Antineuronal antibodies in patients with neurologic complications of primary Sjögren's syndrome.

Neurologic complications of both the central and peripheral nervous systems occur frequently in patients with primary Sjögren's syndrome (primary SS), but the underlying cause of these complications is unknown. We studied the presence of antineuronal antibodies in relation to neurologic complications in a consecutive series of 45 patients with primary SS. Twenty-five patients had neurologic complications: 12 patients with polyneuropathy, three with psychiatric disorders, four with carpal tunnel syndrome, seven with migraine, seven with myalgia, and four with other complications (transverse myelitis, stroke, Bell's palsy, and pyramidal signs). Ten patients had more than one neurologic complication. Eleven patients had major and 14 had minor complications according to criteria used for rating neurologic complications in patients with systemic lupus erythematosus. Antineuronal antibodies were present in six of 11 (55%) patients with major neurologic complications and in four of 34 (11%) of patients without major neurologic complications (p = 0.001). This difference could be attributed mainly to the group of patients with polyneuropathy. Three of the 10 sera of patients with positive antineuronal antibodies had antibodies reacting with a 38-kd neuronal protein on immunoblotting, identical to the anti-Hu antibody reactivity in paraneoplastic neurologic disease associated with small-cell lung cancer.

Imaging of inflammatory arthritis with technetium-99m-labeled IgG.

The accumulation of nonspecific polyclonal human immunoglobulin G (IgG) radiolabeled with 99mTc was compared to that of [99mTc]albumin and [99mTc]nanocolloid in rats with collagen induced arthritis. Serial scintigrams were acquired directly, 4 and 24 hr after injection. A clearly discernable image of the site of synovitis was seen with [99mTc]IgG as early as 4 hr postinjection. The relative intensity of the inflammatory lesion was maximal at 24 hr. Discrimination between arthritic and nonarthritic joints as well as correlations between the relative intensity of the arthritic joint and clinical indices of joint inflammation were superior with IgG compared to albumin or nanocolloid. These studies show that localization and severity of inflammatory joint disease can be detected with radiolabeled nonspecific IgG.

Vascular somatostatin receptors in synovium from patients with rheumatoid arthritis.

The peripheral nervous system and its neuropeptidergic pathways may play an important role in the pathogenesis and development of rheumatoid arthritis. In the present study, the role of the neuropeptide somatostatin (SRIF), which was recently shown to be implicated in inflammatory diseases of the gastrointestinal tract, was evaluated by measuring the expression of somatostatin receptors in synovium from patients with rheumatoid arthritis. Somatostatin receptors were detected using in vitro receptor autoradiography in the synovium from five patients with active disease. No receptors were found in one case, a successfully treated patient with quiescent disease. The receptors were of high affinity and specific for biologically active somatostatin analogs. Displacement by nanomolar concentrations of somatostatin-14, somatostatin-28, and octreotide was observed, suggesting that most of the receptors identified belong to the SRIF1A subtype. The somatostatin receptors were preferentially located in blood vessels, with specific labeling of the veins but not of the arteries. The whole vessel wall was homogeneously labeled including the smooth muscle cells and probably the endothelium. These data suggest that the synovium in active rheumatoid arthritis expresses a high density of somatostatin receptors. Somatostatin may act through these venous receptors to influence the inflammatory process by induction of vasoconstriction, inhibition of plasma extravasation and cell migration, or inhibition of neovascularization.

Subcutaneous fat biopsy in the diagnosis of amyloidosis secondary to chronic arthritis.

Subcutaneous fat biopsy was investigated for its sensitivity in giving a diagnosis in 44 consecutive patients with rheumatoid arthritis or ankylosing spondylitis suspected of systemic amyloidosis. In 26 of these patients amyloidosis could be demonstrated by fat or rectal biopsy or biopsies from organs suspected of amyloid deposition. Fourteen of the 26 (54%) fat biopsy specimens of the patients with amyloidosis were positive after staining with Congo red and 22 (85%) of the rectal biopsy specimens were positive. All 12 kidney biopsy specimens and 4 biopsy specimens from other organs of these 26 patients were positive for amyloidosis. In 2 patients with a negative rectal biopsy specimen, fat biopsy would have obviated the need for a more invasive biopsy. All patients experienced fat biopsy as less demanding compared to other biopsy procedures. These results imply that in patients with chronic arthritis subcutaneous fat biopsy is a useful screening procedure. In this patient group fat biopsy is less sensitive for the diagnosis of amyloidosis compared to rectal biopsy.

Tear fluid analysis in primary Sjögren's syndrome.

Tear fluid analysis was performed in 44 patients with primary SS, 21 patients suspected of having primary SS in whom the syndrome had been excluded, and 24 control subjects. In the primary SS patients the tear fluid levels of lactoferrin and a1-antitrypsin were increased and the tear fluid levels peroxidase, lysozyme and amylase were decreased. However, a considerable overlap in the concentrations of all of the tested substances in the different groups was found and the measurement of these substances cannot be advocated for diagnostic use.

A quantitative index derived from 99mTc-pertechnetate scintigraphy to assist in the diagnosis of primary Sjögren's syndrome.

A safe and simple technique is reported by which primary Sjögren's syndrome can be detected with a relatively high specificity and sensitivity. The method of serial scintigraphy has been used with reasonable success; however, the application of the linearity index as described here produced superior results. In 71 patients investigated, a sensitivity of 87% and specificity of 93% were recorded and make this the method of choice for evaluating patients suspected of having primary Sjögren's syndrome.

Campylobacter jejuni arthritis in secondary amyloidosis.

We describe a case of infectious arthritis caused by C. jejuni which developed after C. jejuni enteritis in a patient with rheumatoid arthritis and hypogammaglobulinaemia. Extraintestinal infections of this enteropathogen are rare, but in patients with hypogammaglobulinaemia C. jejuni bacteriaemia is relatively common. The present patient suffered from hypogammaglobulinaemia due to a nephrotic syndrome in secondary amyloidosis. C. jejuni infection must be considered in patients with hypogammaglobulinaemia and arthritis.

Infectious arthritis caused by Klebsiella. A report of two cases.

Klebsiella arthritis is uncommon. This report describes 2 cases seen in one year in one hospital and reviews the previous 9 well-documented cases. Despite a long delay in diagnosis, antibiotic treatment without drainage procedures resulted in complete cure in one patient and cure with some impairment in the other.

Leucocytoclastic vasculitis as presenting feature of primary Sjögren's syndrome.

Described are two patients whose primary Sjögren's syndrome presented as leucocytoclastic vasculitis of the skin. One patient initially admitted complaints of dryness of the eyes and the mouth after direct questioning, and serologic testing revealed the presence of Ro/SS-A and La/SS-B antibodies. In the other patient the presence of antinuclear antibodies and rheumatoid factors in serum were the only suggestions of the presence of primary Sjögren's syndrome. Primary Sjögren's syndrome should be considered in patients presenting with leucocytoclastic vasculitis.

Amyloidosis mimicking rheumatoid arthritis.

A 49-year-old man presented a clinical picture suggesting seronegative rheumatoid arthritis. He developed severe joint contractions, pasty synovial swelling, macroglossia and proteinurie. Subsequent investigations disclosed light-chain multiple myeloma and A1-amyloid deposits in synovial tissue and skin. A1-amyloidosis should be considered in the differential diagnosis of patients with seronegative polyarthritis. Clues to the diagnosis of amyloid arthropathy are a carpal tunnel syndrome, early occurrence of joint contractures in combination with a relatively mild synovitis and a low ESR as well as the presence of other possible organ involvement with amyloidosis.

Unusual arthritis: be on the alert for leprosy.

A 50-year-old Indonesian man presented with arthritis of the left ankle, wrist and hand joints and a diffusely swollen left hand and foot. A few months later granulomatous skin lesions developed and renewed physical examination revealed a paresis of the intrinsic muscles of the left hand and the left M. extensor hallucis longes and thickening of several peripheral nerves. The skin lesions appeared to be anesthetic. A diagnosis of borderline tuberculoid leprosy was made and treatment resulted in cure with permanent peripheral nerve damage. This case emphasizes the importance of early recognition and treatment of leprosy to prevent nerve damage.

The effect of ranitidine on NSAID related dyspeptic symptoms with and without peptic ulcer disease of patients with rheumatoid arthritis and osteoarthritis.

The efficacy of ranitidine in the treatment of NSAID-related dyspeptic symptoms with and without peptic ulcer disease (PUD) was investigated in 124 patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The patients, who continued the use of NSAIDs were investigated by gastroduodenoscopy. Patients with PUD received open label ranitidine 150 mg b.i.d. and the patients without PUD were randomly allocated to receive ranitidine 150 mg b.i.d. or placebo for 4 weeks. PUD was found in 36 (26%) consecutive patients who presented with dyspeptic symptoms. Of these patients dyspeptic symptoms had disappeared in 8 (26%) of 31 evaluable patients and PUD was healed in 18 (56%) patients after 4 weeks of treatment. After 8 weeks of treatment PUD was healed in 27 (87%) patients. Of the remaining patients without PUD dyspeptic symptoms had disappeared in 24 (26%) of the ranitidine-treated patients which was significantly better (p < 0.02) than the 5 (6%) placebo-treated patients. The minor mucosal lesions found in this patient group improved to a similar extent in the ranitidine and placebo-treated patients although 1 placebo-treated patient deteriorated and 2 placebo-treated patients developed PUD during the 4 weeks of study. The results of this study show that oral ranitidine 150 mg b.i.d. is effective in the treatment of both dyspeptic symptoms and mucosal lesions in RA and OA patient who continue the use of NSAIDs.

The diagnostic value of salivary fluid levels of beta 2-microglobulin, lysozyme and lactoferrin for primary Sjögren's syndrome.

In search of a simple non-invasive diagnostic test for primary Sjögren's syndrome (SS) the concentration of beta 2-microglobulin (beta 2-m), lysozyme (LZM) and lactoferrin (Lf) was measured in stimulated parotid saliva of 39 patients with primary SS, 42 patients suspected of the syndrome in whom the diagnosis could be excluded (NON-SS) and in 41 normal control individuals. Salivary fluid levels of beta 2-m, LZM and Lf exceeding the mean + 2 x standard deviation of healthy control values were found in respectively 58%, 23%, and 26% of the primary SS patients and in 7%, 11% and 0% of the NON-SS patients. The results of this study indicate that due to the low sensitivity the tests are not suitable as a screening procedure for patients suspected of having primary SS. However, measurement of beta 2-m in stimulated parotid saliva may be used as an adjunctive diagnostic test for primary SS.

Severe muscle weakness secondary to paraneoplastic hypophosphatemia in neuroblastoma.

We report a 28-year-old woman who presented with severe proximal muscle weakness secondary to paraneoplastic hypophosphatemia and associated with recurrent neuroblastoma. The biochemical findings included hyperphosphaturia, a reduced serum level of 1,25-dihydroxyvitamin-D3, elevated alkaline phosphatase and normocalcemia which are pathognomic for paraneoplastic hypophosphatemia. Following systemic chemotherapy and supplementation of 1,25-dihydroxyvitamin-D3 a complete remission of the neuroblastoma was achieved and all features of the paraneoplastic hypophosphatemia gradually disappeared. In the differential diagnosis of muscle weakness, hypophosphatemia should be included. Paraneoplastic hypophosphatemia associated with metastatic neuroblastoma has not been reported previously. Diagnosis, mechanism and therapy of paraneoplastic hypophosphatemia are shortly reviewed.

Hypereosinophilic syndrome presenting with diarrhoea and anaemia in a patient with systemic lupus erythematosus.

We describe a patient with quiet systemic lupus erythematosus who developed a hypereosinophilic syndrome. The patient presented with gastrointestinal eosinophilia which caused diarrhoea, malabsorption and anaemia due to deficiencies of vitamins. The hypereosiniphilic syndrome completely resolved after treatment with prednisone.

Primary Sjögren's syndrome: clinical spectrum and mode of presentation based on an analysis of 50 patients selected from a department of rheumatology.

In this study we report on the clinical characteristics at the time of referral and during follow-up of 50 patients with primary Sjögren's syndrome (SS) in a rheumatological practice. The mean age of the patients at the time of diagnosis was 51.5 years. Four of them were men and 46 women. During a mean follow-up period of 9.1 yr (1-21 yr) from symptom onset the most common signs and symptoms were arthralgia (94%), complaints of dryness of the eyes (90%), mouth (82%) and skin (56%), weariness (64%), exanthema (48%), Raynaud's phenomenon (42%) and arthritis (42%). An elevated erythrocyte sedimentation rate (72%), elevated serum gammaglobulin (49%) and leucocytopenia (42%) were the most frequently encountered abnormalities of routine laboratory tests. After the initial hospital evaluation the diagnosis primary SS was made in only 10 (20%) of the patients. The diagnostic delay was on average 3.1 yr. Knowledge of the considerable heterogeneity of the disease may prevent extensive evaluations and provide better clinical care for patients with primary SS.

Two patients with acute thrombocytopenia following gold administration and five-year follow-up.

Thrombocytopenia is a well-known side effect following intramuscular gold therapy in patients with rheumatoid arthritis. Thrombocytopenia may occur at any time and it can be irreversible and sometimes fatal despite cytotoxic or immunosuppressive therapy. We describe two patients who presented with haemorrhagic diathesis on the day after the administration of aurothioglucose. The thrombocytopenia in these patients was caused by aurothioglucose-induced antibody-mediated platelet destruction. Both patients made an uneventful recovery and the platelet count returned to normal within several weeks without further treatment. Antibody-detecting tests were repeated five years later and could not demonstrate the presence of antibodies. Also after incubation with aurothioglucose no antibodies could be demonstrated.

Primary Sjögren's syndrome presenting as autonomic neuropathy. Case report.

Abnormalities of the autonomic nervous system have been described in several connective tissue diseases, but the relation with primary Sjögren's syndrome is unclear. This report describes a patient with primary Sjögren's syndrome who presented with severe autonomic failure. The present knowledge on dysfunction of the autonomic nervous system in primary Sjögren's syndrome and other connective tissue diseases is shortly reviewed.

Polyneuropathy as initial manifestation of necrotizing vasculitis and gangrene in systemic lupus erythematosus.

A patient with necrotizing vasculitis and systemic lupus erythematosus is reported. The vasculitis presented as a symmetrical sensorimotor axonal neuropathy and after three months it resulted in gangrene of a toe. Sural nerve conduction was abnormal and a biopsy of this nerve was diagnostic. Serum anti-endothelial cell antibodies were elevated during activity of the vasculitic process. Treatment with prednisone and cyclophosphamide induced a remission.

[Immunology in medical practice. XIV. Central nervous system complications in systemic autoimmune diseases]. / Immunologie in de medische praktijk. XIV. Complicaties van het centrale zenuwstelsel bij systemische auto-immuunziekten.

Complications of the central nervous system (CNS) are common in systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome. Specific diagnostic tests are lacking and early intervention with immunosuppressive therapy is frequently necessary. Therefore knowledge of these CNS complications is essential for early diagnosis and treatment. Residual cognitive effects were observed in some but not in all tests after prolonged heavy cannabis use. The effects were mostly mild. The relationship of cannabis use, psychotic effects and schizophrenia was unclear; the cannabis conceivably gave relief, but it also appeared that cannabis caused schizophrenia in young people and (or) enhanced the symptoms, especially in young people poorly able to cope with stress or in whom the antipsychotic therapy was unsuccessful.