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.

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.

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.

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.

Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis.

OBJECTIVE: To examine the safety and pharmacokinetics of and clinical response to leflunomide, a de novo pyrimidine synthesis inhibitor, when administered to patients with active rheumatoid arthritis (RA) who have been receiving long-term methotrexate therapy. METHODS: This was an open-label, 52-week study in which 30 patients with RA that remained active despite therapy with methotrexate at 17+/-4 mg/week (mean +/- SD) for > or =6 months were given leflunomide, 10-20 mg/day. Patients were assessed for adverse effects, pharmacokinetic measurements of leflunomide and methotrexate, and clinical response by American College of Rheumatology (ACR) 20% response criteria. RESULTS: Twenty-three patients completed 1 year of treatment. No significant pharmacokinetic interactions between leflunomide and methotrexate were noted. This combination therapy was generally well tolerated clinically, with the exception of elevations of liver enzyme levels. Seven patients withdrew from the treatment regimen: 2 withdrawals were voluntary, 3 were due to persistent elevation of plasma transaminase levels, and 2 were due to lack of efficacy. Of the patients, 16 (53%) met ACR 20% response criteria. Two met ACR criteria for remission after 1 year. CONCLUSION: The combination of methotrexate and leflunomide has therapeutic potential in RA.

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.

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.

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.

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.

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.

Zileuton, a 5-lipoxygenase inhibitor in rheumatoid arthritis.

The effects of zileuton, a new 5-lipoxygenase inhibitor, on leukotriene generation and clinical response in rheumatoid arthritis (RA) was studied in a 4-week randomized double blind placebo controlled study at 2 academic rheumatology centers. Zileuton decreased the mean (+/- SEM) ionophore induced synthesis of leukotriene B4 at Week 1 by 70% from 191.2 +/- 28.5 to 57.5 +/- 17.0 ng/ml. A parallel suppression of all major 5-lipoxygenase pathway products was observed. An improvement in clinical variables was observed in the zileuton and placebo treated population. No unique toxicity was identified in this study. Zileuton inhibited 5-lipoxygenase in RA with a suggestion of clinical response with limited toxicity.

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.

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.

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.