A 42-year-old Hispanic man with no prior medical history presents with a 2-month history of a rash on his face, chest, and arms. He reports that the rash gets worse after sun exposure and he has associated joint pain. He has taken over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) for the joint pain and topical steroids for the rash with no symptomatic relief. Physical examination reveals erythematous patches over the malar cheeks and dorsal nose sparing the nasolabial fold and erythematous macules on the forearms and chest.
Submit your diagnosis to see full explanation.
In systemic lupus erythematosus (SLE), the immune system loses tolerance for self-antigens, resulting in multiorgan damage.1,2 The cutaneous manifestations of SLE were first described by Hippocrates in the fifth century.3,4 In the 13th century, Rogerius reported facial lesions that resembled wolf bites (lupus translates to wolf in Latin).5 Descriptions of lupus written by Cazenave, Bateman, and von Hebra focused on dermatologic aspects of the disease.5 Moritz Kaposi reported systemic symptoms of lupus in 1872, and Sir William Osler is credited as the first to recognize the multiorgan damage that is characteristic of SLE.5,6
Prevalence estimates for SLE vary between 20 and 150 cases per 100,000 individuals and have been increasing with improved recognition of the disease.7 Systemic lupus erythematosus has a predilection for adult women in their 30s or 40s; children comprise only 15% to 20% of cases.5 In the United States, SLE is less common among individuals of European ancestry and more common among the Black population and people of Hispanic and Asian descent. These latter groups also experience greater involvement of internal organs.1,5,7
Studies have linked genes for human leukocyte antigen (HLA) and complement components C1, C2, and C3, as well as at least 70 susceptibility loci to SLE.1 Female hormones have been associated with SLE, explaining the higher prevalence in women.7 Antithyroid antibodies, elevated thyroid-stimulating hormone, and altered autonomic nervous system response to the hypothalamic axis also have been reported in SLE patients.5
Immune dysfunction in SLE is precipitated by a combination of factors such as genetics, emotional factors, and environmental influences (eg, infections and exposure to chemicals or UV light). This dysfunction causes autoantibody development, immune complex deposition, inflammation, and complement activation, which in turn result in tissue injury.8 The lack of self-tolerance depends on how efficiently a patient’s immune system presents antigens to T cells.5 Production of abundant immunoglobulin G (IgG) autoantibodies and circulating abnormal inflammatory cells are mechanisms reported to lead to skin damage in SLE.9 Apoptosis of keratinocytes is also a key event in the development of cutaneous lesions.8
In general, dermatologic findings in SLE are divided into 3 groups: acute cutaneous (ACLE), subacute cutaneous (SCLE), and chronic cutaneous (CCLE).5 These categories are not mutually exclusive and may present concomitantly in any given patient.10
Patients with ACLE display transient photodistributed lesions in the classic dermatologic manifestation of SLE, the bilateral malar erythema or butterfly rash. This rash can appear solely in the center of the face, classically sparing the nasolabial fold, or it may be a generalized maculopapular exanthema. The rash usually is accompanied by systemic effects on other organs, and antidouble-stranded DNA (dsDNA) antibodies may be present.8,10
The other subtypes, SCLE and CCLE, are associated with a relatively lower risk for systemic disease. Although SCLE is also a photosensitive eruption, it lasts longer than ACLE and does not cause atrophy or scarring. The CCLE subtype includes discoid lupus, lupus erythematosus tumidus, lupus erythematosus panniculitis, and chilblain lupus.
Sun exposure can trigger dermatologic findings in SLE, and patients may mistake this rash for a sunburn. Severe facial swelling may occur, although these cutaneous symptoms tend to resolve without residual pigmentation or scarring.11
Patients with SLE also can have nonspecific cutaneous findings. Raynaud phenomenon, livedo reticularis, and urticarial vasculitis are examples of such findings; these conditions suggest a potential underlying autoimmune disease.10,11
The most common areas affected in SLE are the joints, skin, kidneys, hematologic system, central nervous system, and pleural and pericardial serosal surfaces.
Per the 2019 American College of Rheumatology (ACR) guidelines, diagnosis of SLE requires at least 1 positive antinuclear antibody (ANA) test followed by 7 clinical criteria (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal), and 3 immunologic domains (antiphospholipid antibodies, complement proteins, SLE-specific antibodies).12 The Systemic Lupus International Collaborating Clinics require 4 criteria for SLE diagnosis with at least 1 clinical criterion and 1 immunologic criterion or lupus nephritis as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies.13 In both classification systems, immunologic criteria are required for a definitive SLE diagnosis.5
Mucocutaneous SLE is diagnosed via immunohistology and histopathology. Histologic findings vary depending on the subtype but always include vacuolar degeneration and lymphohistiocytic inflammation. The ACLE subtype presents with less pronounced dermal involvement and more vacuolar degeneration of the basal layer with some sparse lymphocytic infiltrate in the upper dermis. Discoid lesions tend to have more follicular plugging, periadnexal inflammation, and scarring.10
Recurrent miscarriages and abnormal complete blood cell count and differential, urinalysis, and/or comprehensive metabolic profile support a diagnosis of SLE. Various antibodies also can be present, including antiphospholipid, anti-RNP, anti-SM, anti-SSA, anti-SSB, anti-dsDNA, and antinuclear antibodies. When indicated, clinicians may wish to obtain supportive imaging such as a chest radiograph, renal imaging, and contrast angiography.5
The differential diagnosis for localized ACLE is contact dermatitis, acne rosacea, seborrheic dermatitis, dermatomyositis, erysipelas, and photodermatitis. These pathologies are differentiated via characteristic clinical features. Generalized ACLE can be confused with erythema multiforme and morbilliform drug reactions, but these conditions do not present with butterfly erythema. The differential diagnosis for SCLE includes polymorphic drug eruption, psoriasis, tinea corporis, and superficial gyrate erythema, which also are distinguished clinically. Several conditions may mimic CCLE depending on the stage and evolution of CCLE lesions. Diseases that mimic the nonscaling pattern of CCLE are polymorphic light eruption, Jessner lymphocytic infiltration of the skin, lymphocytoma cutis, granuloma facile, chilblain, and sarcoidosis. The scaling phase of CCLE may look similar to actinic keratoses, seborrheic dermatitis, tinea faciei, psoriasis, and lichen planus. Both clinical features and histology can help differentiate CCLE from these conditions.11
SLE treatment is complex and usually requires consultations with multiple specialists. Before treatment initiation, disease severity, degree of inflammation, and level of organ dysfunction should be ascertained.5 For skin findings, topical or intralesional corticosteroids and topical calcineurin inhibitors are first-line treatments. Rigorous sun protection also is essential for these patients because the lesions are exacerbated by sunlight.10 Lesions resistant to topical medications may require systemic therapy.10 Systemic medications used to treat SLE include glucocorticoids, antimalarial agents, immunosuppressants, NSAIDs, and biologics that target B cells. Recently, inhibitors of B-lymphocyte stimulators such as belimumab have shown potential for treatment of mild to moderate SLE.1
Biopsy results for the patient in this case were consistent with ACLE and his ANA was positive. He was started on topical steroids and hydroxychloroquine. Rheumatology was consulted to assist with his management.
Dina Zamil, BS, is a medical student and Tara L. Braun, MD, is a resident in the Department of Dermatology at Baylor College of Medicine in Houston, Texas.
1. Kiriakidou M, Ching CL. Systemic lupus erythematosus. Ann Intern Med. 2020;172(11):ITC81-ITC96. doi:10.7326/AITC202006020
2. Deng G-M. Pathogenesis of skin injury of systemic lupus erythematosus. Curr Rheumatol Rep. 2018;20(2):5. doi:10.1007/s11926-018-0713-9
3. Norman RA. The history of lupus erythematosus and discoid lupus: from Hippocrates to the present. Lupus: Open Access. 2016;1(1):1-10. doi:10.35248/2684-16184.108.40.206
4. Adams F. The Genuine Works of Hippocrates. Williams & Wilkins; 1939.
5. Fortuna G, Brennan MT. Systemic lupus erythematosus: epidemiology, pathophysiology, manifestations, and management. Dent Clin North Am. 2013;57(4):631-655. doi:10.1016/j.cden.2013.06.003
6. Oku K, Atsumi T. Systemic lupus erythematosus: nothing stale her infinite variety. Mod Rheumatol. 2018;28(5):758-765. doi:10.1080/14397595.2018.1494239
7. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365(22):2110-2121. doi:10.1056/NEJMra1100359
8. Moura Filho JP, Peixoto RL, Martins LG, et al. Lupus erythematosus: considerations about clinical, cutaneous and therapeutic aspects. An Bras Dermatol. 2014;89(1):118-125. doi:10.1590/abd1806-4841.20142146
9. Li Q, Wu H, Zhou S, Zhao M, Lu Q. An update on the pathogenesis of skin damage in lupus. Curr Rheumatol Rep. 2020;22(5):16. doi:10.1007/s11926-020-00893-9
10. Lee LA, Werth VP. Lupus erythematosus. In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology. 4th ed. Elselvier; 2018:662-680.
11. Bano S, Bombardieri S, Doria A, Iaccarino L, Lehmann P, Mosca M. Lupus erythematosus and the skin. Clin Exp Rheumatol. 2006;24(1 Suppl 40):S26-S35.
12. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheum. 2019;71(9):1400-1412. doi:10.1002/art.40930
13. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-2686. doi:10.1002/art.3447