Painted Butterfly Rash: The Red Queen Effect in a Rembrandt Portrait

This letter invites you to embark on a journey from the complex autoimmune disease of medicine to the representation of a woman in Rembrandt's painting. As in Alice's never-ending race with the Red Queen, the body affected by lupus is engaged in an internal race. The Red Queen Effect is a metaphor for the endless, exhausting battle that the immune system wages against its own tissues. The malar rash, which appears on the face in the form of a butterfly, features in Rembrandt's painting not only as a medical finding, but also as a reflection of the fragility and beauty of the woman's face, which has been hidden in art history. Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease with a relapsing and remitting course. It is multifactorial, and involving epigenetic, genetic, ecological, and environmental factors. Exposure to environmental factors such as UVB radiation, infections, and toxins can trigger a loss of immune tolerance in genetically susceptible individuals and leads to aberrant activation of autoimmunity. SLE is one of the most gender-specific autoimmune diseases. It is more prevalent in women aged 15–44 years. Studies have shown an increased risk of SLE associated with exposure to estrogen, whereas progesterone and testosterone play a protective role by counteracting its effects. Adults diagnosed before the age of 50 typically present with cutaneous symptoms such as a malar rash and lupus nephritis. The butterfly rash, also known as the malar rash, is a pathognomonic feature of acute cutaneous lupus erythematosus. It involves sun-exposed areas such as the cheeks and nasal bridge [1]. Alopecia is a less specific cutaneous feature of SLE. It typically affects the temporal regions, resulting in a patchy pattern of hair loss [2]. The term lupus comes from the Latin for wolf. There are two ideas about the origin of this name: one is that the rash resembles a wolf bite, and the other is that the rash seems to gnaw away at the flesh of the victim. The history of lupus dates to at least the 4th century BC, when Hippocrates recorded the first known documented case. Although the term lupus was first used to describe an ulcerative skin disease, it was not until the mid-nineteenth century that two specific skin diseases were classified as lupus erythematosus and lupus vulgaris. The term lupus may derive from the disease's rapacity and virulence; a work from 1590 described it as a malignant ulcer quickly consuming the nether parts; very hungry, like unto a wolf [3]. The butterfly rash or malar rash has been depicted in various paintings in art history [4-8]. da Mota et al. reported that Adele, the subject of Gustav Klimt's most famous painting, had facial erythema, which, if not artificially created with make-up, could represent a malar rash [4]. Ashrafian reported that Catherine of Aragon, the first wife of Henry VIII and Queen of England, had a malar rash, visible in a miniature portrait. While Catherine's portraits reveal red cheeks, which could easily have been the result of make-up, some images portray red cheeks and a red nose, suggesting the possibility of an underlying butterfly rash [5]. Ashrafian also reported that Botticelli's painting depicts a butterfly rash. Considered one of the world's greatest masterpieces, ‘Primavera’ (or ‘Spring’) was painted by Sandro Botticelli. The authors noted that the figure of Flora (or Spring) in the painting exhibits clear signs of a goiter, including bilateral ptosis and facial flushing consistent with a ‘butterfly’ malar rash, as well as the possibility of periorbital heliotrope rash, which is more prominent around the right eye. These features likely derive from the observations made on one of the models used by Botticelli when painting the piece [6]. Hayakawa et al. identified a butterfly rash and digital deformities in Maria Bockenolle, the subject of a Rembrandt portrait [7]. They concluded that these were due to an overlap syndrome of rheumatoid arthritis and SLE. However, the authors also reported that, without additional information regarding Maria Bockenolle's clinical and physical signs and symptoms, as well as laboratory data, a definitive diagnosis could not be made. Nevertheless, a careful examination of representative paintings, such as those by 17th-century Dutch masters, combined with recent clinical and immunological findings, suggests the presence of an overlapping syndrome. This approach could be valuable for reconstructing the history of rheumatic disorders [7]. Marson et al. reported the presence of a typical malar rash on the face of a child in Le Bénédicité (Hermitage, St Petersburg), a painting by Jean-Baptiste Siméon Chardin (1699–1779), widely regarded as one of the greatest French painters of the 18th century [8]. Rembrandt Harmenszoon van Rijn (1606–1669), usually known as Rembrandt, is widely regarded as the greatest artist the Netherlands has ever produced [9]. Rembrandt produced more self-portraits and portraits than any other major artist in history. According to art historians, he aimed to master facial expressions and develop the tradition of the great painters who preceded him [10]. Figure 1 depicts a woman against a plain, dark background. The painting is rendered in a realistic and simple style. She is wearing a modest black dress with a high ruff collar, which was typical of 17th-century Dutch clothing. As with many of Rembrandt's portraits from the 1630s, the identity of the woman in this painting is unknown. As no additional information about the woman in the portrait is available, the assessment was based solely on visual observation. The butterfly rash is a characteristic dermatological finding in SLE. This rash appears as erythema in the shape of a butterfly, spreading across the cheeks and the nasal bridge. It is often triggered by sun exposure and may appear weeks or even months before a formal SLE diagnosis is made. Upon close inspection of the painting, it is evident that the woman is middle-aged and exhibits a malar rash. Another feature suggestive of SLE that can be identified in the portrait is frontal alopecia. Artistic representations are often more related to the artist's personal inspiration, but sometimes notable diseases have become the subject of representation [11]. There is a strong link between art and medicine. Iconodiagnosis is the medical analysis of artworks in search of clinical signs indicative of medical disorders and diseases. The concept was first introduced in 1983 by the neuropsychiatrist Anneliese Pontius during her research into Crouzon's malformation in prehistoric art from the Cook Islands. The use of iconodiagnosis in medical education is an alternative and stimulating way to train students' observational skills, not only in the physical examination of the patient, but also in the information gathered from their posture, clothing, general demeanor and even their physical aids [12]. In addition to its educational value for medical studies, iconodiagnosis can provide a better understanding of the natural evolution of diseases, their social perception and their impact on history itself [13]. By carefully studying these paintings, healthcare professionals and medical students can combine artistic observation with clinical knowledge to identify and interpret visual indicators of diseases. This method improves interdisciplinary thinking and cultural sensitivity, as well as visual diagnostic skills. The author would like to thank The Metropolitan Museum of Art for providing open access to their digitized collection, which made this analysis possible. The portrait discussed in this article was obtained from the museum's public domain digital archives. The author has nothing to report. The author declares no conflicts of interest. The data that support the findings of this study are openly available in The Metropolitan Museum of Art's online collection database at: https://www.metmuseum.org/art/collection/search/437390. The specific image analyzed is in the public domain and accessible to all users.