Respiratory and otolaryngologic manifestations of giant cell arteritis.

OBJECTIVES: The classical presentation of giant cell arteritis (GCA) includes the new onset of headache, scalp tenderness, facial pain or jaw claudication in an older patient. Many patients with GCA have features consistent with the diagnosis of polymyalgia rheumatic (PMR) and nearly all have elevated markers of inflammation such as the erythrocyte sedimentation rate (ESR) or the serum C-reactive protein (CRP). Respiratory and ear-nose-throat (ENT) signs and symptoms such as cough, tongue infarction, trismus, hearing loss and facial swelling are less commonly described, yet they may be the initial presentation of GCA. Our aim was to review the published literature on the topic of respiratory and otologic manifestations of GCA. METHODS: A literature search was performed on PUBMED and MEDLINE using the following keywords: GCA, temporal arteritis, pulmonary, respiratory, ENT, cough, tongue necrosis. RESULTS: The upper and lower airways manifestations of GCA include a wide variety of conditions that could be caused by ischaemia due to the vasculitis. CONCLUSIONS: It is important to recognize these atypical presentations because they may be the sole initial manifestation of the disease. Early suspicion and confirmation of the diagnosis of GCA can help to prevent more catastrophic consequences of unrecognized disease, including stroke and blindness.

An arthritogenic lymphokine in the rat.

A type II collagen-specific arthritogenic lymphokine has been identified in the rat. Arthritogenic factor (AF) is a 65 kD protein generated in vitro by T cells from rats with collagen arthritis, and it induces an erosive, proliferative synovitis when injected into the knee joint of syngeneic naive recipients. Complement does not appear to be required. These data identify a potential T cell-mediated effector mechanism in this model, and suggest that AF may function in other inflammatory synovial diseases.

Nabumetone: a clinical appraisal.

Nonsteroidal antiinflammatory drugs (NSAIDs) have long been used as therapy for arthritis patients. However, in some patients these drugs can cause gastrointestinal hemorrhage, perforation, or ulcer through direct topical effects, enterohepatic recirculation, and systemic effects. In an effort to address this problem, new NSAIDs have been developed. Nabumetone, which belongs to a new class of NSAID, is a nonacidic agent that has been associated with a low incidence of peptic ulcer. This article examines available clinical data on nabumetone, including studies on gastrointestinal safety and effectiveness in osteoarthritis and rheumatoid arthritis patients, and data that may provide an explanation for nabumetone's low incidence of ulceration.

Total lymphoid irradiation.

Total lymphoid irradiation (TLI) was shown to have potent immunosuppressive effects in patients with Hodgkin's disease. In the last decade a handful of studies assessed the efficacy of TLI in patients with rheumatoid arthritis. A correlation between decline in T-helper cell number and a reduction in disease activity was noted in all studies; however, the toxicity of TLI remains a major problems limiting a more widespread use of this treatment modality.

Herpes zoster radiculopathy.

Herpes zoster-related radiculopathy usually can be easily diagnosed in the presence of cutaneous lesions. Before development of the skin rash, the diagnosis may be in doubt, particularly if motor symptoms and signs are a major clinical feature. We report a patient with herpes zoster-related radiculopathy whose clinical features mimicked other spinal disorders.

Radiophosphate imaging of regional migratory osteoporosis.

A patient with regional migratory osteoporosis had somewhat unusual features in that there was involvement of the small joints of the foot demonstrable by 99mTc-methylene diphosphonate joint imaging.

Unusual digital sparing in rheumatoid arthritis a case of neuropsychoimmunologic involvement.

An unusual pattern of hand involvement in a patient with rheumatoid arthritis (RA) is presented. There is complete sparing of a single digit, despite a severe, destructive polyarthritis involving all the other fingers. Of note, the patient began wearing a treasured family heirloom ring on the nonaffected finger approximately 1 year before the onset of her arthritis. The potential role for psychoimmunologic regulation of rheumatoid arthritis is discussed.

Stiff-man syndrome: from the bedside to the bench.

The study of SMS, a rare disease, has resulted in a better understanding of a more common disorder, IDDM, and has allowed investigators to gain insights into the molecular mechanisms of autoimmunity. Many unanswered questions remain, such as the specific site of disease activity in SMS, both at the bedside (cortex, brain stem, or spinal cord) and at the bench (neuronal cytoplasma or synapse). The association of SMS with neoplastic disease and the development of autonomicdysfunction are not understood. The next decade may provide answers to these puzzling issues.

Polymyalgia rheumatica in patients with a normal erythrocyte sedimentation rate.

OBJECTIVE: To ascertain the frequency of polymyalgia rheumatica (PMR) with a normal erythrocyte sedimentation rate (ESR; < or = 30 mm/hour) and to determine any defining clinical characteristics. METHODS: A retrospective chart review study of all patients meeting the clinical criteria for PMR seen over a 5-year period in a hospital and an office-based rheumatology practice. RESULTS: We evaluated 117 patients; 26 (22.2%) had a pretreatment ESR of < or = 30 mm/hour (mean +/- SD 19.8 +/- 7.5 versus 74.4 +/- 30.3 mm/hour for elevated ESR group; P<0.0001). Of the 26 normal ESR patients, 15 (58%) were female compared with 74 of the 91 elevated ESR patients (81%) (P<0.02, by Fisher's exact test). The mean hemoglobin concentration was significantly lower in the elevated ESR population (mean +/- SD 1.23 +/- 0.15 gm/liter versus 1.38 +/- 0.11 gm/liter; P<0.0001). The duration of symptoms prior to treatment with prednisone was significantly longer for patients with a normal ESR (149 +/- 95 days versus 103 +/- 95 days for elevated ESR patients; P<0.04). CONCLUSION: In our series, PMR with a normal ESR accounted for approximately one-fifth of all PMR patients, more commonly in men. The lack of characteristically abnormal laboratory findings may result in a delay in the proper diagnosis and management of this condition.

Scapholunate dissociation associated with crystal induced synovitis.

We report the development of scapholunate ligament rupture after episodes of gout in 2 patients and in association with chondrocalcinosis in another. One patient required surgical fusion for alleviation of pain. The diagnosis should be considered in patients with prolonged wrist pain refractory to conventional therapies for crystal induced arthritis.

Patterns of medication use before and after bone densitometry: factors associated with appropriate treatment.

OBJECTIVE: We examined the medications used by women before and after bone densitometry to determine whether patient or physician factors were associated with appropriate osteoporosis therapy. METHODS: Appropriate osteoporosis treatment was defined as alendronate, etidronate, calcitonin, or hormone replacement therapy (HRT) for women with any bone mineral density (BMD) t score < -2.5 or no osteoporosis therapy, except HRT, for women with t scores > -1.0. We observed a cohort of women who underwent bone densitometry at one outpatient osteoporosis clinic. Medical history, medication use, and demographic data were collected at the time of bone densitometry. A followup questionnaire assessed the medication use patterns since bone densitometry and attitudes about osteoporosis therapy. RESULTS: We recruited 553 women who underwent bone densitometry in 1996. Their mean age was 62 years and 95% were postmenopausal. Prior to bone density scans, 27% of patients used HRT, 15% used bisphosphonates, and 6% used calcitonin. Scan results and surveys revealed that 40% of patients had BMD below a t score of -2.5 at any site. Of women with osteoporosis 78% reported taking an appropriate medication after their scans. Patients most likely to receive appropriate treatment were those who understood their bone densitometry results (odds ratio, OR, 2.5; 95% confidence interval, CI, 1.3 to 4.8) and patients who were taking an osteoporosis medication (OR 1.9; 95% CI 1.0 to 3.6). Neither the specialty of the referring physician nor patients' medical history was associated with use of appropriate osteoporosis therapy. CONCLUSION: Of women with osteoporosis who underwent bone densitometry 78% received appropriate therapy after this test. Patient factors were associated with the likelihood that they received appropriate therapy, suggesting that strategies aimed at educating patients may improve the use of osteoporosis medications.

Leflunomide-associated weight loss in rheumatoid arthritis.

OBJECTIVE: To determine the frequency of weight loss in patients treated with leflunomide for rheumatoid arthritis at an arthritis referral center. METHODS: We queried 35 rheumatologists at the Robert Breck Brigham Arthritis Center to determine if weight loss had occurred as an adverse event in patients treated with leflunomide between November 1998 and January 2000. Five such patients were identified and their clinical course was reviewed. RESULTS: Five of 70 patients who had begun leflunomide therapy had significant weight loss that could not be linked to other identifiable etiologies. The amount of weight loss was substantial in this group of patients, ranging from 19 pounds to 53 pounds. All patients had normal levels of thyroid-stimulating hormone and no other gastrointestinal complaints; evaluation revealed no other cause for the weight loss. Despite the significant weight loss, 4 of the 5 patients continued to take the drug due to its efficacy. CONCLUSION: Significant weight loss is a potential adverse event in patients with rheumatoid arthritis treated with leflunomide. Awareness of this may obviate the need for extensive medical evaluations.

Generalized skeletal response to 99mtechnetium methylene diphosphonate in rheumatoid arthritis.

The total body retention (TBR) and the 5- and 24-h lumbar spine to soft tissue (LS/ST) ratios of 99mtechnetium methylene diphosphonate was studied in 19 patients with rheumatoid arthritis (RA), 16 patients with metastatic tumors that did not involve the lumbar spine, 10 patients with chronic renal failure and 17 controls. The TBR was significantly higher in all groups compared to the controls. The 5-h LS/ST did not differ between any of the groups although the 24-h LS/ST ratios were significantly elevated in RA and those with chronic renal failure. The 24-h LS/ST in RA was correlated only with disease duration. The results are consistent with a generalized increase in bone turnover in RA and may explain the recognized lack of sensitivity of quantitative scintigraphic techniques in this disorder.

Treatment of stiff-man syndrome with intravenous immune globulin.

OBJECTIVE: To evaluate the efficacy of intravenous immune globulin (IVIG) in the treatment of stiff-man syndrome (SMS). METHODS: An open, unblinded study of 3 patients with active disease and/or disease refractory to treatment with diazepam and/or corticosteroids. RESULTS: All 3 bedridden patients improved substantially shortly after infusion with IVIG and regained function. CONCLUSION: IVIG may be useful for the treatment of SMS.

Diclofenac-associated hepatotoxicity.

Diclofenac sodium, a phenylacetic acid-derived nonsteroidal anti-inflammatory drug (NSAID) recently released in the United States, was associated with the development of significant hepatitis in seven patients, with one associated death. Signs and symptoms developed within several weeks of initiation of drug use and generally resolved 4 to 6 weeks following discontinuation of use of the drug. The only patient rechallenged with the drug developed a recurrence of her hepatic abnormalities. In one patient, fatal, fulminant hepatitis developed despite early withdrawal of the drug. Review of the European literature disclosed three additional fatalities associated with diclofenac therapy. It is unclear whether the incidence of hepatotoxicity is higher with this drug compared with other nonsteroidal anti-inflammatory drugs. Careful patient monitoring is advised, and prompt discontinuation of the drug is suggested when signs or symptoms of liver disease develop.

Suppressive effects of anti-mu serum on the development of collagen arthritis in rats.

Sprague-Dawley rats were maintained in environmentally isolated conditions and some of them were injected beginning at birth with rabbit anti-mu serum to suppress B-cell maturation. All rats were subsequently immunized with chick type II collagen. Ten (28%) of 36 rats injected with anti-mu antiserum failed to develop serum hemagglutinating antibodies to collagen, and there was a significant (P less than 0.0003) reduction in the IgG-specific antibody titer to collagen in these 10 rats compared to the other 26 rats in this group. Only 1 (10%) of the antibody-suppressed rats developed arthritis compared to 20 (77%) of the 26 other rats in the anti-mu-treated group (P less than 0.001). Twenty-two (61%) of 36 immunized rats administered rabbit anti-ovalbumin serum and 14 (88%) of 16 immunized rats kept in the axenic conditions developed arthritis. Delayed-type hypersensitivity to collagen did not differ significantly between the groups. These data provide indirect evidence that antibodies play a role in the inception of collagen arthritis.

Intraarticular injection of arthritogenic factor causes mast cell degranulation, inflammation, fat necrosis, and synovial hyperplasia.

Arthritis resembling human rheumatoid arthritis is produced in rats either by immunization with type II collagen or injection of complete Freund's adjuvant. The development of arthritis in both models may be mediated by a T cell-derived, type II collagen-specific protein that has been termed arthritogenic factor. Here, the morphologic changes produced after intraarticular injection of this factor were determined. T cell lines were derived from type II collagen-immunized rats. Arthritogenic factor was isolated from culture supernatants by affinity chromatography on type II collagen-conjugated Sepharose and injected into rat knees. The synovium covering the infrapatellar fat pad was examined by light and electron microscopy at 6 hours to 7 days after injection. By 6 hours, the synovium and fat pad were edematous and heavily infiltrated with neutrophils and a few mononuclear cells. Fibrin was present in the synovium and joint space. Most mast cells had partially degranulated. By 24 hours, the infiltrate became primarily mononuclear and fewer neutrophils were seen. Fat necrosis and edema occurred in the subsynovium. By 48 hours and 7 days, the synovium was hyperplastic, some fibrin persisted, and macrophages were present. Control knees, injected with material obtained from T cell lines established with the antigen, ovalbumin, and subjected to type II collagen affinity chromatography, had less fibrin deposition, milder cellular infiltrates, and less mast cell degranulation than knees injected with arthritogenic factor. These studies suggest that arthritogenic factor stimulates acute cellular infiltration and mast cell secretion which is followed by fat necrosis, synovial hyperplasia, and mononuclear cell infiltration.

The effects of cyclosporin A on eicosanoid excretion in patients with rheumatoid arthritis.

Alterations in renal eicosanoid levels have been postulated as a factor in cyclosporin A (CSA) nephrotoxicity. The effects of CSA on renal eicosanoid excretion in rheumatoid arthritis were studied over a 24-week period, during which treatment with nonsteroidal antiinflammatory drugs was discontinued. The initial dosage of CSA was 4 mg/kg/day; at week 24, the mean dosage of CSA was 3.9 mg/kg/day. At week 24, the mean (+/- SD) serum creatinine level (1.04 +/- 0.24 mg/dl) was 32% above the baseline value; renal blood flow had decreased by 21% (P less than 0.03) and the glomerular filtration rate had decreased by 16%. There was a significant increase (P less than 0.03) in the 2,3-dinor thromboxane B2 level at week 2, but there was no significant change in the levels of the other eicosanoids. This study demonstrates that after CSA treatment, there is a selective increase in a thromboxane metabolite that parallels an increase in renal vascular resistance, even in the absence of nonsteroidal antiinflammatory drugs, and with unimpaired formation of other vasodilator eicosanoids.

Correlation between antibodies to type II collagen and treatment outcome in bilateral progressive sensorineural hearing loss.

Our aim was to assess whether "idiopathic" bilateral progressive sensorineural hearing loss (BPSHL) has an immunological cause in some patients; antibodies to native type II collagen were sought by an ELISA in eighteen patients with BPSHL, before and after corticosteroid treatment, and in twelve patients with Menière's disease, fifteen with otosclerosis, eighteen with rheumatoid arthritis, nine with fibrositis, and nine healthy controls. A positive result was defined as a mean dilution titre of 2 or more. Eight of eighteen BPSHL patients had positive titres--significantly (p less than 0.005) more than in any other group (one Menière's disease, two otosclerosis, and no others). The mean antibody titre was higher in the BPSHL group than in any other group (2.02 [SEM 0.62] vs 0.17 [0.17]) Menière's disease, 0.44 [0.32] otosclerosis, 0 all others; p less than 0.005). The nine BPSHL patients who showed a clinical response to corticosteroids (improvement in at least one tone by audiogram or 25 db in speech discrimination score) had the highest mean antibody titre (3.46 [0.88] vs 0.59 [0.59] for the nine non-responsive patients; p less than 0.04). We suggest that in some patients with BPSHL, immunity to type II collagen, a major constituent of the inner ear, may be important in the pathogenesis of the disorder.