Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is an auto-immune disease involves nearly all of the organs. SLE is nominated as the ‘great masquerader’ of medicine, which means that it could present with any possible sets of clinical manifestations. Thus, it could imitate the presentation of a vast majority of disorders. So despite having so many para-clinical tools, SLE diagnosis remain highly challengeable for physicians. 

According to the international epidemiologic studies, the incidence of SLE is reported between 0.3 to 23.2 in 100,000 person-years. The highest estimate of SLE prevalence was 241/100,000 in North America and the lowest was 0/847 in Northern Australia. Individuals with Black ethnicity had the highest incidence and prevalence of SLE followed by Asian and White people. There is an extremely female predominance for SLE with the female to male ratio of approximately nine to one. The prevalence of SLE is estimated 40/100,000 in Iran with the female to male ration of nine to one. The mean age at presentation was 24.4 ± 10.4 years.

Similar to other auto-immune disease, a genetically susceptible person will develop an exaggerated self-targeted immune response if he encountered a specific environmental trigger. Up to know, in the light of genome wide association studies, so many loci were identified which contribute in disease pathogenesis. Moreover, several line of evidences supports the role of certain viruses and other micro-organisms which can possibly induce lupogenic immune system cascade. Furthermore, several medications were also identified from long time ago, which can induce certain clinical and serological manifestations in patients mimicking SLE manifestations. This condition named drug-induced Lupus Erythematosus and it is an identified side effect of certain medications like hydralazine, procainamide, sulfasalazine, minocycline and anti-TNF agents. In addition, several other medications were identified which can trigger disease flare-up in known cases of SLE. Although, the sunlight and ultraviolet wave is the most potent environmental trigger for SLE. Ultraviolet wave, induce keratinocytes’ apoptosis and furtherly the apoptotic bodies are spread systemically. Impaired pathways of apoptotic bodies’ clearance which are probably results from genetic polymorphisms, can further accumulate and induce innate immune system and activate plasmacytoid dendritic cells. This activation can further results in adaptive immune system response and consequently leads to auto-antibody synthesis. The immune complexes resulted from these auto-antibodies can further deposit in organs with defective mechanism for immune-complexes’ clearance. Afterward, these immune-complexes induce an exaggerated immune response that consequently cause organ damage.

As it was mentioned previously, SLE can influence all body organs and mimic the presentation of other diseases. But the following signs and symptoms are more common is this patients:

·         Constitutional symptoms: Nearly all of the patients experienced constitutional symptoms during the active states of their SLE; majorly as anorexia, involuntary weight loss and fatigue. These symptoms seem to be secondary to systemic inflammatory cytokines and patients’ catabolic state. These symptoms are correlated with disease activity and patients weight should be monitored in each visit, an involuntary weight loss may be the first sign of flare-up in certain cases.

·         Musculoskeletal manifestations: Eighty-two percent of Iranian patients experience musculoskeletal manifestations during the course of their disease. Patients frequently complain of inflammatory arthralgia of their small joint and less frequently, in their large joints which can be associated with evident signs of inflammation and arthritis. Arthritis of SLE patients is non-erosive and rarely cause a hand deformity which is reversible, named Jaccoud arthropathy. Certain patient’s population, also suffer from rheumatoid arthritis in addition to SLE which is named rhupus in medical terms. Inflammatory myositis may also occur rarely.

·         Dermatological manifestations: Lupus Erythematosus (LE) is a general term of the family with so many diverse cutaneous manifestations. It is divided into acute-cutaneous LE (ACLE), sub-acute cutaneous LE (SCLE) and chronic LE (CLE). ACLE is completely associated with SLE whereas, the association rate of SCLE and CLE with SLE is lower. Malar rash is one of the most common manifestations of ACLE in addition to generalized rash, bullae, palmar erythema and confluent papules of hands’ dorsum which is named lupus hand. The mucous membrane can frequently affect in the form of oral ulcers.

·         Renal involvement: renal involvement is the hall-marks of organ-threatening manifestations of SLE, named lupus nephritis (LN). It could be presented with a wide range of presentations. It can be occurred in a SLE patients with normal urine analysis (U/A) called silent lupus nephritis or on the other hand, it can be presented with an extremely life-threatening condition secondary to uremia and kidney failure, nephrotic range proteinuria and hypertension. LN is classified based on ISN/RPS classification system which is defined by histological findings. Interestingly, LN is unique among other nephritis because there is not a strong correlation between LN histology, laboratory and clinical findings. Patients with nephritic range proteinuria, hematuria and even cellular casts might have minor histological changes. Nonetheless, certain patients with a little elevated creatinine level might have severe features of scar, activity and chronicity in their biopsies.

·         Hematological manifestations: SLE can affect all three lineages of hematopoietic cells. White blood cells are influenced frequently by disease process. Patients can experience neutropenia, lymphopenia or leukopenia that most of the times, it is not severe enough to need targeted therapy. Anemia can also occurred due to central degradation of red blood cells ancestors or they can be degraded peripherally (auto-immune hemolytic anemia). Thrombocytopenia can be also occurred severely enough to cause malignant bleeding diathesis which needs aggressive immunosuppressive treatment.   

·         As it was mentioned previously, all body organs can be involved in SLE course but with lower frequency. SLE is one of the specific disorders affect all three layers of the heart and patients will experience pericarditis, myocarditis and endocarditis. Moreover, the other non-lupus related cardiac disease like coronary artery disease and atherosclerosis are more prevalent among SLE cases due to the side effects of inflammatory condition and also the medications. Lung, central and peripheral nervous system and gastrointestinal system can also be affected.

SLE treatment protocol is designed based on the extent and severity of organs’ involvement. Corticosteroids have the most potent and fastest effect to suppress a disease flare-up and severe life or organ-threatening conditions. But according to the major side effects of steroids, other immunosuppressive agents should use to taper the steroid dosage. These immunosuppressive agents target different points in the immune system and they selected based on the severity of organs’ involvements. Meanwhile, anti-malarial agents are the mainstay to maintain remission in SLE. According to its high efficacy in preventing SLE flare-up and its negligible side effects, it should be prescribed for all patients unless a contraindication is present.

Young woman with the typical "butterfly rash" found in lupus