The course of SLE is variable and unpredictable. Rare acute cases result in death within weeks to months. More often, with appropriate therapy, SLE follows a relapsing and remitting course over a period of years or decades. During acute flares, increased formation of immune complexes results in complement activation, often leading to hypocomplementemia. Disease flares are usually treated with corticosteroids or other immunosuppressive drugs. Even without therapy, in some patients the disease runs an indolent course for years with relatively mild manifestations, such as skin changes and mild hematuria. The overall 5-year and 10-year survivals are approximately 90% and 80%, respectively. The most common causes of death are renal failure and intercurrent infections. Coronary artery disease also is becoming an important cause of death. Patients treated with steroids and immunosuppressive drugs incur the usual risks associated with such therapy.
As mentioned earlier, involvement of skin along with multisystem disease is fairly common in SLE. The following sections describe two syndromes in which the cutaneous involvement is the exclusive or most prominent feature.
Chronic discoid lupus erythematosus is a disease in which the skin manifestations may mimic SLE, but systemic manifestations are rare. It is characterized by the presence of skin plaques, most often on the face and scalp, showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy surrounded by an elevated erythematous border. It progresses to SLE in 5% to 10% of patients, usually after many years. Conversely, some patients with SLE may have prominent discoid lesions in the skin. Approximately 35% of patients have a positive test for generic ANAs, but antibodies to double-stranded DNA are rarely present. Immunofluorescence studies of skin biopsy specimens show deposition of immunoglobulin and C3 at the dermoepidermal junction similar to that in SLE.
The term subacute cutaneous lupus erythematosus refers to a group intermediate between SLE and lupus erythematosus localized only to skin. The skin rash in this disease tends to be widespread and superficial. Most patients have mild systemic symptoms similar to those in SLE. There is a strong association with antibodies to the SS-A antigen and with the HLA-DR3 genotype.
An SLE-like syndrome may develop in patients receiving a variety of drugs, including hydralazine, procainamide, isoniazid, and D-penicillamine. Surprisingly, anti-TNF therapy, which is effective in rheumatoid arthritis and other autoimmune diseases, also can cause drug-induced lupus. Many of these drugs are associated with the development of ANAs, especially antibodies specific for his-tones. The disease remits after withdrawal of the offending drug.
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SLEisasystemicautoimmunediseasecausedbyautoantibodiesproducedagainstnumerousselfantigensandtheformationofimmunecomplexes.
Themajorautoantibodies,andtheonesresponsiblefortheformationofcirculatingimmunecomplexes,aredirectedagainstnuclearantigens.Otherautoantibodiesreactwithredbloodcells,platelets,andvariousphospholipid-proteinscomplexes.
Diseasemanifestationsincludenephritis,skinlesions,andarthritis(causedbythedepositionofimmunecomplexes),hematologicabnormalities(causedbyantibodiesagainstredcells,whitecellsandplatelets)andneurologicabnormalities(causedbyobscuremechanisms).
Theunderlyingcauseofthebreakdowninself-toleranceinSLEisunknown;non-exclusivepossiblitiesincludeexcessivegenerationorpersistenceofnuclearantigens,inindividualswithinheritedsusceptibilitygenes,andenvironmentaltriggers(e.g.,UVirradiation,whichresultsincellularapoptosisandreleaseofnuclearantigens).