Laura Belloli

Vitamin D in systemic sclerosis

Sir, The recently published paper of Caramaschi et al. [1], who reported very low levels of vitamin D in systemic sclerosis (SSc), prompted us to report our data. We studied the serum levels of vitamin D in a cohort of 43 North Italian patients with SSc (age 61±14 years, 42 females, 29 with limited SSc, 11 with diffuse SSc, three with SSc sine scleroderma). Ninety-nine patients with osteoarthritis (OA) (age 65±10 years, 91 females) served as controls. None of the subjects received or was receiving vitamin D supplementation in the previous year. Vitamin D levels were classified as normal (≥30 ng/ ml), insufficient (<30, ≥10 ng/ml) and deficient (<10 ng/ ml) [2]. There were no differences in vitamin D levels between SSc (18.1±15.2 ng/ml, mean±SD) and OA (17.3±12.0 ng/ ml). Normal levels were observed in six SSc patients (14.0%) and in 12 (12.2%) OA patients. No differences were found between the two groups with respect to the prevalence of insufficient vitamin D levels, found in 51.2% of SSc patients and in 62.6% of OA patients (p=0.278), as well as prevalence of deficient vitamin D levels (34.8% vs. 25.2%, SSc vs. OA, p=0.334). Vitamin D levels were independent of the duration of SSc, the different types of SSc and the presence of anticentromere or antitopoisomerase I autoantibodies (data not shown). Our data confirm previous studies reporting low vitamin D levels in the majority of SSc patients [1, 3–6]. The prevalence of vitamin D deficiency or insufficiency found in our patients is very similar to that observed by Caramaschi et al. [1]. However, the low vitamin D levels we found do not seem to be related to the disease itself since no lower values were observed in SSc patients compared to OA patients. The major strength of our study is the comparison we have made between SSc patients with sexand age-matched controls. As far as we know, there is only one published paper that included a control group [7]; although the sample size in this study was small, based on our data, no differences were found between the groups. Because of the considerable variability in the reported vitamin D levels in SSc patients [1, 3–6], the high frequency of hypovitaminosis D in the general population [8], and the fact that our findings did not support a relationship between SSc and vitamin D levels, further studies are required to establish which non SSc-related factors, such as age, body mass index, and lifestyle, can be linked to the low vitamin D levels observed in SSc patients.

Systemic sclerosis and cancer.

To review recent advances and current controversies on the association between systemic sclerosis (SSc) and cancer, PUBMED was searched from 1966 to the present using the terms: systemic sclerosis, cancer, morphoea, sclerotic diseases. Malignancies, mainly in lung and breast, coexist with idiopathic SSc or with SSc-like disorders, but not with localized forms of scleroderma (morphoea), with the exception of squamous cell carcinoma in patients with pansclerotic morphoea and skin ulcers. The mechanisms connecting SSc and malignancies are unknown. The occurrence of different cancer types with SSc or SSc-like disorders suggest different underlying mechanisms, including altered immune response, common genetic and environmental links, disease-dependent factors, tumor-derived biologic substances and therapies. The process of sclerosis itself may favour cancer in certain sites, and a reaction between T cells and neoantigens formed during irradiation has been suggested to explain the frequent development of morphoea after breast irradiation. Radiotherapy, especially when used for breast cancer, may trigger idiopathic SSc or morphoea and influence the severity of preexisting SSc, with the consequence that SSc is considered a relative contraindication to breast radiotherapy. In conclusion, cancer and SSc may be associated, but it is still controversial as to whether there is a causal relationship. Continuing interest in these associations, in particular in the different modalities of associations, may help to understand the underlying biological mechanisms and to identify patients at risk.

Myocardial involvement in systemic sclerosis

OBJECTIVE To identify clinical and/or laboratory characteristics that could be risk factors for myocardial microvascular involvement in patients with SSc. METHODS Twenty-one SSc patients, clinically silent for cardiovascular disease, were consecutively evaluated for myocardial perfusion defects through 99m-Tc sestamibi gated myocardial perfusion SPECT with a stress-rest protocol. RESULTS Eight patients (38%) had myocardial perfusion defects. Perfusion defects were related to skin scores (P < 0.0001), digital ulcers (P = 0.02) and oesophageal involvement (P = 0.046). A trend for anti-Scl 70 antibody positivity was observed in these patients (P = 0.09). Three SPECT-positive patients had re-establishment of normal myocardial perfusion after a course of prostanoid therapy. There were no significant associations between myocardial involvement and age, sex, diffuse/limited SSc, duration of RP or lung involvement. CONCLUSIONS Myocardial perfusion defects in SSc patients are frequent, and the presence of severe skin thickness, digital ulcers and perhaps oesophageal involvement might warrant screening for myocardial involvement. Further studies are necessary to evaluate the effect of prostanoid therapy on myocardial perfusion.

Cancer in Italian Patients with Systemic Sclerosis

The association between cancer and systemic sclerosis (SSc) is known, although the underlying mechanisms remain unclear and epidemiological data is conflicting. Since no data exist on cancer in Italian SSc, we examined the frequency and characteristics of cancer in an Italian cohort of SSc patients to examine whether clinical and/or laboratory SSc-specific features represent a risk for developing malignancies in these patients. A retrospective chart review was carried out of 112 Italian SSc patients of whom 109 were women 3 and were men, aged 63±13 years; 81 patients had limited SSc, 25 had diffuse SSc and 6 had sine scleroderma SSc. Fifteen cancers were found in 14 patients. The majority (60%) occurred after SSc onset (average 16 years), 40% occurred before the onset of SSc (average 14 years). The most frequent was breast cancer (prevalence: 4.5%, relative prevalence:33.3%), followed by uterine cancer and lymphomas (prevalence: 2.7%, relative prevalence: 20% each). Lung cancer was not observed. Cancers were unrelated with SSc type, autoantibodies, organ involvement and treatments. In conclusion, clinical features do not seem to be linked with the risk of developing cancer in SSc patients. Interestingly, and in contrast with published data, no lung cancer was present in our patients, although lung involvement was observed in the majority of them. This finding, consistent with a lower prevalence of lung cancer in the Italian female general population, and the absence of associations between SSc-specific features and cancer, suggests that genetic and environmental factors might play a pivotal role in cancer risk in these patients.

Glucose blood levels after intra-articular steroid injection in diabetic and non-diabetic patients

Sir, The recently published paper of Habib and Safia [1] on the effect of intra-articular corticosteroid injections (IASI) on glucose blood levels prompted us to report our data. We studied 16 patients who needed IASI for inflammatory arthritis; 12 were non-diabetic subjects (age 58±14 years, mean ± SD, two men and ten women) and four patients had diabetes (age 58.7±13 years, one man and three women). Rheumatoid arthritis was present in 12 patients (nine without diabetes, three with diabetes), two patients (one with and one without diabetes) had psoriatic arthritis, one non-diabetic patient had ankylosing spondylitis, and one non-diabetic patient had an acute arthritis due to calcium pyrophosphate dihydrate crystal deposition. All of the patients underwent IASI with 40 mg triamcinolone (Kenacort, Bristol-MyersSquibb), and blood glucose was assessed for 24 h (at baseline in the morning before breakfast, 2 h after injection, immediately before and 2 h after lunch and dinner, and at 12 and at 24 h after injection, before meals). Twelve joints were injected (five knees, five wrists, one shoulder, one ankle) in non-diabetic patients, and four joints (one knee, one shoulder, one elbow, and one ankle) in diabetics. No infectious complications were recorded. Glucose blood levels are shown in Fig. 1. In both groups, blood glucose increased after IASI, with a maximum and significant increase after 2 h in non-diabetic subjects (43% vs. baseline, p=0.0025), while diabetic patients showed a greater increase, with a delayed maximum (after 12 h) but not statistically significant (70%,12 h vs. baseline, p=0.41). Twenty-four hours after IASI, blood glucose returned to baseline in both groups (14% and 20% vs. baseline, nondiabetics and diabetics, respectively). Data on glucose blood levels after IASI are scanty. Habib and Abu-Ahmad [2] in 18 diabetic patients did not find significant effects on blood glucose after 35 mg of methylprednisolone injected into the shoulders; however, more recently, Habib and Safia [1] found a significant increase of blood glucose in six diabetics immediately after 3 mg of betamethasone was injected in the knees, with return to baseline within 18–32 h. In conclusion, Habib and Safia’s [1] and our data have demonstrated that IASI is safe even in diabetic patients. Clin Rheumatol (2009) 28:491–492 DOI 10.1007/s10067-009-1091-5

Interstitial lung disease in systemic sclerosis.

Interstitial lung disease is an early and serious complication of systemic sclerosis (SSc). Because it may be asymptomatic for a long period, and only the early (logistic phase is at present susceptible to treatment, early diagnosis and identification of risk are critical to the outcome. However, identifying SSc patients at risk for developing interstitial lung disease is at present difficult; therefore, a strict monitoring of the disease, especially in the first years, is mandatory. Treatment strategy is aimed at suppressing inflammation. Unfortunately, optimal therapy has not yet been established. Combination of corticosteroids and cyclophosphamide is considered the best therapeutic approach available so far, but doses and duration of treatment need to be determined. Future research should focus on new anti-inflammatory or immunosuppressive agents.

Metastatic Melanoma in a Young Woman Treated with TNF-Alpha 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.

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.

Serum N-terminal pro-brain natriuretic peptide, a marker of skin thickness in systemic sclerosis?

Dear Editor, The recent paper of Choi HJ et al. [1] suggesting that NTproBNP may be a biological marker of skin fibrosis in systemic sclerosis (SSc), prompted us to report our data. We studied 16 SSc patients (15 females, one male) according to the criteria of the American College of Rheumatology [2], aged 57±15 years, 13 patients with limited SSc and three patients with diffuse SSc. None of the patients had pulmonary artery hypertension (PAH) (all were in NYHA functional class I and had systolic pulmonary arterial pressure <30 mmHg on echocardio color Doppler). N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured by immunoassay (Roche Diagnostics). Skin score was measured by the modified Rodnan method [3]. In accordance with Choi HJ et al. [1], we found a significant relationship between serum NT-proBNP levels and skin thickness (R=0.617, p=0.011) (Fig. 1). However, in contrast with Choi’s findings, no relationships were found between NT-proBNP levels, patients’ age (R=0.27, p=0.31) or DLCO (R=0.11, p=0.68). These findings are intriguing, since recent data rather indicate an antifibrogenic effect of natriuretic peptides, at least in the heart [4]. However, ischemia has been suggested to stimulate BNP release directly, and BNP has been found expressed in the intima of human coronary arteries, particularly of diseased vessels [5, 6], and a relationship has been observed between hypoxia and natriuretic peptide secretion [7]. On the other hand, since skin score might be a surrogate marker of SSc severity [8], elevated serum NTproBNP might simply indicate a more severe disease, independent from heart involvement or PAH, or it might identify patients at greater risk for cardiac events or PAH. In conclusion, even though ours and Choi’s data suggest that serum NT-proBNP may be a marker of skin fibrosis in SSc, further studies and a strict follow-up of patients are needed to define the intriguing role of this peptide in SSc patients.

Role of Fetuin-A in Systemic Sclerosis-associated Calcinosis

To the Editor: Calcinosis, a soft-tissue calcification occurring in the setting of normal serum calcium and phosphate levels, has been observed in connective tissue diseases, including systemic sclerosis (SSc)1, more frequently in the limited form (lcSSc) and in patients who are anticentromere antibody (ACA)-positive1. Calcinosis may be exceedingly painful and cause major clinical problems, including ulceration, infection, and joint contractures1. Hypovascularity, hypoxia, and tissue damage seem to favor its development, with genetic factors also playing a role. No treatment exists so far, and even surgical removal is unsatisfactory, since recurrences are common1. Fetuin-A (α-2-Heremans-Schmid glycoprotein, AHSG) is a major inhibitor of systemic calcification, and low serum levels have been associated with vascular and soft-tissue calcifications2. Any situation that lowers serum fetuin-A, including inflammatory conditions, could increase the risk of calcification, because fetuin-A is a negative acute-phase protein. AHSG gene variations seem to influence fetuin-A serum concentration3. Forty-one consecutive Italian patients with SSc [40 women, age 63 ± 13 years, 16 diffuse SSc (dcSSc), 25 lcSSc] were … Address correspondence to Dr. L. Belloli, Via Manzoni 56, Rozzano 20089, Italy. E-mail: laurabelloli{at}tiscali.it