Drug-Induced SCLE-An Update

Rick Sontheimer, MD

In his presentation, Dr Sontheimer summarized recent observations characterizing drug-induced SCLE (DI-SCLE).  In 1977 he and Jim Gilliam co-authored along with the seminal paper on SCLE.  Dr. Sontheimer suggests that when a physician sees a new SCLE patient it is important to ask whether it is idiopathic SCLE or is this a drug-induced form of the disease.  If the dermatologist can pinpoint the drug causing the condition, an internist or family physician, for example, could stop the drug or prescribe a different drug in a different class of medication, which should result in resolution of the rash and symptoms.

 

The idea that SCLE could be drug-induced was introduced in the mid 1980s in a paper reporting five patients whose otherwise typical Ro/SS-A autoantibody (+) SCLE skin lesions appeared after starting HCTZ & resolved upon discontinuing the HCTZ. Ro/SS-A antibody persisted in all except one patient after SCLE skin lesion resolution and one patient was re-challenged with a thiazide-related diuretic with the reappearance of SCLE skin disease activity that resolved after the initial drug discontinuation.

 

Dr. Sontheimer co-authored a recent paper on the subject of DI-SCLE.   (Lowe, G., et al  A Systematic Review of  Drug-Induced Subacute Subacute Cutaneous Lupus Erythematosus Brit J Dermatol 2010:1365-2133)   Data were abstracted prospectively from 117 articles published up to August 2009.  The authors addressed 8 key questions pertaining to clinical and immunologic issues. They found these patients to be, on average, 15 years older than the typical patients, which, may not actually be all that surprising in that, older patients are more likely to be on more medications. The triggering drug classes are below in Figure 1.

There were marked differences among the various triggering drug classes regarding the length of incubation before the rash/symptoms resulted and time to resolution of the DI-SCLE following cessation of the triggering drug. The cardiovascular drugs seemed to have longest incubation period from 6 months up to 5 years. The anti-fungal drug, terbinafine, had a mean incubation time of 5.1 weeks (29 cases) and 1 case with griseofulvin had an incubation time of 2 weeks. The chemotherapy drugs had an incubation time of days to weeks. It is important to remember that the DI-SCLE didn’t occur in patients until after about 2 weeks and in some cases even longer. The research found that RO/SS-A and La/SS-B antibodies remain present after the resolution of DI-SCLE.

There are several interesting reports on the kinetics of autoimmunity and systemic LE. The Oklahoma Medical Research Foundation conducted a study utilizing the military blood bank. The researchers analyzed antibody levels in blood samples taken prior to the individual developing SLE. Approximately 70% of these individuals, who eventually developed SLE, had RO antibody 5 years prior. The idea here is that there is loss of tolerance to auto-antigens that slowly builds up over time, the autoimmune response matures to a point that it either becomes associated with the development of clinical disease in SLE or these antibodies and their immune complexes are involved in creating the clinical phenomenon.

 

The study also found that histone autoantibodies were, in general, not associated with DI-SCLE unlike drug-induced SLE.  There were no data available to answer whether patients who have experienced DI-SCLE have a subsequent risk for developing idiopathic SLE or Sjogren’s syndrome (SjS). The data were also not available to show the pathogenesis of DI-SCLE. Dr. Sontheimer mentioned that a large number of the drugs recognized to trigger SCLE are photosensitizers known to induce photosensitizing skin reactions without associated lupus-like autoimmunity.

What is the optimal medical management of DI-SCLE? Dermatologists should identify and coordinate with the patient’s internist or FP discontinuation of the triggering drug. It is important to remember that it will probably take 6 to 8 weeks before one can determine whether or not the SCLE was due to a specific drug because it takes that amount of time for the drug to “leave” a patient’s system. DI-SCLE can be treated the same as idiopathic SCLE and clinicians should continue to follow-up on the development of SLE/SjS.

In summary, Dr Sontheimer raises the question of drug-induced SCLE versus drug-precipitated SCLE; he feels it is more the latter. The prognosis for subsequent SLE/SjS development is uncertain and there is a need for a biomarker of drug class triggering SCLE considering the setting of poly-pharmacy and conundrums that clinicians face.

 

 

 

Treatment of Cutaneous LE

The fundamental principles behind the treatment of Cutaneous LE and even Systemic LE have not changed much over the past 50-60 years. Basic principles of sun avoidance/broad spectrum UV protection are mandatory in these patients.   Local treatment may include topical steroids/TCIs.  Systemic therapies are introduced depending on the patient medical status with a stepwise progression from hydroxychloroquine, hydroxychloroquine +chloroquine, chloroquine + quinacrine; retinoids, dapsone, thalidomide; MTX, azathioprine, cyclosporine and mycophenylate.

Management of the “difficult to treat” patient often involves an experimental approach.   According to Dr. Sontheimer, monoclonal antibodies that neutralize class 1 interferon, i.e., interferon-alpha activity have been studied in SLE patients who had skin lesions. They were able to follow the skin while they treated the patients so that they could see clinical improvement in addition to looking at laboratory parameters and skin biopsies. Preliminary data suggests that this approach of modulating the pathologic up-regulation of interferon-alpha in the skin could be of clinical benefit.

Other approaches are currently being explored for various refractory forms of cutaneous LE.  These include TNF-inhibition, phosphodiesterase 4 inhibition, IFN-gamma interfering antibodies and small molecule inhibitors CXCR3 receptors.

In conclusion, it is important that dermatologists have a strong knowledge base of these conditions and an understanding of the optimal approaches to treating the conditions and are aware of some of the recent advances currently being studied.