for a somewhat increased number of filled and decayed surfaces, here 3.5 per tooth on the average. Candidosis was present in a total of 30 patients (75%), and angular cheilitis in 14 (35%). Intraoral cultivation of Candida did not correlate with the clinical findings. Very high counts of lactobacilli and mutans streptococci were found in 77% and 47% of the patients, respectively. Decreased unstimulated saliva was significantly correlated to the subjective degree of dryness, while decreased stimulated saliva could be correlated to increased focus scores in labial salivary gland biopsies and to the presence of mucosal candidosis. Statistically significant correlations were also noted between focus scores and the grades of subjective and clinical dryness. Lichenoid lesions were seen in 18% and oral dysfunction in 55% of the 1 degree SS patients. CONCLUSION: The impaired salivary function in 1 degree SS can be related to several subjective complaints and clinical disorders. Increased attention to and treatment of the symptoms noted is a necessity for the early diagnosis and relief of oral distress.

Large vessel occlusion, cerebral infarction and thrombocytopenia in the "primary" antiphospholipid syndrome. Response to anticoagulation.

A 65-year-old white female without lupus developed concurrent thrombocytopenia and disturbed arterial circulation to the brain and lower leg (a minor stroke and lower leg gangrene, necessitating amputation). Laboratory studies disclosed high levels of anticardiolipin antibodies. Anticoagulant treatment restored circulation in the remaining leg and also normalized platelet levels. This case emphasizes the importance of searching for anticardiolipin antibodies in unexplained thrombotic events.

Reiter's syndrome--a comparative study of patients with the complete and the incomplete syndrome.

Eighty patients with Reiter's syndrome (RS) were studied retrospectively. A comparison was made between patients with the complete syndrome and patients with the incomplete syndrome. A comparison was also made between patients with and without HLA-B27. There were no major differences in severity and duration of the arthritic symptoms or in mucocutaneous involvement between the complete and incomplete groups, which indicates that they, in fact, represent the same disease. Most of the patients with sacroiliac joint involvement belonged to the HLA-B27 positive group; otherwise there was no difference in arthritic symptoms between the HLA-B27 positive and the HLA-B27 negative group.

Skeletal scintigraphy with technetium diphosphonate in multiple myeloma--a comparison with skeletal x-ray.

Twenty-one patients with multiple myeloma were examined in close time relation with skeletal X-ray survey and bone scanning using technetium diphosphonate. Results indicate that X-ray is superior to bone scan in detecting myelomatous bone lesions. Approximately twice as many lesions were detected by X-ray as by bone scan. An exception to this general finding is the lumbar spine and rib cage, in which the two methods are equally reliable. Thus, a negative bone scan does not exclude the possibility of a myelomatous bone lesion.

Iron and vitamin deficiencies, endocrine and immune status in patients with primary Sjögren's syndrome.

OBJECTIVES: To study the prevalence of iron and vitamin deficiencies, endocrine disorders and immunological parameters in patients with primary Sjogren's syndrome (1 degree SS). DESIGN AND SUBJECTS: At the time of the establishment of the diagnosis of 1 degree SS in 43 consecutive patients, a clinical examination including haematological analyses was performed. The patients' medical records were also reviewed. SETTING: Patients referred for diagnosis to The University Hospital, Linköping, a secondary or tertiary referral hospital serving the middle part of southern Sweden. RESULTS: In total, current or previously treated iron and vitamin deficiencies were registered for 63% of the 1 degree SS patients (iron 51%, vitamin B12 25%, folate 9%). Current low ferritin was noted in 24%, low iron saturation in 37%, decreased vitamin B12 in 13% and folate in 9%. Thyroid disease was found in a total of 33% and 30% had had autoimmune thyroiditis. Three patients (7%) had verified diabetes mellitus. Erythrocyte sedimentation rate (ESR) was raised in 65% of the patients and 84% had a polyclonal increase of Ig. Rheumatoid factor (RF) was detected in 85%, antinuclear antibody (ANA) in 74%, anti-SS-A in 88% and anti-SS-B in 73% of the patients. CONCLUSION: Iron and vitamin deficiencies and thyroid diseases are common in patients with 1 degree SS. Since these disorders often are treatable and may affect the patients' distress as well as their immune and exocrine function, an active, recurrent search for deficiencies, endocrine diseases and other frequently recorded disorders is recommended.

Wegener's granulomatosis: treatment failure on conventional therapy.

We report a patient with Wegener's granulomatosis who was initially stabilized, but later relapsed with multiorgan involvement while taking high oral doses of cyclophosphamide (3.7 mg/kg body weight/day) and prednisolone. Remission was achieved with a combined therapy consisting of intermittent intravenous boluses of cyclophosphamide, oral prednisolone, plasmapheresis and oral trimethoprim-sulfamethoxazole. Discussion includes evaluation of the relative beneficial effect of the four treatment constituents.

Autoimmune haemolytic anaemia complicating Mycoplasma pneumoniae infection.

Although a positive direct Coombs' test is common in patients with Mycoplasma pneumoniae infection, manifest haemolysis is rare. A case is presented in which M. pneumoniae infection was followed by severe autoimmune haemolytic anaemia with intravascular haemolysis and haemoglobinuria. The presence of cold haemagglutinins suggests that these autoantibodies caused the haemolysis. Corticosteroid treatment corrected the haemolysis, which was of brief duration. Published data indicate that the mycoplasma agent is capable of altering the I-receptors of normal erythrocytes by haemadsorption and production of a soluble haemolysin.

Severe skin necrosis following warfarin therapy in a patient with protein C deficiency.

A female patient with a history of both arterial and venous thrombosis developed extensive skin necrosis following warfarin treatment. When protein C deficiency was diagnosed, successful anticoagulation with warfarin was achieved by prolonging the course of intravenous heparin and introducing warfarin therapy with a low initial dose which was gradually increased. Aspects of the pathogenic mechanism are discussed.

Paraplegia in myelomatosis--a study of 20 cases.

A retrospective study of 20 cases of multiple myelomatosis and paraparesis treated during 1966-77 is presented. All patients but one had been submitted to decompressive laminectomy. A close correlation between duration of paraparesis before operation and prognosis was found, eight patients with a duration of paraparesis of several days remaining paraplegic. No particular paraparesisprone patient group with respect to duration of myelomatous disease, Ig class or various laboratory findings could be identified. In several instances radionuclide scan was effective in localizing vertebral lesion. In most patients radicular type back pain signalled vertebral damage and subsequent paraparesis. In many cases long survival after operation and excellent to good functional results made surgery a worthwhile procedure. The importance of postoperative radiotherapy and adequate chemotherapy is stressed.

Renal pathology of Waldenström's macroglobulinaemia with monoclonal antiglomerular antibodies and nephrotic syndrome.

Severe nephrotic syndrome developed suddenly in a 67-year-old man. IgM M-component and bone marrow findings indicated a diagnosis of Waldenström's macroglobulinaemia. High-titre IgM glomerular autoantibodies were found to reside mainly in the M-component. Immunofluorescent (IF) studies on serial kidney biopsies showed extensive IgM deposits that disappeared after treatment. Light microscopy of kidney biopsy appeared only slightly altered, but combined with electron microscopy could demonstrate changes that correlated well with IF findings. The latest biopsy showed interstitial infiltration in the kidney of atypical lympho-histiocytic cells. Morphological and immunological examination indicated that pathogenetic events started with minimal-change glomerulonephritis, causing release of glomerular antigen, that finally triggered a monoclonal IgM response and lymphoproliferative reaction. Intermittent treatment with chlorambucil and corticoids completely abolished the nephrotic syndrome and at the same time the changes in renal morphology largely disappeared.

Effect of fasting and lactovegetarian diet on rheumatoid arthritis.

16 patients with classical rheumatoid arthritis (RA) selected at random underwent fasting for 7--10 days, followed by a 9-week period on a lactovegetarian diet. 10 RA patients acted as controls, taking normal diet. Pain, stiffness, medication, and clinical and biochemical findings were recorded before fasting, on the first day after the conclusion of the fasting period, and at the end of the lactovegetarian period. After fasting, 5 of 15 patients showed objective signs of improvement, compared with only one of the controls. The fasting patients showed reduced pain, stiffness, consumption of analgetics, several clinical variables, and serum concentration of orosomucoid. At the conclusion of the lactovegetarian diet period only one Diet patient showed objective improvement. No differences were found between the Diet patients and the controls concerning symptoms, drug consumption, or clinical and biochemical variables. We conclude that fasting may produce subjective and objective improvements in RA, though of short duration, but the findings of this investigation do not indicate that lactovegetarian diet has any beneficial effects.

Reactive arthritis after Salmonella among medical doctors--study of an outbreak.

OBJECTIVE: To investigate an outbreak of S. enteritidis enterocolitis which occurred at a radiology symposium in Malmö, Sweden in March, 1990. METHODS: Questionnaires were mailed to the 126 participants after 1 and 6 months inquiring about enterocolitis, joint and eye symptoms and antibiotic treatment. Fifty-one delivered blood samples for serological studies. RESULTS: One hundred thirteen responded to the questionnaire. Enterocolitis was reported by 108 individuals (96%) and 17 (15%) developed reactive arthritis (ReA). Only 3 persons reported conjunctivitis. Antibody response did not differ between patients with uncomplicated enterocolitis or ReA. IgA antibodies had the highest sensitivity to detect infected individuals. Ten out of 65 patients treated with antibiotics (mean 9.1 days) for enterocolitis and 7 out of 48 nontreated reported joint symptoms. At 6 month followup 8 patients had persistent joint complaints. CONCLUSION: Following an outbreak of S. enteritidis dysentery, joint symptoms may be more frequent than previously thought and could not be prevented by early antibiotic treatment. Nor did antibiotics affect the duration of ReA over a 6 month followup period.

IgG subclasses of anti-SS-A/Ro in patients with primary Sjögren's syndrome.

Patients with primary Sjögren's syndrome mostly have high levels of polyclonal IgG, and subclass analysis frequently shows selective IgG1 increase with low IgG2. In this study IgG subclass profiles of anti-SS-A/Ro were examined using ELISA technique. Results show marked IgG subclass restriction of anti-SS-A/Ro autoantibodies (high IgG1/low IgG2). Comparison of the levels of specific IgG subclass autoantibodies with total levels of the corresponding subclass disclosed divergence regarding IgG2, IgG3, and IgG4, but not IgG1. Thus, total levels of IgG1 paralleled the levels of IgG1 anti-SS-A antibodies. Specific autoantibodies of IgG2 subclass could not be detected despite low or normal levels of total IgG2. Elevated levels of specific IgG3 and IgG4 antibodies were seen, although total levels of the corresponding subclasses were within normal limits. These findings may possibly be of relevance with regard to antigen-driven activation of autoantibody-producing plasma cell clones.

Evaluation of lip salivary gland biopsy in 21 patients with primary Sjögren's syndrome.

Lip salivary gland biopsy was performed in 21 (20 female) patients, age 26 to 74 years, with primary Sjögren's syndrome. The procedure helped identify a patient group with many autoimmune phenomena, including hypergammaglobulinemia, autoantibodies, autoimmune thyroiditis, vasculitis, and immunocytoma. A marked association with the HLA-DR3 antigen was noted. It is concluded that lip salivary gland biopsy is a simple and safe procedure that makes possible the identification among non-RA patients with sicca symptoms those who have autoimmune disturbance. This patient group deserves close medical supervision in order to detect autoimmune disease that requires treatment, such as autoimmune thyroiditis and lymphoma.

IgG2 deficiency in primary Sjögren's syndrome and hypergammaglobulinemic purpura.

Total IgG and IgG subclasses were studied in 34 patients with primary Sjögren's syndrome and 4 with hypergammaglobulinemic purpura. Total IgG was elevated in 30/34 patients with Sjögren's syndrome. IgG1 increase was responsible for the main part of total IgG increase, contrasting with low levels of IgG2. The difference in IgG1/IgG2 ratio between 38 patients as a group and 40 normal controls was statistically highly significant, but was not seen in all patients. Six patients had markedly low levels of IgG2, but only two had severe repeated respiratory infections. These observations probably reflect selective autoantibody restriction to the IgG1 subclass. We conclude that patients with Sjögren's syndrome may be IgG2 subclass deficient despite elevated levels of total IgG, but also that such deficiency in most instances does not cause a tendency to infections. IgG subclass analysis may be of value to characterize polyclonal IgG increase, since IgG1 subclass predominance often indicates autoimmune disease.

Respiratory distress syndrome and thrombotic, non-bacterial endocarditis after amitriptyline overdose.

Three patients with documented or suspected amitriptyline poisoning developed a uniform clinical picture with progressive respiratory insufficiency, thrombocytopenia and evidence of embolization. Post-mortem examination revealed equally uniform changes: thrombotic, non-bacterial endocarditis (TNBE) with multiple embolization and marked pulmonary stiffness with extensive invasion of alveoli with connective tissue. The lung pathology and clinical picture of progressive respiratory insufficiency are in agreement with the respiratory distress syndrome (RDS) in the adult. The simultaneous occurrence of RDS and TNBE suggests a similar pathogenesis. Prophylactic measures are described.