Mechanism of action:
Effects are mediated through genomic nuclear glucocorticoid receptors and nongenomic cell surface receptors.
Affects both cell mediated and antibody mediated autoimmunity.
Affects T cell function, induces T-cell apoptosis and suppresses transcription of proinflammatory cytokines. It impairs dendritic cell maturation. It causes suppression of T-cell proliferation and downregulation of of proinflammatory cytokine production such as nuclear factor-kappa B (NF-κB), and the concurrent suppression of the humoral immune response through decreased clonal expansion and antibody production of B cells.
Corticosteroid therapy is frequently effective in a majority of immune-mediated neuromuscular disorders, with GBS being a notable exception. Although randomized, controlled trial data do not exist to support the use of corticosteroids for MG, CIDP, peripheral nerve vasculitis, and idiopathic inflammatory myopathies, broad consensus exists that corticosteroids are effective. In this era, placebo-controlled studies of corticosteroids cannot be performed due to ethical considerations.
Uses:
75% of MG patients improve with CS use. 30% achieve remission, and 45% have marked improvement.
The treatment induction regimen is used when a pressing need for disease control justifies the exposure to high-dose corticosteroids. An initial dose of 1 to 1.5 mg/kg/d is used with a total daily dose rarely exceeding 100 mg/d. Tapering begins in 4 to 8 weeks, either when the patient starts to show signs of disease stabilization or if it appears the patient is not improving. Typically, daily prednisone is tapered by 10 mg every month and more slowly at doses below 10 mg/d.
Prednisone may also be converted to every-other-day dosing. If the patient has been on daily prednisone for over 1 month, the every other-day dose can be tapered slowly down to zero (eg, 60 mg alternating with 50 mg for 1 month; 60 mg alternating with 40 mg for 1 month, etc). If the patient has been on high-dose daily prednisone for less than 1 month, then the dose can be abruptly converted to every-other-day dosing prior to gradual tapering (eg, 60 mg/d converted to 60 or 80 mg every other day). This high-dose regimen has been shown in generalized MG to lead to pharmacological remission in 28% and marked improvement in an additional 53%.
"Start low, and go slow" approach: 10 mg (1 tab) of prednisone daily for 2 weeks., then increased to a total of 15 mg (1 1/2 tabs) daily on 3rd and 4th week, then increase it to a total of 20 mg (2 tabs) daily from 4th week.
The transient exacerbation of myasthenic weakness is well documented after the initiation of corticosteroids. It occurs, on average, about 5 days after corticosteroid initiation, lasts 1 to 7 days, and weakness can vary from mild to sufficient to tip the patient into respiratory failure. Hence: (1) pulse high-dose methylprednisolone should only rarely be considered in MG; and (2) treatment induction with high-dose prednisone should be initiated in the inpatient setting in patients with bulbar or respiratory weakness. If steroid-associated worsening occurs in this setting, it is usually transient, and the dose of prednisone can be maintained until the patient improves. The mechanism behind transient myasthenic weakness with corticosteroids is not fully understood. Studies of repetitive nerve stimulation in MG patients have shown worsening of decrement within 1 to 3 hours of an oral dose followed by resolution 6 to 18 hours later. These data suggest a direct physiochemical effect at the neuromuscular junction or skeletal myofiber, as opposed to glucocorticoid receptor-mediated changes in gene expression.
For OMG. A double-blind, placebo-controlled, randomized study showed that prednisone is also effective in pyridostigmine resistant ocular MG. In this study, patients were assigned either to placebo or to 10 mg of prednisone every other day with a titration up to 40 mg/d as needed to treat diplopia. At 16 weeks, the study showed that treatment failure with persistent diplopia was 100% in the placebo group vs 17% in the prednisone group (P = .02). That study, although small, provided strong evidence that low-dose gradual escalation corticosteroid therapy can be well tolerated and should be the standard of care for cholinesterase inhibitor–resistant diplopia in ocular MG.
Steroids are not good and may be bad to use in GBS, MMN, DADS associated with IgM monoclonal proteins, and MGUS.
For GBS, the evidence is clear: corticosteroids are ineffective and should not be used. For CIDP, however, corticosteroids are accepted as one of the three core therapies along with IVIG and PLEX on the basis of retrospective data and clinical experience.
The PREDICT trial was a randomized, double-blind study in which treatment-naive CIDP patients were assigned to either prednisolone 60 mg/d for 5 weeks, followed by a forced taper, or pulsed-high-dose dexamethasone 40 mg/d for 4 days, followed by placebo tablets for the remainder of the month for 12 months, which was the duration of the study. At the conclusion of the study, the primary outcome of CIDP remission was comparable in both treatment groups, as was overall safety. However, difficulty with quality of sleep and a cushingoid facial appearance were more common in the prednisolone group.
Corticosteroids have also had a significant role in the treatment of idiopathic inflammatory myopathies since the early 1960s. Despite the absence of placebo-controlled trials demonstrating effectiveness in dermatomyositis and polymyositis, corticosteroids are considered by consensus the foundation of modern therapy. In general, corticosteroids are initiated in the presence of functionally limiting weakness or other rheumatic manifestations, such as a rash in dermatomyositis. A dose of 1 mg/kg/d can be used, with a dose not to exceed 80 to 100 mg/d. For patients with a severe inflammatory myopathy phenotype, corticosteroid therapy can be initiated with pulsed-dose intravenous methylprednisolone at 1000 mg/d for 3 to 5 days. A steroid sparing immunosuppressive, typically azathioprine or methotrexate, can be started at the same time, in anticipation of a slow steroid taper over 6 months to 1 year to the lowest tolerated dose with or without IVIG.
Corticosteroids such as prednisone and deflazacort are unique in that, unlike other immunosuppressive and immunomodulatory treatments, they have also been shown to improve strength and pulmonary function, delay functional impairment and cardiomyopathy, and reduce the need for scoliosis surgery in boys with DMD. The mechanism behind the beneficial effect of corticosteroids in DMD remains uncertain, but negative clinical studies with azathioprine indicate it is not immunosuppression. Currently, corticosteroids remain the mainstay of pharmacotherapy in DMD patients, despite the advent of promising exon-skipping genetic therapies. For Becker muscular dystrophy, the role of corticosteroids remains undefined. This is likely due to the broad spectrum of clinical severity that has rendered clinical trials harder to perform in this dystrophinopathy.
Tapering Regimens:
Prednisone 60 mg even day, 50 mg odd day > taper 60 - 40 > 60 -30 > 60-20> 60-18> 60-16>.....60-0. Reduce by 10 mg q2 weeks, when at 20 mg further reduction by 1-2.5 mg every 3 months (single morning dose).
Monitoring while on CS:
BP, cataracts IOP, BS, lipids, DEXA.
In patients receiving CS for > 3 months:
Bone density scan - DEXA
Vitamin D2, 2000 IU daily
Calcium 1000 mg daily
Exercise - aerobic: steroid myopathy is increased by immobility
No more than modest alcohol consumption.
Men >50, women who are postmenopausal:
Biphosphonate (alendronate 10 mg daily or 70 mg weekly or 35 mg thrice a week
GI prophylaxis: PPI, misoprostol
Augment CS dosing perioperatively to avoid risk of AI in patients receiving CS > 1 month
Low sodium, low -CHO, high protein diet (reduce risk of steroid myopathy).
Pneumocystis jerovici prophylaxis: prednisone 20 mg qd x 4 weeks.
AE:
CS facilitates osteopenia and enhances bone resorption. It interferes with bone formation through apoptosis of osteocytes. it inhibits osteoprotegerin an endogenous antiresorptive cytokine.
Prednisone:
Rapid induction: 1.5 mg/kg/d for 2-4 weeks (dose rarely exceeds 100 mg/d), followed by taper and every other day dosing if desired;
Start-low, go-slow regimen: 10 mg/d, increase dose to 60-100 mg/d over 4-8 wk; Initiate and maintain regimen: 20 mg/d;
Taper: every 4 weeks by 10 mg until 10 mg/d, then taper by 1-2.5 mg every 3 months (single morning dose)
2-4 wk, effect may build over time (mo)
SE: Fluid and weight gain, insomnia, mood elevation, hyperglycemia, hypokalemia, hypertension, gastric irritation, bone thinning; long-term use: infection, cataracts, glaucoma, osteonecrosis, adrenal insufficiency, and growth suppression in pediatric use.
Weight, BP; glucose and potassium; yearly bone density for chronic use
Methylprednisolone:
gm/d IV for 3-5 doses
2-4 wk
Arrhythmia, flushing, dysgeusia and as prednisone
Same as prednisone
Corticosteroids or glucocorticoids—commonly referred to as steroids—are prescription medications that reduce inflammation in the body. Inflammation can be caused by various factors, including allergic reactions and autoimmune diseases such as lupus and multiple sclerosis (MS). Our bodies produce their own glucocorticoids as well as something called adrenocorticotropic hormone, or ACTH, which is produced by the pituitary gland. ACTH stimulates steroid production and is sometimes prescribed instead of glucocorticoids.
Common steroids like prednisone, cortisone, and dexamethasone inhibit chemicals that cause inflammation and are often prescribed for reducing the inflammation and swelling at the sites of lesions on the spine and brain in MS, for example. In myasthenia gravis, steroids help signals get through from nerves to muscles to improve muscle strength. The goal of steroids is to calm the immune system and alleviate symptoms such as pain, swelling, and weakness quickly. Sometimes relief occurs within days. In other cases, it can take weeks or months.
Steroids can be administered via injection, by intravenous (IV) infusion, orally, or topically. To reduce pain, steroids are typically injected in and around the painful area. The route and frequency of steroids depends on the underlying disease. For sciatica, for example, a steroid nerve block may need to be repeated every few months, while an MS flare might be treated with IV steroids every day for a few days as needed to treat the attack.
Side effects of steroids, however they are administered, include weight gain, high blood pressure, high blood sugar levels, osteoporosis, high cholesterol levels, acne, easier bruising, water retention, stomach irritation and ulcers, muscle weakness, mood swings, insomnia, and increased body hair. The longer people are on steroids, the more likely they are to experience side effects. The same is true for people who have other health problems such as diabetes (steroids can raise blood sugar) and osteoporosis (steroids can exacerbate bone density loss).
Taking proton pump inhibitors—over-the-counter tablets—can lower the risk of ulcers by reducing stomach acid, but they should not be used for extended periods. Check with your doctor about the dose and how long to use proton pump inhibitors. If you have to stay on them for a long time, your doctor may prescribe antibiotics to help prevent pneumonia, since reducing stomach acid can lead to bacterial overgrowth. Doctors also may advise taking calcium and vitamin D supplements because proton pump inhibitors can deplete those.
Some side effects, such as increased appetite and weight gain, are temporary and disappear after the medication has been discontinued. Others, such as mood changes and trouble sleeping, may last longer. People with diabetes or gestational diabetes should alert their physicians before taking steroids and be monitored for high glucose levels during treatment.
Corticosteroids can push hair follicles into a resting phase, causing them to shed. Once the medication is stopped, the follicles gradually transition back into the growth phase.