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Evaluation
Specialist Referral
It is essential to establish a good working
relationship among the primary care physician, non-lupus specialist (eg general
internist or pediatrician), lupus specialist (eg rheumatologist), nurse,
pharmacist, other healthcare providers, the patient, and his/her family. A team
approach will allow for earlier identification of disease flares and medication
toxicity.
The
patient will initially present to a primary care physician or non-lupus
specialist who is responsible for recognizing the signs and symptoms of systemic
lupus erythematosus in their patients, making an initial diagnosis, treating and
monitoring patients with mild disease, and referring the patient to a
rheumatologist or other lupus specialist (eg nephrologist) and participating in
further systemic lupus erythematosus diagnosis, management, and monitoring of
patients with moderate to severe disease.
The
lupus specialist is an integral part of the medical team managing a systemic
lupus erythematosus patient. Referral to a lupus specialist especially a
rheumatologist is indicated for confirmation of the diagnosis, formulation of a
management plan for the patient, periodic evaluation of disease activity and
severity, management of uncontrolled disease and complications, management of
organ involvement or life-threatening diseases, prevention and/or management of
treatment toxicities, and in special situations (eg pregnancy, antiphospholipid
syndrome, life-threatening disease, concomitant infection, and surgery).
Multidisciplinary care involves the referral of systemic
lupus erythematosus patients to a psychologist, psychiatrist, physical and/or
occupational therapist, ophthalmologist, dermatologist, cardiologist, orthopedic
surgeon, and other specialists when necessary.
Principles of therapy
Patients
require individualized therapy depending on disease manifestations, activity,
and severity.
One of the goals of therapy is to control disease manifestations
(ie aim for remission or low disease activity and flare prevention). Complete
remission means there is no clinical activity (SLEDAI score of 0) without the use
of corticosteroids and immunosuppressants. Low disease activity is SLEDAI of ≤4,
PGA of ≤1, corticosteroid use of ≤7.5 mg/day of Prednisone, and well-tolerated
immunosuppressants in stable doses.
Other goals
of therapy include allowing the patient to have a good quality of life without
major exacerbations, preventing serious organ damage that adversely affects
function or lifespan, and preventing the adverse effects of the drugs used.
Pharmacological therapy
Corticosteroids
Oral
Corticosteroids
Patients with
mild systemic lupus erythematosus do not normally require the use of systemic
corticosteroids, but there are patients whose quality of life is not improved
if not given low-dose corticosteroids. Patients in remission or with low
disease activity should be maintained with the lowest possible glucocorticoid dose.
They are used as initial therapy for severe lupus erythematosus or lupus
vasculitis.
Corticosteroids
decrease inflammation by suppressing the immune system. They decrease
lymphocyte volume and activity, polymorphonuclear lymphocyte migration, and
capillary permeability.
Low-dose corticosteroids may be added to Hydroxychloroquine for
fatigue and fever. High-dose corticosteroids are necessary for the refractory
manifestations of systemic lupus erythematosus and for severe organ involvement
especially central nervous system (CNS), renal, and hematologic manifestations.
High-dose corticosteroids showed improved survival in patients with severe
forms of systemic lupus erythematosus nephritis, may also be useful in severe,
life-threatening thrombocytopenia, and hemolytic anemia, and in pleuritis or
pericarditis.
Corticosteroid use should be <7.5 mg/day (Prednisone
equivalent) during chronic maintenance therapy and tapered (and if possible
withdrawn) as soon as desired response is observed (control of inflammatory manifestations)
to avoid toxicity. Tapering or withdrawing of corticosteroids may be hastened with
the prompt initiation of immunosuppressants. High doses over periods of >2-3
weeks suppress adrenal function.
Topical
Corticosteroids
Topical
corticosteroids are helpful for discoid lesions, especially on the scalp.
Advise using a less potent steroid on the face because it is more prone to
atrophy.
Parenteral
Corticosteroids
Intravenous
pulse dosing of Methylprednisolone gives immediate therapeutic effect and
allows the initiation of oral corticosteroids at a lower dose. Pulse therapy with
intravenous corticosteroids with or without immunosuppressive therapy can be
given to patients with severe organ or life-threatening manifestations.
Disease-Modifying Anti-Rheumatic Drug
(DMARD)
Hydroxychloroquine
Hydroxychloroquine is a 4-aminoquinolone antimalarial, it has immunomodulatory and
anti-inflammatory effects in the treatment of systemic
lupus erythematosus. It works by inhibiting the chemotaxis of eosinophils and
locomotion of neutrophils and impairs complement-dependent antigen-antibody
reactions.
It is recommended
for all systemic lupus erythematosus patients unless contraindicated. It is used
for skin and joint manifestations and is useful for patients with a skin
disease that is unresponsive to topical corticosteroids and in patients with
arthritis that do not respond to non-steroidal anti-inflammatory drugs (NSAIDs).
It is also used for preventing flares, reducing cardiovascular risk, recurrent
infection, and other constitutional symptoms.
It is also
recommended as background treatment for class III/IV systemic lupus
erythematosus patients with nephritis. Patients with continuing treatment with
Hydroxychloroquine showed less renal damage as compared to those on placebo.
Immunosuppressants
The choice
of immunosuppressant will depend on the nature and severity of the disease
manifestation. These agents act as immunosuppressive, cytotoxic, and
anti-inflammatory agents. Consider the addition of immunosuppressants in
patients unresponsive to Hydroxychloroquine therapy (with or without
corticosteroids) or unable to decrease corticosteroid doses below that
acceptable for chronic use. Immunosuppressants can be included in the initial
treatment of organ- or life-threatening systemic lupus erythematosus wherein an
initial course of high intensity immunosuppressive therapy is given followed by
a longer course of less intensive treatment to consolidate the patient’s
response and to prevent relapses.
In the
treatment of severe CNS and severe glomerulonephritis, thrombocytopenia, and
hemolytic anemia, high-dose glucocorticoids and immunosuppressants are used. Concomitant
use with corticosteroids allows lower doses of immunosuppressants.
Azathioprine
Azathioprine antagonizes purine metabolism and
inhibits the synthesis of DNA, RNA, and proteins. It may decrease the proliferation
of immune cells resulting in lower autoimmune activity.
It is used for mild to moderate systemic lupus erythematosus-related
organ involvements (ie renal, neurological, hematological) and can also prevent
flares. It may be used as the initial immunosuppressant for systemic lupus
erythematosus nephritis.
Calcineurin
Inhibitors
Example
drugs: Ciclosporin, Tacrolimus, Voclosporin
Calcineurin
inhibitors can be considered in patients with moderate to severe systemic lupus
erythematosus with arthritis, cutaneous disease, cytopenia, serositis, or
vasculitis if Hydroxychloroquine treatment is insufficient. It can also be
considered in the subsequent treatment of pure class V nephritis.
Cyclophosphamide
Cyclophosphamide
is an alkylating agent that may involve cross-linking of DNA which may
interfere with the growth of normal and neoplastic cells.
It is used
as an initial immunosuppressant for severe systemic lupus erythematosus
nephritis. Concomitant use with Prednisone is the standard treatment for lupus
nephritis as it helps preserve renal function. It is also useful for severe organ- or life-threatening systemic lupus
erythematosus (eg severe CNS, cardiopulmonary, or renal involvement) and as rescue
therapy for non-major organ manifestations unresponsive to other
immunosuppressants. It also prevents lupus flares.
Methotrexate
Methotrexate
works by blocking purine synthesis and increasing the anti-inflammatory
adenosine concentration at the sites of inflammation.
It is used
for mild to moderate non-renal systemic lupus erythematosus and it can also prevent
flares. It may be used as the initial immunosuppressant for severe arthritis.
Mycophenolate
mofetil
Mycophenolate
mofetil is a reversible inhibitor of inosine monophosphate dehydrogenase which
is the rate-limiting step in the de novo purine synthesis.
It is effective
for both renal and non-renal lupus and certain neuropsychiatric diseases. It is
used for moderate to severe non-renal systemic lupus erythematosus and can also
prevent flares. It is recommended as induction and maintenance therapy for
patients with lupus nephritis and has shown better results (less adverse
effects and infections) as compared to an intravenous Cyclophosphamide.
Biologic
Agents
It is
advised to consider giving monoclonal antibodies to patients who are
unresponsive to treatment with maximum tolerable doses of immunosuppressants.
Anifrolumab
Anifrolumab is a human IgG1 kappa monoclonal antibody
that inhibits signaling of type I interferon by binding to subunit 1 of the
type I interferon receptor resulting in the improvement of systemic lupus
erythematosus symptoms.
It is used for the treatment of moderate to severe systemic lupus
erythematosus symptoms in adult patients who are receiving standard therapy (eg
NSAIDs, corticosteroids, antimalarials, and/or immunosuppressants [Azathioprine,
Methotrexate, or Mycophenolate]). It is not recommended for patients with
severe active CNS lupus or severe active lupus nephritis.
Belimumab
Belimumab is a human monoclonal antibody that binds
to a soluble B-lymphocyte stimulator (BLyS/BAFF) to reduce disease activity.
It is used as an add-on therapy for patients with active, autoantibody
positive systemic lupus erythematosus with a high degree of disease activity (eg
positive anti-dsDNA and low complement) despite standard therapy
(Hydroxychloroquine and corticosteroid combinations with or without
immunosuppressants). It may be considered as an add-on therapy to extrarenal
disease that is persistently active or flaring, or to patients with frequent
relapses and/or residual disease activity preventing corticosteroid tapering.
Studies
have shown that patients on Belimumab therapy experienced a reduced risk of
severe flares, improved health-related quality of life, and reduced steroid use
as compared to those on placebo. It is not recommended for patients with severe
active CNS lupus.
Rituximab
Rituximab
is a biologic agent and chimeric monoclonal antibody to CD20 antigen which
regulates cell cycle initiation.
It is used
as rescue therapy for systemic lupus erythematosus patients with organ-threatening
disease refractory or with intolerance or contraindications to standard
immunosuppressive therapy.
Intravenous
Immunoglobulin (IVIg)
IVIg works by
neutralizing circulating myelin antibodies through anti-idiotypic antibodies,
therefore down-regulates proinflammatory cytokines, including interferon-gamma;
blocks receptors on macrophages, suppresses inducer T and B cells, and augments
suppressor T cells; and blocks complement cascade, promotes remyelination and may
increase colony stimulating factor lgG.
It is used
in serious systemic lupus erythematosus flares and refractory severe lupus. It
may be considered in the acute phase of lupus thrombocytopenia if there is an
inadequate response to high-dose corticosteroids or to prevent infectious
complications from corticosteroid therapy.
Nonsteroidal
Anti-inflammatory Drugs (NSAIDs)
NSAIDs work by inhibiting inflammatory reactions and pain by decreasing
prostaglandin synthesis. They provide symptomatic relief of fever, arthritis,
and mild serositis (ie control symptoms in mild non-renal lupus). Systemic
lupus erythematosus patients have a high incidence of NSAID-induced
hepatotoxicity.
Patient Education
Patients must learn to cope with and monitor the disease. He or she should be able to distinguish the signs and symptoms that may precede a disease flare and consult with the physician immediately.
Educate all patients regarding the prevention of cardiovascular complications, possible complications from unplanned pregnancy, poor compliance, recreational drug use, and infection. For married patients, contraception is important during the active phase of the disease. Advise patients to join other systemic lupus erythematosus patients in support groups.
Patients must be advised to wear clothing with long sleeves, use an umbrella or sunscreen lotion and refrain from sunbathing to prevent exacerbation of dermatologic symptoms. Advise patients to use sunscreen with at least a sun-protection factor (SPF) of 15-30 to prevent dermal or systemic disease flares upon exposure to ultraviolet light.
Advise patients to seek medical help when they have a fever. Exposure to immunosuppressive drugs used in systemic lupus erythematosus may predispose patients to infection.
Immunization should be updated for all patients. Patients should have appropriate immunizations (ie influenza, pneumococcal). Patients with systemic lupus erythematosus are often complement deficient and are at risk for encapsulated organisms.
Antibiotic prophylaxis should be provided for all dental, genitourinary, and other invasive procedures for patients at high risk of infections (eg patients with valvular abnormalities, on immunosuppressive therapy). Patients should routinely undergo gynecologic assessments, dental care, and ophthalmologic examination, especially for patients taking corticosteroids and Hydroxychloroquine. Psychological support may also be necessary.
Lifestyle Modification
Patients must have an appropriate
balanced diet to prevent obesity, osteoporosis, and dyslipidemia. Patients on
corticosteroids should have a no-added-salt, low-fat, and calcium-sufficient
diet.
Encourage patients to maintain a
normal lifestyle with regular exercise to maintain appropriate weight and bone
density. Advise patients that fatigue and stress are associated with disease
flares. Smoking cessation is recommended.
The patient’s blood pressure, glucose,
and lipid levels should be assessed and managed appropriately.