ACUTE PHASE REACTIONS AFTER ZOLEDRONIC ACID INFUSION: PROTECTIVE ROLE OF 25-HYDROXYVITAMIN D AND PREVIOUS ORAL BISPHOSPHONATE THERAPY.

OBJECTIVE: The most common adverse reaction to zoledronic acid (ZOL) infusion is the acute phase reaction (APR), characterized by transient, usually mild, flu-like symptoms. Previous treatment with oral amino-bisphosphonates (BPs) was reported as an independent protective factor for APR, and an association between APR and 25-hydroxyvitamin D (25(OH)D) levels in BP-naïve patients treated with ZOL was identified. The aims of our study were to confirm this association and to see if it was different in patients previously treated with oral BPs compared with BP-naïve patients and to investigate the role of 25(OH)D for the time of APR onset. METHODS: We included 153 consecutive patients with postmenopausal osteoporosis undergoing their first ZOL infusion. Sixty-eight had been previously treated with oral BPs. Clinical, demographic, and serologic data were recorded. RESULTS: 25(OH)D levels were significantly lower in patients experiencing APR compared to patients without APR (26.3 ± 12.7 vs. 37.0 ± 13.5 ng/mL, respectively; P<.0001). Patients with 25(OH)D <30 ng/mL had a significantly higher risk of APR (odds ratio [OR] 4.2 [95% confidence interval [CI] 2.1-8.2]) occurring in 65%. APR was significantly less frequent in patients previously treated with oral BPs than in BP-naïve subjects (33.8% [23/68] vs 52.9% [45/85], P = .018), but only a weak association remained after correction for 25(OH)D (OR 0.5, 95% CI 0.3-1.1, P = .08). CONCLUSION: Higher baseline 25(OH)D levels appear to be protective for APR post-ZOL infusion. The role of previous treatment with oral BPs as an independent protective factor for APR should be evaluated in a larger cohort. ABBREVIATIONS: APR = acute phase reaction; BPs = amino-bisphosphonates; CI = confidence interval; 25(OH)D = 25-hydroxyvitamin D; OP = osteoporosis; OR = odds ratio; PTH = parathyroid hormone; ROC = receiver operating characteristic; ZOL = zoledronic acid.

Nailfold videocapillaroscopy and serum VEGF levels in scleroderma are associated with internal organ involvement.

PURPOSE: Nailfold videocapillaroscopy (NVC) identifies the microvascular hallmarks of systemic sclerosis (SSc) and vascular endothelial growth factor (VEGF) and may play a pivotal role in the associated vasculopathy. The aim of the present study was to compare NVC alterations with clinical subsets, internal organ involvement, and serum VEGF levels in a cohort of selected SSc cases. METHODS: We studied 44 patients with SSc who were evaluated within 3 months from enrollment by NVC, skin score, severity index, pulmonary function tests, carbon monoxide diffusing capacity (DLCO), echocardiography, pulmonary high-resolution computed tomography (HRCT), gastroesophageal (GE) endoscopy or manometry or X-ray, and serum autoantibodies. Serum VEGF-A levels were determined by ELISA in 72 SSc patients and 31 healthy controls. RESULTS: Giant capillaries were inversely correlated with age (p = 0.034, r = -0.34) and to the extent of reticular pattern at HRCT (p = 0.04, r = -0.5). Avascular areas were directly correlated with capillaroscopy skin ulcer risk index (CSURI) (p = 0.006, r = +0.4) and severity index (p = 0.004, r = +0.5). The mean capillary density was directly correlated to the ulcer number (p = 0.02, r = +0.4) and to DLCO/alveolar volume (p = 0.02, r = +0.4) and inversely correlated with severity index (p = 0.01, r = -0.4) and skin score (p = 0.02, r = -0.4). Serum VEGF levels were higher in the SSc population vs controls (p = 0.03) and inversely correlated with DLCO (p = 0.01, r =-0.4) and directly with ground-glass and reticular pattern at HRCT (p = 0.04, r = +0.4 for both). CONCLUSIONS: Our data suggest the importance of NVC not only for the diagnosis, but also for the global evaluation of SSc patients. Of note, serum VEGF levels may act as a biomarker of interstitial lung involvement.

Hypophosphatemic Osteomalacia Associated with Tenofovir: a Multidisciplinary Approach is Required.

Tenofovir is widely used as first-line treatment of HIV infection, although its use is sometimes complicated by a reversible proximal renal tubulopathy.We report the case of a 45-year-old woman with chronic HIV infection and personality disorder, who after 12 months of tenofovir, complained of fatigue, diffuse bone pain and gait disturbances. The elevated level of alkaline phosphatase, hypophosphatemia and inappropriate phosphaturia suggested the diagnosis of hypophosphatemic osteomalacia secondary to proximal renal tubulopathy. A dual-energy x-ray absorptiometry showed a bone mineral density below the expected range for age (lumbar spine Z-score -3.3, femoral neck Z-score -2.1). A whole body (99m)Tc-methylene diphosphonate bone scan showed multiple areas of increased focal activity in the lumbar and thoracic spine and in sacroiliac and hip joints consistent with pseudofractures. Two months after tenofovir discontinuation and administration of vitamin D and phosphate, osteomalacia-related symptoms disappeared. Eleven months later, bone and mineral metabolism data were normal and bone scintigraphy did not show any pathological findings.This report highlights the importance of considering the diagnosis of osteomalacia in patients treated with tenofovir and emphasizes the need for monitoring alkaline phosphatase, blood and urinary phosphate and creatinine, especially in patients with risk factors for bone disease.

Metastatic melanoma in a young woman treated with TNF-α inhibitor for psoriatic arthritis: a case report.

INTRODUCTION: The risk of cancer with the use of biologic agents in rheumatic diseases is still a matter of debate. Published data suggest that the extent of cancer risk might differ according to the type of cancer, and there is recent clinical evidence for a significant increased risk for skin cancer, including melanoma. In contrast with the extensive literature on cancer risk in rheumatoid arthritis, little has been reported on the development of malignancies in spondyloarthroparthies. CASE PRESENTATION: We report the case of an otherwise healthy 31-year-old Italian woman with psoriasic arthritis who developed a melanoma of left third toe with metastatic involvement of regional lymphnodes after a 3-year treatment with the TNF-alpha inhibitor adalimumab. CONCLUSION: This case illustrates the possibility of a causal relationship between TNF-alpha inhibitors and melanoma. We believe that vigilance should continue in patients treated with TNF-alpha blocking agents, until the question on the increased incidence of cancers, including skin cancers, associated with these drugs will be defined.

Is there a role for TNFα antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique.

OBJECTIVES: To obtain experiences and expert opinion on treatment of SSc patients with TNF-α antagonists. METHODS: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-α antagonists. Assessment forms on the frequency of TNF-α inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-α inhibitors in SSc. RESULTS: Seventy-nine centres returned information on use of TNF-α antagonists in SSc patients. A total of 65 patients were treated with TNF-α inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-α inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-α antagonists in SSc. Arthritis was suggested as an indication for TNF-α antagonists by 75% of the experts. However, after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-α antagonists decreased and 59% recommended that TNF-α antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-α antagonists for arthritis associated with SSc. CONCLUSIONS: Most of the experts do not recommend the routine use of TNF-α antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-α antagonists are needed before general recommendations can be given.

Polyostotic Paget disease involving bones of the upper extremity.

Paget disease of bone (PD) is a common skeletal disease. It is usually polyostotic and most frequently involves the pelvis, femur, spine, skull, and tibia. The bones of the upper extremity in poly- or monostotic PD are rarely affected. A patient with PD involving the third left metacarpal bone and carpal bones of the right hand is described.

Metastatic gastric cancer presenting with shoulder-hand syndrome: a case report.

INTRODUCTION: Shoulder-hand syndrome is a relatively rare clinical entity classified as a complex regional pain syndrome type 1 and consisting essentially of a painful 'frozen shoulder' with disability, swelling, vasomotor or dystrophic changes in the homolateral hand. The pathophysiology is not completely clear but a predominant 'sympathetic' factor affecting the neural and vascular supply to the affected parts seems to be involved. Shoulder-hand syndrome has been related to many surgical, orthopedic, neurological and medical conditions; it is more often seen after myocardial infarction, hemiplegia and painful conditions of neck and shoulder, such as trauma, tumors, cervical discogenic or intraforaminal diseases and shoulder calcific tendinopathy, but has also been associated with herpetic infections, brain and lung tumors, thoracoplasty and drugs including phenobarbitone and isoniazid. The diagnosis of shoulder-hand syndrome is primarily clinical, but imaging studies, particularly bone scintigraphy, may be useful to exclude other disorders. CASE PRESENTATION: We report the case of a 67-year-old woman who presented with shoulder-hand syndrome as the initial manifestation of gastric cancer which had metastasized to bone. CONCLUSION: Wider investigations are advisable in patients with atypical shoulder-hand syndrome. To the best of the authors' knowledge this is the first case of shoulder-hand syndrome associated with metastatic gastric cancer.

A case of atypical giant cell arteritis diagnosed by positron emission tomography (PET).

The authors describe an atypical case of a patient having giant cell arteritis presenting only with fever, diagnosed by positron emission tomography and subsequently confirmed by temporal artery biopsy.

Acute psycosis in systemic lupus erythematosus.

Psychiatric manifestations are common in systemic lupus erythematosus (SLE) and often represent a challenging diagnostic and therapeutic problem, mainly because the uncertainties of the pathogenic mechanisms. We report a case of acute psychosis occurring in a female with SLE due to the stress of having a severe disease, rather than to SLE per se.

Genetic contribution to carotid vascular disease in patients with systemic lupus erythematosus.

OBJECTIVE: We investigated whether stromelysin, a candidate gene in atherogenesis, plays a role in atherogenesis of systemic lupus erythematosus (SLE), a leading cause of mortality in SLE. PATIENTS AND METHODS: A genetic study using polymorphism located in the promoter region of stromelysin was performed in 55 Italian patients with SLE. Carotid intimal-medial thickness (IMT) was evaluated by B mode ultrasonography. RESULTS: All patients with an "abnormal" (> or =0.9 mm) IMT carried at least one 6A allele, and the degree of IMT was significantly greater in patients carrying at least one 6A allele (0.63 +/- 0.22 vs 0.43 +/- 0.04 mm, 5A/6A + 6A/6A vs 5A/5A, p = 0.018). CONCLUSION: Our data show that polymorphism of stromelysin promoter may be relevant for SLE-related cardiovascular disease.