Systemic lupus erythematosus

SLE, integumentary lupus erythematosus, visceral lupus erythematosus, visceral lupus erythematosus.

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

• Prevalence: 40/100,000.
• Incidence: 5-10/100,000.
• 4 times more common in Africans than in Caucasians or Asians.
• Familial cluster: in about 10%.
• Severity: Hispanic-South American and African American ancestry often have more pronounced courses.
• Females: Males= 8-10:1.
• Patients are rarely younger than 5. years.
• First manifestation usually occurs in young adulthood (15th and 30th years), but "late onset SLE" is possible.

• Multifactorial aetiology and trigger factors.
• UV radiation.
• Genetics (e.g.: Mutation in the TREX1 gene, association with HLA-DR3 (in Caucasians), HLA-DR1 and -DR2 (in Asians)).
• Drugs (see drug-induced lupus erythematosus).
• Estrogens (e.g.: exacerbation in pregnancy).
• Viral infections.

• CD4+ T lymphocytes secrete IL-4 & 6, leading to B-cell activation and eventually autoantibody production and, by extension, immune complex production. 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, formation of immune complexes in the basement membrane is possible.

• General symptoms: ↑ temperature, fatigue, weight loss.
• Skin (in about 80% of patients)
• Face: Erythema perstans (scaly, blurred butterfly erythema), in some cases the entire face may be affected. Approx. 60% of all patients with SLE show butterfly erythema.
• Trunk: multiforme or livedo-like often haemorrahgic, rarely bullous exanthema of the upper trunk. 20-30% of patients show SCLE or DLE-like skin lesions. Up to 20% of patients remain skin symptom-free.
• Palmoplantar: patchy, diffuse, sometimes keratotic erythema.
• Livedo racemosa.
• Teleangiectasia on fingertips and subungual haemorrhages at the nail fold.
• Vasculitic changes can lead to pain and also to gangrene and ulceration.
• Mouth mucosa (in approx. 40% of patients): Enanthema, erosions, ulcerations.
• Lips: Cheilitis
• Myalgias (almost all patients).
• Arthritis (almost all patients) mostly without visible swelling. In 10% there is also polyarthritis.
• Serositis (approx. 50% of patients): In the sense of pleuritis, pericarditis (Libman-Sacks syndrome) or peritonitis.
• Lupus nephritis or nephrotic syndrome (in approx. 40-65% of patients).
• Lymph node swelling.
• Hepatosplenomegaly.
• Gastritis.
• Colitis.
• Psychosis.
• Seizures.
• Scarring alopecia.
• Raynaud's phenomenon.

• Associations:
  • Sweet syndrome.
  • Livedovasculopathy.

• Autoantibodies (except DNA- antibodies) do not correlate with disease activity.

• Autoantibodies against double-stranded DNA and immune complexes with complement activation, which can trigger vasculitis of various organs.

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

1. Clinical
   • s.
2. ARA criteria (not an absolute standard).
   • 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
        • Pleuritis
        • Pericarditis
        • Sometimes peritonitis described.
     7. Neurological abnormalities: non-drug-induced seizures, psychoses
     8. Kidney involvement
        • Proteinuria > 0.5g/24 h or pathological sediment)
     9. Hematological abnormalities
        • Hemolytic anaemia with reticulocytosis.
        • Leucopenia <4'000/mm3.
        • Lymphopenia <1'500 mm3.
        • Thrombocytopenia <100'000/mm3.
     10. Imunological findings (Ak gg. dsDNA, anti-Sm- Ak, antiphospholipid (=anticardiolipin)-Ak, lupus anticoagulant.
     11. ↑ ANAs
         1. If 4 (of 11) criteria apply, SLE can be diagnosed (sensitivity: 96%, specificity: 96%)
3. Serological parameters.
   • Blood count: leukopenia, neutropenia, lymphopenia, eosinopenia, thrombocytopenia, macrocytic anaemia possible.
   • Inflammatory values: CRP and ESR (↑ ESR often correlates with severity of disease)
   • Circulating immune complexes: C3↓, C4↓
   • Electrophoresis: ↑ γ-globulin.
   • Cryoglobulins.
   • Antibody profile!

ANAs in SLE

Source: Plewig, Gerd. Braun-Falco's Dermatology, Venereology 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, oedematous infiltrate.
     • Direct immunofluorescence
       • Lupus band test: banded granular, IgG, C3, (but also IgM and IgA)- deposits at the basement membrane (also in non-lesional, unexposed skin).

1. Light testing
   • Light staircase, then photoprovocation.
   • Screening:
   • Blood pressure and temperature measurement.
   • Urine status:
     • 24h- collected urine (creatinine clearance, immunophoresis).
   • Thoracic X-ray.
   • Pulmonary function (CO diffusion capacity e.g. of interstitial fibrosis, pneumonitis).
   • X-ray resp. Ultrasound of painful joints.
   • Overabdominal sonography.
   • Kidney biopsy: lupus nephritis.
   • Echocardiography: carditis.
   • Capillary microscopy.
   • Lumbar puncture.
   • EEG.
   • MRI with gadolinium contrast, angio-MRI, angiography: in case of v.a. cerebral vasculitis.
   • Ophthalmological presentation: conjunctivitis, sicca symptoms.

• Rapid, chronic course.
• Depending on 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