Analysis of risk factors for complications and adverse obstetrical outcomes in women with Takayasu arteritis: a French retrospective study and literature review.

OBJECTIVE: Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed. METHODS: All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015. RESULTS: The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study. CONCLUSION: This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.

Severe infections in sarcoidosis: Incidence, predictors and long-term outcome in a cohort of 585 patients.

Sarcoidosis is associated with cell-mediated immunodeficiency and treatment of symptomatic sarcoidosis usually includes systemic immunosuppressants. Data relative to incidence, prognosis factors, and outcome of infections are scarce.Retrospective cohort study of 585 patients with biopsy proven sarcoidosis in a tertiary referral specialist clinic, with a nested case-control analysis. Twenty nine patients (4.9%) with severe infections were compared to 116 controls subjects with sarcoidosis, matched according to their gender, ethnicity, age at diagnosis, and treatment with corticosteroids.After a median follow-up of 8 years [range; 1-46], 38 severe infections [mycobacterial infections (n = 14), fungal infections (n = 10), bacterial (n = 8), viral (n = 3) and parasitic (n = 1)] were observed in 30 patients. The incidence of severe infections was 0.71% persons-year (CI 95% 0.5-0.98) and 0.43% persons-year (CI 95% 0.27-0.66). Patients with severe infection were more frequently of male gender (60% vs 46%) and were more likely treated by ≥ 3 immunosuppressive agents (OR = 3.8, IC 95% [1.5-9.64], P = .005) and by cyclophosphamide (OR = 5.55, IC 95% [1.9-16.1], P = .002), and with neurological (OR = 3.36 CI 95% [1.37-8.25], P = .008), or cardiac (OR = 2.65 CI 95% [1.09-6.43], P = .031) involvement of the sarcoidosis, compared to the controls. Two patients died within the 6 months following infection, due to progressive multifocal leucoencephalopathy (n = 1), and of peritonitis (n = 1).Severe infections are observed in 5.1% of our patients with sarcoidosis after a median follow-up of 8 years. Risk factors for severe infections included neurological or cardiac involvement of sarcoidosis, the use of immunosuppressive agents and mainly cyclophosphamide.

Hydroxychloroquine-induced pigmentation in patients with systemic lupus erythematosus: a case-control study.

IMPORTANCE: Hydroxychloroquine-induced pigmentation is not a rare adverse effect. Our data support the hypothesis that hydroxychloroquine-induced pigmentation is secondary to ecchymosis or bruising. OBJECTIVE: To describe the clinical features and outcome of hydroxychloroquine (HCQ)-induced pigmentation in patients with systemic lupus erythematosus (SLE). DESIGN, SETTING, AND PARTICIPANTS: In a case-control study conducted at a French referral center for SLE and antiphospholipid syndrome, 24 patients with SLE, with a diagnosis of HCQ-induced pigmentation, were compared with 517 SLE controls treated with HCQ. MAIN OUTCOMES AND MEASURES: The primary outcome was the clinical features of HCQ-induced pigmentation. Skin biopsies were performed on 5 patients, both in healthy skin and in the pigmented lesions. The statistical associations of HCQ-induced pigmentation with several variables were calculated using univariate and multivariate analyses. RESULTS: Among the 24 patients, skin pigmentation appeared after a median HCQ treatment duration of 6.1 years (range, 3 months-22 years). Twenty-two patients (92%) reported that the appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas, which gave way to a localized blue-gray or brown pigmentation that persisted. Twenty-three patients (96%) had at least 1 condition predisposing them to easy bruising. Results from skin biopsies performed on 5 patients showed that the median concentration of iron was significantly higher in biopsy specimens of pigmented lesions compared with normal skin (4115 vs 413 nmol/g; P < .001). Using multivariate logistic regression, we found that HCQ-induced pigmentation was independently associated with previous treatment with oral anticoagulants and/or antiplatelet agents and with higher blood HCQ concentration. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine-induced pigmentation is not a rare adverse effect of HCQ. Our data support the hypothesis that HCQ-induced pigmentation is secondary to ecchymosis or bruising.

Ocular sarcoidosis.

Sarcoidosis, a chronic multisystem disease, is a common cause of ocular inflammation. Even though clinical features are well-established, diagnosis requires histological confirmation, which remains difficult in patients with uveitis. Thus, the frequency of ocular sarcoidosis is overestimated. A set of criteria has been recently established in order to improve the diagnostic procedure. New imaging tools will enable the ophthalmologist to evaluate the level of ocular inflammation and to monitor its resolution after treatment initiation. Indocyanine green angiography and optical coherence tomography have dramatically improved our understanding of choroidal granulomas and macular edema. Treatment is based on topical and systemic corticosteroids in most of the cases, but immuno-suppressive agents may be necessary. The visual outcome remains favorable but severe complications, including glaucoma, cystoid macular edema and choroidal neovascularization, may need a prompt and aggressive management.

Minor salivary gland biopsy in diagnosing ocular sarcoidosis.

BACKGROUND: To ascertain the sensitivity, specificity, and positive and negative predictive value of minor salivary gland biopsy in subsets of patients with uveitis consistent with ocular sarcoidosis. METHOD: Minor salivary gland biopsies performed in 230 patients with uveitis of indeterminate origin but clinically compatible with ocular sarcoidosis were reviewed. The biopsy results were analysed together with clinical features of uveitis and with the results of other relevant examinations, such as serum levels of angiotensin-I-converting enzyme and lysozyme, tuberculin skin test, chest radiography or CT scan, pulmonary function tests and bronchoalveolar lavage. RESULTS: Only seven of the 230 patients with uveitis had sarcoid granulomas on the minor salivary gland biopsy. All seven of these patients had a granulomatous uveitis and a compatible chest x-ray with sarcoidosis. The profitability of minor salivary gland biopsy can be improved by limiting the procedure to patients having granulomatous uveitis and a compatible chest x-ray. In these conditions, the positivity rate of minor salivary gland biopsy increased from 3% to 24% without loss of sensitivity. CONCLUSION: Minor salivary gland biopsy is most useful for assessing the diagnosis of sarcoid uveitis in a second-line investigation for patients with granulomatous uveitis and a radiologic pattern compatible with sarcoidosis.

Renal sarcoidosis: clinical, laboratory, and histologic presentation and outcome in 47 patients.

We conducted the current study to investigate the clinical, laboratory, and histologic features at presentation and the outcome of renal sarcoidosis (RS). Exhaustive retrospective data were collected by the French Sarcoidosis Group. Forty-seven adult patients were assessed (30 male/17 female, M/F ratio: 1.76). Median estimated glomerular filtration rate (eGFR) was 20.5 mL/min per 1.73 m(2) (range, 4-93 mL/min per 1.73 m(2)). Moderate proteinuria was found in 31 (66%) patients (median, 0.7 g/24 h; range, 0-2.7 g/24 h), microscopic hematuria in 11 (21.7%) patients, aseptic leukocyturia in 13 (28.7%) patients. Fifteen of 47 (32%) patients had hypercalcemia (>2.75 mmol/L). Eleven of the 22 (50%) patients diagnosed between June and September had hypercalcemia compared with only 4 of the 25 (16%) cases diagnosed during the other months (p < 0.001). Thirty-seven patients presented with noncaseating granulomatous interstitial nephritis (GIN), and 10 with interstitial nephritis without granulomas. Apart from hypercalcemia, the clinical phenotype was also remarkable for the high frequency of fever at presentation. All patients initially received prednisone (median duration, 18 mo), 10 received intravenous pulse methylprednisolone. eGFR increased from 20 +/- 19 to 44 +/- 24.7 mL/min per 1.73 m(2) at 1 month (p < 0.001, n = 38), to 47 +/- 19.9 mL/min per 1.73 m(2) at 1 year (p < 0.001, n = 46), to 49.13 +/- 25 mL/min per 1.73 m(2) at last follow-up (p < 0.001, n = 47). A complete response to therapy at 1 year and at last follow-up was strongly correlated with complete response at 1 month (p < 0.01). Renal function improvement was inversely related to initial histologic fibrosis score. A complete response to therapy at 1 year was strongly correlated with hypercalcemia at presentation (p = 0.003). Relapses were purely renal (n = 3) and purely extrarenal (n = 10) or both (n = 4), often a long time after presentation, with in some cases severe cardiac or central nervous system involvement. We conclude that hypercalcemia and fever at presentation are often associated with RS; RS is most often and permanently responsive to corticosteroid treatment, but some degree of persistent renal failure is highly frequent and its degree of severity in the long run is well predicted from both histologic fibrotic renal score and response obtained at 1 month.