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Systemic Lupus : An Immune Attack to its Own Body

by mediconepal
May 14, 2021
in Health Articles
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Lupus (Lystemic Lupus erythematosus or SLE) is an autoimmune disease, in which the immune system attacks the body’s own tissues assuming as though they were foreign .It is not contagious and no one knows exact  causes  behind that body start attacking its own tissues. A person may be born with a certain genetic makeup that affects how the immune system functions or makes him or her at risk for lupus. A combination of factors can trigger the autoimmune process, some of which may affect one person but not another.

Epidemiologically, it is rare disease associated with considerable morbidity and 5-fold increase in mortality compared age and gender matched controls. People of African, Asian, and Native American descent are more likely to develop lupus than are Caucasians. Although it can occur in men and women, 90% of people diagnosed with the disease are women. Women of childbearing age (14 to 45 years old) are most often affected.

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Etiology: –

  • The cause is  unknown. However, there appears to be something that triggers the immune system to attack various areas of the body. That’s why suppressing the immune system is one of the main forms of treatment. Finding the cause is the object of major research efforts.
  • Factors that may contribute to the development of lupus include viruses, environmental chemicals and a genetic factors
  • Female hormones are believed to have role in its development more often than men and this is more true especially women during their reproductive years, a time when hormone levels are highest.

Pathophysiology: –

  • Genetic factors play an important role
  • Higher concordance with monozygotic twins and is strongly associated with polymorphic variants at the HLA focus.
  • Few instances, SLE is associated with inherited mutations in complement components: C1q, C2 and C4, in the immunoglobulin receptor (FcgammaR3b) or in the DNA exonuclease TREX1.
  • Several other genes that predispose to SLE, most of which are involved in regulating immune cell function.
  • Immunological standpoint: characteristic feature of SLE is autoantibody production.
  • These autoantibodies are specific for a wide range of targets but many are directed against antigens present with the cell or nucleus.
  • SLE may occur because of the defects in Apoptosis or in the clearance of Apoptotic cells.
  • Environmental factors (UV light and infections) that cause flares of lupus: increase oxidative stress and cause cell damage.
  • Immune complex formation is an important mechanism of tissue damage in active SLE leading to vasculitis and organ damage.

Clinical features: –

  • During flares of disease activity: fever, weight loss and lymphadenopathy (mild)
  • Constant symptoms: fatigue, malaise and fibromyalgia-like symptoms
  • Arthritis and Arthralgia is a common symptom (in 90% of Patients) and associated with early morning stiffness.
  • Tenosynovitis may also occur but clinical presentation is rare.
  • Jaccoud’s Arthropathy (joint deformity) may occur due to tendon damage but joint erosions do not occur.

Raynaud’s Phenomenon:
Syndrome is a common presentation. Occurs in combination with arthralgia or arthritis.      It’s association with SLE and needs to be differentiated from primary Raynaud’s (which is common in young women).  Secondary Raynaud’s: age of onset over 25yrs, absence of family history and occurrence in male.      Distinguish between primary and secondary can be assessed by the examination of cap nail-fold loops by ophthalmoscope and oil placed on the skin.
Skin:-

  •       Rash is common in SLE and is precipitated by exposure to UV light.  3 distinct types of rashes are in presentation.
    • Butterfly facial rash => (up to 20% of Patients) This is erythematosus, raised and painful/itchy and occur over the cheeks with sparing of the nasolabial folds.
    • SCLE rash => migratory, non-scarring and either annular/psoriasiform.
    • Discoid lupus rash => characterized by hyperkeratosis and follicular plugging with scarring alopecia if it occurs on the scalp.       Diffuse, non-scarring Alopecia may also occur with active disease.
  •       Periungual Erythema (reflecting dilated cap loops)
  •       Vasculitis
  •       Livido reticularis

Kidney:-

      Renal involvement in people with lupus can be life threatening and may occur in up to half of those with lupus. It’s one of the major determinants of prognosis. Regular monitoring of BP and urinalysis is essential.Typical renal lesion: PROLIFERATIVE GOLEMERULONEPHRITIS; characterized by hematuria, proteinuria and urinary casts.

Cardiovascular:-

      Most common manifestation: PERICARDITIS where as   Less common: ENDOCARDITIS and LIBMAN-SACKS ENDOCARDITIS.

Endocarditis => due to accumulation on    heart valves of sterile fibrin containing vegetations which is a manifestation of hypercoagulability associated with antiphospholipid antibodies (APLA).

      Risk of Atherosclerosis, Stroke and MI is greatly increased => due to adverse effects of inflammation on endothelium, chronic steroid therapy and procoagulant effects of APLA.

Lung:-

  •       Lung involvement is common
  •       Frequently manifests as PLEURISY / PLEURAL EFFUSION.
  •       Other features => Pneumonitis, Atelectasis, reduced lung volume and Pulmonary Fibrosis leading      to     breathlessness.
  •       Risk of thromboembolism is increased in Patients with APLA.

Neurological:-

  • Common =>Fatigue, headache and poor concentration.
  •  Specific features of Cerebral Lupus: Visual hallucinations, chorea, organic psychosis, transverse myelitis and lymphocytic meningitis.

Haematological:-

  •       Either of these can occur due to antibody mediated destruction of peripheral blood cells:
    •       Neutropenia
    •       Lymphopenia {degree of L is a good guide to disease activity}
    •       Thrombocytopenia
    •       Haemolytic anemia
  •   Changes in blood counts:
  1. low red cell count(anemia) => may cause fatigue
  2. low white cell count => serious infections
  3. low platelet count => easy bruising or bleeding

      Many Patients are asymptomatic from low blood counts, so it is important for people with lupus to have periodic blood tests in order to detect any problems. Blood clots are more common in people with lupus.     Clots often occur in the legs (DVT) and lungs (pulmonary embolus) and occasionally in the brain (stroke).      Blood clots that develop in lupus Patients may be associated with the production of APL antibodies.

Gastrointestinal

      Mouth ulcers might occur and may/not b painful.   Mesenteric Vasculitis is a serious complication => present with abd pian, bowel infarction/ perforation.

 Classification Criteria for the Diagnosis of SLE by American Rheumatism Association (ARA): –

  1. Malar rash: Fixed erythema, flat or raised, over the malar eminences
  2. Discoid rash: Erythematous circular raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur
  3. Photosensitivity: Exposure to ultraviolet light causes rash
  4. Oral ulcers: Includes oral and nasopharyngeal ulcers, observed by physician
  5. Arthritis: Nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion
  6. Serositis: Pleuritis or pericarditis documented by ECG or rub or evidence of effusion
  7. Renal disorder: Proteinuria >0.5 g/d or 3+, or cellular casts
  8. Neurologic disorder: Seizures or psychosis without other causes
  9. Hematologic disorder: Hemolytic anemia or leukopenia (<4000/L) or lymphopenia (<1500/L) or thrombocytopenia (<100,000/L) in the absence of offending drugs
  10. Immunologic disorder: Anti-dsDNA, anti-Sm, and/or anti-phospholipid
  11. Antinuclear antibodies: An abnormal titer of ANA by immunofluorescence or an equivalent assay at any point in time in the absence of drugs known to induce ANAs

Any combination of 4 or more of 11 criteria, well-documented at any time during a patient’s history, makes it likely that the patient has SLE (specificity and sensitivity are 95% and 75%, respectively).

Investigations: –

  • Diagnosis is based on clinical features and lab findings.
  • Patients screened for ANA and antibodies to extractible nuclear antigens
  • Complement levels are checked along with routine haematology and biochem.
  • Patients with active disease => almost always test +ve for ANA.
  • Anti-ds ANA antibodies => characteristic of severe active SLE but occur in only 30% of cases.
  • Patients with active disease have low levels of C3 and C4 but could b due to inherited compliment deficiency that predisposes to SLE.
  • Typical finding in Active SLE => raised ESR, leucopenia, lymphopenia, anemia, hemolytic anemia and thrombocytopenia.
  • CRP is often normal in active disease but elevated levels are suggestive of coexisting infection.

Management: –

  • Mild symptoms :  for restricted to skin and joints can be used analgesics, Hydoxychloroquine (200-400 mg/d)
  • Corticosteriods and immunosuppressants [Methotrexate/ Azathioprine/ Mycophenolate Mofetil (MMF)] should be taken with the consulation with the doctors . sometimes in ncreased doses of steroids may b required for flares in activity or complications (pleurisy/ pericarditis).
  • During the life-threatening condtion with renal, CNS and    Heart       involvement, High dose corticosteriods and immunosuppressants are required
    •  Commonly used regime (pulse): Methylprednisolone (10 mg/kg IV) + Cyclophosphamide (15 mg/kg IV) -> repeated at 2-3 weekly intervals for 6 cycles.
    •   Adverse effects of Cyclophosphamide: hemorrhagic cystitis but can b minimized by good hydration and co-prescription of Mesna.
    • Renal involvement in SLE: MMF + high dose steriods are also being used -> with similar results but fewer side effects than pulse regimen.
    • Benlysta (belimumab): weakens the immune system by targeting a protein that may reduce the abnormal B cells thought to contribute to lupus. People with active, autoantibody-positive lupus may benefit from Benlysta when given in addition to standard drug therapy.
  • Maintenance Therapy =>
    • after controlling the acute episode, Patients should be switched to oral immunosuppressive med:
    • Typical regimen: oral Prednisolone (40-60 mg/d) on cessation of pulse therapy -> gradually reduce to reach the target of (10-15 mg/d or less) by 3 months.
    • Azathioprine (2-2.5 mg/kg/d) or Methotrexate (10-25 mg/wk) or MMF (2-3 g/d) are also prescribed.
  • Long-term aim:
    • to continue the lowest dose of Corticosteroids and immunosuppressant that’ll maintain remission.
    • CV risk factors (HTN and Hyperlipidemia) should b controlled and advised against smoking.
  • SLE Patients with Anti-phospholipid Antibody Syndrome, who previously had thrombosis: require life-long Warfarin therapy.

Life-style modifications: –

  • There is no cure for lupus, but there are steps you can take to improve your sense of well-being and your quality of life, including exercise like walking, swimming and biking can help prevent muscle wasting and lower your risk for thinning of bone(osteoporosis). Also it will have a positive impact on moodGet enough rest => Pace yourself, alternating periods of activity with periods of rest.
  • Eat well => People with lupus should eat a nutritious, well-balanced diet.
  •  Avoid alcohol => Alcohol can interact with your medications causing stomach and intestinal problems, including ulcers.
  •  Don’t smoke => can impair circulation and worsen symptoms in people with lupus.  smoke also has negative effects on your heart, lungs, and stomach.
  • Play it safe in the sun => To prevent rashes or disease flares from the sun, wearing sunglasses, hat and sunscreen lotion can be used  during  outing on sunny day.
  • Treat fevers and infections promptly => fever may indicate an infection or a lupus flare-up.
  •  Build an honest and open relationship with your doctor. and  Get to know your disease

References :

  • Textbook: Davidson’s Principles and Practice of Medicine (22nd Edition)
  • https://www.sharecare.com/health/lupus/what-is-jaccouds-arthropathy
  • http://www.sciencedirect.com/science/article/pii/S1521694211000933
  • https://www.nlm.nih.gov/medlineplus/ency/article/001478.htm
  • http://www.rightdiagnosis.com/sym/periungual_erythema.htm
  • http://www.lupus.org/research-news/entry/new-american-college-of-rheumatology-guidelines-for-lupus-nephritis
  • http://medicalcriteria.com/criteria/sle.htm
  • http://onlinelibrary.wiley.com/doi/10.1002/acr.21664/epdf

Compiled by :Paras Baloch,Mbbs Final Year, Yangtze University
 

Tags: lupus diseaselupus erythematosuslupus rashlupus skin rash pictureslupus symptomslupus symptoms in womenlupus treatmentnepal health articlesNepal health NewsNepal Health Noticespakistan health articleRecent Health articlesRecent Health NewsSLE articleYangtze University
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