Permission to post "Diagnosis and Treatment of Systemic and Localized Scleroderma, Expert Rev. Dermatol. 6(3), 287–302 (2011)" on the Scleroderma Society of Ontario web-site has kindly been granted by the author, Dr. Dhanita Khanna and Expert Reviews Ltd as the original publisher.
By Dhanita Khanna
Department of Clinical Immunology
and Rheumatology, Sahara Hospital,
Scleroderma or progressive systemic sclerosis is diagnosed clinically by typical features of skin
thickening, Raynaud’s phenomenon and visceral organ involvement, and serologically by distinct
autoantibody subsets. These differentiate the disease into the ‘limited’ and ‘diffuse’ variants. In addition, a distinct form of scleroderma, termed ‘localized’ scleroderma, is characterized by skin
thickening in the absence of visceral involvement. Treatment of scleroderma in the past was
largely symptomatic and with immunosuppressives, acting against the organ system involved
and the aberrant immune system. Recently, with newer insights into disease pathogenesis, drug
therapies targeting the pathogenetic mechanisms of fibrosis, vasculopathy and autoimmunity
are being evolved. Some of these newer therapies are the endothelin receptor blockers,
phosphodiesterase inhibitors, tyrosine kinase inhibitors and autologous stem cell transplant,
while others are still evolving. They may hold the key to improved future outcome of this disease,
which was once thought to be potentially incurable.
Scleroderma is a chronic multisystem connective tissue disorder characterized by a pathophysiological triad of vasculopathy, fibrosis due to excessive deposition of collagen and extracellular matrix components, and autoimmunity. This manifests clinically as Raynaud’s phenomenon, skin thickening and involvement of visceral organs, including the gastrointestinal (GI) tract, lungs, heart and kidneys. The term scleroderma (sclera – hard, derma – skin) is used synonymously with systemic sclerosis,
Diagnosis of scleroderma
In practice, the diagnosis of scleroderma is clinical and is made by the presence of Raynaud’s phenomenon, typical skin thickening and visceral involvement. Laboratory investigations are supportive. Serology for autoantibody profile helps in classifying the subtype of disease and excluding other scleroderma-mimicking conditions. Organ-specific investigations help to determine the extent and stage of visceral involvement due to the disease process.
Preliminary classification criteria have been developed by the American College of Rheumatology (ACR) for the purpose of uniformity in clinical studies . The major criterion is the presence of sclerodermatous skin changes proximal to the metacarpophalangeal joint. Minor criteria are sclerodactly, digital pitting scars or tissue loss of the volar pads of the finger tips and bibasilar pulmonary fibrosis. The diagnosis of scleroderma is based on the presence of the major criteria and two or more minor criteria. However, these criteria may not be applicable in clinical practice and not all patients may fulfill them.
Recently, it has been suggested that nailfold capillary microscopy changes and the presence of anticentromere antibodies (ACA) should be included in the minor criteria so as to more adequately incorporate patients with the limited subset of the disease .
In contrast to established disease, diagnosis of disease in the early stage may be difficult. Such patients may only present with Raynaud’s phenomena and lack other clinical features at onset. In such cases, nailfold capillaroscopy changes (capillary loss and dilatation) and the determination of autoantibodies may serve as
useful investigations for the prediction of evolution to full-blown disease . Recently, a set of criteria have been identified, and are considered to be important in the early diagnosis of scleroderma by the European League against Rheumatism (EULAR) scleroderma trials and research groups. They have been divided into three domains containing seven items each: skin domain (puffy
fingers/puffy swollen digits turning into sclerodactly); vascular domain (Raynaud’s phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). The validation of these items to establish diagnostic criteria is currently ongoing
in a prospective observational cohort .
Two distinct subsets of scleroderma have been identified on the basis of the extent of skin thickening. The limited variant has symmetric skin thickening of the distal extremities (distal to elbows and knees) and face. The diffuse variant has skin thickening of proximal and distal extremities, face and trunk. The major differences between these two subsets are given in Table 1, but some amount of overlap exists. Either of these variants can exist with overlapping syndromes in which features of scleroderma are present with one or more connective tissue disorders, such as systemic lupus erythematosus (SLE) and polymyositis (PM). Another variant is ‘scleroderma sine scleroderma’ characterized by internal organ involvement and serological abnormalities but an absence of classical skin changes. Scleroderma can also occur in the localized form limited to skin and subcutaneous tissue without internal organ involvement, termed ‘localized scleroderma’ (discussed later).
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