SAN ANTONIO — Distinguishing between the various forms of cutaneous lupus can be challenging, even for experienced clinicians. 

If a patient presents with a malar rash — also known as a butterfly rash — think acute cutaneous lupus until proven otherwise. “ That’s nearly always associated with systemic lupus,” Amanda Mixon, a certified physician assistant at UCHealth’s Rheumatology Clinic in Fort Collins, Colorado, said at the Society of Dermatology Physician Associates (SDPA) Fall Dermatology Conference.

Subacute cutaneous lupus typically appears as annular or psoriasiform lesions on sun-exposed areas. These lesions can be associated with SS-A antibodies, but can also be induced by drugs, including hydrochlorothiazide, terbinafine, and proton pump inhibitors. According to Mixon, 30%-50% of affected individuals present with mild systemic features, such as arthralgia and fatigue, “but that’s rarely associated with severe organ damage,” she said. 

Chronic cutaneous lupus appears as discoid lesions or scarring plaques with follicular plugging, hypopigmented or hyperpigmented skin, and the potential for permanent alopecia. An estimated 5%-15% of affected individuals progress to systemic lupus, Mixon said, making it relatively rare for the condition to develop into systemic lupus, but a biopsy can be helpful to make that diagnosis.

Other cutaneous variants include lupus panniculitis, characterized by deep, firm nodules; tumid lupus, which presents as edematous plaques without scale; and chilblain lupus, characterized by acral lesions that are aggravated by cold temperatures. An estimated 5%-10% of these variants develop into systemic lupus.

Predictors of systemic involvement include high-titer antinuclear antibodies (ANA) and positivity for anti-dsDNA or anti-Smith (SM) antibodies, low complements, leukopenia, or anemia, widespread/disseminated cutaneous lesions (especially discoid lupus erythematosus below the neck), and younger age at onset.

“We often will get consults for ANAs of 1:40 or 1:80,” Mixon said. “We really do not get very worked up about those. But if I see an ANA of 1:120, I worry about that patient,” she explained, noting that more antibodies can contribute to chronic inflammation that may attack different parts of the body. “So, a higher-titer ANA raises the suspicion that something more systemic may be going on,” she said. 

Histologic features of cutaneous and systemic lupus are essentially the same. Characteristics include interface dermatitis, vacuolar alteration of the basal layer, necrotic keratinocytes, and mucin deposition, “particularly in chronic discoid lupus,” Mixon said. “Follicular plugging is also common in discoid lupus.”

The clinical and serologic context helps to differentiate cutaneous and systemic lupus. Mixon recommends asking patients questions such as, “How do you feel? Are you having problems doing basic activities like getting a milk carton out of the fridge or combing your hair? Do you feel tired?” Lupus “is a different type of tired,” the feeling of barely being able to function, she said. “It’s very like flu-like. I tell my lupus patients, ‘Your body’s fighting a war inside, so you’re going to feel awful.’ ”

Mixon routinely orders a direct immunofluorescence (DIF) biopsy in cases of suspected lupus. The so-called “lupus band test” shows deposition of IgG, IgM, and C3 at the dermoepidermal junction. “This will help guide you to tell you if this is an underlying autoimmune process,” she said. In cutaneous lupus, DIF is typically positive in lesional skin, while in systemic lupus, DIF can be positive in nonlesional sun-protected skin.

Management of lupus includes the regular use of a broad-spectrum sunscreen with an SPF of at least 50, Mixon said, and hydroxychloroquine remains a cornerstone of treatment. Other common treatments include methotrexate, azathioprine, mycophenolate, and the biologic agents belimumab and anifrolumab, Mixon said, noting that anifrolumab, in particular, is helpful in treating cutaneous lupus.

Mixon disclosed no relevant financial relationships. 

Doug Brunk is a San Diego-based medical journalist.