Mimickers of Systemic Lupus Erythematosus: Case Series and Literature Overview

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a broad and varied clinical presentation. In the absence of definite diagnostic criteria, establishing an SLE diagnosis remains challenging. This case series illustrates that other diseases, such as primary immunodeficiencies and monogenic interferonopathies, can closely mimic SLE, even in the presence of its typical serological markers. Recognizing these disease mimickers is crucial to avoid premature conclusions in clinical evaluation and to ensure the initiation of appropriate therapy. Especially in cases of atypical presentation, unusual disease progression, or resistance to standard therapy, alternative diagnoses should be considered. In this overview, we discuss the diagnostic approach for patients with SLE-like manifestations and provide a comprehensive review of diseases that may mimic SLE.

Keywords: Aicardi–Goutières syndrome; SLE-mimicking disease; inborn errors of immunity; monogenic interferonopathy; neuromyelitis optica spectrum disease; primary immunodeficiency; systemic lupus erythematosus.

Figure 1

CT-scan showing lobar pneumonia (A) and focal bronchiectasis (B); (C) CTLA-4 expression on CD4⁺ T-cells and regulatory T-cells, unstimulated and after 24 h stimulation with aCD3/aCD28, in the patient and healthy donors (HDs), showing decreased CTLA-4 expression on CD4⁺ T-cells and regulatory T-cells during stimulated conditions in the patient compared with HDs; (D) decreased CTLA-4 expression FoxP3⁺ regulatory T-cells demonstrated through flow cytometry.

Figure 2

(A) Inflammatory skin lesions showing vasculitis in hive-like rash. (B) Positive myxovirus resistance protein 1 (MxA) staining in dermatocytes using MxA immunostaining, with original magnification ×10. (C) Increased CD169 expression on CD14⁺ monocytes demonstrated through flow cytometry.

Figure 3

(A) Abnormal appearance and pathological enhancement of the right optic nerve (arrow); (B) white matter lesions in the brachium pontis (arrow); (C) longitudinally extensive spinal cord lesion with swelling and the appearance of bright spotty lesions (arrows).