Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of ‘prescleroderma’

Abstract

In a patient with early topoisomerase antibody-positive scleroderma, antinuclear antibody positivity was fortuitously observed to predate nailfold capillaroscopy changes. Using this case as a template, the prediagnostic phase of the presumed multifactorial disease may be divided into 5 temporal phases--phase 1 representing conception and intrauterine environment, phase 2 representing the extrauterine environment predating environmental exposure; phase 3 representing the early post-environmental exposure interval with no detectable perturbed body status; phase 4 representing the post-environmental exposure interval characterized by autoantibody production and microvascular changes, and phase 5, the symptomatic clinical prediagnostic interval (Raynaud's, skin, musculoskeletal, gastrointestinal, cardiorespiratory) prompting scleroderma diagnosis. Temporal classification of prescleroderma aids in both the understanding and definition of scleroderma 'onset'. If altered nailfold capillaries and autoantibodies develop at comparable rates, and if the findings from this case--that autoantibody changes precede microvascular changes--are truly representative of the preclinical disease phase, then these findings argue that the evolution of the disease is from within the vessel outwards, rather than vice versa.

Early systemic sclerosis: marker autoantibodies and videocapillaroscopy patterns are each associated with distinct clinical, functional and cellular activation markers

“…Nevertheless, the asynchronous appearance of autoantibody positivity and capillaroscopic alterations has been reported in two recent papers. First, Englert and colleagues described the case of one patient in whom anti-Scl-70 positivity, associated with fatigue, weight loss and puffy fingers, predated the appearance of RP and the development of capillaroscopic abnormalities [23]. Second, Moinzadeh and colleagues reported the late appearance of serum autoantibodies in three patients with an NVC scleroderma pattern at admission [24].…”

Rheumatoid Nodules Predating Seroconversion and Rheumatoid Arthritis: An Uncommon Case Report

“…Seroconversion preceding clinical manifestations has been reported not only in patients with RA [12], but also in those with systemic sclerosis [13] or systemic lupus erythematosus [14]. It has also been reported in patients with rheumatoid nodulosis [7], but our case is particular because of the uncommon succession of events: 1) the appearance of nodules in an otherwise healthy woman; 2) the subsequent appearance of slightly positive serum RF levels; and 3) the final increase in RF titre, the appearance of high-titre ACPA, and the onset of overt RA.…”