Association of Sweet's Syndrome and Systemic Lupus Erythematosus.

Sweet's syndrome is an acute febrile neutrophilic dermatosis which usually presents as an idiopathic disorder but can also be drug induced, associated with hematopoetic malignancies and myelodysplastic disorders, and more, infrequently, observed in autoimmune disorders. Sweet's syndrome has been reported in three cases of neonatal lupus, three cases of hydralazine-induced lupus in adults, and in nine pediatric and adult systemic lupus erythematosus (SLE) patients. We describe three additional adult cases of Sweet's associated with SLE and provide a focused review on nondrug-induced, nonneonatal SLE and Sweet's. In two of three new cases, as in the majority of prior cases, the skin rash of Sweet's paralleled underlying SLE disease activity. The pathogenesis of Sweet's remains elusive, but evidence suggests that cytokine dysregulation may be central to the clinical and pathological changes in this condition, as well as in SLE. Further research is needed to define the exact relationship between the two conditions.

Lamivudine is not effective in primary Sjögren's syndrome.

BACKGROUND: Retroviral infection has been implicated in the pathogenesis of primary Sjögren's syndrome. OBJECTIVE: To examine the efficacy of the reverse transcriptase inhibitor lamivudine in patients with this syndrome. METHODS: 16 patients with primary Sjögren's syndrome were randomised to receive either lamivudine 150 mg twice daily or placebo for three months. Measures of lacrimal and salivary function, including minor salivary gland biopsies, were obtained before and after treatment. RESULTS: Treatment with lamivudine did not result in significant improvement in the primary outcome measure of unstimulated whole salivary flow or other secondary measures, including minor salivary gland biopsy focus scores. CONCLUSION: Lamivudine is not effective in patients with primary Sjögren's syndrome, suggesting either that a retroviral aetiology is not present or that it may be important only in early disease.

Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis.

OBJECTIVES: To describe a semi-quantitative scoring method for multi-feature, whole-organ evaluation of the knee in osteoarthritis (OA) based on magnetic resonance imaging (MRI) findings. To determine the inter-observer agreement of this scoring method. To examine associations among the features included in the scoring method. METHODS: Nineteen knees of 19 patients with knee OA were imaged with MRI using conventional pulse sequences and a clinical 1.5 T MRI system. Images were independently analyzed by two musculoskeletal radiologists using a whole-organ MRI scoring method (WORMS) that incorporated 14 features: articular cartilage integrity, subarticular bone marrow abnormality, subarticular cysts, subarticular bone attrition, marginal osteophytes, medial and lateral meniscal integrity, anterior and posterior cruciate ligament integrity, medial and lateral collateral ligament integrity, synovitis/effusion, intraarticular loose bodies, and periarticular cysts/bursitis. Intraclass correlation coefficients (ICC) were determined for each feature as a measure of inter-observer agreement. Associations among the scores for different features were expressed as Spearman Rho. RESULTS: All knees showed structural abnormalities with MRI. Cartilage loss and osteophytes were the most prevalent features (98% and 92%, respectively). One of the least common features was ligament abnormality (8%). Inter-observer agreement for WORMS scores was high (most ICC values were >0.80). The individual features showed strong inter-associations. CONCLUSION: The WORMS method described in this report provides multi-feature, whole-organ assessment of the knee in OA using conventional MR images, and shows high inter-observer agreement among trained readers. This method may be useful in epidemiological studies and clinical trials of OA.

Celecoxib-induced Sweet's syndrome.

Sweet's syndrome and related neutrophilic dermatoses have been associated with a variety of medications. Celecoxib is a new cyclo-oxygenase-2 inhibitor recently approved for arthritis. We describe a 57-year-old man who experienced tender pustulopapular lesions on the dorsal aspects of the hands, neck, and legs 1 week after starting celecoxib. Histopathologic examination of the lesion showed a diffuse dermal neutrophilic infiltrate, edema of the papillary dermis, spongiform pustules, and no leukocytoclastic vasculitis. These findings were consistent with Sweet's syndrome. Without realizing a possible association, the patient rechallenged himself with a second course of the medication, which resulted in a rapid exacerbation of his lesions. After discontinuing the medication for the second time, the patient has had complete clearing of his lesions. To our knowledge, this is the first report of Sweet's syndrome associated with this new class of nonsteroidal anti-inflammatory drugs.

A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS).

OBJECTIVE: To refine and validate the Birmingham Vasculitis Activity Score (BVAS) as a disease-specific activity index for Wegener's granulomatosis (WG). METHODS: Sixteen members of the International Network for the Study of the Systemic Vasculitides (INSSYS) revised the BVAS, with 3 goals: to reduce the redundancy of some component items, to enhance its ability to capture important disease manifestations specific to WG, and to streamline the instrument for use in clinical research. We defined the items and weighted them empirically as either minor (e.g., nasal crusting = 1 point) or major (e.g., alveolar hemorrhage = 3 points). We then validated the new, disease-specific BVAS/WG in 2 simulation exercises and a clinical case series that involved 117 patients with WG. RESULTS: We removed 38 items from the original BVAS, revised 9 items, and added 7 new items. Correlations between the scores on the BVAS/WG and the physician's global assessment (PGA) of disease activity were high, even when patients in remission were excluded. In the clinical case series, Spearman's rank correlation coefficient between the BVAS/WG and the PGA was r = 0.81 (95% confidence interval 0.73-0.87). The interobserver reliability using intraclass (within-case) correlation coefficients in the 2 simulation exercises was r = 0.93 for the BVAS/WG and r = 0.88 for the PGA in the first and r = 0.91 for the BVAS/WG and r = 0.88 for the PGA in the second. There was no significant observer effect in the scoring of the BVAS/WG or the PGA. The discriminant validity of the BVAS/WG was good: r = 0.73 (95% confidence interval 0.43-0.83). CONCLUSION: The BVAS/WG is a valid, disease-specific activity index for WG. Tested in simulation exercises and in actual patients, the BVAS/WG correlates well with the PGA, is sensitive to change, and has good inter- and intraobserver reliability. The INSSYS will use the BVAS/WG to assess the primary outcome in a phase II/III trial of etanercept in WG.

Propylthiouracil-induced microscopic polyangiitis.

The use of propylthiouracil (PTU) has been associated with various forms of vasculitis. We herein describe the case of a patient with Grave's disease who, after years of PTU therapy, developed a necrotizing vasculitis with anti-serine protease-3 antibodies. Despite treatment with corticosteroids and cyclophosphamide, the patient died of intra-alveolar hemorrhage secondary to her vasculitis. Based on the vessel size involved, the organ distribution of pathologic findings, and lack of granulomas, autopsy findings were felt to be more consistent with microscopic polyangiitis (MPA) than with her original clinical diagnosis of Wegener's granulomatosis. Her case satisfied both clinical and pathologic criteria for MPA. An MPA diagnosis is important to consider in similar clinical presentations because therapy may just need to be early withdrawal of an inciting drug, such as PTU, and the initiation of corticosteroids without cytotoxic therapy.

New treatments for rheumatoid arthritis. Available and upcoming slow-acting antirheumatic drugs.

No single therapeutic agent has been found to be universally effective for rheumatoid arthritis, so regimens using combinations of drugs have become the rule. Recently, several new agents with unique mechanisms of action have been introduced and found to produce various degrees of clinical benefit. Among these agents are folate and purine antagonists, alkylating agents, and antipyrimidines. Chimeric (mouse/ human) monoclonal antibody to tumor necrosis factor-alpha and human recombinant interleukin-1 receptor antagonist await approval for general use but have undergone considerable study.

Compressive cervical myelopathy due to calcium pyrophosphate dihydrate deposition disease: report of a case and review of the literature.

Calcium pyrophosphate dihydrate (CPPD) deposition disease is an inflammatory arthropathy that is defined by the deposition of CPPD crystals in articular and periarticular structures. The deposition of CPPD in hyaline cartilage and fibrocartilage leads to the chondrocalcinosis that is characteristic of the disease. It can occur independently or in association with any of a number of inflammatory or endocrine disorders. This form of crystal-induced arthritis tends to affect the peripheral joints, particularly the knees, ankles, shoulders, wrists, and second and third metacarpophalangeal joints, but involvement of the lumbar spine is not uncommon. Cervical spine disease due to CPPD deposition is, however, rare. We report a case of compressive cervical myelopathy due to CPPD deposition disease of the cervical spine in a woman with long-standing rheumatoid arthritis. We also, from a review of the English-language literature, describe the collective reported clinical experience with CPPD deposition disease of the cervical spine.

Adenine phosphoribosyltransferase deficiency with renal deposition of 2,8-dihydroxyadenine leading to nephrolithiasis and chronic renal failure.

Homozygous adenine phosphoribosyltransferase deficiency is a genetic defect that is associated with 2,8-dihydroxyadenine urolithiasis. Since the prevalence of the heterozygous state is found in 0.4% to 1.2% of the population, it is surprising that more cases of 2,8-dihydroxyadenine urolithiasis have not been reported. Herein we describe a patient with complete adenine phosphoribosyltransferase deficiency with 2,8-dihydroxyadenine urolithiasis leading to chronic renal failure. Gene sequencing revealed that the patient is a compound heterozygote. One of the mutations (a T insertion between bases 346 and 347) has been encountered before, but the second (a G-to-A substitution at base 1356) has not been previously reported. Possible explanations for the unexpected rarity of 2,8-dihydroxyadenine urolithiasis are discussed.

Renal insufficiency secondary to 2,8-dihydroxyadenine urolithiasis.

A 48-year-old man with a history of recurrent urolithiasis and chronic renal failure underwent a nephrectomy for a renal mass. At surgery the mass proved to be a calculus impacted in a dilated calyx. Gross examination of the kidney revealed chalky white deposits in the deep medulla and papillary tips. Histologic examination revealed chronic interstitial nephritis with brown spicules within some tubular epithelial cells and larger deposits of brown crystals within tubular lumina, the interstitium of the medulla, and papillary tips. Polarization microscopy revealed individual crystals scattered throughout the renal parenchyma. Although the arrangement of the crystals was reminiscent of uric acid, and, in fact, a clinical diagnosis of gouty nephropathy was made, x-ray diffraction analysis demonstrated crystals of 2,8-dihydroxyadenine. Enzymatic studies confirmed the complete absence of adenine phosphoribosyltransferase activity in erythrocyte lysates.

Methotrexate and histologic hepatic abnormalities: a meta-analysis.

STUDY OBJECTIVE: To determine the risk of liver toxicity from the long-term administration of methotrexate in patients with rheumatoid arthritis or psoriatic arthritis. DESIGN: A meta-analysis of 15 studies examining the relationship between long-term, low-dose methotrexate administration and biopsy evidence of liver fibrosis. PATIENTS: A total of 636 patients from 15 studies. RESULTS: The incidence of progression of liver disease (defined as worsening of at least one grade on the histologic classification of Roenigk) among 636 patients was 27.9% (95% confidence intervals 24.3 to 31.6). The rate of progression of liver disease in the 15 studies was associated with the cumulative dose of methotrexate (p = 0.01). Patients on average had a 6.7% (95% confidence intervals 2.1 to 11.4) chance of progressing at least one histologic grade on liver biopsy for each gram of methotrexate taken. The overall incidence of advanced pathologic changes on liver biopsy (grades IIIB or IV) among 636 patients was 5.0% (95% confidence intervals 3.5 to 7.0). The development of advanced histologic changes was not associated with the cumulative dose of methotrexate (p = 0.08). Patients who according to their history were heavy drinkers (at least 100 g of alcohol per week) were more likely to have advanced changes on liver biopsy (17.8% versus 4.5%, p = 0.0003) and to show histologic progression (73.3% versus 25.9%, p = 0.0002). Patients with psoriasis were more likely than patients with rheumatoid arthritis to have advanced changes (7.7% versus 2.7%, p = 0.003) and histologic progression (33.1% versus 24.3%, p = 0.02). CONCLUSIONS: The risk of liver toxicity in patients undergoing long-term, low-dose methotrexate therapy is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol. Heavy users of alcohol should not receive long-term methotrexate therapy. For most patients who are not heavy users of alcohol, liver biopsies should be done periodically to monitor for the occurrence of liver toxicity.

Clinical response to regional intravenous guanethidine in patients with rheumatoid arthritis.

A novel therapy for rheumatoid arthritis, regional sympathetic blockade using guanethidine, was investigated in 24 patients with active disease. In a randomized double blind short-term (14 days) study, we evaluated the effect of therapy on subjective responses, change in pain, stiffness, and morning stiffness and no objective responses, change in pinch strength, grip strength, and joint tenderness. Compared to placebo, guanethidine produced a decrease in pain (p less than 0.025) and an increase in pinch strength (less than 0.025) over the 2-week duration of the study. The therapeutic effect of guanethidine may be mediated by an interruption of the proinflammatory effects of the sympathetic nervous system.

Eosinophilic vasculitis leading to amaurosis fugax in a patient with acquired immunodeficiency syndrome.

A 49-year-old bisexual man with generalized lymphadenopathy and antihuman T lymphocyte virus, type III, (HTLV-III) antibodies presented with recurrent, unilateral amaurosis fugax. A temporal artery biopsy specimen showed eosinophilic vasculitis. The patient then developed acquired immunodeficiency syndrome with Kaposi's sarcoma. We describe this patient because of the unusual association of large vessel vasculitis and acquired immunodeficiency syndrome.

Digital necrosis: a paraneoplastic syndrome.

We describe a 62-year-old man who presented with digital necrosis as part of a clinical picture which resembled Wegener's granulomatosis. However, an open lung biopsy revealed adenocarcinoma of the lung. To our knowledge he is only the 5th reported patient with lung cancer presenting with digital necrosis. The unusual association of digital necrosis and internal malignancy is discussed.

Methotrexate induced false photosensitivity reaction.

Methotrexate is now being used in the treatment of a variety of intractable rheumatologic conditions. We report a patient with polymyositis who developed mild erythroderma after sun exposure. Forty-eight h later he received his weekly dose of methotrexate. Within 24 h the resolving rash erupted into an intense dusky red dermatitis with eventual formation of confluent bullae. The patient had a methotrexate induced ultraviolet reactivation reaction also known as a "false photosensitivity" reaction. This reaction has been reported in dermatologic publications but not in the rheumatologic literature.