Uveítis anterior crónica en paciente con síndrome de CREST / Chronic anterior uveitis in a patient with CREST syndrome

La esclerosis sistémica es una conectivopatía con unas manifestaciones clínicas muy heterogéneas, relacionándose en un pequeño porcentaje con enfermedades oculares inflamatorias. En el caso concreto de las uveítis, únicamente se han descrito casos aislados en la literatura, sobre todo con relación al síndrome de CREST. Presentamos el caso de una mujer de 53 años, con síndrome de CREST y uveítis anterior crónica, que consideramos de relevancia clínica dada su baja prevalencia

Systemic sclerosis is a connective tissue pathology with very heterogeneous clinical manifestations, associated in a small percentage with inflammatory eye diseases. In the specific case of uveitis, only isolated cases have been reported in the literature, especially in relation to the CREST syndrome. We present the case of a 53-year-old woman with CREST syndrome and chronic anterior uveitis, which we consider of clinical relevance given its low prevalence

Botulinum toxin for treatment of Raynaud phenomenon in CREST syndrome.

Calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome is a form of a rare, clinical subtype of systemic sclerosis, known as limited systemic sclerosis. Limited systemic sclerosis, including CREST syndrome, manifests as fibrotic skin changes restricted to the hands and face, with vascular, musculoskeletal, and visceral involvement. We present a case of a 75-year-old woman with a longstanding history of CREST syndrome complicated by a digital ulceration and persistent pain associated with recalcitrant Raynaud phenomenon. After failing a number of first-line pharmacologic therapies such as diltiazem, sildenafil, and topical nitropaste, the patient was started on a trial of botulinum toxin for the left second digit, with 10 unit injections into both webspaces for a total of 20 units. Following injection, the patient reported no further baseline pain in the affected finger and an over fifty-percent improvement in discomfort with manipulation of the digit at a follow-up time of one week. The ulceration started healing within the following three weeks. This result was maintained at a follow-up time of six weeks.

Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis.

OBJECTIVE: We undertook this hypothesis-generating study to identify skin transcripts correlating with severity of interstitial lung disease (ILD) in systemic sclerosis (SSc). METHODS: Skin biopsy samples from 59 patients enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort or an open-label imatinib study (baseline visit) were examined by global gene expression analysis using Illumina HT-12 arrays. Skin transcripts correlating with concomitantly obtained forced vital capacity (FVC) values and the modified Rodnan skin thickness score (MRSS) were identified by quantitative trait analysis. Also, immunofluorescence staining for selected transcripts was performed in affected skin and lung tissue. Plasma levels of CCL2, soluble SELP, and soluble P-selectin glycoprotein ligand 1 (sPSGL-1) were examined in all patients enrolled in the GENISOS cohort (n = 266). RESULTS: Eighty-two skin transcripts correlated significantly with FVC. This gene list distinguished patients with more severe ILD (FVC <70% predicted) in unsupervised hierarchical clustering analysis (P < 0.001). These genes included SELP, CCL2, and matrix metalloproteinase 3, which are involved in extravasation and adhesion of inflammatory cells. Among the FVC correlates, 8 genes (CCL2, HAPLN3, GPR4, ADCYAP1, WARS, CDC25B, PLP1, and STXBP6) also correlated with the MRSS. Immunofluorescence staining revealed that SELP and CCL2 were also overexpressed in affected skin and lung tissue from SSc patients compared to those from controls. Plasma levels of CCL2 and sPSGL-1 correlated with concomitantly obtained FVC values (r = -0.22, P = 0.001 and r = 0.17, P = 0.015, respectively). This relationship was independent of potential confounders (age, sex, ethnicity, smoking status, anti-topoisomerase I positivity, treatment with immunosuppressive agents, MRSS, disease type, and disease duration). CONCLUSION: A limited number of skin transcripts including genes involved in extravasation and adhesion of inflammatory cells correlate with severity of ILD.

Treatment of systemic sclerosis-associated calcinosis: a case report of rituximab-induced regression of CREST-related calcinosis and review of the literature.

OBJECTIVES: Calcinosis is frequently encountered in patients with systemic sclerosis (SSc) and may be associated with significant morbidity. No treatment has shown so far an unequivocal beneficial effect. METHODS: We performed an extensive internet search (MEDLINE) using the keywords calcinosis, calcification, scleroderma, systemic sclerosis, and treatment. RESULTS: Our patient had extensive Calcinosis, Raynaud, Esophagitis, Sclerodactyly, telangiectasia (CREST)-related calcinosis, frequently ulcerating and painful. Following 2 rituximab courses (consisting of 4 weekly infusions, 375 mg/m(2) each), calcinosis significantly improved and pain disappeared. Pharmacologic agents used in the treatment of SSc-associated calcinosis include diltiazem, minocycline, warfarin, biphosphonates, and intravenous immunoglobulin. Other therapeutic approaches include surgical excision, laser vaporization, and extracorporeal shock wave lithotripsy. CONCLUSIONS: Evidence for all existing therapies is weak and therefore larger scale controlled studies are needed. Rituximab appears as a promising treatment especially in view of recent evidence that this therapy may be also effective in the underlying disease.

[Digital ulcers in systemic sclerosis--an interdisciplinary challenge]. / Digitale Ulzerationen bei Sklerodermie--eine interdisziplinäre Herausforderung.

Digital ulcers in systemic sclerosis are painful ischemic necrotic lesions of the acra. Optimal treatment consists of conventional wound management and medication: iloprost infusions promote primary healing of the ulcers, while the dual endothelin receptor antagonist bosentan is used for secondary prophylaxis of new ulcers. The described case illustrates the essential interdisciplinary collaboration for optimal management of these patients.

[Autoimmune hepatitis and CREST syndrome]. / Hépatite auto-immune associée au syndrome de CREST.

We report the case of an autoimmune hepatitis in a 59-year old woman who was referred for a progressive jaundice. The patient had an history of CREST syndrome. The particularity of this case report is the rare association between these two autoimmune diseases.

Scleroderma and chronic myeloid leukemia: a sheer coincidence, a consequence of long lasting D-penicillamine therapy or a plausible relationship of both diseases?

Systemic sclerosis is a chronic multisystem disorder of unknown etiology characterized by the involvement of skin and visceral organs caused by an accumulation of collagen. It has been reported that the incidence of solid and hematological malignancy increased in systemic sclerosis. Multiple myeloma and chronic lymphocytic leukemia are the most common hematological malignancies seen in patients with systemic sclerosis. Chronic myeloid leukemia (CML) has only rarely been reported so far. We here report a case with CREST (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactly, telangiectasia) who developed CML 7 years after the onset of CREST. Ours is the second case with CML developing after the onset of CREST in the literature. We also briefly discuss the possible tendency to hematological malignancy in systemic sclerosis.

[Risedronate: a possible treatment for extraosseous calcification].

A case report of 51 year-old female, diagnosed as CREST syndrome, presenting with an ectopic calcification in the left shoulder joint, which disappeared soon after the start of risedronate. She had been taking steroid and NSAIDs for the past four years, but the pain and the range of motion of her shoulder became worse and restricted progressively during the last three years only to form extraosseous calcification. Laboratory data showed normal renal function, no inflammatory changes, and no abnormalities in calcium and and phosphate metabolism including parathyroid hormone. Risedronate was administered for glucocorticoid-induced osteoporosis. Although the bone turnover markers, such as serum NTX (N-terminal telopeptides of type I collagen) and BSAP (bone specific alkaline phosphate), did not show remarkable changes, the pain disappeared a week later and the range of motion recovered a month later. The X-ray at 6 months risedronate treatment revealed a complete disappearance of the ectopic calcification. Risedronate, probably through a different process from etidronate, could prevent extraosseous calcification.

Successful long-term treatment with cyclosporin A in protein losing gastroenteropathy.

Protein-losing gastroenteropathy (PLG) can occur as a manifestation of various diseases including autoimmune disorders, and optimal therapy of these underlying diseases may be the only effective remedy for PLG. In the present report, we describe a case of a 54-year-old woman with PLG associated with an autoimmune disease, presumably CREST syndrome. She failed to respond to steroid treatment. Subsequently, cyclosporine was initiated, which resulted in a rapid recovery. The patient was successfully treated with low-dose cyclosporine for five years. There has not been, to our knowledge, any report of PLG successfully treated with cyclosporine. Cyclosporine therapy may be effective not only in inducing but also in maintaining complete remission in patients with autoimmune-associated PLG, especially refractory or intolerable to steroids and/or immunosuppressive therapies.

Open label trial of tamoxifen in scleroderma.

BACKGROUND: Previous reports have suggested that treatment with the selective estrogen antagonist tamoxifen may be effective in diminishing primary and secondary Raynaud's vasospasm, including cases occurring in the setting of scleroderma. Tamoxifen treatment has also been associated with improvement of retroperitoneal fibrosis and desmoid tumors, conditions also associated with abnormal fibroblast proliferation. Tamoxifen increases production of the immunosuppressive cytokine TGF beta which modulates fibroblast activity. The potential effect of tamoxifen on vascular reactivity and fibrotic lesions raised questions about its utility as a therapeutic agent in scleroderma. OBJECTIVE: To determine the utility of tamoxifen therapy in scleroderma. METHODS: Open label preliminary, prospective, proof of concept study of tamoxifen. RESULTS: Fifteen patients (3 male, 12 female) with scleroderma were enrolled (10 diffuse disease, 5 CREST). Mean age was 55 (34-75) years. Mean duration of scleroderma was 9.3 (1-25) years. Two patients were excluded. For 13 patients, mean duration of treatment was 7 (1.5-32) months. Two of 13 patients treated with tamoxifen experienced transient improvement. They did not appear to have clinical features that identified them as a unique subset. Both patients subsequently relapsed, in one case 12 months, and in the other 24 months after treatment. CONCLUSION: Based on these results, we would not recommend tamoxifen for further large scale studies in scleroderma.