Scleroderma

ABSTRACT: Scleroderma presents a formidable therapeutic challenge for both the physician and the patient. Over the years many medications and interventions have been reported to be beneficial in scleroderma. With equal regularity, however, when put to the test of the randomized controlled trial, many of these same medications have subsequently been shown to be ineffective. This is true for both the localized and systemic forms of the disease. Two of the most recent additions to this inauspicious list for systemic sclerosis include D-penicillamine and methotrexate. At the very least these outcomes should point to our deficiencies in understanding the pathogenesis of this unusual disorder. It should raise the possibility that collagen and inflammatory or immune cells are not good therapeutic targets and new targets should be sought. Despite the scope of these problems and the lack of definitive therapy, there is a great deal an individual physician can do to help a patient living with scleroderma. This article presents management approaches to patients with either localized or systemic scleroderma.     

Scleroderma

A 72-year-old man with diabetes-associated scleredema is presented. The patient had a long history of diabetes mellitus that had been difficult to control with complications of retinopathy, nephropathy, and arteriosclerosis leading to myocardial infarcts and stroke. The scleredema has remained stable with 4 months of topical clobetasol ointment twice daily and biweekly physical therapy. Diseases associated with scleredema and therapeutic options are summarized.     

Scleroderma

After a review of some pathogenetic and pathologic aspects of scleroderma, the experimental effects of a group of agents that can inhibit the formation of connective tissue, especially the biosynthesis of collagen, are mentioned. These substances were transferred to clinical therapy of scleroderma. Regular determinations of disease activity and guidance of therapy with quantitative and semiquantitative physical and biochemical technics are of utmost importance because treatment without guidance allows for no disclosure of therapeutic failure or recurrence of the disease in due time for readjustment of the treatment.     

Autoantibodies in Scleroderma

Autoantibodies directed against nuclear, nucleolar, and a number of cytoplasmic components are described in the sera of scleroderma patients. Early studies of autoantibodies that relied on cryopreserved sections of rodent organ substrates showed that approximately 50% of scleroderma patients had anti-nuclear antibodies (ANA). More recent studies that have used tissue culture cell substrates have shown that up to 98% of scleroderma patients have a positive ANA. In all of these studies, the presence of different patterns of staining have suggested that scleroderma sera reacted with a variety of intracellular antigens. The use of molecular and immunochemical techniques has now shown that over 20 intracellular autoantigens are targets of autoantibodies in scleroderma sera. Clinical studies have shown that these autoantibodies are important diagnostic and prognostic markers in scleroderma. In the future, autoantibody testing may be used to monitor the patient's response to immunological therapies.     

局限性硬皮病的研究新进展

对近期局限性硬皮病研究的新进展作一综述,包括临床表现和分型,发病机制(感染、创伤、药物和遗传等相关的病例),多种评价病情的方法及治疗手段(光疗,维A酸联合PUVA,MTX,外用他克莫司、咪喹莫特)。     

Gestagen Treatment of Scleroderma

In accordance with the biochemical conditions of collagen metabolism in progressive scleroderma and an account of previous experimental investigations of different therapeutic agents in the connective tissue, of animals, we. studied the pathogenetic treatment of this disease with gestagens and give, a detailed report of our own experimental research, in animals and the experience, obtained in patients. Evidence has been presented that an increase of the urinary excretion of hydroxyproline in patients with, progressive, scleroderma is an essential effect of the. progesterone therapy.     

Scleroderma: therapeutic options

Although the cause of scleroderma remains elusive, pharmacologic advances and increased understanding of the pathophysiology of this disease provide therapeutic options. Therapy usually addresses the fibrotic, vascular, or immunologic alterations, but general measures can be helpful and should not be overlooked.     

Nifedipine in Scleroderma Ulcerations

ABSTRACT: Cutaneous ulcerations may be due to a variety of causes, including vasculitis. infections, arterial insufficiency, and microvascular damage. The net effect is diminished blood flow to the skin. Nifedipine, a calcium antagonist, has been shown to improve cutaneous blood How and to alleviate reactive vasospastic ischemia (Raynaud's phenomenon). The authors report an ischemic ulcer of scleroderma showing visible improvement with nifedipine therapy.     

Scleroderma and HLA antigens

A possible HLA disease association was investigated in 40 patients (38 female, 2 male) with progressive systemic scleroderma (PSS), and 42 patients (32 female, 10 male) with morphea. HLA ABCDR/DQ, glyoxalase and properdin factor B (GLO and BF) phenotypes of patients were compared with 193 healthy controls. Four PSS family studies were performed. The following relative risk (rR) values were determined in PSS: A1 (1.38), A2 (1.39), B8 (1.67), B15 (3.22) and in morphea: A3 (1.43), B7 (1.39), B40 (1.81), BW60 (2.49), DR2 (2.38) and DRW8 (2.55), indicating a relatively weak, HLA-linked genetic predisposition for the manifestation of these dermatological disorders. The HLA "risk" antigens for the two clinically different subtypes of the disease are also different: raised A1/B8 frequencies such as those in our PSS group are related to high (or pathologic) immune response (autoimmune disorders). In contrast, A3 B7 DR2 elevations such as those recorded in our morphea group correlate with low immune response. Following exposition to certain suspected environmental factors (quartz, chemical solvents, drugs, viral fragments), the HLA phenotype may thus predipose some individuals--predominantly women--to different clinical patterns of the disease. HLA typing may thus be useful in clinical differential diagnosis (recent subtyping protocols) and possibly also for determination of the prognosis, i.e. HLA-B8 seems to be related to an acute, inflammatory course of PSS, and HLA-B7/DR2, to rather mild morphea patterns.