Systemic lupus erythematosus

SLE, lupus erythematosus integumentalis, lupus erythematosus visceralis, visceral lupus erythematosus

Potentially lethal, chronic inflammatory, intermittent autoimmune disease of the vascular connective tissue with cutaneous and visceral involvement. The occurrence of autoantibodies against double-stranded DNA is typical.

• Prevalence: 40/100,000.
• Incidence: 5-10/100,000.
• Four times more common among Africans than Caucasians or Asians.
• Family accumulation: in approx. 10%.
• Severity: In the case of Spanish-South American and African-American descent, more pronounced progressions can often be observed.
• Women: Men = 8-10: 1.
• Patients are rarely younger than 5 years.
• Initial manifestation usually occurs in young adults (15th and 30th LJ), but a "late onset SLE" is possible.

• Multifactorial etiology and trigger factors.
• UV rays.
• Genetics (e.g.: Mutation in the TREX1 gene, association with HLA-DR3 (in Caucasians), HLA-DR1 and -DR2 (in Asians).
• Medicines (see drug-induced lupus erythematosus).
• Estrogens (e.g. exacerbation during pregnancy).
• Viral infections.
• CD4+ T lymphocytes secrete IL-4 & 6, which leads to B-cell activation and ultimately to autoantibody production and, in the broader sense, to the production of immune complexes. Circulating immune complexes can cause deposition in small vessels of visceral organs or the skin, where they can act as triggers for vasculitis. In addition, the formation of immune complexes in the basement membrane is possible.

• Allgemeinsymptome: Erhöhte Temperatur, Müdigkeit, Gewichtsabnahme. 
•  Haut (bei ca. 80% der Patienten) 
•  Gesicht: Erythema perstans (schuppiges, unscharf begrenztes Schmetterlingserythem), in manchen Fällen kann das gesamte Gesicht erfasst sein. Ca. 60% aller Patienten mit SLE zeigen ein Schmetterlingserythem. 
•  Stamm: multiforme oder livedoartige oft hämorrhagische, selten bullöse Exantheme des oberen Rumpfes. 20-30% der Patienten zeigen SCLE oder DLE-ähnliche Hautveränderungen. Bis zu 20% der Patienten bleiben hauterscheinungsfrei. 
•  Palmoplantar: fleckige, diffuse, teils keratotische Erytheme. 
•  Livedo racemosa. 
•  Teleangiektasien an Fingerspitzen und subunguale Blutungen am Nagelfalz. 
•  Vaskulitische Veränderungen können zu Schmerzen und auch zu Gangränen und Ulzerationen führen. 
•  Mundschleimhaut (in ca. 40% der Patienten): Enantheme, Erosionen, Ulzerationen. 
•  Lippen: Cheilitis  
•  Myalgien (fast alle Patienten). 
•  Arthritis (fast alle Patienten) meist ohne sichtbare Schwellung. Bei 10% besteht zusätzlich eine Polyarthritis. 
•  Serositis (ca. 50% der Patienten): Im Sinne einer Pleuritis, Perikarditis (Libman-Sacks-Syndrom) oder Peritonitis. 
•  Lupusnephritis bzw. nephrotisches Syndrom (bei ca. 40–65% der Patienten).  
•  Lymphknotenschwellungen. 
•  Hepatosplenomegalie. 
•  Gastritis. 
•  Kolitis. 
•  Psychosen. 
•  Krampfanfälle. 
•  vernarbende Alopezie. 
•  Raynaud-Phänomen. 
•  Assozationen:   
•  Sweet Syndrom. 
•  Livedovaskulopathie. 
•  Die Autoantikörper (außer DNA-Antikörper) korrelieren nicht mit der Krankheitsaktivität. 
•  Autoantikörper gegen doppelsträngige DNA und Immunkomplexe mit Komplementaktivierung, welche eine Vaskulitis verschiedenster Organe auslösen kann. 

1. Clinic.
2. ARA criteria (not absolute scale).
3. Serological parameters.
4. Dermatopathology and direct immunofluorescence.
5. Light testing.

1. Clinic 
   • s.o.
2. ARA criteria (not absolute scale). 
   • Classification criteria of the American Colleague of Rheumatology: 
     1. butterfly erythema 
     2. Cutaneous LE (SCLE, DLE, scarring alopecia)
     3. Photosensitivity 
     4. Oral, nasopharyngeal, painless ulcerations 
     5. Non-erosive, painful arthritis (≥ Joints)
     6. Serositis 
        • Pleurisy 
        • Pericarditis 
        • Sometimes also described peritonitis.
     7. Neurological abnormalities: non-drug seizures, psychoses 
     8. Kidney involvement 
        • Proteinuria > 0.5g/24 h or pathological sediment)
     9. Hematological abnormalities 
        • Hemolytic anemia with reticulocytosis.
        • Leucopenia <4,000/mm3.
        • Lymphopenia <1,500 mm3.
        • Thrombocytopenia <100,000/mm3.
     10. Imunological findings (AK vs. dsDNA, anti-Sm- Ak, antiphospholipid (= anticardiolipin)-Ak, lupus anticoagulant. 
     11. Increased ANAs 
         1. With 4 (of 11) applicable criteria an SLE can be diagnosed (sensitivity: 96%, specificity: 96%)
3. Serological parameters. 

• Blood count: leukopenia, neutropenia, lymphopenia, eosinopenia, Thrombopenia, macrocytic anemia possible.
• Inflammation values: CRP and BSG (increased BSG often correlates with severity of the disease)
• Circulating immune complexes: C3 reduced, C4 reduced 
• Electrophoresis: Increased γ globulin.
• Cryoglobulins.
• Antibody profile!

ANAs at SLE

Source: Plewig, Gerd.  Braun-Falco's Dermatology, Venerology And Allergology . Berlin: Springer, 2012. print. 

CAVE:

• False-positive Rh fact. (in approx. 33%)
• False-positive syphilisserology (VDRL) (in approx. 25%).

1. Dermatopathology and direct immunofluorescence. 
   • Dermatopathology 
     • Interface dermatitis, perivascular lymphocytic edematous infiltrate.
     • Direct immunofluorescence 
       • Lupus band test: band-shaped granular, IgG, C3, (but also IgM and IgA) - deposits on the basement membrane (also in non lesional, unexposed skin).

1. Light testing 

• Light stairs, then photo provocation.
• Screening:
• Blood pressure and temperature measurement.
• Urine status: 
  • 24-hour collecting urine (creatinine clearance, immunophoresis).
• Thoracic x-ray.
• Lung function (CO diffusion capacity e.g. of interstitial fibrosis, pneumonitis).
• X-ray or ultrasound of aching joints.
• Sonography of the upper abdomen.
• Kidney biopsy: lupus nephritis.
• Echocardiography: Carditis.
• Capillary microscopy.
• Spinal tap.
• EEG.
• MRI with gadolinium contrast, angio-MRI, angiography: in v.a. cerebral vasculitis.
• Ophthalmological presentation: conjunctivitis, sicca symptoms.

• Chronic progression. 
• Depending on the organ involvement, the disease can lead to death.

1. Swaak A, van H, Smeenk R, et al. Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation. Lupus 2001;10:51-8.
2. Shakoor N, Michalska M, Harris CA, Block JA. Drug-induced systemic lupus erythematosus associated with etanercept therapy. The Lancet 2002;359:579-80.
3. Roman MJ, Shanker B-A, Davis A, et al. Prevalence and Correlates of Accelerated Atherosclerosis in Systemic Lupus Erythematosus. New England Journal of Medicine 2003;349:2399-406.
4. Al-Raqum HA, Uppal SS, Al-Mutairy M, Kumari R. Shrinking lung syndrome as a presenting manifestation of systemic lupus erythematosus in a female Kuwaiti. Clin Rheumatol 2005;25:412-4.
5. Petri M, Kim MY, Kalunian KC, et al. Combined Oral Contraceptives in Women with Systemic Lupus Erythematosus. New England Journal of Medicine 2005;353:2550-8.
6. Ramos-Casals M, Nardi N, Lagrutta M, et al. Vasculitis in Systemic Lupus Erythematosus. Medicine 2006;85:95-104.
7. Dall'Era M, Wofsy D. Systemic lupus erythematosus clinical trials—an interim analysis. Nat Rev Rheumatol 2009;5:348-51.
8. Tassiulas IO, Boumpas DT. Clinical Features and Treatment of Systemic Lupus Erythematosus.  Kelley's Textbook of Rheumatology: Elsevier BV; 2009:1263-300.
9. Illei GG, Shirota Y, Yarboro CH, et al. Tocilizumab in systemic lupus erythematosus: Data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum 2010;62:542-52.
10. Almoallim H, Khadawardi H. Anti-Tumour Necrosis Factor-α Induced Systemic Lupus Erythematosus.  Systemic Lupus Erythematosus: InTech; 2012.
11. Takayama A, Ishiguro N, Kawashima M. Coexistence of Bowenoid papulosis and Bowen's disease in a patient with systemic lupus erythematosus. J Dermatol 2012;39:646-9.
12. Oomatia A, Fang H, Petri M, Birnbaum J. Peripheral Neuropathies in Systemic Lupus Erythematosus: Clinical Features, Disease Associations, and Immunologic Characteristics Evaluated Over a Twenty-Five-Year Study Period. Arthritis & Rheumatology 2014;66:1000-9.
13. Soudet S, Delaporte E, Hatron PY. Diffuse calcinosis cutis in systemic lupus erythematosus: an exceptional complication. Lupus 2016.
14. Tenbrock, K. (2016). S1- Leitlinie: Systemischer Lupus erythematodes. Awmf.org. Retrieved 30 May 2016, from
15. http://www.awmf.org/uploads/tx_szleitlinien/027-061l_S1_Systemischer_Lupus_erythematodes_2013-01.pdf
16. Wallace, D. (2016). Overview of the management and prognosis of systemic lupus erythematosus in adults. Uptodate.com. Retrieved 30 May 2016, from http://www.uptodate.com/contents/overview-of-the-management-and-prognosis-of-systemic-lupus-erythematosus-in-adults?source=search_result&search=systemischer+lupus+erythematodes&selectedTitle=2%7E150