Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease

Abstract

The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.

Figure 1. Lung-dominant connective tissue disease. In A, HRCT scan showing reticular opacities, permeated by areas of ground-glass attenuation, and paracicatricial emphysema in the upper lobes. In B, HRCT scan showing peribronchovascular reticular opacities, ground-glass opacities, and traction bronchiectasis in the lower lobes. In C, mediastinal CT scan showing esophageal dilation with an air-fluid level. In D, histological examination of an open lung biopsy specimen showing inflammatory infiltrate in the alveolar septa, consistent with a nonspecific interstitial pneumonia pattern.

Chart 1. Diagnostic criteria for undifferentiated connective tissue disease.a

Chart 2. Provisional criteria for lung-dominant connective tissue disease.a

Chart 3. Findings suggestive of connective tissue disease as the cause of interstitial lung disease.

Figura 1. Colagenose pulmão dominante. Em A, TCAR mostrando opacidades reticulares, permeadas por algumas áreas de vidro fosco, e presença de enfisema paracicatricial em lobos superiores. Em B, TCAR mostrando opacidades reticulares, vidro fosco e bronquiectasias de tração de localização peribroncovascular nos lobos inferiores. Em C, TC de mediastino mostrando dilatação esofágica com nível líquido. Em D, histologia de fragmento de biópsia pulmonar a céu aberto mostrando infiltrado inflamatório em septos alveolares, compatível com o padrão de pneumonia intersticial não específica.

Quadro 1. Critérios diagnósticos de conectivopatia não diferenciada.a

Quadro 2. Critérios provisórios para colagenose pulmão dominante.a

Quadro 3. Aspectos que sugerem a presença de doença do tecido conjuntivo como etiologia da doença pulmonar intersticial.