SYSTEMIC LUPUS ERYTHEMATOSUS

by Prasanna Dahal Pharm D (P.B) Ist year Department of Clinical Pharmacy AH&RC

CONTENTS
INTRODUCTION EPIDIMOLOGY ETIOLOGY PATHOGENESIS CLINICAL MANIFESTATION DIAGNOSIS PHARMACO-THERAPY DRUG DETAILS

INTRODUCTION
Systemic lupus erythematosus (SLE) is a multi system connective tissue disorder characterized by the presence of numerous auto antibodies, circulating immune complexes and widespread immunologically determined tissue damage . It generally involves one organ system at the onset, but can affect other organ systems subsequently displaying a broad range of clinical manifestations

 Discoid lupus erythematosus is a form of lupus erthematosus in which cutaneous lesions appear on the face and elsewhere. The hallmark of SLE is the development of autoantibodies to cellular nuclear components that leads to a chronic inflammatory autoimmune disease

EPIDIMOLOGY
The incidence of SLE varies among ethnic groups with the annual incidence in adults ranging from 1.9 to 5.6 per 100,000 persons per year. There is an increased frequency of SLE among women(10:1) that has been attributed to an estrogen hormonal effect. Less prevalent in whites than in other ethnic groups, including blacks, Native Americans, and Asians.

ETIOLOGY
Environmental agents that may have a role in induction or activation of SLE include sunlight (i.e., ultraviolet light), drugs, chemicals such as hydrazine (found in tobacco) and aromatic amines (found in hair dyes), diet, environmental estrogens, and infection with viruses or bacteria. A number of viruses have been implicated as causative agents in genetically susceptible people, but much of the evidence is incidental. Additionally, androgen may inhibit and estrogen enhance the expression of autoimmunity, and elevated circulating prolactin levels have been associated with lupus in males and females.

PATHOGENESIS

CLINICAL MANIFESTATION

DIAGNOSIS
ESR Urinalysis Complement Test
Tests levels of C3, C4, CH50 Low levels indicates possible presence of disease

FANA Fluorescent antinuclear antibody Ouchterlony Test shows interactions

TREATMENT
SUNSCREEN TOPICAL STERIODS NSAIDs ANTIMALARIALS STEROIDS CYTOTOXICS CALCIUM, VITAMIN D, FOLATE SUPPLEMENTATION INFLUENZA VACCINE (annual) PNEUMOCCOCAL VACCINE (decade)

Category I (Mild SLE)

Category II (Moderate SLE)

Category III (Severe SLE)

Category IV (SLE with miscellaneous features) treatment is based on the symptoms.

yCreams and sun blocks yNonsteroidal antiinflammatory drugs yAntimalarials drugs

Prednisolone Antimalarials Calcium supplements Intermittent use of NSAIDs Rifampicin + INH or INH + Ethambutol as prophylactic for TB

Azathioprine Plasmapheresis Methotrexate Cyclosporine mycophenolate mofetil

STAGE I- Characterized by arthritis, arthralgia, myalgia, fatigue, mild mucocutaneous involvement, low-grade fever, mild serositis, lupus, headache, musculoskeletal complaints are the commonest features. STAGE II-Characterized by high-grade fever, severe mucocutaneous manifestations, marked photosensitivity, moderate to severe serositis, lupus pneumonitis, and mild to moderate myocarditis, nephritis, hemolytic anemia and thrombocytopenia. STAGE III-Characterized by organ/life-threatening features such as focal/diffuse proliferate glomerulonephritis with or without azotaemia /hypertension, lupus cerebritis with recurrent seizures, acute confusional state, coma; systemic necrotizing vacuities such as one causing peripheral gangrene, GI bleeding. STAGE IV- Characterized by antiphospholipid syndrome (recurrent DVT, CVAs, recurrent fontal loss etc.), pure membranous lupus nephritis, chronic sclerosing lupus nephritis, seizures without other evidence of lupus activity, behavioral disorders without other serious manifestations, resistant thrombocytopenia

NEWER THERAPY
Hormone Treatments

Dehydroepiandrosterone (DHEA) Prasterone Danazol

PLASMAPHERESIS

Investigational Treatments Monoclonal Antibodies (MAbs) Epratuzumab Belimumab Rituximab Leflunomide

 Autologous Stem Cell Transplantation:

The procedure first removes the cells from the patient, who then receives high-dose immunotherapy. The stem cells are then reintroduced.
UVA-1 Phototherapy

A treatment which uses ultraviolet A-1 (UVA1) radiation, which are long UVA wave lengths that do not promote sunburn and may actually block inflammatory immune factors

DRUG DOSES
NSAIDS like salicylates doses towards their upper limit is beneficial. Methotrexate: 10-25 mg once a week with folic acid. It should be decreased when CrCl <25 ml/min. Glucocorticoids oral: prednisone, prednisolone 0.5-1 mg/kg body weight per day for severe SLE. 0.07-0.3 mg /kg body weight for mild SLE.

Methyl prednisolone IV: for severe disease 1 g iv every 3 days. Cyclophosphamide: IV 7-25 mg/kg every month for 6 months. ORAL 1.5-3 mg/kg per day Mycophenolate mofetil: 2-3 g/day Azathioprine: 2-3 mg/kg per day PO decrease frequency of dose if Crcl is <50 ml/min. Hydroxychloroquine: 150mg daily reduced gradually until control is achived. Max dose in adults is 2.5mg/kg body weight.

COMPLICATION
Infections, Inflammation, or Hypertension in the Lungs Treating Infections. antibiotics. However, antibiotic drugs such as penicillin or the sulfa drugs may cause sensitivity rashes that can be confused with SLE rash. Treating Lung Inflammation. This condition needs to be treated with corticosteroids or immunosuppressants Treating Pulmonary Hypertension. Drugs known as prostacylins -- which include epoprostenol, iloprost, and treprostinil -- are standard drugs. Viagra is also be used for this condition. Lung transplantation may be required.

Bleeding and Clotting Disorders Antiphospholipid Syndrome and Clotting Disorders. Hydroxychloroquine or aspirin may help prevent blood clots in women with antiphospholipid syndrome (APS),warfarin, ,autologous stem cell transplantation. Excess Bleeding from Thrombocytopenia (Drop in Blood Platelets). combinations of a corticosteroid and either danazol (a male hormone) or the antimalarial hydroxychloroquine. Immunosuppressants or intravenous immunoglobulin IgG. Surgical removal of the spleen

 Kidney Disease
Mycophenolate mofetil Intravenous cyclophosphamide Steroids Kidney transplant or dialysis

Plasmapheresis. Osteoporosis
calcium, vitamin D, bisphosphonates, parathyroid hormone, and selective estrogen-receptor modulators (SERM), such as tamoxifen, raloxifene and tibolone

Heart Disease
treatment of high blood pressure ,high cholesterol levels, diet changes ,drug therapies.

DRUG DETAILS
Methotrexate Methotrexate inhibits cytokine production, inhibits purine biosynthesis, and may stimulate release of adenosine, all of which may lead to its anti-inflammatory properties. The toxicities are mainly gastrointestinal, hematologic, pulmonary, and hepatic. contraindicated in pregnant and nursing women, chronic liver disease, immunodeficiency,, leukopenia, thrombocytopenia, pre-existing blood disorders.

HYDROXYCHLOROQUINE
Mechanism of action: mainly has the disease modifying capacity. Adverse drug reactions: retinopathy, hair loss, photosensitivity, tinnitus, myopathy, seizures, psychosis, leucopoenia, headache, pruritis, urticaria, and difficulty in visual accommodation. DOSE: 150mg daily reduced gradually until control is achived. Max dose in adults is 2.5mg/kg body weight.

Corticosteroids
They interfere with antigen presentation to T lymphocytes, inhibit prostaglandin and leukotriene synthesis, and inhibit neutrophil and monocyte superoxide radical generation ADR- include hypothalamic-pituitaryadrenal suppression, Cushings syndrome, osteoporosis, myopathies, glaucoma, cataracts, gastritis, hypertension, hirsutism, electrolyte imbalances, glucose intolerance, skin atrophy, and increased susceptibility to infections

Cyclophosphamide
Mechanism of action: It is a prodrug, which is converted in thebody to the active metabolites. It acts at any stage of the cell cycle but its main action is blockage at the G2 stage. This arrest of cell division is brought about by alkylation of the DNA in a dose dependent manner. It also exerts immunosuppressive effects possibly due to a cytotoxic effect on lymphocytes. Adverse drug reactions: congestive heart failure, leucopoenia, anorexia, anemia, thrombocytopaenia, cystitis and fibrosis of bladder, alopoecia, mucosal ulceration, ovarian or skin and nail pigmentation, jaundice. Monitoring parameters: serum electrolytes, lipid profile, complete blood count, and urine analysis.ete blood count, CBG, fundoscopy

NSAIDS
Mechanism of action: It inhibits the cyclooxygenase, which is responsible for the synthesis of prostaglandin and thromboxane. It also inhibits the platelet aggregation. Adverse drug reactions: gastric erosion, ulceration and bleeding; Reyes syndrome in the children, hepatotoxicity, CNS depression mainly causes comma, CV collapse. Monitoring parameters: INR, Prothrombin time, bleeding time, liver function tests.

REFERENCES
1. Joseph T Dipiro , Barbara G Wells , Terry L Schwinghammer , Cindy W Hamilton.Text Book Of Pharmacotherapy:A Pathologic Approach By,Mcgraw Hill Publishers.6th edition Page no:1431-40 2. Eric T.Herfindal , Dick R. Gourley .Textbook of Therapeutics, Seventh Edition ,Page no:691-704 3. K.D.Tripathi. Essentials Of Medical Pharmacology.6th Edn. 4. www. medscape.com

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