The Effect of Some Drugs Used in Treatment of Vasculitis on the Complement System in Children

The Effect of Some Drugs Used in Treatment of Vasculitis on the Complement System in Children Attending Assiut University Hospital.

Vasculitis denotes affection of small to medium sized vessels by polyangitis. Antineutrophil cytoplasmic antibodies (ANCA) are immunoglobulin G (IgG) autoantibodies directed against constituents of neutrophil granules leading to neutrophil degeneration which results in cell apoptosis known as "Natoptosis" (NaTosis) of the cells. These lead to vessel endothelial cell damage. So that, ANCA formation seems to be the basic reaction in vasculitis. Complement activation at C3 and C4 was thought to be involved in renal damage ANCA associated vasculitis (AAV).

Vasculitis syndromes include: Henoch-Schonlein Purpura (HSP), connective tissue disorders e.g. Systemic Lupus Erythematosus (SLE), Rheumatoid arthritis...etc; where small vessels are mainly involved in the process of vasculitis. Vasculitis syndromes also include Kawasaki disease where also medium sized vessels are also included. Other vasculitis syndromes are also reported. ANCA associated vasculitis may be due complex interplay of genetic risks, environmental or infection trigger or adaptive immunity leading to insufficient regulation of B cells with pathogenic ANCA generation and neutrophil activation (AAV). Complement activation at C3 and C4 was involved in organ damage, especially renal, in AAV at the alternative complement pathway, factor B and properdin component colocalized with C3 complement in the endothelium of the blood vessels. Furthermore, the common complement pathway was activated as reflected by increased C5a levels. This suggests that both the alternative and common complement pathways are involved in some cases of vasculitis. Furthermore a decrease in these activation factors was observed during remission of vasculitis. This may denote clearance of the degradation of cell component that were blocking inactive vasculitis. In addition, many studies noticed strong increased plasma levels of the anaphlatoxin C5a that has a strong proinflammatory activity on the endothelium of vessels that may be related to disease severity. So much so, that inhibition of C5a levels by immunologic inhibitors may have a therapeutic role in some forms of ANCA positive vasculitis. Various treatment forms have been used for vasculitis syndromes. Drugs used in treatment of Juvenile Idiopathic Arthritis (JIA) are: Non-steroidal Anti-inflammatory Drugs (NSAIDs) such as Salicylates e.g. Aspirin, Selective COX-2 inhibitors e.g. Celecoxib & Non-Selective COX-2 inhibitors e.g. Naproxen. Non-biologic Disease-Modifying Anti-rheumatic drugs such as Methotrexate. Biologic Disease-Modifying Anti-rheumatic Drugs such as Infliximab. Oral or parenteral Glucocorticoids such as Methylprednisolone (According to American College of Rheumatology). In cases of SLE, the American College of Rheumatology (ACR) recommended corticosteroids in the 1st place and change to or add Biologic Disease-Modifying Anti-rheumatic Drugs Agents such as Rituximab. Regarding Henoch-Schonlein Purpura vasculitis, 70% of cases are self-limited. only cases with suspected renal involvement e.g. hematuria, hypertension, headache or proteinuria are to be treated with sreroids.

The aim of this work is to assess the effect of various forms of treatment of vasculitis on C3, C4, C5a & ANCA levels in blood, in infants & children.

Patients in this group will receive: Ibuprofen Oral At a dosage of 30 to 40 mg/kg/day, divided into 3 or 4 doses/day, max 2400 mg/day, given with food, in the form of suspension or tablets. Duration of therapy: 4 - 6 weeks.

Steroids: Pednisone (for mild/moderate cases): Oral Single daily morning dosage of 0.05-2.0 mg/kg/day, or in 2 - 4 divided doses, max 80 mg/d. Duration: 4 - 6 weeks, with gradual tapering to the lowest effective dose. Methylprednisolone (for severe/acute cases): IV 10-30 mg/kg/dose (max 1 g), over 1 hr daily for 1-5 days, followed by oral prednisone, with gradual tapering to the lowest effective dose. The duration is variable according to the condition of the patient.

Patients in this group will receive: Methotrexate Oral At a dosage of 10 to 20 mg/m2/wk (0.35 to 0.65 mg/kg/wk), max dose 25 mg/wk. Duration of therapy: 6 - 12 weeks.

Infants and children with vasculitis attending AssiutU, aged > 1 mo. - 17 yr. of both genders will be included during 2 years of study. Besides full clinical history and thorough examination, all cases will have: CBC, CRP, ESR, Renal function tests & Albumin / creatinine ratio. All cases will have an initial estimation as well as follow up estimation after treatment by Ibuprofen for ANCA, C3, C4 &C5a levels done, measured By ELISA technique.

Infants and children with vasculitis attending AssiutU, aged > 1 mo. - 17 yr. of both genders will be included during 2 years of study. Besides full clinical history and thorough examination, all cases will have: CBC, CRP, ESR, Renal function tests & Albumin / creatinine ratio. All cases will have an initial estimation as well as follow up estimation after treatment by Steroids for ANCA, C3, C4 &C5a levels done, measured By ELISA technique.

Infants and children with vasculitis attending AssiutU, aged > 1 mo. - 17 yr. of both genders will be included during 2 years of study. Besides full clinical history and thorough examination, all cases will have: CBC, CRP, ESR, Renal function tests & Albumin / creatinine ratio. All cases will have an initial estimation as well as follow up estimation after treatment by Methotrexate for ANCA, C3, C4 &C5a levels done, measured By ELISA technique.

An initial estimation as well as follow up estimation after treatment for ANCA, C3, C4 &C5a levels done, measured By ELISA technique.

Inclusion Criteria: Infants & children with vasculitis attending Assiut University Child Hospital (AUCH), aged > 1 mo. - 17yr. of both genders will be included during 2 years of study. Exclusion Criteria: Those cases aged less than one month will be excluded from the study.

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https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Rheumatoid-Arthritis

American College of Rheumatology (ACR) Juvenile Idiopathic Arthritis Guideline Project Plan - June 2017