Systemic scleroderma is a chronic autoimmune disease affecting the skin, internal organs and the musculoskeletal system. The presence of Raynaud phenomenon, anti-nuclear antibodies and pathologic capillaroscopy are early signs of the disease. Limited cutaneous SSc, diffuse cutaneous SSc and SSc-overlap syndromes are the main clinical subtypes. Multidisciplinary care is mandatory. Follow-up examinations should be performed at least annually in order to recognize in a timely fashion treatable organ involvement such as pulmonary arterial hypertension. Besides symptomatic treatment of organ involvement, immunosuppressive therapy is indicated for a progressive inflammatory course.

Idiopathic inflammatory myopathies are a group of acquired skeletal muscle diseases that include polymyositis, dermatomyositis, and inclusion body myositis. Studies have shown many myositis-specific autoantibodies (MSAs) that are useful for the diagnoses as well as classification of idiopathic inflammatory myopathies, because they have been shown to correlate with distinct clinical phenotypes. Anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ, anti-KS, anti-OJ, anti-Ha, and anti-Zo antibodies target aminoacyl tRNA synthetases, and represent anti-synthetase syndrome. Anti-synthetase syndrome is characterized by myositis, interstitial lung disease, arthritis, fever, Raynaud's phenomenon, and mechanic's hands. Anti-Mi-2, anti-MDA5 (anti-CADM140), anti-TIF1 (anti-155/140, anti-p155), anti-NXP-2 (anti-MJ), and anti-SAE antibodies are specific for dermatomyositis. In particular, anti-MDA5 antibodies are clinically associated with amyopathic dermatomyositis developing into rapidly progressive interstitial lung disease, whereas anti-TIF1 and anti-NXP-2 antibodies are closely correlated with cancer-associated dermatomyositis in adults. In addition, anti-TIF1 and anti-NXP-2 antibodies are predominant MSAs found in juvenile dermatomyositis, and the latter was correlated with a high incidence of calcinosis. Furthermore, anti-SRP and anti-3-hydroxy-3-methylglutaryl-coenzyme A (anti-HMG-CoA) antibodies have been found in patients with necrotizing myopathy. Moreover, a recent study suggested the presence of autoantibodies to a 43-kDa muscle protein in patients with inclusion body myositis. Although the pathogenic role of MSAs remains unknown, recent studies have shown that myositis autoantigens are expressed at high levels in regenerating muscle fibers, which may initiate or amplify autoimmune responses in idiopathic inflammatory myopathies.

Background  Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome is a rare multisystem paraneoplastic condition associated with plasma cell dyscrasia. Methods  From our institution's dysproteinemia database, 107 patients met criteria for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome between January 1, 2000, and October 1, 2009. Medical records were reviewed for documented syndrome features at diagnosis. We assessed prevalence of skin findings and associations between dermatologic and other characteristic disease findings. Results  Of the 107 patients, 96 (90%) had a recognized cutaneous manifestation. Hyperpigmentation and hemangioma were most common (47%), followed by hypertrichosis (38%). Vascular skin changes - acrocyanosis (34%), Raynaud phenomenon (20%), hyperemia/erythema (20%), flushing (16%), or rubor (11%) - occurred in 62%; white nails, sclerodermoid changes, and clubbing occurred in 30%, 26%, and 6%, respectively. Mean number of skin findings per patient was 2.9 (median, 3.0; range, 0-7). Presence of cutaneous manifestation was associated with abnormal pulmonary function tests (P < 0.001); immunoglobulin G gammopathy was associated with hyperpigmentation and hypertrichosis. No other significant associations were seen. Conclusions  The high prevalence of skin findings (90%) shows the value of dermatologic evaluation in diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Our data indicate new associations between skin findings and other disease characteristics.

Scleroderma is a multiorganic disease characterized by inflammatory, vascular and sclerotic changes in skin and internal organs. It is considered as a tripartite disease, associated to autoimmune, fibroblast and endothelial defect, due to genetic, environmental and infectious factors. This disease can be classified in systemic and localized form. The Raynaud phenomenon occurs in 90% of the patients with the diagnosis. It explains the microcirculation involvement and the reduction in the number of capillaries. Malformation of nail bed capillaries is readily demonstrated by nail bed microscopy and has been shown to correlate both with disease severity and with degree of internal organ involvement. The MRSS-51 validates the skin involvement and has the main predictive value to determine the patient survival. MRSS-51 should not be considered as an activity disease parameter or used to validate the effectiveness of treatment. Nowadays, multiple treatment alternatives exist for scleroderma disease; however these treatments offer poor results for the cutaneous manifestations.

Cryofibrinogenemia is a cryoprotein that was first identified in 1955 by Korst and Kratochvil. Unlike cryoglobulin, the precipitate forms only in plasma and not in the serum. The presence of cryofibrinogen in plasma can be asymptomatic. Cryofibrinogenemia is considered a rare disorder: its prevalence varies from 0% to 7% in healthy subjects and from 8% to 13% in hospitalized patients. Nevertheless, cryofibrinogenemia, when a cryopathy is clinically suspected, has been reported in 12% to 51% of patients. Skin manifestations are usually the first signs and are usually moderate; in addition, cold intolerance, Raynaud phenomenon, purpura, or livedo reticularis often occurs. Skin necrosis, acral ulcers, and gangrene can lead to surgery and amputation. Systemic manifestations are common, and arterial or venous thrombotic events are frequent. Cryofibrinogenemia may be primary (essential) or secondary to other underlying disorders, such as carcinoma, infection, vasculitis, collagen disease, or associated with cryoglobulinemia. The histological features of cryofibrinogenemia can confirm the presence of cryofibrinogen within small and medium arteries, plus occlusive thrombotic diathesis composed of eosinophilic refractile deposits within vessel lumina. Cryofibrinogenemia is a treatable and potentially reversible disease.In moderate forms, it can be treated by simply avoiding cold temperatures. The use of corticosteroids in association with low-dose aspirin is the treatment of choice for moderate forms, although stanozolol is an alternative maintenance therapy. Immunosuppressive therapies, plasmapheresis, and/or intravenous fibrinolysis are useful at treating severe forms of cryofibrinogenemia. The use of anticoagulants is limited to the management of thrombotic events. Treatment of secondary cryofibrinogenemia involves the management of associated diseases. Regular follow-ups are needed because of the high risk of recurrence. Moreover, up to half of patients with cryofibrinogenemia considered as essential may develop lymphomas in the following years. Compared with cryoglobulinemia, less is known about cryofibrinogenemia. Its diagnosis should be considered when suggestive clinical manifestations are present and when there are specific biopsy findings. Although identification of cryofibrinogen in blood samples is simple and inexpensive, cryofibrinogenemia can be asymptomatic, and a lack of diagnosis criteria can make diagnosis difficult to confirm. This review describes the clinical manifestations and the biological and pathological features and discusses the criteria used to diagnose and manage cryofibrinogenemia.

A 34-year-old female stonemason was referred for expert opinion. The question at issue was, whether she suffered from vibration-induced white finger disease. She was exposed to high-frequency hand-arm vibrations for many years. She reported white finger attacks at the long fingers, which were associated with cold weather. Until this point, physical findings were normal.The cold water provocation test showed a slight delay of the rewarming for the long fingers of the right hand. The nailfold capillary microscopy was normal. DIAGNOSIS AND COURSE: The slight Raynaud's phenomenon was recognized as an occupational disease with a diagnosis of vibration-induced white finger disease. About three years later, the symptoms of the Raynaud's phenomenon had deteriorated, although the patient had finished working with vibrating tools. The cold water provocation test confirmed the deterioration. At this time, the patient had inflamed swellings of some joints caused by rheumatoid arthritis.The differential diagnosis of a Raynaud's phenomenon should include occupational causes. Occupational history is diagnostically indicative. If an occupational disease is assumed, a report must be filed. With respect to German social law, the deterioration of the Raynaud's phenomenon was caused by the rheumatoid arthritis, which is regarded as independent from the job.

OBJECTIVES:

The aim of the present study was to assess the outcome in anti-PL12 patients with antisynthetase syndrome (ASS).

METHODS:

The medical records of anti-PL12 (n=5) patients with ASS were retrospectively analyzed without prior selection. To exclude false-positive patients, we included patients who were successively tested positive for anti-PL12 antibody at least twice by immunodot and/or Western blot.

RESULTS:

Anti-PL12 patients experienced: myositis (n=2), Raynaud's phenomenon (n=2), mechanic's hands (n=1), joint impairment (n=4), digestive involvement (n=2), and interstitial lung disease (ILD) (n=4). The two patients with myositis exhibited deterioration of muscle manifestations despite therapy. As regards outcome of ILD, patients developed resolution (n=1), stabilization (n=1) or deterioration (n=2) of pulmonary status. One patient died of pyogenic pneumonia.

CONCLUSION:

Our series underscores that the presence of anti-PL12 antibody is associated with a particular phenotype of ASS characterized by: (1) less frequent although severe/steroid refractory myositis; (2) less common mechanic's hands and calcinosis cutis; (3) both frequent and severe ILD. Taken together, our findings suggest that PM/DM patients should routinely undergo the search for anti-PL12 antibody as this autoantibody appears to impact patients' prognosis. Furthermore, ILD patients with anti-PL12 antibody should routinely undergo clinical screening for underlying ASS.

Antisynthetase antibody syndrome is a rare autoimmune disease that may present with variable systemic manifestations, mainly polymyositis, interstitial lung disease, skin lesions, and Raynaud's phenomenon. This diagnosis should always come to mind in patients that present with signs of myositis, dermatomyositis, or polymyositis associated with interstitial lung disease. On the following paper, we report the case of a 52-year-old man who presented with a 2-month history of asymmetric polyarthralgia, myalgia, weight loss of 8 kg, and progressive muscle weakness associated with dyspnea, orthopnea, and dysphonia. Further tests revealed myositis, interstitial pneumonia, and elevation of anti-Jo-1 antibodies. A diagnosis of antisynthetase antibody syndrome was made and the patient showed good response to treatment with corticoids and methotrexate. Finally, we present a short review of the literature.

The association between hyperhomocysteinemia (HHcy) and Raynaud's phenomenon (RP) remains a matter of debate. In 18 primary RP, 23 secondary RP and 41 controls, we investigated homocysteine (Hcy) levels along with biochemical and inflammatory parameters. The Hcy levels in both primary and secondary RP were elevated when compared with controls (p < 0.05 and p < 0.01, respectively). As age was higher in secondary RP as compared with controls (p < 0.01), both primary and secondary RP were age-matched with a corresponding control group, and with Hcy maintaining its statistical significance (p < 0.05). No differences in creatinine, B12 vitamin or folic acid were observed between groups (p > 0.05), or in the prevalence of cardiovascular risk factors (p > 0.05). When patients were classified according to presence or absence of digital ulcers, as a sign of microangiopathy severity, the former showed higher Hcy levels than the latter (p = 0.035). Our results indicate that both primary and secondary RP patients show a mild increase in Hcy levels, which is not related to age, vitamin deficiencies or impaired renal function, but is related to microangiopathy severity. Therefore the association of HHcy and RP suggest that Hcy may contribute to endothelial dysregulation, which characterizes this disease. Specific studies should be designed to elucidate the pathogenesis of HHcy in these patients.