The Relationship between Smoking, Raynaud's Phenomenon, Digital Ulcers, and Skin Thickness in the Waikato Systemic Sclerosis Cohort.

Objectives: Systemic sclerosis (SSc) is a heterogeneous complex autoimmune connective tissue disease with variable presentation as a consequence of multisystem involvement. One of the key features of SSc is Raynaud's phenomenon along with vascular endothelial dysfunction that leads to digital ulcers (DUs). Raynaud's tends to be triggered by decreasing thermal gradient exposure, while stress and smoking also play a role. DUs arising as a consequence of severe Raynaud's and vasculopathy are a major cause of morbidity and disability in SSc. We set out to determine the relationship between smoking, Raynaud's phenomenon, DUs, and skin thickness in our Waikato Systemic Sclerosis cohort. Methods: The Waikato Systemic Sclerosis (SSc) database was used to extract data. Variables collected included demographics, age of diagnosis, SSc subtypes, age at first non-Raynaud's phenomenon, medications used for treatment of Raynaud's phenomenon or ulcers, and maximal modified Rodnan skin score (mRSS). Raynaud's phenomenon and finger DUs (severity for each over the past week and since diagnosis) and a Scleroderma Health Assessment Questionnaire (SHAQ) visual analog 10 cm scale were collected. The lead rheumatologist completed a physician's assessment of Raynaud's and the disease severity questionnaire. Results: Of the cohort of 143 patients, 100 patients were eligible to complete the questionnaires. Seventy-five patients returned completed questionnaires. Of these, the majority were female (88%), 52 (69.3%) had limited cutaneous systemic sclerosis (lcSSc), 17 (22.7%) had diffuse cutaneous systemic sclerosis (dcSSc), and 6 (8%) had an overlap syndrome. Thirty-six (48%) had a smoking history (in the time frame of collection of serial data). Mean ± standard deviation (SD) pack-years smoked were 17.11 ± 15.29 years. Thirty-five participants had a history of DUs, with a median of 4 DU (range 1-20). Of 17 patients with dcSSc, 12 (70.6%) had ulcers in comparison with 17 of 52 (32.7%) patients with lcSSc. There was a significant relationship between SSc subtype and the number with ulcers (X2 = 10.1, P = 0.007). There was also a significant relationship between physician severity of Raynaud's and presence of ulcers (t = 6.1, P < 0.001), which was not evident between patients' severity of Raynaud's and presence of ulcers (t = 1.9, P = 0.06). On the SHAQ score, smokers had significantly worse Raynaud's phenomenon over the prior week (t = 3.08, P = 0.03) and were more likely to note DUs over the preceding week, although the latter was not statistically significant (t = 1.95, P = 0.055). There was no association between smoking and skin thickness as measured by mRSS (r = 0.23, P = 0.19). Conclusion: Our study demonstrates that smokers have had worse Raynaud's phenomenon over the past week and they were also more likely to note DUs with a trend toward significance but not statistically significant most likely due to our small sample size. Our study also demonstrated that patients with dcSSc had more ulcers in comparison with lcSSc. This study justifies physicians strongly recommending smoking cessation in patients with SSc.

Increased malignancies in our Waikato cohort of patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) has been associated with an increased risk of malignancy (especially in the skin, lung, breast, and hematological system). AIM: To determine the risk of malignancies in our SSc cohort. METHODS: The NZ National Cancer Registry supplied details of all malignancies recorded in patients attending the Waikato Hospital Systemic Sclerosis Clinics from 2005 to 2018. Prospectively gathered clinical data were used to look for associations between clinical variables and malignancy. RESULTS: Out of the 164 patients in the Waikato SSc cohort, 32 (19.5%) had developed a malignancy. The overall standardized incidence rate was found to be 2.2 (95% CI 1.4-3.4) but was higher for men (4.4, 95% CI 1.4-10.3). The absolute numbers of patients with SSc and malignancies were small and were not adequately powered to investigate the SSc subgroups. The mean age of patients with malignancy was approximately 8 years older than patients without. The most common form of malignancy was skin (14, 43.7%), followed by breast (6, 18.7%), and lymphoma (5, 15.6%). CONCLUSION: This study found an increased risk of malignancy for patients within the Waikato SSc cohort. Risk was greater in male patients and the mean age of patients with malignancies was approximately 8 years older than those without malignancy.

Significance of combined anti-CCP antibodies and rheumatoid factor in a New Zealand cohort of patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) can present as an overlap syndrome with rheumatoid arthritis (SSc-RA overlap). OBJECTIVE: To evaluate the frequency of rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) in our SSc cohort and their association with clinical features. METHODS: Data were gathered prospectively from the Waikato Hospital Systemic Sclerosis Clinics. Patients with SSc and SOS (systemic sclerosis overlap syndrome) underwent baseline auto-antibody profiling including RF and anti-CCP along with annual clinical review. RESULTS: Our cohort comprised of 132 patients (two had incomplete data); 115 (87.1%) were female. Out of 89 limited cutaneous SSc (lcSSc) patients, arthralgia, synovitis, contractures, tendon crepitus and erosions on imaging were found in three, 10, 31, five and nine patients, respectively. Within the 33 diffuse cutaneous SSc (dcSSc) patients, arthralgia, synovitis, contractures, tendon crepitus and erosion were found in 15, five, 27, five and one patient, respectively. In the 10 SOS patients, arthralgia, synovitis and contractures were found in six, three and two patients; none had tendon crepitus or erosions. RF positivity was found in 15.7%, 9% and 20% of patients with lcSSc, dcSSc and SOS, and anti-CCP positivity was found in 13.5%, 6.1% and 0% in lcSSc, dcSSc and SOS patients. A statistically significant relationship of double antibody positivity with arthralgia (P = 0.03) and erosions (P < 0.001) was found. Anti-CCP positivity association with erosions was significant at P = 0.007. CONCLUSION: Our study confirms that articular manifestations are common in SSc. Statistically significant associations of double antibody positivity with arthralgia and erosions were demonstrated. Significant association between anti-CCP antibody and erosions was also confirmed.

High Prevalence of Antithyroid Antibodies in a New Zealand Cohort of Patients With Systemic Sclerosis.

BACKGROUND: Autoimmune thyroid disease affects 1% of the general population, and autoimmune thyroid antibodies are noted in up to 15%. OBJECTIVE: We hypothesized systemic sclerosis (SSc) is associated with higher prevalence of antithyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies) to justify monitoring of thyroid function for earlier detection and treatment. METHODS: Waikato Hospital SSc clinic patients were prospectively tested for thyroid function tests and antithyroid antibodies (ATAs). RESULTS: Of the 75 patients with SSc and 10 patients with SSc overlap syndrome (SOS) followed up in the SSc clinic, anti-Tg and anti-TPO were prospectively tested in 61 (70.6%) of the 85 patients. The cohort comprised 38 patients with limited cutaneous SSc (lcSSc), 15 with diffuse cutaneous SSc, and 8 with SOS.Anti-Tg and anti-TPO antibodies were found in 34.2% in lcSSc patients and 33.3% in diffuse cutaneous SSc patients, whereas in SOS they were found in 25% (Tg) and in 12.5% (TPO) of patients.At baseline, 10 patients (11.7%) had thyroid dysfunction: 8 (9.4%) with subclinical hypothyroidism and 1 each (1.2%) with subclinical hyperthyroidism and with clinical hyperthyroidism.After 18 months, 1 woman with lcSSc, positive for both ATAs, developed clinical hypothyroidism. CONCLUSIONS: There is a higher prevalence of ATAs in SSc and SOS compared with the general population. Screening these patients for ATAs is a reasonable measure.

Clinical utility of hypo- and hyperpigmentation of skin in diffuse cutaneous systemic sclerosis.

AIM: Cutaneous involvement is an early manifestation of systemic sclerosis (SSc). Localized areas of 'salt and pepper skin' (S&P) may develop. We hypothesize that S&P skin occurs frequently in diffuse cutaneous (dc) SSc which can be used in its early diagnosis and may correlate with joint contractures. METHODS: Sixty-five patients were recruited for this study. The demographic profiles of SSc were ascertained from hospital records. These patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria. Patients were examined for skin pigmentary changes, modified Rodnan skin score (mRSS), telengiectasias, calcinosis, arthritis and joint contractures and pruritus. RESULTS: Sixty-five patients (59 female) were recruited with median age of 62.87 years. Forty-four had limited cutaneous SSc, 16 dcSSc, five had scleroderma overlap syndrome. Multivariate stepwise logistic regression indicated that mRSS severity and the presence of contractures were independently (P < 0.05) associated with dcSSc. The strong positive association between S&P and mRSS severity may explain the non-significance of S&P in this analysis. If mRSS severity is not included in the logistic regression analysis, the presence of contractures and S&P (odds ratio = 15.1) show significant (P < 0.01) independent associations with the dcSSc subtype. S&P skin and pruritus were similar in patients with Scl-70 and anti-RNA polymerase antibodies. Anti-centromere antibodies were negatively associated with S&P (χ2 = 7.89, P = 0.005). CONCLUSION: Our study demonstrates strong association of S&P skin with dcSSc (69%), increased risk of pruritus and contractures. Its presence can be used as another clinical tool to diagnose dcSSc in early stages. Observing for S&P skin changes does not require much training.

A cross-sectional study of autoantibody profiles in the Waikato systemic sclerosis cohort, New Zealand.

The autoantibody profiles in New Zealand systemic sclerosis patients have not previously been reported. The aim of this study was to evaluate the autoantibody profiles of patients in the Waikato Hospital Systemic Sclerosis Clinic cohort. The EUROLINE (IgG) Systemic Sclerosis panel test kit (which tests for Scl-70, CENP-A, CENP-B, RP11, RP155, Fib, NOR90, Th/To, PM100, PM75, Ku, PDGFR and Ro-52) was selected for the purpose of this study. All patients attending the Waikato Hospital Systemic Sclerosis clinic were invited to participate. These patients were categorised by systemic sclerosis subtypes [1]. Results were compared with previously published data, including the EUSTAR database. Sixty patients (56 female) were recruited, with a median age of 61 years (range 29-81 years). Forty-one had limited cutaneous systemic sclerosis (lcSSc). Of these lcSSc patients, 31 (75.6%) were positive for CENP-A and CENP-B (anti-centromere) antibodies, 12 (29.3%) for Ro-52 antibodies, 5 (12.2%) for RP11 and RP155, 4 (9.8%) for Scl-70 and 1 (2.4%) each for anti-Fib and Th/To antibodies. Fifteen patients had diffuse cutaneous systemic sclerosis (dcSSc), of which 7 patients (47.6%) were positive for RP11 and RP155, 4 (26.7%) for Scl-70. Three dcSSc patients did not have either of these two major antibodies, but of these 15 dcSSc patients, 4 patients (26.7%) were positive also for Ro-52, 2 (13.3%) for anti-Ku, and 1 (6.7%) each for anti-Fib and NOR90. Four patients had overlap syndrome (OLS), 1 had CENP-A and CENP-B antibodies, 1 had Ro-52 autoantibodies 1 had anti-Ku antibodies. Three patients had no autoantibodies. This is the first study to look at the autoantibody profile of SSc patients in New Zealand. A higher prevalence of antibodies against centromere and RNA polymerase III was demonstrated in our group compared with the EUSTAR database suggesting that antibody prevalence may vary geographically.